Summary | |
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Symbol | INSR |
Name | insulin receptor |
Aliases | CD220; HHF5; IR; CD antigen CD220 |
Chromosomal Location | 19p13.3-p13.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway |
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 the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, 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. |
Biological Process |
GO:0000187 activation of MAPK activity GO:0000271 polysaccharide biosynthetic process GO:0003007 heart morphogenesis GO:0005976 polysaccharide metabolic process GO:0005977 glycogen metabolic process GO:0005978 glycogen biosynthetic process GO:0005979 regulation of glycogen biosynthetic process GO:0005996 monosaccharide metabolic process GO:0006006 glucose metabolic process GO:0006073 cellular glucan metabolic process GO:0006090 pyruvate metabolic process GO:0006091 generation of precursor metabolites and energy GO:0006096 glycolytic process GO:0006109 regulation of carbohydrate metabolic process GO:0006110 regulation of glycolytic process GO:0006112 energy reserve metabolic process GO:0006140 regulation of nucleotide metabolic process GO:0006165 nucleoside diphosphate phosphorylation GO:0006260 DNA replication GO:0006275 regulation of DNA replication GO:0006732 coenzyme metabolic process GO:0006733 oxidoreduction coenzyme metabolic process GO:0006757 ATP generation from ADP GO:0006809 nitric oxide biosynthetic process GO:0007067 mitotic nuclear division GO:0007088 regulation of mitotic nuclear division GO:0007346 regulation of mitotic cell cycle GO:0007507 heart development GO:0007530 sex determination GO:0007548 sex differentiation GO:0008286 insulin receptor signaling pathway GO:0008406 gonad development GO:0008544 epidermis development GO:0008584 male gonad development GO:0008585 female gonad development GO:0008643 carbohydrate transport GO:0008645 hexose transport GO:0009116 nucleoside metabolic process GO:0009118 regulation of nucleoside metabolic process GO:0009119 ribonucleoside metabolic process GO:0009123 nucleoside monophosphate metabolic process GO:0009126 purine nucleoside monophosphate metabolic process GO:0009132 nucleoside diphosphate metabolic process GO:0009135 purine nucleoside diphosphate metabolic process GO:0009141 nucleoside triphosphate metabolic process GO:0009144 purine nucleoside triphosphate metabolic process GO:0009150 purine ribonucleotide metabolic process GO:0009161 ribonucleoside monophosphate metabolic process GO:0009167 purine ribonucleoside monophosphate metabolic process GO:0009179 purine ribonucleoside diphosphate metabolic process GO:0009185 ribonucleoside diphosphate metabolic process GO:0009199 ribonucleoside triphosphate metabolic process GO:0009205 purine ribonucleoside triphosphate metabolic process GO:0009250 glucan biosynthetic process GO:0009894 regulation of catabolic process GO:0009896 positive regulation of catabolic process GO:0010675 regulation of cellular carbohydrate metabolic process GO:0010676 positive regulation of cellular carbohydrate metabolic process GO:0010827 regulation of glucose transport GO:0010828 positive regulation of glucose transport GO:0010906 regulation of glucose metabolic process GO:0010907 positive regulation of glucose metabolic process GO:0010962 regulation of glucan biosynthetic process GO:0015749 monosaccharide transport GO:0015758 glucose transport GO:0015980 energy derivation by oxidation of organic compounds GO:0016051 carbohydrate biosynthetic process GO:0016052 carbohydrate catabolic process GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0019048 modulation by virus of host morphology or physiology GO:0019087 transformation of host cell by virus GO:0019318 hexose metabolic process GO:0019362 pyridine nucleotide metabolic process GO:0030238 male sex determination GO:0030325 adrenal gland development GO:0030335 positive regulation of cell migration GO:0031016 pancreas development GO:0031017 exocrine pancreas development GO:0031329 regulation of cellular catabolic process GO:0031331 positive regulation of cellular catabolic process GO:0032147 activation of protein kinase activity GO:0032148 activation of protein kinase B activity GO:0032868 response to insulin GO:0032869 cellular response to insulin stimulus GO:0032881 regulation of polysaccharide metabolic process GO:0032885 regulation of polysaccharide biosynthetic process GO:0033500 carbohydrate homeostasis GO:0033674 positive regulation of kinase activity GO:0033692 cellular polysaccharide biosynthetic process GO:0034637 cellular carbohydrate biosynthetic process GO:0035270 endocrine system development GO:0035272 exocrine system development GO:0035821 modification of morphology or physiology of other organism GO:0038083 peptidyl-tyrosine autophosphorylation GO:0040017 positive regulation of locomotion GO:0042278 purine nucleoside metabolic process GO:0042593 glucose homeostasis GO:0043255 regulation of carbohydrate biosynthetic process GO:0043405 regulation of MAP kinase activity GO:0043406 positive regulation of MAP kinase activity GO:0043410 positive regulation of MAPK cascade GO:0043434 response to peptide hormone GO:0043467 regulation of generation of precursor metabolites and energy GO:0043470 regulation of carbohydrate catabolic process GO:0043491 protein kinase B signaling GO:0044003 modification