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{
"metadata": {
"accession": "IPR000867",
"entry_id": null,
"type": "domain",
"go_terms": [
{
"identifier": "GO:0005576",
"name": "extracellular region",
"category": {
"code": "C",
"name": "cellular_component"
}
}
],
"source_database": "interpro",
"member_databases": {
"profile": {
"PS51323": "Insulin-like growth factor-binding protein (IGFBP) N-terminal domain profile"
},
"pfam": {
"PF00219": "Insulin-like growth factor binding protein"
},
"smart": {
"SM00121": "Insulin growth factor-binding protein homologues"
}
},
"integrated": null,
"hierarchy": {
"accession": "IPR000867",
"name": "Insulin-like growth factor-binding protein, IGFBP",
"type": "Domain",
"children": []
},
"name": {
"name": "Insulin-like growth factor-binding protein, IGFBP",
"short": "IGFBP-like"
},
"description": [
{
"text": "<p>This entry represents insulin-like growth factors (IGF-I and IGF-II), which bind with high affinity to specific binding proteins in extracellular fluids [[cite:PUB00005642], [cite:PUB00004938], [cite:PUB00015297]]. These IGF-binding proteins (IGFBP) prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cells culture. They seem to alter the interaction of IGFs with their cell surface receptors. There are at least six different IGFBPs and they are structurally related. The following growth-factor inducible proteins are structurally related to IGFBPs and could function as growth-factor binding proteins [[cite:PUB00003068], [cite:PUB00003677]], mouse protein cyr61 and its probable chicken homologue, protein CEF-10 (both known as CCN family member 1); human connective tissue growth factor (CTGF) and its mouse homologue, protein FISP-12 (both known as CCN family member 2); and vertebrate protein NOV (known as CCN family member 3).</p>",
"llm": false,
"checked": false,
"updated": false
},
{
"text": "<p>Insulin-like Growth Factor Binding Proteins (IGFBP) are a group of vertebrate secreted proteins, which bind to IGF-I and IGF-II with high affinity and modulate the biological actions of IGFs. The IGFBP family has six distinct subgroups, IGFBP-1 through 6, based on conservation of gene (intron-exon) organisation, structural similarity, and binding affinity for IGFs. Across species, IGFBP-5 exhibits the most sequence conservation, while IGFBP-6 exhibits the least sequence conservation. The IGFBPs contain inhibitor domain homologues, which are related to MEROPS protease inhibitor family I31 (equistatin, clan IX).</p>\n\n<p>All IGFBPs share a common domain architecture ([interpro:IPR000867]:[interpro:IPR000716]). While the N-terminal ([interpro:IPR000867], IGF binding protein domain), and the C-terminal ([interpro:IPR000716], thyroglobulin type-1 repeat) domains are conserved across vertebrate species, the mid-region is highly variable with respect to protease cleavage sites and phosphorylation and glycosylation sites. IGFBPs contain 16-18 conserved cysteines located in the N-terminal and the C-terminal regions, which form 8-9 disulphide bonds [[cite:PUB00013535]].</p>\n\n<p>As demonstrated for human IGFBP-5, the N terminus is the primary binding site for IGF. This region, comprised of Val49, Tyr50, Pro62 and Lys68-Leu75, forms a hydrophobic patch on the surface of the protein [[cite:PUB00013536]]. The C terminus is also required for high affinity IGF binding, as well as for binding to the extracellular matrix [[cite:PUB00013537]] and for nuclear translocation [[cite:PUB00013538], [cite:PUB00013539]] of IGFBP-3 and -5.</p>\n\n<p>IGFBPs are unusually pleiotropic molecules. Like other binding proteins, IGFBP can prolong the half-life of IGFs via high affinity binding of the ligands. In addition to functioning as simple carrier proteins, serum IGFBPs also serve to regulate the endocrine and paracrine/autocrine actions of IGF by modulating the IGF available to bind to signalling IGF-I receptors [[cite:PUB00013540], [cite:PUB00013541]]. Furthermore, IGFBPs can function as growth modulators independent of IGFs. For example, IGFBP-5 stimulates markers of bone formation in osteoblasts lacking functional IGFs [[cite:PUB00013535]]. The binding of IGFBP to its putative receptor on the cell membrane may stimulate the signalling pathway independent of an IGF receptor, to mediate the effects of IGFBPs in certain target cell types. IGFBP-1 and -2, but not other IGFBPs, contain a C-terminal Arg-Gly-Asp integrin-binding motif. Thus, IGFBP-1 can also stimulate cell migration of CHO and human trophoblast cells through an action mediated by alpha 5 beta 1 integrin [[cite:PUB00013542]]. Finally, IGFBPs transported into the nucleus (via the nuclear localisation signal) may also exert IGF-independent effects by transcriptional activation of genes.</p>",
"llm": false,
"checked": false,
"updated": false
}
],
"wikipedia": null,
"literature": {
"PUB00004938": {
"PMID": 1725860,
"ISBN": null,
"volume": "3",
"issue": "4",
"year": 1991,
"title": "Identification and molecular characterization of insulin-like growth factor binding proteins (IGFBP-1, -2, -3, -4, -5 and -6).",
"URL": null,
"raw_pages": "243-66",
"medline_journal": "Prog Growth Factor Res",
"ISO_journal": "Prog. Growth Factor Res.",
"authors": [
"Shimasaki S",
"Ling N."
