IGF1R: Polycystic Ovarian Syndrome Database

Gene Information

Gene Symbol

IGF1R

Aliases

CD221, IGFIR, IGFR, JTK13

Entrez Gene ID

3480

Gene Name

Insulin like growth factor 1 receptor

Chromosomal Location

15q26.3

HGNC ID

HGNC:5465

Summary

This receptor binds insulin-like growth factor with a high affinity. It has tyrosine kinase activity. The insulin-like growth factor I receptor plays a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. It is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

RefSeq DNA

NG_009492.1

RefSeq mRNA

NM_000875.5, NM_001291858.2

e!Ensembl

Gene	ENSG00000140443
Transcript	ENST00000650285, ENST00000649865, ENST00000558355, ENST00000558898, ENST00000560144
Protein	ENSP00000497069, ENSP00000496919, ENSP00000453630, ENSP00000454115, ENSP00000456950

Gene Ontology (GO)

Show/Hide all(52 )

GO ID	Ontology	Function	Evidence	Reference
GO:0006955	Biological process	Immune response	IMP	16886151
GO:0007165	Biological process	Signal transduction	TAS	3003744
GO:0007169	Biological process	Transmembrane receptor protein tyrosine kinase signaling pathway	IBA	21873635
GO:0008284	Biological process	Positive regulation of cell proliferation	IMP	12138094
GO:0008286	Biological process	Insulin receptor signaling pathway	ISS	19406747
GO:0014065	Biological process	Phosphatidylinositol 3-kinase signaling	IC	7541045
GO:0014068	Biological process	Positive regulation of phosphatidylinositol 3-kinase signaling	IBA	21873635
GO:0030335	Biological process	Positive regulation of cell migration	IMP	12138094
GO:0038083	Biological process	Peptidyl-tyrosine autophosphorylation	IMP	19545541
GO:0042593	Biological process	Glucose homeostasis	IBA	21873635
GO:0043066	Biological process	Negative regulation of apoptotic process	IDA	12556535
GO:0043243	Biological process	Positive regulation of protein complex disassembly	ISS	19406747
GO:0043410	Biological process	Positive regulation of MAPK cascade	IBA	21873635
GO:0046328	Biological process	Regulation of JNK cascade	IBA	21873635
GO:0046328	Biological process	Regulation of JNK cascade	IDA	12556535
GO:0046777	Biological process	Protein autophosphorylation	IDA	1846292, 7679099, 11162456
GO:0048009	Biological process	Insulin-like growth factor receptor signaling pathway	IBA	21873635
GO:0048009	Biological process	Insulin-like growth factor receptor signaling pathway	IDA	7679099
GO:0048015	Biological process	Phosphatidylinositol-mediated signaling	IDA	7692086
GO:0048856	Biological process	Anatomical structure development	IBA	21873635
GO:0051262	Biological process	Protein tetramerization	IDA	1846292
GO:0051389	Biological process	Inactivation of MAPKK activity	IDA	12556535
GO:0051897	Biological process	Positive regulation of protein kinase B signaling	IBA	21873635
GO:0071333	Biological process	Cellular response to glucose stimulus	IBA	21873635
GO:0097062	Biological process	Dendritic spine maintenance	ISS	19406747
GO:0097242	Biological process	Amyloid-beta clearance	IMP	19406747
GO:0120162	Biological process	Positive regulation of cold-induced thermogenesis	ISS	26910308
GO:1904646	Biological process	Cellular response to amyloid-beta	IGI	22635104
GO:0005887	Cellular component	Integral component of plasma membrane	IBA	21873635
GO:0005887	Cellular component	Integral component of plasma membrane	IC	7679099
GO:0005899	Cellular component	Insulin receptor complex	IBA	21873635
GO:0016020	Cellular component	Membrane	IDA	8452530
GO:0030424	Cellular component	Axon	IBA	21873635
GO:0035867	Cellular component	Alphav-beta3 integrin-IGF-1-IGF1R complex	IDA	19578119
GO:0043231	Cellular component	Intracellular membrane-bounded organelle	IDA	8452530
GO:0043235	Cellular component	Receptor complex	IBA	21873635
GO:0043235	Cellular component	Receptor complex	IDA	23382219
GO:0004713	Molecular function	Protein tyrosine kinase activity	IDA	7679099, 11162456
GO:0004713	Molecular function	Protein tyrosine kinase activity	IMP	11884589
GO:0004714	Molecular function	Transmembrane receptor protein tyrosine kinase activity	IBA	21873635
GO:0005009	Molecular function	Insulin-activated receptor activity	IBA	21873635
GO:0005010	Molecular function	Insulin-like growth factor-activated receptor activity	IDA	7679099
GO:0005158	Molecular function	Insulin receptor binding	IDA	8452530
GO:0005515	Molecular function	Protein binding	IPI	7541045, 7589433, 7642582, 8452530, 8603569, 8895367, 8999839, 9480911, 9727029, 10026153, 11724822, 12482592, 12556535, 15878855, 15976035, 15998644, 16926280, 17360667, 20195357, 21645859, 21685939, 22245152, 22261717, 25241761, 25416956, 26027733, 26692333
GO:0005520	Molecular function	Insulin-like growth factor binding	IDA	1846292, 7679099
GO:0031994	Molecular function	Insulin-like growth factor I binding	IDA	19578119
GO:0031994	Molecular function	Insulin-like growth factor I binding	IPI	8452530
GO:0042802	Molecular function	Identical protein binding	IPI	11448933, 17586502, 21645859
GO:0043548	Molecular function	Phosphatidylinositol 3-kinase binding	IPI	7541045
GO:0043559	Molecular function	Insulin binding	IPI	8452530
GO:0043560	Molecular function	Insulin receptor substrate binding	IBA	21873635
GO:0043560	Molecular function	Insulin receptor substrate binding	IPI	7541045

Protein Information

Protein Name

Insulin-like growth factor 1 receptor, IGF-I receptor, soluble IGF1R variant 1, soluble IGF1R variant 2

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

Refseq Proteins

NP_000866.1, NP_001278787.1

UniProt

P08069

PDB

1IGR, 1JQH, 1K3A, 1M7N, 1P4O, 2OJ9, 2ZM3, 3D94, 3F5P, 3I81, 3LVP, 3LW0, 3NW5, 3NW6, 3NW7, 3O23, 3QQU, 4D2R, 4XSS, 5FXQ, 5FXR, 5FXS, 5HZN, 5U8Q, 5U8R

Pfam

Pfam Accession	Pfam ID
PF00757	Furin-like
PF07714	Pkinase_Tyr
PF01030	Recep_L_domain

IGF1R

Altered expression of insulin and insulin-like growth factor-I receptors in follicular and stromal compartments of polycystic ovaries.