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<interpro id="IPR000001" protein_count="655" short_name="Kringle" type="Domain">
<name>Kringle</name>
<abstract>
<p>Kringles are autonomous structural domains, found throughout the blood clotting and fibrinolytic proteins. Kringle domains are believed to play a role in binding mediators (e.g., membranes, other proteins or phospholipids), and in the regulation of proteolytic activity [<cite idref="PUB00002414"/>, <cite idref="PUB00001541"/>, <cite idref="PUB00003257"/>].
Kringle domains [<cite idref="PUB00003400"/>, <cite idref="PUB00000803"/>, <cite idref="PUB00001620"/>] are characterised by a triple loop, 3-disulphide bridge structure, whose conformation is defined by a number of hydrogen bonds and small pieces of anti-parallel beta-sheet. They are found in a varying number of copies in some plasma proteins including prothrombin and urokinase-type plasminogen activator, which are serine proteases belonging to MEROPS peptidase family S1A.</p>
<p>Steroid or nuclear hormone receptors (4A nuclear receptor, NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. Members of the superfamily include the steroid hormone receptors and receptors for thyroid hormone, retinoids, 1,25-dihydroxy-vitamin D3 and a variety of other ligands [<cite idref="PUB00015853"/>]. The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner [<cite idref="PUB00004464"/>, <cite idref="PUB00006168"/>]. In addition to C-terminal ligand-binding domains, these nuclear receptors contain a highly-conserved, N-terminal zinc-finger that mediates specific binding to target DNA sequences, termed ligand-responsive elements. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.</p>
<p>NRs are extremely important in medical research, a large number of them being implicated in diseases such as cancer, diabetes, hormone resistance syndromes, etc. While several NRs act as ligand-inducible transcription factors, many do not yet have a defined ligand and are accordingly termed 'orphan' receptors. During the last decade, more than 300 NRs have been described, many of which are orphans, which cannot easily be named due to current nomenclature confusions in the literature. However, a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members.</p>
</abstract>
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<pub_list>
<publication id="PUB00000803">
<author_list>Patthy L.</author_list>
<title>Evolution of the proteases of blood coagulation and fibrinolysis by assembly from modules.</title>
<db_xref db="PUBMED" dbkey="3891096"/>
<journal>Cell</journal>
<location issue="3" pages="657-63" volume="41"/>
<year>1985</year>
</publication>
<publication id="PUB00001541">
<author_list>Patthy L, Trexler M, Vali Z, Banyai L, Varadi A.</author_list>
<title>Kringles: modules specialized for protein binding. Homology of the gelatin-binding region of fibronectin with the kringle structures of proteases.</title>
<db_xref db="PUBMED" dbkey="6373375"/>
<journal>FEBS Lett.</journal>
<location issue="1" pages="131-6" volume="171"/>
<year>1984</year>
</publication>
<publication id="PUB00002414">
<author_list>McMullen BA, Fujikawa K.</author_list>
<title>Amino acid sequence of the heavy chain of human alpha-factor XIIa (activated Hageman factor).</title>
<db_xref db="PUBMED" dbkey="3886654"/>
<journal>J. Biol. Chem.</journal>
<location issue="9" pages="5328-41" volume="260"/>
<year>1985</year>
</publication>
<publication id="PUB00001620">
<author_list>Ikeo K, Takahashi K, Gojobori T.</author_list>
<title>Evolutionary origin of numerous kringles in human and simian apolipoprotein(a).</title>
<db_xref db="PUBMED" dbkey="1879523"/>
<journal>FEBS Lett.</journal>
<location issue="1-2" pages="146-8" volume="287"/>
<year>1991</year>
</publication>
<publication id="PUB00006168">
<author_list>De Vos P, Schmitt J, Verhoeven G, Stunnenberg HG.</author_list>
<title>Human androgen receptor expressed in HeLa cells activates transcription in vitro.</title>
<db_xref db="PUBMED" dbkey="8165128"/>
<journal>Nucleic Acids Res.</journal>
<location issue="7" pages="1161-6" volume="22"/>
<year>1994</year>
</publication>
<publication id="PUB00015853">
<author_list>Schwabe JW, Teichmann SA.</author_list>
<title>Nuclear receptors: the evolution of diversity.</title>
<db_xref db="PUBMED" dbkey="14747695"/>
<journal>Sci. STKE</journal>
<location issue="217" pages="pe4" volume="2004"/>
<year>2004</year>
</publication>
<publication id="PUB00003257">
<author_list>Atkinson RA, Williams RJ.</author_list>
<title>Solution structure of the kringle 4 domain from human plasminogen by 1H nuclear magnetic resonance spectroscopy and distance geometry.</title>
<db_xref db="PUBMED" dbkey="2157850"/>
<journal>J. Mol. Biol.</journal>
<location issue="3" pages="541-52" volume="212"/>
<year>1990</year>
</publication>
<publication id="PUB00003400">
<author_list>Castellino FJ, Beals JM.</author_list>
<title>The genetic relationships between the kringle domains of human plasminogen, prothrombin, tissue plasminogen activator, urokinase, and coagulation factor XII.</title>
<db_xref db="PUBMED" dbkey="3131537"/>
<journal>J. Mol. Evol.</journal>
<location issue="4" pages="358-69" volume="26"/>
<year>1987</year>
</publication>
<publication id="PUB00004464">
<author_list>Nishikawa J, Kitaura M, Imagawa M, Nishihara T.</author_list>
<title>Vitamin D receptor contains multiple dimerization interfaces that are functionally different.</title>
<db_xref db="PUBMED" dbkey="7899080"/>
<journal>Nucleic Acids Res.</journal>
<location issue="4" pages="606-11" volume="23"/>
<year>1995</year>
</publication>
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<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="1"/>
<taxon_data name="Eukaryota" proteins_count="653"/>
<taxon_data name="Nematoda" proteins_count="5"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="5"/>
<taxon_data name="Arthropoda" proteins_count="34"/>
<taxon_data name="Fruit Fly" proteins_count="2"/>
<taxon_data name="Chordata" proteins_count="529"/>
<taxon_data name="Human" proteins_count="79"/>
<taxon_data name="Mouse" proteins_count="41"/>
<taxon_data name="Virus" proteins_count="1"/>
<taxon_data name="Plastid Group" proteins_count="14"/>
<taxon_data name="Green Plants" proteins_count="14"/>
<taxon_data name="Metazoa" proteins_count="618"/>
<taxon_data name="Plastid Group" proteins_count="14"/>
<taxon_data name="Plastid Group" proteins_count="4"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR018059"/>
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</interpro>
<interpro id="IPR000003" protein_count="452" short_name="RtnoidX_rcpt" type="Family">
<name>Retinoid X receptor</name>
<abstract>
<p>Steroid or nuclear hormone receptors (4A nuclear receptor, NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. Members of the superfamily include the steroid hormone receptors and receptors for thyroid hormone, retinoids, 1,25-dihydroxy-vitamin D3 and a variety of other ligands [<cite idref="PUB00015853"/>]. The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner [<cite idref="PUB00004464"/>, <cite idref="PUB00006168"/>]. In addition to C-terminal ligand-binding domains, these nuclear receptors contain a highly-conserved, N-terminal zinc-finger that mediates specific binding to target DNA sequences, termed ligand-responsive elements. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.</p>
<p>NRs are extremely important in medical research, a large number of them being implicated in diseases such as cancer, diabetes, hormone resistance syndromes, etc. While several NRs act as ligand-inducible transcription factors, many do not yet have a defined ligand and are accordingly termed 'orphan' receptors. During the last decade, more than 300 NRs have been described, many of which are orphans, which cannot easily be named due to current nomenclature confusions in the literature. However, a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members.</p>
<p>The retinoic acid (retinoid X) receptor consists of 3 functional and
structural domains: an N-terminal (modulatory) domain; a DNA binding domain
that mediates specific binding to target DNA sequences (ligand-responsive
elements); and a hormone binding domain. The N-terminal domain differs
between retinoic acid isoforms; the small highly-conserved DNA-binding
domain (~65 residues) occupies the central portion of the protein; and
the ligand binding domain lies at the receptor C terminus.</p>
<p>Synonym(s): 2B nuclear receptor</p>
</abstract>
<class_list>
<classification id="GO:0003677" class_type="GO">
<category>Molecular Function</category>
<description>DNA binding</description>
</classification>
<classification id="GO:0004879" class_type="GO">
<category>Molecular Function</category>
<description>ligand-dependent nuclear receptor activity</description>
</classification>
<classification id="GO:0005496" class_type="GO">
<category>Molecular Function</category>
<description>steroid binding</description>
</classification>
<classification id="GO:0005634" class_type="GO">
<category>Cellular Component</category>
<description>nucleus</description>
</classification>
<classification id="GO:0006355" class_type="GO">
<category>Biological Process</category>
<description>regulation of transcription, DNA-dependent</description>
</classification>
<classification id="GO:0008270" class_type="GO">
<category>Molecular Function</category>
<description>zinc ion binding</description>
</classification>
</class_list>
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<title>Vitamin D receptor contains multiple dimerization interfaces that are functionally different.</title>
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<journal>Nucleic Acids Res.</journal>
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<year>1995</year>
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<author_list>De Vos P, Schmitt J, Verhoeven G, Stunnenberg HG.</author_list>
<title>Human androgen receptor expressed in HeLa cells activates transcription in vitro.</title>
<db_xref db="PUBMED" dbkey="8165128"/>
<journal>Nucleic Acids Res.</journal>
<location issue="7" pages="1161-6" volume="22"/>
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<author_list>Schwabe JW, Teichmann SA.</author_list>
<title>Nuclear receptors: the evolution of diversity.</title>
<db_xref db="PUBMED" dbkey="14747695"/>
<journal>Sci. STKE</journal>
<location issue="217" pages="pe4" volume="2004"/>
<year>2004</year>
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<interpro id="IPR000005" protein_count="22704" short_name="HTH_AraC-typ" type="Domain">
<name>Helix-turn-helix, AraC type</name>
<abstract>
<p>Many bacterial transcription regulation proteins bind DNA through a
'helix-turn-helix' (HTH) motif. One major subfamily of these proteins [<cite idref="PUB00004444"/>, <cite idref="PUB00003566"/>] is related to the arabinose
operon regulatory protein AraC [<cite idref="PUB00004444"/>], <cite idref="PUB00003566"/>. Except for celD [<cite idref="PUB00001933"/>], all of these proteins seem to be positive transcriptional factors.</p>
<p>Although the sequences belonging to this family differ somewhat in length, in nearly every case the HTH motif is situated towards the C terminus in the third quarter of most of the sequences. The minimal DNA binding domain spans roughly 100 residues and comprises two HTH subdomains; the classical HTH domain and another HTH subdomain with similarity to the classical HTH domain but with an insertion of one residue in the turn-region. The N-terminal and central regions of these proteins are presumed to interact with effector molecules and may be involved in dimerisation [<cite idref="PUB00004817"/>].</p>
<p>The known structure of MarA (<db_xref db="SWISSPROT" dbkey="P27246"/>) shows that the AraC domain is alpha helical and shows the two HTH subdomains both bind the major groove of the DNA. The two HTH subdomains are separated by only 27
angstroms, which causes the cognate DNA to bend.</p>
</abstract>
<class_list>
<classification id="GO:0003700" class_type="GO">
<category>Molecular Function</category>
<description>transcription factor activity</description>
</classification>
<classification id="GO:0005622" class_type="GO">
<category>Cellular Component</category>
<description>intracellular</description>
</classification>
<classification id="GO:0006355" class_type="GO">
<category>Biological Process</category>
<description>regulation of transcription, DNA-dependent</description>
</classification>
<classification id="GO:0043565" class_type="GO">
<category>Molecular Function</category>
<description>sequence-specific DNA binding</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P06134"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00001933">
<author_list>Parker LL, Hall BG.</author_list>
<title>Characterization and nucleotide sequence of the cryptic cel operon of Escherichia coli K12.</title>
<db_xref db="PUBMED" dbkey="2179047"/>
<journal>Genetics</journal>
<location issue="3" pages="455-71" volume="124"/>
<year>1990</year>
</publication>
<publication id="PUB00003566">
<author_list>Henikoff S, Wallace JC, Brown JP.</author_list>
<title>Finding protein similarities with nucleotide sequence databases.</title>
<db_xref db="PUBMED" dbkey="2314271"/>
<journal>Meth. Enzymol.</journal>
<location pages="111-32" volume="183"/>
<year>1990</year>
</publication>
<publication id="PUB00004444">
<author_list>Gallegos MT, Michan C, Ramos JL.</author_list>
<title>The XylS/AraC family of regulators.</title>
<db_xref db="PUBMED" dbkey="8451183"/>
<journal>Nucleic Acids Res.</journal>
<location issue="4" pages="807-10" volume="21"/>
<year>1993</year>
</publication>
<publication id="PUB00004817">
<author_list>Bustos SA, Schleif RF.</author_list>
<title>Functional domains of the AraC protein.</title>
<db_xref db="PUBMED" dbkey="8516313"/>
<journal>Proc. Natl. Acad. Sci. U.S.A.</journal>
<location issue="12" pages="5638-42" volume="90"/>
<year>1993</year>
</publication>
</pub_list>
<parent_list>
<rel_ref ipr_ref="IPR012287"/>
</parent_list>
<child_list>
<rel_ref ipr_ref="IPR018062"/>
<rel_ref ipr_ref="IPR020449"/>
</child_list>
<found_in>
<rel_ref ipr_ref="IPR011983"/>
<rel_ref ipr_ref="IPR016220"/>
<rel_ref ipr_ref="IPR016221"/>
<rel_ref ipr_ref="IPR016981"/>
<rel_ref ipr_ref="IPR018060"/>
</found_in>
<member_list>
<db_xref protein_count="22704" db="PFAM" dbkey="PF00165" name="HTH_AraC"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00165"/>
<db_xref db="MSDsite" dbkey="PS00041"/>
<db_xref db="BLOCKS" dbkey="IPB000005"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00040"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1bl0"/>
<db_xref db="PDB" dbkey="1d5y"/>
<db_xref db="PDB" dbkey="1xs9"/>
<db_xref db="CATH" dbkey="1.10.10.60"/>
<db_xref db="SCOP" dbkey="a.4.1.8"/>
<db_xref db="SCOP" dbkey="i.11.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="22594"/>
<taxon_data name="Cyanobacteria" proteins_count="150"/>
<taxon_data name="Synechocystis PCC 6803" proteins_count="4"/>
<taxon_data name="Archaea" proteins_count="4"/>
<taxon_data name="Eukaryota" proteins_count="100"/>
<taxon_data name="Rice spp." proteins_count="4"/>
<taxon_data name="Fungi" proteins_count="43"/>
<taxon_data name="Virus" proteins_count="1"/>
<taxon_data name="Unclassified" proteins_count="2"/>
<taxon_data name="Unclassified" proteins_count="3"/>
<taxon_data name="Plastid Group" proteins_count="54"/>
<taxon_data name="Green Plants" proteins_count="54"/>
<taxon_data name="Metazoa" proteins_count="45"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR018062"/>
<sec_ac acc="IPR020449"/>
</sec_list>
</interpro>
<interpro id="IPR000006" protein_count="253" short_name="Metallothionein_vert" type="Family">
<name>Metallothionein, vertebrate</name>
<abstract>
<p>Metallothioneins (MT) are small proteins that bind heavy metals, such as zinc, copper, cadmium, nickel, etc. They have a high content of cysteine residues that bind the metal ions through clusters of thiolate bonds [<cite idref="PUB00003570"/>, <cite idref="PUB00001490"/>]. An empirical classification into three classes has been proposed by Fowler and coworkers [<cite idref="PUB00005944"/>] and Kojima [<cite idref="PUB00003571"/>]. Members of class I are defined to include polypeptides related in the positions of their cysteines to equine MT-1B, and include mammalian MTs as well as from crustaceans and molluscs. Class II groups MTs from a variety of species, including sea urchins,
fungi, insects and cyanobacteria. Class III MTs are atypical polypeptides composed of gamma-glutamylcysteinyl units [<cite idref="PUB00005944"/>].</p>
<p>This original classification system has been found to be limited, in the sense that it does not allow clear differentiation of patterns of structural similarities, either between or within classes. Consequently, all class I and class II MTs (the proteinaceous sequences) have now been grouped into families of phylogenetically-related and thus alignable sequences. This system subdivides the MT superfamily into families, subfamilies, subgroups, and isolated isoforms and alleles. </p>
<p>The metallothionein superfamily comprises all polypeptides that resemble equine renal metallothionein in several respects [<cite idref="PUB00005944"/>]: e.g., low molecular weight; high metal content; amino acid composition with high Cys and low aromatic residue content; unique sequence with characteristic distribution of cysteines, and spectroscopic manifestations indicative of metal thiolate clusters. A MT family subsumes MTs that share particular sequence-specific features and are thought to be evolutionarily related. The inclusion of a MT within a family presupposes that its amino acid sequence is alignable with that of all members. Fifteen MT families have been characterised, each family being identified by its number and its taxonomic range: e.g., Family 1: vertebrate MTs [see http://www.bioc.unizh.ch/mtpage/protali.html]. </p>
<p> The members of family 1 are recognised by the sequence pattern K-x(1,2)-C-C-x-C-C-P-x(2)-C located at the beginning of the third exon.
The taxonomic range of the members extends to vertebrates.
Known characteristics: 60 to 68 AAs; 20 Cys (21 in one case), 19 of them are totally conserved; the protein sequence is divided into two structural domains, containing 9 and 11 Cys all binding 3 and 4 bivalent metal ions, respectively. The gene is composed of 3 exons, 2 introns and the splicing sites are conserved. Family 1 includes subfamilies: m1, m2, m3, m4, m, a, a1, a2, b, ba, t, all of them hit the same InterPro entry.
</p>
</abstract>
<class_list>
<classification id="GO:0046872" class_type="GO">
<category>Molecular Function</category>
<description>metal ion binding</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P02795"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P02802"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P04355"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00001490">
<author_list>Kagi JH, Kojima Y.</author_list>
<title>Chemistry and biochemistry of metallothionein.</title>
<db_xref db="PUBMED" dbkey="2959513"/>
<journal>Experientia Suppl.</journal>
<location pages="25-61" volume="52"/>
<year>1987</year>
</publication>
<publication id="PUB00003570">
<author_list>Kagi JH.</author_list>
<title>Overview of metallothionein.</title>
<db_xref db="PUBMED" dbkey="1779825"/>
<journal>Meth. Enzymol.</journal>
<location pages="613-26" volume="205"/>
<year>1991</year>
</publication>
<publication id="PUB00003571">
<author_list>Kojima Y.</author_list>
<title>Definitions and nomenclature of metallothioneins.</title>
<db_xref db="PUBMED" dbkey="1779826"/>
<journal>Meth. Enzymol.</journal>
<location pages="8-10" volume="205"/>
<year>1991</year>
</publication>
<publication id="PUB00005944">
<author_list>Fowler BA, Hildebrand CE, Kojima Y, Webb M.</author_list>
<title>Nomenclature of metallothionein.</title>
<db_xref db="PUBMED" dbkey="2959504"/>
<journal>Experientia Suppl.</journal>
<location pages="19-22" volume="52"/>
<year>1987</year>
</publication>
</pub_list>
<parent_list>
<rel_ref ipr_ref="IPR003019"/>
</parent_list>
<contains>
<rel_ref ipr_ref="IPR017854"/>
<rel_ref ipr_ref="IPR018064"/>
</contains>
<member_list>
<db_xref protein_count="250" db="PANTHER" dbkey="PTHR23299" name="Metallothionein_vert"/>
<db_xref protein_count="220" db="PRINTS" dbkey="PR00860" name="MTVERTEBRATE"/>
<db_xref protein_count="238" db="GENE3D" dbkey="G3DSA:4.10.10.10" name="Metallothionein_vert"/>
</member_list>
<external_doc_list>
<db_xref db="MSDsite" dbkey="PS00203"/>
<db_xref db="COMe" dbkey="PRX001296"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00180"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1dfs"/>
<db_xref db="PDB" dbkey="1dft"/>
<db_xref db="PDB" dbkey="1ji9"/>
<db_xref db="PDB" dbkey="1m0g"/>
<db_xref db="PDB" dbkey="1m0j"/>
<db_xref db="PDB" dbkey="1mhu"/>
<db_xref db="PDB" dbkey="1mrb"/>
<db_xref db="PDB" dbkey="1mrt"/>
<db_xref db="PDB" dbkey="2mhu"/>
<db_xref db="PDB" dbkey="2mrb"/>
<db_xref db="PDB" dbkey="2mrt"/>
<db_xref db="PDB" dbkey="4mt2"/>
<db_xref db="CATH" dbkey="4.10.10.10"/>
<db_xref db="SCOP" dbkey="g.46.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Eukaryota" proteins_count="253"/>
<taxon_data name="Chordata" proteins_count="249"/>
<taxon_data name="Human" proteins_count="27"/>
<taxon_data name="Mouse" proteins_count="15"/>
<taxon_data name="Metazoa" proteins_count="251"/>
<taxon_data name="Plastid Group" proteins_count="2"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000007" protein_count="355" short_name="Tubby_C" type="Domain">
<name>Tubby, C-terminal</name>
<abstract>
<p> Tubby, an autosomal recessive mutation, mapping to mouse chromosome 7, was recently found to be the result of a splicing defect in a novel gene with unknown function. This mutation maps to the tub gene [<cite idref="PUB00000932"/>, <cite idref="PUB00004232"/>]. The mouse tubby mutation is the cause of maturity-onset obesity, insulin resistance and sensory deficits. By contrast with the rapid juvenile-onset weight gain seen in diabetes (db) and obese (ob) mice, obesity in tubby mice develops gradually, and strongly resembles the late-onset obesity observed in the human population. Excessive deposition of adipose tissue culminates in a two-fold increase of body weight. Tubby mice also suffer retinal degeneration and neurosensory hearing loss. The tripartite character of the tubby phenotype is highly similar to human obesity syndromes, such as Alstrom and Bardet-Biedl. Although these phenotypes indicate a vital role for tubby proteins, no biochemical function has yet been ascribed to any family member [<cite idref="PUB00007281"/>], although it has been suggested that the phenotypic features of tubby mice may be the result of cellular apoptosis triggered by expression of the mutated tub gene. TUB is the founding-member of the tubby-like proteins, the TULPs. TULPs are found in multicellular organisms from both the plant and animal kingdoms. Ablation of members of this protein family cause disease phenotypes that are indicative of their importance in nervous-system function and development [<cite idref="PUB00014197"/>].</p>
<p>Mammalian TUB is a hydrophilic protein of ~500 residues. The N-terminal (<db_xref db="INTERPRO" dbkey="IPR005398"/>) portion of the protein is conserved neither in length nor sequence, but, in TUB, contains the nuclear localisation signal and may have transcriptional-activation activity. The C-terminal 250 residues are highly conserved. The C-terminal extremity contains a cysteine residue that might play an important role in the normal functioning of these proteins. The crystal structure of the C-terminal core domain from mouse tubby has been determined to 1.9A resolution. This domain is arranged as a 12-stranded, all anti-parallel, closed beta-barrel that surrounds a central alpha helix, (which is at the extreme carboxyl terminus of the protein) that forms most of the hydrophobic core. Structural analyses suggest that TULPs constitute a unique family of bipartite transcription factors [<cite idref="PUB00007281"/>].</p>
</abstract>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O00294"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="O80699"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P50586"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q09306"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q10LG8"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00000932">
<author_list>Kleyn PW, Fan W, Kovats SG, Lee JJ, Pulido JC, Wu Y, Berkemeier LR, Misumi DJ, Holmgren L, Charlat O, Woolf EA, Tayber O, Brody T, Shu P, Hawkins F, Kennedy B, Baldini L, Ebeling C, Alperin GD, Deeds J, Lakey ND, Culpepper J, Chen H, Glucksmann-Kuis MA, Carlson GA, Duyk GM, Moore KJ.</author_list>
<title>Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family.</title>
<db_xref db="PUBMED" dbkey="8612280"/>
<journal>Cell</journal>
<location issue="2" pages="281-90" volume="85"/>
<year>1996</year>
</publication>
<publication id="PUB00004232">
<author_list>Noben-Trauth K, Naggert JK, North MA, Nishina PM.</author_list>
<title>A candidate gene for the mouse mutation tubby.</title>
<db_xref db="PUBMED" dbkey="8606774"/>
<journal>Nature</journal>
<location issue="6574" pages="534-8" volume="380"/>
<year>1996</year>
</publication>
<publication id="PUB00007281">
<author_list>Boggon TJ, Shan WS, Santagata S, Myers SC, Shapiro L.</author_list>
<title>Implication of tubby proteins as transcription factors by structure-based functional analysis.</title>
<db_xref db="PUBMED" dbkey="10591637"/>
<journal>Science</journal>
<location issue="5447" pages="2119-25" volume="286"/>
<year>1999</year>
</publication>
<publication id="PUB00014197">
<author_list>Carroll K, Gomez C, Shapiro L.</author_list>
<title>Tubby proteins: the plot thickens.</title>
<db_xref db="PUBMED" dbkey="14708010"/>
<journal>Nat. Rev. Mol. Cell Biol.</journal>
<location issue="1" pages="55-63" volume="5"/>
<year>2004</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR018066"/>
</contains>
<member_list>
<db_xref protein_count="345" db="PFAM" dbkey="PF01167" name="Tub"/>
<db_xref protein_count="284" db="PRINTS" dbkey="PR01573" name="SUPERTUBBY"/>
<db_xref protein_count="324" db="GENE3D" dbkey="G3DSA:3.20.90.10" name="Tubby_C"/>
<db_xref protein_count="345" db="SSF" dbkey="SSF54518" name="Tubby_C"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF01167"/>
<db_xref db="MSDsite" dbkey="PS01200"/>
<db_xref db="MSDsite" dbkey="PS01201"/>
<db_xref db="BLOCKS" dbkey="IPB000007"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00923"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1c8z"/>
<db_xref db="PDB" dbkey="1i7e"/>
<db_xref db="PDB" dbkey="1s31"/>
<db_xref db="PDB" dbkey="2fim"/>
<db_xref db="PDB" dbkey="3c5n"/>
<db_xref db="CATH" dbkey="3.20.90.10"/>
<db_xref db="SCOP" dbkey="d.23.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Eukaryota" proteins_count="355"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="16"/>
<taxon_data name="Rice spp." proteins_count="48"/>
<taxon_data name="Fungi" proteins_count="10"/>
<taxon_data name="Other Eukaryotes" proteins_count="16"/>
<taxon_data name="Other Eukaryotes" proteins_count="1"/>
<taxon_data name="Nematoda" proteins_count="2"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="2"/>
<taxon_data name="Arthropoda" proteins_count="40"/>
<taxon_data name="Fruit Fly" proteins_count="5"/>
<taxon_data name="Chordata" proteins_count="64"/>
<taxon_data name="Human" proteins_count="13"/>
<taxon_data name="Mouse" proteins_count="16"/>
<taxon_data name="Plastid Group" proteins_count="161"/>
<taxon_data name="Green Plants" proteins_count="161"/>
<taxon_data name="Metazoa" proteins_count="124"/>
<taxon_data name="Plastid Group" proteins_count="38"/>
<taxon_data name="Plastid Group" proteins_count="3"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000008" protein_count="5988" short_name="C2_Ca-dep" type="Domain">
<name>C2 calcium-dependent membrane targeting</name>
<abstract>
The C2 domain is a Ca2+-dependent membrane-targeting module found in many cellular proteins involved in signal transduction or membrane trafficking. C2 domains are unique among membrane targeting domains in that they show wide range of lipid selectivity for the major components of cell membranes, including phosphatidylserine and phosphatidylcholine. This C2 domain is about 116 amino-acid residues and is located between the two copies of
the C1 domain in Protein Kinase C (that bind phorbol esters and diacylglycerol) (see <db_xref db="PROSITEDOC" dbkey="PDOC00379"/>)
and the protein kinase catalytic domain (see <db_xref db="PROSITEDOC" dbkey="PDOC00100"/>). Regions with
significant homology [<cite idref="PUB00002925"/>] to the C2-domain have been found in many proteins.
The C2 domain is thought to be involved in calcium-dependent phospholipid
binding [<cite idref="PUB00002815"/>] and in membrane targetting processes such as subcellular localisation. <p>The 3D structure of the
C2 domain of synaptotagmin has been reported
[<cite idref="PUB00000918"/>], the domain forms an eight-stranded beta sandwich constructed around a
conserved 4-stranded motif, designated a C2 key [<cite idref="PUB00000918"/>]. Calcium binds in
a cup-shaped depression formed by the N- and C-terminal loops of the
C2-key motif. Structural analyses of several C2 domains have shown them to consist of similar ternary structures in which three Ca<sup>2+</sup>-binding loops are located at the end of an 8 stranded antiparallel beta sandwich. </p>
</abstract>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="A0FGR8"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P11792"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P27715"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P28867"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q9VVI3"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00000918">
<author_list>Sutton RB, Davletov BA, Berghuis AM, Sudhof TC, Sprang SR.</author_list>
<title>Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold.</title>
<db_xref db="PUBMED" dbkey="7697723"/>
<journal>Cell</journal>
<location issue="6" pages="929-38" volume="80"/>
<year>1995</year>
</publication>
<publication id="PUB00002815">
<author_list>Davletov BA, Sudhof TC.</author_list>
<title>A single C2 domain from synaptotagmin I is sufficient for high affinity Ca2+/phospholipid binding.</title>
<db_xref db="PUBMED" dbkey="8253763"/>
<journal>J. Biol. Chem.</journal>
<location issue="35" pages="26386-90" volume="268"/>
<year>1993</year>
</publication>
<publication id="PUB00002925">
<author_list>Brose N, Hofmann K, Hata Y, Sudhof TC.</author_list>
<title>Mammalian homologues of Caenorhabditis elegans unc-13 gene define novel family of C2-domain proteins.</title>
<db_xref db="PUBMED" dbkey="7559667"/>
<journal>J. Biol. Chem.</journal>
<location issue="42" pages="25273-80" volume="270"/>
<year>1995</year>
</publication>
</pub_list>
<parent_list>
<rel_ref ipr_ref="IPR008973"/>
</parent_list>
<child_list>
<rel_ref ipr_ref="IPR018029"/>
</child_list>
<contains>
<rel_ref ipr_ref="IPR001565"/>
<rel_ref ipr_ref="IPR020477"/>
</contains>
<found_in>
<rel_ref ipr_ref="IPR001192"/>
<rel_ref ipr_ref="IPR011402"/>
<rel_ref ipr_ref="IPR014375"/>
<rel_ref ipr_ref="IPR014376"/>
<rel_ref ipr_ref="IPR014638"/>
<rel_ref ipr_ref="IPR014705"/>
<rel_ref ipr_ref="IPR015427"/>
<rel_ref ipr_ref="IPR015428"/>
<rel_ref ipr_ref="IPR016279"/>
<rel_ref ipr_ref="IPR016280"/>
<rel_ref ipr_ref="IPR017147"/>
</found_in>
<member_list>
<db_xref protein_count="5145" db="PFAM" dbkey="PF00168" name="C2"/>
<db_xref protein_count="5888" db="SMART" dbkey="SM00239" name="C2"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00168"/>
<db_xref db="BLOCKS" dbkey="IPB000008"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00380"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1a25"/>
<db_xref db="PDB" dbkey="1bci"/>
<db_xref db="PDB" dbkey="1bdy"/>
<db_xref db="PDB" dbkey="1byn"/>
<db_xref db="PDB" dbkey="1cjy"/>
<db_xref db="PDB" dbkey="1djg"/>
<db_xref db="PDB" dbkey="1djh"/>
<db_xref db="PDB" dbkey="1dji"/>
<db_xref db="PDB" dbkey="1djw"/>
<db_xref db="PDB" dbkey="1djx"/>
<db_xref db="PDB" dbkey="1djy"/>
<db_xref db="PDB" dbkey="1djz"/>
<db_xref db="PDB" dbkey="1dqv"/>
<db_xref db="PDB" dbkey="1dsy"/>
<db_xref db="PDB" dbkey="1gmi"/>
<db_xref db="PDB" dbkey="1k5w"/>
<db_xref db="PDB" dbkey="1qas"/>
<db_xref db="PDB" dbkey="1qat"/>
<db_xref db="PDB" dbkey="1rh8"/>
<db_xref db="PDB" dbkey="1rlw"/>
<db_xref db="PDB" dbkey="1rsy"/>
<db_xref db="PDB" dbkey="1tjm"/>
<db_xref db="PDB" dbkey="1tjx"/>
<db_xref db="PDB" dbkey="1ugk"/>
<db_xref db="PDB" dbkey="1uov"/>
<db_xref db="PDB" dbkey="1uow"/>
<db_xref db="PDB" dbkey="1v27"/>
<db_xref db="PDB" dbkey="1w15"/>
<db_xref db="PDB" dbkey="1w16"/>
<db_xref db="PDB" dbkey="1wfj"/>
<db_xref db="PDB" dbkey="1wfm"/>
<db_xref db="PDB" dbkey="1yrk"/>
<db_xref db="PDB" dbkey="2bwq"/>
<db_xref db="PDB" dbkey="2chd"/>
<db_xref db="PDB" dbkey="2cjs"/>
<db_xref db="PDB" dbkey="2cjt"/>
<db_xref db="PDB" dbkey="2cm5"/>
<db_xref db="PDB" dbkey="2cm6"/>
<db_xref db="PDB" dbkey="2d8k"/>
<db_xref db="PDB" dbkey="2enp"/>
<db_xref db="PDB" dbkey="2ep6"/>
<db_xref db="PDB" dbkey="2fju"/>
<db_xref db="PDB" dbkey="2fk9"/>
<db_xref db="PDB" dbkey="2isd"/>
<db_xref db="PDB" dbkey="2k3h"/>
<db_xref db="PDB" dbkey="2nq3"/>
<db_xref db="PDB" dbkey="2nsq"/>
<db_xref db="PDB" dbkey="2r83"/>
<db_xref db="PDB" dbkey="2rd0"/>
<db_xref db="PDB" dbkey="2uzp"/>
<db_xref db="PDB" dbkey="2yrb"/>
<db_xref db="PDB" dbkey="2zkm"/>
<db_xref db="PDB" dbkey="3bxj"/>
<db_xref db="PDB" dbkey="3fdw"/>
<db_xref db="PDB" dbkey="3rpb"/>
<db_xref db="CATH" dbkey="2.20.170.10"/>
<db_xref db="CATH" dbkey="2.60.40.150"/>
<db_xref db="SCOP" dbkey="b.7.1.1"/>
<db_xref db="SCOP" dbkey="b.7.1.2"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="3"/>
<taxon_data name="Cyanobacteria" proteins_count="1"/>
<taxon_data name="Eukaryota" proteins_count="5994"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="161"/>
<taxon_data name="Rice spp." proteins_count="274"/>
<taxon_data name="Fungi" proteins_count="816"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="68"/>
<taxon_data name="Other Eukaryotes" proteins_count="57"/>
<taxon_data name="Other Eukaryotes" proteins_count="82"/>
<taxon_data name="Nematoda" proteins_count="76"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="76"/>
<taxon_data name="Arthropoda" proteins_count="839"/>
<taxon_data name="Fruit Fly" proteins_count="132"/>
<taxon_data name="Chordata" proteins_count="1924"/>
<taxon_data name="Human" proteins_count="436"/>
<taxon_data name="Mouse" proteins_count="371"/>
<taxon_data name="Virus" proteins_count="1"/>
<taxon_data name="Other Eukaryotes" proteins_count="54"/>
<taxon_data name="Plastid Group" proteins_count="1230"/>
<taxon_data name="Green Plants" proteins_count="1230"/>
<taxon_data name="Metazoa" proteins_count="4034"/>
<taxon_data name="Plastid Group" proteins_count="243"/>
<taxon_data name="Plastid Group" proteins_count="109"/>
<taxon_data name="Other Eukaryotes" proteins_count="84"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR018029"/>
</sec_list>
</interpro>
<interpro id="IPR000009" protein_count="339" short_name="PP2A_PR55" type="Family">
<name>Protein phosphatase 2A, regulatory subunit PR55</name>
<abstract>
Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase implicated
in many cellular processes, including the regulation of metabolic enzymes
and proteins involved in signal transduction [<cite idref="PUB00000344"/>, <cite idref="PUB00003499"/>]. PP2A is a trimer
composed of a 36 kDa catalytic subunit, a 65 kDa regulatory subunit
(subunit A) and a variable third subunit (subunit B) [<cite idref="PUB00000344"/>, <cite idref="PUB00003499"/>].
<p>One form of the third subunit is a 55 kDa protein (PR55), which exists in
<taxon tax_id="7227">Drosophila melanogaster</taxon> and yeast, and has up to three forms in mammals [<cite idref="PUB00000344"/>, <cite idref="PUB00003499"/>]. PR55 may act
as a substrate recognition unit, or may help to target the enzyme to the
correct subcellular location [<cite idref="PUB00000344"/>].</p>
</abstract>
<class_list>
<classification id="GO:0000159" class_type="GO">
<category>Cellular Component</category>
<description>protein phosphatase type 2A complex</description>
</classification>
<classification id="GO:0007165" class_type="GO">
<category>Biological Process</category>
<description>signal transduction</description>
</classification>
<classification id="GO:0008601" class_type="GO">
<category>Molecular Function</category>
<description>protein phosphatase type 2A regulator activity</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P36872"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P63151"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q00362"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q38821"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q6P1F6"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00000344">
<author_list>Mayer RE, Hendrix P, Cron P, Matthies R, Stone SR, Goris J, Merlevede W, Hofsteenge J, Hemmings BA.</author_list>
<title>Structure of the 55-kDa regulatory subunit of protein phosphatase 2A: evidence for a neuronal-specific isoform.</title>
<db_xref db="PUBMED" dbkey="1849734"/>
<journal>Biochemistry</journal>
<location issue="15" pages="3589-97" volume="30"/>
<year>1991</year>
</publication>
<publication id="PUB00003499">
<author_list>Pallas DC, Weller W, Jaspers S, Miller TB, Lane WS, Roberts TM.</author_list>
<title>The third subunit of protein phosphatase 2A (PP2A), a 55-kilodalton protein which is apparently substituted for by T antigens in complexes with the 36- and 63-kilodalton PP2A subunits, bears little resemblance to T antigens.</title>
<db_xref db="PUBMED" dbkey="1370560"/>
<journal>J. Virol.</journal>
<location issue="2" pages="886-93" volume="66"/>
<year>1992</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR001680"/>
<rel_ref ipr_ref="IPR011046"/>
<rel_ref ipr_ref="IPR018067"/>
<rel_ref ipr_ref="IPR019775"/>
<rel_ref ipr_ref="IPR019781"/>
</contains>
<member_list>
<db_xref protein_count="326" db="PANTHER" dbkey="PTHR11871" name="Pp2A_PR55"/>
<db_xref protein_count="224" db="PIRSF" dbkey="PIRSF037309" name="PP2A_PR55"/>
<db_xref protein_count="332" db="PRINTS" dbkey="PR00600" name="PP2APR55"/>
</member_list>
<external_doc_list>
<db_xref db="MSDsite" dbkey="PS01024"/>
<db_xref db="MSDsite" dbkey="PS01025"/>
<db_xref db="BLOCKS" dbkey="IPB000009"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00785"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="2"/>
<taxon_data name="Cyanobacteria" proteins_count="1"/>
<taxon_data name="Eukaryota" proteins_count="337"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="5"/>
<taxon_data name="Rice spp." proteins_count="15"/>
<taxon_data name="Fungi" proteins_count="73"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="6"/>
<taxon_data name="Other Eukaryotes" proteins_count="3"/>
<taxon_data name="Other Eukaryotes" proteins_count="1"/>
<taxon_data name="Nematoda" proteins_count="1"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="1"/>
<taxon_data name="Arthropoda" proteins_count="77"/>
<taxon_data name="Fruit Fly" proteins_count="2"/>
<taxon_data name="Chordata" proteins_count="76"/>
<taxon_data name="Human" proteins_count="18"/>
<taxon_data name="Mouse" proteins_count="10"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
<taxon_data name="Plastid Group" proteins_count="59"/>
<taxon_data name="Green Plants" proteins_count="59"/>
<taxon_data name="Metazoa" proteins_count="243"/>
<taxon_data name="Plastid Group" proteins_count="4"/>
<taxon_data name="Plastid Group" proteins_count="14"/>
<taxon_data name="Other Eukaryotes" proteins_count="6"/>
<taxon_data name="Other Eukaryotes" proteins_count="4"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000010" protein_count="956" short_name="Prot_inh_cystat" type="Domain">
<name>Proteinase inhibitor I25, cystatin</name>
<abstract>
<p>Peptide proteinase inhibitors can be found as single domain proteins or as single or multiple domains within proteins; these are referred to as either simple or compound inhibitors, respectively. In many cases they are synthesised as part of a larger precursor protein, either as a prepropeptide or as an N-terminal domain associated with an inactive peptidase or zymogen. This domain prevents access of the substrate to the active site. Removal of the N-terminal inhibitor domain either by interaction with a second peptidase or by autocatalytic cleavage activates the zymogen. Other inhibitors interact direct with proteinases using a simple noncovalent lock and key mechanism; while yet others use a conformational change-based trapping mechanism that depends on their structural and thermodynamic properties. </p>
<p>The cystatins are cysteine proteinase inhibitors belonging to MEROPS inhibitor family I25, clan IH [<cite idref="PUB00003412"/>, <cite idref="PUB00014312"/>, <cite idref="PUB00001614"/>]. They mainly inhibit peptidases belonging to peptidase families C1 (papain family) and C13 (legumain family). The cystatin family includes:</p>
<ul>
<li>
The Type 1 cystatins, which are intracellular cystatins that are present in the cytosol of many cell types, but can also appear in body fluids at significant concentrations. They are single-chain polypeptides of about 100 residues, which have neither disulphide bonds nor carbohydrate side chains. </li>
<li>The Type 2 cystatins, which are mainly extracellular secreted polypeptides synthesised with a 19-28 residue signal peptide. They are broadly distributed and found in most body fluids. </li>
<li>The Type 3 cystatins, which are multidomain proteins. The mammalian representatives of this group are the kininogens. There are three different kininogens in mammals: H- (high molecular mass, <db_xref db="INTERPRO" dbkey="IPR002395"/>) and L- (low molecular mass) kininogen which are found in a number of species, and T-kininogen that is found only in rat. </li>
<li>Unclassified cystatins. These are cystatin-like proteins found in a range of organisms: plant phytocystatins, fetuin in mammals, insect cystatins and a puff adder venom cystatin which inhibits metalloproteases of the MEROPS peptidase family M12 (astacin/adamalysin). Also a number of the cystatins-like proteins have been shown to be devoid of inhibitory activity. </li>
</ul>
<p>All true cystatins inhibit cysteine peptidases of the papain family (MEROPS peptidase family C1), and some also inhibit legumain family enzymes (MEROPS peptidase family C13). These peptidases play key roles in physiological processes, such as intracellular protein degradation (cathepsins B, H and L), are pivotal in the remodelling of bone (cathepsin K), and may be important in the control of antigen presentation (cathepsin S, mammalian legumain). Moreover, the activities of such peptidases are increased in pathophysiological conditions, such as cancer metastasis and inflammation. Additionally, such peptidases are essential for several pathogenic parasites and bacteria. Thus in animals cystatins not only have capacity to regulate normal body processes and perhaps cause disease when down-regulated, but in other organisms may also participate in defence against biotic and abiotic stress. </p>
</abstract>
<class_list>
<classification id="GO:0004869" class_type="GO">
<category>Molecular Function</category>
<description>cysteine-type endopeptidase inhibitor activity</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O08677"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="O76096"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P09229"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P23779"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q41906"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00001614">
<author_list>Turk V, Bode W.</author_list>
<title>The cystatins: protein inhibitors of cysteine proteinases.</title>
<db_xref db="PUBMED" dbkey="1855589"/>
<journal>FEBS Lett.</journal>
<location issue="2" pages="213-9" volume="285"/>
<year>1991</year>
</publication>
<publication id="PUB00003412">
<author_list>Rawlings ND, Barrett AJ.</author_list>
<title>Evolution of proteins of the cystatin superfamily.</title>
<db_xref db="PUBMED" dbkey="2107324"/>
<journal>J. Mol. Evol.</journal>
<location issue="1" pages="60-71" volume="30"/>
<year>1990</year>
</publication>
<publication id="PUB00014312">
<author_list>Abrahamson M, Alvarez-Fernandez M, Nathanson CM.</author_list>
<title>Cystatins.</title>
<db_xref db="PUBMED" dbkey="14587292"/>
<journal>Biochem. Soc. Symp.</journal>
<location issue="70" pages="179-99"/>
<year>2003</year>
</publication>
</pub_list>
<child_list>
<rel_ref ipr_ref="IPR001713"/>
</child_list>
<contains>
<rel_ref ipr_ref="IPR001363"/>
<rel_ref ipr_ref="IPR018073"/>
<rel_ref ipr_ref="IPR020381"/>
</contains>
<member_list>
<db_xref protein_count="937" db="PFAM" dbkey="PF00031" name="Cystatin"/>
<db_xref protein_count="845" db="SMART" dbkey="SM00043" name="CY"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00031"/>
<db_xref db="MSDsite" dbkey="PS00287"/>
<db_xref db="BLOCKS" dbkey="IPB000010"/>
<db_xref db="MEROPS" dbkey="C1"/>
<db_xref db="MEROPS" dbkey="C13"/>
<db_xref db="MEROPS" dbkey="I25"/>
<db_xref db="MEROPS" dbkey="M10"/>
<db_xref db="MEROPS" dbkey="M12"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00259"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1a67"/>
<db_xref db="PDB" dbkey="1a90"/>
<db_xref db="PDB" dbkey="1cew"/>
<db_xref db="PDB" dbkey="1cyu"/>
<db_xref db="PDB" dbkey="1cyv"/>
<db_xref db="PDB" dbkey="1dvc"/>
<db_xref db="PDB" dbkey="1dvd"/>
<db_xref db="PDB" dbkey="1eqk"/>
<db_xref db="PDB" dbkey="1g96"/>
<db_xref db="PDB" dbkey="1gd3"/>
<db_xref db="PDB" dbkey="1gd4"/>
<db_xref db="PDB" dbkey="1n9j"/>
<db_xref db="PDB" dbkey="1nb3"/>
<db_xref db="PDB" dbkey="1nb5"/>
<db_xref db="PDB" dbkey="1r4c"/>
<db_xref db="PDB" dbkey="1rn7"/>
<db_xref db="PDB" dbkey="1roa"/>
<db_xref db="PDB" dbkey="1stf"/>
<db_xref db="PDB" dbkey="1tij"/>
<db_xref db="PDB" dbkey="1yvb"/>
<db_xref db="CATH" dbkey="3.10.450.10"/>
<db_xref db="SCOP" dbkey="d.17.1.2"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="39"/>
<taxon_data name="Eukaryota" proteins_count="873"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="11"/>
<taxon_data name="Rice spp." proteins_count="35"/>
<taxon_data name="Other Eukaryotes" proteins_count="3"/>
<taxon_data name="Other Eukaryotes" proteins_count="3"/>
<taxon_data name="Nematoda" proteins_count="3"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="3"/>
<taxon_data name="Arthropoda" proteins_count="122"/>
<taxon_data name="Fruit Fly" proteins_count="6"/>
<taxon_data name="Chordata" proteins_count="376"/>
<taxon_data name="Human" proteins_count="40"/>
<taxon_data name="Mouse" proteins_count="69"/>
<taxon_data name="Virus" proteins_count="44"/>
<taxon_data name="Plastid Group" proteins_count="305"/>
<taxon_data name="Green Plants" proteins_count="305"/>
<taxon_data name="Metazoa" proteins_count="546"/>
<taxon_data name="Plastid Group" proteins_count="11"/>
<taxon_data name="Other Eukaryotes" proteins_count="4"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR001713"/>
</sec_list>
</interpro>
<interpro id="IPR000011" protein_count="359" short_name="UBQ-activ_enz_E1-like" type="Region">
<name>Ubiquitin-activating enzyme, E1-like</name>
<abstract>
<p>The post-translational attachment of ubiquitin (<db_xref db="INTERPRO" dbkey="IPR000626"/>) to proteins (ubiquitinylation) alters the function, location or trafficking of a protein, or targets it to the 26S proteasome for degradation [<cite idref="PUB00015621"/>, <cite idref="PUB00015619"/>, <cite idref="PUB00015625"/>]. Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2, <db_xref db="INTERPRO" dbkey="IPR000608"/>), and a ubiquitin ligase (E3, <db_xref db="INTERPRO" dbkey="IPR000569"/>, <db_xref db="INTERPRO" dbkey="IPR003613"/>), which work sequentially in a cascade [<cite idref="PUB00015620"/>]. The E1 enzyme is responsible for activating ubiquitin, the first step in ubiquitinylation. The E1 enzyme hydrolyses ATP and adenylates the C-terminal glycine residue of ubiquitin, and then links this residue to the active site cysteine of E1, yielding a ubiquitin-thioester and free AMP. To be fully active, E1 must non-covalently bind to and adenylate a second ubiquitin molecule. The E1 enzyme can then transfer the thioester-linked ubiquitin molecule to a cysteine residue on the ubiquitin-conjugating enzyme, E2, in an ATP-dependent reaction.</p>
</abstract>
<class_list>
<classification id="GO:0006464" class_type="GO">
<category>Biological Process</category>
<description>protein modification process</description>
</classification>
<classification id="GO:0008641" class_type="GO">
<category>Molecular Function</category>
<description>small protein activating enzyme activity</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="A2VE14"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="O42939"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P22515"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q02053"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q9UBE0"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00015619">
<author_list>Burger AM, Seth AK.</author_list>
<title>The ubiquitin-mediated protein degradation pathway in cancer: therapeutic implications.</title>
<db_xref db="PUBMED" dbkey="15454246"/>
<journal>Eur. J. Cancer</journal>
<location issue="15" pages="2217-29" volume="40"/>
<year>2004</year>
</publication>
<publication id="PUB00015620">
<author_list>Passmore LA, Barford D.</author_list>
<title>Getting into position: the catalytic mechanisms of protein ubiquitylation.</title>
<db_xref db="PUBMED" dbkey="14998368"/>
<journal>Biochem. J.</journal>
<location issue="Pt 3" pages="513-25" volume="379"/>
<year>2004</year>
</publication>
<publication id="PUB00015621">
<author_list>Pickart CM, Fushman D.</author_list>
<title>Polyubiquitin chains: polymeric protein signals.</title>
<db_xref db="PUBMED" dbkey="15556404"/>
<location issue="6" pages="610-6" volume="8"/>
<year>2004</year>
</publication>
<publication id="PUB00015625">
<author_list>Sun L, Chen ZJ.</author_list>
<title>The novel functions of ubiquitination in signaling.</title>
<db_xref db="PUBMED" dbkey="15196553"/>
<journal>Curr. Opin. Cell Biol.</journal>
<location issue="2" pages="119-26" volume="16"/>
<year>2004</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR000594"/>
<rel_ref ipr_ref="IPR009036"/>
<rel_ref ipr_ref="IPR018074"/>
<rel_ref ipr_ref="IPR019572"/>
</contains>
<found_in>
<rel_ref ipr_ref="IPR018075"/>
</found_in>
<member_list>
<db_xref protein_count="359" db="PRINTS" dbkey="PR01849" name="UBIQUITINACT"/>
</member_list>
<external_doc_list>
<db_xref db="MSDsite" dbkey="PS00536"/>
<db_xref db="MSDsite" dbkey="PS00865"/>
<db_xref db="BLOCKS" dbkey="IPB000011"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00463"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1y8q"/>
<db_xref db="PDB" dbkey="1y8r"/>
<db_xref db="CATH" dbkey="3.40.50.720"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Eukaryota" proteins_count="359"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="6"/>
<taxon_data name="Rice spp." proteins_count="13"/>
<taxon_data name="Fungi" proteins_count="110"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="6"/>
<taxon_data name="Other Eukaryotes" proteins_count="6"/>
<taxon_data name="Other Eukaryotes" proteins_count="5"/>
<taxon_data name="Nematoda" proteins_count="3"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="3"/>
<taxon_data name="Arthropoda" proteins_count="43"/>
<taxon_data name="Fruit Fly" proteins_count="9"/>
<taxon_data name="Chordata" proteins_count="55"/>
<taxon_data name="Human" proteins_count="10"/>
<taxon_data name="Mouse" proteins_count="10"/>
<taxon_data name="Other Eukaryotes" proteins_count="4"/>
<taxon_data name="Plastid Group" proteins_count="50"/>
<taxon_data name="Green Plants" proteins_count="50"/>
<taxon_data name="Metazoa" proteins_count="225"/>
<taxon_data name="Plastid Group" proteins_count="38"/>
<taxon_data name="Plastid Group" proteins_count="14"/>
<taxon_data name="Other Eukaryotes" proteins_count="6"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000012" protein_count="3972" short_name="RetroV_VpR/X" type="Family">
<name>Retroviral VpR/VpX protein</name>
<abstract>
<taxon tax_id="12721">Human immunodeficiency virus</taxon> (HIV) is the human retrovirus associated with AIDS (acquired immune deficiency syndrome), and SIV its simian counterpart. Three main groups of primate lentivirus are known, designated <taxon tax_id="11676">Human immunodeficiency virus 1</taxon> (HIV-1), <taxon tax_id="11709">Human immunodeficiency virus 2</taxon> (HIV-2)/<taxon tax_id="11711">Simian immunodeficiency virus - mac</taxon> (SIVMAC)/<taxon tax_id="11712">Simian immunodeficiency virus - sm</taxon> (SIVSM) and <taxon tax_id="11726">Simian immunodeficiency virus - agm</taxon> (SIVAGM). <taxon tax_id="12830">Simian immunodeficiency virus - mnd</taxon> (SIVMND) has been suggested to represent a fourth distinct group [<cite idref="PUB00004048"/>]. These groups are believed to have diverged from a common ancestor long before the spread of AIDS in humans. Genetic variation in HIV-1 and HIV-2 has been studied extensively, and the nucleotide sequences reported for several strains [<cite idref="PUB00000018"/>].<p> ORF analysis has revealed two open reading frames, yielding the so-called R- and X-ORF proteins, whose functions are unknown, but which show a high degree of sequence similarity.</p>
</abstract>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P05954"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00000018">
<author_list>Hasegawa A, Tsujimoto H, Maki N, Ishikawa K, Miura T, Fukasawa M, Miki K, Hayami M.</author_list>
<title>Genomic divergence of HIV-2 from Ghana.</title>
<db_xref db="PUBMED" dbkey="2611042"/>
<journal>AIDS Res. Hum. Retroviruses</journal>
<location issue="6" pages="593-604" volume="5"/>
<year>1989</year>
</publication>
<publication id="PUB00004048">
<author_list>Tsujimoto H, Hasegawa A, Maki N, Fukasawa M, Miura T, Speidel S, Cooper RW, Moriyama EN, Gojobori T, Hayami M.</author_list>
<title>Sequence of a novel simian immunodeficiency virus from a wild-caught African mandrill.</title>
<db_xref db="PUBMED" dbkey="2797181"/>
<journal>Nature</journal>
<location issue="6242" pages="539-41" volume="341"/>
<year>1989</year>
</publication>
</pub_list>
<member_list>
<db_xref protein_count="3972" db="PFAM" dbkey="PF00522" name="VPR"/>
<db_xref protein_count="3833" db="PRINTS" dbkey="PR00444" name="HIVVPRVPX"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00522"/>
<db_xref db="BLOCKS" dbkey="IPB000012"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1bde"/>
<db_xref db="PDB" dbkey="1ceu"/>
<db_xref db="PDB" dbkey="1dsj"/>
<db_xref db="PDB" dbkey="1dsk"/>
<db_xref db="PDB" dbkey="1esx"/>
<db_xref db="PDB" dbkey="1fi0"/>
<db_xref db="PDB" dbkey="1kzs"/>
<db_xref db="PDB" dbkey="1kzt"/>
<db_xref db="PDB" dbkey="1kzv"/>
<db_xref db="PDB" dbkey="1m8l"/>
<db_xref db="PDB" dbkey="1vpc"/>
<db_xref db="PDB" dbkey="1x9v"/>
<db_xref db="CATH" dbkey="1.10.1690.10"/>
<db_xref db="CATH" dbkey="1.20.5.90"/>
<db_xref db="SCOP" dbkey="j.11.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Virus" proteins_count="3972"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000013" protein_count="41" short_name="Peptidase_M7" type="Family">
<name>Peptidase M7, snapalysin</name>
<abstract>
<p>In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:</p>
<ul>
<li>Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.</li>
<li>Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule.</li>
</ul>
<p>In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding. </p>
<p>Metalloproteases are the most diverse of the four main types of protease, with more than 50 families identified to date. In these enzymes, a divalent cation, usually zinc, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. The known metal ligands are His, Glu, Asp or Lys and at least one other residue is required for catalysis, which may play an electrophillic role.