by symbiont of host morphology or physiology GO:0044042 glucan metabolic process GO:0044262 cellular carbohydrate metabolic process GO:0044264 cellular polysaccharide metabolic process GO:0044723 single-organism carbohydrate metabolic process GO:0044724 single-organism carbohydrate catabolic process GO:0045137 development of primary sexual characteristics GO:0045428 regulation of nitric oxide biosynthetic process GO:0045429 positive regulation of nitric oxide biosynthetic process GO:0045725 positive regulation of glycogen biosynthetic process GO:0045730 respiratory burst GO:0045740 positive regulation of DNA replication GO:0045787 positive regulation of cell cycle GO:0045821 positive regulation of glycolytic process GO:0045840 positive regulation of mitotic nuclear division GO:0045860 positive regulation of protein kinase activity GO:0045913 positive regulation of carbohydrate metabolic process GO:0045927 positive regulation of growth GO:0045931 positive regulation of mitotic cell cycle GO:0045979 positive regulation of nucleoside metabolic process GO:0045981 positive regulation of nucleotide metabolic process GO:0045995 regulation of embryonic development GO:0046031 ADP metabolic process GO:0046034 ATP metabolic process GO:0046128 purine ribonucleoside metabolic process GO:0046209 nitric oxide metabolic process GO:0046323 glucose import GO:0046324 regulation of glucose import GO:0046326 positive regulation of glucose import GO:0046496 nicotinamide nucleotide metabolic process GO:0046545 development of primary female sexual characteristics GO:0046546 development of primary male sexual characteristics GO:0046660 female sex differentiation GO:0046661 male sex differentiation GO:0046777 protein autophosphorylation GO:0046939 nucleotide phosphorylation GO:0048608 reproductive structure development GO:0048638 regulation of developmental growth GO:0048639 positive regulation of developmental growth GO:0048732 gland development GO:0051052 regulation of DNA metabolic process GO:0051054 positive regulation of DNA metabolic process GO:0051186 cofactor metabolic process GO:0051193 regulation of cofactor metabolic process GO:0051194 positive regulation of cofactor metabolic process GO:0051196 regulation of coenzyme metabolic process GO:0051197 positive regulation of coenzyme metabolic process GO:0051259 protein oligomerization GO:0051262 protein tetramerization GO:0051272 positive regulation of cellular component movement GO:0051290 protein heterotetramerization GO:0051291 protein heterooligomerization GO:0051321 meiotic cell cycle GO:0051445 regulation of meiotic cell cycle GO:0051446 positive regulation of meiotic cell cycle GO:0051701 interaction with host GO:0051783 regulation of nuclear division GO:0051785 positive regulation of nuclear division GO:0051817 modification of morphology or physiology of other organism involved in symbiotic interaction GO:0051896 regulation of protein kinase B signaling GO:0051897 positive regulation of protein kinase B signaling GO:0055123 digestive system development GO:0060263 regulation of respiratory burst GO:0060267 positive regulation of respiratory burst GO:0061458 reproductive system development GO:0070873 regulation of glycogen metabolic process GO:0070875 positive regulation of glycogen metabolic process 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:0071902 positive regulation of protein serine/threonine kinase activity GO:0072524 pyridine-containing compound metabolic process GO:0072593 reactive oxygen species metabolic process GO:0090068 positive regulation of cell cycle process GO:1900542 regulation of purine nucleotide metabolic process GO:1900544 positive regulation of purine nucleotide metabolic process GO:1901652 response to peptide GO:1901653 cellular response to peptide GO:1901657 glycosyl compound metabolic process GO:1903409 reactive oxygen species biosynthetic process GO:1903426 regulation of reactive oxygen species biosynthetic process GO:1903428 positive regulation of reactive oxygen species biosynthetic process GO:1903578 regulation of ATP metabolic process GO:1903580 positive regulation of ATP metabolic process GO:1904407 positive regulation of nitric oxide metabolic process GO:2000147 positive regulation of cell motility GO:2000194 regulation of female gonad development GO:2000241 regulation of reproductive process GO:2000243 positive regulation of reproductive process GO:2000377 regulation of reactive oxygen species metabolic process GO:2000379 positive regulation of reactive oxygen species metabolic process GO:2001057 reactive nitrogen species metabolic process |
Molecular Function |
GO:0004713 protein tyrosine kinase activity GO:0004714 transmembrane receptor protein tyrosine kinase activity GO:0004716 receptor signaling protein tyrosine kinase activity GO:0005009 insulin-activated receptor activity GO:0005057 receptor signaling protein activity GO:0005159 insulin-like growth factor receptor binding GO:0005520 insulin-like growth factor binding GO:0005525 GTP binding GO:0017046 peptide hormone binding GO:0019001 guanyl nucleotide binding GO:0019199 transmembrane receptor protein kinase activity GO:0019838 growth factor binding GO:0031994 insulin-like growth factor I binding GO:0031995 insulin-like growth factor II binding GO:0032561 guanyl ribonucleotide 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 GO:0051425 PTB domain binding |
