Browse IGF1R

Summary
SymbolIGF1R
Nameinsulin-like growth factor 1 receptor
Aliases JTK13; CD221; IGFIR; MGC18216; IGFR; IGF-I receptor; insulin-like growth factor I receptor; soluble IGF1R va ......
Chromosomal Location15q26.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cell membrane Single-pass type I membrane protein
Domain PF00757 Furin-like cysteine rich region
PF07714 Protein tyrosine kinase
PF01030 Receptor L domain
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.

> Gene Ontology
 
Biological Process GO:0001933 negative regulation of protein phosphorylation
GO:0006260 DNA replication
GO:0006275 regulation of DNA replication
GO:0006469 negative regulation of protein kinase activity
GO:0007254 JNK cascade
GO:0008286 insulin receptor signaling pathway
GO:0014065 phosphatidylinositol 3-kinase signaling
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0030335 positive regulation of cell migration
GO:0031098 stress-activated protein kinase signaling cascade
GO:0032868 response to insulin
GO:0032869 cellular response to insulin stimulus
GO:0032872 regulation of stress-activated MAPK cascade
GO:0033673 negative regulation of kinase activity
GO:0038083 peptidyl-tyrosine autophosphorylation
GO:0040017 positive regulation of locomotion
GO:0042326 negative regulation of phosphorylation
GO:0043405 regulation of MAP kinase activity
GO:0043409 negative regulation of MAPK cascade
GO:0043434 response to peptide hormone
GO:0045740 positive regulation of DNA replication
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:0048017 inositol lipid-mediated signaling
GO:0051052 regulation of DNA metabolic process
GO:0051054 positive regulation of DNA metabolic process
GO:0051259 protein oligomerization
GO:0051262 protein tetramerization
GO:0051272 positive regulation of cellular component movement
GO:0051348 negative regulation of transferase activity
GO:0051389 inactivation of MAPKK activity
GO:0051403 stress-activated MAPK cascade
GO:0070302 regulation of stress-activated protein kinase signaling cascade
GO:0071375 cellular response to peptide hormone stimulus
GO:0071417 cellular response to organonitrogen compound
GO:0071900 regulation of protein serine/threonine kinase activity
GO:1901652 response to peptide
GO:1901653 cellular response to peptide
GO:1902532 negative regulation of intracellular signal transduction
GO:2000147 positive regulation of cell motility
Molecular Function 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:0005520 insulin-like growth factor binding
GO:0017046 peptide hormone binding
GO:0019199 transmembrane receptor protein kinase activity
GO:0019838 growth factor binding
GO:0031994 insulin-like growth factor I binding
GO:0033218 amide binding
GO:0042277 peptide binding
GO:0042562 hormone binding
GO:0043548 phosphatidylinositol 3-kinase binding
GO:0043559 insulin binding
GO:0043560 insulin receptor substrate binding
Cellular Component GO:0035867 alphav-beta3 integrin-IGF-1-IGF1R complex
GO:0043235 receptor complex
> KEGG and Reactome Pathway
 
