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EBI Dbfetch

Insulin-like growth factor binding protein, N-terminal

AccessionIPR009030; (Growth_fac_rcpt_N_dom) matches 26121 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
OtherEukaryotes: 1314
PlastidGroup: 14
PlastidGroup: 296
Eukaryota: 296
Eukaryota: 1314
Eukaryota: 37
Bacteria: 1
Bacteria: 132
Chordata: 13566
FruitFly: 367
Fungi: 252
Metazoa: 18252
OtherEukaryotes: 37
Viruses: 36
Arthropoda: 237
Fungi: 102
Nematoda: 157
Chordata: 12607
Bacteria: 1
PlastidGroup: 11
Eukaryota: 14
Virus: 36
Metazoa: 135
Fungi: 2
Bacteria: 5
Cyanobacteria: 5
Eukaryota: 173
PlastidGroup: 173
OtherEukaryotes: 2
Eukaryota: 2
Virus: 7
Bacteria: 1
Eukaryota: 540
PlastidGroup: 540
GreenPlants: 540
Eukaryota: 19048
Eukaryota: 2478
PlastidGroup: 2478
Bacteria: 12
Eukaryota: 166
PlastidGroup: 166
Bacteria: 99
Bacteria: 1
Bacteria: 1
Eukaryota: 29
OtherEukaryotes: 29
Bacteria: 4
Archaea: 26
Arthropoda: 2223
Eukaryota: 25925
Human: 484
Mouse: 330
Nematoda: 812
Rice: 64
Bacteria: 6
Chordata: 384
Cyanobacteria: 5
GreenPlants: 153
Metazoa: 18035
Unclassified: 1
Archaea: 19
Fungi: 120
GreenPlants: 387
Nematoda: 655
Unclassified: 1
Archaea: 2
Arthropoda: 1986
Chordata: 575
Fungi: 1
Metazoa: 200
Virus: 29
Eukaryota: 1817
OtherEukaryotes: 1817
Fungi: 10
Metazoa: 82
Fungi: 17

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