Cellular Component |
GO:0005899 insulin receptor complex GO:0005901 caveola GO:0010008 endosome membrane GO:0043235 receptor complex GO:0044440 endosomal part GO:0044853 plasma membrane raft GO:0045121 membrane raft GO:0061695 transferase complex, transferring phosphorus-containing groups GO:0098589 membrane region GO:0098802 plasma membrane receptor complex GO:0098857 membrane microdomain GO:1902911 protein kinase complex |
KEGG |
hsa04014 Ras signaling pathway hsa04015 Rap1 signaling pathway hsa04022 cGMP-PKG signaling pathway hsa04066 HIF-1 signaling pathway hsa04068 FoxO signaling pathway hsa04150 mTOR signaling pathway hsa04151 PI3K-Akt signaling pathway hsa04152 AMPK signaling pathway hsa04520 Adherens junction hsa04910 Insulin signaling pathway hsa04913 Ovarian steroidogenesis hsa04960 Aldosterone-regulated sodium reabsorption |
Reactome |
R-HSA-1280218: Adaptive Immune System R-HSA-2172127: DAP12 interactions R-HSA-2424491: DAP12 signaling R-HSA-186763: Downstream signal transduction R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR) R-HSA-2454202: Fc epsilon receptor (FCERI) signaling R-HSA-180292: GAB1 signalosome R-HSA-74713: IRS activation R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-77387: Insulin receptor recycling R-HSA-74751: Insulin receptor signalling cascade R-HSA-187037: NGF signalling via TRKA from the plasma membrane R-HSA-199418: Negative regulation of the PI3K/AKT network R-HSA-198203: PI3K/AKT activation R-HSA-6811558: PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-1257604: PIP3 activates AKT signaling R-HSA-2730905: Role of LAT2/NTAL/LAB on calcium mobilization R-HSA-162582: Signal Transduction R-HSA-74749: Signal attenuation R-HSA-177929: Signaling by EGFR R-HSA-74752: Signaling by Insulin receptor R-HSA-186797: Signaling by PDGF R-HSA-1433557: Signaling by SCF-KIT R-HSA-983705: Signaling by the B Cell Receptor (BCR) R-HSA-166520: Signalling by NGF |
Summary | |
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Symbol | INSR |
Name | insulin receptor |
Aliases | CD220; HHF5; IR; CD antigen CD220 |
Chromosomal Location | 19p13.3-p13.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Literatures that report relations between INSR 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. |
There is no record. |
Summary | |
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Symbol | INSR |
Name | insulin receptor |
Aliases | CD220; HHF5; IR; CD antigen CD220 |
Chromosomal Location | 19p13.3-p13.2 |
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
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Statistical results of INSR in screening data sets for detecting immune reponses.
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Summary | |
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Symbol | INSR |
Name | insulin receptor |
Aliases | CD220; HHF5; IR; CD antigen CD220 |
Chromosomal Location | 19p13.3-p13.2 |
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 |
Points in the above scatter plot represent the expression difference of INSR in various data sets.
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Points in the above scatter plot represent the mutation difference of INSR in various data sets.
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Summary | |
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Symbol | INSR |
Name | insulin receptor |
Aliases | CD220; HHF5; IR; CD antigen CD220 |
Chromosomal Location | 19p13.3-p13.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of INSR. 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. |
Summary | |
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Symbol | INSR |
Name | insulin receptor |
Aliases | CD220; HHF5; IR; CD antigen CD220 |
Chromosomal Location | 19p13.3-p13.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of INSR. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by INSR. > Immunoinhibitor > Immunostimulator > MHC molecule |
Summary | |
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Symbol | INSR |
Name | insulin receptor |
Aliases | CD220; HHF5; IR; CD antigen CD220 |
Chromosomal Location | 19p13.3-p13.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of INSR. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor |
Summary | |
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Symbol | INSR |
Name | insulin receptor |
Aliases | CD220; HHF5; IR; CD antigen CD220 |
Chromosomal Location | 19p13.3-p13.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Distribution of INSR expression across immune and molecular subtypes. > Immune subtype > Molecular subtype |
Summary | |
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Symbol | INSR |
Name | insulin receptor |
Aliases | CD220; HHF5; IR; CD antigen CD220 |
Chromosomal Location | 19p13.3-p13.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Associations between INSR and clinical features. > Overall survival analysis > Cancer stage > Tumor grade |
Summary | |
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Symbol | INSR |
Name | insulin receptor |
Aliases | CD220; HHF5; IR; CD antigen CD220 |
Chromosomal Location | 19p13.3-p13.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Drugs targeting INSR collected from DrugBank database. |
Details on drugs targeting INSR.
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