Irs1 insulin receptor substrate 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Irs1provided by MGI
Official Full Name: insulin receptor substrate 1provided by MGI
Primary source: MGI:MGI:99454
See related: Ensembl:ENSMUSG00000055980 AllianceGenome:MGI:99454
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: G972R; IRS-1
Summary: Enables phosphatidylinositol 3-kinase binding activity and protein kinase binding activity. Involved in cellular response to fatty acid. Acts upstream of or within several processes, including cellular response to insulin stimulus; positive regulation of phosphatidylinositol 3-kinase activity; and protein kinase B signaling. Located in several cellular components, including ciliary basal body; nucleus; and plasma membrane. Is expressed in several structures, including alimentary system; brain; genitourinary system; hemolymphoid system gland; and liver and biliary system. Used to study type 2 diabetes mellitus. Human ortholog(s) of this gene implicated in Alzheimer's disease; coronary artery disease; and type 2 diabetes mellitus. Orthologous to human IRS1 (insulin receptor substrate 1). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in ovary adult (RPKM 15.6), subcutaneous fat pad adult (RPKM 14.2) and 20 other tissues See more
Orthologs: human all
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Genomic context

Location:: 1 C5; 1 42.0 cM

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	1	NC_000067.7 (82210826..82269160, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (82233105..82291439, complement)

Chromosome 1 - NC_000067.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Myocardin reverses insulin resistance and ameliorates cardiomyopathy by increasing IRS-1 expression in a murine model of lipodystrophy caused by adipose deficiency of vacuolar H[+]-ATPase V0d1 subunit.
Title: Myocardin reverses insulin resistance and ameliorates cardiomyopathy by increasing IRS-1 expression in a murine model of lipodystrophy caused by adipose deficiency of vacuolar H(+)-ATPase V0d1 subunit.
Kinesin light chain 1 stabilizes insulin receptor substrate 1 to regulate the IGF-1-AKT signaling pathway during myoblast differentiation.
Title: Kinesin light chain 1 stabilizes insulin receptor substrate 1 to regulate the IGF-1-AKT signaling pathway during myoblast differentiation.
MiR-222-3p suppresses C2C12 myoblast proliferation and differentiation via the inhibition of IRS-1/PI3K/Akt pathway.
Title: MiR-222-3p suppresses C2C12 myoblast proliferation and differentiation via the inhibition of IRS-1/PI3K/Akt pathway.
Phosphorylation of insulin receptor substrates (IRS-1 and IRS-2) is attenuated following cecal ligation and puncture in mice.
Title: Phosphorylation of insulin receptor substrates (IRS-1 and IRS-2) is attenuated following cecal ligation and puncture in mice.
H19 inhibition increases HDAC6 and regulates IRS1 levels and insulin signaling in the skeletal muscle during diabetes.
Title: H19 inhibition increases HDAC6 and regulates IRS1 levels and insulin signaling in the skeletal muscle during diabetes.
Cathepsin K activity controls cachexia-induced muscle atrophy via the modulation of IRS1 ubiquitination.
Title: Cathepsin K activity controls cachexia-induced muscle atrophy via the modulation of IRS1 ubiquitination.
Differential involvement of insulin receptor substrate (IRS)-1 and IRS-2 in brain insulin signaling is associated with the effects on amyloid pathology in a mouse model of Alzheimer's disease.
Title: Differential involvement of insulin receptor substrate (IRS)-1 and IRS-2 in brain insulin signaling is associated with the effects on amyloid pathology in a mouse model of Alzheimer's disease.
FGF15/FGF19 alleviates insulin resistance and upregulates placental IRS1/GLUT expression in pregnant mice fed a high-fat diet.
Title: FGF15/FGF19 alleviates insulin resistance and upregulates placental IRS1/GLUT expression in pregnant mice fed a high-fat diet.
Programmed cell death 5 improves skeletal muscle insulin resistance by inhibiting IRS-1 ubiquitination through stabilization of MDM2.
Title: Programmed cell death 5 improves skeletal muscle insulin resistance by inhibiting IRS-1 ubiquitination through stabilization of MDM2.
SUR1, newly expressed in astrocytes, mediates neuropathic pain in a mouse model of peripheral nerve injury.
Title: SUR1, newly expressed in astrocytes, mediates neuropathic pain in a mouse model of peripheral nerve injury.

