P85A_RAT
ID P85A_RAT Reviewed; 724 AA.
AC Q63787; O55085; P70544; Q63790;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Phosphatidylinositol 3-kinase regulatory subunit alpha;
DE Short=PI3-kinase regulatory subunit alpha;
DE Short=PI3K regulatory subunit alpha;
DE Short=PtdIns-3-kinase regulatory subunit alpha;
DE AltName: Full=Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha;
DE Short=PI3-kinase subunit p85-alpha;
DE Short=PtdIns-3-kinase regulatory subunit p85-alpha;
GN Name=Pik3r1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS P85-ALPHA AND P55-ALPHA).
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=8621382; DOI=10.1074/jbc.271.10.5317;
RA Inukai K., Anai M., van Breda E., Hosaka T., Katagiri H., Funaki M.,
RA Fukushima Y., Ogihara T., Yazaki Y., Kikuchi M., Oka Y., Asano T.;
RT "A novel 55-kDa regulatory subunit for phosphatidylinositol 3-kinase
RT structurally similar to p55PIK is generated by alternative splicing of the
RT p85alpha gene.";
RL J. Biol. Chem. 271:5317-5320(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P50-ALPHA).
RC TISSUE=Liver;
RX PubMed=9065454; DOI=10.1074/jbc.272.12.7873;
RA Inukai K., Funaki M., Ogihara T., Katagiri H., Kanda A., Anai M.,
RA Fukushima Y., Hosaka T., Suzuki M., Shin B., Takata K., Yazaki Y.,
RA Kikuchi M., Oka Y., Asano T.;
RT "p85alpha gene generates three isoforms of regulatory subunit for
RT phosphatidylinositol 3-kinase (PI 3-Kinase), p50alpha, p55alpha, and
RT p85alpha, with different PI 3-kinase activity elevating responses to
RT insulin.";
RL J. Biol. Chem. 272:7873-7882(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P50-ALPHA).
RC TISSUE=Liver;
RX PubMed=8921377; DOI=10.1006/geno.1996.0527;
RA Fruman D.A., Cantley L.C., Carpenter C.L.;
RT "Structural organization and alternative splicing of the murine
RT phosphoinositide 3-kinase p85 alpha gene.";
RL Genomics 37:113-121(1996).
RN [4]
RP ACTIVATION BY FGFR4.
RX PubMed=7518429; DOI=10.1016/s0021-9258(17)32309-8;
RA Vainikka S., Joukov V., Wennstrom S., Bergman M., Pelicci P.G., Alitalo K.;
RT "Signal transduction by fibroblast growth factor receptor-4 (FGFR-4).
RT Comparison with FGFR-1.";
RL J. Biol. Chem. 269:18320-18326(1994).
RN [5]
RP INTERACTION WITH PTK2/FAK1.
RX PubMed=8824286; DOI=10.1074/jbc.271.42.26329;
RA Chen H.C., Appeddu P.A., Isoda H., Guan J.L.;
RT "Phosphorylation of tyrosine 397 in focal adhesion kinase is required for
RT binding phosphatidylinositol 3-kinase.";
RL J. Biol. Chem. 271:26329-26334(1996).
RN [6]
RP INTERACTION WITH IRS1.
RX PubMed=8628286; DOI=10.1128/mcb.16.5.2195;
RA Antonetti D.A., Algenstaedt P., Kahn C.R.;
RT "Insulin receptor substrate 1 binds two novel splice variants of the
RT regulatory subunit of phosphatidylinositol 3-kinase in muscle and brain.";
RL Mol. Cell. Biol. 16:2195-2203(1996).
RN [7]
RP ACTIVATION BY FGFR1.
RX PubMed=11353842; DOI=10.1073/pnas.111114298;
RA Ong S.H., Hadari Y.R., Gotoh N., Guy G.R., Schlessinger J., Lax I.;
RT "Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor
RT receptors is mediated by coordinated recruitment of multiple docking
RT proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:6074-6079(2001).
