HCSGD entry for IRS1

1. General information

Official gene symbolIRS1
Entrez ID3667
Gene full nameinsulin receptor substrate 1
Other gene symbolsHIRS-1
Links to Entrez GeneLinks to Entrez Gene

2. Neighbors in the network

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3. Gene ontology annotation

GO ID

GO term

Evidence

Category

GO:0002053Positive regulation of mesenchymal cell proliferationIEAbiological_process
GO:0004871Signal transducer activityIEAmolecular_function
GO:0005068Transmembrane receptor protein tyrosine kinase adaptor activityISSmolecular_function
GO:0005080Protein kinase C bindingISSmolecular_function
GO:0005158Insulin receptor bindingIPImolecular_function
GO:0005159Insulin-like growth factor receptor bindingIPImolecular_function
GO:0005515Protein bindingIPImolecular_function
GO:0005634NucleusISScellular_component
GO:0005737CytoplasmISScellular_component
GO:0005829CytosolTAScellular_component
GO:0005886Plasma membraneTAScellular_component
GO:0005899Insulin receptor complexISScellular_component
GO:0005901CaveolaIDAcellular_component
GO:0007165Signal transductionTASbiological_process
GO:0007173Epidermal growth factor receptor signaling pathwayTASbiological_process
GO:0008284Positive regulation of cell proliferationNASbiological_process
GO:0008286Insulin receptor signaling pathwayIDA IMP IPI TASbiological_process
GO:0008543Fibroblast growth factor receptor signaling pathwayTASbiological_process
GO:0010468Regulation of gene expressionIEAbiological_process
GO:0010907Positive regulation of glucose metabolic processIMPbiological_process
GO:0014065Phosphatidylinositol 3-kinase signalingIDAbiological_process
GO:0016042Lipid catabolic processIEAbiological_process
GO:0030335Positive regulation of cell migrationIEAbiological_process
GO:0030879Mammary gland developmentIEAbiological_process
GO:0032000Positive regulation of fatty acid beta-oxidationIMPbiological_process
GO:0032868Response to insulinIDAbiological_process
GO:0032869Cellular response to insulin stimulusIMPbiological_process
GO:0034504Protein localization to nucleusIEAbiological_process
GO:0038095Fc-epsilon receptor signaling pathwayTASbiological_process
GO:0042169SH2 domain bindingISSmolecular_function
GO:0042593Glucose homeostasisTASbiological_process
GO:0043231Intracellular membrane-bounded organelleISScellular_component
GO:0043434Response to peptide hormoneISSbiological_process
GO:0043491Protein kinase B signalingIEAbiological_process
GO:0043548Phosphatidylinositol 3-kinase bindingIPI ISSmolecular_function
GO:0043552Positive regulation of phosphatidylinositol 3-kinase activityISSbiological_process
GO:0045087Innate immune responseTASbiological_process
GO:0045725Positive regulation of glycogen biosynthetic processIMP NASbiological_process
GO:0046326Positive regulation of glucose importIMPbiological_process
GO:0046627Negative regulation of insulin receptor signaling pathwayISSbiological_process
GO:0046628Positive regulation of insulin receptor signaling pathwayISSbiological_process
GO:0046676Negative regulation of insulin secretionIDAbiological_process
GO:0048009Insulin-like growth factor receptor signaling pathwayIPIbiological_process
GO:0048011Neurotrophin TRK receptor signaling pathwayTASbiological_process
GO:0048015Phosphatidylinositol-mediated signalingTASbiological_process
GO:0060397JAK-STAT cascade involved in growth hormone signaling pathwayTASbiological_process
GO:2001275Positive regulation of glucose import in response to insulin stimulusIDAbiological_process
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4. Expression levels in datasets

  • Meta-analysis result

p-value upp-value downFDR upFDR down
0.97164525660.00150460850.99999024730.0754339048

  • Individual experiment result
    ( "-" represent NA in the specific microarray platform )

Data sourceUp or downLog fold change
GSE11954Down-0.1538688638
GSE13712_SHEARDown-0.3175156848
GSE13712_STATICDown-0.1137339848
GSE19018Up0.3397587382
GSE19899_A1Down-0.7031074657
GSE19899_A2Down-0.9745863610
PubMed_21979375_A1Down-2.1170213873
PubMed_21979375_A2Down-1.0647847160
GSE35957Down-0.7416179711
GSE36640Down-0.5525254358
GSE54402Down-0.7104626262
GSE9593Down-1.2078689423
GSE43922Down-0.7902777402
GSE24585Down-0.5944760705
GSE37065Up0.0962251312
GSE28863_A1Up0.7643239262
GSE28863_A2Up0.5913286581
GSE28863_A3Down-0.4091545810
GSE28863_A4Down-0.3623342406
GSE48662Down-0.6168385884

