UniProt:Q63787 Pik3r1

chain
  • initiator methionine:1
  • chain:2-724
checksum 95C65CF612873B84
comment
  • FUNCTION 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. Modulates the cellular response to ER stress by promoting nuclear translocation of XBP1 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 PIK3R1 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts (via SH2 domains) with CCDC88A/GIV (tyrosine-phosphorylated form); the interaction enables recruitment of PIK3R1 to the EGFR receptor, enhancing PI3K activity and cell migration (By similarity). Interacts with phosphorylated LAT, LAX1, TRAT1 and LIME1 upon TCR and/or activation. Interacts with phosphorylated TOM1L1. Interacts with CBLB. The SH2 domains interact with the YTHM motif of phosphorylated INSR in vitro. Also interacts with tyrosine-phosphorylated IGF1R in vitro. Interacts with CD28 and CD3Z upon T-cell activation. Interacts with NISCH, SOCS7 and HCST. Interacts with RUFY3. Interacts with AXL, FASLG, FER, FGR, HCK, KIT and BCR. Interacts with PDGFRA (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated). Interacts with ERBB4 (phosphorylated). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Interacts with LYN (via SH3 domain); this enhances enzyme activity. Interacts with NTRK1 (phosphorylated upon ligand-binding). Interacts with PIK3R2; the interaction is dissociated in an insulin-dependent manner. Interacts with XBP1; the interaction is direct and induces translocation of XBP1 into the nucleus in a ER stress- and/or insulin-dependent but PI3K-independent manner (By similarity). Interacts with FGFR1, FGFR2, FGFR3 and FGFR4 (phosphorylated) (Probable). Interacts with IRS1 and phosphorylated IRS4 (PubMed:8628286). Interacts with PTK2/FAK1 (PubMed:8824286). Interacts with FAM83B; activates the PI3K/AKT signaling cascade (By similarity). Interacts with APPL1 and APPL2 (By similarity). Interacts with SRC (By similarity). Interacts with ALOX5; this interaction bridges ALOX5 with CD40 after CD40 ligation in B cells and leads to the production of reactive oxygen species (ROS) (By similarity). Interacts with TYK2 (By similarity). Interacts with nephrin NPHN1; the interaction is reduced by high glucose levels (By similarity). Interacts with CD28 (By similarity). Interacts with ICOS (By similarity).INTERACTION The P85-alpha isoform is widely expressed. Expression of the P55-alpha isoform is highest in brain and skeletal muscle. The P50-alpha isoform is abundant in liver with lower levels in brain and muscle.DOMAIN The SH3 domain mediates the binding to CBLB.PTM Polyubiquitinated in T-cells by CBLB; which does not promote proteasomal degradation but impairs association with CD28 and CD3Z upon T-cell activation.PTM Phosphorylated. Tyrosine phosphorylated in response to signaling by FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylated by CSF1R. 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. Phosphorylated in response to KIT and KITLG/SCF. Phosphorylated by FGR and ERBB4 (By similarity).PTM In adipose tissue, polyubiquitinated by the BCR(KBTBD2) E3 ubiquitin ligase complex; recognized by KBTBD2 through the SH2 domains, undergoes 'Lys-48'-linked polyubiquitination leading to its degradation.SIMILARITY Belongs to the PI3K p85 subunit family.
crossReference
databaseName UniProt
dbId 97650
description
  • recommendedName: Phosphatidylinositol 3-kinase regulatory subunit alpha shortName: PI3-kinase regulatory subunit alpha shortName: PI3K regulatory subunit alpha shortName: PtdIns-3-kinase regulatory subunit alpha alternativeName: Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha shortName: PI3-kinase subunit p85-alpha shortName: PtdIns-3-kinase regulatory subunit p85-alpha
displayName UniProt:Q63787 Pik3r1
geneName
  • Pik3r1
identifier Q63787
isSequenceChanged false
keyword
  • 3D-structure
  • Acetylation
  • Alternative splicing
  • GTPase activation
  • Phosphoprotein
  • Protein transport
  • Reference proteome
  • Repeat
  • SH2 domain
  • SH3 domain
  • Stress response
  • Transport
  • Ubl conjugation
modified [InstanceEdit:9963647] Weiser, Joel, 2025-08-15
moleculeType Protein
name
  • Pik3r1
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • P85A_RAT
  • O55085
  • P70544
  • Q63790
sequenceLength 724
species [Species:48895] Rattus norvegicus
stId uniprot:Q63787
url http://purl.uniprot.org/uniprot/Q63787
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