Growth factor receptor cysteine-rich domain superfamily

AccessionIPR009030; (Growth_fac_rcpt_cys_sf) matches 43220 proteins
FullNameGrowth factor receptor cysteine-rich domain superfamily
SignaturesSSF: SSF57184 SSF57184

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: 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:; CATH:; CATH:; CATH:; 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: 3
OtherEukaryotes: 1417
PlastidGroup: 14
Bacteria: 8
Eukaryota: 173
OtherEukaryotes: 27
PlastidGroup: 345
Virus: 7
Eukaryota: 971
PlastidGroup: 971
Eukaryota: 33842
Eukaryota: 3612
Fungi: 7
Eukaryota: 345
Bacteria: 13
Eukaryota: 27
Bacteria: 277
Eukaryota: 1417
Eukaryota: 60
Bacteria: 28
Eukaryota: 29
Bacteria: 3
Bacteria: 3
Bacteria: 1
Bacteria: 383
Chordata: 19392
Cyanobacteria: 8
FruitFly: 367
Fungi: 486
GreenPlants: 971
Human: 514
OtherEukaryotes: 60
PlastidGroup: 3612
Viruses: 49
Bacteria: 33
Chordata: 384
Metazoa: 32448
Nematoda: 1189
OtherEukaryotes: 29
PlastidGroup: 173
Unclassified: 4
Archaea: 27
Chordata: 18250
Fungi: 237
Nematoda: 1530
Bacteria: 7
Chordata: 758
Fungi: 25
Virus: 31
Eukaryota: 1950
OtherEukaryotes: 1950
PlastidGroup: 24
Eukaryota: 14
Fungi: 17
Virus: 49
Metazoa: 179
Bacteria: 1
Virus: 10
Fungi: 40
Eukaryota: 197
PlastidGroup: 197
Bacteria: 2
Eukaryota: 85
OtherEukaryotes: 85
Bacteria: 1
Archaea: 37
Arthropoda: 7576
Eukaryota: 42746
Metazoa: 32758
Mouse: 337
Nematoda: 2719
Rice: 84
Arthropoda: 492
Fungi: 127
GreenPlants: 188
GreenPlants: 783
Metazoa: 49
Unclassified: 1
Archaea: 2
Arthropoda: 7084
Metazoa: 207
Cyanobacteria: 1
Metazoa: 82
Bacteria: 3