PIK3R2
Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase that phosphorylates phosphatidylinositol and similar compounds, creating second messengers important in growth signaling pathways. PI3K functions as a heterodimer of a regulatory and a catalytic subunit. The protein encoded by this gene is a regulatory component of PI3K. Three transcript variants, one protein coding and the other two non-protein coding, have been found for this gene.
Function
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).
Biological Process
B cell differentiation1 PublicationIC:ComplexPortal
Cellular glucose homeostasisISS:UniProtKB
Cellular response to insulin stimulusISS:UniProtKB
Immune response1 PublicationIC:ComplexPortal
Insulin receptor signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of MAPK cascadeManual Assertion Based On ExperimentIMP:BHF-UCL
Phosphatidylinositol 3-kinase signalingManual Assertion Based On ExperimentIDA:UniProtKB
Phosphatidylinositol phosphate biosynthetic processManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of protein import into nucleusISS:UniProtKB
Positive regulation of transcription by RNA polymerase IIISS:UniProtKB
Protein transportIEA:UniProtKB-KW
Regulation of autophagyManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of phosphatidylinositol 3-kinase activityManual Assertion Based On ExperimentIBA:GO_Central
Response to endoplasmic reticulum stressISS:UniProtKB
T cell differentiation1 PublicationIC:ComplexPortal
Cellular Location
cytosol
nucleus
phosphatidylinositol 3-kinase complex
phosphatidylinositol 3-kinase complex, class IA
Involvement in disease
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (MPPH1):
A syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome.
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).
Ubiquitinated. Polyubiquitination by the SCF(FBXL2) complex probably promotes proteasomal degradation of PIK3R2.