<?xml version="1.0" encoding="ISO-8859-1"?>
<!-- edited with XML Spy v4.4 U (http://www.xmlspy.com) by LYNN WHITE (EMBL OUTSTATION THE EBI) -->
<!DOCTYPE interprodb SYSTEM "interpro.dtd">
<interprodb>
<release>
<dbinfo dbname="INTERPRO" version="5.1" entry_count="5630" file_date="12-JUL-2002 00:00:00"/>
<dbinfo dbname="SWISS" version="40.22" entry_count="110823" file_date="24-JUN-2002 00:00:00"/>
<dbinfo dbname="TREMBL" version="21.2" entry_count="671586" file_date="05-JUL-2002 00:00:00"/>
<dbinfo dbname="PRINTS" version="33.0" entry_count="1650" file_date="24-JAN-2002 00:00:00"/>
<dbinfo dbname="PREFILE" version="N/A" entry_count="252" file_date="18-JUL-2001 00:00:00"/>
<dbinfo dbname="PROSITE" version="17.5" entry_count="1565" file_date="21-JUN-2002 00:00:00"/>
<dbinfo dbname="PFAM" version="7.3" entry_count="3865" file_date="17-MAY-2002 00:00:00"/>
<dbinfo dbname="PRODOM" version="2001.3" entry_count="1346" file_date="28-JAN-2002 00:00:00"/>
<dbinfo dbname="SMART" version="3.1" entry_count="509" file_date="16-NOV-2000 00:00:00"/>
<dbinfo dbname="TIGRFAMs" version="1.2" entry_count="814" file_date="03-AUG-2001 00:00:00"/>
</release>
<interpro id="IPR000001" type="Domain" short_name="Kringle" protein_count="129">
<name>Kringle</name>
<abstract>
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 serine proteases and
plasma proteins.</abstract>
<example_list>
<example><db_xref dbkey="P00748" db="SWISS"/>Blood coagulation factor XII (Hageman factor) (1 copy)</example>
<example><db_xref dbkey="P00749" db="SWISS"/>Urokinase-type plasminogen activator (1 copy)</example>
<example><db_xref dbkey="Q08048" db="SWISS"/>Hepatocyte growth factor (HGF) (4 copies)</example>
<example><db_xref dbkey="Q04756" db="SWISS"/>Hepatocyte growth factor activator <cite idref="PUB00003400"/> (1 copy) <cite idref="PUB00002776"/></example>
<example>
<db_xref dbkey="P06867" db="SWISS"/>
Plasminogen (5 copies)
</example>
<example>
<db_xref dbkey="P26927" db="SWISS"/>
Hepatocyte growth factor like protein (4 copies) <cite idref="PUB00000355"/>
</example>
<example>
<db_xref dbkey="P00735" db="SWISS"/>
Thrombin (2 copies)
</example>
<example>
<db_xref dbkey="P15638" db="SWISS"/>
Tissue plasminogen activator (TPA) (2 copies)
</example>
<example>
<db_xref dbkey="P08519" db="SWISS"/>
Apolipoprotein A (38 copies)
</example>
</example_list>
<pub_list>
<publication id="PUB00002414">
<author_list>Fujikawa K., McMullen B.A.</author_list>
<title>Primary structure of the heavy chain of human factor XIIa.</title>
<db_xref db="MEDLINE" dbkey="85182674"/>
<journal>J. Biol. Chem.</journal>
<location firstpage="5328" lastpage="5341" volume="260"/>
<year>1985</year>
</publication>
<publication id="PUB00001541">
<author_list>Patthy L., Trexler M., Vali V., Banyai L., Varadi A.</author_list>
<title>Kringles: Modules specialized for protein binding.</title>
<db_xref db="MEDLINE" dbkey="84208845"/>
<journal>FEBS Lett.</journal>
<location firstpage="131" lastpage="136" volume="171"/>
<year>1984</year>
</publication>
<publication id="PUB00003257">
<author_list>Atkinson R.A., Williams R.J.P.</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="MEDLINE" dbkey="90219023"/>
<journal>J. Mol. Biol.</journal>
<location firstpage="541" lastpage="552" volume="212"/>
<year>1990</year>
</publication>
<publication id="PUB00003400">
<author_list>Castellino F.J., Beals J.M.</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="MEDLINE" dbkey="88230478"/>
<journal>J. Mol. Evol.</journal>
<location firstpage="358" lastpage="369" volume="26"/>
<year>1987</year>
</publication>
<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="MEDLINE" dbkey="85228216"/>
<journal>Cell</journal>
<location firstpage="657" lastpage="663" volume="41"/>
<year>1985</year>
</publication>
<publication id="PUB00001620">
<author_list>Takahashi K., Ikeo K., Gojobori T.</author_list>
<title>Evolutionary origin of numerous kringles in human and simian apolipoprotein(a).</title>
<db_xref db="MEDLINE" dbkey="91348198"/>
