DegronMD - P08069(IGF1R)

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.; FUNCTION: 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. View more >>

GO - Biological processes (BP): amyloid-beta clearance [GO:0097242]; axonogenesis [GO:0007409]; cardiac atrium development [GO:0003230]; cellular response to aldosterone [GO:1904045]; cellular response to amyloid-beta [GO:1904646]; cellular response to angiotensin [GO:1904385]; cellular response to dexamethasone stimulus [GO:0071549]; cellular response to estradiol stimulus [GO:0071392]; cellular response to glucose stimulus [GO:0071333]; cellular response to insulin-like growth factor stimulus [GO:1990314]; cellular response to mechanical stimulus [GO:0071260]; cellular response to progesterone stimulus [GO:0071393]; cellular response to testosterone stimulus [GO:0071394]; cellular response to transforming growth factor beta stimulus [GO:0071560]; cellular senescence [GO:0090398]; cerebellum development [GO:0021549]; dendritic spine maintenance [GO:0097062]; establishment of cell polarity [GO:0030010]; estrous cycle [GO:0044849]; glucose homeostasis [GO:0042593]; hippocampus development [GO:0021766]; immune response [GO:0006955]; insulin-like growth factor receptor signaling pathway [GO:0048009]; insulin receptor signaling pathway [GO:0008286]; negative regulation of apoptotic process [GO:0043066]; negative regulation of cholangiocyte apoptotic process [GO:1904193]; negative regulation of hepatocyte apoptotic process [GO:1903944]; negative regulation of MAPK cascade [GO:0043409]; negative regulation of muscle cell apoptotic process [GO:0010656]; peptidyl-tyrosine autophosphorylation [GO:0038083]; phosphatidylinositol 3-kinase signaling [GO:0014065]; phosphatidylinositol-mediated signaling [GO:0048015]; positive regulation of axon regeneration [GO:0048680]; positive regulation of cell migration [GO:0030335]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of cold-induced thermogenesis [GO:0120162]; positive regulation of cytokinesis [GO:0032467]; positive regulation of DNA metabolic process [GO:0051054]; positive regulation of kinase activity [GO:0033674]; positive regulation of MAPK cascade [GO:0043410]; positive regulation of osteoblast proliferation [GO:0033690]; positive regulation of phosphatidylinositol 3-kinase signaling [GO:0014068]; positive regulation of protein-containing complex disassembly [GO:0043243]; positive regulation of protein kinase B signaling [GO:0051897]; positive regulation of smooth muscle cell proliferation [GO:0048661]; positive regulation of steroid hormone biosynthetic process [GO:0090031]; protein autophosphorylation [GO:0046777]; regulation of JNK cascade [GO:0046328]; response to ethanol [GO:0045471]; response to L-glutamate [GO:1902065]; response to nicotine [GO:0035094]; response to vitamin E [GO:0033197]; signal transduction [GO:0007165]; transcytosis [GO:0045056]; transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S1365L	TCGA-A5-A0G2	UCEC	TCGA	PQSST	DEG_SPOP_SBC_1	1362:1366	Mutation altering degron motif	0.7667
p.S1365L	SIDM00061	Ovarian Carcinoma	GDSC	PQSST	DEG_SPOP_SBC_1	1362:1366	Mutation altering degron motif	0.7667
p.S1313F	TCGA-BH-A0HF	BRCA	TCGA	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation altering degron motif	0.9093
p.V1303I	TCGA-CN-4740	HNSC	TCGA	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.1667
p.V1303I	SIDM00999	Bladder Carcinoma	GDSC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.1667
p.P1304H	TCGA-D3-A1Q1	SKCM	TCGA	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.1944
p.R1319T	TCGA-DU-A7T6	LGG	TCGA	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.1667
p.R1357L	TCGA-EE-A3AA	SKCM	TCGA	PQSST	DEG_SPOP_SBC_1	1362:1366	Mutation rewiring degron network	0.1944
p.T1366A	TCGA-IB-7651	PAAD	TCGA	PQSST	DEG_SPOP_SBC_1	1362:1366	Mutation altering degron motif	0.825
p.S1312F	DO1749	BRCA	ICGC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation altering degron motif	0.9093
p.K1353N	DO224739	COCA	ICGC	PQSST	DEG_SPOP_SBC_1	1362:1366	Mutation rewiring degron network	0.0833
p.M1299I	DO233646	GACA	ICGC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.0556
p.S1310A	DO233840	GACA	ICGC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation altering degron motif	0.7588
p.V1302I	DO14846	HNSC	ICGC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.1389
p.V1302I	ACH-000973	Bladder Cancer	CCLE	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.1389
p.R1318T	DO51814	LGG	ICGC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.1944
p.G1321E	DO231941	LICA	ICGC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation blocking phosphorylation signal	0.5556
p.S1307A	DO228405	LICA	ICGC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.2778
p.S1301I	DO229024	LICA	ICGC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.1111
p.E1355V	DO50762	LICA	ICGC	PQSST	DEG_SPOP_SBC_1	1362:1366	Mutation rewiring degron network	0.1389
p.S1312P	DO45055	LINC	ICGC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation altering degron motif	0.7863
p.S1364L	DO220873	MELA	ICGC	PQSST	DEG_SPOP_SBC_1	1362:1366	Mutation altering degron motif	0.7667
p.S1364L	DO41235	UCEC	ICGC	PQSST	DEG_SPOP_SBC_1	1362:1366	Mutation altering degron motif	0.7667
p.T1365A	DO46657	PAAD	ICGC	PQSST	DEG_SPOP_SBC_1	1362:1366	Mutation altering degron motif	0.7139
p.R1356L	DO37571	SKCM	ICGC	PQSST	DEG_SPOP_SBC_1	1362:1366	Mutation rewiring degron network	0.1667
p.P1303H	DO37445	SKCM	ICGC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.1667
p.R1353H	SIDM01043	Other Sarcomas	GDSC	PQSST	DEG_SPOP_SBC_1	1362:1366	Mutation rewiring degron network	0.0833
p.S1308L	SIDM00217	Colorectal Carcinoma	GDSC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.3056
p.S1308L	SNU-1040	large intestine	COSMIC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.3056
p.D1318N	SIDM01228	Melanoma	GDSC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.1944
p.D1318N	CHL-1	skin	COSMIC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.1944
p.D1317N	ACH-000931	Skin Cancer	CCLE	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.2222
p.D1317N	ACH-001024	Skin Cancer	CCLE	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.2222
p.D1317N	ACH-001041	Skin Cancer	CCLE	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.2222
p.D1317N	CHL-1	skin	COSMIC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.2222
p.S1307L	ACH-000999	Colon/Colorectal Cancer	CCLE	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.2778
p.S1307L	SNU-1040	large intestine	COSMIC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation rewiring degron network	0.2778
p.S1311L	SNU-1040	large intestine	COSMIC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation altering degron motif	0.8778
p.S1310L	SNU-1040	large intestine	COSMIC	ASSSS	DEG_SPOP_SBC_1	1309:1313	Mutation altering degron motif	0.7667

Kaplan plot for IGF1R in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

IGF1R

UniProt ID: P08069

Entrez ID: 3480

Protein name: Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor) (CD antigen CD221) [Cleaved into: Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain]

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for IGF1R in