Of the known metalloproteases, around half contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site [<cite idref="PUB00003579"/>]. The HEXXH motif is relatively common, but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases [<cite idref="PUB00003579"/>].</p>
<p>This group of metallopeptidases belong to the MEROPS peptidase family M7 (snapalysin family, clan MA(M)). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA.</p>
<p>With a molecular weight of around 16kDa, Streptomyces extracellular neutral protease is one of the smallest known proteases [<cite idref="PUB00003579"/>]; it is capable of hydrolysing milk proteins [<cite idref="PUB00003579"/>]. The enzyme is synthesised as a proenzyme with a signal peptide, a propeptide and an active domain that contains the conserved HEXXH motif characteristic of metalloproteases. Although family M7 shows active site sequence similarity to other members, it differs in one major respect: the third zinc ligand appears to be an aspartate residue rather than the usual histidine.</p>
</abstract>
<class_list>
<classification id="GO:0004222" class_type="GO">
<category>Molecular Function</category>
<description>metalloendopeptidase activity</description>
</classification>
<classification id="GO:0005576" class_type="GO">
<category>Cellular Component</category>
<description>extracellular region</description>
</classification>
<classification id="GO:0006508" class_type="GO">
<category>Biological Process</category>
<description>proteolysis</description>
</classification>
<classification id="GO:0008270" class_type="GO">
<category>Molecular Function</category>
<description>zinc ion binding</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P56406"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00003579">
<author_list>Rawlings ND, Barrett AJ.</author_list>
<title>Evolutionary families of metallopeptidases.</title>
<db_xref db="PUBMED" dbkey="7674922"/>
<journal>Meth. Enzymol.</journal>
<location pages="183-228" volume="248"/>
<year>1995</year>
</publication>
</pub_list>
<member_list>
<db_xref protein_count="41" db="PFAM" dbkey="PF02031" name="Peptidase_M7"/>
<db_xref protein_count="34" db="PIRSF" dbkey="PIRSF016573" name="Peptidase_M7"/>
<db_xref protein_count="39" db="PRINTS" dbkey="PR00787" name="NEUTRALPTASE"/>
<db_xref protein_count="38" db="PRODOM" dbkey="PD016028" name="Peptidase_M7"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF02031"/>
<db_xref db="BLOCKS" dbkey="IPB000013"/>
<db_xref db="EC" dbkey="3.4.24.77"/>
<db_xref db="MEROPS" dbkey="M7"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1c7k"/>
<db_xref db="PDB" dbkey="1kuh"/>
<db_xref db="CATH" dbkey="3.40.390.10"/>
<db_xref db="SCOP" dbkey="d.92.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="41"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000014" protein_count="31843" short_name="PAS" type="Domain">
<name>PAS</name>
<abstract>
<p>PAS domains are involved in many signalling proteins where they
are used as a signal sensor domain. PAS domains appear in archaea,
bacteria and eukaryotes. Several PAS-domain proteins are known to
detect their signal by way of an associated cofactor. Haeme,
flavin, and a 4-hydroxycinnamyl chromophore are used in different
proteins. The PAS domain was named after three proteins that it
occurs in: </p>
<li>Per- period circadian protein</li>
<li>Arnt- Ah receptor nuclear translocator protein</li>
<li>Sim- single-minded protein.</li>
<p>PAS domains are often associated with
PAC domains <db_xref db="INTERPRO" dbkey="IPR001610"/>. It appears that these domains are directly linked, and that together they form the conserved 3D PAS fold. The division between the PAS and PAC domains is caused by major differences in sequences in the region connecting these two motifs [<cite idref="PUB00014500"/>]. In human PAS kinase, this region has been shown to be very flexible, and adopts different conformations depending on the bound ligand [<cite idref="PUB00014501"/>].
Probably the most surprising identification of a PAS domain was that in
EAG-like K<sup>+</sup>-channels [<cite idref="PUB00005472"/>].</p>
</abstract>
<class_list>
<classification id="GO:0004871" class_type="GO">
<category>Molecular Function</category>
<description>signal transducer activity</description>
</classification>
<classification id="GO:0007165" class_type="GO">
<category>Biological Process</category>
<description>signal transduction</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O44712"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="O54943"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="O60658"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P07663"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P19541"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00005472">
<author_list>Zhulin IB, Taylor BL, Dixon R.</author_list>
<title>PAS domain S-boxes in Archaea, Bacteria and sensors for oxygen and redox.</title>
<db_xref db="PUBMED" dbkey="9301332"/>
<journal>Trends Biochem. Sci.</journal>
<location issue="9" pages="331-3" volume="22"/>
<year>1997</year>
</publication>
<publication id="PUB00014500">
<author_list>Hefti MH, Francoijs KJ, de Vries SC, Dixon R, Vervoort J.</author_list>
<title>The PAS fold. A redefinition of the PAS domain based upon structural prediction.</title>
<db_xref db="PUBMED" dbkey="15009198"/>
<journal>Eur. J. Biochem.</journal>
<location issue="6" pages="1198-208" volume="271"/>
<year>2004</year>
</publication>
<publication id="PUB00014501">
<author_list>Amezcua CA, Harper SM, Rutter J, Gardner KH.</author_list>
<title>Structure and interactions of PAS kinase N-terminal PAS domain: model for intramolecular kinase regulation.</title>
<db_xref db="PUBMED" dbkey="12377121"/>
<journal>Structure</journal>
<location issue="10" pages="1349-61" volume="10"/>
<year>2002</year>
</publication>
</pub_list>
<child_list>
<rel_ref ipr_ref="IPR013655"/>
<rel_ref ipr_ref="IPR013656"/>
<rel_ref ipr_ref="IPR013767"/>
</child_list>
<found_in>
<rel_ref ipr_ref="IPR001294"/>
<rel_ref ipr_ref="IPR001321"/>
<rel_ref ipr_ref="IPR003949"/>
<rel_ref ipr_ref="IPR003950"/>
<rel_ref ipr_ref="IPR011785"/>
<rel_ref ipr_ref="IPR012129"/>
<rel_ref ipr_ref="IPR012130"/>
<rel_ref ipr_ref="IPR012226"/>
<rel_ref ipr_ref="IPR012704"/>
<rel_ref ipr_ref="IPR014285"/>
<rel_ref ipr_ref="IPR014310"/>
<rel_ref ipr_ref="IPR014409"/>
<rel_ref ipr_ref="IPR015524"/>
<rel_ref ipr_ref="IPR017181"/>
<rel_ref ipr_ref="IPR017232"/>
</found_in>
<member_list>
<db_xref protein_count="21263" db="PROFILE" dbkey="PS50112" name="PAS"/>
<db_xref protein_count="30445" db="SMART" dbkey="SM00091" name="PAS"/>
<db_xref protein_count="21449" db="TIGRFAMs" dbkey="TIGR00229" name="sensory_box"/>
</member_list>
<external_doc_list>
<db_xref db="BLOCKS" dbkey="IPB000014"/>
<db_xref db="PROSITEDOC" dbkey="PDOC50112"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1byw"/>
<db_xref db="PDB" dbkey="1d06"/>
<db_xref db="PDB" dbkey="1d7e"/>
<db_xref db="PDB" dbkey="1dp6"/>
<db_xref db="PDB" dbkey="1dp8"/>
<db_xref db="PDB" dbkey="1dp9"/>
<db_xref db="PDB" dbkey="1drm"/>
<db_xref db="PDB" dbkey="1ew0"/>
<db_xref db="PDB" dbkey="1f98"/>
<db_xref db="PDB" dbkey="1f9i"/>
<db_xref db="PDB" dbkey="1g28"/>
<db_xref db="PDB" dbkey="1gsv"/>
<db_xref db="PDB" dbkey="1gsw"/>
<db_xref db="PDB" dbkey="1gsx"/>
<db_xref db="PDB" dbkey="1jnu"/>
<db_xref db="PDB" dbkey="1kou"/>
<db_xref db="PDB" dbkey="1ll8"/>
<db_xref db="PDB" dbkey="1lsv"/>
<db_xref db="PDB" dbkey="1lsw"/>
<db_xref db="PDB" dbkey="1lsx"/>
<db_xref db="PDB" dbkey="1lt0"/>
<db_xref db="PDB" dbkey="1mzu"/>
<db_xref db="PDB" dbkey="1n9l"/>
<db_xref db="PDB" dbkey="1n9n"/>
<db_xref db="PDB" dbkey="1n9o"/>
<db_xref db="PDB" dbkey="1nwz"/>
<db_xref db="PDB" dbkey="1odv"/>
<db_xref db="PDB" dbkey="1ot6"/>
<db_xref db="PDB" dbkey="1ot9"/>
<db_xref db="PDB" dbkey="1ota"/>
<db_xref db="PDB" dbkey="1otb"/>
<db_xref db="PDB" dbkey="1otd"/>
<db_xref db="PDB" dbkey="1ote"/>
<db_xref db="PDB" dbkey="1oti"/>
<db_xref db="PDB" dbkey="1p97"/>
<db_xref db="PDB" dbkey="1s1y"/>
<db_xref db="PDB" dbkey="1s1z"/>
<db_xref db="PDB" dbkey="1s4r"/>
<db_xref db="PDB" dbkey="1s4s"/>
<db_xref db="PDB" dbkey="1s66"/>
<db_xref db="PDB" dbkey="1s67"/>
<db_xref db="PDB" dbkey="1t18"/>
<db_xref db="PDB" dbkey="1t19"/>
<db_xref db="PDB" dbkey="1t1a"/>
<db_xref db="PDB" dbkey="1t1b"/>
<db_xref db="PDB" dbkey="1t1c"/>
<db_xref db="PDB" dbkey="1ts0"/>
<db_xref db="PDB" dbkey="1ts6"/>
<db_xref db="PDB" dbkey="1ts7"/>
<db_xref db="PDB" dbkey="1ts8"/>
<db_xref db="PDB" dbkey="1ugu"/>
<db_xref db="PDB" dbkey="1uwn"/>
<db_xref db="PDB" dbkey="1uwp"/>
<db_xref db="PDB" dbkey="1v9y"/>
<db_xref db="PDB" dbkey="1v9z"/>
<db_xref db="PDB" dbkey="1vb6"/>
<db_xref db="PDB" dbkey="1wa9"/>
<db_xref db="PDB" dbkey="1xfn"/>
<db_xref db="PDB" dbkey="1xfq"/>
<db_xref db="PDB" dbkey="1xj2"/>
<db_xref db="PDB" dbkey="1xj3"/>
<db_xref db="PDB" dbkey="1xj4"/>
<db_xref db="PDB" dbkey="1xj6"/>
<db_xref db="PDB" dbkey="1y28"/>
<db_xref db="PDB" dbkey="1ztu"/>
<db_xref db="PDB" dbkey="2a24"/>
<db_xref db="PDB" dbkey="2cmn"/>
<db_xref db="PDB" dbkey="2d01"/>
<db_xref db="PDB" dbkey="2d02"/>
<db_xref db="PDB" dbkey="2i9v"/>
<db_xref db="PDB" dbkey="2o9b"/>
<db_xref db="PDB" dbkey="2o9c"/>
<db_xref db="PDB" dbkey="2ohh"/>
<db_xref db="PDB" dbkey="2ohi"/>
<db_xref db="PDB" dbkey="2ohj"/>
<db_xref db="PDB" dbkey="2owh"/>
<db_xref db="PDB" dbkey="2owj"/>
<db_xref db="PDB" dbkey="2phy"/>
<db_xref db="PDB" dbkey="2pyp"/>
<db_xref db="PDB" dbkey="2pyr"/>
<db_xref db="PDB" dbkey="2qj5"/>
<db_xref db="PDB" dbkey="2qj7"/>
<db_xref db="PDB" dbkey="2qws"/>
<db_xref db="PDB" dbkey="2r78"/>
<db_xref db="PDB" dbkey="2vea"/>
<db_xref db="PDB" dbkey="2vv6"/>
<db_xref db="PDB" dbkey="2vv7"/>
<db_xref db="PDB" dbkey="2vv8"/>
<db_xref db="PDB" dbkey="3b33"/>
<db_xref db="PDB" dbkey="3bwl"/>
<db_xref db="PDB" dbkey="3f1n"/>
<db_xref db="PDB" dbkey="3f1o"/>
<db_xref db="PDB" dbkey="3f1p"/>
<db_xref db="PDB" dbkey="3phy"/>
<db_xref db="PDB" dbkey="3pyp"/>
<db_xref db="CATH" dbkey="3.30.450.20"/>
<db_xref db="CATH" dbkey="3.60.15.10"/>
<db_xref db="SCOP" dbkey="d.110.3.1"/>
<db_xref db="SCOP" dbkey="d.110.3.2"/>
<db_xref db="SCOP" dbkey="d.110.3.5"/>
<db_xref db="SCOP" dbkey="d.110.3.6"/>
<db_xref db="SCOP" dbkey="d.110.3.7"/>
<db_xref db="SCOP" dbkey="d.110.3.9"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="27271"/>
<taxon_data name="Cyanobacteria" proteins_count="1122"/>
<taxon_data name="Synechocystis PCC 6803" proteins_count="33"/>
<taxon_data name="Archaea" proteins_count="997"/>
<taxon_data name="Eukaryota" proteins_count="3570"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="64"/>
<taxon_data name="Rice spp." proteins_count="44"/>
<taxon_data name="Fungi" proteins_count="548"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="23"/>
<taxon_data name="Other Eukaryotes" proteins_count="112"/>
<taxon_data name="Other Eukaryotes" proteins_count="82"/>
<taxon_data name="Nematoda" proteins_count="17"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="17"/>
<taxon_data name="Arthropoda" proteins_count="772"/>
<taxon_data name="Fruit Fly" proteins_count="39"/>
<taxon_data name="Chordata" proteins_count="848"/>
<taxon_data name="Human" proteins_count="110"/>
<taxon_data name="Mouse" proteins_count="109"/>
<taxon_data name="Virus" proteins_count="1"/>
<taxon_data name="Unclassified" proteins_count="3"/>
<taxon_data name="Unclassified" proteins_count="1"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
<taxon_data name="Plastid Group" proteins_count="892"/>
<taxon_data name="Green Plants" proteins_count="892"/>
<taxon_data name="Metazoa" proteins_count="2256"/>
<taxon_data name="Plastid Group" proteins_count="120"/>
<taxon_data name="Plastid Group" proteins_count="26"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
<taxon_data name="Other Eukaryotes" proteins_count="20"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR013655"/>
<sec_ac acc="IPR013656"/>
<sec_ac acc="IPR013767"/>
</sec_list>
</interpro>
<interpro id="IPR000015" protein_count="2173" short_name="Fimb_usher" type="Family">
<name>Fimbrial biogenesis outer membrane usher protein</name>
<abstract>
In Gram-negative bacteria the biogenesis of fimbriae (or pili) requires a two-
component assembly and transport system which is composed of a periplasmic
chaperone (see <db_xref db="PROSITEDOC" dbkey="PDOC00552"/>) and an outer membrane protein which has been
termed a molecular 'usher' [<cite idref="PUB00002841"/>, <cite idref="PUB00002237"/>, <cite idref="PUB00005083"/>]. <p>The usher protein is rather large (from 86 to
100 Kd) and seems to be mainly composed of membrane-spanning beta-sheets, a
structure reminiscent of porins.
Although the degree of sequence similarity of these proteins is not very high
they share a number of characteristics. One of these is the presence of two pairs
of cysteines, the first one located in the N-terminal part and the second
at the C-terminal extremity that are probably involved in disulphide bonds.
The best conserved region is located in the central part of these proteins.</p>
</abstract>
<class_list>
<classification id="GO:0005215" class_type="GO">
<category>Molecular Function</category>
<description>transporter activity</description>
</classification>
<classification id="GO:0006810" class_type="GO">
<category>Biological Process</category>
<description>transport</description>
</classification>
<classification id="GO:0016020" class_type="GO">
<category>Cellular Component</category>
<description>membrane</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P07110"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00002237">
<author_list>Schifferli DM, Alrutz MA.</author_list>
<title>Permissive linker insertion sites in the outer membrane protein of 987P fimbriae of Escherichia coli.</title>
<db_xref db="PUBMED" dbkey="7906265"/>
<journal>J. Bacteriol.</journal>
<location issue="4" pages="1099-110" volume="176"/>
<year>1994</year>
</publication>
<publication id="PUB00002841">
<author_list>Jacob-Dubuisson F, Striker R, Hultgren SJ.</author_list>
<title>Chaperone-assisted self-assembly of pili independent of cellular energy.</title>
<db_xref db="PUBMED" dbkey="7909802"/>
<journal>J. Biol. Chem.</journal>
<location issue="17" pages="12447-55" volume="269"/>
<year>1994</year>
</publication>
<publication id="PUB00005083">
<author_list>Van Rosmalen M, Saier MH Jr.</author_list>
<title>Structural and evolutionary relationships between two families of bacterial extracytoplasmic chaperone proteins which function cooperatively in fimbrial assembly.</title>
<db_xref db="PUBMED" dbkey="7906046"/>
<journal>Res. Microbiol.</journal>
<location issue="7" pages="507-27" volume="144"/>
<year>1993</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR018030"/>
</contains>
<member_list>
<db_xref protein_count="2173" db="PFAM" dbkey="PF00577" name="Usher"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00577"/>
<db_xref db="MSDsite" dbkey="PS01151"/>
<db_xref db="BLOCKS" dbkey="IPB000015"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00886"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1zdv"/>
<db_xref db="PDB" dbkey="1zdx"/>
<db_xref db="PDB" dbkey="1ze3"/>
<db_xref db="PDB" dbkey="3bwu"/>
<db_xref db="SCOP" dbkey="b.167.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="2168"/>
<taxon_data name="Cyanobacteria" proteins_count="2"/>
<taxon_data name="Synechocystis PCC 6803" proteins_count="1"/>
<taxon_data name="Eukaryota" proteins_count="5"/>
<taxon_data name="Rice spp." proteins_count="1"/>
<taxon_data name="Plastid Group" proteins_count="5"/>
<taxon_data name="Green Plants" proteins_count="5"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000018" protein_count="25" short_name="P2Y4_purnocptor" type="Family">
<name>P2Y4 purinoceptor</name>
<abstract>
<p>G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [<cite idref="PUB00004961"/>]. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/). </p>
<p>The rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7
transmembrane (TM) helices [<cite idref="PUB00000131"/>, <cite idref="PUB00002477"/>, <cite idref="PUB00004960"/>].</p>
<p>In addition to their role in energy metabolism, purines (especially
adenosine and adenine nucleotides) produce a wide range of pharmacological
effects mediated by activation of cell surface receptors [<cite idref="PUB00005868"/>]. ATP is a
co-transmitter in sympathetic nerves in the autonomic nervous system,
where it exerts an important physiological role in the regulation of
smooth muscle activity, stimulating relaxation of intestinal smooth muscle
and contraction of the bladder. Receptors for adenine nucleotides are
involved in a number of other physiological pathways, including stimulation
of platelet activation by ADP, which is released from the vascular
endothelium following injury. ATP has excitatory effects in the CNS [<cite idref="PUB00005868"/>].
Distinct receptors exist for adenosine. The main effects of adenosine in
the periphery include vasodilation, bronchoconstriction, immunosuppression,
inhibition of platelet aggregation, cardiac depression, stimulation of
nociceptive afferents, inhibition of neurotransmitter release, and
inhibition of the release of hormones. In the CNS, adenosine exerts a
pre- and post-synaptic depressant action, reducing motor activity,
depressing respiration, inducing sleep and relieving anxiety. The
physiological role of adenosine is believed to be to adjust energy demands
in line with oxygen supply [<cite idref="PUB00005868"/>].</p>
<p>Purinoceptors have been classified as P1 or P2, depending on their
preference for adenosine or adenine nucleotides respectively. Adenosine
receptors (P1 purinoceptors) are characterised by their affinity for
adenosine and by the ability of methylxanthines to act as antagonists [<cite idref="PUB00005868"/>].
Adenosine has very low affinity for P2 purinoceptors.</p>
<p>The P2Y receptor is found in smooth muscle (e.g., taeni caeci) and in
vascular tissue, where it induces vasodilation through endothelium-dependent
release of nitric oxide. The receptor activates phosphoinositide metabolism
through a pertussis-toxin-insensitive G-protein, probably belonging to
the Gi/Go class [<cite idref="PUB00005868"/>].</p>
<p>A new subtype of P2 purinoceptors has been isolated [<cite idref="PUB00002940"/>]. Its deduced amino acid sequence is consistent with a GPCR that is 51% identical to the human P2Y2 receptor and 35% identical to the chicken P2Y1 receptor [<cite idref="PUB00002940"/>]. P2Y4 is expressed in the placenta, with low levels in the lung and vascular smoothmuscle. In cells stably expressing the receptor, UTP and UDP have been shown to stimulate the formation of inositol phosphates with equivalent potency and maximal effect, while ATP behaves as a partial agonist, and ADP is almost inactive [<cite idref="PUB00002940"/>]. The receptor is thus a new member of the P2 purinergic receptor family that functionally behaves as a pyrimidinergic receptor [<cite idref="PUB00002940"/>]. P2Y4 can couple to both Gi and Gq proteins to activate phospholipase C [<cite idref="PUB00007771"/>].</p>
</abstract>
<class_list>
<classification id="GO:0007186" class_type="GO">
<category>Biological Process</category>
<description>G-protein coupled receptor protein signaling pathway</description>
</classification>
<classification id="GO:0016021" class_type="GO">
<category>Cellular Component</category>
<description>integral to membrane</description>
</classification>
<classification id="GO:0045028" class_type="GO">
<category>Molecular Function</category>
<description>purinergic nucleotide receptor activity, G-protein coupled</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O35811"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P51582"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q9JJS7"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00000131">
<author_list>Birnbaumer L.</author_list>
<title>G proteins in signal transduction.</title>
<db_xref db="PUBMED" dbkey="2111655"/>
<journal>Annu. Rev. Pharmacol. Toxicol.</journal>
<location pages="675-705" volume="30"/>
<year>1990</year>
</publication>
<publication id="PUB00002477">
<author_list>Casey PJ, Gilman AG.</author_list>
<title>G protein involvement in receptor-effector coupling.</title>
<db_xref db="PUBMED" dbkey="2830256"/>
<journal>J. Biol. Chem.</journal>
<location issue="6" pages="2577-80" volume="263"/>
<year>1988</year>
</publication>
<publication id="PUB00002940">
<author_list>Communi D, Pirotton S, Parmentier M, Boeynaems JM.</author_list>
<title>Cloning and functional expression of a human uridine nucleotide receptor.</title>
<db_xref db="PUBMED" dbkey="8537336"/>
<journal>J. Biol. Chem.</journal>
<location issue="52" pages="30849-52" volume="270"/>
<year>1995</year>
</publication>
<publication id="PUB00004960">
<author_list>Attwood TK, Findlay JB.</author_list>
<title>Design of a discriminating fingerprint for G-protein-coupled receptors.</title>
<db_xref db="PUBMED" dbkey="8386361"/>
<journal>Protein Eng.</journal>
<location issue="2" pages="167-76" volume="6"/>
<year>1993</year>
</publication>
<publication id="PUB00007771">
<author_list>Communi D, Janssens R, Suarez-Huerta N, Robaye B, Boeynaems JM.</author_list>
<title>Advances in signalling by extracellular nucleotides. the role and transduction mechanisms of P2Y receptors.</title>
<db_xref db="PUBMED" dbkey="10889463"/>
<journal>Cell. Signal.</journal>
<location issue="6" pages="351-60" volume="12"/>
<year>2000</year>
</publication>
<publication id="PUB00004961">
<author_list>Attwood TK, Findlay JB.</author_list>
<title>Fingerprinting G-protein-coupled receptors.</title>
<db_xref db="PUBMED" dbkey="8170923"/>
<journal>Protein Eng.</journal>
<location issue="2" pages="195-203" volume="7"/>
<year>1994</year>
</publication>
<publication id="PUB00005868">
<author_list>Watson S, Arkinstall S.</author_list>
<title>Adenosine and adenine nucleotides.</title>
<book_title>ISBN:0127384405</book_title>
<location pages="19-31"/>
<year>1994</year>
</publication>
</pub_list>
<parent_list>
<rel_ref ipr_ref="IPR002286"/>
</parent_list>
<member_list>
<db_xref protein_count="24" db="PANTHER" dbkey="PTHR19264:SF154" name="P2Y4_purnocptor"/>
<db_xref protein_count="20" db="PRINTS" dbkey="PR01066" name="P2Y4PRNOCPTR"/>
</member_list>
<external_doc_list>
<db_xref db="BLOCKS" dbkey="IPB000018"/>
<db_xref db="IUPHAR" dbkey="2396"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Eukaryota" proteins_count="25"/>
<taxon_data name="Chordata" proteins_count="25"/>
<taxon_data name="Human" proteins_count="4"/>
<taxon_data name="Mouse" proteins_count="2"/>
<taxon_data name="Metazoa" proteins_count="25"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000020" protein_count="188" short_name="Anaphylatoxin/fibulin" type="Domain">
<name>Anaphylatoxin/fibulin</name>
<abstract>
<p>Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defence [<cite idref="PUB00003181"/>]. They have a wide variety of biological activities and are proteolytically activated by cleavage at a specific site, forming a- and b-fragments [<cite idref="PUB00002512"/>]. A-fragments form distinct structural domains of approximately 76 amino acids, coded for by a single exon within the complement protein gene. The C3a, C4a and C5a components are referred to as anaphylatoxins [<cite idref="PUB00002512"/>, <cite idref="PUB00001343"/>]: they cause smooth muscle contraction, histamine release from mast cells, and enhanced vascular permeability [<cite idref="PUB00001343"/>]. They also mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals [<cite idref="PUB00001343"/>]. The proteins are highly hydrophilic, with a mainly alpha-helical structure held together by 3 disulphide bridges [<cite idref="PUB00001343"/>].</p>
<p> Fibulins are secreted glycoproteins that become incorporated into a fibrillar extracellular matrix when expressed by cultured cells or added exogenously to cell monolayers [<cite idref="PUB00003065"/>, <cite idref="PUB00011223"/>]. The five known members of the family share an elongated structure and many calcium-binding sites, owing to the presence of tandem arrays of epidermal growth factor-like domains. They have overlapping binding sites for several basement-membrane proteins, tropoelastin, fibrillin, fibronectin and proteoglycans, and they participate in diverse supramolecular structures. The amino-terminal domain I of fibulin consists of three anaphylatoxin-like (AT) modules, each approximately 40 residues long and containing four or six cysteines. The structure of an AT module was determined for the complement-derived anaphylatoxin C3a, and was found to be a compact alpha-helical fold that is stabilised by three disulphide bridges in the pattern Cys1-4, Cys2-5 and Cys3-6 (where Cys is cysteine). The bulk of the remaining portion of the fibulin molecule is a series of nine EGF-like repeats [<cite idref="PUB00003073"/>]. </p>
</abstract>
<class_list>
<classification id="GO:0005576" class_type="GO">
<category>Cellular Component</category>
<description>extracellular region</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O77469"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P01029"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P01031"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P01032"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00001343">
<author_list>Gennaro R, Simonic T, Negri A, Mottola C, Secchi C, Ronchi S, Romeo D.</author_list>
<title>C5a fragment of bovine complement. Purification, bioassays, amino-acid sequence and other structural studies.</title>
<db_xref db="PUBMED" dbkey="3081348"/>
<journal>Eur. J. Biochem.</journal>
<location issue="1" pages="77-86" volume="155"/>
<year>1986</year>
</publication>
<publication id="PUB00002512">
<author_list>Ogata RT, Rosa PA, Zepf NE.</author_list>
<title>Sequence of the gene for murine complement component C4.</title>
<db_xref db="PUBMED" dbkey="2777798"/>
<journal>J. Biol. Chem.</journal>
<location issue="28" pages="16565-72" volume="264"/>
<year>1989</year>
</publication>
<publication id="PUB00003065">
<author_list>Argraves WS, Tran H, Burgess WH, Dickerson K.</author_list>
<title>Fibulin is an extracellular matrix and plasma glycoprotein with repeated domain structure.</title>
<db_xref db="PUBMED" dbkey="2269669"/>
<journal>J. Cell Biol.</journal>
<location issue="6 Pt 2" pages="3155-64" volume="111"/>
<year>1990</year>
</publication>
<publication id="PUB00011223">
<author_list>Timpl R, Sasaki T, Kostka G, Chu ML.</author_list>
<title>Fibulins: a versatile family of extracellular matrix proteins.</title>
<db_xref db="PUBMED" dbkey="12778127"/>
<journal>Nat. Rev. Mol. Cell Biol.</journal>
<location issue="6" pages="479-89" volume="4"/>
<year>2003</year>
</publication>
<publication id="PUB00003073">
<author_list>Pan TC, Sasaki T, Zhang RZ, Fassler R, Timpl R, Chu ML.</author_list>
<title>Structure and expression of fibulin-2, a novel extracellular matrix protein with multiple EGF-like repeats and consensus motifs for calcium binding.</title>
<db_xref db="PUBMED" dbkey="8245130"/>
<journal>J. Cell Biol.</journal>
<location issue="5" pages="1269-77" volume="123"/>
<year>1993</year>
</publication>
<publication id="PUB00003181">
<author_list>Fritzinger DC, Petrella EC, Connelly MB, Bredehorst R, Vogel CW.</author_list>
<title>Primary structure of cobra complement component C3.</title>
<db_xref db="PUBMED" dbkey="1431125"/>
<journal>J. Immunol.</journal>
<location issue="11" pages="3554-62" volume="149"/>
<year>1992</year>
</publication>
</pub_list>
<child_list>
<rel_ref ipr_ref="IPR018081"/>
</child_list>
<found_in>
<rel_ref ipr_ref="IPR017048"/>
</found_in>
<member_list>
<db_xref protein_count="182" db="PFAM" dbkey="PF01821" name="ANATO"/>
<db_xref protein_count="143" db="PROSITE" dbkey="PS01177" name="ANAPHYLATOXIN_1"/>
<db_xref protein_count="178" db="PROFILE" dbkey="PS01178" name="ANAPHYLATOXIN_2"/>
<db_xref protein_count="155" db="SMART" dbkey="SM00104" name="ANATO"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF01821"/>
<db_xref db="MSDsite" dbkey="PS01177"/>
<db_xref db="BLOCKS" dbkey="IPB000020"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00906"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1c5a"/>
<db_xref db="PDB" dbkey="1cfa"/>
<db_xref db="PDB" dbkey="1kjs"/>
<db_xref db="CATH" dbkey="1.20.91.20"/>
<db_xref db="SCOP" dbkey="a.50.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Eukaryota" proteins_count="188"/>
<taxon_data name="Nematoda" proteins_count="3"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="3"/>
<taxon_data name="Arthropoda" proteins_count="5"/>
<taxon_data name="Chordata" proteins_count="178"/>
<taxon_data name="Human" proteins_count="46"/>
<taxon_data name="Mouse" proteins_count="19"/>
<taxon_data name="Metazoa" proteins_count="188"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR018081"/>
</sec_list>
</interpro>
<interpro id="IPR000021" protein_count="435" short_name="Hok/gef_toxin" type="Family">
<name>Hok/gef cell toxic protein</name>
<abstract>
The hok/gef family of Gram-negative bacterial proteins are toxic to cells
when over-expressed, killing the cells from within by interfering with a
vital function in the cell membrane [<cite idref="PUB00003728"/>]. Some family members (flm) increase the stability of unstable RNA [<cite idref="PUB00003728"/>], some (pnd) induce the degradation of stable RNA at higher than optimum growth temperatures [<cite idref="PUB00000587"/>], while others affect the release of cellular magnesium by membrane alterations [<cite idref="PUB00000587"/>]. The
proteins are short (50-70 residues), consisting of an N-terminal hydrophobic (possibly membrane spanning) domain, and a C-terminal periplasmic region, which contains the toxic domain. The C-terminal region contains a conserved cysteine residue that mediates homo-dimerisation in the gef protein, although dimerisation is not necessary for the toxic effect [<cite idref="PUB00003810"/>].
</abstract>
<class_list>
<classification id="GO:0016020" class_type="GO">
<category>Cellular Component</category>
<description>membrane</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P0ACG4"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00000587">
<author_list>Sakikawa T, Akimoto S, Ohnishi Y.</author_list>
<title>The pnd gene in E. coli plasmid R16: nucleotide sequence and gene expression leading to cell Mg2+ release and stable RNA degradation.</title>
<db_xref db="PUBMED" dbkey="2465777"/>
<journal>Biochim. Biophys. Acta</journal>
<location issue="2" pages="158-66" volume="1007"/>
<year>1989</year>
</publication>
<publication id="PUB00003728">
<author_list>Golub EI, Panzer HA.</author_list>
<title>The F factor of Escherichia coli carries a locus of stable plasmid inheritance stm, similar to the parB locus of plasmid RI.</title>
<db_xref db="PUBMED" dbkey="3070354"/>
<journal>Mol. Gen. Genet.</journal>
<location issue="2" pages="353-7" volume="214"/>
<year>1988</year>
</publication>
<publication id="PUB00003810">
<author_list>Poulsen LK, Refn A, Molin S, Andersson P.</author_list>
<title>Topographic analysis of the toxic Gef protein from Escherichia coli.</title>
<db_xref db="PUBMED" dbkey="1943700"/>
<journal>Mol. Microbiol.</journal>
<location issue="7" pages="1627-37" volume="5"/>
<year>1991</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR018084"/>
</contains>
<member_list>
<db_xref protein_count="435" db="PFAM" dbkey="PF01848" name="HOK_GEF"/>
<db_xref protein_count="385" db="PRINTS" dbkey="PR00281" name="HOKGEFTOXIC"/>
<db_xref protein_count="405" db="PRODOM" dbkey="PD005979" name="Hok/gef_toxin"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF01848"/>
<db_xref db="MSDsite" dbkey="PS00556"/>
<db_xref db="BLOCKS" dbkey="IPB000021"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00481"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="424"/>
<taxon_data name="Virus" proteins_count="8"/>
<taxon_data name="Unclassified" proteins_count="3"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000022" protein_count="5636" short_name="Carboxyl_trans" type="Domain">
<name>Carboxyl transferase</name>
<abstract>
<p>Members in this domain include biotin dependent carboxylases
[<cite idref="PUB00001442"/>, <cite idref="PUB00002227"/>].
The carboxyl transferase domain carries out the following reaction;
transcarboxylation from biotin to an acceptor molecule. There are
two recognised types of carboxyl transferase. One of them uses acyl-CoA
and the other uses 2-oxo acid as the acceptor molecule of carbon dioxide.
All of the members in this family utilise acyl-CoA as the acceptor
molecule.</p>
</abstract>
<class_list>
<classification id="GO:0016874" class_type="GO">
<category>Molecular Function</category>
<description>ligase activity</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O00763"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P34385"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q00955"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q3ULD5"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q9V9A7"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00001442">
<author_list>Toh H, Kondo H, Tanabe T.</author_list>
<title>Molecular evolution of biotin-dependent carboxylases.</title>
<db_xref db="PUBMED" dbkey="8102604"/>
<journal>Eur. J. Biochem.</journal>
<location issue="3" pages="687-96" volume="215"/>
<year>1993</year>
</publication>
<publication id="PUB00002227">
<author_list>Thornton CG, Kumar GK, Haase FC, Phillips NF, Woo SB, Park VM, Magner WJ, Shenoy BC, Wood HG, Samols D.</author_list>
<title>Primary structure of the monomer of the 12S subunit of transcarboxylase as deduced from DNA and characterization of the product expressed in Escherichia coli.</title>
<db_xref db="PUBMED" dbkey="8366018"/>
<journal>J. Bacteriol.</journal>
<location issue="17" pages="5301-8" volume="175"/>
<year>1993</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR011762"/>
<rel_ref ipr_ref="IPR011763"/>
</contains>
<found_in>
<rel_ref ipr_ref="IPR000438"/>
<rel_ref ipr_ref="IPR005783"/>
<rel_ref ipr_ref="IPR017556"/>
</found_in>
<member_list>
<db_xref protein_count="5637" db="PFAM" dbkey="PF01039" name="Carboxyl_trans"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF01039"/>
<db_xref db="BLOCKS" dbkey="IPB000022"/>
<db_xref db="EC" dbkey="6.4.1.2"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1od2"/>
<db_xref db="PDB" dbkey="1od4"/>
<db_xref db="PDB" dbkey="1on3"/>
<db_xref db="PDB" dbkey="1on9"/>
<db_xref db="PDB" dbkey="1pix"/>
<db_xref db="PDB" dbkey="1uyr"/>
<db_xref db="PDB" dbkey="1uys"/>
<db_xref db="PDB" dbkey="1uyt"/>
<db_xref db="PDB" dbkey="1uyv"/>
<db_xref db="PDB" dbkey="1vrg"/>
<db_xref db="PDB" dbkey="1w2x"/>
<db_xref db="PDB" dbkey="1x0u"/>
<db_xref db="PDB" dbkey="1xnv"/>
<db_xref db="PDB" dbkey="1xnw"/>
<db_xref db="PDB" dbkey="1xny"/>
<db_xref db="PDB" dbkey="1xo6"/>
<db_xref db="PDB" dbkey="2a7s"/>
<db_xref db="PDB" dbkey="2bzr"/>
<db_xref db="PDB" dbkey="2f9y"/>
<db_xref db="CATH" dbkey="3.90.226.10"/>
<db_xref db="SCOP" dbkey="c.14.1.4"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="3755"/>
<taxon_data name="Cyanobacteria" proteins_count="56"/>
<taxon_data name="Synechocystis PCC 6803" proteins_count="1"/>
<taxon_data name="Archaea" proteins_count="91"/>
<taxon_data name="Eukaryota" proteins_count="1789"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="11"/>
<taxon_data name="Rice spp." proteins_count="14"/>
<taxon_data name="Fungi" proteins_count="150"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="12"/>
<taxon_data name="Other Eukaryotes" proteins_count="4"/>
<taxon_data name="Nematoda" proteins_count="6"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="6"/>
<taxon_data name="Arthropoda" proteins_count="41"/>
<taxon_data name="Fruit Fly" proteins_count="5"/>
<taxon_data name="Chordata" proteins_count="110"/>
<taxon_data name="Human" proteins_count="29"/>
<taxon_data name="Mouse" proteins_count="18"/>
<taxon_data name="Unclassified" proteins_count="2"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
<taxon_data name="Plastid Group" proteins_count="1366"/>
<taxon_data name="Green Plants" proteins_count="1366"/>
<taxon_data name="Metazoa" proteins_count="333"/>
<taxon_data name="Plastid Group" proteins_count="36"/>
<taxon_data name="Plastid Group" proteins_count="19"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
<taxon_data name="Other Eukaryotes" proteins_count="6"/>
<taxon_data name="Other Eukaryotes" proteins_count="3"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000023" protein_count="2630" short_name="Phosphofructokinase" type="Domain">
<name>Phosphofructokinase</name>
<abstract>
The enzyme-catalysed transfer of a phosphoryl group from ATP is an
important reaction in a wide variety of biological processes [<cite idref="PUB00004002"/>]. One
enzyme that utilises this reaction is phosphofructokinase (PFK), which
catalyses the phosphorylation of fructose-6-phosphate to fructose-1,6-
bisphosphate, a key regulatory step in the glycolytic pathway [<cite idref="PUB00014238"/>, <cite idref="PUB00000020"/>].