<journal>FEBS Lett.</journal>
<location firstpage="146" lastpage="148" volume="287"/>
<year>1991</year>
</publication>
<publication id="PUB00000355">
<author_list>Friezner Degen S.J., Stuart L.A., Han S., Jamison C.S.</author_list>
<title>Characterization of the mouse cDNA and gene coding for a hepatocyte growth factor-like protein: expression during development.</title>
<db_xref db="MEDLINE" dbkey="92002017"/>
<journal>Biochemistry</journal>
<location firstpage="9781" lastpage="9791" volume="30"/>
<year>1991</year>
</publication>
<publication id="PUB00002776">
<author_list>Miyazawa K., Shimomura T., Kitamura A., Kondo J., Morimoto Y., Kitamura N.</author_list>
<title>Molecular cloning and sequence analysis of the cDNA for a human serine protease reponsible for activation of hepatocyte growth factor. Structural similarity of the protease precursor to blood coagulation factor XII.</title>
<db_xref db="MEDLINE" dbkey="93252878"/>
<journal>J. Biol. Chem.</journal>
<location firstpage="10024" lastpage="10028" volume="268"/>
<year>1993</year>
</publication>
</pub_list>
<member_list>
<db_xref protein_count="91" db="PRINTS" dbkey="PR00018" name="KRINGLE"/>
<db_xref protein_count="126" db="PROFILE" dbkey="PS50070" name="KRINGLE_2"/>
<db_xref protein_count="161" db="PROSITE" dbkey="PS00021" name="KRINGLE_1"/>
<db_xref protein_count="128" db="PFAM" dbkey="PF00051" name="kringle"/>
<db_xref protein_count="126" db="PRODOM" dbkey="PD000395" name="Kringle"/>
<db_xref protein_count="115" db="SMART" dbkey="SM00130" name="KR"/>
</member_list>
<external_doc_list>
<db_xref db="BLOCKS" dbkey="IPB000001"/>
<db_xref db="PDOC" dbkey="PDOC00020"/>
</external_doc_list>
</interpro>
<interpro id="IPR000002" type="Domain" short_name="Fizzy" protein_count="57">
<name>Cdc20/Fizzy</name>
<abstract>
<p>The Cdc20/Fizzy region is almost always associated with the G-protein beta WD-40 repeat (<db_xref db="INTERPRO" dbkey="IPR001680"/>). Ubiquitin-mediated proteolysis due to the anaphase-promoting complex/cyclosome
(APC/C) is essential for separation of sister chromatids, requiring degradation of the anaphase inhibitor Pds1, and for exit from mitosis, requiring inactivation of cyclin B Cdk1 kinases <cite idref="PUB00006167"/>. In <taxon tax_id="4890">yeast</taxon> Cdc20 is required for two microtubule-dependent processes, nuclear movements prior to anaphase and chromosome separation. APC(Cdc20) allows activation of Cdc14 and promotes exit from mitosis by mediating proteolysis of Pds1 and the S phase cyclin Clb5 in the yeast <taxon tax_id="4932">Saccharomyces cerevisiae</taxon>. </p>
<p>This domain is also found in a number of, as yet, uncharacterised proteins. These include a <taxon tax_id="40674">mammalian</taxon> protein, p55CDC, that is present in dividing cells and is
associated with protein kinase activity.</p>
</abstract>
<example_list>
<example>
<db_xref dbkey="P26309" db="SWISS"/>Cell division control protein (Cdc20) from S. cerevisiae
</example>
<example>
<db_xref dbkey="Q09786" db="SWISS"/>A hypothetical protein from S. pombe
</example>
</example_list>
<pub_list>
<publication id="PUB00006167">
<author_list>Shirayama M., Toth A., Galova M., Nasmyth K.</author_list>
<title>APC(Cdc20) promotes exit from mitosis by destroying the anaphase inhibitor Pds1 and cyclin Clb5.</title>
<db_xref db="MEDLINE" dbkey="20110935"/>
<journal>Nature</journal>
<location firstpage="203" lastpage="207" volume="402" issue="6758"/>
<year>1999</year>
</publication>
</pub_list>
<member_list>
<db_xref protein_count="59" db="PREFILE" dbkey="PS50218" name="FIZZY_DOMAIN"/>
<db_xref protein_count="55" db="PRODOM" dbkey="PD004563" name="Fizzy"/>
</member_list>
<external_doc_list>
<db_xref db="QDOC" dbkey="QDOC50218"/>
</external_doc_list>
</interpro>
<interpro id="IPR000003" type="Family" short_name="RtnoidX_receptor" protein_count="75">
<name>Retinoid X receptor</name>
<abstract>
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. 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.