],
"DOI_URL": "http://dx.doi.org/10.1016/0955-2235(91)90003-M"
},
"PUB00003677": {
"PMID": 1309586,
"ISBN": null,
"volume": "12",
"issue": "1",
"year": 1992,
"title": "Proviral rearrangements and overexpression of a new cellular gene (nov) in myeloblastosis-associated virus type 1-induced nephroblastomas.",
"URL": null,
"raw_pages": "10-21",
"medline_journal": "Mol Cell Biol",
"ISO_journal": "Mol. Cell. Biol.",
"authors": [
"Joliot V",
"Martinerie C",
"Dambrine G",
"Plassiart G",
"Brisac M",
"Crochet J",
"Perbal B."
],
"DOI_URL": "http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=EBI&pubmedid=1309586&action=stream&blobtype=pdf"
},
"PUB00013541": {
"PMID": 12379489,
"ISBN": null,
"volume": "175",
"issue": "1",
"year": 2002,
"title": "Specifying the cellular responses to IGF signals: roles of IGF-binding proteins.",
"URL": null,
"raw_pages": "41-54",
"medline_journal": "J Endocrinol",
"ISO_journal": "J. Endocrinol.",
"authors": [
"Duan C."
],
"DOI_URL": "http://dx.doi.org/10.1677/joe.0.1750041"
},
"PUB00013540": {
"PMID": 12379487,
"ISBN": null,
"volume": "175",
"issue": "1",
"year": 2002,
"title": "IGF-binding proteins are multifunctional and act via IGF-dependent and -independent mechanisms.",
"URL": null,
"raw_pages": "19-31",
"medline_journal": "J Endocrinol",
"ISO_journal": "J. Endocrinol.",
"authors": [
"Mohan S",
"Baylink DJ."
],
"DOI_URL": "http://dx.doi.org/10.1677/joe.0.1750019"
},
"PUB00013542": {
"PMID": 7504269,
"ISBN": null,
"volume": "90",
"issue": "22",
"year": 1993,
"title": "Insulin-like growth factor binding protein 1 stimulates cell migration and binds to the alpha 5 beta 1 integrin by means of its Arg-Gly-Asp sequence.",
"URL": null,
"raw_pages": "10553-7",
"medline_journal": "Proc Natl Acad Sci U S A",
"ISO_journal": "Proc. Natl. Acad. Sci. U.S.A.",
"authors": [
"Jones JI",
"Gockerman A",
"Busby WH Jr",
"Wright G",
"Clemmons DR."
],
"DOI_URL": "http://ukpmc.ac.uk/articlerender.cgi?tool=EBI&pubmedid=7504269"
},
"PUB00013538": {
"PMID": 7519375,
"ISBN": null,
"volume": "19",
"issue": "7",
"year": 1994,
"title": "Nuclear localization signal in insulin-like growth factor-binding protein type 3.",
"URL": null,
"raw_pages": "278",
"medline_journal": "Trends Biochem Sci",
"ISO_journal": "Trends Biochem. Sci.",
"authors": [
"Radulescu RT."
],
"DOI_URL": "http://dx.doi.org/10.1016/0968-0004(94)90004-3"
},
"PUB00013537": {
"PMID": 9725901,
"ISBN": null,
"volume": "9",
"issue": "9",
"year": 1998,
"title": "Binding of insulin-like growth factor (IGF)-binding protein-5 to smooth-muscle cell extracellular matrix is a major determinant of the cellular response to IGF-I.",
"URL": null,
"raw_pages": "2383-92",
"medline_journal": "Mol Biol Cell",
"ISO_journal": "Mol. Biol. Cell",
"authors": [
"Parker A",
"Rees C",
"Clarke J",
"Busby WH Jr",
"Clemmons DR."