5. Regulation relationships with compounds/drugs/microRNAs

  • Compounds

Not regulated by compounds

  • Drugs

Name

Drug

Accession number

[4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACIDDB08513 -

  • MicroRNAs

  • mirTarBase

MiRNA_name

mirBase ID

miRTarBase ID

Experiment

Support type

References (Pubmed ID)

hsa-miR-145-5pMIMAT0000437MIRT000731Luciferase reporter assay//Northern blot//qRT-PCR//Western blot//Reporter assay;OtherFunctional MTI17827156
hsa-miR-145-5pMIMAT0000437MIRT000731qRT-PCR//Western blotFunctional MTI19391107
hsa-miR-145-5pMIMAT0000437MIRT000731Luciferase reporter assayFunctional MTI22431718
hsa-miR-145-5pMIMAT0000437MIRT000731Luciferase reporter assay//Western blotFunctional MTI23201159
hsa-miR-7-5pMIMAT0000252MIRT003807Western blotFunctional MTI18483236
hsa-miR-126-3pMIMAT0000445MIRT004355qRT-PCR//Luciferase reporter assay//Western blotFunctional MTI18834857
hsa-miR-126-3pMIMAT0000445MIRT004355Luciferase reporter assayFunctional MTI21464990
hsa-miR-148a-3pMIMAT0000243MIRT006859Luciferase reporter assay//Western blotFunctional MTI22935141
hsa-miR-152-3pMIMAT0000438MIRT006860Luciferase reporter assay//Western blotFunctional MTI22935141
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  • mirRecord

MicroRNA name

mirBase ID

Target site number

MiRNA mature ID

Test method inter

MiRNA regulation site

Reporter target site

Pubmed ID

hsa-miR-145-5pMIMAT00004371hsa-miR-145{Western blot}{overexpression by mature miRNA transfection}17827156
hsa-miR-145-5pMIMAT00004372hsa-miR-145{Western blot}{overexpression by mature miRNA transfection}17827156
hsa-miR-7-5pMIMAT00002521hsa-miR-7{Western blot}{overexpression by miRNA precursor transfection}18483236
hsa-miR-126-3pMIMAT00004451hsa-miR-126{Western blot}{overexpression}18834857
hsa-miR-223-3pMIMAT0000280NAhsa-miR-223{Western blot}{overexpression}19502786
hsa-miR-96-5pMIMAT0000095NAhsa-miR-96{Western blot}{overexpression}19502786
hsa-miR-217MIMAT0000274NAhsa-miR-217{Western blot}{overexpression}19502786
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6. Text-mining results about the gene

Gene occurances in abstracts of cellular senescence-associated articles: 6 abstracts the gene occurs.


PubMed ID of the article

Sentenece the gene occurs

25077541We demonstrate that miR-17 targets both ADCY5 and IRS1, upregulating the downstream signals MKP7, FoxO3, LC3B, and HIF1alpha, and downregulating mTOR, c-myc, cyclin D1, and JNK
25077541Silencing either ADCY5 or IRS1 promoted autophagy and repressed cellular senescence and apoptosis
22442749The downstream target of mTORC1, the kinase S6K1, induces insulin resistance by phosphorylation of insulin receptor substrate-1, thereby increasing the metabolic burden of beta-cells
22418434Phosphoproteome analysis revealed that phosphorylation of IRS1 Ser-1097 was markedly decreased in NUAK1-deficient muscle
22418434Consistent with this, insulin signaling was enhanced in the soleus muscle of MNUAK1KO mice, as evidenced by increased phosphorylation of IRS1 Tyr-608, AKT Thr-308, and TBC1D4 Thr-649
20634317The signaling protein insulin receptor substrate-1 (IRS-1), shown here to be a transcriptional target of Wnt, is induced in this setting
20634317The increased level of IRS-1 drives activation of mitochondrial biogenesis; furthermore, in insulin-responsive cell types, it enhances insulin signaling, raising the possibility that Wnt proteins may be used to modulate glucose homeostasis
19526322The expression of the GLUT4 and IRS-1 genes peaked during differentiation and then decreased in aged cells
19526322LPS decreased the mRNA levels of C/EBPalpha and PPARgamma at all time points, as well as those of GLUT4, IRS-1 and adiponectin
18498745In this report, we identified insulin receptor substrate 1 (IRS-1), a critical mediator of the insulin/insulin-like growth factor 1 signaling, as a proteolytic target of the CUL7 E3 ligase in a manner that depends on mammalian target of rapamycin and the p70 S6 kinase activities
18498745Interestingly, while embryonic fibroblasts of Cul7-/- mice were found to accumulate IRS-1 and exhibit increased activation of IRS-1's downstream Akt and MEK/ERK pathways, these null cells grew poorly and displayed phenotypes reminiscent of those associated with oncogene-induced senescence
18498745Taken together, our findings demonstrate a key role for the CUL7 E3 in targeting IRS-1 for degradation, a process that may contribute to the regulation of cellular senescence
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