EBI Dbfetch

Insulin-like growth factor binding protein, N-terminal

AccessionIPR009030; (Growth_fac_rcpt_N_dom) matches 23042 proteins
FullNameInsulin-like growth factor binding protein, N-terminal
SignaturesGENE3D: G3DSA: G3DSA:
SSF: SSF57184 SSF57184
Found inIPR005127; IPR009168; IPR011398; IPR012210; IPR012211; IPR012213; IPR016246; IPR016324; IPR020691; IPR022321; IPR022322; IPR022326; IPR022327;
ContainsIPR003341; IPR006212; IPR011641; IPR011936;

The growth factor receptor domain is a cysteine-rich region that is found in a variety of eukaryotic proteins that are involved in the mechanism of signal transduction by receptor tyrosine kinases. Proteins containing the growth factor receptor domain include the insulin-like growth factor-binding proteins (IGFBP) [], the type-1 insulin-like growth-factor receptor (IGF-1R) [], and the receptor protein-tyrosine kinase Erbb-3 (ErbB3) []. The general structure of the growth factor receptor domain is a disulphide-bound fold containing a beta-hairpin with two adjacent disulphides.

IGFBPs control the distribution, function and activity of insulin-like growth factors (IGFs) IGF-I and IGF-II, which are key regulators of cell proliferation, differentiation and transformation. All IGFBPs share a common domain organisation, where the highest conservation is found in the N-terminal Cys-rich IGF-binding domain. The N-terminal domain contains 10-12 conserved cysteine residues.

IGF-1R is a member of the tyrosine-kinase receptor superfamily that is involved in both normal growth and development and malignant transformation. The Cys-rich domain is flanked by two L-domains, and together they contribute to hormone binding and ligand specificity, even though they do not bind ligand directly. The Cys-rich region is composed of eight disulphide-bonded modules, seven of which form a rod-shaped domain.

ErbB3 is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. The extracellular region of ErbB3 is made up of two Cys-rich domains and two L-domains, arranged alternately. The two L-domains and the first Cys-rich domain are structurally homologous to those found in IGF-1R. The two Cys-rich domains are extended repeats of seven small disulphide-containing modules. A beta-hairpin loop extends from the first Cys-rich domain to contact the C-terminal portion of the second Cys-rich domain, creating a large pore structure.

ExamplesSWISSPROT: O15943;
  1. Garrett TP, McKern NM, Lou M, Frenkel MJ, Bentley JD, Lovrecz GO, Elleman TC, Cosgrove LJ, Ward CW. (1998)
    Crystal structure of the first three domains of the type-1 insulin-like growth factor receptor.
    Nature 394: 395-9
    [PUBMED:9690478] [PUB00004283]
  2. Zeslawski W, Beisel HG, Kamionka M, Kalus W, Engh RA, Huber R, Lang K, Holak TA. (2001)
    The interaction of insulin-like growth factor-I with the N-terminal domain of IGFBP-5.
    EMBO J. 20: 3638-44
    [PUBMED:11447105] [PUB00011763]
  3. Cho HS, Leahy DJ. (2002)
    Structure of the extracellular region of HER3 reveals an interdomain tether.
    Science 297: 1330-3
    [PUBMED:12154198] [PUB00011765]
Database linksPDB: 1adx; PDB: 1ajj; PDB: 1boe; PDB: 1cix; PDB: 1d2j; PDB: 1dqb; PDB: 1dx5; PDB: 1emn; PDB: 1emo; PDB: 1f5y; PDB: 1f8z; PDB: 1h30; PDB: 1h59; PDB: 1hj7; PDB: 1hz8; PDB: 1i0u; PDB: 1igr; PDB: 1ijq; PDB: 1ivo; PDB: 1ldl; PDB: 1ldr; PDB: 1lmj; PDB: 1m6b; PDB: 1mox; PDB: 1n7d; PDB: 1n8y; PDB: 1n8z; PDB: 1nql; PDB: 1s78; PDB: 1tmr; PDB: 1toz; PDB: 1uzj; PDB: 1uzk; PDB: 1uzp; PDB: 1uzq; PDB: 1wqj; PDB: 1xfe; PDB: 1yy9; PDB: 1z6c; PDB: 1zaq; PDB: 2a91; PDB: 2adx; PDB: 2ahx; PDB: 2bo2; PDB: 2bou; PDB: 2box; PDB: 2c5d; PDB: 2dsp; PDB: 2dsq; PDB: 2dsr; PDB: 2dtg; PDB: 2fcw; PDB: 2hr7; PDB: 2jwa; PDB: 2ks1; PDB: 2vj3; PDB: 2w86; PDB: 3b2u; PDB: 3b2v; PDB: 3be1; PDB: 3bps; PDB: 3c09; PDB: 3gis; PDB: 3h3b; PDB: 3i2t; PDB: 3ltg; PDB: 3p0y; CATH:; CATH:; CATH:; CATH:; CATH:; CATH:; CATH: 4.10.400.10; SCOP: b.29.1.4; SCOP: c.10.2.5; SCOP: g.12.1.1; SCOP: g.3.11.1; SCOP: g.3.6.2; SCOP: g.3.9.1;
Taxonomy DistributionCaenorhabditis elegans: 61
Bacteria: 1
Eukaryota: 11
Fungi: 2
OtherEukaryotes: 808
PlastidGroup: 14
Bacteria: 5
Eukaryota: 173
OtherEukaryotes: 2
PlastidGroup: 294
Virus: 7
Bacteria: 1
Eukaryota: 494
PlastidGroup: 494
Eukaryota: 16523
Eukaryota: 2484
Eukaryota: 294
Bacteria: 9
Eukaryota: 163
Eukaryota: 2
Bacteria: 103
Eukaryota: 808
Eukaryota: 29
Bacteria: 4
Bacteria: 1
Archaea: 24
Bacteria: 131
Chordata: 11470
Cyanobacteria: 5
Fungi: 197
GreenPlants: 494
Human: 470
Metazoa: 15782
PlastidGroup: 2484
Viruses: 36
Arthropoda: 228
Chordata: 384
Fungi: 77
Metazoa: 15565
Nematoda: 147
OtherEukaryotes: 29
PlastidGroup: 173
Unclassified: 1
Archaea: 19
Chordata: 10511
Nematoda: 544
PlastidGroup: 163
Arthropoda: 1877
Bacteria: 1
Chordata: 575
Virus: 29
Eukaryota: 1817
Fungi: 8
OtherEukaryotes: 1817
PlastidGroup: 11
Eukaryota: 14
Virus: 36
Metazoa: 135
Bacteria: 1
Eukaryota: 37
OtherEukaryotes: 37
Arthropoda: 2105
Eukaryota: 22849
FruitFly: 360
Mouse: 328
Nematoda: 691
Rice: 64
Bacteria: 5
Cyanobacteria: 5
GreenPlants: 153
Fungi: 92
GreenPlants: 341
Unclassified: 1
Fungi: 1
Metazoa: 197
Metazoa: 82
Fungi: 17