Irs2 insulin receptor substrate 2 [Rattus norvegicus (Norway rat)] - Gene

Summary

Symbol: Irs2provided by RGD
Full Name: insulin receptor substrate 2provided by RGD
Primary source: RGD:69316
See related: EnsemblRapid:ENSRNOG00000023509 AllianceGenome:RGD:69316
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: 4PS; IRS-2
Summary: Enables several functions, including 14-3-3 protein binding activity; insulin receptor binding activity; and phosphatidylinositol 3-kinase binding activity. Involved in cellular response to glucose stimulus; cellular response to peptide; and insulin receptor signaling pathway. Predicted to be active in cytosol and plasma membrane. Biomarker of metabolic dysfunction-associated steatotic liver disease and osteoporosis. Human ortholog(s) of this gene implicated in type 2 diabetes mellitus. Orthologous to human IRS2 (insulin receptor substrate 2). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in Adrenal (RPKM 102.1), Kidney (RPKM 88.2) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 16q12.5

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	16	NC_086034.1 (85190310..85214543)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	16	NC_051351.1 (78488249..78512482)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	16	NC_005115.4 (83824515..83848569)

Chromosome 16 - NC_086034.1 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?

The inflammatory role of dysregulated IRS2 in pulmonary vascular remodeling under hypoxic conditions.
Title: The inflammatory role of dysregulated IRS2 in pulmonary vascular remodeling under hypoxic conditions.
Disruption of insulin receptor substrate-2 impairs growth but not insulin function in rats.
Title: Disruption of insulin receptor substrate-2 impairs growth but not insulin function in rats.
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.
a radical increase in the phosphorylation of IRS2 at serine 731 prevents the recruitment of GRB2 adaptor protein which may fail further to connect the Ras and other pathways required to the cell for its survival and to maintain integrity
Title: Altered expression of IRS2 and GRB2 in demyelination of peripheral neurons: Implications in diabetic neuropathy.
Chronic periapical lesions are associated with decreased insulin signaling - evaluated according to insulin receptor substrate (pp185-insulin receptor substrate 1 [IRS-1]/insulin receptor substrate 2 [IRS-2]) tyrosine phosphorylation status, IRS-1 serine phosphorylation status, and IRS-1 and IRS-2 content - in the skeletal muscle of rats
Title: Periapical Lesions Decrease Insulin Signaling in Rat Skeletal Muscle.
IRS-2 was one of the targets of miR-126. MiR-126 inhibited the beta-cell proliferation through IRS-2 instead of IRS-1. MiR-126 may take part in the glucose homeostasis both through its target IRS-2 and IRS-1.
Title: MiR-126 Suppresses the Glucose-Stimulated Proliferation via IRS-2 in INS-1 β Cells.
reduced insulin secretion during protein restriction directly increased hepatic IRS-2 as a rapid response on day 1, while additional mechanisms contributed to the upregulation of IRS-2 on day 7
Title: Insulin injection restored increased insulin receptor substrate (IRS)-2 protein during short-term protein restriction but did not affect reduced insulin-like growth factor (IGF)-I mRNA or increased triglyceride accumulation in the liver of rats.
Data suggest P38/Mapk14 (mitogen activated protein kinase 14) is involved in glucolipotoxicity-induced apoptosis in pancreatic beta-cells via phosphorylation of Irs2; thus, P38/Irs2 play roles in beta-cell response to hyperglycemia/hyperlipidemia.
Title: P38 plays an important role in glucolipotoxicity-induced apoptosis in INS-1 cells.
The study identified the serine phosphorylation (p-Ser) sites induced by PKC-Beta activation or AngII, which inhibits insulin-induced p-Tyr sites on IRS2 and its signals in endothelial cells.
Title: Serine phosphorylation sites on IRS2 activated by angiotensin II and protein kinase C to induce selective insulin resistance in endothelial cells.
Data suggest that down-regulation of insulin signaling pathway (Irs1, Irs2, and insulin-like growth factor-1) in type II diabetic osteoporosis model occurs either sooner or more dramatically in bone as compared to liver, kidney or skeletal muscle.
Title: Altered gene expression involved in insulin signaling pathway in type II diabetic osteoporosis rats model.

Submit: New GeneRIF Correction See all GeneRIFs (38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

UniSTS:496713 (e-PCR)
- UniSTS:496713

Irs2 (e-PCR), detects polymorphism
- UniSTS:496713

PMC152262P2 (e-PCR)
- UniSTS:271210

D16Wox21 (e-PCR)
- UniSTS:240558

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables 14-3-3 protein binding	IDA Inferred from Direct Assay more info	PubMed
enables insulin receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables insulin receptor binding	IMP Inferred from Mutant Phenotype more info	PubMed
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	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 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 binding	ISO Inferred from Sequence Orthology more info
enables protein phosphatase binding	IPI Inferred from Physical Interaction 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 transmembrane receptor protein tyrosine kinase adaptor activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within brain development	ISO Inferred from Sequence Orthology more info
acts_upstream_of cell migration	ISO Inferred from Sequence Orthology more info
acts_upstream_of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in cellular response to glucose stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to insulin stimulus	IDA Inferred from Direct Assay more info	PubMed
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 peptide	IEP Inferred from Expression Pattern more info	PubMed
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	IMP Inferred from Mutant Phenotype more info	PubMed
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
involved_in insulin-like growth factor receptor signaling pathway	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 B cell apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of kinase activity	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of long-chain fatty acid import across plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of B cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of D-glucose import	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of cell population proliferation	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	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 secretion	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	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of type B pancreatic cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in response to glucose	ISO Inferred from Sequence Orthology more info
acts_upstream_of type B pancreatic cell proliferation	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	ISO Inferred from Sequence Orthology more info
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
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 2

Names: tyrosine kinase substrate

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_001168633.1 → NP_001162104.1 insulin receptor substrate 2

See identical proteins and their annotated locations for NP_001162104.1

Status: PROVISIONAL

Source sequence(s)

JAXUCZ010000016

UniProtKB/TrEMBL

A6IWQ8, F1MAL5

Related

ENSRNOP00000036862.5, ENSRNOT00000032918.8

Conserved Domains (3) summary

cd01204
Location:192 → 295

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

cd01257
Location:32 → 148

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

pfam00169
Location:32 → 145

PH; PH domain