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>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</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</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref dbkey="Q06726" db="SWISS"/>
</example>
<example>
<db_xref dbkey="P81559" db="SWISS"/>
</example>
<example>
<db_xref dbkey="Q64104" db="SWISS"/>
</example>
<example>
<db_xref dbkey="Q91766" db="SWISS"/>
</example>
<example>
<db_xref dbkey="P28701" db="SWISS"/>
</example>
<example>
<db_xref dbkey="O75454" db="SWISS"/>
</example>
</example_list>
<pub_list>
<publication id="PUB00004464">
<author_list>Nishihara T., Nishikawa J.-I., Kitaura M., Imagawa M.</author_list>
<title>Vitamin D receptor contains multiple dimerisation interfaces that are functionally different.</title>
<db_xref db="MEDLINE" dbkey="95206940"/>
<journal>Nucleic Acids Res.</journal>
<location firstpage="606" lastpage="611" volume="23"/>
<year>1995</year>
</publication>
<publication id="PUB00006168">
<author_list>Schmitt J., De Vos P., Verhoeven G., Stunnenberg H.G.</author_list>
<title>Human androgen receptor expressed in HeLa cells activates transcription in vitro.</title>
<db_xref db="MEDLINE" dbkey="94218237"/>
<journal>Nucleic Acids Res.</journal>
<location firstpage="1161" lastpage="1166" volume="22" issue="7"/>
<year>1994</year>
</publication>
</pub_list>
<parent_list>
<rel_ref ipr_ref="IPR001723"/>
</parent_list>
<contains>
<rel_ref ipr_ref="IPR000536"/>
</contains>
<member_list>
<db_xref protein_count="75" db="PRINTS" dbkey="PR00545" name="RETINOIDXR"/>
</member_list>
</interpro>
<interpro id="IPR000004" type="Domain" short_name="SapB" protein_count="135">
<name>Saposin type B</name>
<abstract>
Saposins are small lysosomal proteins that serve as activators of various
lysosomal lipid-degrading enzymes <cite idref="PUB00005747"/>. They probably act by isolating the
lipid substrate from the membrane surroundings, thus making it more
accessible to the soluble degradative enzymes. All <taxon tax_id="40674">mammalian</taxon> saposins
are synthesized as a single precursor molecule (prosaposin) which contains
four Saposin-B domains, yielding the active saposins after proteolytic
cleavage, and two Saposin-A domains that are removed in the activation
reaction.
The Saposin-B domains also occur in other
proteins, many of them active in the lysis of membranes <cite idref="PUB00005721"/>, <cite idref="PUB00005765"/>. <p>The 3D-structure of NK-lysin has recently been determined <cite idref="PUB00005798"/> and found to
be very different from the one predicted in <cite idref="PUB00005747"/>.