Submit: New GeneRIF Correction See all GeneRIFs (200)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (8) 1 citation
Chemically induced (ENU) (2) 1 citation
Spontaneous (3) 1 citation
Endonuclease-mediated (3)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Irs1 (e-PCR), detects polymorphism
- UniSTS:532238

20.MMHAP18FLG2.seq (e-PCR)
- UniSTS:123459

UniSTS:464712 (e-PCR)
- UniSTS:464712

Irs1 (e-PCR), detects polymorphism
- UniSTS:464712

UniSTS:464713 (e-PCR)
- UniSTS:464713

Irs1 (e-PCR), detects polymorphism
- UniSTS:464713

D1S3698 (e-PCR)
- UniSTS:474276

D9Wox26 (e-PCR)
- UniSTS:518850

Irs1 (e-PCR), detects polymorphism
- UniSTS:143605

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables SH2 domain binding	ISO Inferred from Sequence Orthology more info
enables insulin receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables insulin receptor binding	ISO Inferred from Sequence Orthology more info
enables insulin-like growth factor receptor binding	ISO Inferred from Sequence Orthology more info
enables phosphatidylinositol 3-kinase activator activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables phosphatidylinositol 3-kinase binding	IBA Inferred from Biological aspect of Ancestor more info
enables phosphatidylinositol 3-kinase binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol 3-kinase binding	ISO Inferred from Sequence Orthology more info
enables phosphotyrosine residue binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	ISO Inferred from Sequence Orthology more info
enables protein kinase C binding	ISO Inferred from Sequence Orthology more info
enables protein kinase binding	IDA Inferred from Direct Assay more info	PubMed
enables protein kinase binding	ISO Inferred from Sequence Orthology more info
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info
enables protein-macromolecule adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein-macromolecule adaptor activity	IGI Inferred from Genetic Interaction more info	PubMed
enables signaling receptor complex adaptor activity	ISO Inferred from Sequence Orthology more info
enables transmembrane receptor protein tyrosine kinase adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables transmembrane receptor protein tyrosine kinase adaptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables transmembrane receptor protein tyrosine kinase adaptor activity	ISO Inferred from Sequence Orthology more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of cell migration	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cellular response to fatty acid	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cellular response to insulin stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to insulin stimulus	ISO Inferred from Sequence Orthology more info
involved_in cytokine-mediated signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of epithelial cell migration	IGI Inferred from Genetic Interaction more info	PubMed
involved_in insulin receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within insulin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in insulin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within insulin receptor signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in insulin receptor signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in insulin receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in insulin receptor signaling pathway	ISO Inferred from Sequence Orthology more info
NOT acts_upstream_of_or_within insulin secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in insulin-like growth factor receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in insulin-like growth factor receptor signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in insulin-like growth factor receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in insulin-like growth factor receptor signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within lipid catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within mammary gland development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of insulin receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of insulin secretion	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of somatostatin secretion	ISO Inferred from Sequence Orthology more info
involved_in phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of epithelial cell migration	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of fatty acid beta-oxidation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of glucagon secretion	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of glucose import	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of glucose metabolic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of glycogen biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of insulin receptor signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of mesenchymal cell proliferation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of phosphorylation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein localization to nucleus	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein localization to nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to caffeine	ISO Inferred from Sequence Orthology more info
involved_in response to insulin	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within signal transduction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in caveola	ISO Inferred from Sequence Orthology more info
located_in ciliary basal body	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	TAS Traceable Author Statement more info
part_of insulin receptor complex	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: insulin receptor substrate 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_010570.4 → NP_034700.2 insulin receptor substrate 1

See identical proteins and their annotated locations for NP_034700.2

Status: VALIDATED

Source sequence(s)

AC123690, AC137845

Consensus CDS

CCDS15096.1

UniProtKB/Swiss-Prot

P35569

UniProtKB/TrEMBL

Q543V3

Related

ENSMUSP00000063795.3, ENSMUST00000069799.3

Conserved Domains (3) summary

cd01204
Location:155 → 258

PTB_IRS; Insulin receptor substrate phosphotyrosine-binding domain (PTBi)

cd01257
Location:11 → 118

PH_IRS; Insulin receptor substrate (IRS) pleckstrin homology (PH) domain

pfam00169
Location:17 → 110

PH; PH domain