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15  structures 327  species 0  interactions 4832  sequences 79  architectures

Family: IGFBP (PF00219)

Summary: Insulin-like growth factor binding protein

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This is the Wikipedia entry entitled "Insulin-like growth factor binding protein". More...

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Insulin-like growth factor binding protein Provide feedback

No Pfam abstract.

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000867

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 ( INTERPRO : INTERPRO ). While the N-terminal ( INTERPRO , IGF binding protein domain), and the C-terminal ( INTERPRO , 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 [ PUBMED:11874691 ].

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 [ PUBMED:9822601 ]. The C terminus is also required for high affinity IGF binding, as well as for binding to the extracellular matrix [ PUBMED:9725901 ] and for nuclear translocation [ PUBMED:7519375 , PUBMED:9660801 ] 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 [ PUBMED:12379487 , PUBMED:12379489 ]. Furthermore, IGFBPs can function as growth modulators independent of IGFs. For example, IGFBP-5 stimulates markers of bone formation in osteoblasts lacking functional IGFs [ PUBMED:11874691 ]. 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 [ PUBMED:7504269 ]. 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 [ PUBMED:7680510 , PUBMED:1725860 , PUBMED:2480830 ]. 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 [ PUBMED:1654338 , PUBMED:1309586 ], mouse protein cyr61 and its probable chicken homologue, protein CEF-10; human connective tissue growth factor (CTGF) and its mouse homologue, protein FISP-12; and vertebrate protein NOV.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan GF_recep_C-rich (CL0547), which has the following description:

The cysteine-rich regions of growth factor receptor tyrosine kinases consist of eight disulphide-linked modules [1].

The clan contains the following 5 members:

amfpi-1 Furin-like Furin-like_2 GF_recep_IV IGFBP


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

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Seed source: Prosite
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD
Number in seed: 186
Number in full: 4832
Average length of the domain: 54.80 aa
Average identity of full alignment: 43 %
Average coverage of the sequence by the domain: 15.68 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 28.0 28.0
Trusted cut-off 28.0 28.0
Noise cut-off 27.9 27.9
Model length: 55
Family (HMM) version: 20
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
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Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the IGFBP domain has been found. There are 15 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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