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Details on Person UniProt:O00459 PIK3R2

Class:IdReferenceGeneProduct:61194
_chainChangeLogchain:1-728 added on Fri February 6 2015
_displayNameUniProt:O00459 PIK3R2
_timestamp2025-08-15 21:47:30
chainchain:1-728
checksumADAC3E4B61F3F44A
commentFUNCTION Regulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Binds to activated (phosphorylated) protein-tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Indirectly regulates autophagy (PubMed:23604317). Promotes nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement (By similarity).SUBUNIT Heterodimer of a regulatory subunit PIK3R2 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD) (PubMed:23604317). Interacts with AXL (PubMed:9178760). Interacts with FLT1 (tyrosine-phosphorylated) and FLT4 (tyrosine-phosphorylated) (PubMed:15102829, PubMed:9600074). Interacts with NYAP1, NYAP2 and MYO16 (By similarity). Interacts with FBXL2; PIK3R2 is a substrate of the SCF(FBXL2) complex (PubMed:23604317). Interacts with PTPN13; dephosphorylates PIK3R2 (PubMed:23604317). Interacts with XBP1 isoform 2; the interaction is direct and induces translocation of XBP1 isoform 2 into the nucleus in a ER stress- and/or insulin-dependent but PI3K-independent manner (By similarity). Interacts with PIK3R1; the interaction is dissociated in an insulin-dependent manner (By similarity). Interacts with SRC (PubMed:28903391).INTERACTION The SH2 2 domain is required for interaction with FBXL2 and PTPN13.PTM Phosphorylated in response to signaling from activated receptor-type protein kinases (PubMed:19690332, PubMed:20068231). Dephosphorylated by PTPRJ (PubMed:18348712). Dephosphorylated at Tyr-655 by PTPN13. Phosphorylation of Tyr-655 impairs while its dephosphorylation promotes interaction with FBXL2 and SCF(FBXL2)-mediated polyubiquitination (PubMed:23604317).PTM Ubiquitinated. Polyubiquitination by the SCF(FBXL2) complex probably promotes proteasomal degradation of PIK3R2.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the PI3K p85 subunit family.
descriptionrecommendedName: Phosphatidylinositol 3-kinase regulatory subunit beta shortName: PI3-kinase regulatory subunit beta shortName: PI3K regulatory subunit beta shortName: PtdIns-3-kinase regulatory subunit beta alternativeName: Phosphatidylinositol 3-kinase 85 kDa regulatory subunit beta shortName: PI3-kinase subunit p85-beta shortName: PtdIns-3-kinase regulatory subunit p85-beta
geneNamePIK3R2
identifierO00459
isSequenceChangedFALSE
keyword3D-structure
Disease variant
GTPase activation
Phosphoprotein
Protein transport
Proteomics identification
Reference proteome
Repeat
SH2 domain
SH3 domain
Stress response
Transport
Ubl conjugation
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
namePIK3R2
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8995595] ENSEMBL:ENSG00000105647 PIK3R2 [Homo sapiens]
secondaryIdentifierP85B_HUMAN
Q5EAT5
Q9UPH9
sequenceLength728
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:74791] PIK3R2 [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:3080554] K63polyUb-PIK3R2 [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:9860512] p-Y464-PIK3R2 [cytosol] [Homo sapiens]
(referenceSequence)[GroupModifiedResidue:3080566] ubiquitinylated lysine (K63-polyubiquitin [cytosol]) at unknown position
[ModifiedResidue:9860492] O4'-phospho-L-tyrosine at 464
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