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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
TypeDomain
SignaturesGENE3D: G3DSA:4.10.40.20 G3DSA:4.10.40.20
SSF: SSF57184 SSF57184
Found inIPR005127; IPR009168; IPR011398; IPR012210; IPR012211; IPR012213; IPR016246; IPR016324; IPR020691; IPR022321; IPR022322; IPR022326; IPR022327;
ContainsIPR003341; IPR006212; IPR011641; IPR011936;
Abstract

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;
SWISSPROT: O60494;
SWISSPROT: P00534;
SWISSPROT: P01132;
SWISSPROT: P14585;
References
  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: 1.20.5.100; CATH: 2.10.220.10; CATH: 2.10.25.10; CATH: 2.60.120.200; CATH: 3.80.20.20; CATH: 4.10.40.20; 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

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