PFK exists as a homotetramer in bacteria and mammals (where each monomer
possesses 2 similar domains), and as an octomer in yeast (where there are
4 alpha- (PFK1) and 4 beta-chains (PFK2), the latter, like the mammalian
monomers, possessing 2 similar domains [<cite idref="PUB00000020"/>]). <p>PFK is ~300 amino acids in length, and structural studies of the
bacterial enzyme have shown it comprises two similar (alpha/beta) lobes: one involved in
ATP binding and the other housing both the substrate-binding site and the allosteric site (a regulatory binding site distinct from the active site, but that affects enzyme
activity). The identical tetramer subunits adopt 2
different conformations: in a 'closed' state, the bound magnesium ion
bridges the phosphoryl groups of the enzyme products (ADP and fructose-1,6-
bisphosphate); and in an 'open' state, the magnesium ion binds only the ADP
[<cite idref="PUB00003237"/>], as the 2 products are now further apart. These conformations are
thought to be successive stages of a reaction pathway that requires subunit
closure to bring the 2 molecules sufficiently close to react [<cite idref="PUB00003237"/>].</p>
<p>Deficiency in PFK leads to glycogenosis type VII (Tauri's disease), an
autosomal recessive disorder characterised by severe nausea, vomiting,
muscle cramps and myoglobinuria in response to bursts of intense or
vigorous exercise [<cite idref="PUB00000020"/>]. Sufferers are usually able to lead a reasonably
ordinary life by learning to adjust activity levels [<cite idref="PUB00000020"/>].</p>
</abstract>
<class_list>
<classification id="GO:0003872" class_type="GO">
<category>Molecular Function</category>
<description>6-phosphofructokinase activity</description>
</classification>
<classification id="GO:0005945" class_type="GO">
<category>Cellular Component</category>
<description>6-phosphofructokinase complex</description>
</classification>
<classification id="GO:0006096" class_type="GO">
<category>Biological Process</category>
<description>glycolysis</description>
</classification>
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<pub_list>
<publication id="PUB00000020">
<author_list>Raben N, Exelbert R, Spiegel R, Sherman JB, Nakajima H, Plotz P, Heinisch J.</author_list>
<title>Functional expression of human mutant phosphofructokinase in yeast: genetic defects in French Canadian and Swiss patients with phosphofructokinase deficiency.</title>
<db_xref db="PUBMED" dbkey="7825568"/>
<journal>Am. J. Hum. Genet.</journal>
<location issue="1" pages="131-41" volume="56"/>
<year>1995</year>
</publication>
<publication id="PUB00003237">
<author_list>Shirakihara Y, Evans PR.</author_list>
<title>Crystal structure of the complex of phosphofructokinase from Escherichia coli with its reaction products.</title>
<db_xref db="PUBMED" dbkey="2975709"/>
<journal>J. Mol. Biol.</journal>
<location issue="4" pages="973-94" volume="204"/>
<year>1988</year>
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<publication id="PUB00004002">
<author_list>Hellinga HW, Evans PR.</author_list>
<title>Mutations in the active site of Escherichia coli phosphofructokinase.</title>
<db_xref db="PUBMED" dbkey="2953977"/>
<journal>Nature</journal>
<location issue="6121" pages="437-9" volume="327"/>
<year>1987</year>
</publication>
<publication id="PUB00014238">
<author_list>Wegener G, Krause U.</author_list>
<title>Different modes of activating phosphofructokinase, a key regulatory enzyme of glycolysis, in working vertebrate muscle.</title>
<db_xref db="PUBMED" dbkey="12023862"/>
<journal>Biochem. Soc. Trans.</journal>
<location issue="2" pages="264-70" volume="30"/>
<year>2002</year>
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<taxon_data name="Plastid Group" proteins_count="199"/>
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<taxon_data name="Plastid Group" proteins_count="53"/>
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<interpro id="IPR000024" protein_count="595" short_name="Frizzled_Cys-rich" type="Domain">
<name>Frizzled cysteine-rich domain</name>
<abstract>
The Frizzled CRD (cysteine rich domain) is conserved in diverse proteins including several receptor tyrosine kinases
[<cite idref="PUB00001039"/>, <cite idref="PUB00005055"/>, <cite idref="PUB00005486"/>].
In <taxon tax_id="7227">Drosophila melanogaster</taxon>, members of the Frizzled family of tissue-polarity genes encode proteins that appear to function as cell-surface receptors for Wnts. The Frizzled genes belong to the seven transmembrane class of receptors (7TMR) and have in their extracellular region a cysteine-rich domain that has been implicated as the Wnt binding domain. Sequence similarity between the cysteine-rich domain of Frizzled and several receptor tyrosine kinases, which have roles in development, include the muscle-specific receptor tyrosine kinase (MuSK), the neuronal specific kinase (NSK2), and ROR1 and ROR2.
The structure of this domain is known and is composed mainly of alpha helices.
This domain contains ten conserved cysteines that form five disulphide bridges.
</abstract>
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<author_list>Xu YK, Nusse R.</author_list>
<title>The Frizzled CRD domain is conserved in diverse proteins including several receptor tyrosine kinases.</title>
<db_xref db="PUBMED" dbkey="9637908"/>
<journal>Curr. Biol.</journal>
<location issue="12" pages="R405-6" volume="8"/>
<year>1998</year>
</publication>
<publication id="PUB00005055">
<author_list>Saldanha J, Singh J, Mahadevan D.</author_list>
<title>Identification of a Frizzled-like cysteine rich domain in the extracellular region of developmental receptor tyrosine kinases.</title>
<db_xref db="PUBMED" dbkey="9684897"/>
<journal>Protein Sci.</journal>
<location issue="7" pages="1632-5" volume="7"/>
<year>1998</year>
</publication>
<publication id="PUB00005486">
<author_list>Rehn M, Pihlajaniemi T, Hofmann K, Bucher P.</author_list>
<title>The frizzled motif: in how many different protein families does it occur?</title>
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<journal>Trends Biochem. Sci.</journal>
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<year>1998</year>
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<name>Melatonin receptor</name>
<abstract>
<p>G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [<cite idref="PUB00004961"/>]. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/). </p>
<p>The rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7
transmembrane (TM) helices [<cite idref="PUB00000131"/>, <cite idref="PUB00002477"/>, <cite idref="PUB00004960"/>].</p>
<p>Melatonin is secreted by the pineal gland during darkness [<cite idref="PUB00005892"/>]. It regulates
a variety of neuroendocrine functions and is thought to play an essential
role in circadian rhythms. Drugs that modify the action of melatonin,
and hence influence circadian cycles, are of clinical interest (for example,
in the treatment of jet-lag). Melatonin receptors are found in the
retina, in the pars tuberalis of the pituitary, and in discrete areas of
the brain. The receptor inhibits adenylyl cyclase via a pertussis-toxin-sensitive G-protein, probably of the Gi/Go class [<cite idref="PUB00005892"/>].</p>
</abstract>
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<description>G-protein coupled receptor protein signaling pathway</description>
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<category>Molecular Function</category>
<description>melatonin receptor activity</description>
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<category>Cellular Component</category>
<description>integral to membrane</description>
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<author_list>Birnbaumer L.</author_list>
<title>G proteins in signal transduction.</title>
<db_xref db="PUBMED" dbkey="2111655"/>
<journal>Annu. Rev. Pharmacol. Toxicol.</journal>
<location pages="675-705" volume="30"/>
<year>1990</year>
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<author_list>Casey PJ, Gilman AG.</author_list>
<title>G protein involvement in receptor-effector coupling.</title>
<db_xref db="PUBMED" dbkey="2830256"/>
<journal>J. Biol. Chem.</journal>
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<author_list>Attwood TK, Findlay JB.</author_list>
<title>Design of a discriminating fingerprint for G-protein-coupled receptors.</title>
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<journal>Protein Eng.</journal>
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<author_list>Attwood TK, Findlay JB.</author_list>
<title>Fingerprinting G-protein-coupled receptors.</title>
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<journal>Protein Eng.</journal>
<location issue="2" pages="195-203" volume="7"/>
<year>1994</year>
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<author_list>Watson S, Arkinstall S.</author_list>
<title>Melatonin.</title>
<book_title>ISBN:0127384405</book_title>
<location pages="192-3"/>
<year>1994</year>
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<interpro id="IPR000026" protein_count="399" short_name="Gua-sp_ribonuclease_N1/T1" type="Family">
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<abstract>
<p>Ribonuclease N1 (RNase N1) is a guanine-specific ribonuclease from fungi. RNase T1 and other bacteria RNases are related.</p>
<p>The enzyme hydrolyses the phosphodiester bonds in RNA and oligoribonucleotides [<cite idref="PUB00000397"/>], resulting in 3'-nucleoside monophosphates via 2',3'-cyclophosphate intermediates.</p>
</abstract>
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<category>Molecular Function</category>
<description>RNA binding</description>
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<category>Molecular Function</category>
<description>endoribonuclease activity</description>
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<journal>Biochemistry</journal>
<location issue="7" pages="1644-53" volume="33"/>
<year>1994</year>
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<db_xref db="PDB" dbkey="1rgl"/>
<db_xref db="PDB" dbkey="1rhl"/>
<db_xref db="PDB" dbkey="1rls"/>
<db_xref db="PDB" dbkey="1rms"/>
<db_xref db="PDB" dbkey="1rn1"/>
<db_xref db="PDB" dbkey="1rn4"/>
<db_xref db="PDB" dbkey="1rnb"/>
<db_xref db="PDB" dbkey="1rnt"/>
<db_xref db="PDB" dbkey="1rsn"/>
<db_xref db="PDB" dbkey="1rtu"/>
<db_xref db="PDB" dbkey="1sar"/>
<db_xref db="PDB" dbkey="1t2h"/>
<db_xref db="PDB" dbkey="1t2i"/>
<db_xref db="PDB" dbkey="1trp"/>
<db_xref db="PDB" dbkey="1trq"/>
<db_xref db="PDB" dbkey="1tto"/>
<db_xref db="PDB" dbkey="1uci"/>
<db_xref db="PDB" dbkey="1ucj"/>
<db_xref db="PDB" dbkey="1uck"/>
<db_xref db="PDB" dbkey="1ucl"/>
<db_xref db="PDB" dbkey="1x1u"/>
<db_xref db="PDB" dbkey="1x1w"/>
<db_xref db="PDB" dbkey="1x1x"/>
<db_xref db="PDB" dbkey="1x1y"/>
<db_xref db="PDB" dbkey="1ygw"/>
<db_xref db="PDB" dbkey="1ynv"/>
<db_xref db="PDB" dbkey="1yvs"/>
<db_xref db="PDB" dbkey="2aad"/>
<db_xref db="PDB" dbkey="2aae"/>
<db_xref db="PDB" dbkey="2bir"/>
<db_xref db="PDB" dbkey="2bu4"/>
<db_xref db="PDB" dbkey="2c4b"/>
<db_xref db="PDB" dbkey="2f4y"/>
<db_xref db="PDB" dbkey="2f56"/>
<db_xref db="PDB" dbkey="2f5m"/>
<db_xref db="PDB" dbkey="2f5w"/>
<db_xref db="PDB" dbkey="2gsp"/>
<db_xref db="PDB" dbkey="2hoh"/>
<db_xref db="PDB" dbkey="2rbi"/>
<db_xref db="PDB" dbkey="2rnt"/>
<db_xref db="PDB" dbkey="2sar"/>
<db_xref db="PDB" dbkey="3bir"/>
<db_xref db="PDB" dbkey="3bu4"/>
<db_xref db="PDB" dbkey="3gsp"/>
<db_xref db="PDB" dbkey="3hoh"/>
<db_xref db="PDB" dbkey="3rnt"/>
<db_xref db="PDB" dbkey="4bir"/>
<db_xref db="PDB" dbkey="4bu4"/>
<db_xref db="PDB" dbkey="4gsp"/>
<db_xref db="PDB" dbkey="4hoh"/>
<db_xref db="PDB" dbkey="4rnt"/>
<db_xref db="PDB" dbkey="5bir"/>
<db_xref db="PDB" dbkey="5bu4"/>
<db_xref db="PDB" dbkey="5gsp"/>
<db_xref db="PDB" dbkey="5hoh"/>
<db_xref db="PDB" dbkey="5rnt"/>
<db_xref db="PDB" dbkey="6gsp"/>
<db_xref db="PDB" dbkey="6rnt"/>
<db_xref db="PDB" dbkey="7gsp"/>
<db_xref db="PDB" dbkey="7rnt"/>
<db_xref db="PDB" dbkey="8rnt"/>
<db_xref db="PDB" dbkey="9rnt"/>
<db_xref db="CATH" dbkey="3.10.450.30"/>
<db_xref db="SCOP" dbkey="d.1.1.2"/>
<db_xref db="SCOP" dbkey="d.1.1.3"/>
<db_xref db="SCOP" dbkey="d.1.1.4"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="288"/>
<taxon_data name="Cyanobacteria" proteins_count="2"/>
<taxon_data name="Archaea" proteins_count="2"/>
<taxon_data name="Eukaryota" proteins_count="109"/>
<taxon_data name="Fungi" proteins_count="109"/>
<taxon_data name="Metazoa" proteins_count="109"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR001887"/>
</sec_list>
</interpro>
<interpro id="IPR000028" protein_count="155" short_name="Chloroperoxidase" type="Family">
<name>Chloroperoxidase</name>
<abstract>
<p>Chloroperoxidase (CPO), also known as Heme haloperoxidase, is a ~250 residue heme-containing glycoprotein that is secreted by various fungi. Chloroperoxidase was first identified in <taxon tax_id="5474">Caldariomyces fumago</taxon> where it catalyzes the hydrogen
peroxide-dependent chlorination of cyclopentanedione during the biosynthesis
of the antibiotic caldarioymcin. Additionally, heme haloperoxidase catalyzes
the iodination and bromination of a wide range of substrates. Besides
performing H2O2-dependent halogenation reactions, the enzyme catalyzes
dehydrogenation reactions. Chloroperoxidase also functions as a catalase, facilitating the decomposition of hydrogen peroxide to oxygen and water. Furthermore, chloroperoxidase catalyzes P450-like oxygen insertion reactions. The capability of chloroperoxidase to perform these diverse reactions makes it one of the most versatile of all known heme proteins [<cite idref="PUB00052607"/>, <cite idref="PUB00052608"/>].</p>
<p>Despite functional similarities with other heme enzymes, chloroperoxidase
folds into a novel tertiary structure dominated by eight helical segments [<cite idref="PUB00005255"/>]. Structurally, chloroperoxidase is unique, but it shares
features with both peroxidases and P450 enzymes. As in cytochrome P450
enzymes, the proximal heme ligand is a cysteine,
but similar to peroxidases, the distal side of the heme is polar. However,
unlike other peroxidases, the normally conserved distal arginine is lacking
and the catalytic acid base is a glutamic acid and not a histidine [<cite idref="PUB00040032"/>].</p>
</abstract>
<class_list>
<classification id="GO:0004601" class_type="GO">
<category>Molecular Function</category>
<description>peroxidase activity</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P04963"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00005255">
<author_list>Sundaramoorthy M, Terner J, Poulos TL.</author_list>
<title>The crystal structure of chloroperoxidase: a heme peroxidase--cytochrome P450 functional hybrid.</title>
<db_xref db="PUBMED" dbkey="8747463"/>
<journal>Structure</journal>
<location issue="12" pages="1367-77" volume="3"/>
<year>1995</year>
</publication>
<publication id="PUB00040032">
<author_list>Kuhnel K, Blankenfeldt W, Terner J, Schlichting I.</author_list>
<title>Crystal structures of chloroperoxidase with its bound substrates and complexed with formate, acetate, and nitrate.</title>
<db_xref db="PUBMED" dbkey="16790441"/>
<journal>J. Biol. Chem.</journal>
<location issue="33" pages="23990-8" volume="281"/>
<year>2006</year>
</publication>
<publication id="PUB00052608">
<author_list>Manoj KM, Hager LP.</author_list>
<title>Chloroperoxidase, a janus enzyme.</title>
<db_xref db="PUBMED" dbkey="18220360"/>
<journal>Biochemistry</journal>
<location issue="9" pages="2997-3003" volume="47"/>
<year>2008</year>
</publication>
<publication id="PUB00052607">
<author_list>Hofrichter M, Ullrich R.</author_list>
<title>Heme-thiolate haloperoxidases: versatile biocatalysts with biotechnological and environmental significance.</title>
<db_xref db="PUBMED" dbkey="16628447"/>
<journal>Appl. Microbiol. Biotechnol.</journal>
<location issue="3" pages="276-88" volume="71"/>
<year>2006</year>
</publication>
</pub_list>
<member_list>
<db_xref protein_count="148" db="PFAM" dbkey="PF01328" name="Peroxidase_2"/>
<db_xref protein_count="155" db="PROFILE" dbkey="PS51405" name="HEME_HALOPEROXIDASE"/>
<db_xref protein_count="148" db="GENE3D" dbkey="G3DSA:1.10.489.10" name="Chloroperoxidase"/>
<db_xref protein_count="145" db="SSF" dbkey="SSF47571" name="Chloroperoxidase"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF01328"/>
<db_xref db="COMe" dbkey="PRX000234"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1cpo"/>
<db_xref db="PDB" dbkey="2civ"/>
<db_xref db="PDB" dbkey="2ciw"/>
<db_xref db="PDB" dbkey="2cix"/>
<db_xref db="PDB" dbkey="2ciy"/>
<db_xref db="PDB" dbkey="2ciz"/>
<db_xref db="PDB" dbkey="2cj0"/>
<db_xref db="PDB" dbkey="2cj1"/>
<db_xref db="PDB" dbkey="2cj2"/>
<db_xref db="PDB" dbkey="2cpo"/>
<db_xref db="PDB" dbkey="2j18"/>
<db_xref db="PDB" dbkey="2j19"/>
<db_xref db="PDB" dbkey="2j5m"/>
<db_xref db="CATH" dbkey="1.10.489.10"/>
<db_xref db="SCOP" dbkey="a.39.3.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Eukaryota" proteins_count="155"/>
<taxon_data name="Fungi" proteins_count="146"/>
<taxon_data name="Metazoa" proteins_count="146"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000030" protein_count="938" short_name="Uncharacterised_PPE" type="Family">
<name>Uncharacterised protein family, PPE protein</name>
<abstract>
This mycobacterial family is named after a conserved amino-terminal region of about 180
amino acids, the PPE motif. The carboxy termini of proteins belonging to the PPE family are variable, and on the basis of this region at least three groups can be distinguished. The MPTR subgroup is characterised by tandem copies of a motif NXGXGNXG. The second subgroup contains a conserved motif at about position 350.
The third group shares only similarity in the amino terminal region.
The function of these proteins is uncertain but it has been suggested that they may be related to antigenic variation of <taxon tax_id="1773">Mycobacterium tuberculosis</taxon> [<cite idref="PUB00004280"/>].
</abstract>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O06246"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00004280">
<author_list>Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG.</author_list>
<title>Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.</title>
<db_xref db="PUBMED" dbkey="9634230"/>
<journal>Nature</journal>
<location issue="6685" pages="537-44" volume="393"/>
<year>1998</year>
</publication>
</pub_list>
<member_list>
<db_xref protein_count="938" db="PFAM" dbkey="PF00823" name="PPE"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00823"/>
<db_xref db="BLOCKS" dbkey="IPB000030"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="2g38"/>
<db_xref db="SCOP" dbkey="a.25.4.2"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="937"/>
<taxon_data name="Virus" proteins_count="1"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000031" protein_count="2381" short_name="AIR_COase_core" type="Domain">
<name>1-(5-Phosphoribosyl)-5-amino-4-imidazole-carboxylate (AIR) carboxylase</name>
<abstract>
<p>Phosphoribosylaminoimidazole carboxylase is a fusion protein in plants and fungi, but consists of two non-interacting proteins in bacteria, PurK and PurE.
PurK, N5-carboxyaminoimidazole ribonucleotide (N5_CAIR) synthetase, catalyzes the conversion of 5-aminoimidazole ribonucleotide (AIR), ATP, and bicarbonate to N5-CAIR, ADP, and Pi. PurE converts N5-CAIR to CAIR, the sixth step of de novo purine biosynthesis. In the presence of high concentrations of bicarbonate, PurE is reported able to convert AIR to CAIR directly and without ATP. Some members of this family contain two copies of this domain [<cite idref="PUB00016905"/>]. The crystal structure of PurE indicates a unique quaternary structure that confirms the octameric nature of the enzyme [<cite idref="PUB00016906"/>].</p>
</abstract>
<class_list>
<classification id="GO:0004638" class_type="GO">
<category>Molecular Function</category>
<description>phosphoribosylaminoimidazole carboxylase activity</description>
</classification>
<classification id="GO:0006189" class_type="GO">
<category>Biological Process</category>
<description>'de novo' IMP biosynthetic process</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P21264"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P22234"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q10457"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q9DCL9"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q9I7S8"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00016905">
<author_list>Meyer E, Kappock TJ, Osuji C, Stubbe J.</author_list>
<title>Evidence for the direct transfer of the carboxylate of N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) to generate 4-carboxy-5-aminoimidazole ribonucleotide catalyzed by Escherichia coli PurE, an N5-CAIR mutase.</title>
<db_xref db="PUBMED" dbkey="10074353"/>
<journal>Biochemistry</journal>
<location issue="10" pages="3012-8" volume="38"/>
<year>1999</year>
</publication>
<publication id="PUB00016906">
<author_list>Mathews II, Kappock TJ, Stubbe J, Ealick SE.</author_list>
<title>Crystal structure of Escherichia coli PurE, an unusual mutase in the purine biosynthetic pathway.</title>
<db_xref db="PUBMED" dbkey="10574791"/>
<journal>Structure</journal>
<location issue="11" pages="1395-406" volume="7"/>
<year>1999</year>
</publication>
</pub_list>
<found_in>
<rel_ref ipr_ref="IPR016301"/>
</found_in>
<member_list>
<db_xref protein_count="1991" db="PANTHER" dbkey="PTHR23046" name="AIR_carboxyl"/>
<db_xref protein_count="2381" db="PFAM" dbkey="PF00731" name="AIRC"/>
<db_xref protein_count="1974" db="TIGRFAMs" dbkey="TIGR01162" name="purE"/>
<db_xref protein_count="2293" db="GENE3D" dbkey="G3DSA:3.40.50.7700" name="AIR_carboxyl"/>
<db_xref protein_count="2369" db="SSF" dbkey="SSF52255" name="AIR_carboxyl"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00731"/>
<db_xref db="BLOCKS" dbkey="IPB000031"/>
<db_xref db="EC" dbkey="4.1.1.21"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1d7a"/>
<db_xref db="PDB" dbkey="1o4v"/>
<db_xref db="PDB" dbkey="1qcz"/>
<db_xref db="PDB" dbkey="1u11"/>
<db_xref db="PDB" dbkey="1xmp"/>
<db_xref db="PDB" dbkey="2ate"/>
<db_xref db="PDB" dbkey="2fw1"/>
<db_xref db="PDB" dbkey="2fw6"/>
<db_xref db="PDB" dbkey="2fw7"/>
<db_xref db="PDB" dbkey="2fw8"/>
<db_xref db="PDB" dbkey="2fw9"/>
<db_xref db="PDB" dbkey="2fwa"/>
<db_xref db="PDB" dbkey="2fwb"/>
<db_xref db="PDB" dbkey="2fwi"/>
<db_xref db="PDB" dbkey="2fwj"/>
<db_xref db="PDB" dbkey="2fwp"/>
<db_xref db="PDB" dbkey="2nsh"/>
<db_xref db="PDB" dbkey="2nsj"/>
<db_xref db="PDB" dbkey="2nsl"/>
<db_xref db="PDB" dbkey="2ywx"/>
<db_xref db="CATH" dbkey="3.40.50.7700"/>
<db_xref db="SCOP" dbkey="c.23.8.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="2074"/>
<taxon_data name="Cyanobacteria" proteins_count="109"/>
<taxon_data name="Synechocystis PCC 6803" proteins_count="2"/>
<taxon_data name="Archaea" proteins_count="137"/>
<taxon_data name="Eukaryota" proteins_count="170"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="3"/>
<taxon_data name="Rice spp." proteins_count="4"/>
<taxon_data name="Fungi" proteins_count="76"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="6"/>
<taxon_data name="Nematoda" proteins_count="1"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="1"/>
<taxon_data name="Arthropoda" proteins_count="25"/>
<taxon_data name="Fruit Fly" proteins_count="1"/>
<taxon_data name="Chordata" proteins_count="22"/>
<taxon_data name="Human" proteins_count="2"/>
<taxon_data name="Mouse" proteins_count="2"/>
<taxon_data name="Plastid Group" proteins_count="26"/>
<taxon_data name="Green Plants" proteins_count="26"/>
<taxon_data name="Metazoa" proteins_count="133"/>
<taxon_data name="Plastid Group" proteins_count="3"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000032" protein_count="3118" short_name="PTS_HPr_prot-like" type="Domain">
<name>Phosphotransferase system, phosphocarrier HPr protein-like</name>
<abstract>
<p>This entry represents a structural domain found in both the histidine-containing phosphocarrier protein HPr, as well as its structural homologues, which includes the catabolite repression protein Crh found in <taxon tax_id="1423">Bacillus subtilis</taxon>. This domain has a alpha+beta structure found in two layers with an overall architecture of an open faced beta-sandwich in which a beta-sheet is packed against three alpha-helices. </p>
<p>The histidine-containing phosphocarrier protein (HPr) is a central component of the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS), which transfers metabolic carbohydrates across the cell membrane in many bacterial species [<cite idref="PUB00003612"/>, <cite idref="PUB00000073"/>]. PTS catalyses the phosphorylation of incoming sugar substrates concomitant with their translocation across the cell membrane. The general mechanism of the PTS is as follows: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred to Enzyme I (EI) of the PTS, which in turn transfers it to the phosphoryl carrier protein (HPr) [<cite idref="PUB00003342"/>, <cite idref="PUB00005243"/>]. Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease complex (enzymes EII/EIII). </p>
<p>HPr [<cite idref="PUB00004777"/>, <cite idref="PUB00005010"/>] is a small cytoplasmic protein of 70 to 90 amino acid residues. In some bacteria, HPr is a domain in a larger protein that includes a EIII(Fru) (IIA) domain and in some cases also the EI domain. A conserved histidine in the N-terminal section of HPr serves as an acceptor for the phosphoryl group of EI. In the central part of HPr, there is a conserved serine which (in Gram-positive bacteria only) is phosphorylated by an ATP-dependent protein kinase; a process which probably play a regulatory role in sugar transport. Regulatory phosphorylation at the conserved Ser residue does not appear to induce large structural changes to the HPr domain, in particular in the region of the active site [<cite idref="PUB00025027"/>, <cite idref="PUB00032584"/>].</p>
</abstract>
<class_list>
<classification id="GO:0005351" class_type="GO">
<category>Molecular Function</category>
<description>sugar:hydrogen symporter activity</description>
</classification>
<classification id="GO:0009401" class_type="GO">
<category>Biological Process</category>
<description>phosphoenolpyruvate-dependent sugar phosphotransferase system</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O06976"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00000073">
<author_list>Meadow ND, Fox DK, Roseman S.</author_list>
<title>The bacterial phosphoenolpyruvate: glycose phosphotransferase system.</title>
<db_xref db="PUBMED" dbkey="2197982"/>
<journal>Annu. Rev. Biochem.</journal>
<location pages="497-542" volume="59"/>
<year>1990</year>
</publication>
<publication id="PUB00003342">
<author_list>van Nuland NA, Boelens R, Scheek RM, Robillard GT.</author_list>
<title>High-resolution structure of the phosphorylated form of the histidine-containing phosphocarrier protein HPr from Escherichia coli determined by restrained molecular dynamics from NMR-NOE data.</title>
<db_xref db="PUBMED" dbkey="7853396"/>
<journal>J. Mol. Biol.</journal>
<location issue="1" pages="180-93" volume="246"/>
<year>1995</year>
</publication>
<publication id="PUB00003612">
<author_list>Postma PW, Lengeler JW, Jacobson GR.</author_list>
<title>Phosphoenolpyruvate:carbohydrate phosphotransferase systems of bacteria.</title>
<db_xref db="PUBMED" dbkey="8246840"/>
<journal>Microbiol. Rev.</journal>
<location issue="3" pages="543-94" volume="57"/>
<year>1993</year>
</publication>
<publication id="PUB00004777">
<author_list>Herzberg O, Reddy P, Sutrina S, Saier MH Jr, Reizer J, Kapadia G.</author_list>
<title>Structure of the histidine-containing phosphocarrier protein HPr from Bacillus subtilis at 2.0-A resolution.</title>
<db_xref db="PUBMED" dbkey="1549615"/>
<journal>Proc. Natl. Acad. Sci. U.S.A.</journal>
<location issue="6" pages="2499-503" volume="89"/>
<year>1992</year>
</publication>
<publication id="PUB00032584">
<author_list>Sridharan S, Razvi A, Scholtz JM, Sacchettini JC.</author_list>
<title>The HPr proteins from the thermophile Bacillus stearothermophilus can form domain-swapped dimers.</title>
<db_xref db="PUBMED" dbkey="15713472"/>
<journal>J. Mol. Biol.</journal>
<location issue="3" pages="919-31" volume="346"/>
<year>2005</year>
</publication>
<publication id="PUB00025027">
<author_list>Audette GF, Engelmann R, Hengstenberg W, Deutscher J, Hayakawa K, Quail JW, Delbaere LT.</author_list>
<title>The 1.9 A resolution structure of phospho-serine 46 HPr from Enterococcus faecalis.</title>
<db_xref db="PUBMED" dbkey="11054290"/>
<journal>J. Mol. Biol.</journal>
<location issue="4" pages="545-53" volume="303"/>
<year>2000</year>
</publication>
<publication id="PUB00005010">
<author_list>Reizer J, Hoischen C, Reizer A, Pham TN, Saier MH Jr.</author_list>
<title>Sequence analyses and evolutionary relationships among the energy-coupling proteins Enzyme I and HPr of the bacterial phosphoenolpyruvate: sugar phosphotransferase system.</title>
<db_xref db="PUBMED" dbkey="7686067"/>
<journal>Protein Sci.</journal>
<location issue="4" pages="506-21" volume="2"/>
<year>1993</year>
</publication>
<publication id="PUB00005243">
<author_list>Liao DI, Herzberg O.</author_list>
<title>Refined structures of the active Ser83-->Cys and impaired Ser46-->Asp histidine-containing phosphocarrier proteins.</title>
<db_xref db="PUBMED" dbkey="7704530"/>
<journal>Structure</journal>
<location issue="12" pages="1203-16" volume="2"/>
<year>1994</year>
</publication>
</pub_list>
<child_list>
<rel_ref ipr_ref="IPR005698"/>
</child_list>
<contains>
<rel_ref ipr_ref="IPR001020"/>
<rel_ref ipr_ref="IPR002114"/>
</contains>
<found_in>
<rel_ref ipr_ref="IPR016258"/>
<rel_ref ipr_ref="IPR016910"/>
</found_in>
<member_list>
<db_xref protein_count="3109" db="PROFILE" dbkey="PS51350" name="PTS_HPR_DOM"/>
<db_xref protein_count="2835" db="GENE3D" dbkey="G3DSA:3.30.1340.10" name="PTS_HPr_protein"/>
<db_xref protein_count="3066" db="SSF" dbkey="SSF55594" name="HPr_protein"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00381"/>
<db_xref db="BLOCKS" dbkey="IPB000032"/>
<db_xref db="EC" dbkey="2.7.11"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1cm2"/>
<db_xref db="PDB" dbkey="1cm3"/>
<db_xref db="PDB" dbkey="1fu0"/>
<db_xref db="PDB" dbkey="1ggr"/>
<db_xref db="PDB" dbkey="1hdn"/>
<db_xref db="PDB" dbkey="1j6t"/>
<db_xref db="PDB" dbkey="1jem"/>
<db_xref db="PDB" dbkey="1k1c"/>
<db_xref db="PDB" dbkey="1ka5"/>
<db_xref db="PDB" dbkey="1kkl"/>
<db_xref db="PDB" dbkey="1kkm"/>
<db_xref db="PDB" dbkey="1mo1"/>
<db_xref db="PDB" dbkey="1mu4"/>
<db_xref db="PDB" dbkey="1opd"/>
<db_xref db="PDB" dbkey="1pch"/>
<db_xref db="PDB" dbkey="1pfh"/>
<db_xref db="PDB" dbkey="1poh"/>
<db_xref db="PDB" dbkey="1ptf"/>
<db_xref db="PDB" dbkey="1qfr"/>
<db_xref db="PDB" dbkey="1qr5"/>
<db_xref db="PDB" dbkey="1rzr"/>
<db_xref db="PDB" dbkey="1sph"/>
<db_xref db="PDB" dbkey="1txe"/>
<db_xref db="PDB" dbkey="1vrc"/>
<db_xref db="PDB" dbkey="1y51"/>
<db_xref db="PDB" dbkey="1zvv"/>
<db_xref db="PDB" dbkey="2ak7"/>
<db_xref db="PDB" dbkey="2hid"/>
<db_xref db="PDB" dbkey="2hpr"/>
<db_xref db="PDB" dbkey="2jel"/>
<db_xref db="PDB" dbkey="2nzu"/>
<db_xref db="PDB" dbkey="2nzv"/>
<db_xref db="PDB" dbkey="2oen"/>
<db_xref db="PDB" dbkey="2rlz"/>
<db_xref db="PDB" dbkey="3ccd"/>
<db_xref db="PDB" dbkey="3eza"/>
<db_xref db="PDB" dbkey="3ezb"/>
<db_xref db="PDB" dbkey="3eze"/>
<db_xref db="CATH" dbkey="3.30.1340.10"/>
<db_xref db="SCOP" dbkey="d.94.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="3109"/>
<taxon_data name="Cyanobacteria" proteins_count="5"/>
<taxon_data name="Archaea" proteins_count="5"/>
<taxon_data name="Eukaryota" proteins_count="4"/>
<taxon_data name="Fungi" proteins_count="1"/>
<taxon_data name="Plastid Group" proteins_count="3"/>
<taxon_data name="Green Plants" proteins_count="3"/>
<taxon_data name="Metazoa" proteins_count="1"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR005698"/>
</sec_list>
</interpro>
<interpro id="IPR000033" protein_count="721" short_name="LDL_rcpt_classB_YWTD_rpt" type="Repeat">
<name>Low-density lipoprotein receptor, class B (YWTD) repeat</name>
<abstract>
<p> The low-density lipoprotein receptor (LDLR) is the major cholesterol-carrying lipoprotein of plasma, acting to regulate cholesterol homeostasis in mammalian cells. The LDL receptor binds LDL and transports it into cells by acidic endocytosis. In order to be internalized, the receptor-ligand complex must first cluster into clathrin-coated pits. Once inside the cell, the LDLR separates from its ligand, which is degraded in the lysosomes, while the receptor returns to the cell surface [<cite idref="PUB00017008"/>]. The internal dissociation of the LDLR with its ligand is mediated by proton pumps within the walls of the endosome that lower the pH. The LDLR is a multi-domain protein, containing: </p>
<p>
<ul>
<li>The ligand-binding domain contains seven or eight 40-amino acid LDLR class A (cysteine-rich) repeats, each of which contains a coordinated calcium ion and six cysteine residues involved in disulphide bond formation [<cite idref="PUB00000798"/>]. Similar domains have been found in other extracellular and membrane proteins [<cite idref="PUB00004868"/>]. </li>
</ul>
</p>
<p>
<ul>
<li>The second conserved region contains two EGF repeats, followed by six LDLR class B (YWTD) repeats, and another EGF repeat. The LDLR class B repeats each contain a conserved YWTD motif, and is predicted to form a beta-propeller structure [<cite idref="PUB00003391"/>]. This region is critical for ligand release and recycling of the receptor [<cite idref="PUB00017009"/>].</li>
</ul>
</p>
<p>
<ul>
<li>The third domain is rich in serine and threonine residues and contains clustered O-linked carbohydrate chains.</li>
</ul>
</p>
<p>
<ul>
<li>The fourth domain is the hydrophobic transmembrane region.</li>
</ul>
</p>
<p>
<ul>
<li>The fifth domain is the cytoplasmic tail that directs the receptor to clathrin-coated pits.</li>
</ul>
</p>
<p>LDLR is closely related in structure to several other receptors, including LRP1, LRP1b, megalin/LRP2, VLDL receptor, lipoprotein receptor, MEGF7/LRP4, and LRP8/apolipoprotein E receptor2); these proteins participate in a wide range of physiological processes, including the regulation of lipid metabolism, protection against atherosclerosis, neurodevelopment, and transport of nutrients and vitamins [<cite idref="PUB00042617"/>].</p>
<p>This entry represents the LDLR classB (YWTD) repeat, the structure of which has been solved [<cite idref="PUB00017010"/>]. The six YWTD repeats together fold into a six-bladed beta-propeller. Each blade of the propeller consists of four antiparallel beta-strands; the innermost strand of each blade is labeled 1 and the outermost strand, 4. The sequence repeats are offset with respect to the blades of the propeller, such that any given 40-residue YWTD repeat spans strands 24 of one propeller blade and strand 1 of the subsequent blade. This offset ensures circularization of the propeller because the last strand of the final sequence repeat acts as an innermost strand 1 of the blade that harbors strands 24 from the first sequence repeat. The repeat is found in a variety of proteins that include, vitellogenin receptor from <taxon tax_id="7227">Drosophila melanogaster</taxon>, low-density lipoprotein (LDL) receptor [<cite idref="PUB00000798"/>], preproepidermal growth factor, and nidogen (entactin).</p>
</abstract>
<class_list>
<classification id="GO:0016020" class_type="GO">
<category>Cellular Component</category>
<description>membrane</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P01130"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P01132"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P13368"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P98158"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q04833"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00000798">
<author_list>Yamamoto T, Davis CG, Brown MS, Schneider WJ, Casey ML, Goldstein JL, Russell DW.</author_list>
<title>The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA.</title>
<db_xref db="PUBMED" dbkey="6091915"/>
<journal>Cell</journal>
<location issue="1" pages="27-38" volume="39"/>
<year>1984</year>
</publication>
<publication id="PUB00003391">
<author_list>Springer TA.</author_list>
<title>An extracellular beta-propeller module predicted in lipoprotein and scavenger receptors, tyrosine kinases, epidermal growth factor precursor, and extracellular matrix components.</title>
<db_xref db="PUBMED" dbkey="9790844"/>
<journal>J. Mol. Biol.</journal>
<location issue="4" pages="837-62" volume="283"/>
<year>1998</year>
</publication>
<publication id="PUB00004868">
<author_list>Daly NL, Scanlon MJ, Djordjevic JT, Kroon PA, Smith R.</author_list>
<title>Three-dimensional structure of a cysteine-rich repeat from the low-density lipoprotein receptor.</title>
<db_xref db="PUBMED" dbkey="7603991"/>
<journal>Proc. Natl. Acad. Sci. U.S.A.</journal>
<location issue="14" pages="6334-8" volume="92"/>
<year>1995</year>
</publication>
<publication id="PUB00042617">
<author_list>May P, Woldt E, Matz RL, Boucher P.</author_list>
<title>The LDL receptor-related protein (LRP) family: an old family of proteins with new physiological functions.</title>
<db_xref db="PUBMED" dbkey="17457719"/>
<journal>Ann. Med.</journal>
<location issue="3" pages="219-28" volume="39"/>
<year>2007</year>
</publication>
<publication id="PUB00017008">
<author_list>Brown MS, Goldstein JL.</author_list>
<title>A receptor-mediated pathway for cholesterol homeostasis.</title>
<db_xref db="PUBMED" dbkey="3513311"/>
<journal>Science</journal>
<location issue="4746" pages="34-47" volume="232"/>
<year>1986</year>
</publication>
<publication id="PUB00017009">
<author_list>Davis CG, Goldstein JL, Sudhof TC, Anderson RG, Russell DW, Brown MS.</author_list>
<title>Acid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region.</title>
<db_xref db="PUBMED" dbkey="3494949"/>
<journal>Nature</journal>
<location issue="6115" pages="760-5" volume="326"/>
<year>1987</year>
</publication>
<publication id="PUB00017010">
<author_list>Jeon H, Meng W, Takagi J, Eck MJ, Springer TA, Blacklow SC.</author_list>
<title>Implications for familial hypercholesterolemia from the structure of the LDL receptor YWTD-EGF domain pair.</title>
<db_xref db="PUBMED" dbkey="11373616"/>
<journal>Nat. Struct. Biol.</journal>
<location issue="6" pages="499-504" volume="8"/>
<year>2001</year>
</publication>
</pub_list>
<found_in>
<rel_ref ipr_ref="IPR011042"/>
<rel_ref ipr_ref="IPR016317"/>
<rel_ref ipr_ref="IPR017049"/>
</found_in>
<member_list>
<db_xref protein_count="546" db="PFAM" dbkey="PF00058" name="Ldl_recept_b"/>
<db_xref protein_count="561" db="PROFILE" dbkey="PS51120" name="LDLRB"/>
<db_xref protein_count="709" db="SMART" dbkey="SM00135" name="LY"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00058"/>
<db_xref db="BLOCKS" dbkey="IPB000033"/>
<db_xref db="PROSITEDOC" dbkey="PDOC51120"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1ijq"/>
<db_xref db="PDB" dbkey="1n7d"/>
<db_xref db="PDB" dbkey="1npe"/>
<db_xref db="CATH" dbkey="2.120.10.30"/>
<db_xref db="SCOP" dbkey="b.68.5.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="49"/>
<taxon_data name="Cyanobacteria" proteins_count="1"/>
<taxon_data name="Archaea" proteins_count="9"/>
<taxon_data name="Eukaryota" proteins_count="662"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="2"/>
<taxon_data name="Rice spp." proteins_count="4"/>
<taxon_data name="Fungi" proteins_count="34"/>
<taxon_data name="Other Eukaryotes" proteins_count="10"/>
<taxon_data name="Nematoda" proteins_count="12"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="12"/>
<taxon_data name="Arthropoda" proteins_count="240"/>
<taxon_data name="Fruit Fly" proteins_count="31"/>
<taxon_data name="Chordata" proteins_count="310"/>
<taxon_data name="Human" proteins_count="56"/>
<taxon_data name="Mouse" proteins_count="51"/>
<taxon_data name="Unclassified" proteins_count="1"/>
<taxon_data name="Plastid Group" proteins_count="9"/>
<taxon_data name="Green Plants" proteins_count="9"/>
<taxon_data name="Metazoa" proteins_count="642"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000034" protein_count="191" short_name="Laminin_B_type_IV" type="Domain">
<name>Laminin B type IV</name>
<abstract>
<p>Laminins represent a distinct family of extracellular matrix proteins present only in basement membranes in almost every animal tissue. They are heterotrimeric molecules composed of alpha, beta and gamma subunits (formerly A, B1, and B2, respectively [<cite idref="PUB00016907"/>]) and form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains, [<cite idref="PUB00001500"/>, <cite idref="PUB00016908"/>]. Most of the globular domains of the short arms correspond to one of two different motifs, the 200-residue laminin N-terminal (domain VI) (LN) module and the 250-residue laminin domain IV (L4) module [<cite idref="PUB00016909"/>]. All alpha chains share a unique C-terminal G domain which consists of five laminin G modules. The laminins can self-assemble, bind to other matrix macromolecules, and have unique and shared cell interactions mediated by integrins, dystroglycan, and other receptors. There are at least 14 laminin isoforms that regulate a variety of cellular functions including cell adhesion, migration, proliferation, signalling and differentiation [<cite idref="PUB00016910"/>, <cite idref="PUB00016908"/>, <cite idref="PUB00016911"/>].</p>
<p>The laminin B domain (also known as domain IV) is an extracellular module of unknown function. It is found in a number of different proteins that include, heparan sulphate proteoglycan from basement membrane, a laminin-like protein from <taxon tax_id="6239">Caenorhabditis elegans</taxon> and laminin. Laminin IV domain is not found in short laminin chains (alpha4 or beta3). </p>
</abstract>
<class_list>
<classification id="GO:0007155" class_type="GO">
<category>Biological Process</category>
<description>cell adhesion</description>
</classification>
<classification id="GO:0031012" class_type="GO">
<category>Cellular Component</category>
<description>extracellular matrix</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="A0JP86"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="O15230"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P02468"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P15215"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q06561"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00001500">
<author_list>Beck K, Hunter I, Engel J.</author_list>
<title>Structure and function of laminin: anatomy of a multidomain glycoprotein.</title>
<db_xref db="PUBMED" dbkey="2404817"/>
<journal>FASEB J.</journal>
<location issue="2" pages="148-60" volume="4"/>
<year>1990</year>
</publication>
<publication id="PUB00016907">
<author_list>Burgeson RE, Chiquet M, Deutzmann R, Ekblom P, Engel J, Kleinman H, Martin GR, Meneguzzi G, Paulsson M, Sanes J.</author_list>
<title>A new nomenclature for the laminins.</title>
<db_xref db="PUBMED" dbkey="7921537"/>
<journal>Matrix Biol.</journal>
<location issue="3" pages="209-11" volume="14"/>
<year>1994</year>
</publication>
<publication id="PUB00016908">
<author_list>Timpl R, Brown JC.</author_list>
<title>The laminins.</title>
<db_xref db="PUBMED" dbkey="7827749"/>
<journal>Matrix Biol.</journal>
<location issue="4" pages="275-81" volume="14"/>
<year>1994</year>
</publication>
<publication id="PUB00016909">
<author_list>Schulze B, Mann K, Poschl E, Yamada Y, Timpl R.</author_list>
<title>Structural and functional analysis of the globular domain IVa of the laminin alpha 1 chain and its impact on an adjacent RGD site.</title>
<db_xref db="PUBMED" dbkey="8615779"/>
<journal>Biochem. J.</journal>
<location pages="847-51" volume="314 ( Pt 3)"/>
<year>1996</year>
</publication>
<publication id="PUB00016911">
<author_list>Tunggal P, Smyth N, Paulsson M, Ott MC.</author_list>
<title>Laminins: structure and genetic regulation.</title>
<db_xref db="PUBMED" dbkey="11054872"/>
<journal>Microsc. Res. Tech.</journal>
<location issue="3" pages="214-27" volume="51"/>
<year>2000</year>
</publication>
<publication id="PUB00016910">
<author_list>Aumailley M, Smyth N.</author_list>
<title>The role of laminins in basement membrane function.</title>
<db_xref db="PUBMED" dbkey="9758133"/>
<journal>J. Anat.</journal>
<location pages="1-21" volume="193 ( Pt 1)"/>
<year>1998</year>
</publication>
</pub_list>
<child_list>
<rel_ref ipr_ref="IPR018031"/>
</child_list>
<member_list>
<db_xref protein_count="183" db="PFAM" dbkey="PF00052" name="Laminin_B"/>
<db_xref protein_count="190" db="PROFILE" dbkey="PS51115" name="LAMININ_IVA"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00052"/>
<db_xref db="BLOCKS" dbkey="IPB000034"/>
<db_xref db="PROSITEDOC" dbkey="PDOC51115"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="1"/>
<taxon_data name="Archaea" proteins_count="2"/>
<taxon_data name="Eukaryota" proteins_count="188"/>
<taxon_data name="Nematoda" proteins_count="8"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="8"/>
<taxon_data name="Arthropoda" proteins_count="78"/>
<taxon_data name="Fruit Fly" proteins_count="14"/>
<taxon_data name="Chordata" proteins_count="82"/>
<taxon_data name="Human" proteins_count="19"/>
<taxon_data name="Mouse" proteins_count="17"/>
<taxon_data name="Metazoa" proteins_count="187"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR018031"/>
</sec_list>
</interpro>
<interpro id="IPR000035" protein_count="241" short_name="Alkylbase_DNA_glycsylse_CS" type="Conserved_site">
<name>Alkylbase DNA glycosidase, conserved site</name>
<abstract>
<p>Alkylbase DNA glycosidases [<cite idref="PUB00000053"/>] are DNA repair enzymes that hydrolyse the deoxyribose N-glycosidic bond to excise various alkylated bases from a damaged DNA polymer. In <taxon tax_id="562">Escherichia coli</taxon> there are two alkylbase DNA glycosidases: one (gene tag) which is constitutively expressed and which is specific for the removal of 3-methyladenine (<db_xref db="EC" dbkey="3.2.2.20"/>), and one (gene alkA) which is induced during adaptation to alkylation and which can remove a variety of alkylation products (<db_xref db="EC" dbkey="3.2.2.21"/>). Tag and alkA do not share any region of sequence similarity. In yeast there is an alkylbase DNA glycosidase (gene MAG1) [<cite idref="PUB00001200"/>, <cite idref="PUB00001201"/>], which can remove 3-methyladenine or 7-methyladenine and which is structurally related to alkA. MAG and alkA are both proteins of about 300 amino acid residues. While the C- and N-terminal ends appear to be unrelated, there is a central region of about 130 residues which is well conserved.</p>
</abstract>
<class_list>
<classification id="GO:0003905" class_type="GO">
<category>Molecular Function</category>
<description>alkylbase DNA N-glycosylase activity</description>
</classification>
<classification id="GO:0006281" class_type="GO">
<category>Biological Process</category>
<description>DNA repair</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O94468"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P04395"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P22134"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00000053">
<author_list>Lindahl T, Sedgwick B, Sekiguchi M, Nakabeppu Y.</author_list>
<title>Regulation and expression of the adaptive response to alkylating agents.</title>
<db_xref db="PUBMED" dbkey="3052269"/>
<journal>Annu. Rev. Biochem.</journal>
<location pages="133-57" volume="57"/>
<year>1988</year>
</publication>
<publication id="PUB00001200">
<author_list>Berdal KG, Bjoras M, Bjelland S, Seeberg E.</author_list>
<title>Cloning and expression in Escherichia coli of a gene for an alkylbase DNA glycosylase from Saccharomyces cerevisiae; a homologue to the bacterial alkA gene.</title>
<db_xref db="PUBMED" dbkey="2265619"/>
<journal>EMBO J.</journal>
<location issue="13" pages="4563-8" volume="9"/>
<year>1990</year>
</publication>
<publication id="PUB00001201">
<author_list>Chen J, Derfler B, Samson L.</author_list>
<title>Saccharomyces cerevisiae 3-methyladenine DNA glycosylase has homology to the AlkA glycosylase of E. coli and is induced in response to DNA alkylation damage.</title>
<db_xref db="PUBMED" dbkey="2265620"/>
<journal>EMBO J.</journal>
<location issue="13" pages="4569-75" volume="9"/>
<year>1990</year>
</publication>
</pub_list>
<found_in>
<rel_ref ipr_ref="IPR003265"/>
<rel_ref ipr_ref="IPR011257"/>
</found_in>
<member_list>
<db_xref protein_count="241" db="PROSITE" dbkey="PS00516" name="ALKYLBASE_DNA_GLYCOS"/>
</member_list>
<external_doc_list>
<db_xref db="MSDsite" dbkey="PS00516"/>
<db_xref db="EC" dbkey="3.2.2.21"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00447"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1diz"/>
<db_xref db="PDB" dbkey="1mpg"/>
<db_xref db="PDB" dbkey="1pvs"/>
<db_xref db="PDB" dbkey="3cvs"/>
<db_xref db="PDB" dbkey="3cvt"/>
<db_xref db="PDB" dbkey="3cw7"/>
<db_xref db="PDB" dbkey="3cwa"/>
<db_xref db="PDB" dbkey="3cws"/>
<db_xref db="PDB" dbkey="3cwt"/>
<db_xref db="PDB" dbkey="3cwu"/>
<db_xref db="PDB" dbkey="3d4v"/>
<db_xref db="CATH" dbkey="1.10.1670.10"/>
<db_xref db="CATH" dbkey="1.10.340.30"/>
<db_xref db="SCOP" dbkey="a.96.1.3"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="214"/>
<taxon_data name="Archaea" proteins_count="3"/>
<taxon_data name="Eukaryota" proteins_count="23"/>
<taxon_data name="Fungi" proteins_count="23"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="7"/>
<taxon_data name="Unclassified" proteins_count="1"/>
<taxon_data name="Metazoa" proteins_count="23"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000036" protein_count="171" short_name="Peptidase_A26" type="Family">
<name>Peptidase A26, omptin</name>
<abstract>
<p>In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:</p>
<ul>
<li>Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.</li>
<li>Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule.</li>
</ul>
<p>In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding. </p>
<p>Aspartic endopeptidases <db_xref db="EC" dbkey="3.4.23."/> of vertebrate, fungal and retroviral origin have been characterised [<cite idref="PUB00006548"/>]. More recently, aspartic endopeptidases associated with the processing of bacterial type 4 prepilin [<cite idref="PUB00020023"/>] and archaean preflagellin have been described [<cite idref="PUB00035904"/>, <cite idref="PUB00014343"/>].</p>
<p>Structurally, aspartic endopeptidases are bilobal enzymes, each lobe contributing a catalytic Asp residue, with an extended active site cleft localised between the two lobes of the molecule. One lobe has probably evolved from the other through a gene duplication event in the distant past. In modern-day enzymes, although the three-dimensional structures are very similar, the amino acid sequences are more divergent, except for the catalytic site motif, which is very conserved. The presence and position of disulphide bridges are other conserved features of aspartic peptidases.
