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insulin-like growth factor [IGF]-1 receptor (somatomedin-C receptor, CD221, IGF1R)

Function: - binds insulin-like growth factor 1 (IGF1) with a high affinity & IGF2 with a lower affinity - tyrosine-protein kinase activity actvates IGF1-stimulated downstream signaling cascade - interacts with PIK3R1 & with the PTB/PID domains of IRS1 & SHC1 in vitro when autophosphorylated on Tyr - autophosphorylation activates the kinase activity - cytoplasmic domain of the beta subunit is autophosphorylated on Tyr in response to insulin-like growth factor 1 (IG1) - phosphorylation of Tyr-980 is required for IRS1- & SHC1- binding Structure: - tetramer of 2 alpha & 2 beta chains linked by disulfide bonds - alpha chains contribute to the formation of the ligand-binding domain - beta chain carries the kinase domain - belongs to the protein kinase superfamily, Tyr protein kinase family, insulin receptor subfamily - contains 3 fibronectin F3 modules - contains 1 protein kinase domain Compartment: membrane Expression: expressed in a variety of tissues Pathology: - defects in IGF1R may be a cause in some cases of IGF1 resistance

Interactions

molecular events

Related

IGF1 receptor Ag in tissue insulin-like growth factor-1; mechano growth factor; MGF; somatomedin-C (IGF1, IBP1)

General

multisubunit protein tyrosine kinase receptor (RTK)

Properties

SIZE: entity length = 1367 aa MW = 155 kD COMPARTMENT: cellular membrane STATE: active state MOTIF: signal sequence {1-30} N-glycosylation site {N51} N-glycosylation site {N102} N-glycosylation site {N135} cysteine residue {C215} MODIFICATION: cysteine residue {C224} cysteine residue {C219} MODIFICATION: cysteine residue {C230} cysteine residue {C224} MODIFICATION: cysteine residue {C215} cysteine residue {C230} MODIFICATION: cysteine residue {C219} cysteine residue {C231} MODIFICATION: cysteine residue {C239} cysteine residue {C235} MODIFICATION: cysteine residue {C248} cysteine residue {C239} MODIFICATION: cysteine residue {C231} N-glycosylation site {N244} cysteine residue {C248} MODIFICATION: cysteine residue {C235} cysteine residue {C251} MODIFICATION: cysteine residue {C260} cysteine residue {C260} MODIFICATION: cysteine residue {C251} cysteine residue {C264} MODIFICATION: cysteine residue {C276} cysteine residue {C276} MODIFICATION: cysteine residue {C264} cysteine residue {C282} MODIFICATION: cysteine residue {C303} cysteine residue {C303} MODIFICATION: cysteine residue {C282} cysteine residue {C307} MODIFICATION: cysteine residue {C321} N-glycosylation site {N314} cysteine residue {C321} MODIFICATION: cysteine residue {C307} cysteine residue {C324} MODIFICATION: cysteine residue {C328} cysteine residue {C328} MODIFICATION: cysteine residue {C324} N-glycosylation site {N417} N-glycosylation site {N438} fibronectin type III domain or F3 module {488-606} MOTIF: N-glycosylation site {N534} N-glycosylation site {N607} fibronectin type III domain or F3 module {611-689} MOTIF: N-glycosylation site {N622} N-glycosylation site {N640} N-glycosylation site {N747} N-glycosylation site {N756} N-glycosylation site {N764} fibronectin type III domain or F3 module {831-926} MOTIF: N-glycosylation site {N900} N-glycosylation site {N913} transmembrane domain {936-959} IRS1- and SHC1-binding {977-980} MOTIF: Tyr phosphorylation site {Y980} kinase domain SITE: 999-1274 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 1005-1013 ATP-binding site NAME: ATP-binding site SITE: 1033-1033 aspartate residue {D1135} Tyr phosphorylation site {Y1161} Tyr phosphorylation site {Y1165} Tyr phosphorylation site {Y1166} SUBUNITS: insulin-like growth factor [IGF]-1 receptor alpha MOTIF: signal sequence {1-30} N-glycosylation site {58-438} (7) cysteine residue {C215} MODIFICATION: cysteine residue {C224} cysteine residue {C224} MODIFICATION: cysteine residue {C215} FIBRONECTIN TYPE-III 1 {488-606} MOTIF: N-glycosylation site {N534} N-glycosylation site {N607} FIBRONECTIN TYPE-III 2 {611-689} MOTIF: N-glycosylation site {N622} N-glycosylation site {N640} insulin-like growth factor [IGF]-1 receptor beta MOTIF: N-glycosylation site {N747} N-glycosylation site {N756} N-glycosylation site {N764} FIBRONECTIN TYPE-III 3 {831-926} MOTIF: N-glycosylation site {N900} N-glycosylation site {N913} transmembrane domain {936-959} kinase domain SITE: 999-1274 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 1005-1013 ATP-binding site NAME: ATP-binding site SITE: 1033-1033 aspartate residue {D1135} Tyr phosphorylation site {Y1165}

Database Correlations

OMIM correlations MORBIDMAP 147370 UniProt P08069 PFAM correlations KEGG correlations ENZYME 2.7.10.1

References

  1. UniProt :accession P08069
  2. Wikipedia; IGF-1 receptor entry http://en.wikipedia.org/wiki/IGF-1_receptor
  3. Nishibe S et al Selectivity of phospholipase C phosphorylation by the epidermal growth factor receptor, the insulin receptor, and their cytoplasmic domains. Proc Natl Acad Sci U S A. 1990 Jan;87(1):424-8. Erratum in: Proc Natl Acad Sci U S A 1990 Apr;87(8):3253. Kim JJ [corrected to Kim JW]. PMID: 2153302
  4. Yarden Y, Ullrich A. Growth factor receptor tyrosine kinases. Annu Rev Biochem. 1988;57:443-78. Review. PMID: 3052279

Component-of

molecular complex

Components

insulin-like growth factor [IGF]-1 receptor alpha (somatomedin-C receptor alpha) insulin-like growth factor [IGF]-1 receptor beta (somatomedin-C receptor beta)