CC -!- FUNCTION: Binds to activated (phosphorylated) protein-Tyr kinases,
CC through its SH2 domain, and acts as an adapter, mediating the
CC association of the p110 catalytic unit to the plasma membrane.
CC Necessary for the insulin-stimulated increase in glucose uptake and
CC glycogen synthesis in insulin-sensitive tissues. Plays an important
CC role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF,
CC KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling.
CC Modulates the cellular response to ER stress by promoting nuclear
CC translocation of XBP1 in a ER stress- and/or insulin-dependent manner
CC during metabolic overloading in the liver and hence plays a role in
CC glucose tolerance improvement (By similarity).
CC {ECO:0000250|UniProtKB:P26450, ECO:0000250|UniProtKB:P27986}.
CC -!- SUBUNIT: Heterodimer of a regulatory subunit PIK3R1 and a p110
CC catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts (via SH2
CC domains) with CCDC88A/GIV (tyrosine-phosphorylated form); the
CC interaction enables recruitment of PIK3R1 to the EGFR receptor,
CC enhancing PI3K activity and cell migration (By similarity). Interacts
CC with phosphorylated LAT, LAX1, TRAT1 and LIME1 upon TCR and/or
CC activation. Interacts with phosphorylated TOM1L1. Interacts with CBLB.
CC The SH2 domains interact with the YTHM motif of phosphorylated INSR in
CC vitro. Also interacts with tyrosine-phosphorylated IGF1R in vitro.
CC Interacts with CD28 and CD3Z upon T-cell activation. Interacts with
CC NISCH, SOCS7 and HCST. Interacts with RUFY3. Interacts with AXL, FASLG,
CC FER, FGR, HCK, KIT and BCR. Interacts with PDGFRA (tyrosine
CC phosphorylated) and PDGFRB (tyrosine phosphorylated). Interacts (via
CC SH2 domain) with CSF1R (tyrosine phosphorylated). Interacts with ERBB4
CC (phosphorylated). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine
CC phosphorylated). Interacts with LYN (via SH3 domain); this enhances
CC enzyme activity. Interacts with NTRK1 (phosphorylated upon ligand-
CC binding). Interacts with PIK3R2; the interaction is dissociated in an
CC insulin-dependent manner. Interacts with XBP1; the interaction is
CC direct and induces translocation of XBP1 into the nucleus in a ER
CC stress- and/or insulin-dependent but PI3K-independent manner (By
CC similarity). Interacts with FGFR1, FGFR2, FGFR3 and FGFR4
CC (phosphorylated) (Probable). Interacts with IRS1 and phosphorylated
CC IRS4 (PubMed:8628286). Interacts with PTK2/FAK1 (PubMed:8824286).
CC Interacts with FAM83B; activates the PI3K/AKT signaling cascade (By
CC similarity). Interacts with APPL1 and APPL2 (By similarity). Interacts
CC with SRC (By similarity). Interacts with ALOX5; this interaction
CC bridges ALOX5 with CD40 after CD40 ligation in B cells and leads to the
CC production of reactive oxygen species (ROS) (By similarity). Interacts
CC with TYK2 (By similarity). {ECO:0000250|UniProtKB:P23727,
CC ECO:0000250|UniProtKB:P26450, ECO:0000250|UniProtKB:P27986,
CC ECO:0000269|PubMed:8628286, ECO:0000269|PubMed:8824286, ECO:0000305}.
CC -!- INTERACTION:
CC Q63787; P21575: Dnm1; NbExp=2; IntAct=EBI-518443, EBI-80070;
CC Q63787; P62813: Gabra1; NbExp=4; IntAct=EBI-518443, EBI-6258192;
CC Q63787; P35570: Irs1; NbExp=2; IntAct=EBI-518443, EBI-520230;
CC Q63787; Q91V33: Khdrbs1; NbExp=2; IntAct=EBI-518443, EBI-518436;
CC Q63787; A0MZ67: Shtn1; NbExp=2; IntAct=EBI-518443, EBI-1392040;
CC Q63787; P18545: PDE6G; Xeno; NbExp=2; IntAct=EBI-518443, EBI-2622029;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=p85-alpha;
CC IsoId=Q63787-1; Sequence=Displayed;
CC Name=p55-alpha;
CC IsoId=Q63787-2; Sequence=VSP_004709, VSP_004710;
CC Name=p50-alpha;
CC IsoId=Q63787-3; Sequence=VSP_004711, VSP_004712;
CC -!- TISSUE SPECIFICITY: The P85-alpha isoform is widely expressed.