All or most aspartate peptidases are endopeptidases. These enzymes have been assigned into clans (proteins which are evolutionary related), and further sub-divided into families, largely on the basis of their tertiary structure.</p>
<p>This group of aspartic peptidases belongs to the MEROPS family A26 (clan AF). The omptin family, comprises a number of novel outer membrane-associated
serine proteases that are distinct from trypsin-like proteases in that
they cleave polypeptides between two basically-charged amino acids [<cite idref="PUB00002071"/>]. The enzyme is sensitive to the serine protease inhibitor diisopropylfluoro-phosphate, to divalent cations such as Cu<sup>2+</sup>, Zn<sup>2+</sup> and Fe<sup>2+</sup> [<cite idref="PUB00002071"/>], and is
temperature regulated, activity decreasing at lower temperatures [<cite idref="PUB00002071"/>, <cite idref="PUB00002246"/>]. Temperature regulation is most prominently shown in the <taxon tax_id="632">Yersinia pestis</taxon>
coagulase/fibrinolysin protein, where coagulase activity is prevalent
below 30 degrees Celsius, and fibrinolysin (protease) activity is prevalent
above this point, the optimum temperature being 37 degrees [<cite idref="PUB00003795"/>]. It is possible that this assists in 'flea blockage' and transmission of the bacteria to animals [<cite idref="PUB00003795"/>].</p>
<p>The <taxon tax_id="562">Escherichia coli</taxon> OmpT has previously been classified as a serine protease with Ser(99) and His(212) as active site residues. The X-ray structure of the enzyme is inconsistent with this classification, and the involvement of a nucleophilic water molecule that is activated by the Asp(210)/His(212) catalytic dyad classifies this as a aspartic endopeptidase where activity is also strongly dependent on Asp(83) and Asp(85). Both may function in binding of the water molecule and/or oxyanion stabilisation. The proposed mechanism implies a novel proteolytic catalytic site [<cite idref="PUB00011706"/>, <cite idref="PUB00011707"/>].</p>
</abstract>
<class_list>
<classification id="GO:0004175" class_type="GO">
<category>Molecular Function</category>
<description>endopeptidase activity</description>
</classification>
<classification id="GO:0006508" class_type="GO">
<category>Biological Process</category>
<description>proteolysis</description>
</classification>
<classification id="GO:0009279" class_type="GO">
<category>Cellular Component</category>
<description>cell outer membrane</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P09169"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00002071">
<author_list>Sugimura K, Nishihara T.</author_list>
<title>Purification, characterization, and primary structure of Escherichia coli protease VII with specificity for paired basic residues: identity of protease VII and OmpT.</title>
<db_xref db="PUBMED" dbkey="3056908"/>
<journal>J. Bacteriol.</journal>
<location issue="12" pages="5625-32" volume="170"/>
<year>1988</year>
</publication>
<publication id="PUB00002246">
<author_list>Kaufmann A, Stierhof YD, Henning U.</author_list>
<title>New outer membrane-associated protease of Escherichia coli K-12.</title>
<db_xref db="PUBMED" dbkey="8288530"/>
<journal>J. Bacteriol.</journal>
<location issue="2" pages="359-67" volume="176"/>
<year>1994</year>
</publication>
<publication id="PUB00003795">
<author_list>McDonough KA, Falkow S.</author_list>
<title>A Yersinia pestis-specific DNA fragment encodes temperature-dependent coagulase and fibrinolysin-associated phenotypes.</title>
<db_xref db="PUBMED" dbkey="2526282"/>
<journal>Mol. Microbiol.</journal>
<location issue="6" pages="767-75" volume="3"/>
<year>1989</year>
</publication>
<publication id="PUB00006548">
<author_list>Szecsi PB.</author_list>
<title>The aspartic proteases.</title>
<db_xref db="PUBMED" dbkey="1455179"/>
<journal>Scand. J. Clin. Lab. Invest. Suppl.</journal>
<location pages="5-22" volume="210"/>
<year>1992</year>
</publication>
<publication id="PUB00011706">
<author_list>Kramer RA, Vandeputte-Rutten L, de Roon GJ, Gros P, Dekker N, Egmond MR.</author_list>
<title>Identification of essential acidic residues of outer membrane protease OmpT supports a novel active site.</title>
<db_xref db="PUBMED" dbkey="11576541"/>
<journal>FEBS Lett.</journal>
<location issue="3" pages="426-30" volume="505"/>
<year>2001</year>
</publication>
<publication id="PUB00014343">
<author_list>Bardy SL, Jarrell KF.</author_list>
<title>Cleavage of preflagellins by an aspartic acid signal peptidase is essential for flagellation in the archaeon Methanococcus voltae.</title>
<db_xref db="PUBMED" dbkey="14622420"/>
<journal>Mol. Microbiol.</journal>
<location issue="4" pages="1339-47" volume="50"/>
<year>2003</year>
</publication>
<publication id="PUB00011707">
<author_list>Vandeputte-Rutten L, Kramer RA, Kroon J, Dekker N, Egmond MR, Gros P.</author_list>
<title>Crystal structure of the outer membrane protease OmpT from Escherichia coli suggests a novel catalytic site.</title>
<db_xref db="PUBMED" dbkey="11566868"/>
<journal>EMBO J.</journal>
<location issue="18" pages="5033-9" volume="20"/>
<year>2001</year>
</publication>
<publication id="PUB00035904">
<author_list>Ng SY, Chaban B, Jarrell KF.</author_list>
<title>Archaeal flagella, bacterial flagella and type IV pili: a comparison of genes and posttranslational modifications.</title>
<db_xref db="PUBMED" dbkey="16983194"/>
<journal>J. Mol. Microbiol. Biotechnol.</journal>
<location issue="3-5" pages="167-91" volume="11"/>
<year>2006</year>
</publication>
<publication id="PUB00020023">
<author_list>LaPointe CF, Taylor RK.</author_list>
<title>The type 4 prepilin peptidases comprise a novel family of aspartic acid proteases.</title>
<db_xref db="PUBMED" dbkey="10625704"/>
<journal>J. Biol. Chem.</journal>
<location issue="2" pages="1502-10" volume="275"/>
<year>2000</year>
</publication>
</pub_list>
<parent_list>
<rel_ref ipr_ref="IPR020080"/>
</parent_list>
<contains>
<rel_ref ipr_ref="IPR020079"/>
</contains>
<member_list>
<db_xref protein_count="170" db="PFAM" dbkey="PF01278" name="Omptin"/>
<db_xref protein_count="150" db="PIRSF" dbkey="PIRSF001522" name="Peptidase_A26"/>
<db_xref protein_count="161" db="PRINTS" dbkey="PR00482" name="OMPTIN"/>
<db_xref protein_count="162" db="GENE3D" dbkey="G3DSA:2.40.128.90" name="Peptidase_A26"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF01278"/>
<db_xref db="MSDsite" dbkey="PS00834"/>
<db_xref db="MSDsite" dbkey="PS00835"/>
<db_xref db="BLOCKS" dbkey="IPB000036"/>
<db_xref db="EC" dbkey="3.4.23"/>
<db_xref db="MEROPS" dbkey="A26"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00657"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1i78"/>
<db_xref db="CATH" dbkey="2.40.128.90"/>
<db_xref db="SCOP" dbkey="f.4.4.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="171"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000037" protein_count="2049" short_name="SsrA-bd_prot" type="Family">
<name>SsrA-binding protein</name>
<abstract>
<p>This entry represents SsrA-binding protein (aka small protein B or SmpB), which is a unique RNA-binding protein that is conserved throughout the bacterial kingdom and is an essential component of the SsrA quality-control system. Tight recognition of codon-anticodon pairings by the ribosome ensures the accuracy and fidelity of protein synthesis. In eubacteria, translational surveillance and ribosome rescue are performed by the 'tmRNA-SmpB' system (transfer messenger RNA-small protein B). SmpB binds specifically to the ssrA RNA (tmRNA) and is required for stable association of ssrA with ribosomes. SsrA RNA recognises ribosomes stalled on defective messages and acts to mediate the addition of a short peptide tag to the C terminus of the partially synthesised nascent polypeptide chain. Within a stalled ribosome, SmpB interacts with the three universally conserved bases G530, A1492 and A1493 that form the 30S subunit decoding centre, in which canonical codon-anticodon pairing occurs [<cite idref="PUB00045920"/>]. The SsrA-tagged protein is then degraded by C-terminal-specific proteases. Formation of an SmpB-SsrA complex appears to be critical in mediating SsrA activity after aminoacylation with alanine but prior to the transpeptidation reaction that couples this alanine to the nascent chain [<cite idref="PUB00006449"/>]. The SmpB protein has functional and structural similarities with initiation factor 1, and is proposed to be a functional mimic of the pairing between a codon and an anticodon. </p>
</abstract>
<class_list>
<classification id="GO:0003723" class_type="GO">
<category>Molecular Function</category>
<description>RNA binding</description>
</classification>
<classification id="GO:0006412" class_type="GO">
<category>Biological Process</category>
<description>translation</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="A2BTJ8"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="O66640"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P74355"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00006449">
<author_list>Karzai AW, Susskind MM, Sauer RT.</author_list>
<title>SmpB, a unique RNA-binding protein essential for the peptide-tagging activity of SsrA (tmRNA).</title>
<db_xref db="PUBMED" dbkey="10393194"/>
<journal>EMBO J.</journal>
<location issue="13" pages="3793-9" volume="18"/>
<year>1999</year>
</publication>
<publication id="PUB00045920">
<author_list>Nonin-Lecomte S, Germain-Amiot N, Gillet R, Hallier M, Ponchon L, Dardel F, Felden B.</author_list>
<title>Ribosome hijacking: a role for small protein B during trans-translation.</title>
<db_xref db="PUBMED" dbkey="19132006"/>
<journal>EMBO Rep.</journal>
<location issue="2" pages="160-5" volume="10"/>
<year>2009</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR020081"/>
</contains>
<member_list>
<db_xref protein_count="2032" db="PFAM" dbkey="PF01668" name="SmpB"/>
<db_xref protein_count="2014" db="PRODOM" dbkey="PD004488" name="SmpB"/>
<db_xref protein_count="2022" db="TIGRFAMs" dbkey="TIGR00086" name="smpB"/>
<db_xref protein_count="1941" db="GENE3D" dbkey="G3DSA:2.40.280.10" name="SmpB"/>
<db_xref protein_count="2040" db="SSF" dbkey="SSF74982" name="SmpB"/>
<db_xref protein_count="1894" db="HAMAP" dbkey="MF_00023" name="SmpB"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF01668"/>
<db_xref db="MSDsite" dbkey="PS01317"/>
<db_xref db="BLOCKS" dbkey="IPB000037"/>
<db_xref db="PROSITEDOC" dbkey="PDOC01021"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1j1h"/>
<db_xref db="PDB" dbkey="1k8h"/>
<db_xref db="PDB" dbkey="1p6v"/>
<db_xref db="PDB" dbkey="1wjx"/>
<db_xref db="PDB" dbkey="2czj"/>
<db_xref db="CATH" dbkey="2.40.280.10"/>
<db_xref db="SCOP" dbkey="b.111.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="2041"/>
<taxon_data name="Cyanobacteria" proteins_count="55"/>
<taxon_data name="Synechocystis PCC 6803" proteins_count="1"/>
<taxon_data name="Eukaryota" proteins_count="8"/>
<taxon_data name="Fungi" proteins_count="1"/>
<taxon_data name="Arthropoda" proteins_count="1"/>
<taxon_data name="Metazoa" proteins_count="3"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000038" protein_count="1164" short_name="Cell_Div_GTP-bd" type="Family">
<name>Cell division/GTP binding protein</name>
<abstract>
<p>Septins constitute a eukaryotic family of guanine nucleotide-binding proteins, most of which polymerise to form filaments [<cite idref="PUB00021050"/>]. Members of the family were first identified by genetic screening for <taxon tax_id="4932">Saccharomyces cerevisiae</taxon> (Baker's yeast) mutants defective in cytokinesis [<cite idref="PUB00010278"/>]. Temperature-sensitive mutations in four genes, CDC3, CDC10, CDC11 and CDC12, were found to cause cell-cycle arrest and defects in bud growth and cytokinesis. The protein products of these genes localise at the division plane between mother and daughter cells, indicating a role in mother-daughter separation during cytokinesis [<cite idref="PUB00010277"/>]. Members of the family were therefore termed septins to reflect their role in septation and cell division. The identification of septin homologues in higher eukaryotes, which localise to the cleavage furrow in dividing cells, supports an orthologous function in cytokinesis. Septins have since been identified in most eukaryotes, except plants [<cite idref="PUB00010366"/>].</p>
<p>Septins are approximately 40-50 kDa in molecular mass, and typically comprise a conserved central core domain (more than 35% sequence identity between mammalian and yeast homologues) flanked by more divergent N- and C-termini. Most septins possess a P-loop motif in their N-terminal domain (which is characteristic of GTP-binding proteins), and a predicted C-terminal coiled-coil domain [<cite idref="PUB00010351"/>].</p>
<p>A number of septin interaction partners have been identified in yeast, many of which are components of the budding site selection machinery, kinase cascades or of the ubiquitination pathway. It has been proposed that septins may act as a scaffold that provides an interaction matrix for other proteins [<cite idref="PUB00010366"/>, <cite idref="PUB00010351"/>]. In mammals, septins have been shown to regulate vesicle dynamics [<cite idref="PUB00010422"/>]. Mammalian septins have also been implicated in a variety of other cellular processes, including apoptosis, carcinogenesis and neurodegeneration [<cite idref="PUB00010316"/>].</p>
<p>This entry represents a variety of septins and homologous sequences involved in the cell division process.</p>
</abstract>
<class_list>
<classification id="GO:0005525" class_type="GO">
<category>Molecular Function</category>
<description>GTP binding</description>
</classification>
<classification id="GO:0007049" class_type="GO">
<category>Biological Process</category>
<description>cell cycle</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="A0LY86"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P25342"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P40797"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P42208"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q14141"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00010277">
<author_list>Haarer BK, Pringle JR.</author_list>
<title>Immunofluorescence localization of the Saccharomyces cerevisiae CDC12 gene product to the vicinity of the 10-nm filaments in the mother-bud neck.</title>
<db_xref db="PUBMED" dbkey="3316985"/>
<journal>Mol. Cell. Biol.</journal>
<location issue="10" pages="3678-87" volume="7"/>
<year>1987</year>
</publication>
<publication id="PUB00010278">
<author_list>Hartwell LH.</author_list>
<title>Genetic control of the cell division cycle in yeast. IV. Genes controlling bud emergence and cytokinesis.</title>
<db_xref db="PUBMED" dbkey="4950437"/>
<journal>Exp. Cell Res.</journal>
<location issue="2" pages="265-76" volume="69"/>
<year>1971</year>
</publication>
<publication id="PUB00010316">
<author_list>Kinoshita M, Kumar S, Mizoguchi A, Ide C, Kinoshita A, Haraguchi T, Hiraoka Y, Noda M.</author_list>
<title>Nedd5, a mammalian septin, is a novel cytoskeletal component interacting with actin-based structures.</title>
<db_xref db="PUBMED" dbkey="9203580"/>
<journal>Genes Dev.</journal>
<location issue="12" pages="1535-47" volume="11"/>
<year>1997</year>
</publication>
<publication id="PUB00010351">
<author_list>Field CM, Kellogg D.</author_list>
<title>Septins: cytoskeletal polymers or signalling GTPases?</title>
<db_xref db="PUBMED" dbkey="10481176"/>
<journal>Trends Cell Biol.</journal>
<location issue="10" pages="387-94" volume="9"/>
<year>1999</year>
</publication>
<publication id="PUB00021050">
<author_list>Kinoshita M.</author_list>
<title>The septins.</title>
<db_xref db="PUBMED" dbkey="14611653"/>
<journal>Genome Biol.</journal>
<location issue="11" pages="236" volume="4"/>
<year>2003</year>
</publication>
<publication id="PUB00010366">
<author_list>Longtine MS, Theesfeld CL, McMillan JN, Weaver E, Pringle JR, Lew DJ.</author_list>
<title>Septin-dependent assembly of a cell cycle-regulatory module in Saccharomyces cerevisiae.</title>
<db_xref db="PUBMED" dbkey="10805747"/>
<journal>Mol. Cell. Biol.</journal>
<location issue="11" pages="4049-61" volume="20"/>
<year>2000</year>
</publication>
<publication id="PUB00010422">
<author_list>Kinoshita M, Noda M.</author_list>
<title>Roles of septins in the mammalian cytokinesis machinery.</title>
<db_xref db="PUBMED" dbkey="11942624"/>
<journal>Cell Struct. Funct.</journal>
<location issue="6" pages="667-70" volume="26"/>
<year>2001</year>
</publication>
</pub_list>
<child_list>
<rel_ref ipr_ref="IPR016491"/>
</child_list>
<member_list>
<db_xref protein_count="1131" db="PANTHER" dbkey="PTHR18884" name="Cell_Div_GTP_bd"/>
<db_xref protein_count="945" db="PFAM" dbkey="PF00735" name="Septin"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00735"/>
<db_xref db="BLOCKS" dbkey="IPB000038"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="114"/>
<taxon_data name="Cyanobacteria" proteins_count="7"/>
<taxon_data name="Eukaryota" proteins_count="1048"/>
<taxon_data name="Fungi" proteins_count="462"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="44"/>
<taxon_data name="Other Eukaryotes" proteins_count="3"/>
<taxon_data name="Nematoda" proteins_count="4"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="4"/>
<taxon_data name="Arthropoda" proteins_count="96"/>
<taxon_data name="Fruit Fly" proteins_count="11"/>
<taxon_data name="Chordata" proteins_count="361"/>
<taxon_data name="Human" proteins_count="93"/>
<taxon_data name="Mouse" proteins_count="49"/>
<taxon_data name="Unclassified" proteins_count="2"/>
<taxon_data name="Other Eukaryotes" proteins_count="32"/>
<taxon_data name="Plastid Group" proteins_count="20"/>
<taxon_data name="Green Plants" proteins_count="20"/>
<taxon_data name="Metazoa" proteins_count="967"/>
<taxon_data name="Plastid Group" proteins_count="20"/>
<taxon_data name="Other Eukaryotes" proteins_count="6"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR016491"/>
</sec_list>
</interpro>
<interpro id="IPR000039" protein_count="330" short_name="Ribosomal_L18e" type="Family">
<name>Ribosomal protein L18e</name>
<abstract>
<p>Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [<cite idref="PUB00007068"/>, <cite idref="PUB00007069"/>]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. </p>
<p>Many of ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [<cite idref="PUB00007069"/>, <cite idref="PUB00007070"/>].</p>
<p>Members of this family are large subunit ribosomal proteins which are found in the Eukaryota and Archaea. These proteins have 115 to 187 amino-acid residues. The family consists of:<ul>
<li>Vertebrate L18 (known as L14 in Xenopus) [<cite idref="PUB00000657"/>]</li>
<li>Plant L18</li>
<li>Yeast L18 (Rp28)</li>
<li>
<taxon tax_id="2238">Haloarcula marismortui</taxon> (Halobacterium marismortui) HL29</li>
<li>
<taxon tax_id="2285">Sulfolobus acidocaldarius</taxon> HL29e</li>
</ul>
</p>
</abstract>
<class_list>
<classification id="GO:0003735" class_type="GO">
<category>Molecular Function</category>
<description>structural constituent of ribosome</description>
</classification>
<classification id="GO:0005622" class_type="GO">
<category>Cellular Component</category>
<description>intracellular</description>
</classification>
<classification id="GO:0005840" class_type="GO">
<category>Cellular Component</category>
<description>ribosome</description>
</classification>
<classification id="GO:0006412" class_type="GO">
<category>Biological Process</category>
<description>translation</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O45946"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P07279"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P35980"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q07020"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q9VS34"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00000657">
<author_list>Puder M, Barnard GF, Staniunas RJ, Steele GD Jr, Chen LB.</author_list>
<title>Nucleotide and deduced amino acid sequence of human ribosomal protein L18.</title>
<db_xref db="PUBMED" dbkey="8218404"/>
<journal>Biochim. Biophys. Acta</journal>
<location issue="1" pages="134-6" volume="1216"/>
<year>1993</year>
</publication>
<publication id="PUB00007068">
<author_list>Ramakrishnan V, Moore PB.</author_list>
<title>Atomic structures at last: the ribosome in 2000.</title>
<db_xref db="PUBMED" dbkey="11297922"/>
<journal>Curr. Opin. Struct. Biol.</journal>
<location issue="2" pages="144-54" volume="11"/>
<year>2001</year>
</publication>
<publication id="PUB00007069">
<author_list>Maguire BA, Zimmermann RA.</author_list>
<title>The ribosome in focus.</title>
<db_xref db="PUBMED" dbkey="11290319"/>
<journal>Cell</journal>
<location issue="6" pages="813-6" volume="104"/>
<year>2001</year>
</publication>
<publication id="PUB00007070">
<author_list>Chandra Sanyal S, Liljas A.</author_list>
<title>The end of the beginning: structural studies of ribosomal proteins.</title>
<db_xref db="PUBMED" dbkey="11114498"/>
<journal>Curr. Opin. Struct. Biol.</journal>
<location issue="6" pages="633-6" volume="10"/>
<year>2000</year>
</publication>
</pub_list>
<parent_list>
<rel_ref ipr_ref="IPR021131"/>
</parent_list>
<contains>
<rel_ref ipr_ref="IPR021132"/>
</contains>
<member_list>
<db_xref protein_count="330" db="PANTHER" dbkey="PTHR10934" name="Ribosomal_L18e"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00828"/>
<db_xref db="MSDsite" dbkey="PS01106"/>
<db_xref db="BLOCKS" dbkey="IPB000039"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00850"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Archaea" proteins_count="24"/>
<taxon_data name="Eukaryota" proteins_count="305"/>
<taxon_data name="Plastid Group" proteins_count="2"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="3"/>
<taxon_data name="Rice spp." proteins_count="6"/>
<taxon_data name="Fungi" proteins_count="66"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="4"/>
<taxon_data name="Other Eukaryotes" proteins_count="5"/>
<taxon_data name="Other Eukaryotes" proteins_count="1"/>
<taxon_data name="Nematoda" proteins_count="1"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="1"/>
<taxon_data name="Arthropoda" proteins_count="42"/>
<taxon_data name="Fruit Fly" proteins_count="1"/>
<taxon_data name="Chordata" proteins_count="70"/>
<taxon_data name="Human" proteins_count="4"/>
<taxon_data name="Mouse" proteins_count="4"/>
<taxon_data name="Unclassified" proteins_count="1"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
<taxon_data name="Plastid Group" proteins_count="54"/>
<taxon_data name="Green Plants" proteins_count="54"/>
<taxon_data name="Metazoa" proteins_count="202"/>
<taxon_data name="Plastid Group" proteins_count="23"/>
<taxon_data name="Plastid Group" proteins_count="9"/>
<taxon_data name="Other Eukaryotes" proteins_count="1"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000040" protein_count="233" short_name="AML1_Runt" type="Family">
<name>Acute myeloid leukemia 1 protein (AML 1)/Runt</name>
<abstract>
The AML1 gene is rearranged by the t(8;21) translocation in acute myeloid
leukemia [<cite idref="PUB00004459"/>]. The gene is highly similar to the <taxon tax_id="7227">Drosophila melanogaster</taxon> segmentation
gene runt and to the mouse transcription factor PEBP2 alpha subunit gene [<cite idref="PUB00004459"/>].
The region of shared similarity, known as the Runt domain, is responsible
for DNA-binding and protein-protein interaction.
<p> In addition to the highly-conserved Runt domain, the AML-1 gene product
carries a putative ATP-binding site (GRSGRGKS), and has a C-terminal region
rich in proline and serine residues. The protein (known as acute myeloid
leukemia 1 protein, oncogene AML-1, core-binding factor (CBF), alpha-B
subunit, etc.) binds to the core site, 5'-pygpyggt-3', of a number of
enhancers and promoters. </p>
<p>The protein is a heterodimer of alpha- and beta-subunits. The alpha-subunit
binds DNA as a monomer, and appears to have a role in the development of
normal hematopoiesis. CBF is a nuclear protein expressed in numerous tissue
types, except brain and heart; highest levels have been found to occur in
thymus, bone marrow and peripheral blood.</p>
</abstract>
<class_list>
<classification id="GO:0003677" class_type="GO">
<category>Molecular Function</category>
<description>DNA binding</description>
</classification>
<classification id="GO:0005524" class_type="GO">
<category>Molecular Function</category>
<description>ATP binding</description>
</classification>
<classification id="GO:0005634" class_type="GO">
<category>Cellular Component</category>
<description>nucleus</description>
</classification>
<classification id="GO:0006355" class_type="GO">
<category>Biological Process</category>
<description>regulation of transcription, DNA-dependent</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P22814"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q01196"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q03347"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q63046"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00004459">
<author_list>Miyoshi H, Ohira M, Shimizu K, Mitani K, Hirai H, Imai T, Yokoyama K, Soeda E, Ohki M.</author_list>
<title>Alternative splicing and genomic structure of the AML1 gene involved in acute myeloid leukemia.</title>
<db_xref db="PUBMED" dbkey="7651838"/>
<journal>Nucleic Acids Res.</journal>
<location issue="14" pages="2762-9" volume="23"/>
<year>1995</year>
</publication>
</pub_list>
<child_list>
<rel_ref ipr_ref="IPR016554"/>
</child_list>
<contains>
<rel_ref ipr_ref="IPR013524"/>
<rel_ref ipr_ref="IPR013711"/>
</contains>
<member_list>
<db_xref protein_count="233" db="PANTHER" dbkey="PTHR11950" name="AML1_Runt"/>
<db_xref protein_count="207" db="PRINTS" dbkey="PR00967" name="ONCOGENEAML1"/>
</member_list>
<external_doc_list>
<db_xref db="BLOCKS" dbkey="IPB000040"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1cmo"/>
<db_xref db="PDB" dbkey="1co1"/>
<db_xref db="PDB" dbkey="1e50"/>
<db_xref db="PDB" dbkey="1ean"/>
<db_xref db="PDB" dbkey="1eao"/>
<db_xref db="PDB" dbkey="1eaq"/>
<db_xref db="PDB" dbkey="1h9d"/>
<db_xref db="PDB" dbkey="1hjb"/>
<db_xref db="PDB" dbkey="1hjc"/>
<db_xref db="PDB" dbkey="1io4"/>
<db_xref db="PDB" dbkey="1ljm"/>
<db_xref db="PDB" dbkey="2j6w"/>
<db_xref db="CATH" dbkey="2.60.40.720"/>
<db_xref db="SCOP" dbkey="b.2.5.6"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Eukaryota" proteins_count="233"/>
<taxon_data name="Nematoda" proteins_count="1"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="1"/>
<taxon_data name="Arthropoda" proteins_count="99"/>
<taxon_data name="Fruit Fly" proteins_count="8"/>
<taxon_data name="Chordata" proteins_count="122"/>
<taxon_data name="Human" proteins_count="22"/>
<taxon_data name="Mouse" proteins_count="12"/>
<taxon_data name="Metazoa" proteins_count="233"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR016554"/>
</sec_list>
</interpro>
<interpro id="IPR000043" protein_count="1367" short_name="S-Ado-L-homoCys_hydrolase" type="Family">
<name>S-adenosyl-L-homocysteine hydrolase</name>
<abstract>
<p>S-adenosyl-L-homocysteine hydrolase (<db_xref db="EC" dbkey="3.3.1.1"/>) (AdoHcyase) is an enzyme of the activated methyl cycle, responsible for the reversible hydration of S-adenosyl-L-homocysteine into adenosine and homocysteine. AdoHcyase is an ubiquitous enzyme which binds and requires NAD<sup>+</sup> as a cofactor. AdoHcyase is a highly conserved protein [<cite idref="PUB00004791"/>] of about 430 to 470 amino acids. The family contains a glycine-rich region in the central part of AdoHcyase, which is thought to be involved in NAD-binding.</p>
</abstract>
<class_list>
<classification id="GO:0004013" class_type="GO">
<category>Molecular Function</category>
<description>adenosylhomocysteinase activity</description>
</classification>
<classification id="GO:0006730" class_type="GO">
<category>Biological Process</category>
<description>one-carbon metabolic process</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P23526"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P27604"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P39954"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P50245"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P50247"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00004791">
<author_list>Sganga MW, Aksamit RR, Cantoni GL, Bauer CE.</author_list>
<title>Mutational and nucleotide sequence analysis of S-adenosyl-L-homocysteine hydrolase from Rhodobacter capsulatus.</title>
<db_xref db="PUBMED" dbkey="1631127"/>
<journal>Proc. Natl. Acad. Sci. U.S.A.</journal>
<location issue="14" pages="6328-32" volume="89"/>
<year>1992</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR015878"/>
<rel_ref ipr_ref="IPR016040"/>
<rel_ref ipr_ref="IPR020082"/>
</contains>
<member_list>
<db_xref protein_count="1355" db="PANTHER" dbkey="PTHR23420" name="Ad_hcy_hydrolase"/>
<db_xref protein_count="1333" db="PFAM" dbkey="PF05221" name="AdoHcyase"/>
<db_xref protein_count="1200" db="PIRSF" dbkey="PIRSF001109" name="Ad_hcy_hydrolase"/>
<db_xref protein_count="1188" db="TIGRFAMs" dbkey="TIGR00936" name="ahcY"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF05221"/>
<db_xref db="MSDsite" dbkey="PS00738"/>
<db_xref db="MSDsite" dbkey="PS00739"/>
<db_xref db="BLOCKS" dbkey="IPB000043"/>
<db_xref db="EC" dbkey="3.3.1.1"/>
<db_xref db="PRIAM" dbkey="PRI000861"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00603"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1a7a"/>
<db_xref db="PDB" dbkey="1b3r"/>
<db_xref db="PDB" dbkey="1d4f"/>
<db_xref db="PDB" dbkey="1k0u"/>
<db_xref db="PDB" dbkey="1ky4"/>
<db_xref db="PDB" dbkey="1ky5"/>
<db_xref db="PDB" dbkey="1li4"/>
<db_xref db="PDB" dbkey="1v8b"/>
<db_xref db="PDB" dbkey="1xwf"/>
<db_xref db="PDB" dbkey="2h5l"/>
<db_xref db="PDB" dbkey="3d64"/>
<db_xref db="CATH" dbkey="3.40.50.1480"/>
<db_xref db="CATH" dbkey="3.40.50.720"/>
<db_xref db="SCOP" dbkey="c.2.1.4"/>
<db_xref db="SCOP" dbkey="c.23.12.3"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="872"/>
<taxon_data name="Cyanobacteria" proteins_count="55"/>
<taxon_data name="Synechocystis PCC 6803" proteins_count="1"/>
<taxon_data name="Archaea" proteins_count="94"/>
<taxon_data name="Eukaryota" proteins_count="401"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="14"/>
<taxon_data name="Rice spp." proteins_count="4"/>
<taxon_data name="Fungi" proteins_count="70"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="7"/>
<taxon_data name="Other Eukaryotes" proteins_count="4"/>
<taxon_data name="Other Eukaryotes" proteins_count="1"/>
<taxon_data name="Nematoda" proteins_count="1"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="1"/>
<taxon_data name="Arthropoda" proteins_count="57"/>
<taxon_data name="Fruit Fly" proteins_count="5"/>
<taxon_data name="Chordata" proteins_count="83"/>
<taxon_data name="Human" proteins_count="15"/>
<taxon_data name="Mouse" proteins_count="16"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
<taxon_data name="Plastid Group" proteins_count="112"/>
<taxon_data name="Green Plants" proteins_count="112"/>
<taxon_data name="Metazoa" proteins_count="237"/>
<taxon_data name="Plastid Group" proteins_count="28"/>
<taxon_data name="Plastid Group" proteins_count="10"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000044" protein_count="25" short_name="Uncharacterised_lipoprot_MG045" type="Family">
<name>Uncharacterised lipoprotein MG045</name>
<abstract>
<p> Mycoplasma genitalium has the smallest known genome of any free-living organism. Its complete genome sequence has been determined by whole-genome random sequencing and assembly [<cite idref="PUB00005212"/>]. Only 470 putative coding regions were identified, including genes for DNA replication, transcription and translation, DNA repair, cellular transport and energy metabolism [<cite idref="PUB00005212"/>]. A hypothetical protein from the MG045 gene [<cite idref="PUB00002233"/>] has a homologue of similarly unknown function in M.pneumoniae; these, in turn, share regions of similarity with a family of putative lipoproteins from Ureaplasma parvum and Ureaplasma urealyticum. </p>
</abstract>
<class_list>
<classification id="GO:0016020" class_type="GO">
<category>Cellular Component</category>
<description>membrane</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P47291"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00002233">
<author_list>Peterson SN, Hu PC, Bott KF, Hutchison CA 3rd.</author_list>
<title>A survey of the Mycoplasma genitalium genome by using random sequencing.</title>
<db_xref db="PUBMED" dbkey="8253680"/>
<journal>J. Bacteriol.</journal>
<location issue="24" pages="7918-30" volume="175"/>
<year>1993</year>
</publication>
<publication id="PUB00005212">
<author_list>Fraser CM, Gocayne JD, White O, Adams MD, Clayton RA, Fleischmann RD, Bult CJ, Kerlavage AR, Sutton G, Kelley JM, Fritchman RD, Weidman JF, Small KV, Sandusky M, Fuhrmann J, Nguyen D, Utterback TR, Saudek DM, Phillips CA, Merrick JM, Tomb JF, Dougherty BA, Bott KF, Hu PC, Lucier TS, Peterson SN, Smith HO, Hutchison CA 3rd, Venter JC.</author_list>
<title>The minimal gene complement of Mycoplasma genitalium.</title>
<db_xref db="PUBMED" dbkey="7569993"/>
<journal>Science</journal>
<location issue="5235" pages="397-403" volume="270"/>
<year>1995</year>
</publication>
</pub_list>
<member_list>
<db_xref protein_count="25" db="PRINTS" dbkey="PR00905" name="MG045FAMILY"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF02030"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="25"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000045" protein_count="2278" short_name="Peptidase_A24A_prepilin_IV" type="Domain">
<name>Peptidase A24A, prepilin type IV</name>
<abstract>
<p>In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:</p>
<ul>
<li>Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.</li>
<li>Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule.</li>
</ul>
<p>In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding. </p>
<p>Aspartic endopeptidases <db_xref db="EC" dbkey="3.4.23."/> of vertebrate, fungal and retroviral origin have been characterised [<cite idref="PUB00006548"/>]. More recently, aspartic endopeptidases associated with the processing of bacterial type 4 prepilin [<cite idref="PUB00020023"/>] and archaean preflagellin have been described [<cite idref="PUB00035904"/>, <cite idref="PUB00014343"/>].</p>
<p>Structurally, aspartic endopeptidases are bilobal enzymes, each lobe contributing a catalytic Asp residue, with an extended active site cleft localised between the two lobes of the molecule. One lobe has probably evolved from the other through a gene duplication event in the distant past. In modern-day enzymes, although the three-dimensional structures are very similar, the amino acid sequences are more divergent, except for the catalytic site motif, which is very conserved. The presence and position of disulphide bridges are other conserved features of aspartic peptidases.
All or most aspartate peptidases are endopeptidases. These enzymes have been assigned into clans (proteins which are evolutionary related), and further sub-divided into families, largely on the basis of their tertiary structure.</p>
<p>This group of aspartic endopeptidases belong to MEROPS peptidase family A24 (type IV prepilin peptidase family, clan AD), subfamily A24A.</p>
<p>Bacteria produce a number of protein precursors that undergo post-translational methylation and proteolysis prior to secretion as active
proteins. Type IV prepilin leader peptidases are enzymes that mediate this type of post-translational modification. Type IV pilin is a protein found on the surface of <taxon tax_id="287">Pseudomonas aeruginosa</taxon>, <taxon tax_id="485">Neisseria gonorrhoeae</taxon> and other Gram-negative
pathogens. Pilin subunits attach the infecting organism to the surface of
host epithelial cells. They are synthesised as prepilin subunits, which
differ from mature pilin by virtue of containing a 6-8 residue leader
peptide consisting of charged amino acids. Mature type IV pilins also
contain a methylated N-terminal phenylalanine residue.</p>
<p> The bifunctional enzyme prepilin peptidase (PilD) from <taxon tax_id="287">Pseudomonas aeruginosa</taxon> is a key determinant in both type-IV pilus biogenesis and extracellular protein secretion, in its roles as a leader peptidase and methyl transferase (MTase). It is responsible for endopeptidic cleavage of the unique leader peptides that characterise type-IV pilin precursors, as well as proteins with homologous leader sequences that are essential components of the general secretion pathway found in a variety of Gram-negative pathogens. Following removal of the leader peptides, the same enzyme is responsible for the second posttranslational modification that characterises the type-IV pilins and their homologues, namely N-methylation of the newly exposed N-terminal amino acid residue [<cite idref="PUB00014532"/>]. </p>
</abstract>
<class_list>
<classification id="GO:0004190" class_type="GO">
<category>Molecular Function</category>
<description>aspartic-type endopeptidase activity</description>
</classification>
<classification id="GO:0016020" class_type="GO">
<category>Cellular Component</category>
<description>membrane</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="A2T195"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="O26521"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P72640"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00006548">
<author_list>Szecsi PB.</author_list>
<title>The aspartic proteases.</title>
<db_xref db="PUBMED" dbkey="1455179"/>
<journal>Scand. J. Clin. Lab. Invest. Suppl.</journal>
<location pages="5-22" volume="210"/>
<year>1992</year>
</publication>
<publication id="PUB00014343">
<author_list>Bardy SL, Jarrell KF.</author_list>
<title>Cleavage of preflagellins by an aspartic acid signal peptidase is essential for flagellation in the archaeon Methanococcus voltae.</title>
<db_xref db="PUBMED" dbkey="14622420"/>
<journal>Mol. Microbiol.</journal>
<location issue="4" pages="1339-47" volume="50"/>
<year>2003</year>
</publication>
<publication id="PUB00014532">
<author_list>Lory S, Strom MS.</author_list>
<title>Structure-function relationship of type-IV prepilin peptidase of Pseudomonas aeruginosa--a review.</title>
<db_xref db="PUBMED" dbkey="9224881"/>
<journal>Gene</journal>
<location issue="1" pages="117-21" volume="192"/>
<year>1997</year>
</publication>
<publication id="PUB00020023">
<author_list>LaPointe CF, Taylor RK.</author_list>
<title>The type 4 prepilin peptidases comprise a novel family of aspartic acid proteases.</title>
<db_xref db="PUBMED" dbkey="10625704"/>
<journal>J. Biol. Chem.</journal>
<location issue="2" pages="1502-10" volume="275"/>
<year>2000</year>
</publication>
<publication id="PUB00035904">
<author_list>Ng SY, Chaban B, Jarrell KF.</author_list>
<title>Archaeal flagella, bacterial flagella and type IV pili: a comparison of genes and posttranslational modifications.</title>
<db_xref db="PUBMED" dbkey="16983194"/>
<journal>J. Mol. Microbiol. Biotechnol.</journal>
<location issue="3-5" pages="167-91" volume="11"/>
<year>2006</year>
</publication>
</pub_list>
<found_in>
<rel_ref ipr_ref="IPR014032"/>
</found_in>
<member_list>
<db_xref protein_count="2278" db="PFAM" dbkey="PF01478" name="Peptidase_A24"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF01478"/>
<db_xref db="BLOCKS" dbkey="IPB000045"/>
<db_xref db="MEROPS" dbkey="A24"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="2185"/>
<taxon_data name="Cyanobacteria" proteins_count="47"/>
<taxon_data name="Synechocystis PCC 6803" proteins_count="1"/>
<taxon_data name="Archaea" proteins_count="87"/>
<taxon_data name="Eukaryota" proteins_count="3"/>
<taxon_data name="Chordata" proteins_count="1"/>
<taxon_data name="Mouse" proteins_count="1"/>
<taxon_data name="Unclassified" proteins_count="1"/>
<taxon_data name="Unclassified" proteins_count="2"/>
<taxon_data name="Plastid Group" proteins_count="2"/>
<taxon_data name="Green Plants" proteins_count="2"/>
<taxon_data name="Metazoa" proteins_count="1"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000046" protein_count="25" short_name="NK1_rcpt" type="Family">
<name>Neurokinin NK1 receptor</name>
<abstract>
<p>G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [<cite idref="PUB00004961"/>]. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/). </p>
<p>The rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7
transmembrane (TM) helices [<cite idref="PUB00000131"/>, <cite idref="PUB00002477"/>, <cite idref="PUB00004960"/>].</p>
<p>Neuropeptide receptors are present in very small quantities in the cell
and are embedded tightly in the plasma membrane. The neuropeptides exhibit
a high degree of functional diversity through both regulation of peptide
production and through peptide-receptor interaction [<cite idref="PUB00002518"/>]. The mammalian
tachykinin system consists of 3 distinct peptides: substance P, substance
K and neuromedin K. All possess a common spectrum of biological activities,
including sensory transmission in the nervous system and contraction/
relaxation of peripheral smooth muscles, and each interacts with a
specific receptor type.</p>
<p>In the brain, high concentrations of the NK1 receptor are found in striatum,
olfactory bulb, dendate gyrus, locus coeruleus and spinal chord [<cite idref="PUB00010571"/>]. In
peripheral tissues NK1 receptors are found in smooth muscle (e.g., ileum
and bladder), enteric neurons, secretory glands (e.g. parotid), cells of
the immune system and vascular endothelium. NK1 receptors activate the
phosphoinositide pathway through a pertussis-toxin-insensitive G-protein [<cite idref="PUB00010572"/>].</p>
</abstract>
<class_list>
<classification id="GO:0004995" class_type="GO">
<category>Molecular Function</category>
<description>tachykinin receptor activity</description>
</classification>
<classification id="GO:0005886" class_type="GO">
<category>Cellular Component</category>
<description>plasma membrane</description>
</classification>
<classification id="GO:0007186" class_type="GO">
<category>Biological Process</category>
<description>G-protein coupled receptor protein signaling pathway</description>
</classification>
<classification id="GO:0016021" class_type="GO">
<category>Cellular Component</category>
<description>integral to membrane</description>
</classification>
</class_list>
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</example>
<example>
<db_xref db="SWISSPROT" dbkey="P25103"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P30548"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00000131">
<author_list>Birnbaumer L.</author_list>
<title>G proteins in signal transduction.</title>
<db_xref db="PUBMED" dbkey="2111655"/>
<journal>Annu. Rev. Pharmacol. Toxicol.</journal>
<location pages="675-705" volume="30"/>
<year>1990</year>
</publication>
<publication id="PUB00002477">
<author_list>Casey PJ, Gilman AG.</author_list>
<title>G protein involvement in receptor-effector coupling.</title>
<db_xref db="PUBMED" dbkey="2830256"/>
<journal>J. Biol. Chem.</journal>
<location issue="6" pages="2577-80" volume="263"/>
<year>1988</year>
</publication>
<publication id="PUB00002518">
<author_list>Yokota Y, Sasai Y, Tanaka K, Fujiwara T, Tsuchida K, Shigemoto R, Kakizuka A, Ohkubo H, Nakanishi S.</author_list>
<title>Molecular characterization of a functional cDNA for rat substance P receptor.</title>
<db_xref db="PUBMED" dbkey="2478537"/>
<journal>J. Biol. Chem.</journal>
<location issue="30" pages="17649-52" volume="264"/>
<year>1989</year>
</publication>
<publication id="PUB00004960">
<author_list>Attwood TK, Findlay JB.</author_list>
<title>Design of a discriminating fingerprint for G-protein-coupled receptors.</title>
<db_xref db="PUBMED" dbkey="8386361"/>
<journal>Protein Eng.</journal>
<location issue="2" pages="167-76" volume="6"/>
<year>1993</year>
</publication>
<publication id="PUB00004961">
<author_list>Attwood TK, Findlay JB.</author_list>
<title>Fingerprinting G-protein-coupled receptors.</title>
<db_xref db="PUBMED" dbkey="8170923"/>
<journal>Protein Eng.</journal>
<location issue="2" pages="195-203" volume="7"/>
<year>1994</year>
</publication>
<publication id="PUB00010571">
<author_list>Yip J, Chahl LA.</author_list>
<title>Localization of tachykinin receptors and Fos-like immunoreactivity induced by substance P in guinea-pig brain.</title>
<db_xref db="PUBMED" dbkey="11071315"/>
<journal>Clin. Exp. Pharmacol. Physiol.</journal>
<location issue="11" pages="943-6" volume="27"/>
<year>2000</year>
</publication>
<publication id="PUB00010572">
<author_list>Gilbert R, Ryan JS, Horackova M, Smith FM, Kelly ME.</author_list>
<title>Actions of substance P on membrane potential and ionic currents in guinea pig stellate ganglion neurons.</title>
<db_xref db="PUBMED" dbkey="9575785"/>
<journal>Am. J. Physiol.</journal>
<location issue="4 Pt 1" pages="C892-903" volume="274"/>
<year>1998</year>
</publication>
</pub_list>
<parent_list>
<rel_ref ipr_ref="IPR001681"/>
</parent_list>
<member_list>
<db_xref protein_count="25" db="PRINTS" dbkey="PR01024" name="NEUROKININ1R"/>
</member_list>
<external_doc_list>
<db_xref db="BLOCKS" dbkey="IPB000046"/>
<db_xref db="IUPHAR" dbkey="3029"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Eukaryota" proteins_count="25"/>
<taxon_data name="Chordata" proteins_count="25"/>
<taxon_data name="Human" proteins_count="4"/>
<taxon_data name="Mouse" proteins_count="3"/>
<taxon_data name="Metazoa" proteins_count="25"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000047" protein_count="1740" short_name="HTH_lambrepressr" type="Domain">
<name>Helix-turn-helix motif, lambda-like repressor</name>
<abstract>
Helix-turn-helix (HTH) motifs are found in all known DNA binding proteins
that regulate gene expression. The motif consists of approximately 20
residues and is characterised by 2 alpha-helices, which make intimate
contacts with the DNA and are joined by a short turn. The second helix of
the HTH motif binds to DNA via a number of hydrogen bonds and hydrophobic
interactions, which occur between specific side chains and the exposed
bases and thymine methyl groups within the major groove of the DNA [<cite idref="PUB00002521"/>]. The
first helix helps to stabilise the structure [<cite idref="PUB00003978"/>].
