P23727 · P85A_BOVIN
- ProteinPhosphatidylinositol 3-kinase regulatory subunit alpha
- GenePIK3R1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids724 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePhosphatidylinositol 3-kinase regulatory subunit alpha
- Short namesPI3-kinase regulatory subunit alpha; PI3K regulatory subunit alpha; PtdIns-3-kinase regulatory subunit alpha
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Bovinae > Bos
Accessions
- Primary accessionP23727
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylserine | ||||
Sequence: S | ||||||
Chain | PRO_0000080757 | 2-724 | Phosphatidylinositol 3-kinase regulatory subunit alpha | |||
Sequence: SAEGYQYRALYDYKKEREEDIDLHLGDILTVNKGSLVALGFSDGQEAKPEEIGWLNGYNETTGERGDFPGTYVEYIGRKKISPPTPKPRPPRPLPVAPGPSKTEADSEQQASTLPDLAEQFAPPDVAPPLLIKLVEAIEKKGLECSTLYRTQSSSNPAELRQLLDCDTASLDLEMFDVHVLADAFKRYLLDLPNPVIPVAVSSELISLAPEVQSSEEYIQLLKKLIRSPSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSELFSPLLFRFPAASSENTEHLIKIIEILISTEWNERQPAPALPPKPPKPTTVANNGMNNNMSLQDAEWYWGDISREEVNEKLRDTADGTFLVRDASTKMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFNSVVELINHYRNESLAQYNPKLDVKLLYPVSKYQQDQVVKEDNIEAVGKKLHEYNTQFQEKSREYDRLYEDYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNETEIQRIMHNYEKLKSRISEIVDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVRQKKLNEWLGNENTEDQYSLVEDDEDLPHHDEKTWNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVLHYQHTSLVQHNDSLNVTLAYPVYAQQRR | ||||||
Modified residue | 154 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 279 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 467 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 580 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 608 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
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 in response to KIT and KITLG/SCF. Phosphorylated on tyrosine residues by TEK/TIE2. Phosphorylated by FGR. Phosphorylated by CSF1R. Phosphorylated by ERBB4. Dephosphorylated by PTPRJ (By similarity).
Phosphorylated by PIK3CA at Ser-608; phosphorylation is stimulated by insulin and PDGF. The relevance of phosphorylation by PIK3CA is however unclear
Phosphorylated by PIK3CA at Ser-608; phosphorylation is stimulated by insulin and PDGF. The relevance of phosphorylation by PIK3CA is however unclear
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.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
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 PIK3R2; the interaction is dissociated in an insulin-dependent manner (By similarity).
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 phosphorylated LAT, LAX1, TRAT1 and LIME1 upon TCR and/or BCR activation. 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 SOCS7. Interacts with IRS1 and phosphorylated IRS4. Interacts with NISCH, RUFY3 and HCST. Interacts with LYN (via SH3 domain); this enhances enzyme activity. Interacts with AXL, FASLG, FER, FGR, HCK, KIT and BCR. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity).
Interacts with PDGFRA (tyrosine phosphorylated). Interacts with ERBB4 (phosphorylated) (By similarity).
Interacts with NTRK1 (phosphorylated upon ligand-binding). Interacts with PTK2/FAK1 (By similarity).
Interacts with PDGFRB (tyrosine phosphorylated) (PubMed:1375321).
Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (By similarity).
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 PIK3R2; the interaction is dissociated in an insulin-dependent manner (By similarity).
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 phosphorylated LAT, LAX1, TRAT1 and LIME1 upon TCR and/or BCR activation. 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 SOCS7. Interacts with IRS1 and phosphorylated IRS4. Interacts with NISCH, RUFY3 and HCST. Interacts with LYN (via SH3 domain); this enhances enzyme activity. Interacts with AXL, FASLG, FER, FGR, HCK, KIT and BCR. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity).
Interacts with PDGFRA (tyrosine phosphorylated). Interacts with ERBB4 (phosphorylated) (By similarity).
Interacts with NTRK1 (phosphorylated upon ligand-binding). Interacts with PTK2/FAK1 (By similarity).
Interacts with PDGFRB (tyrosine phosphorylated) (PubMed:1375321).
Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (By similarity).
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).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | P23727 | Inpp5d Q9ES52-1 | 2 | EBI-520244, EBI-1452545 | |
XENO | P23727 | KHDRBS1 Q07666 | 2 | EBI-520244, EBI-1364 | |
XENO | P23727 | PDGFRB P09619 | 6 | EBI-520244, EBI-641237 | |
BINARY | P23727 | PIK3CA P32871 | 4 | EBI-520244, EBI-1373130 | |
BINARY | P23727 | PIK3R1 P23727 | 4 | EBI-520244, EBI-520244 | |
XENO | P23727 | RAB5A P20339 | 5 | EBI-520244, EBI-399437 |
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 3-79 | SH3 | ||||
Sequence: AEGYQYRALYDYKKEREEDIDLHLGDILTVNKGSLVALGFSDGQEAKPEEIGWLNGYNETTGERGDFPGTYVEYIGR | ||||||
Region | 79-112 | Disordered | ||||
Sequence: RKKISPPTPKPRPPRPLPVAPGPSKTEADSEQQA | ||||||
Compositional bias | 84-99 | Pro residues | ||||
Sequence: PPTPKPRPPRPLPVAP | ||||||
Domain | 113-301 | Rho-GAP | ||||
Sequence: STLPDLAEQFAPPDVAPPLLIKLVEAIEKKGLECSTLYRTQSSSNPAELRQLLDCDTASLDLEMFDVHVLADAFKRYLLDLPNPVIPVAVSSELISLAPEVQSSEEYIQLLKKLIRSPSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSELFSPLLFRFPAASSENTEHLIKIIEILISTEWNER | ||||||
Domain | 333-428 | SH2 1 | ||||
Sequence: WYWGDISREEVNEKLRDTADGTFLVRDASTKMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFNSVVELINHYRNESLAQYNPKLDVKLLYPV | ||||||
Domain | 624-718 | SH2 2 | ||||
Sequence: WNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVLHYQHTSLVQHNDSLNVTLAYPV |
Domain
The SH3 domain mediates the binding to CBLB.
Sequence similarities
Belongs to the PI3K p85 subunit family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length724
- Mass (Da)83,497
- Last updated1991-11-01 v1
- ChecksumEBDF6E754BBF7321
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 84-99 | Pro residues | ||||
Sequence: PPTPKPRPPRPLPVAP |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M61745 EMBL· GenBank· DDBJ | AAA79511.1 EMBL· GenBank· DDBJ | mRNA |