PIK3R1

Phosphatidylinositol 3-kinase phosphorylates the inositol ring of phosphatidylinositol at the 3-prime position. The enzyme comprises a 110 kD catalytic subunit and a regulatory subunit of either 85, 55, or 50 kD. This gene encodes the 85 kD regulatory subunit. Phosphatidylinositol 3-kinase plays an important role in the metabolic actions of insulin, and a mutation in this gene has been associated with insulin resistance. Alternative splicing of this gene results in four transcript variants encoding different isoforms.

Phosphoinositide-3-Kinase Regulatory Subunit 1

GRB1; Phosphatidylinositol 3-kinase regulatory subunit alpha; PI3-kinase regulatory subunit alpha; PI3K regulatory subunit alpha; PtdIns-3-kinase regulatory subunit alpha; Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha; PI3-kinase subunit p85-alpha; PtdIns-3-kinase regulatory subunit p85-alpha

Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (PubMed:17626883, PubMed:19805105, PubMed:7518429).
Modulates the cellular response to ER stress by promoting 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 (PubMed:20348923).

B cell differentiation1 PublicationIC:ComplexPortal
Cellular glucose homeostasisISS:UniProtKB
Cellular response to insulin stimulusISS:UniProtKB
Cellular response to UVIEA:Ensembl
Extrinsic apoptotic signaling pathway via death domain receptorsIEA:Ensembl
Growth hormone receptor signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Immune response1 PublicationIC:ComplexPortal
Insulin receptor signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Insulin-like growth factor receptor signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Intrinsic apoptotic signaling pathway in response to DNA damageIEA:Ensembl
Negative regulation of apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of cell-matrix adhesionIEA:Ensembl
Negative regulation of osteoclast differentiationIEA:Ensembl
Negative regulation of stress fiber assemblyISS:BHF-UCL
Phosphatidylinositol 3-kinase signalingManual Assertion Based On ExperimentIDA:BHF-UCL
Phosphatidylinositol phosphate biosynthetic processISS:UniProtKB
Positive regulation of cell migrationIEA:Ensembl
Positive regulation of endoplasmic reticulum unfolded protein responseManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of filopodium assemblyISS:BHF-UCL
Positive regulation of focal adhesion disassemblyISS:BHF-UCL
Positive regulation of glucose importBy SimilarityISS:BHF-UCL
Positive regulation of lamellipodium assemblyISS:BHF-UCL
Positive regulation of protein import into nucleusManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of protein localization to plasma membraneBy SimilarityISS:BHF-UCL
Positive regulation of RNA splicingManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of tumor necrosis factor productionIEA:Ensembl
Protein import into nucleusIEA:Ensembl
Protein phosphorylationIEA:Ensembl
Protein stabilizationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of insulin receptor signaling pathwayIEA:Ensembl
Regulation of phosphatidylinositol 3-kinase activityISS:BHF-UCL
Response to endoplasmic reticulum stressManual Assertion Based On ExperimentIDA:UniProtKB
Substrate adhesion-dependent cell spreadingISS:BHF-UCL
T cell differentiation1 PublicationIC:ComplexPortal

cell-cell junction
cis-Golgi network
cytoplasm
cytosol
membrane
nucleus
perinuclear endoplasmic reticulum membrane
perinuclear region of cytoplasm
phosphatidylinositol 3-kinase complex
phosphatidylinositol 3-kinase complex, class IA
plasma membrane

Agammaglobulinemia 7, autosomal recessive (AGM7):
A primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life.
SHORT syndrome (SHORTS):
A rare, multisystem disease characterized by short stature, anomalies of the anterior chamber of the eye, characteristic facial features such as triangular facies, lack of facial fat, and hypoplastic nasal alae with overhanging columella, partial lipodystrophy, hernias, hyperextensibility, and delayed dentition. The clinical phenotype can include insulin resistance, nephrocalcinosis, and hearing deficits. Developmental milestones and cognition are normal.
Immunodeficiency 36 (IMD36):
A primary immunodeficiency characterized by impaired B-cell function, hypogammaglobulinemia and recurrent infections.

Polyubiquitinated in T-cells by CBLB; which does not promote proteasomal degradation but impairs association with CD28 and CD3Z upon T-cell activation.
Phosphorylated. Tyrosine phosphorylated in response to signaling by FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylated by CSF1R. Phosphorylated by ERBB4. Phosphorylated on tyrosine residues by TEK/TIE2. Dephosphorylated by PTPRJ. Phosphorylated by PIK3CA at Ser-608; phosphorylation is stimulated by insulin and PDGF. The relevance of phosphorylation by PIK3CA is however unclear (By similarity).
Phosphorylated in response to KIT and KITLG/SCF. Phosphorylated by FGR.