Dbfetch

Growth factor receptor cysteine-rich domain

AccessionIPR009030; (Growth_fac_rcpt_) matches 41657 proteins
FullNameGrowth factor receptor cysteine-rich domain
TypeDomain
SignaturesSSF: SSF57184 SSF57184
Found inIPR005127; IPR009168; IPR011398; IPR012210; IPR012211; IPR012213; IPR016246; IPR016324; IPR020691; IPR022321; IPR022322; IPR022326; IPR022327;
ContainsIPR003341; IPR006212; IPR011936;
Abstract

This 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 members of the epidermal growth factor (EGF) receptor family [], such as 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.

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]
  4. Ward CW, Hoyne PA, Flegg RH. (1995)
    Insulin and epidermal growth factor receptors contain the cysteine repeat motif found in the tumor necrosis factor receptor.
    Proteins 22: 141-53
    [PUBMED:7567962] [PUB00076912]
Database linksPDB: 1adx; PDB: 1ajj; PDB: 1boe; 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: 1jl9; PDB: 1ldl; PDB: 1ldr; PDB: 1lmj; PDB: 1m6b; PDB: 1mox; PDB: 1n7d; PDB: 1n8y; PDB: 1n8z; PDB: 1nql; PDB: 1p9j; 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: 2fcw; PDB: 2hr7; PDB: 2jwa; PDB: 2k2s; PDB: 2k2t; PDB: 2ks1; PDB: 2vj3; PDB: 2w2m; PDB: 2w2n; PDB: 2w2o; PDB: 2w2p; PDB: 2w2q; PDB: 2w86; PDB: 2x10; PDB: 3b2u; PDB: 3b2v; PDB: 3be1; PDB: 3bps; PDB: 3c09; PDB: 3fby; PDB: 3fl7; PDB: 3gcw; PDB: 3gcx; PDB: 3gis; PDB: 3h3b; PDB: 3i2t; PDB: 3ltf; PDB: 3ltg; PDB: 3mbw; PDB: 3mx0; PDB: 3mzw; PDB: 3n85; PDB: 3njp; PDB: 3p0y; PDB: 3p11; PDB: 3p5b; PDB: 3qwq; PDB: 3u2p; PDB: 3u7u; PDB: 3u9u; PDB: 3v64; PDB: 3v65; PDB: 3w11; PDB: 4cud; PDB: 4cue; PDB: 4cuf; PDB: 4d0e; PDB: 4d0f; PDB: 4hrl; PDB: 4hrm; PDB: 4hrn; PDB: 4krl; PDB: 4krm; PDB: 4kro; PDB: 4krp; PDB: 4leo; PDB: 4oga; PDB: 4p59; PDB: 4ra0; CATH: 1.20.5.100; CATH: 2.10.220.10; CATH: 2.10.25.10; CATH: 2.10.50.10; CATH: 2.120.10.30; CATH: 2.60.120.200; CATH: 2.60.40.10; CATH: 2.60.40.1770; 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.3.9.1;
Taxonomy DistributionCaenorhabditis elegans: 65
Bacteria: 1
Eukaryota: 24
Fungi: 3
OtherEukaryotes: 1417
PlastidGroup: 14
Bacteria: 7
Eukaryota: 173
OtherEukaryotes: 27
PlastidGroup: 316
Virus: 7
Bacteria: 1
Eukaryota: 960
PlastidGroup: 960
Eukaryota: 3596
Fungi: 6
Eukaryota: 316
Bacteria: 13
Eukaryota: 195
Eukaryota: 27
Bacteria: 245
Eukaryota: 1417
Eukaryota: 60
Bacteria: 25
Eukaryota: 29
Bacteria: 1
Bacteria: 331
Chordata: 18597
Cyanobacteria: 7
FruitFly: 367
Fungi: 390
GreenPlants: 960
OtherEukaryotes: 60
PlastidGroup: 3596
Viruses: 46
Chordata: 384
Metazoa: 31143
Nematoda: 1155
OtherEukaryotes: 29
PlastidGroup: 173
Chordata: 17638
PlastidGroup: 195
Bacteria: 5
Chordata: 575
Fungi: 15
Virus: 31
Eukaryota: 1950
OtherEukaryotes: 1950
PlastidGroup: 24
Eukaryota: 14
Fungi: 17
Virus: 46
Metazoa: 136
Eukaryota: 32398
Virus: 7
Bacteria: 2
Eukaryota: 85
OtherEukaryotes: 85
Bacteria: 1
Bacteria: 3
Bacteria: 3
Archaea: 31
Arthropoda: 7239
Eukaryota: 41244
Human: 494
Metazoa: 31410
Mouse: 335
Nematoda: 2686
Rice: 84
Arthropoda: 402
Bacteria: 21
Fungi: 113
GreenPlants: 182
Unclassified: 4
Archaea: 22
Fungi: 215
GreenPlants: 778
Metazoa: 49
Nematoda: 1531
Unclassified: 1
Archaea: 2
Arthropoda: 6837
Metazoa: 202
Metazoa: 82
Bacteria: 3