Growth factor receptor cysteine-rich domain

AccessionIPR009030; (Growth_fac_rcpt_) matches 34457 proteins
FullNameGrowth factor receptor cysteine-rich domain
SignaturesSSF: SSF57184 SSF57184
Found inIPR005127; IPR009168; IPR011398; IPR012210; IPR012211; IPR012213; IPR016246; IPR016324; IPR020691; IPR022321; IPR022322; IPR022326; IPR022327;
ContainsIPR003341; IPR006212; IPR011936;

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.

  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: 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: 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.3.9.1;
Taxonomy DistributionCaenorhabditis elegans: 65
Bacteria: 1
Eukaryota: 24
Fungi: 2
OtherEukaryotes: 1325
PlastidGroup: 14
Bacteria: 5
Eukaryota: 173
OtherEukaryotes: 27
PlastidGroup: 315
Virus: 7
Bacteria: 1
Eukaryota: 827
PlastidGroup: 827
Eukaryota: 26171
Eukaryota: 3110
Fungi: 6
Eukaryota: 315
Bacteria: 12
Eukaryota: 191
Bacteria: 1
Eukaryota: 27
Bacteria: 160
Bacteria: 1
Eukaryota: 1325
Eukaryota: 37
Bacteria: 11
Eukaryota: 29
Bacteria: 1
Archaea: 26
Bacteria: 211
Chordata: 15572
Cyanobacteria: 5
FruitFly: 367
Fungi: 366
GreenPlants: 827
Human: 498
Metazoa: 25207
Nematoda: 2294
OtherEukaryotes: 37
PlastidGroup: 3110
Rice: 78
Viruses: 43
Arthropoda: 356
Chordata: 384
Cyanobacteria: 5
GreenPlants: 180
Metazoa: 24989
Nematoda: 1117
OtherEukaryotes: 29
PlastidGroup: 173
Unclassified: 4
Archaea: 19
Chordata: 14613
Nematoda: 1177
PlastidGroup: 191
Archaea: 2
Arthropoda: 5061
Bacteria: 4
Chordata: 575
Fungi: 14
Metazoa: 201
Virus: 30
Eukaryota: 1844
Fungi: 13
Metazoa: 82
OtherEukaryotes: 1844
PlastidGroup: 24
Eukaryota: 14
Fungi: 17
Metazoa: 136
Virus: 43
Unclassified: 1
Virus: 6
Eukaryota: 85
OtherEukaryotes: 85
Bacteria: 3
Arthropoda: 5417
Eukaryota: 34172
Mouse: 336
Bacteria: 11
Fungi: 128
Fungi: 182
GreenPlants: 647