Homo sapiens Protein: IGF1R
InnateDB Protein IDBP-31434.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol IGF1R
Protein Name insulin-like growth factor 1 receptor
Synonyms CD221; IGFIR; IGFR; JTK13;
Species Homo sapiens
Ensembl Protein ENSP00000268035
InnateDB Gene IDBG-31432 (IGF1R)
Protein Structure
UniProt Annotation
Function Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K- driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R.When present in a hybrid receptor with INSR, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.
Subcellular Localization Cell membrane {ECO:0000269PubMed:17524361}; Single-pass type I membrane protein {ECO:0000269PubMed:17524361}.
Disease Associations Insulin-like growth factor 1 resistance (IGF1RES) [MIM:270450]: A disorder characterized by intrauterine growth retardation, poor postnatal growth and increased plasma IGF1 levels. {ECO:0000269PubMed:14657428, ECO:0000269PubMed:15928254}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Tissue Specificity Found as a hybrid receptor with INSR in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta (at protein level). Expressed in a variety of tissues. Overexpressed in tumors, including melanomas, cancers of the colon, pancreas prostate and kidney. {ECO:0000269PubMed:12019176, ECO:0000269PubMed:8247543, ECO:0000269PubMed:9202395, ECO:0000269PubMed:9355755}.
Number of Interactions This gene and/or its encoded proteins are associated with 118 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.
Experimentally validated
Total 118 [view]
Protein-Protein 116 [view]
Protein-DNA 2 [view]
Protein-RNA 0
Predicted by orthology
Total 5 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0001965 G-protein alpha-subunit binding
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004714 transmembrane receptor protein tyrosine kinase activity
GO:0005010 insulin-like growth factor-activated receptor activity
GO:0005158 insulin receptor binding
GO:0005515 protein binding
GO:0005520 insulin-like growth factor binding
GO:0005524 ATP binding
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0031994 insulin-like growth factor I binding
GO:0042802 identical protein binding
GO:0043548 phosphatidylinositol 3-kinase binding
GO:0043559 insulin binding
GO:0043560 insulin receptor substrate binding
Biological Process
GO:0006468 protein phosphorylation
GO:0006955 immune response
GO:0007165 signal transduction
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007409 axonogenesis
GO:0007420 brain development
GO:0008284 positive regulation of cell proliferation
GO:0008286 insulin receptor signaling pathway
GO:0008544 epidermis development
GO:0009887 organ morphogenesis
GO:0010656 negative regulation of muscle cell apoptotic process
GO:0014065 phosphatidylinositol 3-kinase signaling
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0030010 establishment of cell polarity
GO:0030238 male sex determination
GO:0030335 positive regulation of cell migration
GO:0030879 mammary gland development
GO:0031017 exocrine pancreas development
GO:0031175 neuron projection development
GO:0032467 positive regulation of cytokinesis
GO:0033197 response to vitamin E
GO:0038083 peptidyl-tyrosine autophosphorylation
GO:0043066 negative regulation of apoptotic process
GO:0043409 negative regulation of MAPK cascade
GO:0043410 positive regulation of MAPK cascade
GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity
GO:0045087 innate immune response (InnateDB)
GO:0045740 positive regulation of DNA replication
GO:0045840 positive regulation of mitosis
GO:0046328 regulation of JNK cascade
GO:0046777 protein autophosphorylation
GO:0048009 insulin-like growth factor receptor signaling pathway
GO:0048015 phosphatidylinositol-mediated signaling
GO:0051054 positive regulation of DNA metabolic process
GO:0051262 protein tetramerization
GO:0051291 protein heterooligomerization
GO:0051389 inactivation of MAPKK activity
GO:0051897 positive regulation of protein kinase B signaling
GO:0051898 negative regulation of protein kinase B signaling
GO:0060740 prostate gland epithelium morphogenesis
GO:0090031 positive regulation of steroid hormone biosynthetic process
Cellular Component
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0005901 caveola
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0043005 neuron projection
GO:0043231 intracellular membrane-bounded organelle
GO:0043235 receptor complex
Protein Structure and Domains
InterPro IPR000494 EGF receptor, L domain
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR003961 Fibronectin, type III
IPR006211 Furin-like cysteine-rich domain
IPR006212 Furin-like repeat
IPR009030 Insulin-like growth factor binding protein, N-terminal
IPR011009 Protein kinase-like domain
IPR016246 Tyrosine-protein kinase, insulin-like receptor
IPR020635 Tyrosine-protein kinase, catalytic domain
PFAM PF01030
Post-translational Modifications
SwissProt P08069
PhosphoSite PhosphoSite-P08069
UniProt Splice Variant
Entrez Gene 3480
UniGene Hs.714162
RefSeq NP_000866
OMIM 147370
HPRD 00932
EMBL AB425196 AC055807 AC069029 AC118658 AC118660 AY332722 BC113610 BC113612 M69229 X04434
GenPept AAB59399 AAI13611 AAI13613 AAP81165 BAG11657 CAA28030