Irs1 insulin receptor substrate 1 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Irs1provided by RGD
Official Full Name: insulin receptor substrate 1provided by RGD
Primary source: RGD:2922
See related: Ensembl:ENSRNOG00000014597 AllianceGenome:RGD:2922
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: IRS1IRM
Summary: Enables several functions, including SH2 domain binding activity; protein kinase binding activity; and signaling receptor binding activity. Involved in several processes, including cellular response to peptide hormone stimulus; regulation of insulin receptor signaling pathway; and regulation of peptide hormone secretion. Located in cytosol; intracellular membrane-bounded organelle; and plasma membrane. Part of insulin receptor complex. Used to study end stage renal disease; obesity; and type 2 diabetes mellitus. Biomarker of Alzheimer's disease; non-alcoholic fatty liver disease; and osteoporosis. 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: Biased expression in Muscle (RPKM 289.3), Heart (RPKM 135.2) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 9q34

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	9	NC_086027.1 (91001137..91053959, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	9	NC_051344.1 (83552964..83605797, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	9	NC_005108.4 (88033668..88086488, complement)

Chromosome 9 - NC_086027.1 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: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

[Effect of miR-96-5p targeting IRS1 on apoptosis of PC12 cells induced by aluminum maltol].
Title: [Effect of miR-96-5p targeting IRS1 on apoptosis of PC12 cells induced by aluminum maltol].
Long Non-coding RNA SPAG5-AS1 Attenuates Diabetic Retinal Vascular Dysfunction by Inhibiting Human Retinal Microvascular Endothelial Cell Proliferation, Migration, and Tube Formation by Regulating the MicroRNA-1224-5p/IRS-1 Axis.
Title: Long Non-coding RNA SPAG5-AS1 Attenuates Diabetic Retinal Vascular Dysfunction by Inhibiting Human Retinal Microvascular Endothelial Cell Proliferation, Migration, and Tube Formation by Regulating the MicroRNA-1224-5p/IRS-1 Axis.
IRS1 expression in hippocampus is age-dependent and is required for mature spine maintenance and neuritogenesis.
Title: IRS1 expression in hippocampus is age-dependent and is required for mature spine maintenance and neuritogenesis.
Changes of LRP6/beta-catenin pathway in adipose tissue of rats with intrauterine growth restriction with catch-up growth.
Title: Changes of LRP6/β-catenin pathway in adipose tissue of rats with intrauterine growth restriction with catch-up growth.
Overexpression of mechanical sensitive miR-337-3p alleviates ectopic ossification in rat tendinopathy model via targeting IRS1 and Nox4 of tendon-derived stem cells.
Title: Overexpression of mechanical sensitive miR-337-3p alleviates ectopic ossification in rat tendinopathy model via targeting IRS1 and Nox4 of tendon-derived stem cells.
Insulinreceptor substrate 1 protects against injury in endothelial cell models of oxLDLinduced atherosclerosis by inhibiting ER stress/oxidative stressmediated apoptosis and activating the Akt/FoxO1 signaling pathway.
Title: Insulin‑receptor substrate 1 protects against injury in endothelial cell models of ox‑LDL‑induced atherosclerosis by inhibiting ER stress/oxidative stress‑mediated apoptosis and activating the Akt/FoxO1 signaling pathway.
Activation of Wnt/beta-catenin signaling restores insulin sensitivity in insulin resistant neurons through transcriptional regulation of IRS-1.
Title: Activation of Wnt/β-catenin signaling restores insulin sensitivity in insulin resistant neurons through transcriptional regulation of IRS-1.
Imbalanced insulin substrate-1 and insulin substrate-2 signaling trigger hepatic steatosis in vitamin D deficient rats: 8-methoxypsoralen, a vitamin D receptor ligand with a promising anti-steatotic action.
Title: Imbalanced insulin substrate-1 and insulin substrate-2 signaling trigger hepatic steatosis in vitamin D deficient rats: 8-methoxypsoralen, a vitamin D receptor ligand with a promising anti-steatotic action.
This study was performed to clarify the effect of microRNA-128 on the cardiac microvascular endothelial cell injury in coronary heart disease by binding to insulin receptor substrate 1 (IRS1).
Title: MicroRNA-128 confers protection against cardiac microvascular endothelial cell injury in coronary heart disease via negative regulation of IRS1.
miR-494-3p reduces insulin sensitivity in diabetic cardiomyocytes by down-regulating IRS1.
Title: [miR-494-3p reduces insulin sensitivity in diabetic cardiomyocytes by down-regulation of insulin receptor substrate 1].

Submit: New GeneRIF Correction See all GeneRIFs (122)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

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

D9Wox25 (e-PCR)
- UniSTS:518849

D9Wox26 (e-PCR)
- UniSTS:518850

Gene Ontology Provided by RGD

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

Process	Evidence Code	Pubs
acts_upstream_of cell migration	ISO Inferred from Sequence Orthology more info
involved_in cellular response to angiotensin	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to brain-derived neurotrophic factor stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to fatty acid	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cellular response to insulin stimulus	ISO Inferred from Sequence Orthology more info
involved_in cellular response to insulin stimulus	ISO Inferred from Sequence Orthology more info
involved_in cellular response to radiation	IEP Inferred from Expression Pattern more info	PubMed
involved_in cytokine-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in cytokine-mediated signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of epithelial cell migration	ISO Inferred from Sequence Orthology more info
involved_in insulin receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in insulin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in insulin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within insulin receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in insulin receptor signaling pathway	ISO Inferred from Sequence Orthology more info
NOT acts_upstream_of_or_within insulin secretion	ISO Inferred from Sequence Orthology more info
involved_in insulin-like growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in insulin-like growth factor receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in insulin-like growth factor receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within lipid catabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within mammary gland development	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of insulin receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of insulin secretion	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of insulin secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of insulin secretion	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of somatostatin secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA Inferred from Electronic Annotation 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	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of fatty acid beta-oxidation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of fatty acid beta-oxidation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of glucagon secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of glucose import	IEA Inferred from Electronic Annotation 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	IEA Inferred from Electronic Annotation 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	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of insulin receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
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	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of phosphorylation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein localization to nucleus	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in response to activity	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to caffeine	IDA Inferred from Direct Assay more info	PubMed
involved_in response to caffeine	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to insulin	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in caveola	IEA Inferred from Electronic Annotation more info
located_in caveola	ISO Inferred from Sequence Orthology more info
located_in ciliary basal body	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IEA Inferred from Electronic Annotation 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	IMP Inferred from Mutant Phenotype more info	PubMed
located_in intracellular membrane-bounded organelle	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: insulin receptor substrate 1

Names: IRS-1; pp185

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_012969.2 → NP_037101.2 insulin receptor substrate 1

Status: PROVISIONAL

Source sequence(s)

JAXUCZ010000009

UniProtKB/Swiss-Prot

P35570

UniProtKB/TrEMBL

A6JW94, G3V7V7

Related

ENSRNOP00000019579.4, ENSRNOT00000019579.6

Conserved Domains (2) 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