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Details on Person UniProt:Q9Y4H2 IRS2
| Class:Id | ReferenceGeneProduct:57529 |
|---|---|
| _chainChangeLog | chain:1-1338 added on Sat February 7 2015 |
| _displayName | UniProt:Q9Y4H2 IRS2 |
| _timestamp | 2026-02-20 22:00:12 |
| chain | chain:1-1338 |
| checksum | 58E569E8BDBAF3D7 |
| comment | FUNCTION Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:25879670). Plays therefore an important role in development, growth, glucose homeostasis as well as lipid metabolism (PubMed:24616100). Upon phosphorylation by the insulin receptor, functions as a signaling scaffold that propagates insulin action through binding to SH2 domain-containing proteins including the p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 or SHP2 (PubMed:15316008, PubMed:19109239). Recruitment of GRB2 leads to the activation of the guanine nucleotide exchange factor SOS1 which in turn triggers the Ras/Raf/MEK/MAPK signaling cascade (By similarity). Activation of the PI3K/AKT pathway is responsible for most of insulin metabolic effects in the cell, and the Ras/Raf/MEK/MAPK is involved in the regulation of gene expression and in cooperation with the PI3K pathway regulates cell growth and differentiation. Acts a positive regulator of the Wnt/beta-catenin signaling pathway through suppression of DVL2 autophagy-mediated degradation leading to cell proliferation (PubMed:24616100). Plays a role in cell cycle progression by promoting a robust spindle assembly checkpoint (SAC) during M-phase (PubMed:32554797). In macrophages, IL4-induced tyrosine phosphorylation of IRS2 leads to the recruitment and activation of phosphoinositide 3-kinase (PI3K) (PubMed:19109239).SUBUNIT Interacts with PHIP. Interacts with SH2B1; this interaction enhances leptin-induced activation of the PI3-kinase pathway (PubMed:15316008). Interacts with GRB2 (PubMed:19109239). Interacts with PIK3R1 (PubMed:15316008). Interacts with DVL2; this interaction promotes the Wnt/beta-catenin signaling pathway (PubMed:24616100).SUBCELLULAR LOCATION Phosphorylation fluctuates in a cell-cycle dependent manner with hyperphosphorylation during mitosis (PubMed:32554797). Phosphorylated at Ser-560 and Ser-1109 by PLK1; these phosphorylations prevent the activation of the PI3K pathway upon growth factor stimulation by inhibiting the binding between IRS2 and the PI3K pathway components and increasing the level of IRS2 protein degradation. In addition, they prevent premature mitotic exit (By similarity).PTM Monoubiquitinated by NEDD4; leading to enhanced IGF1 signaling. During cell cycle, ubiquitination and proteasomal degradation are controlled by FZR1 (PubMed:32554797). |
| description | recommendedName: Insulin receptor substrate 2 shortName: IRS-2 |
| geneName | IRS2 |
| identifier | Q9Y4H2 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Cytoplasm Isopeptide bond Methylation Phosphoprotein Proteomics identification Reference proteome Transducer Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | IRS2 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8999576] ENSEMBL:ENSG00000185950 IRS2 [Homo sapiens] |
| secondaryIdentifier | IRS2_HUMAN Q96RR2 Q9BZG0 Q9Y6I5 |
| sequenceLength | 1338 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:57528] IRS2 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:74774] p-Y-IRS2 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:198334] p-Y-IRS2 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2424307] p-4Y-IRS2 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2428927] IRS2 [plasma membrane] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:74773] O4'-phospho-L-tyrosine at unknown position [ModifiedResidue:198292] O4'-phospho-L-tyrosine at unknown position [ModifiedResidue:2424298] O4'-phospho-L-tyrosine at 1253 [ModifiedResidue:2424300] O4'-phospho-L-tyrosine at 919 [ModifiedResidue:2424309] O4'-phospho-L-tyrosine at 766 [ModifiedResidue:2424310] O4'-phospho-L-tyrosine at 675 |
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No pathways have been reviewed or authored by UniProt:Q9Y4H2 IRS2 (57529)