<p>The HTH motif is very similar in sequence and structure to the N-terminal
region of the lamda [<cite idref="PUB00000036"/>] and other repressor proteins, and has also been
identified in many other DNA-binding proteins on the basis of sequence and
structural similarity [<cite idref="PUB00002521"/>]. One of the principal differences between HTH
motifs in these different proteins arises from the stereochemical
requirement for glycine in the turn, which is needed to avoid steric
interference of the beta-carbon with the main chain: for cro and other
repressors the Gly appears to be mandatory, while for many of the homeotic
and other DNA-binding proteins the requirement is relaxed.</p>
</abstract>
<class_list>
<classification id="GO:0003700" class_type="GO">
<category>Molecular Function</category>
<description>transcription factor activity</description>
</classification>
<classification id="GO:0005634" class_type="GO">
<category>Cellular Component</category>
<description>nucleus</description>
</classification>
<classification id="GO:0006355" class_type="GO">
<category>Biological Process</category>
<description>regulation of transcription, DNA-dependent</description>
</classification>
</class_list>
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<example>
<db_xref db="SWISSPROT" dbkey="O08686"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="O23208"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P02836"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P20269"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P56178"/>
</example>
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<pub_list>
<publication id="PUB00000036">
<author_list>Pabo CO, Sauer RT.</author_list>
<title>Protein-DNA recognition.</title>
<db_xref db="PUBMED" dbkey="6236744"/>
<journal>Annu. Rev. Biochem.</journal>
<location pages="293-321" volume="53"/>
<year>1984</year>
</publication>
<publication id="PUB00002521">
<author_list>Brennan RG, Matthews BW.</author_list>
<title>The helix-turn-helix DNA binding motif.</title>
<db_xref db="PUBMED" dbkey="2644244"/>
<journal>J. Biol. Chem.</journal>
<location issue="4" pages="1903-6" volume="264"/>
<year>1989</year>
</publication>
<publication id="PUB00003978">
<author_list>Sauer RT, Yocum RR, Doolittle RF, Lewis M, Pabo CO.</author_list>
<title>Homology among DNA-binding proteins suggests use of a conserved super-secondary structure.</title>
<db_xref db="PUBMED" dbkey="6896364"/>
<journal>Nature</journal>
<location issue="5873" pages="447-51" volume="298"/>
<year>1982</year>
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<contains>
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<found_in>
<rel_ref ipr_ref="IPR000747"/>
<rel_ref ipr_ref="IPR001356"/>
<rel_ref ipr_ref="IPR009057"/>
<rel_ref ipr_ref="IPR012287"/>
<rel_ref ipr_ref="IPR015703"/>
<rel_ref ipr_ref="IPR015704"/>
<rel_ref ipr_ref="IPR015705"/>
<rel_ref ipr_ref="IPR020479"/>
</found_in>
<member_list>
<db_xref protein_count="1740" db="PRINTS" dbkey="PR00031" name="HTHREPRESSR"/>
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<external_doc_list>
<db_xref db="BLOCKS" dbkey="IPB000047"/>
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<db_xref db="PDB" dbkey="1du0"/>
<db_xref db="PDB" dbkey="1enh"/>
<db_xref db="PDB" dbkey="1hdd"/>
<db_xref db="PDB" dbkey="1p7i"/>
<db_xref db="PDB" dbkey="1p7j"/>
<db_xref db="PDB" dbkey="1ztr"/>
<db_xref db="PDB" dbkey="2hdd"/>
<db_xref db="PDB" dbkey="2jwt"/>
<db_xref db="PDB" dbkey="2p81"/>
<db_xref db="PDB" dbkey="3hdd"/>
<db_xref db="CATH" dbkey="1.10.10.60"/>
<db_xref db="SCOP" dbkey="a.4.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Eukaryota" proteins_count="1739"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="30"/>
<taxon_data name="Rice spp." proteins_count="61"/>
<taxon_data name="Fungi" proteins_count="7"/>
<taxon_data name="Nematoda" proteins_count="13"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="13"/>
<taxon_data name="Arthropoda" proteins_count="358"/>
<taxon_data name="Fruit Fly" proteins_count="31"/>
<taxon_data name="Chordata" proteins_count="658"/>
<taxon_data name="Human" proteins_count="59"/>
<taxon_data name="Mouse" proteins_count="54"/>
<taxon_data name="Virus" proteins_count="1"/>
<taxon_data name="Plastid Group" proteins_count="338"/>
<taxon_data name="Green Plants" proteins_count="338"/>
<taxon_data name="Metazoa" proteins_count="1401"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000048" protein_count="4511" short_name="IQ_CaM-bd_region" type="Region">
<name>IQ calmodulin-binding region</name>
<abstract>
<p>Calmodulin (CaM) is recognised as a major calcium sensor and orchestrator of regulatory events through its interaction with a diverse group of cellular proteins. Three classes of recognition motifs exist for many of the known CaM binding proteins; the IQ motif as a consensus for Ca<sup>2+</sup>-independent binding and two related motifs for Ca<sup>2+</sup>-dependent binding, termed
18-14 and 1-5-10 based on the position of conserved hydrophobic residues [<cite idref="PUB00001532"/>].</p>
<p>The regulatory domain of scallop myosin is a three-chain protein complex that
switches on this motor in response to Ca<sup>2+</sup> binding. Side-chain interactions link the two light chains in tandem to adjacent segments of the heavy chain bearing the IQ-sequence motif. The Ca<sup>2+</sup>-binding site is a novel EF-hand motif on the essential light chain and is stabilised by linkages involving the heavy chain and both light chains, accounting for the requirement of all three chains for Ca<sup>2+</sup> binding and regulation in the intact myosin molecule [<cite idref="PUB00004175"/>].</p>
</abstract>
<example_list>
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<example>
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<example>
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<example>
<db_xref db="SWISSPROT" dbkey="P19524"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P27671"/>
</example>
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<pub_list>
<publication id="PUB00001532">
<author_list>Rhoads AR, Friedberg F.</author_list>
<title>Sequence motifs for calmodulin recognition.</title>
<db_xref db="PUBMED" dbkey="9141499"/>
<journal>FASEB J.</journal>
<location issue="5" pages="331-40" volume="11"/>
<year>1997</year>
</publication>
<publication id="PUB00004175">
<author_list>Xie X, Harrison DH, Schlichting I, Sweet RM, Kalabokis VN, Szent-Gyorgyi AG, Cohen C.</author_list>
<title>Structure of the regulatory domain of scallop myosin at 2.8 A resolution.</title>
<db_xref db="PUBMED" dbkey="8127365"/>
<journal>Nature</journal>
<location issue="6469" pages="306-12" volume="368"/>
<year>1994</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR018243"/>
</contains>
<found_in>
<rel_ref ipr_ref="IPR001422"/>
<rel_ref ipr_ref="IPR001696"/>
<rel_ref ipr_ref="IPR008052"/>
<rel_ref ipr_ref="IPR008053"/>
<rel_ref ipr_ref="IPR008054"/>
<rel_ref ipr_ref="IPR012008"/>
<rel_ref ipr_ref="IPR012105"/>
<rel_ref ipr_ref="IPR015650"/>
</found_in>
<member_list>
<db_xref protein_count="2291" db="PFAM" dbkey="PF00612" name="IQ"/>
<db_xref protein_count="4216" db="PROFILE" dbkey="PS50096" name="IQ"/>
<db_xref protein_count="3768" db="SMART" dbkey="SM00015" name="IQ"/>
</member_list>
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<db_xref db="PANDIT" dbkey="PF00612"/>
<db_xref db="BLOCKS" dbkey="IPB000048"/>
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<structure_db_links>
<db_xref db="PDB" dbkey="1b7t"/>
<db_xref db="PDB" dbkey="1br1"/>
<db_xref db="PDB" dbkey="1br2"/>
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<db_xref db="PDB" dbkey="1d0z"/>
<db_xref db="PDB" dbkey="1d1a"/>
<db_xref db="PDB" dbkey="1d1b"/>
<db_xref db="PDB" dbkey="1d1c"/>
<db_xref db="PDB" dbkey="1dfk"/>
<db_xref db="PDB" dbkey="1dfl"/>
<db_xref db="PDB" dbkey="1fmv"/>
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<db_xref db="PDB" dbkey="1qvi"/>
<db_xref db="PDB" dbkey="1s5g"/>
<db_xref db="PDB" dbkey="1scm"/>
<db_xref db="PDB" dbkey="1sr6"/>
<db_xref db="PDB" dbkey="1vom"/>
<db_xref db="PDB" dbkey="1w7i"/>
<db_xref db="PDB" dbkey="1w7j"/>
<db_xref db="PDB" dbkey="1wdc"/>
<db_xref db="PDB" dbkey="2mys"/>
<db_xref db="CATH" dbkey="4.10.270.10"/>
<db_xref db="SCOP" dbkey="c.37.1.9"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="198"/>
<taxon_data name="Cyanobacteria" proteins_count="6"/>
<taxon_data name="Archaea" proteins_count="3"/>
<taxon_data name="Eukaryota" proteins_count="4305"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="118"/>
<taxon_data name="Rice spp." proteins_count="224"/>
<taxon_data name="Fungi" proteins_count="344"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="24"/>
<taxon_data name="Other Eukaryotes" proteins_count="31"/>
<taxon_data name="Other Eukaryotes" proteins_count="37"/>
<taxon_data name="Nematoda" proteins_count="30"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="30"/>
<taxon_data name="Arthropoda" proteins_count="585"/>
<taxon_data name="Fruit Fly" proteins_count="90"/>
<taxon_data name="Chordata" proteins_count="1326"/>
<taxon_data name="Human" proteins_count="235"/>
<taxon_data name="Mouse" proteins_count="210"/>
<taxon_data name="Virus" proteins_count="6"/>
<taxon_data name="Unclassified" proteins_count="1"/>
<taxon_data name="Other Eukaryotes" proteins_count="20"/>
<taxon_data name="Plastid Group" proteins_count="946"/>
<taxon_data name="Green Plants" proteins_count="946"/>
<taxon_data name="Metazoa" proteins_count="2519"/>
<taxon_data name="Plastid Group" proteins_count="314"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
<taxon_data name="Plastid Group" proteins_count="180"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
<taxon_data name="Other Eukaryotes" proteins_count="52"/>
<taxon_data name="Other Eukaryotes" proteins_count="20"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000049" protein_count="1178" short_name="ET-Flavoprotein_bsu_CS" type="Conserved_site">
<name>Electron transfer flavoprotein, beta-subunit, conserved site</name>
<abstract>
The electron transfer flavoprotein (ETF) [<cite idref="PUB00004936"/>, <cite idref="PUB00005086"/>]
serves as a specific electron
acceptor for various mitochondrial dehydrogenases. ETF transfers electrons to
the main respiratory chain via ETF-ubiquinone oxidoreductase. ETF is an
heterodimer that consist of an alpha and a beta subunit and which bind one
molecule of FAD per dimer. A similar system also exists in some bacteria.
The beta subunit of ETF is a protein of about 28 Kd which is structurally
related to the bacterial nitrogen fixation protein fixA which could play a
role in a redox process and feed electrons to ferredoxin.
The beta subunit protein is distantly related to and forms a
heterodimer with the alpha subunit <db_xref db="INTERPRO" dbkey="IPR001308"/>.
</abstract>
<class_list>
<classification id="GO:0009055" class_type="GO">
<category>Molecular Function</category>
<description>electron carrier activity</description>
</classification>
</class_list>
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</example>
<example>
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</example>
<example>
<db_xref db="SWISSPROT" dbkey="P42940"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q9DCW4"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q9LSW8"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00004936">
<author_list>Finocchiaro G, Ikeda Y, Ito M, Tanaka K.</author_list>
<title>Biosynthesis, molecular cloning and sequencing of electron transfer flavoprotein.</title>
<db_xref db="PUBMED" dbkey="2326318"/>
<journal>Prog. Clin. Biol. Res.</journal>
<location pages="637-52" volume="321"/>
<year>1990</year>
</publication>
<publication id="PUB00005086">
<author_list>Tsai MH, Saier MH Jr.</author_list>
<title>Phylogenetic characterization of the ubiquitous electron transfer flavoprotein families ETF-alpha and ETF-beta.</title>
<db_xref db="PUBMED" dbkey="8525056"/>
<journal>Res. Microbiol.</journal>
<location issue="5" pages="397-404" volume="146"/>
<year>1995</year>
</publication>
</pub_list>
<found_in>
<rel_ref ipr_ref="IPR012255"/>
<rel_ref ipr_ref="IPR014729"/>
<rel_ref ipr_ref="IPR014730"/>
</found_in>
<member_list>
<db_xref protein_count="1178" db="PROSITE" dbkey="PS01065" name="ETF_BETA"/>
</member_list>
<external_doc_list>
<db_xref db="MSDsite" dbkey="PS01065"/>
<db_xref db="COMe" dbkey="PRX000051"/>
<db_xref db="BLOCKS" dbkey="IPB000049"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00816"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1efp"/>
<db_xref db="PDB" dbkey="1efv"/>
<db_xref db="PDB" dbkey="1o94"/>
<db_xref db="PDB" dbkey="1o95"/>
<db_xref db="PDB" dbkey="1o96"/>
<db_xref db="PDB" dbkey="1o97"/>
<db_xref db="PDB" dbkey="1t9g"/>
<db_xref db="PDB" dbkey="2a1t"/>
<db_xref db="PDB" dbkey="2a1u"/>
<db_xref db="PDB" dbkey="3clr"/>
<db_xref db="PDB" dbkey="3cls"/>
<db_xref db="PDB" dbkey="3clt"/>
<db_xref db="PDB" dbkey="3clu"/>
<db_xref db="CATH" dbkey="3.40.50.620"/>
<db_xref db="SCOP" dbkey="c.26.2.3"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="1066"/>
<taxon_data name="Cyanobacteria" proteins_count="3"/>
<taxon_data name="Archaea" proteins_count="4"/>
<taxon_data name="Eukaryota" proteins_count="107"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="3"/>
<taxon_data name="Rice spp." proteins_count="3"/>
<taxon_data name="Fungi" proteins_count="41"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="6"/>
<taxon_data name="Arthropoda" proteins_count="23"/>
<taxon_data name="Fruit Fly" proteins_count="2"/>
<taxon_data name="Chordata" proteins_count="17"/>
<taxon_data name="Human" proteins_count="2"/>
<taxon_data name="Mouse" proteins_count="1"/>
<taxon_data name="Unclassified" proteins_count="1"/>
<taxon_data name="Plastid Group" proteins_count="16"/>
<taxon_data name="Green Plants" proteins_count="16"/>
<taxon_data name="Metazoa" proteins_count="87"/>
<taxon_data name="Plastid Group" proteins_count="2"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000052" protein_count="996" short_name="Pltvir_coat" type="Domain">
<name>Potex/carlavirus coat protein</name>
<abstract>
<p>Potexviruses and Carlaviruses are plant-infecting viruses whose genome consist of a single-stranded RNA molecule encapsided in a coat protein. The genome of many Potexviruses is known and their coat protein sequence has been shown to be rather well conserved [<cite idref="PUB00003128"/>]. The same observation applies to the coat protein of a variety of Carlaviruses whose sequences are related to those of Potexviruses [<cite idref="PUB00003127"/>, <cite idref="PUB00003145"/>]. The coat proteins of Potexviruses and of Carlaviruses
contain from 190 to 300 amino acid residues. The best conserved region of these coat proteins is located in the central part.</p>
</abstract>
<class_list>
<classification id="GO:0005198" class_type="GO">
<category>Molecular Function</category>
<description>structural molecule activity</description>
</classification>
<classification id="GO:0019028" class_type="GO">
<category>Cellular Component</category>
<description>viral capsid</description>
</classification>
</class_list>
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<pub_list>
<publication id="PUB00003127">
<author_list>MacKenzie DJ, Tremaine JH, Stace-Smith R.</author_list>
<title>Organization and interviral homologies of the 3'-terminal portion of potato virus S RNA.</title>
<db_xref db="PUBMED" dbkey="2732711"/>
<journal>J. Gen. Virol.</journal>
<location pages="1053-63" volume="70 ( Pt 5)"/>
<year>1989</year>
</publication>
<publication id="PUB00003128">
<author_list>Abouhaidar MG, Lai R.</author_list>
<title>Nucleotide sequence of the 3'-terminal region of clover yellow mosaic virus RNA.</title>
<db_xref db="PUBMED" dbkey="2738582"/>
<journal>J. Gen. Virol.</journal>
<location pages="1871-5" volume="70 ( Pt 7)"/>
<year>1989</year>
</publication>
<publication id="PUB00003145">
<author_list>Henderson J, Gibbs MJ, Edwards ML, Clarke VA, Gardner KA, Cooper JI.</author_list>
<title>Partial nucleotide sequence of poplar mosaic virus RNA confirms its classification as a carlavirus.</title>
<db_xref db="PUBMED" dbkey="1629709"/>
<journal>J. Gen. Virol.</journal>
<location pages="1887-90" volume="73 ( Pt 7)"/>
<year>1992</year>
</publication>
</pub_list>
<member_list>
<db_xref protein_count="996" db="PFAM" dbkey="PF00286" name="Flexi_CP"/>
<db_xref protein_count="955" db="PRINTS" dbkey="PR00232" name="POTXCARLCOAT"/>
<db_xref protein_count="838" db="PROSITE" dbkey="PS00418" name="POTEX_CARLAVIRUS_COAT"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00286"/>
<db_xref db="MSDsite" dbkey="PS00418"/>
<db_xref db="BLOCKS" dbkey="IPB000052"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00346"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Virus" proteins_count="996"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000053" protein_count="1187" short_name="Pyrmidine_PPase" type="Family">
<name>Pyrimidine-nucleoside phosphorylase</name>
<abstract>
<p>Two highly similar activities are represented in this group: thymidine phosphorylase (TP, gene deoA, <db_xref db="EC" dbkey="2.4.2.4"/>) and pyrimidine-nucleoside phosphorylase (PyNP, gene pdp, <db_xref db="EC" dbkey="2.4.2.2"/>). Both are dimeric enzymes that function in the salvage pathway to catalyse the reversible phosphorolysis of pyrimidine nucleosides to the free base and sugar moieties. In the case of thymidine phosphorylase, thymidine (and to a lesser extent, 2'-deoxyuridine) is lysed to produce thymine (or uracil) and 2'-deoxyribose-1-phosphate. Pyrimidine-nucleoside phosphorylase performs the analogous reaction on thymidine (to produce the same products) and uridine (to produce uracil and ribose-1-phosphate). PyNP is typically the only pyrimidine nucleoside phosphorylase encoded by Gram positive bacteria, while eukaryotes and proteobacteria encode two: TP, and the unrelated uridine phosphorylase. In humans, TP was originally characterised as platelet-derived endothelial cell growth factor and gliostatin [<cite idref="PUB00010722"/>]. Structurally, the enzymes are homodimers, each composed of a rigid all alpha-helix lobe and a mixed alpha-helix/beta-sheet lobe, which are connected by a flexible hinge [<cite idref="PUB00010723"/>, <cite idref="PUB00010724"/>]. Prior to substrate binding, the lobes are separated by a large cleft. A functional active site and subsequent catalysis occurs upon closing of the cleft. The active site, composed of a phosphate binding site and a (deoxy)ribonucleotide binding site within the cleft region, is highly conserved between the two enzymes of this group. Active site residues (Escherichia coli DeoA numbering) include the phosphate binding Lys84 and Ser86 (close to a glycine-rich loop), Ser113, and Thr123, and the pyrimidine nucleoside-binding Arg171, Ser186, and Lys190. Sequence comparison between the active site residues for both enzymes reveals only one difference [<cite idref="PUB00010724"/>], which has been proposed to partially mediate substrate specificity. In TP, position 111 is a methionine, while the analogous position in PyNP is lysine. It should be noted that the uncharacterised archaeal members of this family differ in a number of respects from either of the characterised activities. The residue at position 108 is lysine, indicating the activity might be PyNP-like (though the determinants of substrate specificity have not been fully elucidated). Position 171 is glutamate (negative charge side chain) rather than arginine (positive charge side chain). In addition, a large loop that may "lock in" the substrates within the active site is much smaller than in the characterised members. It is not clear what effect these and other differences have on activity and specificity.</p>
</abstract>
<class_list>
<classification id="GO:0006206" class_type="GO">
<category>Biological Process</category>
<description>pyrimidine base metabolic process</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="A0B6C9"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P07650"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P19971"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q5FVR2"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q99N42"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00010722">
<author_list>Griffiths L, Stratford IJ.</author_list>
<title>Platelet-derived endothelial cell growth factor thymidine phosphorylase in tumour growth and response to therapy.</title>
<db_xref db="PUBMED" dbkey="9310231"/>
<journal>Br. J. Cancer</journal>
<location issue="6" pages="689-93" volume="76"/>
<year>1997</year>
</publication>
<publication id="PUB00010723">
<author_list>Pugmire MJ, Cook WJ, Jasanoff A, Walter MR, Ealick SE.</author_list>
<title>Structural and theoretical studies suggest domain movement produces an active conformation of thymidine phosphorylase.</title>
<db_xref db="PUBMED" dbkey="9698549"/>
<journal>J. Mol. Biol.</journal>
<location issue="2" pages="285-99" volume="281"/>
<year>1998</year>
</publication>
<publication id="PUB00010724">
<author_list>Pugmire MJ, Ealick SE.</author_list>
<title>The crystal structure of pyrimidine nucleoside phosphorylase in a closed conformation.</title>
<db_xref db="PUBMED" dbkey="9817849"/>
<journal>Structure</journal>
<location issue="11" pages="1467-79" volume="6"/>
<year>1998</year>
</publication>
</pub_list>
<child_list>
<rel_ref ipr_ref="IPR013466"/>
<rel_ref ipr_ref="IPR018090"/>
</child_list>
<contains>
<rel_ref ipr_ref="IPR000312"/>
<rel_ref ipr_ref="IPR013102"/>
<rel_ref ipr_ref="IPR017459"/>
<rel_ref ipr_ref="IPR017872"/>
<rel_ref ipr_ref="IPR020072"/>
</contains>
<member_list>
<db_xref protein_count="1182" db="PANTHER" dbkey="PTHR10515" name="Pyrmidine_PPase"/>
<db_xref protein_count="1120" db="PIRSF" dbkey="PIRSF000478" name="TP_PyNP"/>
</member_list>
<external_doc_list>
<db_xref db="BLOCKS" dbkey="IPB000053"/>
<db_xref db="EC" dbkey="2.4.2.4"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00557"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1azy"/>
<db_xref db="PDB" dbkey="1brw"/>
<db_xref db="PDB" dbkey="1otp"/>
<db_xref db="PDB" dbkey="1tpt"/>
<db_xref db="PDB" dbkey="1uou"/>
<db_xref db="PDB" dbkey="2dsj"/>
<db_xref db="PDB" dbkey="2j0f"/>
<db_xref db="PDB" dbkey="2tpt"/>
<db_xref db="CATH" dbkey="1.20.970.10"/>
<db_xref db="CATH" dbkey="3.40.1030.10"/>
<db_xref db="CATH" dbkey="3.90.1170.30"/>
<db_xref db="SCOP" dbkey="a.46.2.1"/>
<db_xref db="SCOP" dbkey="c.27.1.1"/>
<db_xref db="SCOP" dbkey="d.41.3.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="1121"/>
<taxon_data name="Archaea" proteins_count="46"/>
<taxon_data name="Eukaryota" proteins_count="20"/>
<taxon_data name="Chordata" proteins_count="15"/>
<taxon_data name="Human" proteins_count="5"/>
<taxon_data name="Mouse" proteins_count="1"/>
<taxon_data name="Metazoa" proteins_count="17"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR013466"/>
<sec_ac acc="IPR018090"/>
</sec_list>
</interpro>
<interpro id="IPR000054" protein_count="454" short_name="Ribosomal_L31e" type="Family">
<name>Ribosomal protein L31e</name>
<abstract>
<p>Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [<cite idref="PUB00007068"/>, <cite idref="PUB00007069"/>]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. </p>
<p>Many of ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [<cite idref="PUB00007069"/>, <cite idref="PUB00007070"/>].</p>
<p>A number of eukaryotic and archaebacterial large subunit ribosomal
proteins can be grouped on the basis of sequence similarities.
These proteins have 87 to 128 amino-acid residues. This family consists of:
<li>Yeast L34</li>
<li>Archaeal L31 [<cite idref="PUB00000605"/>]</li>
<li>Plants L31</li>
<li>Mammalian L31 [<cite idref="PUB00001348"/>]</li>
</p>
</abstract>
<class_list>
<classification id="GO:0003735" class_type="GO">
<category>Molecular Function</category>
<description>structural constituent of ribosome</description>
</classification>
<classification id="GO:0005622" class_type="GO">
<category>Cellular Component</category>
<description>intracellular</description>
</classification>
<classification id="GO:0005840" class_type="GO">
<category>Cellular Component</category>
<description>ribosome</description>
</classification>
<classification id="GO:0006412" class_type="GO">
<category>Biological Process</category>
<description>translation</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P0C2H8"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P62899"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P62900"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q9U332"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q9V597"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00000605">
<author_list>Bergmann U, Arndt E.</author_list>
<title>Evidence for an additional archaebacterial gene cluster in Halobacterium marismortui encoding ribosomal proteins HL46e and HL30.</title>
<db_xref db="PUBMED" dbkey="2207169"/>
<journal>Biochim. Biophys. Acta</journal>
<location issue="1-3" pages="56-60" volume="1050"/>
<year>1990</year>
</publication>
<publication id="PUB00001348">
<author_list>Tanaka T, Kuwano Y, Kuzumaki T, Ishikawa K, Ogata K.</author_list>
<title>Nucleotide sequence of cloned cDNA specific for rat ribosomal protein L31.</title>
<db_xref db="PUBMED" dbkey="3816785"/>
<journal>Eur. J. Biochem.</journal>
<location issue="1" pages="45-8" volume="162"/>
<year>1987</year>
</publication>
<publication id="PUB00007068">
<author_list>Ramakrishnan V, Moore PB.</author_list>
<title>Atomic structures at last: the ribosome in 2000.</title>
<db_xref db="PUBMED" dbkey="11297922"/>
<journal>Curr. Opin. Struct. Biol.</journal>
<location issue="2" pages="144-54" volume="11"/>
<year>2001</year>
</publication>
<publication id="PUB00007069">
<author_list>Maguire BA, Zimmermann RA.</author_list>
<title>The ribosome in focus.</title>
<db_xref db="PUBMED" dbkey="11290319"/>
<journal>Cell</journal>
<location issue="6" pages="813-6" volume="104"/>
<year>2001</year>
</publication>
<publication id="PUB00007070">
<author_list>Chandra Sanyal S, Liljas A.</author_list>
<title>The end of the beginning: structural studies of ribosomal proteins.</title>
<db_xref db="PUBMED" dbkey="11114498"/>
<journal>Curr. Opin. Struct. Biol.</journal>
<location issue="6" pages="633-6" volume="10"/>
<year>2000</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR020052"/>
</contains>
<member_list>
<db_xref protein_count="417" db="PANTHER" dbkey="PTHR10956" name="Ribosomal_L31e"/>
<db_xref protein_count="453" db="PFAM" dbkey="PF01198" name="Ribosomal_L31e"/>
<db_xref protein_count="427" db="PRODOM" dbkey="PD006030" name="Ribosomal_L31e"/>
<db_xref protein_count="430" db="GENE3D" dbkey="G3DSA:3.10.440.10" name="Ribosomal_L31e"/>
<db_xref protein_count="443" db="SSF" dbkey="SSF54575" name="Ribosomal_L31e"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF01198"/>
<db_xref db="MSDsite" dbkey="PS01144"/>
<db_xref db="BLOCKS" dbkey="IPB000054"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00881"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1ffk"/>
<db_xref db="PDB" dbkey="1jj2"/>
<db_xref db="PDB" dbkey="1k73"/>
<db_xref db="PDB" dbkey="1k8a"/>
<db_xref db="PDB" dbkey="1k9m"/>
<db_xref db="PDB" dbkey="1kc8"/>
<db_xref db="PDB" dbkey="1kd1"/>
<db_xref db="PDB" dbkey="1kqs"/>
<db_xref db="PDB" dbkey="1m1k"/>
<db_xref db="PDB" dbkey="1m90"/>
<db_xref db="PDB" dbkey="1n8r"/>
<db_xref db="PDB" dbkey="1nji"/>
<db_xref db="PDB" dbkey="1q7y"/>
<db_xref db="PDB" dbkey="1q81"/>
<db_xref db="PDB" dbkey="1q82"/>
<db_xref db="PDB" dbkey="1q86"/>
<db_xref db="PDB" dbkey="1qvf"/>
<db_xref db="PDB" dbkey="1qvg"/>
<db_xref db="PDB" dbkey="1s72"/>
<db_xref db="PDB" dbkey="1vq4"/>
<db_xref db="PDB" dbkey="1vq5"/>
<db_xref db="PDB" dbkey="1vq6"/>
<db_xref db="PDB" dbkey="1vq7"/>
<db_xref db="PDB" dbkey="1vq8"/>
<db_xref db="PDB" dbkey="1vq9"/>
<db_xref db="PDB" dbkey="1vqk"/>
<db_xref db="PDB" dbkey="1vql"/>
<db_xref db="PDB" dbkey="1vqm"/>
<db_xref db="PDB" dbkey="1vqn"/>
<db_xref db="PDB" dbkey="1vqo"/>
<db_xref db="PDB" dbkey="1vqp"/>
<db_xref db="PDB" dbkey="1w2b"/>
<db_xref db="PDB" dbkey="1yhq"/>
<db_xref db="PDB" dbkey="1yi2"/>
<db_xref db="PDB" dbkey="1yij"/>
<db_xref db="PDB" dbkey="1yit"/>
<db_xref db="PDB" dbkey="1yj9"/>
<db_xref db="PDB" dbkey="1yjn"/>
<db_xref db="PDB" dbkey="1yjw"/>
<db_xref db="PDB" dbkey="2otj"/>
<db_xref db="PDB" dbkey="2otl"/>
<db_xref db="PDB" dbkey="2qa4"/>
<db_xref db="PDB" dbkey="2qex"/>
<db_xref db="PDB" dbkey="3cc2"/>
<db_xref db="PDB" dbkey="3cc4"/>
<db_xref db="PDB" dbkey="3cc7"/>
<db_xref db="PDB" dbkey="3cce"/>
<db_xref db="PDB" dbkey="3ccj"/>
<db_xref db="PDB" dbkey="3ccl"/>
<db_xref db="PDB" dbkey="3ccm"/>
<db_xref db="PDB" dbkey="3ccq"/>
<db_xref db="PDB" dbkey="3ccr"/>
<db_xref db="PDB" dbkey="3ccs"/>
<db_xref db="PDB" dbkey="3ccu"/>
<db_xref db="PDB" dbkey="3ccv"/>
<db_xref db="PDB" dbkey="3cd6"/>
<db_xref db="PDB" dbkey="3cma"/>
<db_xref db="PDB" dbkey="3cme"/>
<db_xref db="PDB" dbkey="3cpw"/>
<db_xref db="CATH" dbkey="3.10.440.10"/>
<db_xref db="SCOP" dbkey="d.29.1.1"/>
<db_xref db="SCOP" dbkey="i.1.1.2"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Archaea" proteins_count="95"/>
<taxon_data name="Eukaryota" proteins_count="359"/>
<taxon_data name="Plastid Group" proteins_count="2"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="5"/>
<taxon_data name="Rice spp." proteins_count="8"/>
<taxon_data name="Fungi" proteins_count="74"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="11"/>
<taxon_data name="Other Eukaryotes" proteins_count="6"/>
<taxon_data name="Other Eukaryotes" proteins_count="1"/>
<taxon_data name="Nematoda" proteins_count="1"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="1"/>
<taxon_data name="Arthropoda" proteins_count="42"/>
<taxon_data name="Fruit Fly" proteins_count="1"/>
<taxon_data name="Chordata" proteins_count="88"/>
<taxon_data name="Human" proteins_count="12"/>
<taxon_data name="Mouse" proteins_count="11"/>
<taxon_data name="Other Eukaryotes" proteins_count="5"/>
<taxon_data name="Plastid Group" proteins_count="59"/>
<taxon_data name="Green Plants" proteins_count="59"/>
<taxon_data name="Metazoa" proteins_count="241"/>
<taxon_data name="Plastid Group" proteins_count="28"/>
<taxon_data name="Plastid Group" proteins_count="8"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000055" protein_count="2980" short_name="Restrct_endonuc_I_S_EcoBI" type="Domain">
<name>Restriction endonuclease, type I, S subunit, EcoBI</name>
<abstract>
<p>There are four classes of restriction endonucleases: types I, II,III and IV. All types of enzymes recognise specific short DNA sequences and carry out the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. They differ in their recognition sequence, subunit composition, cleavage position, and cofactor requirements [<cite idref="PUB00035705"/>, <cite idref="PUB00035707"/>], as summarised below:</p>
<p>
<ul>
<li>Type I enzymes (<db_xref db="EC" dbkey="3.1.21.3"/>) cleave at sites remote from recognition site; require both ATP and S-adenosyl-L-methionine to function; multifunctional protein with both restriction and methylase (<db_xref db="EC" dbkey="2.1.1.72"/>) activities.</li>
<li>Type II enzymes (<db_xref db="EC" dbkey="3.1.21.4"/>) cleave within or at short specific distances from recognition site; most require magnesium; single function (restriction) enzymes independent of methylase.</li>
<li>Type III enzymes (<db_xref db="EC" dbkey="3.1.21.5"/>) cleave at sites a short distance from recognition site; require ATP (but doesn't hydrolyse it); S-adenosyl-L-methionine stimulates reaction but is not required; exists as part of a complex with a modification methylase methylase (<db_xref db="EC" dbkey="2.1.1.72"/>).</li>
<li>Type IV enzymes target methylated DNA.</li>
</ul>
</p>
<p>Type I restriction endonucleases are components of prokaryotic DNA restriction-modification mechanisms that protects the organism against invading foreign DNA. Type I enzymes have three different subunits subunits - M (modification), S (specificity) and R (restriction) - that form multifunctional enzymes with restriction (<db_xref db="EC" dbkey="3.1.21.3"/>), methylase (<db_xref db="EC" dbkey="2.1.1.72"/>) and ATPase activities [<cite idref="PUB00035705"/>, <cite idref="PUB00035706"/>]. The S subunit is required for both restriction and modification and is responsible for recognition of the DNA sequence specific for the system. The M subunit is necessary for modification, and the R subunit is required for restriction. These enzymes use S-Adenosyl-L-methionine (AdoMet) as the methyl group donor in the methylation reaction, and have a requirement for ATP. They recognise asymmetric DNA sequences split into two domains of specific sequence, one 3-4 bp long and another 4-5 bp long, separated by a nonspecific spacer 6-8 bp in length. Cleavage occurs a considerable distance from the recognition sites, rarely less than 400 bp away and up to 7000 bp away. Adenosyl residues are methylated, one on each strand of the recognition sequence. These enzymes are widespread in eubacteria and archaea. In enteric bacteria they have been subdivide into four families: types IA, IB, IC and ID.</p>
<p>This entry represents the S subunit of type I restriction endonucleases such as EcoBI and EcoKI (<db_xref db="EC" dbkey="3.1.21.3"/>), which recognise the DNA sequence 5' TGAN(8)TGCT and 5'-AACN(6)GTGC, respectively [<cite idref="PUB00035711"/>, <cite idref="PUB00035712"/>]. The M and S subunits together form a methyltransferase that methylates two adenine residues in complementary strands of a bipartite DNA recognition sequence. In the presence of the R subunit the complex can also act as an endonuclease, binding to the same target sequence but cutting the DNA some distance from this site. Whether the DNA is cut or modified depends on the methylation state of the target sequence: when the target site is unmodified, the DNA is cut; when the target site is hemi-methylated, the complex acts as a maintenance methyltransferase to modify the DNA, methylating both strands [<cite idref="PUB00003392"/>]. Most of the proteins in this family have two copies of the domain.</p>
</abstract>
<class_list>
<classification id="GO:0003677" class_type="GO">
<category>Molecular Function</category>
<description>DNA binding</description>
</classification>
<classification id="GO:0006304" class_type="GO">
<category>Biological Process</category>
<description>DNA modification</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="Q49434"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q57594"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00003392">
<author_list>Janscak P, Bickle TA.</author_list>
<title>The DNA recognition subunit of the type IB restriction-modification enzyme EcoAI tolerates circular permutions of its polypeptide chain.</title>
<db_xref db="PUBMED" dbkey="9837717"/>
<journal>J. Mol. Biol.</journal>
<location issue="4" pages="937-48" volume="284"/>
<year>1998</year>
</publication>
<publication id="PUB00035705">
<author_list>Sistla S, Rao DN.</author_list>
<title>S-Adenosyl-L-methionine-dependent restriction enzymes.</title>
<db_xref db="PUBMED" dbkey="15121719"/>
<journal>Crit. Rev. Biochem. Mol. Biol.</journal>
<location issue="1" pages="1-19" volume="39"/>
<year>2004</year>
</publication>
<publication id="PUB00035706">
<author_list>Bourniquel AA, Bickle TA.</author_list>
<title>Complex restriction enzymes: NTP-driven molecular motors.</title>
<db_xref db="PUBMED" dbkey="12595133"/>
<journal>Biochimie</journal>
<location issue="11" pages="1047-59" volume="84"/>
<year>2002</year>
</publication>
<publication id="PUB00035707">
<author_list>Williams RJ.</author_list>
<title>Restriction endonucleases: classification, properties, and applications.</title>
<db_xref db="PUBMED" dbkey="12665693"/>
<journal>Mol. Biotechnol.</journal>
<location issue="3" pages="225-43" volume="23"/>
<year>2003</year>
</publication>
<publication id="PUB00035711">
<author_list>Kasarjian JK, Kodama Y, Iida M, Matsuda K, Ryu J.</author_list>
<title>Four new type I restriction enzymes identified in Escherichia coli clinical isolates.</title>
<db_xref db="PUBMED" dbkey="16040596"/>
<journal>Nucleic Acids Res.</journal>
<location issue="13" pages="e114" volume="33"/>
<year>2005</year>
</publication>
<publication id="PUB00035712">
<author_list>Cajthamlova K, Sisakova E, Weiser J, Weiserova M.</author_list>
<title>Phosphorylation of Type IA restriction-modification complex enzyme EcoKI on the HsdR subunit.</title>
<db_xref db="PUBMED" dbkey="17439637"/>
<journal>FEMS Microbiol. Lett.</journal>
<location issue="1" pages="171-7" volume="270"/>
<year>2007</year>
</publication>
</pub_list>
<found_in>
<rel_ref ipr_ref="IPR017043"/>
</found_in>
<member_list>
<db_xref protein_count="2980" db="PFAM" dbkey="PF01420" name="Methylase_S"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF01420"/>
<db_xref db="BLOCKS" dbkey="IPB000055"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1ydx"/>
<db_xref db="PDB" dbkey="1yf2"/>
<db_xref db="SCOP" dbkey="d.287.1.2"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="2895"/>
<taxon_data name="Cyanobacteria" proteins_count="92"/>
<taxon_data name="Synechocystis PCC 6803" proteins_count="2"/>
<taxon_data name="Archaea" proteins_count="81"/>
<taxon_data name="Eukaryota" proteins_count="1"/>
<taxon_data name="Fungi" proteins_count="1"/>
<taxon_data name="Virus" proteins_count="1"/>
<taxon_data name="Unclassified" proteins_count="1"/>
<taxon_data name="Unclassified" proteins_count="1"/>
<taxon_data name="Metazoa" proteins_count="1"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000056" protein_count="2590" short_name="Ribul_P_3_epim" type="Family">
<name>Ribulose-phosphate 3-epimerase</name>
<abstract>
Ribulose-phosphate 3-epimerase (<db_xref db="EC" dbkey="5.1.3.1"/>) (also known as pentose-5-phosphate 3-epimerase or PPE) is the enzyme that converts D-ribulose 5-phosphate into D-xylulose 5-phosphate in Calvin's reductive pentose phosphate cycle. In <taxon tax_id="106590">Ralstonia eutropha</taxon> (Alcaligenes eutrophus) two copies of the gene coding for PPE are known [<cite idref="PUB00002204"/>], one is chromosomally encoded <db_xref db="SWISSPROT" dbkey="P40117"/>, the other one is on a plasmid <db_xref db="SWISSPROT" dbkey="Q04539"/>. PPE has been found in a wide range of bacteria, archaebacteria, fungi and plants. All the proteins have from 209 to 241 amino acid residues. The enzyme has a TIM barrel structure.