A group of <taxon tax_id="3193">plant</taxon> aspartic proteases related to cyprosin. These proteins
have a peculiar SAP-B domain where the two halves are 'swapped' <cite idref="PUB00005742"/>.</p>
</abstract>
<example_list>
<example>
<db_xref dbkey="P28039" db="SWISS"/>Mammalian Acyloxyacyl-hydrolase
</example>
<example>
<db_xref dbkey="P42210" db="SWISS"/>Plant aspartic proteinase
</example>
<example>
<db_xref dbkey="P17405" db="SWISS"/>Mammalian acid sphingomyelinase
</example>
<example>
<db_xref dbkey="Q07831" db="SWISS"/>Nonpathogenic pore-forming peptide from entamoeba
</example>
<example>
<db_xref dbkey="P10960" db="SWISS"/>Saposins Sap-A, Sap-B, Sap-C, Sap-D
</example>
</example_list>
<pub_list>
<publication id="PUB00005747">
<author_list>O'Hara P.J., Munford R.S., Sheppard P.O.</author_list>
<title>Saposin-like proteins (SAPLIP) carry out diverse functions on a common backbone structure.</title>
<db_xref db="MEDLINE" dbkey="96048294"/>
<journal>J. Lipid Res.</journal>
<location firstpage="1653" lastpage="1663" volume="36" issue="8"/>
<year>1995</year>
</publication>
<publication id="PUB00005721">
<author_list>Ponting C.P.</author_list>
<title>Acid sphingomyelinase possesses a domain homologous to its activator proteins: saposins B and D.</title>
<db_xref db="MEDLINE" dbkey="94272336"/>
<journal>Protein Sci.</journal>
<location firstpage="359" lastpage="361" volume="3" issue="2"/>
<year>1994</year>
</publication>
<publication id="PUB00005765">
<author_list>Hofmann K., Tschopp J.</author_list>
<title>Cytotoxic T cells: more weapons for new targets?</title>
<db_xref db="MEDLINE" dbkey="97021725"/>
<journal>Trends Microbiol.</journal>
<location firstpage="91" lastpage="94" volume="4" issue="3"/>
<year>1996</year>
</publication>
<publication id="PUB00005798">
<author_list>Liepinsh E., Otting G., Andersson M., Ruysschaert J.M.</author_list>
<title>Saposin fold revealed by the NMR structure of NK-lysin.</title>
<db_xref db="MEDLINE" dbkey="97475218"/>
<journal>Nat. Struct. Biol.</journal>
<location firstpage="793" lastpage="795" volume="4" issue="10"/>
<year>1997</year>
</publication>
<publication id="PUB00005742">
<author_list>Ponting C.P., Russell R.B.</author_list>
<title>Swaposins: circular permutations within genes encoding saposin homologues.</title>
<db_xref db="MEDLINE" dbkey="95334819"/>
<journal>Trends Biochem. Sci.</journal>
<location firstpage="179" lastpage="180" volume="20" issue="5"/>
<year>1995</year>
</publication>
</pub_list>
<child_list>
<rel_ref ipr_ref="IPR003258"/>
</child_list>
<member_list>
<db_xref protein_count="133" db="PREFILE" dbkey="PS50015" name="SAP_B"/>
<db_xref protein_count="71" db="PRODOM" dbkey="PD001732" name="SapB"/>
<db_xref protein_count="109" db="SMART" dbkey="SM00118" name="SAPB"/>
</member_list>
<external_doc_list>
<db_xref db="QDOC" dbkey="QDOC50015"/>
</external_doc_list>
</interpro>
<interpro id="IPR000005" type="Domain" short_name="HTHAraC" protein_count="765">
<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 dimerization <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</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</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref dbkey="Q04248" db="SWISS"/>Virulence regulon transcriptional activator
</example>
<example>
<db_xref dbkey="P28809" db="SWISS"/>mmsAB peron regulatory protein
</example>
<example>
<db_xref dbkey="Q48413" db="SWISS"/>
</example>
<example>
<db_xref dbkey="P35319" db="SWISS"/>Transcription regulator
</example>
<example>
<db_xref dbkey="Q52620" db="SWISS"/>Regulatory factor of blood coagulation
</example>
<example>
<db_xref dbkey="P17410" db="SWISS"/>CelD, the Escherichia coli cel operon repressor.
</example>
<example>
<db_xref dbkey="P19219" db="SWISS"/>AdaA, a Bacillus subtilis bifunctional protein that acts both as a transcriptional activator of the ada operon and as a methylphosphotriester-DNA alkyltransferase.
</example>
<example>
<db_xref dbkey="P03021" db="SWISS"/>AraC, the arabinose operon regulatory protein, which activates the transcription of the araBAD genes.
</example>
<example>
<db_xref dbkey="P27246" db="SWISS"/>MarA, which may be a transcriptional activator of genes involved in the multiple antibiotic resistance (mar) phenotype.