KEGG hsa04014 Ras signaling pathway
hsa04015 Rap1 signaling pathway
hsa04066 HIF-1 signaling pathway
hsa04068 FoxO signaling pathway
hsa04114 Oocyte meiosis
hsa04140 Regulation of autophagy
hsa04144 Endocytosis
hsa04150 mTOR signaling pathway
hsa04151 PI3K-Akt signaling pathway
hsa04152 AMPK signaling pathway
hsa04510 Focal adhesion
hsa04520 Adherens junction
hsa04550 Signaling pathways regulating pluripotency of stem cells
hsa04730 Long-term depression
hsa04913 Ovarian steroidogenesis
hsa04914 Progesterone-mediated oocyte maturation
Reactome R-HSA-2428924: IGF1R signaling cascade
R-HSA-2428928: IRS-related events triggered by IGF1R
R-HSA-2428933: SHC-related events triggered by IGF1R
R-HSA-162582: Signal Transduction
R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
Summary
SymbolIGF1R
Nameinsulin-like growth factor 1 receptor
Aliases JTK13; CD221; IGFIR; MGC18216; IGFR; IGF-I receptor; insulin-like growth factor I receptor; soluble IGF1R va ......
Chromosomal Location15q26.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between IGF1R and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between IGF1R and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
16517711Breast CarcinomaInhibit immunity (T cell function); immunotherapy targetImmunization with murine breast cancer cells treated with antisense oligodeoxynucleotides to type I insulin-like growth factor receptor induced an antitumoral effect mediated by a CD8+ response involving Fas/Fas ligand cytotoxic pathway.
18829562RhabdomyosarcomaInhibit immunity; Immunotherapy targetAddiction to elevated insulin-like growth factor I receptor and initial modulation of the AKT pathway define the responsiveness of rhabdomyosarcoma to the targeting antibody. Insulin-like growth factor I receptor (IGF-IR) and its ligands are overexpressed by tumors, mediating proliferation and protecting against stress-induced apoptosis.
Summary
SymbolIGF1R
Nameinsulin-like growth factor 1 receptor
Aliases JTK13; CD221; IGFIR; MGC18216; IGFR; IGF-I receptor; insulin-like growth factor I receptor; soluble IGF1R va ......
Chromosomal Location15q26.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of IGF1R in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolIGF1R
Nameinsulin-like growth factor 1 receptor
Aliases JTK13; CD221; IGFIR; MGC18216; IGFR; IGF-I receptor; insulin-like growth factor I receptor; soluble IGF1R va ......
Chromosomal Location15q26.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of IGF1R in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.4210.238
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.4880.763
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.3640.785
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.1320.774
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.0380.988
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.3420.912
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.0590.906
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.5740.761
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.5030.81
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.6030.544
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.3230.34
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.3080.00384
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of IGF1R in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277318.52.715.80.0147
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275918.53.415.10.0291
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.55.93.61
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.79.1-1.41
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38277.907.90.26
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22139.109.10.519
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11139.109.10.458
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 6116.7016.71
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolIGF1R
Nameinsulin-like growth factor 1 receptor
Aliases JTK13; CD221; IGFIR; MGC18216; IGFR; IGF-I receptor; insulin-like growth factor I receptor; soluble IGF1R va ......
Chromosomal Location15q26.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IGF1R. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolIGF1R
Nameinsulin-like growth factor 1 receptor
Aliases JTK13; CD221; IGFIR; MGC18216; IGFR; IGF-I receptor; insulin-like growth factor I receptor; soluble IGF1R va ......
Chromosomal Location15q26.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IGF1R. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IGF1R.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolIGF1R
Nameinsulin-like growth factor 1 receptor
Aliases JTK13; CD221; IGFIR; MGC18216; IGFR; IGF-I receptor; insulin-like growth factor I receptor; soluble IGF1R va ......
Chromosomal Location15q26.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IGF1R. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolIGF1R
Nameinsulin-like growth factor 1 receptor
Aliases JTK13; CD221; IGFIR; MGC18216; IGFR; IGF-I receptor; insulin-like growth factor I receptor; soluble IGF1R va ......
Chromosomal Location15q26.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of IGF1R expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolIGF1R
Nameinsulin-like growth factor 1 receptor
Aliases JTK13; CD221; IGFIR; MGC18216; IGFR; IGF-I receptor; insulin-like growth factor I receptor; soluble IGF1R va ......
Chromosomal Location15q26.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between IGF1R and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolIGF1R
Nameinsulin-like growth factor 1 receptor
Aliases JTK13; CD221; IGFIR; MGC18216; IGFR; IGF-I receptor; insulin-like growth factor I receptor; soluble IGF1R va ......
Chromosomal Location15q26.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting IGF1R collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting IGF1R.
ID Name Drug Type Targets #Targets
DB00030Insulin HumanBiotechCPE, CTSD, IDE, IGF1R, IGFBP7, INSR, LRP2, NOV, PCSK1, PCSK2, RB1, ......12
DB00046Insulin LisproBiotechIGF1R, INSR2
DB00047Insulin GlargineBiotechIGF1R, INSR2
DB00071Insulin PorkBiotechCPE, CTSD, HLA-DQA2, HLA-DQB1, IDE, IGF1R, IGFBP7, INSR, LRP2, NOV ......14
DB01277MecaserminBiotechIGF1R, IGF2R, IGFBP3, INSR4
DB04395Phosphoaminophosphonic Acid-Adenylate EsterSmall MoleculeACTA1, CCT3, CFTR, CSNK2A1, DAPK1, DTYMK, EPHA2, EPHB2, GALK1, GSK ......26
DB05023ATL1101Small MoleculeIGF1R1
DB05184XL228Small MoleculeABL1, ABL2, IGF1R, SRC4
DB05897rhIGFBP-3Small MoleculeIGF1R1
DB06075LinsitinibSmall MoleculeIGF1R1
DB07156(4Z)-6-bromo-4-({[4-(pyrrolidin-1-ylmethyl)phenyl]amino}methylidene)isoquinoline-1,3(2H,4H)-dioneSmall MoleculeIGF1R1
DB074743-[5-(1H-IMIDAZOL-1-YL)-7-METHYL-1H-BENZIMIDAZOL-2-YL]-4-[(PYRIDIN-2-YLMETHYL)AMINO]PYRIDIN-2(1H)-ONESmall MoleculeIGF1R1
DB09098SomatremBiotechGHR, IGF1R2
DB12250CixutumumabBiotechIGF1R1
DB12267BrigatinibSmall MoleculeABL1, ALK, EGFR, ERBB2, ERBB4, FLT3, IGF1R, INSR, MET9