</abstract>
<class_list>
<classification id="GO:0004750" class_type="GO">
<category>Molecular Function</category>
<description>ribulose-phosphate 3-epimerase activity</description>
</classification>
<classification id="GO:0005975" class_type="GO">
<category>Biological Process</category>
<description>carbohydrate metabolic process</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P46969"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P74061"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q8VEE0"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q96AT9"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q9SE42"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00002204">
<author_list>Kusian B, Yoo JG, Bednarski R, Bowien B.</author_list>
<title>The Calvin cycle enzyme pentose-5-phosphate 3-epimerase is encoded within the cfx operons of the chemoautotroph Alcaligenes eutrophus.</title>
<db_xref db="PUBMED" dbkey="1429456"/>
<journal>J. Bacteriol.</journal>
<location issue="22" pages="7337-44" volume="174"/>
<year>1992</year>
</publication>
</pub_list>
<parent_list>
<rel_ref ipr_ref="IPR011060"/>
</parent_list>
<member_list>
<db_xref protein_count="2560" db="PANTHER" dbkey="PTHR11749" name="Ribul_P_3_epim"/>
<db_xref protein_count="2544" db="PFAM" dbkey="PF00834" name="Ribul_P_3_epim"/>
<db_xref protein_count="2075" db="PROSITE" dbkey="PS01085" name="RIBUL_P_3_EPIMER_1"/>
<db_xref protein_count="2031" db="PROSITE" dbkey="PS01086" name="RIBUL_P_3_EPIMER_2"/>
<db_xref protein_count="2075" db="TIGRFAMs" dbkey="TIGR01163" name="rpe"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00834"/>
<db_xref db="MSDsite" dbkey="PS01085"/>
<db_xref db="MSDsite" dbkey="PS01086"/>
<db_xref db="BLOCKS" dbkey="IPB000056"/>
<db_xref db="EC" dbkey="5.1.3"/>
<db_xref db="PRIAM" dbkey="PRI000772"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00833"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1h1y"/>
<db_xref db="PDB" dbkey="1h1z"/>
<db_xref db="PDB" dbkey="1rpx"/>
<db_xref db="PDB" dbkey="1tqj"/>
<db_xref db="PDB" dbkey="1tqx"/>
<db_xref db="PDB" dbkey="2fli"/>
<db_xref db="PDB" dbkey="3ct7"/>
<db_xref db="PDB" dbkey="3ctl"/>
<db_xref db="PDB" dbkey="3cu2"/>
<db_xref db="CATH" dbkey="3.20.20.70"/>
<db_xref db="SCOP" dbkey="c.1.2.2"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="2300"/>
<taxon_data name="Cyanobacteria" proteins_count="58"/>
<taxon_data name="Synechocystis PCC 6803" proteins_count="1"/>
<taxon_data name="Archaea" proteins_count="38"/>
<taxon_data name="Eukaryota" proteins_count="252"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="5"/>
<taxon_data name="Rice spp." proteins_count="7"/>
<taxon_data name="Fungi" proteins_count="69"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="5"/>
<taxon_data name="Other Eukaryotes" proteins_count="1"/>
<taxon_data name="Other Eukaryotes" proteins_count="1"/>
<taxon_data name="Nematoda" proteins_count="1"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="1"/>
<taxon_data name="Arthropoda" proteins_count="23"/>
<taxon_data name="Fruit Fly" proteins_count="1"/>
<taxon_data name="Chordata" proteins_count="44"/>
<taxon_data name="Human" proteins_count="12"/>
<taxon_data name="Mouse" proteins_count="6"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
<taxon_data name="Plastid Group" proteins_count="59"/>
<taxon_data name="Green Plants" proteins_count="59"/>
<taxon_data name="Metazoa" proteins_count="145"/>
<taxon_data name="Plastid Group" proteins_count="13"/>
<taxon_data name="Plastid Group" proteins_count="15"/>
<taxon_data name="Plastid Group" proteins_count="3"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000057" protein_count="22" short_name="IL8B_rcpt" type="Family">
<name>Interleukin 8B receptor</name>
<abstract>
<p>G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [<cite idref="PUB00004961"/>]. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/). </p>
<p>The rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7
transmembrane (TM) helices [<cite idref="PUB00000131"/>, <cite idref="PUB00002477"/>, <cite idref="PUB00004960"/>].</p>
<p>Interleukin-8 (IL8) is a pro-inflammatory cytokine involved in the cellular
response to inflammation, being a powerful chemoattractant for neutrophils
[<cite idref="PUB00005143"/>]. There are 2 similar cell surface receptors for IL8: type 1 (IL-8RA) is
a high affinity receptor for IL8 alone; while type 2 (IL-8RB) is a high
affinity receptor for IL8, growth related gene (GRO) and neutrophil-activating protein-2 (NAP-2). The affinity of type 1 receptors for IL8 is
higher than that of type 2 receptors [<cite idref="PUB00005143"/>, <cite idref="PUB00001953"/>]. The receptors are coupled to
<taxon tax_id="520">Bordetella pertussis</taxon> toxin-sensitive GTP-binding proteins [<cite idref="PUB00001646"/>]. Signal
transduction depends on the activation of a phospholipase C specific for
phosphatidylinositol-4,5-bisphosphate, producing 2 second messengers:
inositol triphosphate and diacylglycerol [<cite idref="PUB00001646"/>]. Inositol triphosphate induces
a rise in the levels of cytosolic free calcium, while diacylglycerol
activates protein kinase C, leading to activation of neutrophils [<cite idref="PUB00001646"/>].</p>
<p>IL8RB receptors are found in high density in neutrophils, monocytes,
basophils, and melanoma cells, and in lower density in T-cells. IL8
has been reported to stimulate the phosphoinositide pathway through an
uncharacterised G-protein; pertussis toxin also inhibits several of its
actions [<cite idref="PUB00005876"/>]. The IL8RB receptor shares around 80% similarity with the
IL8RA receptor.</p>
</abstract>
<class_list>
<classification id="GO:0004918" class_type="GO">
<category>Molecular Function</category>
<description>interleukin-8 receptor activity</description>
</classification>
<classification id="GO:0006935" class_type="GO">
<category>Biological Process</category>
<description>chemotaxis</description>
</classification>
<classification id="GO:0016021" class_type="GO">
<category>Cellular Component</category>
<description>integral to membrane</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O97571"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P25025"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P35343"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00000131">
<author_list>Birnbaumer L.</author_list>
<title>G proteins in signal transduction.</title>
<db_xref db="PUBMED" dbkey="2111655"/>
<journal>Annu. Rev. Pharmacol. Toxicol.</journal>
<location pages="675-705" volume="30"/>
<year>1990</year>
</publication>
<publication id="PUB00001646">
<author_list>Baggiolini M, Clark-Lewis I.</author_list>
<title>Interleukin-8, a chemotactic and inflammatory cytokine.</title>
<db_xref db="PUBMED" dbkey="1639201"/>
<journal>FEBS Lett.</journal>
<location issue="1" pages="97-101" volume="307"/>
<year>1992</year>
</publication>
<publication id="PUB00001953">
<author_list>Mollereau C, Muscatelli F, Mattei MG, Vassart G, Parmentier M.</author_list>
<title>The high-affinity interleukin 8 receptor gene (IL8RA) maps to the 2q33-q36 region of the human genome: cloning of a pseudogene (IL8RBP) for the low-affinity receptor.</title>
<db_xref db="PUBMED" dbkey="8486366"/>
<journal>Genomics</journal>
<location issue="1" pages="248-51" volume="16"/>
<year>1993</year>
</publication>
<publication id="PUB00002477">
<author_list>Casey PJ, Gilman AG.</author_list>
<title>G protein involvement in receptor-effector coupling.</title>
<db_xref db="PUBMED" dbkey="2830256"/>
<journal>J. Biol. Chem.</journal>
<location issue="6" pages="2577-80" volume="263"/>
<year>1988</year>
</publication>
<publication id="PUB00004960">
<author_list>Attwood TK, Findlay JB.</author_list>
<title>Design of a discriminating fingerprint for G-protein-coupled receptors.</title>
<db_xref db="PUBMED" dbkey="8386361"/>
<journal>Protein Eng.</journal>
<location issue="2" pages="167-76" volume="6"/>
<year>1993</year>
</publication>
<publication id="PUB00004961">
<author_list>Attwood TK, Findlay JB.</author_list>
<title>Fingerprinting G-protein-coupled receptors.</title>
<db_xref db="PUBMED" dbkey="8170923"/>
<journal>Protein Eng.</journal>
<location issue="2" pages="195-203" volume="7"/>
<year>1994</year>
</publication>
<publication id="PUB00005143">
<author_list>Holmes WE, Lee J, Kuang WJ, Rice GC, Wood WI.</author_list>
<title>Structure and functional expression of a human interleukin-8 receptor.</title>
<db_xref db="PUBMED" dbkey="1840701"/>
<journal>Science</journal>
<location issue="5025" pages="1278-80" volume="253"/>
<year>1991</year>
</publication>
<publication id="PUB00005876">
<author_list>Watson S, Arkinstall S.</author_list>
<title>Chemokines.</title>
<book_title>ISBN:0127384405</book_title>
<location pages="83-8"/>
<year>1994</year>
</publication>
</pub_list>
<parent_list>
<rel_ref ipr_ref="IPR000174"/>
</parent_list>
<member_list>
<db_xref protein_count="22" db="PRINTS" dbkey="PR00573" name="INTRLEUKN8BR"/>
</member_list>
<external_doc_list>
<db_xref db="BLOCKS" dbkey="IPB000057"/>
<db_xref db="IUPHAR" dbkey="2212"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Eukaryota" proteins_count="22"/>
<taxon_data name="Chordata" proteins_count="22"/>
<taxon_data name="Human" proteins_count="6"/>
<taxon_data name="Mouse" proteins_count="1"/>
<taxon_data name="Metazoa" proteins_count="22"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000058" protein_count="711" short_name="Znf_AN1" type="Domain">
<name>Zinc finger, AN1-type</name>
<abstract>
<p>Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from <taxon tax_id="8355">Xenopus laevis</taxon> (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [<cite idref="PUB00035807"/>, <cite idref="PUB00035805"/>, <cite idref="PUB00035806"/>, <cite idref="PUB00035804"/>, <cite idref="PUB00014077"/>]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few [<cite idref="PUB00035812"/>]. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. </p>
<p>This entry represents the AN1-type zinc finger domain, which has a dimetal (zinc)-bound alpha/beta fold. This domain was first identified as a zinc finger at the C terminus of AN1 <db_xref db="SWISSPROT" dbkey="Q91889"/>, a ubiquitin-like
protein in <taxon tax_id="8355">Xenopus laevis</taxon> [<cite idref="PUB00001828"/>]. The AN1-type zinc finger contains six conserved cysteines and two histidines that could potentially coordinate 2 zinc atoms.</p>
<p>Certain stress-associated proteins (SAP) contain AN1 domain, often in combination with A20 zinc finger domains (SAP8) or C2H2 domains (SAP16) [<cite idref="PUB00042925"/>]. For example, the human protein Znf216 has an A20 zinc-finger at the N terminus and an AN1 zinc-finger at the C terminus, acting to negatively regulate the NFkappaB activation pathway and to interact with components of the immune response like RIP, IKKgamma and TRAF6. The interact of Znf216 with IKK-gamma and RIP is mediated by the A20 zinc-finger domain, while its interaction with TRAF6 is mediated by the AN1 zinc-finger domain; therefore, both zinc-finger domains are involved in regulating the immune response [<cite idref="PUB00042926"/>]. The AN1 zinc finger domain is also found in proteins containing a ubiquitin-like domain, which are involved in the ubiquitination pathway [<cite idref="PUB00001828"/>]. Proteins containing an AN1-type zinc finger include:</p>
<p>
<ul>
<li>Ascidian posterior end mark 6 (pem-6) protein [<cite idref="PUB00018493"/>].</li>
<li>Human AWP1 protein (associated with PRK1), which is expressed during early embryogenesis [<cite idref="PUB00018494"/>].</li>
<li>Human immunoglobulin mu binding protein 2 (SMUBP-2), mutations in which cause muscular atrophy with respiratory distress type 1 [<cite idref="PUB00018517"/>].</li>
</ul>
</p>
<p>More information about these proteins can be found at Protein of the Month: Zinc Fingers [<cite idref="PUB00035813"/>].</p>
</abstract>
<class_list>
<classification id="GO:0008270" class_type="GO">
<category>Molecular Function</category>
<description>zinc ion binding</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="A2YEZ6"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="O88878"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P38935"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P53899"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q6NNI8"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00001828">
<author_list>Linnen JM, Bailey CP, Weeks DL.</author_list>
<title>Two related localized mRNAs from Xenopus laevis encode ubiquitin-like fusion proteins.</title>
<db_xref db="PUBMED" dbkey="8390387"/>
<journal>Gene</journal>
<location issue="2" pages="181-8" volume="128"/>
<year>1993</year>
</publication>
<publication id="PUB00014077">
<author_list>Matthews JM, Sunde M.</author_list>
<title>Zinc fingers--folds for many occasions.</title>
<db_xref db="PUBMED" dbkey="12665246"/>
<journal>IUBMB Life</journal>
<location issue="6" pages="351-5" volume="54"/>
<year>2002</year>
</publication>
<publication id="PUB00018493">
<author_list>Satou Y, Satoh N.</author_list>
<title>Posterior end mark 2 (pem-2), pem-4, pem-5, and pem-6: maternal genes with localized mRNA in the ascidian embryo.</title>
<db_xref db="PUBMED" dbkey="9441682"/>
<journal>Dev. Biol.</journal>
<location issue="2" pages="467-81" volume="192"/>
<year>1997</year>
</publication>
<publication id="PUB00018494">
<author_list>Duan W, Sun B, Li TW, Tan BJ, Lee MK, Teo TS.</author_list>
<title>Cloning and characterization of AWP1, a novel protein that associates with serine/threonine kinase PRK1 in vivo.</title>
<db_xref db="PUBMED" dbkey="11054541"/>
<journal>Gene</journal>
<location issue="1-2" pages="113-21" volume="256"/>
<year>2000</year>
</publication>
<publication id="PUB00018517">
<author_list>Liepinsh E, Leonchiks A, Sharipo A, Guignard L, Otting G.</author_list>
<title>Solution structure of the R3H domain from human Smubp-2.</title>
<db_xref db="PUBMED" dbkey="12547203"/>
<journal>J. Mol. Biol.</journal>
<location issue="1" pages="217-23" volume="326"/>
<year>2003</year>
</publication>
<publication id="PUB00035804">
<author_list>Gamsjaeger R, Liew CK, Loughlin FE, Crossley M, Mackay JP.</author_list>
<title>Sticky fingers: zinc-fingers as protein-recognition motifs.</title>
<db_xref db="PUBMED" dbkey="17210253"/>
<journal>Trends Biochem. Sci.</journal>
<location issue="2" pages="63-70" volume="32"/>
<year>2007</year>
</publication>
<publication id="PUB00035805">
<author_list>Hall TM.</author_list>
<title>Multiple modes of RNA recognition by zinc finger proteins.</title>
<db_xref db="PUBMED" dbkey="15963892"/>
<journal>Curr. Opin. Struct. Biol.</journal>
<location issue="3" pages="367-73" volume="15"/>
<year>2005</year>
</publication>
<publication id="PUB00035806">
<author_list>Brown RS.</author_list>
<title>Zinc finger proteins: getting a grip on RNA.</title>
<db_xref db="PUBMED" dbkey="15718139"/>
<journal>Curr. Opin. Struct. Biol.</journal>
<location issue="1" pages="94-8" volume="15"/>
<year>2005</year>
</publication>
<publication id="PUB00035807">
<author_list>Klug A.</author_list>
<title>Zinc finger peptides for the regulation of gene expression.</title>
<db_xref db="PUBMED" dbkey="10529348"/>
<journal>J. Mol. Biol.</journal>
<location issue="2" pages="215-8" volume="293"/>
<year>1999</year>
</publication>
<publication id="PUB00035812">
<author_list>Laity JH, Lee BM, Wright PE.</author_list>
<title>Zinc finger proteins: new insights into structural and functional diversity.</title>
<db_xref db="PUBMED" dbkey="11179890"/>
<journal>Curr. Opin. Struct. Biol.</journal>
<location issue="1" pages="39-46" volume="11"/>
<year>2001</year>
</publication>
<publication id="PUB00035813">
<author_list>McDowall J.</author_list>
<title>Protein of the Month: Zinc Fingers.</title>
<url>http://www.ebi.ac.uk/interpro/potm/2007_3/Page1.htm</url>
<year>2007</year>
</publication>
<publication id="PUB00042926">
<author_list>Huang J, Teng L, Li L, Liu T, Li L, Chen D, Xu LG, Zhai Z, Shu HB.</author_list>
<title>ZNF216 Is an A20-like and IkappaB kinase gamma-interacting inhibitor of NFkappaB activation.</title>
<db_xref db="PUBMED" dbkey="14754897"/>
<journal>J. Biol. Chem.</journal>
<location issue="16" pages="16847-53" volume="279"/>
<year>2004</year>
</publication>
<publication id="PUB00042925">
<author_list>Vij S, Tyagi AK.</author_list>
<title>Genome-wide analysis of the stress associated protein (SAP) gene family containing A20/AN1 zinc-finger(s) in rice and their phylogenetic relationship with Arabidopsis.</title>
<db_xref db="PUBMED" dbkey="17033811"/>
<journal>Mol. Genet. Genomics</journal>
<location issue="6" pages="565-75" volume="276"/>
<year>2006</year>
</publication>
</pub_list>
<member_list>
<db_xref protein_count="702" db="PFAM" dbkey="PF01428" name="zf-AN1"/>
<db_xref protein_count="631" db="PROFILE" dbkey="PS51039" name="ZF_AN1"/>
<db_xref protein_count="505" db="SMART" dbkey="SM00154" name="ZnF_AN1"/>
<db_xref protein_count="607" db="GENE3D" dbkey="G3DSA:4.10.1110.10" name="Znf_AN1"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF01428"/>
<db_xref db="BLOCKS" dbkey="IPB000058"/>
<db_xref db="PROSITEDOC" dbkey="PDOC51039"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1wfe"/>
<db_xref db="PDB" dbkey="1wfh"/>
<db_xref db="PDB" dbkey="1wfl"/>
<db_xref db="PDB" dbkey="1wfp"/>
<db_xref db="PDB" dbkey="1wg2"/>
<db_xref db="CATH" dbkey="4.10.1110.10"/>
<db_xref db="SCOP" dbkey="g.80.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Archaea" proteins_count="35"/>
<taxon_data name="Eukaryota" proteins_count="671"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="15"/>
<taxon_data name="Rice spp." proteins_count="55"/>
<taxon_data name="Fungi" proteins_count="122"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="10"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
<taxon_data name="Nematoda" proteins_count="4"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="4"/>
<taxon_data name="Arthropoda" proteins_count="88"/>
<taxon_data name="Fruit Fly" proteins_count="13"/>
<taxon_data name="Chordata" proteins_count="129"/>
<taxon_data name="Human" proteins_count="22"/>
<taxon_data name="Mouse" proteins_count="12"/>
<taxon_data name="Virus" proteins_count="5"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
<taxon_data name="Plastid Group" proteins_count="217"/>
<taxon_data name="Green Plants" proteins_count="217"/>
<taxon_data name="Metazoa" proteins_count="377"/>
<taxon_data name="Plastid Group" proteins_count="44"/>
<taxon_data name="Plastid Group" proteins_count="14"/>
<taxon_data name="Other Eukaryotes" proteins_count="11"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000059" protein_count="242" short_name="NUDIX_hydrolase_NudL_CS" type="Conserved_site">
<name>NUDIX hydrolase, NudL, conserved site</name>
<abstract>
<p>Nudix hydrolases, which are commonly found in all kingdoms of life, are pyrophosphohydrolases predominantly acting on substrates that contain a nucleotide diphosphate linked to another moiety X [<cite idref="PUB00006662"/>, <cite idref="PUB00034750"/>]. These substrates include nucleoside triphosphates, nucleotide sugars, dinucleoside polyphosphates, dinucleotide coenzymes and capped RNAs. In some cases, phosphohydrolase activity has been observed with nucleoside diphopshates and some non-nucletoide substrates. These enzymes posses an almost universally conserved, charateristic twenty-three-amino acid motif, Gx(5)Ex(5)[UA]xREx(2)EExGU (where U is an aliphatic, hydrophobic amino acid residue), necessary for catalytic activity. Some members of this family protect cells by degrading potentially mutagenic oxidised nucleotides, while others control the levels of metabolic intermediates and signalling compounds.</p>
<p>This entry represents a number of proteins which contain the characteristic Nudix domain. One of the characterised protein in this entry, PCD1, is a peroxisomal coenzyme A (CoA) diphosphatase catalysing the cleavage of coenzyme A into ADP and phosphopantetheine, with a strong preference for oxidised CoA disulphide as its substrate [<cite idref="PUB00034751"/>]. PCD1 may function, therefore, to maintain the capacity for beta-oxidation of fatty acids. It has also been shown to degrade oxo-dGTP and so may also be involved in protecting the cell from mutagenic oxidised nucleotides [<cite idref="PUB00034752"/>].</p>
</abstract>
<class_list>
<classification id="GO:0000287" class_type="GO">
<category>Molecular Function</category>
<description>magnesium ion binding</description>
</classification>
<classification id="GO:0009132" class_type="GO">
<category>Biological Process</category>
<description>nucleoside diphosphate metabolic process</description>
</classification>
<classification id="GO:0016818" class_type="GO">
<category>Molecular Function</category>
<description>hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides</description>
</classification>
<classification id="GO:0030145" class_type="GO">
<category>Molecular Function</category>
<description>manganese ion binding</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="A1ABY1"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P0C024"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q12524"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q23236"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q99P30"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00006662">
<author_list>Bessman MJ, Frick DN, O'Handley SF.</author_list>
<title>The MutT proteins or "Nudix" hydrolases, a family of versatile, widely distributed, "housecleaning" enzymes.</title>
<db_xref db="PUBMED" dbkey="8810257"/>
<journal>J. Biol. Chem.</journal>
<location issue="41" pages="25059-62" volume="271"/>
<year>1996</year>
</publication>
<publication id="PUB00034750">
<author_list>McLennan AG.</author_list>
<title>The Nudix hydrolase superfamily.</title>
<db_xref db="PUBMED" dbkey="16378245"/>
<journal>Cell. Mol. Life Sci.</journal>
<location issue="2" pages="123-43" volume="63"/>
<year>2006</year>
</publication>
<publication id="PUB00034752">
<author_list>Nunoshiba T, Ishida R, Sasaki M, Iwai S, Nakabeppu Y, Yamamoto K.</author_list>
<title>A novel Nudix hydrolase for oxidized purine nucleoside triphosphates encoded by ORFYLR151c (PCD1 gene) in Saccharomyces cerevisiae.</title>
<db_xref db="PUBMED" dbkey="15475388"/>
<journal>Nucleic Acids Res.</journal>
<location issue="18" pages="5339-48" volume="32"/>
<year>2004</year>
</publication>
<publication id="PUB00034751">
<author_list>Cartwright JL, Gasmi L, Spiller DG, McLennan AG.</author_list>
<title>The Saccharomyces cerevisiae PCD1 gene encodes a peroxisomal nudix hydrolase active toward coenzyme A and its derivatives.</title>
<db_xref db="PUBMED" dbkey="10922370"/>
<journal>J. Biol. Chem.</journal>
<location issue="42" pages="32925-30" volume="275"/>
<year>2000</year>
</publication>
</pub_list>
<found_in>
<rel_ref ipr_ref="IPR000086"/>
<rel_ref ipr_ref="IPR015797"/>
</found_in>
<member_list>
<db_xref protein_count="242" db="PROSITE" dbkey="PS01293" name="UPF0035"/>
</member_list>
<external_doc_list>
<db_xref db="MSDsite" dbkey="PS01293"/>
<db_xref db="BLOCKS" dbkey="IPB000059"/>
<db_xref db="EC" dbkey="3.6.1"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00995"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="221"/>
<taxon_data name="Eukaryota" proteins_count="21"/>
<taxon_data name="Rice spp." proteins_count="1"/>
<taxon_data name="Fungi" proteins_count="9"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="6"/>
<taxon_data name="Nematoda" proteins_count="1"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="1"/>
<taxon_data name="Chordata" proteins_count="8"/>
<taxon_data name="Human" proteins_count="1"/>
<taxon_data name="Mouse" proteins_count="1"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
<taxon_data name="Green Plants" proteins_count="1"/>
<taxon_data name="Metazoa" proteins_count="20"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000060" protein_count="2160" short_name="BCCT_transporter" type="Family">
<name>BCCT transporter</name>
<abstract>
<p>These prokaryotic transport proteins belong to a family known as BCCT (for Betaine /
Carnitine / Choline Transporters) and are specific for compounds containing
a quaternary nitrogen atom. The BCCT proteins contain 12 transmembrane regions
and are energized by proton symport. They contain a conserved region with four
tryptophans in their central region [<cite idref="PUB00002302"/>].</p>
</abstract>
<class_list>
<classification id="GO:0005215" class_type="GO">
<category>Molecular Function</category>
<description>transporter activity</description>
</classification>
<classification id="GO:0006810" class_type="GO">
<category>Biological Process</category>
<description>transport</description>
</classification>
<classification id="GO:0016020" class_type="GO">
<category>Cellular Component</category>
<description>membrane</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P54582"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00002302">
<author_list>Kappes RM, Kempf B, Bremer E.</author_list>
<title>Three transport systems for the osmoprotectant glycine betaine operate in Bacillus subtilis: characterization of OpuD.</title>
<db_xref db="PUBMED" dbkey="8752321"/>
<journal>J. Bacteriol.</journal>
<location issue="17" pages="5071-9" volume="178"/>
<year>1996</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR018093"/>
</contains>
<member_list>
<db_xref protein_count="2160" db="PFAM" dbkey="PF02028" name="BCCT"/>
<db_xref protein_count="1568" db="TIGRFAMs" dbkey="TIGR00842" name="bcct"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF02028"/>
<db_xref db="MSDsite" dbkey="PS01303"/>
<db_xref db="BLOCKS" dbkey="IPB000060"/>
<db_xref db="PROSITEDOC" dbkey="PDOC01007"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="2123"/>
<taxon_data name="Cyanobacteria" proteins_count="14"/>
<taxon_data name="Archaea" proteins_count="20"/>
<taxon_data name="Eukaryota" proteins_count="17"/>
<taxon_data name="Fungi" proteins_count="1"/>
<taxon_data name="Plastid Group" proteins_count="7"/>
<taxon_data name="Green Plants" proteins_count="7"/>
<taxon_data name="Metazoa" proteins_count="8"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000061" protein_count="495" short_name="Surp" type="Domain">
<name>SWAP/Surp</name>
<abstract>
SWAP is derived from the Suppressor-of-White-APricot splicing
regulator from <taxon tax_id="7227">Drosophila melanogaster</taxon>. The domain is found in regulators responsible for pervasive, nonsex-specific alternative pre-mRNA
splicing characteristics and has been found in splicing regulatory proteins [<cite idref="PUB00002852"/>]. These ancient, conserved
SWAP proteins share a colinearly arrayed series of novel
sequence motifs [<cite idref="PUB00006690"/>].
</abstract>
<class_list>
<classification id="GO:0003723" class_type="GO">
<category>Molecular Function</category>
<description>RNA binding</description>
</classification>
<classification id="GO:0006396" class_type="GO">
<category>Biological Process</category>
<description>RNA processing</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P12297"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P32524"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q10580"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q15459"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q8CH02"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00002852">
<author_list>Denhez F, Lafyatis R.</author_list>
<title>Conservation of regulated alternative splicing and identification of functional domains in vertebrate homologs to the Drosophila splicing regulator, suppressor-of-white-apricot.</title>
<db_xref db="PUBMED" dbkey="8206918"/>
<journal>J. Biol. Chem.</journal>
<location issue="23" pages="16170-9" volume="269"/>
<year>1994</year>
</publication>
<publication id="PUB00006690">
<author_list>Spikes DA, Kramer J, Bingham PM, Van Doren K.</author_list>
<title>SWAP pre-mRNA splicing regulators are a novel, ancient protein family sharing a highly conserved sequence motif with the prp21 family of constitutive splicing proteins.</title>
<db_xref db="PUBMED" dbkey="7971282"/>
<journal>Nucleic Acids Res.</journal>
<location issue="21" pages="4510-9" volume="22"/>
<year>1994</year>
</publication>
</pub_list>
<member_list>
<db_xref protein_count="447" db="PFAM" dbkey="PF01805" name="Surp"/>
<db_xref protein_count="475" db="PROFILE" dbkey="PS50128" name="SURP"/>
<db_xref protein_count="482" db="SMART" dbkey="SM00648" name="SWAP"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF01805"/>
<db_xref db="BLOCKS" dbkey="IPB000061"/>
<db_xref db="PROSITEDOC" dbkey="PDOC50128"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1ug0"/>
<db_xref db="PDB" dbkey="1x4o"/>
<db_xref db="PDB" dbkey="1x4p"/>
<db_xref db="PDB" dbkey="2dt6"/>
<db_xref db="PDB" dbkey="2dt7"/>
<db_xref db="SCOP" dbkey="a.217.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Eukaryota" proteins_count="495"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="26"/>
<taxon_data name="Rice spp." proteins_count="18"/>
<taxon_data name="Fungi" proteins_count="83"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="6"/>
<taxon_data name="Other Eukaryotes" proteins_count="1"/>
<taxon_data name="Other Eukaryotes" proteins_count="1"/>
<taxon_data name="Nematoda" proteins_count="4"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="4"/>
<taxon_data name="Arthropoda" proteins_count="72"/>
<taxon_data name="Fruit Fly" proteins_count="8"/>
<taxon_data name="Chordata" proteins_count="90"/>
<taxon_data name="Human" proteins_count="17"/>
<taxon_data name="Mouse" proteins_count="11"/>
<taxon_data name="Other Eukaryotes" proteins_count="5"/>
<taxon_data name="Plastid Group" proteins_count="113"/>
<taxon_data name="Green Plants" proteins_count="113"/>
<taxon_data name="Metazoa" proteins_count="274"/>
<taxon_data name="Plastid Group" proteins_count="56"/>
<taxon_data name="Plastid Group" proteins_count="29"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
<taxon_data name="Other Eukaryotes" proteins_count="8"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000062" protein_count="2350" short_name="Thymidylate_kin-like" type="Family">
<name>Thymidylate kinase-like</name>
<abstract>
<p>Thymidylate kinase (<db_xref db="EC" dbkey="2.7.4.9"/>; dTMP kinase) catalyzes the phosphorylation of thymidine 5'-monophosphate (dTMP) to form thymidine 5'-diphosphate (dTDP) in the presence of ATP and magnesium: </p>
<reaction>
ATP + thymidine 5'-phosphate = ADP + thymidine 5'-diphosphate
</reaction>
<p>Thymidylate kinase is an ubiquitous enzyme of about 25 Kd and is important in the dTTP synthesis pathway for DNA synthesis. The function of dTMP kinase in eukaryotes comes from the study of a cell cycle mutant, cdc8, in <taxon tax_id="4932">Saccharomyces cerevisiae</taxon>. Structural and functional analyses suggest that the cDNA codes for authentic human dTMP kinase. The mRNA levels and enzyme activities corresponded to cell cycle progression and cell growth stages[<cite idref="PUB00016913"/>]. </p>
<p>This entry reprsents known and predicted kinases, and related enzymes such as UMP-CMP kinase.</p>
</abstract>
<class_list>
<classification id="GO:0005524" class_type="GO">
<category>Molecular Function</category>
<description>ATP binding</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P00572"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P23919"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P97930"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q22018"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q55593"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00016913">
<author_list>Huang SH, Tang A, Drisco B, Zhang SQ, Seeger R, Li C, Jong A.</author_list>
<title>Human dTMP kinase: gene expression and enzymatic activity coinciding with cell cycle progression and cell growth.</title>
<db_xref db="PUBMED" dbkey="8024690"/>
<journal>DNA Cell Biol.</journal>
<location issue="5" pages="461-71" volume="13"/>
<year>1994</year>
</publication>
</pub_list>
<child_list>
<rel_ref ipr_ref="IPR014505"/>
<rel_ref ipr_ref="IPR018094"/>
</child_list>
<contains>
<rel_ref ipr_ref="IPR018095"/>
</contains>
<member_list>
<db_xref protein_count="2350" db="PFAM" dbkey="PF02223" name="Thymidylate_kin"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF02223"/>
<db_xref db="MSDsite" dbkey="PS01331"/>
<db_xref db="BLOCKS" dbkey="IPB000062"/>
<db_xref db="EC" dbkey="2.7.4.9"/>
<db_xref db="PROSITEDOC" dbkey="PDOC01034"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1e2d"/>
<db_xref db="PDB" dbkey="1e2e"/>
<db_xref db="PDB" dbkey="1e2f"/>
<db_xref db="PDB" dbkey="1e2g"/>
<db_xref db="PDB" dbkey="1e2q"/>
<db_xref db="PDB" dbkey="1e98"/>
<db_xref db="PDB" dbkey="1e99"/>
<db_xref db="PDB" dbkey="1e9a"/>
<db_xref db="PDB" dbkey="1e9b"/>
<db_xref db="PDB" dbkey="1e9c"/>
<db_xref db="PDB" dbkey="1e9d"/>
<db_xref db="PDB" dbkey="1e9e"/>
<db_xref db="PDB" dbkey="1e9f"/>
<db_xref db="PDB" dbkey="1g3u"/>
<db_xref db="PDB" dbkey="1gsi"/>
<db_xref db="PDB" dbkey="1gtv"/>
<db_xref db="PDB" dbkey="1mrn"/>
<db_xref db="PDB" dbkey="1mrs"/>
<db_xref db="PDB" dbkey="1n5i"/>
<db_xref db="PDB" dbkey="1n5j"/>
<db_xref db="PDB" dbkey="1n5k"/>
<db_xref db="PDB" dbkey="1n5l"/>
<db_xref db="PDB" dbkey="1nmx"/>
<db_xref db="PDB" dbkey="1nmy"/>
<db_xref db="PDB" dbkey="1nmz"/>
<db_xref db="PDB" dbkey="1nn0"/>
<db_xref db="PDB" dbkey="1nn1"/>
<db_xref db="PDB" dbkey="1nn3"/>
<db_xref db="PDB" dbkey="1nn5"/>
<db_xref db="PDB" dbkey="1tmk"/>
<db_xref db="PDB" dbkey="1w2g"/>
<db_xref db="PDB" dbkey="1w2h"/>
<db_xref db="PDB" dbkey="2axp"/>
<db_xref db="PDB" dbkey="2tmk"/>
<db_xref db="PDB" dbkey="2v54"/>
<db_xref db="PDB" dbkey="2w0s"/>
<db_xref db="PDB" dbkey="3tmk"/>
<db_xref db="PDB" dbkey="4tmk"/>
<db_xref db="PDB" dbkey="5tmp"/>
<db_xref db="CATH" dbkey="3.40.50.300"/>
<db_xref db="SCOP" dbkey="c.37.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="1953"/>
<taxon_data name="Cyanobacteria" proteins_count="55"/>
<taxon_data name="Synechocystis PCC 6803" proteins_count="1"/>
<taxon_data name="Archaea" proteins_count="127"/>
<taxon_data name="Eukaryota" proteins_count="215"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="5"/>
<taxon_data name="Rice spp." proteins_count="4"/>
<taxon_data name="Fungi" proteins_count="68"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="6"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
<taxon_data name="Nematoda" proteins_count="1"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="1"/>
<taxon_data name="Arthropoda" proteins_count="28"/>
<taxon_data name="Fruit Fly" proteins_count="7"/>
<taxon_data name="Chordata" proteins_count="30"/>
<taxon_data name="Human" proteins_count="5"/>
<taxon_data name="Mouse" proteins_count="5"/>
<taxon_data name="Virus" proteins_count="54"/>
<taxon_data name="Unclassified" proteins_count="1"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
<taxon_data name="Plastid Group" proteins_count="29"/>
<taxon_data name="Green Plants" proteins_count="29"/>
<taxon_data name="Metazoa" proteins_count="139"/>
<taxon_data name="Plastid Group" proteins_count="21"/>
<taxon_data name="Plastid Group" proteins_count="13"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
<taxon_data name="Other Eukaryotes" proteins_count="4"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR014505"/>
<sec_ac acc="IPR018094"/>
</sec_list>
</interpro>
<interpro id="IPR000064" protein_count="4879" short_name="NLP_P60" type="Domain">
<name>NLP/P60</name>
<abstract>
<p>The <taxon tax_id="562">Escherichia coli</taxon> NLPC/Listeria P60 domain occurs at the C terminus of a number of different bacterial and viral proteins. The viral proteins are either described as tail assembly proteins or Gp19. In bacteria, the proteins are variously described as being putative tail component of prophage, invasin, invasion associated protein, putative lipoprotein, cell wall hydrolase, or putative endopeptidase. </p>
<p>The E. coli NLPC/Listeria P60 domain is contained within the boundaries of the cysteine peptidase domain that defines the MEROPS peptidase family C40 (clan C-). A type example being dipeptidyl-peptidase VI from <taxon tax_id="1421">Bacillus sphaericus</taxon> and gamma-glutamyl-diamino acid-endopeptidase precursor from <taxon tax_id="1358">Lactococcus lactis</taxon> <db_xref db="EC" dbkey="3.4.19.11"/>. This group also contains proteins classified as non-peptidase homologues in that they either have been found experimentally to be without peptidase activity, or lack amino acid residues that are believed to be essential for the catalytic activity of peptidases in the C40 family.
</p>
</abstract>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P03729"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P0AFV4"/>
</example>
</example_list>
<pub_list/>
<found_in>
<rel_ref ipr_ref="IPR011929"/>
</found_in>
<member_list>
<db_xref protein_count="4879" db="PFAM" dbkey="PF00877" name="NLPC_P60"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00877"/>
<db_xref db="BLOCKS" dbkey="IPB000064"/>
<db_xref db="MEROPS" dbkey="C40"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="2hbw"/>
<db_xref db="CATH" dbkey="3.90.1720.10"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="4787"/>
<taxon_data name="Cyanobacteria" proteins_count="52"/>
<taxon_data name="Synechocystis PCC 6803" proteins_count="1"/>
<taxon_data name="Archaea" proteins_count="3"/>
<taxon_data name="Eukaryota" proteins_count="37"/>
<taxon_data name="Rice spp." proteins_count="1"/>
<taxon_data name="Fungi" proteins_count="16"/>
<taxon_data name="Other Eukaryotes" proteins_count="9"/>
<taxon_data name="Other Eukaryotes" proteins_count="3"/>
<taxon_data name="Arthropoda" proteins_count="1"/>
<taxon_data name="Chordata" proteins_count="1"/>
<taxon_data name="Mouse" proteins_count="1"/>
<taxon_data name="Virus" proteins_count="52"/>
<taxon_data name="Plastid Group" proteins_count="4"/>
<taxon_data name="Green Plants" proteins_count="4"/>
<taxon_data name="Metazoa" proteins_count="18"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000065" protein_count="150" short_name="Leptin" type="Family">
<name>Obesity factor</name>
<abstract>
Leptin, a metabolic monitor of food intake and energy need, is expressed
by the ob obesity gene. The protein may function as part of a signalling
pathway from adipose tissue that acts to regulate the size of the body
fat depot [<cite idref="PUB00004193"/>], the hormone effectively turning the brain's appetite
message off when it senses that the body is satiated. Obese humans have
high levels of the protein, suggesting a similarity to type II (adult
onset) diabetes, in which sufferers over-produce insulin, but can't respond
to it metabolically - they have become insulin resistant. Similarly, it is
thought that obese individuals may be leptin resistant.
</abstract>
<class_list>
<classification id="GO:0005179" class_type="GO">
<category>Molecular Function</category>
<description>hormone activity</description>
</classification>
<classification id="GO:0005576" class_type="GO">
<category>Cellular Component</category>
<description>extracellular region</description>
</classification>
<classification id="GO:0007165" class_type="GO">
<category>Biological Process</category>
<description>signal transduction</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O02720"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P41159"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P41160"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00004193">
<author_list>Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM.</author_list>
<title>Positional cloning of the mouse obese gene and its human homologue.</title>
<db_xref db="PUBMED" dbkey="7984236"/>
<journal>Nature</journal>
<location issue="6505" pages="425-32" volume="372"/>
<year>1994</year>
</publication>
</pub_list>
<parent_list>
<rel_ref ipr_ref="IPR009079"/>
</parent_list>
<member_list>
<db_xref protein_count="135" db="PANTHER" dbkey="PTHR11724" name="Leptin"/>
<db_xref protein_count="145" db="PFAM" dbkey="PF02024" name="Leptin"/>
<db_xref protein_count="84" db="PIRSF" dbkey="PIRSF001837" name="Leptin"/>
<db_xref protein_count="132" db="PRINTS" dbkey="PR00495" name="LEPTIN"/>
<db_xref protein_count="145" db="PRODOM" dbkey="PD005698" name="Leptin"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF02024"/>
<db_xref db="BLOCKS" dbkey="IPB000065"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1ax8"/>
<db_xref db="CATH" dbkey="1.20.1250.10"/>
<db_xref db="SCOP" dbkey="a.26.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Eukaryota" proteins_count="150"/>
<taxon_data name="Chordata" proteins_count="150"/>
<taxon_data name="Human" proteins_count="6"/>
<taxon_data name="Mouse" proteins_count="2"/>
<taxon_data name="Metazoa" proteins_count="150"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000066" protein_count="374" short_name="Antenna_a/b" type="Family">
<name>Antenna complex, alpha/beta subunit</name>
<abstract>
In photosynthetic bacteria the antenna complexes function as light-harvesting
systems that absorb light radiation and transfer the excitation energy to the
reaction centres. The antenna complexes are generally composed of two
polypeptides (alpha and beta chains); two or three bacteriochlorophyll (BChl)
molecules and some carotenoids [<cite idref="PUB00001417"/>, <cite idref="PUB00003468"/>].
Both the alpha and the beta chains of antenna complexes are small proteins of
42 to 68 residues which share a three-domain organisation. They are composed
of a N-terminal hydrophilic cytoplasmic domain followed by a transmembrane
region and a C-terminal hydrophilic periplasmic domain. In the transmembrane
region of both chains there is a conserved histidine which is most probably
involved in the binding of the magnesium atom of a bacteriochlorophyll group.
The beta chains contain an additional conserved histidine which is located at
the C-terminal extremity of the cytoplasmic domain and which is also thought
to be involved in bacteriochlorophyll-binding.
</abstract>
<class_list>
<classification id="GO:0016021" class_type="GO">
<category>Cellular Component</category>
<description>integral to membrane</description>
</classification>
<classification id="GO:0019684" class_type="GO">
<category>Biological Process</category>
<description>photosynthesis, light reaction</description>
</classification>
<classification id="GO:0030077" class_type="GO">
<category>Cellular Component</category>
<description>plasma membrane light-harvesting complex</description>
</classification>
<classification id="GO:0045156" class_type="GO">
<category>Molecular Function</category>
<description>electron transporter, transferring electrons within the cyclic electron transport pathway of photosynthesis activity</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P02947"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00001417">
<author_list>Wagner-Huber R, Brunisholz RA, Bissig I, Frank G, Suter F, Zuber H.</author_list>
<title>The primary structure of the antenna polypeptides of Ectothiorhodospira halochloris and Ectothiorhodospira halophila. Four core-type antenna polypeptides in E. halochloris and E. halophila.</title>
<db_xref db="PUBMED" dbkey="1577009"/>
<journal>Eur. J. Biochem.</journal>
<location issue="3" pages="917-25" volume="205"/>
<year>1992</year>
</publication>
<publication id="PUB00003468">
<author_list>Brunisholz RA, Zuber H.</author_list>
<title>Structure, function and organization of antenna polypeptides and antenna complexes from the three families of Rhodospirillaneae.</title>
<db_xref db="PUBMED" dbkey="1460542"/>
<journal>J. Photochem. Photobiol. B, Biol.</journal>
<location issue="1-2" pages="113-40" volume="15"/>
<year>1992</year>
</publication>
</pub_list>
<child_list>
<rel_ref ipr_ref="IPR002362"/>
<rel_ref ipr_ref="IPR018332"/>
</child_list>
<contains>
<rel_ref ipr_ref="IPR002361"/>
</contains>
<member_list>
<db_xref protein_count="368" db="PFAM" dbkey="PF00556" name="LHC"/>
<db_xref protein_count="367" db="SSF" dbkey="SSF56918" name="Antenna_a/b"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00556"/>
<db_xref db="COMe" dbkey="PRX000801"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1dx7"/>
<db_xref db="PDB" dbkey="1ijd"/>
<db_xref db="PDB" dbkey="1jo5"/>
<db_xref db="PDB" dbkey="1kzu"/>
<db_xref db="PDB" dbkey="1lgh"/>
<db_xref db="PDB" dbkey="1nkz"/>
<db_xref db="PDB" dbkey="1wrg"/>
<db_xref db="PDB" dbkey="1xrd"/>
<db_xref db="PDB" dbkey="2fkw"/>
<db_xref db="CATH" dbkey="1.20.5.250"/>
<db_xref db="CATH" dbkey="4.10.220.20"/>
<db_xref db="SCOP" dbkey="f.3.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="374"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR002362"/>
<sec_ac acc="IPR018332"/>
</sec_list>
</interpro>
<interpro id="IPR000067" protein_count="1067" short_name="FlgMring_FLIF" type="Family">
<name>Flagellar FliF M-ring protein</name>
<abstract>
This family corresponds to the FliF protein. FliF is the major protein
of the M-ring in bacterial flagellar basal body [<cite idref="PUB00002086"/>].
The basal body consists of four rings (L,P,S and M) surrounding the
flagellar rod, which is believed to transmit motor rotation to the filament
[<cite idref="PUB00003254"/>].
The M ring is integral to the inner membrane of the cell, and may be
connected to the rod via the S (supramembrane) ring, which lies just distal
to it. The L and P rings reside in the outer membrane and periplasmic space,
respectively.
FliF lacks a signal peptide and is predicted to have considerable
alpha-helical structure, including an N-terminal sequence that is likely
to be membrane-spanning [<cite idref="PUB00002086"/>]. Overall, however, FliF has a relatively
hydrophilic sequence, with a high charge density, especially towards its
C terminus [<cite idref="PUB00002086"/>].
</abstract>
<class_list>
<classification id="GO:0001539" class_type="GO">
<category>Biological Process</category>
<description>ciliary or flagellar motility</description>
</classification>
<classification id="GO:0003774" class_type="GO">
<category>Molecular Function</category>
<description>motor activity</description>
</classification>
<classification id="GO:0009431" class_type="GO">
<category>Cellular Component</category>
<description>bacterial-type flagellum basal body, MS ring</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O52069"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00002086">
<author_list>Jones CJ, Homma M, Macnab RM.</author_list>
<title>L-, P-, and M-ring proteins of the flagellar basal body of Salmonella typhimurium: gene sequences and deduced protein sequences.</title>
<db_xref db="PUBMED" dbkey="2544561"/>
<journal>J. Bacteriol.</journal>
<location issue="7" pages="3890-900" volume="171"/>
<year>1989</year>
</publication>
<publication id="PUB00003254">
<author_list>Homma M, Kutsukake K, Hasebe M, Iino T, Macnab RM.</author_list>
<title>FlgB, FlgC, FlgF and FlgG. A family of structurally related proteins in the flagellar basal body of Salmonella typhimurium.</title>
<db_xref db="PUBMED" dbkey="2129540"/>
<journal>J. Mol. Biol.</journal>
<location issue="2" pages="465-77" volume="211"/>
<year>1990</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR006182"/>
<rel_ref ipr_ref="IPR013556"/>
</contains>
<member_list>
<db_xref protein_count="1054" db="PRINTS" dbkey="PR01009" name="FLGMRINGFLIF"/>
<db_xref protein_count="1042" db="TIGRFAMs" dbkey="TIGR00206" name="fliF"/>
</member_list>
<external_doc_list>
<db_xref db="BLOCKS" dbkey="IPB000067"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="1062"/>
<taxon_data name="Eukaryota" proteins_count="3"/>
<taxon_data name="Rice spp." proteins_count="1"/>
<taxon_data name="Unclassified" proteins_count="2"/>
<taxon_data name="Plastid Group" proteins_count="3"/>
<taxon_data name="Green Plants" proteins_count="3"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000068" protein_count="101" short_name="GPCR_3_Ca_sens_rcpt-rel" type="Family">
<name>GPCR, family 3, extracellular calcium-sensing receptor-related</name>
<abstract>
<p>G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [<cite idref="PUB00004961"/>]. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/). </p>
<p>The metabotropic glutamate receptors are functionally and pharmacologically distinct from the ionotropic glutamate receptors. They are coupled to G-proteins and stimulate the inositol phosphate/Ca<sup>2+</sup> intracellular signalling pathway [<cite idref="PUB00004090"/>, <cite idref="PUB00005138"/>, <cite idref="PUB00002720"/>, <cite idref="PUB00004309"/>]. At least eight sub-types of metabotropic receptor (MGR1-8) have been identified in cloning studies. The sub-types differ in their agonist pharmacology and signal transduction pathways [<cite idref="PUB00005885"/>].</p>
<p>The calcium-sensing receptor (CaSR) is an integral membrane protein that
senses changes in the extracellular concentration of calcium ions. The
activity of the receptor is mediated by a G-protein that activates a
phosphatidyl-inositol-calcium second messenger system. The sequences of the
receptors show a high degree of similarity to the TM signature that
characterises the metabotropic glutamate receptors. In addition, the
sequences contain a large extracellular domain that includes clusters of
acidic amino acid residues, which may be involved in calcium binding [<cite idref="PUB00004161"/>].