</example>
</example_list>
<pub_list>
<publication id="PUB00004444">
<author_list>Gallegos M.-T., Michan C., Ramos J.L.</author_list>
<title>The XylS/AraC family of regulators.</title>
<db_xref db="MEDLINE" dbkey="93197143"/>
<journal>Nucleic Acids Res.</journal>
<location firstpage="807" lastpage="810" volume="21"/>
<year>1993</year>
</publication>
<publication id="PUB00003566">
<author_list>Henikoff S., Wallace J.C., Brown J.P.</author_list>
<title>Finding protein similarities with nucleotide sequence databases.</title>
<db_xref db="MEDLINE" dbkey="90190362"/>
<journal>Meth. Enzymol.</journal>
<location firstpage="111" lastpage="132" volume="183"/>
<year>1990</year>
</publication>
<publication id="PUB00001933">
<author_list>Parker L.L., Hall B.G.</author_list>
<title>Characterisation and nucleotide sequence of the cryptic cel operon of Escherichia coli K12.</title>
<db_xref db="MEDLINE" dbkey="90185127"/>
<journal>Genetics</journal>
<location firstpage="455" lastpage="471" volume="124"/>
<year>1990</year>
</publication>
<publication id="PUB00004817">
<author_list>Bustos S.A., Schleif R.F.</author_list>
<title>Functional domains of the AraC protein.</title>
<db_xref db="MEDLINE" dbkey="93296193"/>
<journal>Proc. Natl. Acad. Sci. U.S.A.</journal>
<location firstpage="5638" lastpage="5642" volume="90"/>
<year>1993</year>
</publication>
</pub_list>
<member_list>
<db_xref protein_count="478" db="PRINTS" dbkey="PR00032" name="HTHARAC"/>
<db_xref protein_count="762" db="PROFILE" dbkey="PS01124" name="HTH_ARAC_FAMILY_2"/>
<db_xref protein_count="855" db="PROSITE" dbkey="PS00041" name="HTH_ARAC_FAMILY_1"/>
<db_xref protein_count="747" db="PFAM" dbkey="PF00165" name="HTH_AraC"/>
<db_xref protein_count="683" db="SMART" dbkey="SM00342" name="HTH_ARAC"/>
</member_list>
<external_doc_list>
<db_xref db="BLOCKS" dbkey="IPB000005"/>
<db_xref db="PDOC" dbkey="PDOC00040"/>
</external_doc_list>
</interpro>
<interpro id="IPR000010" type="Family" short_name="Cystatin" protein_count="219">
<name>Cysteine proteases inhibitor</name>
<abstract>
Members of this family are inhibitors of cysteine proteases <cite idref="PUB00005324"/>, <cite idref="PUB00003412"/>, <cite idref="PUB00001614"/>, which are found in the tissues and body fluids of <taxon tax_id="33208">animals</taxon>, as well as in <taxon tax_id="3193">plants</taxon>. They can be grouped into three distinct but related families. These are the type 1 cystatins (or stefins), type 2 cystatins, and the kininogens.
