Protein Domain : IPR000867

Type:  Domain Name:  Insulin-like growth factor-binding protein, IGFBP
Description:  The insulin family of proteins groups together several evolutionarily related active peptides []: these include insulin [, ], relaxin [, ], insect prothoracicotropic hormone (bombyxin) [], insulin-like growth factors (IGF1 and IGF2) [, ], mammalian Leydig cell-specific insulin-like peptide (gene INSL3), early placenta insulin-like peptide (ELIP) (gene INSL4), locust insulin-related peptide (LIRP), molluscan insulin-related peptides (MIP), and Caenorhabditis elegans insulin-like peptides. The 3D structures of a number of family members have been determined [, , ]. The fold comprises two polypeptide chains (A and B) linked by two disulphide bonds: all share a conserved arrangement of 4 cysteines in their A chain, the first of which is linked by a disulphide bond to the third, while the second and fourth are linked by interchain disulphide bonds to cysteines in the B chain. Insulin is found in many animals, and is involved in the regulation of normal glucose homeostasis. It also has other specific physiological effects, such as increasing the permeability of cells to monosaccharides, amino acids and fatty acids, and accelerating glycolysis and glycogen synthesis in the liver []. Insulin exerts its effects by interaction with a cell-surface receptor, which may also result in the promotion of cell growth []. Insulin is synthesised as a prepropeptide from which an endoplasmic reticulum-targeting sequence is cleaved to yield proinsulin. The sequence of prosinsulin contains 2 well-conserved regions (designated A and B), separated by an intervening connecting region (C), which is variable between species []. The connecting region is cleaved, liberating the active protein, which contains the A and B chains, held together by 2 disulphide bonds []. 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). All IGFBPs share a common domain architecture (:). While the N-terminal (, IGF binding protein domain), and the C-terminal (, 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 []. 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 []. The C terminus is also required for high affinity IGF binding, as well as for binding to the extracellular matrix [] and for nuclear translocation [, ] of IGFBP-3 and -5. 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 [, ]. Furthermore, IGFBPs can function as growth modulators independent of IGFs. For example, IGFBP-5 stimulates markers of bone formation in osteoblasts lacking functional IGFs []. 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 []. Finally, IGFBPs transported into the nucleus (via the nuclear localisation signal) may also exert IGF-independent effects by transcriptional activation of genes.This entry represents insulin-like growth factors (IGF-I and IGF-II), which bind to specific binding proteins in extracellular fluids with high affinity [, , ]. These IGF-bindingproteins (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 [, ], mouse protein cyr61 and its probable chicken homolog, protein CEF-10; human connective tissue growth factor (CTGF) and its mouse homolog, protein FISP-12; and vertebrate protein NOV. Short Name:  IGFBP-like
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0 Child Features

0 Contains

3 Cross Referencess

Identifier
PF00219
PS51323
SM00121

0 Found In

3 GO Annotations

GO Term Gene Name
GO:0005520 IPR000867
GO:0001558 IPR000867
GO:0005576 IPR000867

3 Ontology Annotations

GO Term Gene Name
GO:0005520 IPR000867
GO:0001558 IPR000867
GO:0005576 IPR000867

1 Parent Features

DB identifier Type Name
IPR009030 Domain Insulin-like growth factor binding protein, N-terminal

2 Proteins

DB identifier UniProt Accession Secondary Identifier Organism Name Length
Pum0055s0043.1.p A0A1X6PI24 PAC:38014629 Porphyra umbilicalis 890  
Joasc.16G119000.1.p PAC:45757564 Joinvillea ascendens 135  

22 Publications

First Author Title Year Journal Volume Pages PubMed ID
            1654338
            1309586
            503234
            6243748
            6107857
            1725860
            7680510
            11874691
            9822601
            9725901
            7519375
            9660801
            12379487
            12379489
            7504269
            2480830
            2036417
            9141131
            10601981
            8735594
            8683595
            1319992