Defects in CaSR that result in reduced activity of the receptor cause
familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), inherited conditions characterised by altered calcium
homeostasis [<cite idref="PUB00002009"/>, <cite idref="PUB00003100"/>]. FHH-affected individuals exhibit mild or modest hypercalcemia, relative hypocalciuria and inappropriately normal PTH levels. By
contrast, NSHPT is a rare autosomal recessive life-threatening disorder
characterised by high serum calcium concentrations, skeletal demineralisation and parathyroid hyperplasia. In addition, defects resulting from
receptor activation at subnormal Ca<sup>2+</sup> levels cause autosomal dominant
hypocalcemia [<cite idref="PUB00003896"/>].</p>
<p>This entry represents the extracellular calcium-sensing receptors and related proteins in GPCR family 3, such as the taste receptors.</p>
</abstract>
<class_list>
<classification id="GO:0004930" class_type="GO">
<category>Molecular Function</category>
<description>G-protein coupled receptor activity</description>
</classification>
<classification id="GO:0007186" class_type="GO">
<category>Biological Process</category>
<description>G-protein coupled receptor protein signaling pathway</description>
</classification>
<classification id="GO:0016021" class_type="GO">
<category>Cellular Component</category>
<description>integral to membrane</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="A3QP01"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="O70410"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P41180"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00002009">
<author_list>Ward BK, Stuckey BG, Gutteridge DH, Laing NG, Pullan PT, Ratajczak T.</author_list>
<title>A novel mutation (L174R) in the Ca2+-sensing receptor gene associated with familial hypocalciuric hypercalcemia.</title>
<db_xref db="PUBMED" dbkey="9298824"/>
<journal>Hum. Mutat.</journal>
<location issue="3" pages="233-5" volume="10"/>
<year>1997</year>
</publication>
<publication id="PUB00002720">
<author_list>Abe T, Sugihara H, Nawa H, Shigemoto R, Mizuno N, Nakanishi S.</author_list>
<title>Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction.</title>
<db_xref db="PUBMED" dbkey="1320017"/>
<journal>J. Biol. Chem.</journal>
<location issue="19" pages="13361-8" volume="267"/>
<year>1992</year>
</publication>
<publication id="PUB00003100">
<author_list>Pearce SH, Trump D, Wooding C, Besser GM, Chew SL, Grant DB, Heath DA, Hughes IA, Paterson CR, Whyte MP.</author_list>
<title>Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism.</title>
<db_xref db="PUBMED" dbkey="8675635"/>
<journal>J. Clin. Invest.</journal>
<location issue="6" pages="2683-92" volume="96"/>
<year>1995</year>
</publication>
<publication id="PUB00003896">
<author_list>Pollak MR, Brown EM, Estep HL, McLaine PN, Kifor O, Park J, Hebert SC, Seidman CE, Seidman JG.</author_list>
<title>Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation.</title>
<db_xref db="PUBMED" dbkey="7874174"/>
<journal>Nat. Genet.</journal>
<location issue="3" pages="303-7" volume="8"/>
<year>1994</year>
</publication>
<publication id="PUB00004161">
<author_list>Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O, Sun A, Hediger MA, Lytton J, Hebert SC.</author_list>
<title>Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid.</title>
<db_xref db="PUBMED" dbkey="8255296"/>
<journal>Nature</journal>
<location issue="6455" pages="575-80" volume="366"/>
<year>1993</year>
</publication>
<publication id="PUB00004961">
<author_list>Attwood TK, Findlay JB.</author_list>
<title>Fingerprinting G-protein-coupled receptors.</title>
<db_xref db="PUBMED" dbkey="8170923"/>
<journal>Protein Eng.</journal>
<location issue="2" pages="195-203" volume="7"/>
<year>1994</year>
</publication>
<publication id="PUB00005885">
<author_list>Watson S, Arkinstall S.</author_list>
<title>Glutamate.</title>
<book_title>ISBN:0127384405</book_title>
<location pages="130-41"/>
<year>1994</year>
</publication>
<publication id="PUB00005138">
<author_list>Houamed KM, Kuijper JL, Gilbert TL, Haldeman BA, O'Hara PJ, Mulvihill ER, Almers W, Hagen FS.</author_list>
<title>Cloning, expression, and gene structure of a G protein-coupled glutamate receptor from rat brain.</title>
<db_xref db="PUBMED" dbkey="1656524"/>
<journal>Science</journal>
<location issue="5010" pages="1318-21" volume="252"/>
<year>1991</year>
</publication>
<publication id="PUB00004090">
<author_list>Masu M, Tanabe Y, Tsuchida K, Shigemoto R, Nakanishi S.</author_list>
<title>Sequence and expression of a metabotropic glutamate receptor.</title>
<db_xref db="PUBMED" dbkey="1847995"/>
<journal>Nature</journal>
<location issue="6312" pages="760-5" volume="349"/>
<year>1991</year>
</publication>
<publication id="PUB00004309">
<author_list>Tanabe Y, Masu M, Ishii T, Shigemoto R, Nakanishi S.</author_list>
<title>A family of metabotropic glutamate receptors.</title>
<db_xref db="PUBMED" dbkey="1309649"/>
<journal>Neuron</journal>
<location issue="1" pages="169-79" volume="8"/>
<year>1992</year>
</publication>
</pub_list>
<parent_list>
<rel_ref ipr_ref="IPR000337"/>
</parent_list>
<child_list>
<rel_ref ipr_ref="IPR015531"/>
</child_list>
<contains>
<rel_ref ipr_ref="IPR001828"/>
</contains>
<member_list>
<db_xref protein_count="101" db="PRINTS" dbkey="PR00592" name="CASENSINGR"/>
</member_list>
<external_doc_list>
<db_xref db="BLOCKS" dbkey="IPB000068"/>
<db_xref db="IUPHAR" dbkey="2926"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Eukaryota" proteins_count="101"/>
<taxon_data name="Chordata" proteins_count="93"/>
<taxon_data name="Human" proteins_count="13"/>
<taxon_data name="Mouse" proteins_count="10"/>
<taxon_data name="Metazoa" proteins_count="101"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR015531"/>
</sec_list>
</interpro>
<interpro id="IPR000069" protein_count="3797" short_name="Env_glycoprot_M_flavivir" type="Domain">
<name>Envelope glycoprotein M, flavivirus</name>
<abstract>
<p>Flaviviruses are small enveloped viruses with virions comprised of
three proteins called C, M and E [<cite idref="PUB00003522"/>, <cite idref="PUB00000171"/>, <cite idref="PUB00003500"/>]. The envelope glycoprotein M is made as a precursor, called prM. The precursor portion of the protein is the signal peptide for the proteins entry into the membrane. prM is cleaved to form M in a late-stage cleavage event. Associated with this cleavage is a change in the infectivity and fusion activity of the virus.</p>
</abstract>
<class_list>
<classification id="GO:0019028" class_type="GO">
<category>Cellular Component</category>
<description>viral capsid</description>
</classification>
<classification id="GO:0019058" class_type="GO">
<category>Biological Process</category>
<description>viral infectious cycle</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P03314"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00000171">
<author_list>Heinz FX, Auer G, Stiasny K, Holzmann H, Mandl C, Guirakhoo F, Kunz C.</author_list>
<title>The interactions of the flavivirus envelope proteins: implications for virus entry and release.</title>
<db_xref db="PUBMED" dbkey="7913359"/>
<journal>Arch. Virol. Suppl.</journal>
<location pages="339-48" volume="9"/>
<year>1994</year>
</publication>
<publication id="PUB00003500">
<author_list>Konishi E, Mason PW.</author_list>
<title>Proper maturation of the Japanese encephalitis virus envelope glycoprotein requires cosynthesis with the premembrane protein.</title>
<db_xref db="PUBMED" dbkey="8437237"/>
<journal>J. Virol.</journal>
<location issue="3" pages="1672-5" volume="67"/>
<year>1993</year>
</publication>
<publication id="PUB00003522">
<author_list>Schalich J, Allison SL, Stiasny K, Mandl CW, Kunz C, Heinz FX.</author_list>
<title>Recombinant subviral particles from tick-borne encephalitis virus are fusogenic and provide a model system for studying flavivirus envelope glycoprotein functions.</title>
<db_xref db="PUBMED" dbkey="8676481"/>
<journal>J. Virol.</journal>
<location issue="7" pages="4549-57" volume="70"/>
<year>1996</year>
</publication>
</pub_list>
<found_in>
<rel_ref ipr_ref="IPR014412"/>
</found_in>
<member_list>
<db_xref protein_count="3797" db="PFAM" dbkey="PF01004" name="Flavi_M"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF01004"/>
<db_xref db="EC" dbkey="2.1.1.56"/>
<db_xref db="EC" dbkey="2.1.1.57"/>
<db_xref db="EC" dbkey="2.7.7.48"/>
<db_xref db="EC" dbkey="3.4.21.91"/>
<db_xref db="EC" dbkey="3.6.1.15"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Virus" proteins_count="3797"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000070" protein_count="1139" short_name="Pectinesterase_cat" type="Domain">
<name>Pectinesterase, catalytic</name>
<abstract>
<p>Pectinesterase <db_xref db="EC" dbkey="3.1.1.11"/> (pectin methylesterase) catalyses the de-esterification of pectin into pectate and methanol. Pectin is one of the main components of the plant cell wall. In plants, pectinesterase plays an important role in cell wall metabolism during fruit ripening. In plant bacterial pathogens such as <taxon tax_id="554">Erwinia carotovora</taxon> and in fungal pathogens such as <taxon tax_id="5061">Aspergillus niger</taxon>, pectinesterase is involved in maceration and soft-rotting of plant tissue. Plant pectinesterases are regulated by pectinesterase inhibitors, which are ineffective against microbial enzymes [<cite idref="PUB00016279"/>].</p>
<p>Prokaryotic and eukaryotic pectinesterases share a few regions of sequence similarity. The crystal structure of pectinesterase from <taxon tax_id="556">Erwinia chrysanthemi</taxon> revealed a beta-helix structure similar to that found in pectinolytic enzymes, though it is different from most structures of esterases [<cite idref="PUB00016280"/>]. The putative catalytic residues are in a similar location to those of the active site and substrate-binding cleft of pectate lyase.</p>
</abstract>
<class_list>
<classification id="GO:0005618" class_type="GO">
<category>Cellular Component</category>
<description>cell wall</description>
</classification>
<classification id="GO:0030599" class_type="GO">
<category>Molecular Function</category>
<description>pectinesterase activity</description>
</classification>
<classification id="GO:0042545" class_type="GO">
<category>Biological Process</category>
<description>cell wall modification</description>
</classification>
</class_list>
<example_list>
<example>
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<example>
<db_xref db="SWISSPROT" dbkey="P14280"/>
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<pub_list>
<publication id="PUB00016279">
<author_list>Di Matteo A, Giovane A, Raiola A, Camardella L, Bonivento D, De Lorenzo G, Cervone F, Bellincampi D, Tsernoglou D.</author_list>
<title>Structural basis for the interaction between pectin methylesterase and a specific inhibitor protein.</title>
<db_xref db="PUBMED" dbkey="15722470"/>
<journal>Plant Cell</journal>
<location issue="3" pages="849-58" volume="17"/>
<year>2005</year>
</publication>
<publication id="PUB00016280">
<author_list>Jenkins J, Mayans O, Smith D, Worboys K, Pickersgill RW.</author_list>
<title>Three-dimensional structure of Erwinia chrysanthemi pectin methylesterase reveals a novel esterase active site.</title>
<db_xref db="PUBMED" dbkey="11162105"/>
<journal>J. Mol. Biol.</journal>
<location issue="4" pages="951-60" volume="305"/>
<year>2001</year>
</publication>
</pub_list>
<parent_list>
<rel_ref ipr_ref="IPR012334"/>
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<contains>
<rel_ref ipr_ref="IPR018040"/>
</contains>
<member_list>
<db_xref protein_count="1141" db="PFAM" dbkey="PF01095" name="Pectinesterase"/>
</member_list>
<external_doc_list>
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<db_xref db="MSDsite" dbkey="PS00503"/>
<db_xref db="MSDsite" dbkey="PS00800"/>
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<db_xref db="PDB" dbkey="1qjv"/>
<db_xref db="PDB" dbkey="1xg2"/>
<db_xref db="PDB" dbkey="2nsp"/>
<db_xref db="PDB" dbkey="2nst"/>
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<db_xref db="PDB" dbkey="2ntp"/>
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<db_xref db="CATH" dbkey="2.160.20.10"/>
<db_xref db="SCOP" dbkey="b.80.1.5"/>
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<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="353"/>
<taxon_data name="Cyanobacteria" proteins_count="3"/>
<taxon_data name="Archaea" proteins_count="2"/>
<taxon_data name="Eukaryota" proteins_count="786"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="79"/>
<taxon_data name="Rice spp." proteins_count="142"/>
<taxon_data name="Fungi" proteins_count="84"/>
<taxon_data name="Arthropoda" proteins_count="1"/>
<taxon_data name="Plastid Group" proteins_count="690"/>
<taxon_data name="Green Plants" proteins_count="690"/>
<taxon_data name="Metazoa" proteins_count="85"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000071" protein_count="24951" short_name="Lentvrl_matrix_N" type="Domain">
<name>Immunodeficiency lentiviral matrix, N-terminal</name>
<abstract>
<p>Retroviral matrix proteins (or major core proteins) are components of envelope-associated capsids, which line the inner surface of virus envelopes and are associated with viral membranes [<cite idref="PUB00014063"/>]. Matrix proteins are produced as part of Gag precursor polyproteins. During viral maturation, the Gag polyprotein is cleaved into major structural proteins by the viral protease, yielding the matrix (MA), capsid (CA), nucleocapsid (NC), and some smaller peptides. Gag-derived proteins govern the entire assembly and release of the virus particles, with matrix proteins playing key roles in Gag stability, capsid assembly, transport and budding. Although matrix proteins from different retroviruses appear to perform similar functions and can have similar structural folds, their primary sequences can be very different.</p>
<p>This entry represents matrix proteins from immunodeficiency lentiviruses, such as <taxon tax_id="12721">Human immunodeficiency virus</taxon> (HIV) and <taxon tax_id="11723">Simian immunodeficiency virus</taxon> (SIV-cpz) [<cite idref="PUB00016321"/>]. The structure of the HIV protein consists of 5 alpha helices, a short 3.10 helix and a 3-stranded mixed beta-sheet [<cite idref="PUB00003338"/>].</p>
</abstract>
<class_list>
<classification id="GO:0005198" class_type="GO">
<category>Molecular Function</category>
<description>structural molecule activity</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O12158"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00003338">
<author_list>Massiah MA, Starich MR, Paschall C, Summers MF, Christensen AM, Sundquist WI.</author_list>
<title>Three-dimensional structure of the human immunodeficiency virus type 1 matrix protein.</title>
<db_xref db="PUBMED" dbkey="7966331"/>
<journal>J. Mol. Biol.</journal>
<location issue="2" pages="198-223" volume="244"/>
<year>1994</year>
</publication>
<publication id="PUB00014063">
<author_list>Conte MR, Matthews S.</author_list>
<title>Retroviral matrix proteins: a structural perspective.</title>
<db_xref db="PUBMED" dbkey="9657938"/>
<journal>Virology</journal>
<location issue="2" pages="191-8" volume="246"/>
<year>1998</year>
</publication>
<publication id="PUB00016321">
<author_list>Freed EO.</author_list>
<title>HIV-1 replication.</title>
<db_xref db="PUBMED" dbkey="12465460"/>
<journal>Somat. Cell Mol. Genet.</journal>
<location issue="1-6" pages="13-33" volume="26"/>
<year>2001</year>
</publication>
</pub_list>
<parent_list>
<rel_ref ipr_ref="IPR012344"/>
</parent_list>
<member_list>
<db_xref protein_count="24951" db="PFAM" dbkey="PF00540" name="Gag_p17"/>
<db_xref protein_count="24741" db="PRINTS" dbkey="PR00234" name="HIV1MATRIX"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00540"/>
<db_xref db="BLOCKS" dbkey="IPB000071"/>
</external_doc_list>
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<db_xref db="PDB" dbkey="1ecw"/>
<db_xref db="PDB" dbkey="1ed1"/>
<db_xref db="PDB" dbkey="1hiw"/>
<db_xref db="PDB" dbkey="1l6n"/>
<db_xref db="PDB" dbkey="1m9c"/>
<db_xref db="PDB" dbkey="1m9d"/>
<db_xref db="PDB" dbkey="1m9e"/>
<db_xref db="PDB" dbkey="1m9f"/>
<db_xref db="PDB" dbkey="1m9x"/>
<db_xref db="PDB" dbkey="1m9y"/>
<db_xref db="PDB" dbkey="1tam"/>
<db_xref db="PDB" dbkey="1uph"/>
<db_xref db="PDB" dbkey="2gol"/>
<db_xref db="PDB" dbkey="2h3f"/>
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</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Virus" proteins_count="24951"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000072" protein_count="349" short_name="PD_growth_factor" type="Domain">
<name>Platelet-derived growth factor (PDGF)</name>
<abstract>
Platelet-derived growth factor (PDGF) [<cite idref="PUB00000590"/>, <cite idref="PUB00001228"/>] is a potent mitogen for cells of
mesenchymal origin, including smooth muscle cells and glial cells. In both mouse and human, the PDGF signalling network consists of four ligands, PDGFA-D, and two receptors, PDGFRalpha and PDGFRbeta. All PDGFs function as secreted, disulphide-linked
homodimers, but only PDGFA and B can form functional heterodimers. PDGFRs also function as homo- and heterodimers. All known PDGFs have characteristic `PDGF domains',
which include eight conserved cysteines that are involved in inter- and intramolecular bonds.
Alternate splicing of the A chain transcript can give rise to two different
forms that differ only in their C-terminal extremity. The transforming protein
of <taxon tax_id="11970">Woolly monkey sarcoma virus</taxon> (WMSV) (Simian sarcoma virus), encoded by the v-sis oncogene, is derived from the B chain of PDGF.
<p>PDGFs are mitogenic during early developmental stages, driving the proliferation of undifferentiated mesenchyme and some progenitor populations. During later maturation stages, PDGF signalling has been implicated in tissue remodelling and cellular differentiation, and in inductive events involved in patterning and morphogenesis. In addition to driving
mesenchymal proliferation, PDGFs have been shown to direct the migration, differentiation and function of a variety of specialised mesenchymal and migratory cell types, both during development and in the
adult animal [<cite idref="PUB00014075"/>]. Other growth factors in this family include vascular endothelial growth factors B and C (VEGF-B, VEGF-C) [<cite idref="PUB00004886"/>, <cite idref="PUB00001288"/>] which are active in angiogenesis and endothelial cell growth, and placenta growth factor (PlGF) which is also active in angiogenesis [<cite idref="PUB00004494"/>]. </p>
<p>PDGF is structurally related to a number of other growth factors which also form disulphide-linked homo- or heterodimers.</p>
</abstract>
<class_list>
<classification id="GO:0008083" class_type="GO">
<category>Molecular Function</category>
<description>growth factor activity</description>
</classification>
<classification id="GO:0016020" class_type="GO">
<category>Cellular Component</category>
<description>membrane</description>
</classification>
</class_list>
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<example>
<db_xref db="SWISSPROT" dbkey="P01127"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P20033"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P52584"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P67861"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q72TD6"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00000590">
<author_list>Hannink M, Donoghue DJ.</author_list>
<title>Structure and function of platelet-derived growth factor (PDGF) and related proteins.</title>
<db_xref db="PUBMED" dbkey="2546599"/>
<journal>Biochim. Biophys. Acta</journal>
<location issue="1" pages="1-10" volume="989"/>
<year>1989</year>
</publication>
<publication id="PUB00001228">
<author_list>Heldin CH.</author_list>
<title>Structural and functional studies on platelet-derived growth factor.</title>
<db_xref db="PUBMED" dbkey="1425569"/>
<journal>EMBO J.</journal>
<location issue="12" pages="4251-9" volume="11"/>
<year>1992</year>
</publication>
<publication id="PUB00001288">
<author_list>Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K.</author_list>
<title>A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases.</title>
<db_xref db="PUBMED" dbkey="8617204"/>
<journal>EMBO J.</journal>
<location issue="2" pages="290-98" volume="15"/>
<year>1996</year>
</publication>
<publication id="PUB00004494">
<author_list>Maglione D, Guerriero V, Viglietto G, Ferraro MG, Aprelikova O, Alitalo K, Del Vecchio S, Lei KJ, Chou JY, Persico MG.</author_list>
<title>Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14.</title>
<db_xref db="PUBMED" dbkey="7681160"/>
<journal>Oncogene</journal>
<location issue="4" pages="925-31" volume="8"/>
<year>1993</year>
</publication>
<publication id="PUB00004886">
<author_list>Olofsson B, Pajusola K, Kaipainen A, von Euler G, Joukov V, Saksela O, Orpana A, Pettersson RF, Alitalo K, Eriksson U.</author_list>
<title>Vascular endothelial growth factor B, a novel growth factor for endothelial cells.</title>
<db_xref db="PUBMED" dbkey="8637916"/>
<journal>Proc. Natl. Acad. Sci. U.S.A.</journal>
<location issue="6" pages="2576-81" volume="93"/>
<year>1996</year>
</publication>
<publication id="PUB00014075">
<author_list>Hoch RV, Soriano P.</author_list>
<title>Roles of PDGF in animal development.</title>
<db_xref db="PUBMED" dbkey="12952899"/>
<journal>Development</journal>
<location issue="20" pages="4769-84" volume="130"/>
<year>2003</year>
</publication>
</pub_list>
<found_in>
<rel_ref ipr_ref="IPR015583"/>
</found_in>
<member_list>
<db_xref protein_count="298" db="PFAM" dbkey="PF00341" name="PDGF"/>
<db_xref protein_count="232" db="PROSITE" dbkey="PS00249" name="PDGF_1"/>
<db_xref protein_count="333" db="PROFILE" dbkey="PS50278" name="PDGF_2"/>
<db_xref protein_count="342" db="SMART" dbkey="SM00141" name="PDGF"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00341"/>
<db_xref db="MSDsite" dbkey="PS00249"/>
<db_xref db="BLOCKS" dbkey="IPB000072"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00222"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1bj1"/>
<db_xref db="PDB" dbkey="1cz8"/>
<db_xref db="PDB" dbkey="1flt"/>
<db_xref db="PDB" dbkey="1fzv"/>
<db_xref db="PDB" dbkey="1kat"/>
<db_xref db="PDB" dbkey="1mjv"/>
<db_xref db="PDB" dbkey="1mkg"/>
<db_xref db="PDB" dbkey="1mkk"/>
<db_xref db="PDB" dbkey="1pdg"/>
<db_xref db="PDB" dbkey="1qty"/>
<db_xref db="PDB" dbkey="1rv6"/>
<db_xref db="PDB" dbkey="1tzh"/>
<db_xref db="PDB" dbkey="1tzi"/>
<db_xref db="PDB" dbkey="1vpf"/>
<db_xref db="PDB" dbkey="1vpp"/>
<db_xref db="PDB" dbkey="1wq8"/>
<db_xref db="PDB" dbkey="1wq9"/>
<db_xref db="PDB" dbkey="2c7w"/>
<db_xref db="PDB" dbkey="2fjg"/>
<db_xref db="PDB" dbkey="2fjh"/>
<db_xref db="PDB" dbkey="2gnn"/>
<db_xref db="PDB" dbkey="2qr0"/>
<db_xref db="PDB" dbkey="2vpf"/>
<db_xref db="PDB" dbkey="2vwe"/>
<db_xref db="PDB" dbkey="3bdy"/>
<db_xref db="CATH" dbkey="2.10.90.10"/>
<db_xref db="SCOP" dbkey="g.17.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="2"/>
<taxon_data name="Eukaryota" proteins_count="321"/>
<taxon_data name="Rice spp." proteins_count="1"/>
<taxon_data name="Fungi" proteins_count="1"/>
<taxon_data name="Nematoda" proteins_count="1"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="1"/>
<taxon_data name="Arthropoda" proteins_count="60"/>
<taxon_data name="Fruit Fly" proteins_count="8"/>
<taxon_data name="Chordata" proteins_count="246"/>
<taxon_data name="Human" proteins_count="28"/>
<taxon_data name="Mouse" proteins_count="20"/>
<taxon_data name="Virus" proteins_count="25"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
<taxon_data name="Green Plants" proteins_count="1"/>
<taxon_data name="Metazoa" proteins_count="320"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000073" protein_count="23474" short_name="AB_hydrolase_1" type="Domain">
<name>Alpha/beta hydrolase fold-1</name>
<abstract>
<p>The alpha/beta hydrolase fold [<cite idref="PUB00004958"/>] is common to a number of hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is an alpha/beta-sheet (rather than a barrel), containing 8 strands connected by helices [<cite idref="PUB00004958"/>]. The enzymes are believed to have diverged from a common ancestor, preserving the arrangement of the catalytic residues. All have a catalytic triad, the elements of which are borne on loops, which are the best conserved structural features of the fold. Esterase (EST) from <taxon tax_id="303">Pseudomonas putida</taxon> is a member of the alpha/beta hydrolase fold superfamily of enzymes [<cite idref="PUB00038968"/>].</p>
<p>In most of the family members the beta-strands are parallels, but some have an inversion of the first strands, which gives it an antiparallel orientation. The catalytic triad residues are presented on loops. One of these is the nucleophile elbow and is the most conserved feature of the fold. Some other members lack one or all of the catalytic residues. Some members are therefore inactive but others are involved in surface recognition. The ESTHER database [<cite idref="PUB00043470"/>] gathers and annotates all the published information related to gene and protein sequences of this superfamily [<cite idref="PUB00043472"/>].</p>
<p>This entry represents fold-1 of alpha/beta hydrolase.</p>
</abstract>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="A6ZRW8"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="O18391"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P07098"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P34914"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P41879"/>
</example>
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<pub_list>
<publication id="PUB00004958">
<author_list>Ollis DL, Cheah E, Cygler M, Dijkstra B, Frolow F, Franken SM, Harel M, Remington SJ, Silman I, Schrag J.</author_list>
<title>The alpha/beta hydrolase fold.</title>
<db_xref db="PUBMED" dbkey="1409539"/>
<journal>Protein Eng.</journal>
<location issue="3" pages="197-211" volume="5"/>
<year>1992</year>
</publication>
<publication id="PUB00038968">
<author_list>Elmi F, Lee HT, Huang JY, Hsieh YC, Wang YL, Chen YJ, Shaw SY, Chen CJ.</author_list>
<title>Stereoselective esterase from Pseudomonas putida IFO12996 reveals alpha/beta hydrolase folds for D-beta-acetylthioisobutyric acid synthesis.</title>
<db_xref db="PUBMED" dbkey="16321951"/>
<journal>J. Bacteriol.</journal>
<location issue="24" pages="8470-6" volume="187"/>
<year>2005</year>
</publication>
</pub_list>
<child_list>
<rel_ref ipr_ref="IPR000639"/>
<rel_ref ipr_ref="IPR019913"/>
</child_list>
<contains>
<rel_ref ipr_ref="IPR000952"/>
</contains>
<found_in>
<rel_ref ipr_ref="IPR005945"/>
<rel_ref ipr_ref="IPR006296"/>
<rel_ref ipr_ref="IPR008220"/>
<rel_ref ipr_ref="IPR010076"/>
<rel_ref ipr_ref="IPR010125"/>
<rel_ref ipr_ref="IPR010963"/>
<rel_ref ipr_ref="IPR011287"/>
<rel_ref ipr_ref="IPR012020"/>
<rel_ref ipr_ref="IPR016292"/>
<rel_ref ipr_ref="IPR016812"/>
<rel_ref ipr_ref="IPR017209"/>
<rel_ref ipr_ref="IPR017727"/>
<rel_ref ipr_ref="IPR022485"/>
</found_in>
<member_list>
<db_xref protein_count="23475" db="PFAM" dbkey="PF00561" name="Abhydrolase_1"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00561"/>
<db_xref db="BLOCKS" dbkey="IPB000073"/>
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<structure_db_links>
<db_xref db="PDB" dbkey="1a7u"/>
<db_xref db="PDB" dbkey="1a88"/>
<db_xref db="PDB" dbkey="1a8q"/>
<db_xref db="PDB" dbkey="1a8s"/>
<db_xref db="PDB" dbkey="1a8u"/>
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<db_xref db="PDB" dbkey="1b6g"/>
<db_xref db="PDB" dbkey="1be0"/>
<db_xref db="PDB" dbkey="1bee"/>
<db_xref db="PDB" dbkey="1bez"/>
<db_xref db="PDB" dbkey="1bn6"/>
<db_xref db="PDB" dbkey="1bn7"/>
<db_xref db="PDB" dbkey="1bro"/>
<db_xref db="PDB" dbkey="1brt"/>
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<db_xref db="PDB" dbkey="1cqw"/>
<db_xref db="PDB" dbkey="1cqz"/>
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<db_xref db="PDB" dbkey="1cv2"/>
<db_xref db="PDB" dbkey="1cvl"/>
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<db_xref db="PDB" dbkey="1dwo"/>
<db_xref db="PDB" dbkey="1dwp"/>
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<db_xref db="PDB" dbkey="1e89"/>
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<db_xref db="PDB" dbkey="1ys1"/>
<db_xref db="PDB" dbkey="1ys2"/>
<db_xref db="PDB" dbkey="1zd2"/>
<db_xref db="PDB" dbkey="1zd3"/>
<db_xref db="PDB" dbkey="1zd4"/>
<db_xref db="PDB" dbkey="1zd5"/>
<db_xref db="PDB" dbkey="1zoi"/>
<db_xref db="PDB" dbkey="2b61"/>
<db_xref db="PDB" dbkey="2bfn"/>
<db_xref db="PDB" dbkey="2d0d"/>
<db_xref db="PDB" dbkey="2dhc"/>
<db_xref db="PDB" dbkey="2dhd"/>
<db_xref db="PDB" dbkey="2dhe"/>
<db_xref db="PDB" dbkey="2eda"/>
<db_xref db="PDB" dbkey="2edc"/>
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<db_xref db="PDB" dbkey="2g4l"/>
<db_xref db="PDB" dbkey="2had"/>
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<db_xref db="PDB" dbkey="2pky"/>
<db_xref db="PDB" dbkey="2pl5"/>
<db_xref db="PDB" dbkey="2psd"/>
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<db_xref db="PDB" dbkey="2qvb"/>
<db_xref db="PDB" dbkey="2r11"/>
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<db_xref db="PDB" dbkey="2ri6"/>
<db_xref db="PDB" dbkey="2v9z"/>
<db_xref db="PDB" dbkey="2vat"/>
<db_xref db="PDB" dbkey="2vav"/>
<db_xref db="PDB" dbkey="2vax"/>
<db_xref db="PDB" dbkey="2yas"/>
<db_xref db="PDB" dbkey="2yxp"/>
<db_xref db="PDB" dbkey="3bdi"/>
<db_xref db="PDB" dbkey="3bwx"/>
<db_xref db="PDB" dbkey="3c6x"/>
<db_xref db="PDB" dbkey="3c6y"/>
<db_xref db="PDB" dbkey="3c6z"/>
<db_xref db="PDB" dbkey="3c70"/>
<db_xref db="PDB" dbkey="3fob"/>
<db_xref db="PDB" dbkey="3lip"/>
<db_xref db="PDB" dbkey="3yas"/>
<db_xref db="PDB" dbkey="4lip"/>
<db_xref db="PDB" dbkey="4yas"/>
<db_xref db="PDB" dbkey="5lip"/>
<db_xref db="PDB" dbkey="5yas"/>
<db_xref db="PDB" dbkey="6yas"/>
<db_xref db="PDB" dbkey="7yas"/>
<db_xref db="CATH" dbkey="3.40.50.1820"/>
<db_xref db="SCOP" dbkey="c.69.1.10"/>
<db_xref db="SCOP" dbkey="c.69.1.11"/>
<db_xref db="SCOP" dbkey="c.69.1.12"/>
<db_xref db="SCOP" dbkey="c.69.1.18"/>
<db_xref db="SCOP" dbkey="c.69.1.20"/>
<db_xref db="SCOP" dbkey="c.69.1.26"/>
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<db_xref db="SCOP" dbkey="c.69.1.35"/>
<db_xref db="SCOP" dbkey="c.69.1.40"/>
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<db_xref db="SCOP" dbkey="c.69.1.8"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="18902"/>
<taxon_data name="Cyanobacteria" proteins_count="655"/>
<taxon_data name="Synechocystis PCC 6803" proteins_count="15"/>
<taxon_data name="Archaea" proteins_count="226"/>
<taxon_data name="Eukaryota" proteins_count="4316"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="154"/>
<taxon_data name="Rice spp." proteins_count="259"/>
<taxon_data name="Fungi" proteins_count="1519"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="93"/>
<taxon_data name="Other Eukaryotes" proteins_count="21"/>
<taxon_data name="Other Eukaryotes" proteins_count="25"/>
<taxon_data name="Nematoda" proteins_count="28"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="28"/>
<taxon_data name="Arthropoda" proteins_count="776"/>
<taxon_data name="Fruit Fly" proteins_count="88"/>
<taxon_data name="Chordata" proteins_count="398"/>
<taxon_data name="Human" proteins_count="83"/>
<taxon_data name="Mouse" proteins_count="59"/>
<taxon_data name="Virus" proteins_count="11"/>
<taxon_data name="Unclassified" proteins_count="18"/>
<taxon_data name="Unclassified" proteins_count="2"/>
<taxon_data name="Other Eukaryotes" proteins_count="3"/>
<taxon_data name="Plastid Group" proteins_count="1119"/>
<taxon_data name="Green Plants" proteins_count="1119"/>
<taxon_data name="Metazoa" proteins_count="2853"/>
<taxon_data name="Plastid Group" proteins_count="118"/>
<taxon_data name="Plastid Group" proteins_count="49"/>
<taxon_data name="Other Eukaryotes" proteins_count="48"/>
<taxon_data name="Other Eukaryotes" proteins_count="7"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR000639"/>
<sec_ac acc="IPR019913"/>
</sec_list>
</interpro>
<interpro id="IPR000074" protein_count="272" short_name="ApoA1_A4_E" type="Family">
<name>Apolipoprotein A1/A4/E</name>
<abstract>
<p> Exchangeable apolipoproteins (apoA, apoC and apoE) have the same genomic structure and are members of a multi-gene family that probably evolved from a common ancestral gene. This entry includes the ApoA1, ApoA4 and ApoE proteins. ApoA1 and ApoA4 are part of the APOA1/C3/A4/A5 gene cluster on chromosome 11 [<cite idref="PUB00015448"/>]. Apolipoproteins function in lipid transport as structural components of lipoprotein particles, cofactors for enzymes and ligands for cell-surface receptors. In particular, apoA1 is the major protein component of high-density lipoproteins; apoA4 is thought to act primarily in intestinal lipid absorption; and apoE is a blood plasma protein that mediates the transport and uptake of cholesterol and lipid by way of its high affinity interaction with different cellular receptors, including the low-density lipoprotein (LDL) receptor. Recent findings with apoA1 and apoE suggest that the tertiary structures of these two members of the human exchangeable apolipoprotein gene family are related [<cite idref="PUB00015449"/>]. The three-dimensional structure of the LDL receptor-binding domain of apoE indicates that the protein forms an unusually elongated four-helix bundle that may be stabilised by a tightly packed hydrophobic core that includes leucine zipper-type interactions and by numerous salt bridges on the mostly charged surface. Basic amino acids important for LDL receptor binding are clustered into a surface patch on one long helix [<cite idref="PUB00005140"/>].</p>
</abstract>
<class_list>
<classification id="GO:0005576" class_type="GO">
<category>Cellular Component</category>
<description>extracellular region</description>
</classification>
<classification id="GO:0006869" class_type="GO">
<category>Biological Process</category>
<description>lipid transport</description>
</classification>
<classification id="GO:0008289" class_type="GO">
<category>Molecular Function</category>
<description>lipid binding</description>
</classification>
<classification id="GO:0042157" class_type="GO">
<category>Biological Process</category>
<description>lipoprotein metabolic process</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O18759"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P02647"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P08226"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00005140">
<author_list>Wilson C, Wardell MR, Weisgraber KH, Mahley RW, Agard DA.</author_list>
<title>Three-dimensional structure of the LDL receptor-binding domain of human apolipoprotein E.</title>
<db_xref db="PUBMED" dbkey="2063194"/>
<journal>Science</journal>
<location issue="5014" pages="1817-22" volume="252"/>
<year>1991</year>
</publication>
<publication id="PUB00015448">
<author_list>Fullerton SM, Buchanan AV, Sonpar VA, Taylor SL, Smith JD, Carlson CS, Salomaa V, Stengard JH, Boerwinkle E, Clark AG, Nickerson DA, Weiss KM.</author_list>
<title>The effects of scale: variation in the APOA1/C3/A4/A5 gene cluster.</title>
<db_xref db="PUBMED" dbkey="15108119"/>
<journal>Hum. Genet.</journal>
<location issue="1" pages="36-56" volume="115"/>
<year>2004</year>
</publication>
<publication id="PUB00015449">
<author_list>Saito H, Lund-Katz S, Phillips MC.</author_list>
<title>Contributions of domain structure and lipid interaction to the functionality of exchangeable human apolipoproteins.</title>
<db_xref db="PUBMED" dbkey="15234552"/>
<journal>Prog. Lipid Res.</journal>
<location issue="4" pages="350-80" volume="43"/>
<year>2004</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR013326"/>
</contains>
<member_list>
<db_xref protein_count="272" db="PFAM" dbkey="PF01442" name="Apolipoprotein"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF01442"/>
<db_xref db="BLOCKS" dbkey="IPB000074"/>
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<structure_db_links>
<db_xref db="PDB" dbkey="1av1"/>
<db_xref db="PDB" dbkey="1b68"/>
<db_xref db="PDB" dbkey="1bz4"/>
<db_xref db="PDB" dbkey="1ea8"/>
<db_xref db="PDB" dbkey="1gs9"/>
<db_xref db="PDB" dbkey="1gw3"/>
<db_xref db="PDB" dbkey="1gw4"/>
<db_xref db="PDB" dbkey="1h7i"/>
<db_xref db="PDB" dbkey="1le2"/>
<db_xref db="PDB" dbkey="1le4"/>
<db_xref db="PDB" dbkey="1lpe"/>
<db_xref db="PDB" dbkey="1nfn"/>
<db_xref db="PDB" dbkey="1nfo"/>
<db_xref db="PDB" dbkey="1odp"/>
<db_xref db="PDB" dbkey="1odq"/>
<db_xref db="PDB" dbkey="1odr"/>
<db_xref db="PDB" dbkey="1oef"/>
<db_xref db="PDB" dbkey="1oeg"/>
<db_xref db="PDB" dbkey="1or2"/>
<db_xref db="PDB" dbkey="1or3"/>
<db_xref db="CATH" dbkey="1.20.120.20"/>
<db_xref db="CATH" dbkey="1.20.5.20"/>
<db_xref db="SCOP" dbkey="a.24.1.1"/>
<db_xref db="SCOP" dbkey="h.5.1.1"/>
<db_xref db="SCOP" dbkey="j.39.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="79"/>
<taxon_data name="Archaea" proteins_count="1"/>
<taxon_data name="Eukaryota" proteins_count="192"/>
<taxon_data name="Chordata" proteins_count="188"/>
<taxon_data name="Human" proteins_count="9"/>
<taxon_data name="Mouse" proteins_count="19"/>
<taxon_data name="Metazoa" proteins_count="188"/>
<taxon_data name="Plastid Group" proteins_count="4"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000076" protein_count="95" short_name="KCL_cotranspt" type="Family">
<name>K-Cl co-transporter</name>
<abstract>
<p>The K-Cl co-transporter (KCC) mediates the coupled movement of K<sup>+</sup> and Cl<sup>-</sup>
ions across the plasma membrane of many animal cells. This transport is
involved in the regulatory volume decrease in response to cell swelling in
red blood cells, and has been proposed to play a role in the vectorial
movement of Cl<sup>-</sup> across kidney epithelia. The transport process involves one
for one electroneutral movement of K<sup>+</sup> together with Cl<sup>-</sup>, and, in all
known mammalian cells, the net movement is outward [<cite idref="PUB00002955"/>].</p>
<p>In neurones, it appears to play a unique role in maintaining low
intracellular Cl<sup>-</sup>concentration, which is required for the functioning of Cl<sup>-</sup>
dependent fast synaptic inhibition, mediated by certain neurotransmitters,
such as gamma-aminobutyric acid (GABA) and glycine.</p>
<p>Two isoforms of the K-Cl co-transporter have been described, termed KCC1 and
KCC2, containing 1085 and 1116 amino acids, respectively. They are both
predicted to have 12 transmembrane (TM) regions in a central hydrophobic
domain, together with hydrophilic N- and C-termini that are likely
cytoplasmic. Comparison of their sequences with those of other
ion-transporting membrane proteins reveals that they are part of a new
superfamily of cation-chloride co-transporters, which includes the Na-Cl and
Na-K-2Cl co-transporters. KCC1 is widely expressed in human tissues, while
KCC2 is expressed only in brain neurones, making it likely that this is the
isoform responsible for maintaining low Cl<sup>-</sup> concentration in neurones [<cite idref="PUB00002956"/>, <cite idref="PUB00004291"/>].</p>
</abstract>
<class_list>
<classification id="GO:0005215" class_type="GO">
<category>Molecular Function</category>
<description>transporter activity</description>
</classification>
<classification id="GO:0006811" class_type="GO">
<category>Biological Process</category>
<description>ion transport</description>
</classification>
<classification id="GO:0016020" class_type="GO">
<category>Cellular Component</category>
<description>membrane</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="Q28677"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q91V14"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q9H2X9"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00002955">
<author_list>Gillen CM, Brill S, Payne JA, Forbush B 3rd.</author_list>
<title>Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human. A new member of the cation-chloride cotransporter family.</title>
<db_xref db="PUBMED" dbkey="8663127"/>
<journal>J. Biol. Chem.</journal>
<location issue="27" pages="16237-44" volume="271"/>
<year>1996</year>
</publication>
<publication id="PUB00002956">
<author_list>Payne JA, Stevenson TJ, Donaldson LF.</author_list>
<title>Molecular characterization of a putative K-Cl cotransporter in rat brain. A neuronal-specific isoform.</title>
<db_xref db="PUBMED" dbkey="8663311"/>
<journal>J. Biol. Chem.</journal>
<location issue="27" pages="16245-52" volume="271"/>
<year>1996</year>
</publication>
<publication id="PUB00004291">
<author_list>Rivera C, Voipio J, Payne JA, Ruusuvuori E, Lahtinen H, Lamsa K, Pirvola U, Saarma M, Kaila K.</author_list>
<title>The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation.</title>
<db_xref db="PUBMED" dbkey="9930699"/>
<journal>Nature</journal>
<location issue="6716" pages="251-5" volume="397"/>
<year>1999</year>
</publication>
</pub_list>
<parent_list>
<rel_ref ipr_ref="IPR004842"/>
</parent_list>
<child_list>
<rel_ref ipr_ref="IPR000622"/>
</child_list>
<contains>
<rel_ref ipr_ref="IPR004841"/>
<rel_ref ipr_ref="IPR018491"/>
</contains>
<member_list>
<db_xref protein_count="95" db="PRINTS" dbkey="PR01081" name="KCLTRNSPORT"/>
</member_list>
<external_doc_list>
<db_xref db="BLOCKS" dbkey="IPB000076"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Eukaryota" proteins_count="95"/>
<taxon_data name="Arthropoda" proteins_count="19"/>
<taxon_data name="Fruit Fly" proteins_count="4"/>
<taxon_data name="Chordata" proteins_count="76"/>
<taxon_data name="Human" proteins_count="23"/>
<taxon_data name="Mouse" proteins_count="23"/>
<taxon_data name="Metazoa" proteins_count="95"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR000622"/>
</sec_list>
</interpro>
<interpro id="IPR000077" protein_count="319" short_name="Ribosomal_L39" type="Family">
<name>Ribosomal protein L39e</name>
<abstract>
<p>Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [<cite idref="PUB00007068"/>, <cite idref="PUB00007069"/>]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. </p>
<p>Many of ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [<cite idref="PUB00007069"/>, <cite idref="PUB00007070"/>].</p>
<p>A number of eukaryotic and archaebacterial large subunit ribosomal proteins can be grouped on the basis of sequence similarities.
These proteins are very basic. About 50 residues long, they are the smallest
proteins of eukaryotic-type ribosomes.</p>
</abstract>
<class_list>
<classification id="GO:0003735" class_type="GO">
<category>Molecular Function</category>
<description>structural constituent of ribosome</description>
</classification>
<classification id="GO:0005622" class_type="GO">
<category>Cellular Component</category>
<description>intracellular</description>
</classification>
<classification id="GO:0005840" class_type="GO">
<category>Cellular Component</category>
<description>ribosome</description>
</classification>
<classification id="GO:0006412" class_type="GO">
<category>Biological Process</category>
<description>translation</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O16130"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P04650"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P52814"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P62891"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P62892"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00007068">
<author_list>Ramakrishnan V, Moore PB.</author_list>
<title>Atomic structures at last: the ribosome in 2000.</title>
<db_xref db="PUBMED" dbkey="11297922"/>
<journal>Curr. Opin. Struct. Biol.</journal>
<location issue="2" pages="144-54" volume="11"/>
<year>2001</year>
</publication>
<publication id="PUB00007069">
<author_list>Maguire BA, Zimmermann RA.</author_list>
<title>The ribosome in focus.</title>
<db_xref db="PUBMED" dbkey="11290319"/>
<journal>Cell</journal>
<location issue="6" pages="813-6" volume="104"/>
<year>2001</year>
</publication>
<publication id="PUB00007070">
<author_list>Chandra Sanyal S, Liljas A.</author_list>
<title>The end of the beginning: structural studies of ribosomal proteins.</title>
<db_xref db="PUBMED" dbkey="11114498"/>
<journal>Curr. Opin. Struct. Biol.</journal>
<location issue="6" pages="633-6" volume="10"/>
<year>2000</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR020083"/>
</contains>
<member_list>
<db_xref protein_count="311" db="PANTHER" dbkey="PTHR19970" name="Ribosomal_L39"/>
<db_xref protein_count="319" db="PFAM" dbkey="PF00832" name="Ribosomal_L39"/>
<db_xref protein_count="296" db="GENE3D" dbkey="G3DSA:1.10.1620.10" name="Ribosomal_L39"/>
<db_xref protein_count="316" db="SSF" dbkey="SSF48662" name="Ribosomal_L39"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00832"/>
<db_xref db="MSDsite" dbkey="PS00051"/>
<db_xref db="BLOCKS" dbkey="IPB000077"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00050"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1ffk"/>
<db_xref db="PDB" dbkey="1jj2"/>
<db_xref db="PDB" dbkey="1k73"/>
<db_xref db="PDB" dbkey="1k8a"/>
<db_xref db="PDB" dbkey="1k9m"/>
<db_xref db="PDB" dbkey="1kc8"/>
<db_xref db="PDB" dbkey="1kd1"/>
<db_xref db="PDB" dbkey="1kqs"/>
<db_xref db="PDB" dbkey="1m1k"/>
<db_xref db="PDB" dbkey="1m90"/>
<db_xref db="PDB" dbkey="1n8r"/>
<db_xref db="PDB" dbkey="1nji"/>
<db_xref db="PDB" dbkey="1q7y"/>
<db_xref db="PDB" dbkey="1q81"/>
<db_xref db="PDB" dbkey="1q82"/>
<db_xref db="PDB" dbkey="1q86"/>
<db_xref db="PDB" dbkey="1qvf"/>
<db_xref db="PDB" dbkey="1qvg"/>
<db_xref db="PDB" dbkey="1s72"/>
<db_xref db="PDB" dbkey="1vq4"/>
<db_xref db="PDB" dbkey="1vq5"/>
<db_xref db="PDB" dbkey="1vq6"/>
<db_xref db="PDB" dbkey="1vq7"/>
<db_xref db="PDB" dbkey="1vq8"/>
<db_xref db="PDB" dbkey="1vq9"/>
<db_xref db="PDB" dbkey="1vqk"/>
<db_xref db="PDB" dbkey="1vql"/>
<db_xref db="PDB" dbkey="1vqm"/>
<db_xref db="PDB" dbkey="1vqn"/>
<db_xref db="PDB" dbkey="1vqo"/>
<db_xref db="PDB" dbkey="1vqp"/>
<db_xref db="PDB" dbkey="1w2b"/>
<db_xref db="PDB" dbkey="1yhq"/>
<db_xref db="PDB" dbkey="1yi2"/>
<db_xref db="PDB" dbkey="1yij"/>
<db_xref db="PDB" dbkey="1yit"/>
<db_xref db="PDB" dbkey="1yj9"/>
<db_xref db="PDB" dbkey="1yjn"/>
<db_xref db="PDB" dbkey="1yjw"/>
<db_xref db="PDB" dbkey="2otj"/>
<db_xref db="PDB" dbkey="2otl"/>
<db_xref db="PDB" dbkey="2qa4"/>
<db_xref db="PDB" dbkey="2qex"/>
<db_xref db="PDB" dbkey="3cc2"/>
<db_xref db="PDB" dbkey="3cc4"/>
<db_xref db="PDB" dbkey="3cc7"/>
<db_xref db="PDB" dbkey="3cce"/>
<db_xref db="PDB" dbkey="3ccj"/>
<db_xref db="PDB" dbkey="3ccl"/>
<db_xref db="PDB" dbkey="3ccm"/>
<db_xref db="PDB" dbkey="3ccq"/>
<db_xref db="PDB" dbkey="3ccr"/>
<db_xref db="PDB" dbkey="3ccs"/>
<db_xref db="PDB" dbkey="3ccu"/>
<db_xref db="PDB" dbkey="3ccv"/>
<db_xref db="PDB" dbkey="3cd6"/>
<db_xref db="PDB" dbkey="3cma"/>
<db_xref db="PDB" dbkey="3cme"/>
<db_xref db="PDB" dbkey="3cpw"/>
<db_xref db="CATH" dbkey="1.10.1620.10"/>
<db_xref db="SCOP" dbkey="a.137.1.1"/>
<db_xref db="SCOP" dbkey="i.1.1.2"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Archaea" proteins_count="86"/>
<taxon_data name="Eukaryota" proteins_count="233"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="4"/>
<taxon_data name="Rice spp." proteins_count="7"/>
<taxon_data name="Fungi" proteins_count="52"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="5"/>
<taxon_data name="Other Eukaryotes" proteins_count="1"/>
<taxon_data name="Nematoda" proteins_count="1"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="1"/>
<taxon_data name="Arthropoda" proteins_count="39"/>
<taxon_data name="Fruit Fly" proteins_count="1"/>
<taxon_data name="Chordata" proteins_count="43"/>
<taxon_data name="Human" proteins_count="3"/>
<taxon_data name="Mouse" proteins_count="3"/>
<taxon_data name="Other Eukaryotes" proteins_count="3"/>
<taxon_data name="Plastid Group" proteins_count="29"/>
<taxon_data name="Green Plants" proteins_count="29"/>
<taxon_data name="Metazoa" proteins_count="170"/>
<taxon_data name="Plastid Group" proteins_count="17"/>
<taxon_data name="Plastid Group" proteins_count="8"/>
<taxon_data name="Other Eukaryotes" proteins_count="1"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000079" protein_count="174" short_name="HMG14/HMG17" type="Family">
<name>High mobility group protein HMG14/HMG17</name>
<abstract>
<p>High mobility group (HMG) proteins constitute a family of relatively low molecular weight non-histone components in chromatin. HMG14 and HMG17 are highly-similar proteins of about 100 amino acid residues; the sequence of chicken HMG14 is almost as similar to chicken HMG17 as it is to mammalian HMG14 polypeptides [<cite idref="PUB00001764"/>]. The proteins bind to the inner side of the nucleosomal DNA, altering the interaction between the DNA and the histone octamer. It is thought that they may be involved in the process that confers specific chromatin conformations to transcribable regions in the genome [<cite idref="PUB00002433"/>].</p>
<p>The SMART signature describes a nucleosomal binding domain, which facilitates binding of proteins to nucleosomes in chromatin. The domain is most commonly found in the high mobility group (HMG) proteins, HMG14 and HMG17, however, it is also found in other proteins which bind to nucleosomes, e.g. NBP-45. NBP-45 is a nucleosomal binding protein, first identified in mice [<cite idref="PUB00009423"/>], which is related to HMG14 and HMG17. NBP-45 binds specifically to nucleosome core particles, and can function as a transcriptional activator. These findings led to the suggestion that this domain, common to NBP-45, HMG14 and HMG17 is responsible for binding of the proteins to nucleosomes in chromatin.</p>
</abstract>
<class_list>
<classification id="GO:0000785" class_type="GO">
<category>Cellular Component</category>
<description>chromatin</description>
</classification>
<classification id="GO:0003677" class_type="GO">
<category>Molecular Function</category>
<description>DNA binding</description>
</classification>
<classification id="GO:0005634" class_type="GO">
<category>Cellular Component</category>
<description>nucleus</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="A6NN55"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="B4F777"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P09602"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00001764">
<author_list>Dodgson JB, Browne DL, Black AJ.</author_list>
<title>Chicken chromosomal protein HMG-14 and HMG-17 cDNA clones: isolation, characterization and sequence comparison.</title>
<db_xref db="PUBMED" dbkey="3384337"/>
<journal>Gene</journal>
<location issue="2" pages="287-95" volume="63"/>
<year>1988</year>
</publication>
<publication id="PUB00002433">
<author_list>Landsman D, Soares N, Gonzalez FJ, Bustin M.</author_list>
<title>Chromosomal protein HMG-17. Complete human cDNA sequence and evidence for a multigene family.</title>
<db_xref db="PUBMED" dbkey="3754870"/>
<journal>J. Biol. Chem.</journal>
<location issue="16" pages="7479-84" volume="261"/>
<year>1986</year>
</publication>
<publication id="PUB00009423">
<author_list>Shirakawa H, Landsman D, Postnikov YV, Bustin M.</author_list>
<title>NBP-45, a novel nucleosomal binding protein with a tissue-specific and developmentally regulated expression.</title>
<db_xref db="PUBMED" dbkey="10692437"/>
<journal>J. Biol. Chem.</journal>
<location issue="9" pages="6368-74" volume="275"/>
<year>2000</year>
</publication>
</pub_list>
<member_list>
<db_xref protein_count="158" db="PANTHER" dbkey="PTHR23087" name="HMG_14_17"/>
<db_xref protein_count="172" db="PFAM" dbkey="PF01101" name="HMG14_17"/>
<db_xref protein_count="166" db="PRINTS" dbkey="PR00925" name="NONHISHMG17"/>
<db_xref protein_count="138" db="PROSITE" dbkey="PS00355" name="HMG14_17"/>
<db_xref protein_count="166" db="SMART" dbkey="SM00527" name="HMG17"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF01101"/>
<db_xref db="MSDsite" dbkey="PS00355"/>
<db_xref db="BLOCKS" dbkey="IPB000079"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00307"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="1"/>
<taxon_data name="Eukaryota" proteins_count="173"/>
<taxon_data name="Fungi" proteins_count="1"/>
<taxon_data name="Arthropoda" proteins_count="1"/>
<taxon_data name="Chordata" proteins_count="169"/>
<taxon_data name="Human" proteins_count="18"/>
<taxon_data name="Mouse" proteins_count="14"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
<taxon_data name="Green Plants" proteins_count="1"/>
<taxon_data name="Metazoa" proteins_count="172"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000081" protein_count="2038" short_name="Peptidase_C3" type="Domain">
<name>Peptidase C3, picornavirus core protein 2A</name>
<abstract>
<p>In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:</p>
<ul>
<li>Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.</li>
<li>Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule.</li>
</ul>
<p>In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding. </p>
<p>Cysteine peptidases have characteristic molecular topologies, which can be seen not only in their three-dimensional structures, but commonly also in the two-dimensional structures. These are peptidases in which the nucleophile is the sulphydryl group of a cysteine residue. Cysteine proteases are divided into clans (proteins which are evolutionary related), and further sub-divided into families, on the basis of the architecture of their catalytic dyad or triad [<cite idref="PUB00011704"/>]. </p>
<p>This domain defines cysteine peptidases belong to MEROPS peptidase family C3 (picornain, clan PA(C)), subfamilies 3CA and 3CB. The protein fold of this peptidase domain for members of this family resembles that of the serine peptidase, chymotrypsin [<cite idref="PUB00004181"/>], the type example for clan PA.</p>
<p>Picornaviral proteins are expressed as a single polyprotein
which is cleaved by the viral 3C cysteine protease [<cite idref="PUB00003174"/>]. The poliovirus polyprotein is selectively cleaved between the Gln-|-Gly bond. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.