<p>Kininogen is the precursor of the active peptide bradykinin that plays a role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII. They are also inhibitors of cysteine proteases. Structurally, kininogens are made of three contiguous type-2 cystatin domains, followed by an additional domain (of variable length) which contains the sequence of bradykinin. The first of the three cystatin domains seems to have lost its inhibitory activity.</p>
</abstract>
<class_list>
<classification id="GO:0004869" class_type="GO">
<category>Molecular Function</category>
<description>cysteine protease inhibitor</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref dbkey="P09229" db="SWISS"/>Cysteine proteinase inhibitor of rice
</example>
<example>
<db_xref dbkey="P29701" db="SWISS"/>Mammalian fetuin
</example>
<example>
<db_xref dbkey="P28325" db="SWISS"/>Type 2 cystatin
</example>
<example>
<db_xref dbkey="P37842" db="SWISS"/>Potato multicystatin, an eight-domain cysteine proteinase inhibitor
</example>
<example>
<db_xref dbkey="P01045" db="SWISS"/>Kininogen
</example>
<example>
<db_xref dbkey="Q28986" db="SWISS"/>Type 1 cystatin
</example>
<example>
<db_xref dbkey="P31727" db="SWISS"/>Sarcocystatin A from the flesh fish
</example>
</example_list>
<pub_list>
<publication id="PUB00005324">
<author_list>Barrett A.J.</author_list>
<journal>Trends Biochem. Sci.</journal>
<location firstpage="193" lastpage="196" volume="12"/>
<year>1987</year>
</publication>
<publication id="PUB00003412">
<author_list>Rawlings N.D., Barrett A.J.</author_list>
<title>Evolution of proteins of the cystatin superfamily.</title>
<db_xref db="MEDLINE" dbkey="90189177"/>
<journal>J. Mol. Evol.</journal>
<location firstpage="60" lastpage="71" volume="30"/>
<year>1990</year>
</publication>
<publication id="PUB00001614">
<author_list>Bode W., Turk V.</author_list>
<title>The cystatins: protein inhibitors of cysteine proteinases.</title>
<db_xref db="MEDLINE" dbkey="91309737"/>
<journal>FEBS Lett.</journal>
<location firstpage="213" lastpage="219" volume="285"/>
<year>1991</year>
</publication>
</pub_list>
<child_list>
<rel_ref ipr_ref="IPR001363"/>
<rel_ref ipr_ref="IPR001713"/>
<rel_ref ipr_ref="IPR003243"/>
<rel_ref ipr_ref="IPR003244"/>
</child_list>
<member_list>
<db_xref protein_count="199" db="PROSITE" dbkey="PS00287" name="CYSTATIN"/>
<db_xref protein_count="209" db="PFAM" dbkey="PF00031" name="cystatin"/>
<db_xref protein_count="205" db="SMART" dbkey="SM00043" name="CY"/>
</member_list>
<external_doc_list>
<db_xref db="BLOCKS" dbkey="IPB000010"/>
<db_xref db="PDOC" dbkey="PDOC00259"/>
</external_doc_list>
<sec_list>
<sec_ac acc="IPR000078"/>
</sec_list>
</interpro>
<interpro id="IPR000413" type="Family" short_name="Integrin_alpha" protein_count="126">
<name>Integrins alpha chain</name>
<abstract>
Integrins <cite idref="PUB00000811"/>, <cite idref="PUB00001505"/> are a large family of cell surface receptors that mediate cell
to cell as well as cell to matrix adhesion. Some integrins recognize the R-G-D
sequence in their extracellular matrix protein ligand. Structurally, integrins
consist of a dimer of an alpha and a beta chain. Each subunit has a large
N-terminal extracellular domain followed by a transmembrane domain and a short
C-terminal cytoplasmic region. Some alpha subunits are cleaved post-
translationally to produce a heavy and a light chain linked by a disulfide
bond. Integrin alpha chains share a conserved sequence which is found at
the beginning of the cytoplasmic domain, just after the end of the
transmembrane region. The exact pairing of alpha- and beta-subunits determines
ligand specificity, localisation and function. Within the N-terminal domain of alpha subunits, seven sequence repeats, each
of approximately 60 amino acids, have been found <cite idref="PUB00006166"/>. It has been predicted
that these repeats assume a beta-propeller fold. The domains contain seven
four-stranded beta-sheets arranged in a torus around a pseudosymmetry axis
<cite idref="PUB00005772"/>. Integrin ligands and a putative Mg<sup>2+</sup> ion are predicted to bind to the
upper face of the propeller, in a manner analogous to the way in which the
trimeric G-protein beta subunit (G beta) (which also has a beta-propeller
fold) binds the G protein alpha subunit <cite idref="PUB00005772"/>.
</abstract>
<class_list>
<classification id="GO:0004895" class_type="GO">
<category>Molecular Function</category>
<description>cell adhesion receptor</description>
</classification>
<classification id="GO:0007155" class_type="GO">
<category>Biological Process</category>
<description>cell adhesion</description>
</classification>
<classification id="GO:0007160" class_type="GO">
<category>Biological Process</category>
<description>cell-matrix adhesion</description>
</classification>
<classification id="GO:0008305" class_type="GO">
<category>Cellular Component</category>
<description>integrin</description>
</classification>
</class_list>
<example_list>
<example>
<db_xref dbkey="P23229" db="SWISS"/>The alpha-6 chain (VLA-6) which, with the beta-1 chain, forms a platelet laminin receptor.