],
"DOI_URL": "http://www.molbiolcell.org/cgi/content/abstract/9/9/2383"
},
"PUB00013539": {
"PMID": 9660801,
"ISBN": null,
"volume": "273",
"issue": "29",
"year": 1998,
"title": "Insulin-like growth factor-binding protein (IGFBP)-3 and IGFBP-5 share a common nuclear transport pathway in T47D human breast carcinoma cells.",
"URL": null,
"raw_pages": "18347-52",
"medline_journal": "J Biol Chem",
"ISO_journal": "J. Biol. Chem.",
"authors": [
"Schedlich LJ",
"Young TF",
"Firth SM",
"Baxter RC."
],
"DOI_URL": "http://dx.doi.org/10.1074/jbc.273.29.18347"
},
"PUB00005642": {
"PMID": 7680510,
"ISBN": null,
"volume": "47",
"issue": null,
"year": 1993,
"title": "Insulin-like growth factor binding proteins.",
"URL": null,
"raw_pages": "1-114",
"medline_journal": "Vitam Horm",
"ISO_journal": "Vitam. Horm.",
"authors": [
"Rechler MM."
],
"DOI_URL": null
},
"PUB00013536": {
"PMID": 9822601,
"ISBN": null,
"volume": "17",
"issue": "22",
"year": 1998,
"title": "Structure of the IGF-binding domain of the insulin-like growth factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I receptor interactions.",
"URL": null,
"raw_pages": "6558-72",
"medline_journal": "EMBO J",
"ISO_journal": "EMBO J.",
"authors": [
"Kalus W",
"Zweckstetter M",
"Renner C",
"Sanchez Y",
"Georgescu J",
"Grol M",
"Demuth D",
"Schumacher R",
"Dony C",
"Lang K",
"Holak TA."
],
"DOI_URL": "http://dx.doi.org/10.1093/emboj/17.22.6558"
},
"PUB00013535": {
"PMID": 11874691,
"ISBN": null,
"volume": "172",
"issue": "3",
"year": 2002,
"title": "IGF-binding protein-5: flexible player in the IGF system and effector on its own.",
"URL": null,
"raw_pages": "423-40",
"medline_journal": "J Endocrinol",
"ISO_journal": "J. Endocrinol.",
"authors": [
"Schneider MR",
"Wolf E",
"Hoeflich A",
"Lahm H."
],
"DOI_URL": "http://dx.doi.org/10.1677/joe.0.1720423"
},
"PUB00003068": {
"PMID": 1654338,
"ISBN": null,
"volume": "114",
"issue": "6",
"year": 1991,
"title": "Connective tissue growth factor: a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10.",
"URL": null,
"raw_pages": "1285-94",
"medline_journal": "J Cell Biol",
"ISO_journal": "J. Cell Biol.",
"authors": [
"Bradham DM",
"Igarashi A",
"Potter RL",
"Grotendorst GR."
],
"DOI_URL": "http://dx.doi.org/10.1083/jcb.114.6.1285"
},
"PUB00015297": {
"PMID": 2480830,
"ISBN": null,
"volume": "45",
"issue": "2",
"year": 1989,
"title": "Structural and functional analysis of insulin-like growth factors.",
"URL": null,
"raw_pages": "465-80",
"medline_journal": "Br Med Bull",
"ISO_journal": "Br. Med. Bull.",
"authors": [
"Clemmons DR."
],
"DOI_URL": "http://bmb.oxfordjournals.org/cgi/content/abstract/45/2/465"
}
},
"set_info": null,
"overlaps_with": [
{
"accession": "IPR009030",
"name": "Growth factor receptor cysteine-rich domain superfamily",
"type": "homologous_superfamily"
}
],
"counters": {
"subfamilies": 0,
"domain_architectures": 223,
"interactions": 0,
"matches": 19829,
"pathways": 25,
"proteins": 19821,
"proteomes": 1116,
"sets": 0,
"structural_models": {
"alphafold": 18362,
"bfvd": 0
},
"structures": 13,
"taxa": 4218
},
"entry_annotations": {
"alignment:seed": 160,
"alignment:full": 12976
},
"cross_references": {
"prositedoc": {
"displayName": "PROSITE Doc",
"description": "PROSITE is a database of protein families and domains.",
"rank": 18,
"accessions": [
{
"accession": "PDOC00194",
"url": "http://prosite.expasy.org/PDOC00194"
}
]
}
},
"is_llm": false,
"is_reviewed_llm": false,
"is_updated_llm": false,
"representative_structure": {
"accession": "1wqj",
"name": "Structural Basis for the Regulation of Insulin-Like Growth Factors (IGFs) by IGF Binding Proteins (IGFBPs)"
}
}
}