</p>
</abstract>
<class_list>
<classification id="GO:0006508" class_type="GO">
<category>Biological Process</category>
<description>proteolysis</description>
</classification>
<classification id="GO:0008233" class_type="GO">
<category>Molecular Function</category>
<description>peptidase activity</description>
</classification>
<classification id="GO:0016032" class_type="GO">
<category>Biological Process</category>
<description>viral reproduction</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O91734"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00003174">
<author_list>Zoll J, van Kuppeveld FJ, Galama JM, Melchers WJ.</author_list>
<title>Genetic analysis of mengovirus protein 2A: its function in polyprotein processing and virus reproduction.</title>
<db_xref db="PUBMED" dbkey="9460917"/>
<journal>J. Gen. Virol.</journal>
<location pages="17-25" volume="79 ( Pt 1)"/>
<year>1998</year>
</publication>
<publication id="PUB00004181">
<author_list>Allaire M, Chernaia MM, Malcolm BA, James MN.</author_list>
<title>Picornaviral 3C cysteine proteinases have a fold similar to chymotrypsin-like serine proteinases.</title>
<db_xref db="PUBMED" dbkey="8164744"/>
<journal>Nature</journal>
<location issue="6475" pages="72-6" volume="369"/>
<year>1994</year>
</publication>
<publication id="PUB00011704">
<author_list>Barrett AJ, Rawlings ND.</author_list>
<title>Evolutionary lines of cysteine peptidases.</title>
<db_xref db="PUBMED" dbkey="11517925"/>
<journal>Biol. Chem.</journal>
<location issue="5" pages="727-33" volume="382"/>
<year>2001</year>
</publication>
</pub_list>
<member_list>
<db_xref protein_count="1286" db="PFAM" dbkey="PF00947" name="Pico_P2A"/>
<db_xref protein_count="2030" db="PRODOM" dbkey="PD001306" name="Peptidase_C3"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00947"/>
<db_xref db="EC" dbkey="2.7.7.48"/>
<db_xref db="EC" dbkey="3.4.22.28"/>
<db_xref db="EC" dbkey="3.4.22.29"/>
<db_xref db="EC" dbkey="3.6.1.15"/>
<db_xref db="MEROPS" dbkey="C3"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1al2"/>
<db_xref db="PDB" dbkey="1ar6"/>
<db_xref db="PDB" dbkey="1ar7"/>
<db_xref db="PDB" dbkey="1ar8"/>
<db_xref db="PDB" dbkey="1ar9"/>
<db_xref db="PDB" dbkey="1asj"/>
<db_xref db="PDB" dbkey="1bev"/>
<db_xref db="PDB" dbkey="1cqq"/>
<db_xref db="PDB" dbkey="1d4m"/>
<db_xref db="PDB" dbkey="1eah"/>
<db_xref db="PDB" dbkey="1ev1"/>
<db_xref db="PDB" dbkey="1hri"/>
<db_xref db="PDB" dbkey="1hrv"/>
<db_xref db="PDB" dbkey="1hxs"/>
<db_xref db="PDB" dbkey="1k5m"/>
<db_xref db="PDB" dbkey="1na1"/>
<db_xref db="PDB" dbkey="1ncq"/>
<db_xref db="PDB" dbkey="1oop"/>
<db_xref db="PDB" dbkey="1piv"/>
<db_xref db="PDB" dbkey="1po1"/>
<db_xref db="PDB" dbkey="1po2"/>
<db_xref db="PDB" dbkey="1pov"/>
<db_xref db="PDB" dbkey="1pvc"/>
<db_xref db="PDB" dbkey="1r08"/>
<db_xref db="PDB" dbkey="1r09"/>
<db_xref db="PDB" dbkey="1rmu"/>
<db_xref db="PDB" dbkey="1ruc"/>
<db_xref db="PDB" dbkey="1rud"/>
<db_xref db="PDB" dbkey="1rue"/>
<db_xref db="PDB" dbkey="1ruf"/>
<db_xref db="PDB" dbkey="1rug"/>
<db_xref db="PDB" dbkey="1ruh"/>
<db_xref db="PDB" dbkey="1rui"/>
<db_xref db="PDB" dbkey="1ruj"/>
<db_xref db="PDB" dbkey="1rvf"/>
<db_xref db="PDB" dbkey="1vba"/>
<db_xref db="PDB" dbkey="1vbb"/>
<db_xref db="PDB" dbkey="1vbc"/>
<db_xref db="PDB" dbkey="1vbd"/>
<db_xref db="PDB" dbkey="1vbe"/>
<db_xref db="PDB" dbkey="1vrh"/>
<db_xref db="PDB" dbkey="2hrv"/>
<db_xref db="PDB" dbkey="2hwb"/>
<db_xref db="PDB" dbkey="2hwc"/>
<db_xref db="PDB" dbkey="2plv"/>
<db_xref db="PDB" dbkey="2r04"/>
<db_xref db="PDB" dbkey="2r06"/>
<db_xref db="PDB" dbkey="2r07"/>
<db_xref db="PDB" dbkey="2rm2"/>
<db_xref db="PDB" dbkey="2rmu"/>
<db_xref db="PDB" dbkey="2rr1"/>
<db_xref db="PDB" dbkey="2rs1"/>
<db_xref db="PDB" dbkey="2rs3"/>
<db_xref db="PDB" dbkey="2rs5"/>
<db_xref db="PDB" dbkey="4rhv"/>
<db_xref db="CATH" dbkey="2.40.10.10"/>
<db_xref db="CATH" dbkey="2.60.120.20"/>
<db_xref db="SCOP" dbkey="b.121.4.1"/>
<db_xref db="SCOP" dbkey="b.47.1.4"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Virus" proteins_count="2038"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000082" protein_count="409" short_name="SEA" type="Domain">
<name>SEA</name>
<abstract>
SEA is an extracellular domain associated with
O-glycosylation [<cite idref="PUB00005026"/>].
Proteins found to contain SEA-modules include, agrin, enterokinase, 63 kDa <taxon tax_id="7668">Strongylocentrotus purpuratus</taxon> (Purple sea urchin)
sperm protein, perlecan (heparan sulphate proteoglycan core, mucin 1 and the cell surface antigen, 114/A10, and two functionally uncharacterised,
probably extracellular, <taxon tax_id="6239">Caenorhabditis elegans</taxon> proteins. Despite the functional
diversity of these adhesive proteins, a common denominator seems to be their
existence in heavily glycosylated environments. In addition, the better characterised
proteins all contain O-glycosidic-linked carbohydrates such as
heparan sulphate that contribute considerably to their molecular masses. The common
module might regulate or assist binding to neighbouring carbohydrate moieties.
<p>Enterokinase, the initiator of intestinal digestion, is a
mosaic protease composed of a distinctive assortment of
domains [<cite idref="PUB00004849"/>]. </p>
</abstract>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P15941"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P31696"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P34576"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q05793"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q07929"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00004849">
<author_list>Kitamoto Y, Yuan X, Wu Q, McCourt DW, Sadler JE.</author_list>
<title>Enterokinase, the initiator of intestinal digestion, is a mosaic protease composed of a distinctive assortment of domains.</title>
<db_xref db="PUBMED" dbkey="8052624"/>
<journal>Proc. Natl. Acad. Sci. U.S.A.</journal>
<location issue="16" pages="7588-92" volume="91"/>
<year>1994</year>
</publication>
<publication id="PUB00005026">
<author_list>Bork P, Patthy L.</author_list>
<title>The SEA module: a new extracellular domain associated with O-glycosylation.</title>
<db_xref db="PUBMED" dbkey="7670383"/>
<journal>Protein Sci.</journal>
<location issue="7" pages="1421-5" volume="4"/>
<year>1995</year>
</publication>
</pub_list>
<found_in>
<rel_ref ipr_ref="IPR011163"/>
<rel_ref ipr_ref="IPR017051"/>
<rel_ref ipr_ref="IPR017118"/>
<rel_ref ipr_ref="IPR017329"/>
<rel_ref ipr_ref="IPR017343"/>
</found_in>
<member_list>
<db_xref protein_count="358" db="PFAM" dbkey="PF01390" name="SEA"/>
<db_xref protein_count="262" db="PROFILE" dbkey="PS50024" name="SEA"/>
<db_xref protein_count="185" db="SMART" dbkey="SM00200" name="SEA"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF01390"/>
<db_xref db="BLOCKS" dbkey="IPB000082"/>
<db_xref db="PROSITEDOC" dbkey="PDOC50024"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1ivz"/>
<db_xref db="CATH" dbkey="3.30.70.960"/>
<db_xref db="SCOP" dbkey="d.58.41.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="13"/>
<taxon_data name="Archaea" proteins_count="1"/>
<taxon_data name="Eukaryota" proteins_count="395"/>
<taxon_data name="Fungi" proteins_count="2"/>
<taxon_data name="Nematoda" proteins_count="7"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="7"/>
<taxon_data name="Arthropoda" proteins_count="58"/>
<taxon_data name="Fruit Fly" proteins_count="8"/>
<taxon_data name="Chordata" proteins_count="289"/>
<taxon_data name="Human" proteins_count="96"/>
<taxon_data name="Mouse" proteins_count="38"/>
<taxon_data name="Metazoa" proteins_count="392"/>
<taxon_data name="Other Eukaryotes" proteins_count="3"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000083" protein_count="125" short_name="Fibrnctn1" type="Domain">
<name>Fibronectin, type I</name>
<abstract>
<p>Fibronectin type I repeats are one of the three repeats found in the fibronectin protein.
Fibronectin is a plasma protein that binds cell surfaces and various compounds
including collagen, fibrin, heparin, DNA, and actin. Type I domain (FN1) is approximately
40 residues in length. Four conserved cysteines are involved in disulphide bonds. The 3D
structure of the FN1 domain has been determined [<cite idref="PUB00004065"/>, <cite idref="PUB00003289"/>, <cite idref="PUB00005265"/>]. It consists of two antiparallel
beta-sheets, first a double-stranded one, that is linked by a disulphide bond to a
triple-stranded beta-sheet. The second conserved disulphide bridge links the C-terminal
adjacent strands of the domain.</p>
<p> In human tissue plasminogen activator chain A the FN1 domain together with the
following epidermal growth factor (EGF)-like domain are involved in
fibrin-binding [<cite idref="PUB00002685"/>]. It has been suggested that these two modules form a single structural
and functional unit [<cite idref="PUB00005265"/>]. The two domains keep their specific tertiary structure, but interact
intimately to bury a hydrophobic core; the inter-module linker makes up the third strand of
the EGF-module's major beta-sheet.</p>
</abstract>
<class_list>
<classification id="GO:0005576" class_type="GO">
<category>Cellular Component</category>
<description>extracellular region</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="P00750"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P11276"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P98119"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00002685">
<author_list>Bennett WF, Paoni NF, Keyt BA, Botstein D, Jones AJ, Presta L, Wurm FM, Zoller MJ.</author_list>
<title>High resolution analysis of functional determinants on human tissue-type plasminogen activator.</title>
<db_xref db="PUBMED" dbkey="1900516"/>
<journal>J. Biol. Chem.</journal>
<location issue="8" pages="5191-201" volume="266"/>
<year>1991</year>
</publication>
<publication id="PUB00003289">
<author_list>Downing AK, Driscoll PC, Harvey TS, Dudgeon TJ, Smith BO, Baron M, Campbell ID.</author_list>
<title>Solution structure of the fibrin binding finger domain of tissue-type plasminogen activator determined by 1H nuclear magnetic resonance.</title>
<db_xref db="PUBMED" dbkey="1602484"/>
<journal>J. Mol. Biol.</journal>
<location issue="3" pages="821-33" volume="225"/>
<year>1992</year>
</publication>
<publication id="PUB00004065">
<author_list>Baron M, Norman D, Willis A, Campbell ID.</author_list>
<title>Structure of the fibronectin type 1 module.</title>
<db_xref db="PUBMED" dbkey="2112232"/>
<journal>Nature</journal>
<location issue="6276" pages="642-6" volume="345"/>
<year>1990</year>
</publication>
<publication id="PUB00005265">
<author_list>Smith BO, Downing AK, Driscoll PC, Dudgeon TJ, Campbell ID.</author_list>
<title>The solution structure and backbone dynamics of the fibronectin type I and epidermal growth factor-like pair of modules of tissue-type plasminogen activator.</title>
<db_xref db="PUBMED" dbkey="7582899"/>
<journal>Structure</journal>
<location issue="8" pages="823-33" volume="3"/>
<year>1995</year>
</publication>
</pub_list>
<found_in>
<rel_ref ipr_ref="IPR001314"/>
<rel_ref ipr_ref="IPR014394"/>
</found_in>
<member_list>
<db_xref protein_count="119" db="PFAM" dbkey="PF00039" name="fn1"/>
<db_xref protein_count="117" db="PROSITE" dbkey="PS01253" name="FN1_1"/>
<db_xref protein_count="122" db="PROFILE" dbkey="PS51091" name="FN1_2"/>
<db_xref protein_count="110" db="SMART" dbkey="SM00058" name="FN1"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00039"/>
<db_xref db="MSDsite" dbkey="PS01253"/>
<db_xref db="BLOCKS" dbkey="IPB000083"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00965"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1e88"/>
<db_xref db="PDB" dbkey="1e8b"/>
<db_xref db="PDB" dbkey="1fbr"/>
<db_xref db="PDB" dbkey="1o9a"/>
<db_xref db="PDB" dbkey="1qgb"/>
<db_xref db="PDB" dbkey="1qo6"/>
<db_xref db="PDB" dbkey="1tpg"/>
<db_xref db="PDB" dbkey="1tpm"/>
<db_xref db="PDB" dbkey="1tpn"/>
<db_xref db="PDB" dbkey="2cg6"/>
<db_xref db="PDB" dbkey="2cg7"/>
<db_xref db="PDB" dbkey="2cku"/>
<db_xref db="PDB" dbkey="2fn2"/>
<db_xref db="PDB" dbkey="2rky"/>
<db_xref db="PDB" dbkey="2rkz"/>
<db_xref db="PDB" dbkey="2rl0"/>
<db_xref db="PDB" dbkey="3cal"/>
<db_xref db="CATH" dbkey="2.10.10.10"/>
<db_xref db="CATH" dbkey="2.10.25.10"/>
<db_xref db="CATH" dbkey="2.10.70.10"/>
<db_xref db="SCOP" dbkey="g.14.1.2"/>
<db_xref db="SCOP" dbkey="g.27.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Eukaryota" proteins_count="125"/>
<taxon_data name="Chordata" proteins_count="125"/>
<taxon_data name="Human" proteins_count="28"/>
<taxon_data name="Mouse" proteins_count="22"/>
<taxon_data name="Metazoa" proteins_count="125"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000084" protein_count="1081" short_name="PE_region_N" type="Domain">
<name>PE N-terminal</name>
<abstract>
This family is named after a PE motif near to the amino
terminus. The carboxyl terminus of this family
are variable and fall into several classes. The
largest class of PE proteins is the highly repetitive
PGRS class which have a high glycine content.
The function of these proteins is uncertain but it
has been suggested that they may be related to
antigenic variation of <taxon tax_id="1773">Mycobacterium tuberculosis</taxon> [<cite idref="PUB00004280"/>].
</abstract>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O53416"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00004280">
<author_list>Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG.</author_list>
<title>Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.</title>
<db_xref db="PUBMED" dbkey="9634230"/>
<journal>Nature</journal>
<location issue="6685" pages="537-44" volume="393"/>
<year>1998</year>
</publication>
</pub_list>
<member_list>
<db_xref protein_count="1082" db="PFAM" dbkey="PF00934" name="PE"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00934"/>
<db_xref db="BLOCKS" dbkey="IPB000084"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="2g38"/>
<db_xref db="SCOP" dbkey="a.25.4.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="1082"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000085" protein_count="1825" short_name="RuvA" type="Family">
<name>Bacterial DNA recombination protein RuvA</name>
<abstract>
<p>In prokaryotes, RuvA, RuvB, and RuvC process the universal DNA intermediate of homologous recombination, termed Holliday junction. The tetrameric DNA helicase RuvA specifically binds to the Holliday junction and facilitates the isomerization of the junction from the stacked folded configuration to the square-planar structure [<cite idref="PUB00013198"/>]. In the RuvA tetramer, each subunit consists of three domains, I, II and III, where I and II form the major core that is responsible for Holliday junction binding and base pair rearrangements of Holliday junction executed at the crossover point, whereas domain III regulates branch migration through direct contact with RuvB.</p>
</abstract>
<class_list>
<classification id="GO:0003678" class_type="GO">
<category>Molecular Function</category>
<description>DNA helicase activity</description>
</classification>
<classification id="GO:0006281" class_type="GO">
<category>Biological Process</category>
<description>DNA repair</description>
</classification>
<classification id="GO:0006310" class_type="GO">
<category>Biological Process</category>
<description>DNA recombination</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="A2BQZ1"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P0A809"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P73554"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00013198">
<author_list>Yamada K, Miyata T, Tsuchiya D, Oyama T, Fujiwara Y, Ohnishi T, Iwasaki H, Shinagawa H, Ariyoshi M, Mayanagi K, Morikawa K.</author_list>
<title>Crystal structure of the RuvA-RuvB complex: a structural basis for the Holliday junction migrating motor machinery.</title>
<db_xref db="PUBMED" dbkey="12408833"/>
<journal>Mol. Cell</journal>
<location issue="3" pages="671-81" volume="10"/>
<year>2002</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR003583"/>
<rel_ref ipr_ref="IPR010994"/>
<rel_ref ipr_ref="IPR011114"/>
<rel_ref ipr_ref="IPR013849"/>
</contains>
<member_list>
<db_xref protein_count="1766" db="TIGRFAMs" dbkey="TIGR00084" name="ruvA"/>
<db_xref protein_count="1822" db="HAMAP" dbkey="MF_00031" name="DNA_helic_RuvA"/>
</member_list>
<external_doc_list>
<db_xref db="BLOCKS" dbkey="IPB000085"/>
<db_xref db="EC" dbkey="3.6.1"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1bdx"/>
<db_xref db="PDB" dbkey="1bvs"/>
<db_xref db="PDB" dbkey="1c7y"/>
<db_xref db="PDB" dbkey="1cuk"/>
<db_xref db="PDB" dbkey="1d8l"/>
<db_xref db="PDB" dbkey="1hjp"/>
<db_xref db="PDB" dbkey="1ixr"/>
<db_xref db="PDB" dbkey="1ixs"/>
<db_xref db="PDB" dbkey="2h5x"/>
<db_xref db="CATH" dbkey="1.10.150.20"/>
<db_xref db="CATH" dbkey="1.10.8.10"/>
<db_xref db="CATH" dbkey="2.40.50.140"/>
<db_xref db="SCOP" dbkey="a.5.1.1"/>
<db_xref db="SCOP" dbkey="a.60.2.1"/>
<db_xref db="SCOP" dbkey="b.40.4.2"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="1820"/>
<taxon_data name="Cyanobacteria" proteins_count="56"/>
<taxon_data name="Synechocystis PCC 6803" proteins_count="1"/>
<taxon_data name="Archaea" proteins_count="4"/>
<taxon_data name="Eukaryota" proteins_count="1"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000086" protein_count="21099" short_name="NUDIX_hydrolase_dom" type="Domain">
<name>NUDIX hydrolase domain</name>
<abstract>
MutT is a small bacterial protein (~12-15Kd) involved in the GO system [<cite idref="PUB00002202"/>]
responsible for removing an oxidatively damaged form of guanine (8-hydroxy-
guanine or 7,8-dihydro-8-oxoguanine) from DNA and the nucleotide pool.
8-oxo-dGTP is inserted opposite dA and dC residues of template DNA with near equal efficiency, leading to A.T to G.C transversions. MutT
specifically degrades 8-oxo-dGTP to the monophosphate, with the concomitant
release of pyrophosphate. A short conserved N-terminal region of mutT
(designated the MutT domain) is also found in a variety of other
prokaryotic, viral and eukaryotic proteins [<cite idref="PUB00004433"/>, <cite idref="PUB00003856"/>, <cite idref="PUB00002808"/>, <cite idref="PUB00006677"/>].
<p>The generic name `NUDIX hydrolases' (NUcleoside DIphosphate linked
to some other moiety X) has been coined for this domain family [<cite idref="PUB00006662"/>]. The
family can be divided into a number of subgroups, of which MutT anti-
mutagenic activity represents only one type; most of the rest hydrolyse
diverse nucleoside diphosphate derivatives (including ADP-ribose, GDP-
mannose, TDP-glucose, NADH, UDP-sugars, dNTP and NTP).</p>
</abstract>
<class_list>
<classification id="GO:0016787" class_type="GO">
<category>Molecular Function</category>
<description>hydrolase activity</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O22951"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="O95989"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P53550"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q8R2U6"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q9U2M7"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00002202">
<author_list>Michaels ML, Miller JH.</author_list>
<title>The GO system protects organisms from the mutagenic effect of the spontaneous lesion 8-hydroxyguanine (7,8-dihydro-8-oxoguanine).</title>
<db_xref db="PUBMED" dbkey="1328155"/>
<journal>J. Bacteriol.</journal>
<location issue="20" pages="6321-5" volume="174"/>
<year>1992</year>
</publication>
<publication id="PUB00002808">
<author_list>Sakumi K, Furuichi M, Tsuzuki T, Kakuma T, Kawabata S, Maki H, Sekiguchi M.</author_list>
<title>Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis.</title>
<db_xref db="PUBMED" dbkey="8226881"/>
<journal>J. Biol. Chem.</journal>
<location issue="31" pages="23524-30" volume="268"/>
<year>1993</year>
</publication>
<publication id="PUB00003856">
<author_list>Mejean V, Salles C, Bullions LC, Bessman MJ, Claverys JP.</author_list>
<title>Characterization of the mutX gene of Streptococcus pneumoniae as a homologue of Escherichia coli mutT, and tentative definition of a catalytic domain of the dGTP pyrophosphohydrolases.</title>
<db_xref db="PUBMED" dbkey="8170394"/>
<journal>Mol. Microbiol.</journal>
<location issue="2" pages="323-30" volume="11"/>
<year>1994</year>
</publication>
<publication id="PUB00004433">
<author_list>Koonin EV.</author_list>
<title>A highly conserved sequence motif defining the family of MutT-related proteins from eubacteria, eukaryotes and viruses.</title>
<db_xref db="PUBMED" dbkey="8233837"/>
<journal>Nucleic Acids Res.</journal>
<location issue="20" pages="4847" volume="21"/>
<year>1993</year>
</publication>
<publication id="PUB00006662">
<author_list>Bessman MJ, Frick DN, O'Handley SF.</author_list>
<title>The MutT proteins or "Nudix" hydrolases, a family of versatile, widely distributed, "housecleaning" enzymes.</title>
<db_xref db="PUBMED" dbkey="8810257"/>
<journal>J. Biol. Chem.</journal>
<location issue="41" pages="25059-62" volume="271"/>
<year>1996</year>
</publication>
<publication id="PUB00006677">
<author_list>McLennan AG.</author_list>
<title>The MutT motif family of nucleotide phosphohydrolases in man and human pathogens (review).</title>
<db_xref db="PUBMED" dbkey="10373642"/>
<journal>Int. J. Mol. Med.</journal>
<location issue="1" pages="79-89" volume="4"/>
<year>1999</year>
</publication>
</pub_list>
<parent_list>
<rel_ref ipr_ref="IPR015797"/>
</parent_list>
<child_list>
<rel_ref ipr_ref="IPR003293"/>
<rel_ref ipr_ref="IPR003561"/>
<rel_ref ipr_ref="IPR003562"/>
<rel_ref ipr_ref="IPR003563"/>
<rel_ref ipr_ref="IPR003564"/>
<rel_ref ipr_ref="IPR003565"/>
<rel_ref ipr_ref="IPR004385"/>
<rel_ref ipr_ref="IPR011876"/>
<rel_ref ipr_ref="IPR014078"/>
<rel_ref ipr_ref="IPR017397"/>
<rel_ref ipr_ref="IPR021161"/>
</child_list>
<contains>
<rel_ref ipr_ref="IPR000059"/>
<rel_ref ipr_ref="IPR020084"/>
<rel_ref ipr_ref="IPR020476"/>
</contains>
<found_in>
<rel_ref ipr_ref="IPR003300"/>
<rel_ref ipr_ref="IPR003301"/>
</found_in>
<member_list>
<db_xref protein_count="19640" db="PFAM" dbkey="PF00293" name="NUDIX"/>
<db_xref protein_count="20025" db="GENE3D" dbkey="G3DSA:3.90.79.10" name="NUDIX_hydrolase"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00293"/>
<db_xref db="MSDsite" dbkey="PS00893"/>
<db_xref db="BLOCKS" dbkey="IPB000086"/>
<db_xref db="EC" dbkey="3.6.1"/>
<db_xref db="PROSITEDOC" dbkey="PDOC00695"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1f3y"/>
<db_xref db="PDB" dbkey="1g0s"/>
<db_xref db="PDB" dbkey="1g9q"/>
<db_xref db="PDB" dbkey="1ga7"/>
<db_xref db="PDB" dbkey="1hx3"/>
<db_xref db="PDB" dbkey="1hzt"/>
<db_xref db="PDB" dbkey="1i9a"/>
<db_xref db="PDB" dbkey="1iry"/>
<db_xref db="PDB" dbkey="1jkn"/>
<db_xref db="PDB" dbkey="1jrk"/>
<db_xref db="PDB" dbkey="1k26"/>
<db_xref db="PDB" dbkey="1k2e"/>
<db_xref db="PDB" dbkey="1khz"/>
<db_xref db="PDB" dbkey="1kt9"/>
<db_xref db="PDB" dbkey="1ktg"/>
<db_xref db="PDB" dbkey="1mk1"/>
<db_xref db="PDB" dbkey="1mp2"/>
<db_xref db="PDB" dbkey="1mqe"/>
<db_xref db="PDB" dbkey="1mqw"/>
<db_xref db="PDB" dbkey="1mr2"/>
<db_xref db="PDB" dbkey="1mut"/>
<db_xref db="PDB" dbkey="1nfs"/>
<db_xref db="PDB" dbkey="1nfz"/>
<db_xref db="PDB" dbkey="1nqy"/>
<db_xref db="PDB" dbkey="1nqz"/>
<db_xref db="PDB" dbkey="1ow2"/>
<db_xref db="PDB" dbkey="1ppv"/>
<db_xref db="PDB" dbkey="1ppw"/>
<db_xref db="PDB" dbkey="1ppx"/>
<db_xref db="PDB" dbkey="1pun"/>
<db_xref db="PDB" dbkey="1puq"/>
<db_xref db="PDB" dbkey="1pus"/>
<db_xref db="PDB" dbkey="1pvf"/>
<db_xref db="PDB" dbkey="1q27"/>
<db_xref db="PDB" dbkey="1q33"/>
<db_xref db="PDB" dbkey="1q54"/>
<db_xref db="PDB" dbkey="1qvj"/>
<db_xref db="PDB" dbkey="1r67"/>
<db_xref db="PDB" dbkey="1rrq"/>
<db_xref db="PDB" dbkey="1rrs"/>
<db_xref db="PDB" dbkey="1rya"/>
<db_xref db="PDB" dbkey="1sjy"/>
<db_xref db="PDB" dbkey="1soi"/>
<db_xref db="PDB" dbkey="1su2"/>
<db_xref db="PDB" dbkey="1sz3"/>
<db_xref db="PDB" dbkey="1tum"/>
<db_xref db="PDB" dbkey="1u20"/>
<db_xref db="PDB" dbkey="1v8i"/>
<db_xref db="PDB" dbkey="1v8l"/>
<db_xref db="PDB" dbkey="1v8m"/>
<db_xref db="PDB" dbkey="1v8n"/>
<db_xref db="PDB" dbkey="1v8r"/>
<db_xref db="PDB" dbkey="1v8s"/>
<db_xref db="PDB" dbkey="1v8t"/>
<db_xref db="PDB" dbkey="1v8u"/>
<db_xref db="PDB" dbkey="1v8v"/>
<db_xref db="PDB" dbkey="1v8w"/>
<db_xref db="PDB" dbkey="1v8y"/>
<db_xref db="PDB" dbkey="1vc8"/>
<db_xref db="PDB" dbkey="1vc9"/>
<db_xref db="PDB" dbkey="1vcd"/>
<db_xref db="PDB" dbkey="1vhg"/>
<db_xref db="PDB" dbkey="1vhz"/>
<db_xref db="PDB" dbkey="1viq"/>
<db_xref db="PDB" dbkey="1viu"/>
<db_xref db="PDB" dbkey="1vk6"/>
<db_xref db="PDB" dbkey="1vrl"/>
<db_xref db="PDB" dbkey="1x51"/>
<db_xref db="PDB" dbkey="1x83"/>
<db_xref db="PDB" dbkey="1x84"/>
<db_xref db="PDB" dbkey="1xsb"/>
<db_xref db="PDB" dbkey="1xsc"/>
<db_xref db="PDB" dbkey="2a6t"/>
<db_xref db="PDB" dbkey="2a8p"/>
<db_xref db="PDB" dbkey="2a8q"/>
<db_xref db="PDB" dbkey="2a8r"/>
<db_xref db="PDB" dbkey="2a8s"/>
<db_xref db="PDB" dbkey="2a8t"/>
<db_xref db="PDB" dbkey="2azw"/>
<db_xref db="PDB" dbkey="2b06"/>
<db_xref db="PDB" dbkey="2b0v"/>
<db_xref db="PDB" dbkey="2b2k"/>
<db_xref db="PDB" dbkey="2fb1"/>
<db_xref db="PDB" dbkey="2fkb"/>
<db_xref db="PDB" dbkey="2fml"/>
<db_xref db="PDB" dbkey="2fvv"/>
<db_xref db="PDB" dbkey="2g73"/>
<db_xref db="PDB" dbkey="2g74"/>
<db_xref db="PDB" dbkey="2gt2"/>
<db_xref db="PDB" dbkey="2gt4"/>
<db_xref db="PDB" dbkey="2o5f"/>
<db_xref db="PDB" dbkey="2pqv"/>
<db_xref db="PDB" dbkey="2q9p"/>
<db_xref db="PDB" dbkey="2qkl"/>
<db_xref db="PDB" dbkey="2vnp"/>
<db_xref db="PDB" dbkey="2vnq"/>
<db_xref db="PDB" dbkey="3cng"/>
<db_xref db="CATH" dbkey="3.90.79.10"/>
<db_xref db="SCOP" dbkey="a.242.1.1"/>
<db_xref db="SCOP" dbkey="d.113.1.1"/>
<db_xref db="SCOP" dbkey="d.113.1.2"/>
<db_xref db="SCOP" dbkey="d.113.1.3"/>
<db_xref db="SCOP" dbkey="d.113.1.4"/>
<db_xref db="SCOP" dbkey="d.113.1.5"/>
<db_xref db="SCOP" dbkey="d.113.1.6"/>
<db_xref db="SCOP" dbkey="d.113.1.7"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="18277"/>
<taxon_data name="Cyanobacteria" proteins_count="293"/>
<taxon_data name="Synechocystis PCC 6803" proteins_count="8"/>
<taxon_data name="Archaea" proteins_count="343"/>
<taxon_data name="Eukaryota" proteins_count="2300"/>
<taxon_data name="Plastid Group" proteins_count="3"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="36"/>
<taxon_data name="Rice spp." proteins_count="76"/>
<taxon_data name="Fungi" proteins_count="764"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="37"/>
<taxon_data name="Other Eukaryotes" proteins_count="15"/>
<taxon_data name="Other Eukaryotes" proteins_count="24"/>
<taxon_data name="Nematoda" proteins_count="13"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="13"/>
<taxon_data name="Arthropoda" proteins_count="291"/>
<taxon_data name="Fruit Fly" proteins_count="32"/>
<taxon_data name="Chordata" proteins_count="324"/>
<taxon_data name="Human" proteins_count="49"/>
<taxon_data name="Mouse" proteins_count="54"/>
<taxon_data name="Virus" proteins_count="170"/>
<taxon_data name="Unclassified" proteins_count="9"/>
<taxon_data name="Other Eukaryotes" proteins_count="10"/>
<taxon_data name="Plastid Group" proteins_count="501"/>
<taxon_data name="Green Plants" proteins_count="501"/>
<taxon_data name="Metazoa" proteins_count="1479"/>
<taxon_data name="Plastid Group" proteins_count="108"/>
<taxon_data name="Plastid Group" proteins_count="52"/>
<taxon_data name="Other Eukaryotes" proteins_count="35"/>
<taxon_data name="Other Eukaryotes" proteins_count="11"/>
</taxonomy_distribution>
<sec_list>
<sec_ac acc="IPR003293"/>
<sec_ac acc="IPR003561"/>
<sec_ac acc="IPR003562"/>
<sec_ac acc="IPR003563"/>
<sec_ac acc="IPR003564"/>
<sec_ac acc="IPR003565"/>
<sec_ac acc="IPR004385"/>
<sec_ac acc="IPR011876"/>
<sec_ac acc="IPR014078"/>
<sec_ac acc="IPR017397"/>
<sec_ac acc="IPR021161"/>
</sec_list>
</interpro>
<interpro id="IPR000089" protein_count="10637" short_name="Biotin_lipoyl" type="Domain">
<name>Biotin/lipoyl attachment</name>
<abstract>
The biotin / lipoyl attachment domain has a conserved lysine residue that binds biotin or lipoic acid. Biotin plays a catalytic role in some carboxyl transfer reactions and is covalently attached, via an amide bond, to a lysine residue in enzymes requiring this coenzyme [<cite idref="PUB00002740"/>]. E2 acyltransferases have an essential cofactor, lipoic acid, which is covalently bound via an amide linkage to a lysine group [<cite idref="PUB00000614"/>]. The lipoic acid cofactor is found in a variety of proteins that include, H-protein of the glycine cleavage system (GCS), mammalian and yeast pyruvate dehydrogenases and fast migrating protein (FMP) (gene acoC) from <taxon tax_id="106590">Ralstonia eutropha</taxon> (Alcaligenes eutrophus).
</abstract>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="O00330"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="O17732"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P53395"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q00955"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q0WQF7"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00000614">
<author_list>Russell GC, Guest JR.</author_list>
<title>Sequence similarities within the family of dihydrolipoamide acyltransferases and discovery of a previously unidentified fungal enzyme.</title>
<db_xref db="PUBMED" dbkey="1825611"/>
<journal>Biochim. Biophys. Acta</journal>
<location issue="2" pages="225-32" volume="1076"/>
<year>1991</year>
</publication>
<publication id="PUB00002740">
<author_list>Shenoy BC, Xie Y, Park VL, Kumar GK, Beegen H, Wood HG, Samols D.</author_list>
<title>The importance of methionine residues for the catalysis of the biotin enzyme, transcarboxylase. Analysis by site-directed mutagenesis.</title>
<db_xref db="PUBMED" dbkey="1526981"/>
<journal>J. Biol. Chem.</journal>
<location issue="26" pages="18407-12" volume="267"/>
<year>1992</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR001882"/>
<rel_ref ipr_ref="IPR003016"/>
<rel_ref ipr_ref="IPR011053"/>
</contains>
<found_in>
<rel_ref ipr_ref="IPR005930"/>
<rel_ref ipr_ref="IPR006255"/>
<rel_ref ipr_ref="IPR006256"/>
<rel_ref ipr_ref="IPR006257"/>
<rel_ref ipr_ref="IPR014084"/>
<rel_ref ipr_ref="IPR014276"/>
<rel_ref ipr_ref="IPR015761"/>
<rel_ref ipr_ref="IPR017695"/>
</found_in>
<member_list>
<db_xref protein_count="10487" db="PFAM" dbkey="PF00364" name="Biotin_lipoyl"/>
<db_xref protein_count="10472" db="PROFILE" dbkey="PS50968" name="BIOTINYL_LIPOYL"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF00364"/>
<db_xref db="COMe" dbkey="PRX001138"/>
<db_xref db="BLOCKS" dbkey="IPB000089"/>
<db_xref db="PROSITEDOC" dbkey="PDOC50968"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1a6x"/>
<db_xref db="PDB" dbkey="1bdo"/>
<db_xref db="PDB" dbkey="1dcz"/>
<db_xref db="PDB" dbkey="1dd2"/>
<db_xref db="PDB" dbkey="1fyc"/>
<db_xref db="PDB" dbkey="1ghj"/>
<db_xref db="PDB" dbkey="1ghk"/>
<db_xref db="PDB" dbkey="1gjx"/>
<db_xref db="PDB" dbkey="1iyu"/>
<db_xref db="PDB" dbkey="1iyv"/>
<db_xref db="PDB" dbkey="1k8m"/>
<db_xref db="PDB" dbkey="1k8o"/>
<db_xref db="PDB" dbkey="1lab"/>
<db_xref db="PDB" dbkey="1lac"/>
<db_xref db="PDB" dbkey="1o78"/>
<db_xref db="PDB" dbkey="1pmr"/>
<db_xref db="PDB" dbkey="1qjo"/>
<db_xref db="PDB" dbkey="1y8n"/>
<db_xref db="PDB" dbkey="1y8o"/>
<db_xref db="PDB" dbkey="1y8p"/>
<db_xref db="PDB" dbkey="1z6h"/>
<db_xref db="PDB" dbkey="1z7t"/>
<db_xref db="PDB" dbkey="2b8f"/>
<db_xref db="PDB" dbkey="2b8g"/>
<db_xref db="PDB" dbkey="2bdo"/>
<db_xref db="PDB" dbkey="2d5d"/>
<db_xref db="PDB" dbkey="2evb"/>
<db_xref db="PDB" dbkey="2pnr"/>
<db_xref db="PDB" dbkey="2q8i"/>
<db_xref db="PDB" dbkey="3bdo"/>
<db_xref db="CATH" dbkey="2.40.50.100"/>
<db_xref db="SCOP" dbkey="b.84.1.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="9150"/>
<taxon_data name="Cyanobacteria" proteins_count="122"/>
<taxon_data name="Synechocystis PCC 6803" proteins_count="3"/>
<taxon_data name="Archaea" proteins_count="160"/>
<taxon_data name="Eukaryota" proteins_count="1323"/>
<taxon_data name="Plastid Group" proteins_count="1"/>
<taxon_data name="Arabidopsis thaliana" proteins_count="37"/>
<taxon_data name="Rice spp." proteins_count="35"/>
<taxon_data name="Fungi" proteins_count="487"/>
<taxon_data name="Saccharomyces cerevisiae" proteins_count="46"/>
<taxon_data name="Other Eukaryotes" proteins_count="16"/>
<taxon_data name="Nematoda" proteins_count="10"/>
<taxon_data name="Caenorhabditis elegans" proteins_count="10"/>
<taxon_data name="Arthropoda" proteins_count="123"/>
<taxon_data name="Fruit Fly" proteins_count="13"/>
<taxon_data name="Chordata" proteins_count="162"/>
<taxon_data name="Human" proteins_count="35"/>
<taxon_data name="Mouse" proteins_count="21"/>
<taxon_data name="Unclassified" proteins_count="6"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
<taxon_data name="Plastid Group" proteins_count="282"/>
<taxon_data name="Green Plants" proteins_count="282"/>
<taxon_data name="Metazoa" proteins_count="832"/>
<taxon_data name="Plastid Group" proteins_count="85"/>
<taxon_data name="Plastid Group" proteins_count="42"/>
<taxon_data name="Plastid Group" proteins_count="2"/>
<taxon_data name="Other Eukaryotes" proteins_count="12"/>
<taxon_data name="Other Eukaryotes" proteins_count="3"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000090" protein_count="1144" short_name="Flg_Motor_Flig" type="Family">
<name>Flagellar motor switch protein FliG</name>
<abstract>
<p>The flagellar motor switch in <taxon tax_id="562">Escherichia coli</taxon> and <taxon tax_id="602">Salmonella typhimurium</taxon> regulates the
direction of flagellar rotation and hence controls swimming behaviour [<cite idref="PUB00001834"/>].
The switch is a complex apparatus that responds to signals transduced by the
chemotaxis sensory signalling system during chemotactic behaviour [<cite idref="PUB00001834"/>]. CheY,
the chemotaxis response regulator, is believed to act directly on the switch
to induce tumbles in the swimming pattern, but no physical interactions of
CheY and switch proteins have yet been demonstrated. </p>
<p>The switch complex comprises at least three proteins - FliG, FliM and FliN.
It has been shown that FliG interacts with FliM, FliM interacts with itself,
and FliM interacts with FliN [<cite idref="PUB00002290"/>]. Several residues within the middle third
of FliG appear to be strongly involved in the FliG-FliM interaction, with
residues near the N- or C-termini being less important [<cite idref="PUB00002290"/>]. Such clustering
suggests that FliG-FliM interaction plays a central role in switching.</p>
<p>Analysis of the FliG, FliM and FliN sequences shows that none are especially
hydrophobic or appear to be integral membrane proteins [<cite idref="PUB00002083"/>]. This result is
consistent with other evidence suggesting that the proteins may be
peripheral to the membrane, possibly mounted on the basal body M ring [<cite idref="PUB00002083"/>, <cite idref="PUB00004790"/>]. FliG is present in about 25 copies per flagellum. This structure of the
C-terminal domain is known, this domain functions
specifically in motor rotation [<cite idref="PUB00004294"/>].</p>
</abstract>
<class_list>
<classification id="GO:0001539" class_type="GO">
<category>Biological Process</category>
<description>ciliary or flagellar motility</description>
</classification>
<classification id="GO:0003774" class_type="GO">
<category>Molecular Function</category>
<description>motor activity</description>
</classification>
<classification id="GO:0006935" class_type="GO">
<category>Biological Process</category>
<description>chemotaxis</description>
</classification>
<classification id="GO:0009288" class_type="GO">
<category>Cellular Component</category>
<description>bacterial-type flagellum</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref db="SWISSPROT" dbkey="Q9WY63"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00001834">
<author_list>Roman SJ, Frantz BB, Matsumura P.</author_list>
<title>Gene sequence, overproduction, purification and determination of the wild-type level of the Escherichia coli flagellar switch protein FliG.</title>
<db_xref db="PUBMED" dbkey="8224881"/>
<journal>Gene</journal>
<location issue="1" pages="103-8" volume="133"/>
<year>1993</year>
</publication>
<publication id="PUB00002083">
<author_list>Kihara M, Homma M, Kutsukake K, Macnab RM.</author_list>
<title>Flagellar switch of Salmonella typhimurium: gene sequences and deduced protein sequences.</title>
<db_xref db="PUBMED" dbkey="2656645"/>
<journal>J. Bacteriol.</journal>
<location issue="6" pages="3247-57" volume="171"/>
<year>1989</year>
</publication>
<publication id="PUB00002290">
<author_list>Marykwas DL, Berg HC.</author_list>
<title>A mutational analysis of the interaction between FliG and FliM, two components of the flagellar motor of Escherichia coli.</title>
<db_xref db="PUBMED" dbkey="8631704"/>
<journal>J. Bacteriol.</journal>
<location issue="5" pages="1289-94" volume="178"/>
<year>1996</year>
</publication>
<publication id="PUB00004790">
<author_list>Francis NR, Irikura VM, Yamaguchi S, DeRosier DJ, Macnab RM.</author_list>
<title>Localization of the Salmonella typhimurium flagellar switch protein FliG to the cytoplasmic M-ring face of the basal body.</title>
<db_xref db="PUBMED" dbkey="1631122"/>
<journal>Proc. Natl. Acad. Sci. U.S.A.</journal>
<location issue="14" pages="6304-8" volume="89"/>
<year>1992</year>
</publication>
<publication id="PUB00004294">
<author_list>Lloyd SA, Whitby FG, Blair DF, Hill CP.</author_list>
<title>Structure of the C-terminal domain of FliG, a component of the rotor in the bacterial flagellar motor.</title>
<db_xref db="PUBMED" dbkey="10440379"/>
<journal>Nature</journal>
<location issue="6743" pages="472-5" volume="400"/>
<year>1999</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR011002"/>
</contains>
<member_list>
<db_xref protein_count="1131" db="PFAM" dbkey="PF01706" name="FliG_C"/>
<db_xref protein_count="1123" db="PRINTS" dbkey="PR00954" name="FLGMOTORFLIG"/>
<db_xref protein_count="853" db="TIGRFAMs" dbkey="TIGR00207" name="fliG"/>
</member_list>
<external_doc_list>
<db_xref db="PANDIT" dbkey="PF01706"/>
<db_xref db="BLOCKS" dbkey="IPB000090"/>
</external_doc_list>
<structure_db_links>
<db_xref db="PDB" dbkey="1lkv"/>
<db_xref db="PDB" dbkey="1qc7"/>
<db_xref db="CATH" dbkey="1.10.220.30"/>
<db_xref db="SCOP" dbkey="a.118.14.1"/>
</structure_db_links>
<taxonomy_distribution>
<taxon_data name="Bacteria" proteins_count="1143"/>
<taxon_data name="Eukaryota" proteins_count="1"/>
<taxon_data name="Metazoa" proteins_count="1"/>
</taxonomy_distribution>
</interpro>
<interpro id="IPR000091" protein_count="139" short_name="Huntingtin" type="Family">
<name>Huntingtin</name>
<abstract>
Huntington's disease (HD) is a mid-life onset, inherited, neurodegenerative
disorder characterised by motor impairment, involuntary movements (chorea),
psychiatric disorders and dementia [<cite idref="PUB00003898"/>]. The disease results from the
expansion of a polyglutamine-encoding CAG repeat in a gene of unknown
function. Moderate expansion of glutamine-coding CAG repeats has been
found in other neurological diseases (e.g. spinobulbar muscular atrophy
and Machado-Joseph disease), in all of which the pathological mechanism
linked to the expansion of the polyglutamine tract in the protein remains
a mystery.
<p>The HD transcript is highly conserved, significant differences, as already
noted, occurring in the N-terminal Gln-repeat region. Huntingtin normally
contains 10-35 repeats, but shows 36-120 repeats in the disease form.
Migration differences between normal and mutated huntingtin in a denaturing
polyacrylamide gel suggest that the poly-Gln stretch disrupts the protein
conformation. This finding is consistent with the observation that
Gln repeats may form tightly-linked beta-sheets that could act as polar
zippers [<cite idref="PUB00004844"/>].</p>
</abstract>
<class_list>
<classification id="GO:0005634" class_type="GO">
<category>Cellular Component</category>
<description>nucleus</description>
</classification>
<classification id="GO:0005737" class_type="GO">
<category>Cellular Component</category>
<description>cytoplasm</description>
</classification>
</class_list>
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<example>
<db_xref db="SWISSPROT" dbkey="P42858"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P42859"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="P51111"/>
</example>
<example>
<db_xref db="SWISSPROT" dbkey="Q76P24"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00003898">
<author_list>Baxendale S, Abdulla S, Elgar G, Buck D, Berks M, Micklem G, Durbin R, Bates G, Brenner S, Beck S.</author_list>
<title>Comparative sequence analysis of the human and pufferfish Huntington's disease genes.</title>
<db_xref db="PUBMED" dbkey="7647794"/>
<journal>Nat. Genet.</journal>
<location issue="1" pages="67-76" volume="10"/>
<year>1995</year>
</publication>
<publication id="PUB00004844">
<author_list>Perutz MF, Johnson T, Suzuki M, Finch JT.</author_list>
<title>Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases.</title>
<db_xref db="PUBMED" dbkey="8202492"/>
<journal>Proc. Natl. Acad. Sci. U.S.A.</journal>
<location issue="12" pages="5355-8" volume="91"/>
<year>1994</year>
</publication>
</pub_list>
<contains>
<rel_ref ipr_ref="IPR000357"/>
<rel_ref ipr_ref="IPR016024"/>
</contains>
<member_list>
<db_xref protein_count="138" db="PANTHER" dbkey="PTHR10170" name="Huntingtin"/>
<db_xref protein_count="52" db="PRINTS" dbkey="PR00375" name="HUNTINGTIN"/>
</member_list>
<external_doc_list>
<db_xref db="BLOCKS" dbkey="IPB000091"/>
</external_doc_list>
<taxonomy_distribution>
<taxon_data name="Eukaryota" proteins_count="139"/>
<taxon_data name="Arthropoda" proteins_count="25"/>
<taxon_data name="Fruit Fly" proteins_count="3"/>
<taxon_data name="Chordata" proteins_count="25"/>
<taxon_data name="Human" proteins_count="4"/>
<taxon_data name="Mouse" proteins_count="1"/>
<taxon_data name="Metazoa" proteins_count="137"/>
<taxon_data name="Other Eukaryotes" proteins_count="2"/>
</taxonomy_distribution>
</interpro>
</interprodb>