</example>
<example>
<db_xref dbkey="P53708" db="SWISS"/>The alpha-8 chain which, with the beta-1 chain plays a possible role in cell-cell interactions during axon-growth and fasciculation.
</example>
<example>
<db_xref dbkey="P08648" db="SWISS"/>The alpha-5 chain (VLA-5) (CD49e) which, with the beta-1 chain, forms a receptor specific to fibronectin.
</example>
<example>
<db_xref dbkey="P12080" db="SWISS"/>The Drosophila position-specific antigen 2 alpha chain (PS2).
</example>
<example>
<db_xref dbkey="P26006" db="SWISS"/>The alpha-3 chain (VLA-3) (Galactoprotein B3).
</example>
<example>
<db_xref dbkey="P56199" db="SWISS"/>The alpha-1 chain (VLA-1) (CD49a) which, with the beta-1 chain, acts as a receptor for laminin and collagen.
</example>
<example>
<db_xref dbkey="P13612" db="SWISS"/>The alpha-4 chain (VLA-4) (CD49d) which, with the beta-1 chain, interacts with vascular cell adhesion protein 1 (VCAM-1).
</example>
<example>
<db_xref dbkey="P17301" db="SWISS"/>The alpha-2 chain (VLA-2) (CD49b) which, with the beta-1 chain, acts as a receptor that binds collagen.
</example>
</example_list>
<pub_list>
<publication id="PUB00000811">
<author_list>Hynes R.O.</author_list>
<title>Integrins: a family of cell surface receptors.</title>
<db_xref db="MEDLINE" dbkey="87131067"/>
<journal>Cell</journal>
<location firstpage="549" lastpage="554" volume="48"/>
<year>1987</year>
</publication>
<publication id="PUB00001505">
<author_list>Albelda S.M., Buck C.A.</author_list>
<title>Integrins and other cell adhesion molecules.</title>
<db_xref db="MEDLINE" dbkey="90337122"/>
<journal>FASEB J.</journal>
<location firstpage="2868" lastpage="2880" volume="4"/>
<year>1990</year>
</publication>
<publication id="PUB00006166">
<author_list>Springer T.A., Corbi A.L., Miller L.J., O'Connor K., Larson R.S.</author_list>
<title>cDNA cloning and complete primary structure of the alpha subunit of a leukocyte adhesion glycoprotein, p150,95.</title>
<db_xref db="MEDLINE" dbkey="88166645"/>
<journal>EMBO J.</journal>
<location firstpage="4023" lastpage="4028" volume="6" issue="13"/>
<year>1987</year>
</publication>
<publication id="PUB00005772">
<author_list>Springer T.A.</author_list>
<title>Folding of the N-terminal, ligand-binding region of integrin alpha-subunits into a beta-propeller domain.</title>
<db_xref db="MEDLINE" dbkey="97144395"/>
<journal>Proc. Natl. Acad. Sci. U.S.A.</journal>
<location firstpage="65" lastpage="72" volume="94" issue="1"/>
<year>1997</year>
</publication>
</pub_list>
<member_list>
<db_xref protein_count="79" db="PRINTS" dbkey="PR01185" name="INTEGRINA"/>
<db_xref protein_count="112" db="PREFILE" dbkey="PS50107" name="INTEGRIN_ALPHA_2"/>
<db_xref protein_count="104" db="PROSITE" dbkey="PS00242" name="INTEGRIN_ALPHA"/>
<db_xref protein_count="75" db="PFAM" dbkey="PF00357" name="integrin_A"/>
<db_xref protein_count="117" db="PFAM" dbkey="PF01839" name="FG-GAP"/>
<db_xref protein_count="110" db="SMART" dbkey="SM00191" name="Int_alpha"/>
</member_list>
<external_doc_list>
<db_xref db="BLOCKS" dbkey="IPB000413"/>
<db_xref db="PDOC" dbkey="PDOC00215"/>
<db_xref db="PROPRO" dbkey="integrins_alpha"/>
</external_doc_list>
<sec_list>
<sec_ac acc="IPR002458"/>
<sec_ac acc="IPR002476"/>
</sec_list>
</interpro>
<deleted_entries>
<del_ref id="IPR000001"/>
<del_ref id="IPR000005"/>
<del_ref id="IPR000019"/>
<del_ref id="IPR000027"/>
<del_ref id="IPR000078"/>
</deleted_entries>
</interprodb>