CC Expression of the P55-alpha isoform is highest in brain and skeletal
CC muscle. The P50-alpha isoform is abundant in liver with lower levels in
CC brain and muscle.
CC -!- DOMAIN: The SH3 domain mediates the binding to CBLB. {ECO:0000250}.
CC -!- PTM: Polyubiquitinated in T-cells by CBLB; which does not promote
CC proteasomal degradation but impairs association with CD28 and CD3Z upon
CC T-cell activation. {ECO:0000250}.
CC -!- PTM: Phosphorylated. Tyrosine phosphorylated in response to signaling
CC by FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylated by CSF1R.
CC Phosphorylated on tyrosine residues by TEK/TIE2. Dephosphorylated by
CC PTPRJ. Phosphorylated by PIK3CA at Ser-608; phosphorylation is
CC stimulated by insulin and PDGF. The relevance of phosphorylation by
CC PIK3CA is however unclear. Phosphorylated in response to KIT and
CC KITLG/SCF. Phosphorylated by FGR and ERBB4 (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the PI3K p85 subunit family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D64045; BAA18932.1; -; mRNA.
DR EMBL; D64048; BAA18933.1; -; mRNA.
DR EMBL; U50412; AAC52846.1; -; mRNA.
DR EMBL; D78486; BAA24426.1; -; mRNA.
DR RefSeq; NP_037137.1; NM_013005.1. [Q63787-1]
DR PDB; 1FU5; NMR; -; A=322-431.
DR PDB; 1FU6; NMR; -; A=322-431.
DR PDBsum; 1FU5; -.
DR PDBsum; 1FU6; -.
DR AlphaFoldDB; Q63787; -.
DR BMRB; Q63787; -.
DR SMR; Q63787; -.
DR BioGRID; 247545; 10.
DR DIP; DIP-33696N; -.
DR IntAct; Q63787; 18.
DR MINT; Q63787; -.
DR STRING; 10116.ENSRNOP00000025687; -.
DR iPTMnet; Q63787; -.
DR PhosphoSitePlus; Q63787; -.
DR jPOST; Q63787; -.
DR PaxDb; Q63787; -.
DR PRIDE; Q63787; -.
DR GeneID; 25513; -.
DR KEGG; rno:25513; -.
DR UCSC; RGD:3329; rat. [Q63787-1]
DR CTD; 5295; -.
DR RGD; 3329; Pik3r1.
DR eggNOG; KOG4637; Eukaryota.
DR InParanoid; Q63787; -.
DR PhylomeDB; Q63787; -.
DR Reactome; R-RNO-109704; PI3K Cascade.
DR Reactome; R-RNO-112399; IRS-mediated signalling.
DR Reactome; R-RNO-114604; GPVI-mediated activation cascade.
DR Reactome; R-RNO-1250342; PI3K events in ERBB4 signaling.
DR Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
DR Reactome; R-RNO-1266695; Interleukin-7 signaling.
DR Reactome; R-RNO-1433557; Signaling by SCF-KIT.
DR Reactome; R-RNO-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-RNO-180292; GAB1 signalosome.
DR Reactome; R-RNO-186763; Downstream signal transduction.
DR Reactome; R-RNO-1963642; PI3K events in ERBB2 signaling.
DR Reactome; R-RNO-198203; PI3K/AKT activation.
DR Reactome; R-RNO-201556; Signaling by ALK.
DR Reactome; R-RNO-202424; Downstream TCR signaling.
DR Reactome; R-RNO-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-RNO-210993; Tie2 Signaling.
DR Reactome; R-RNO-2424491; DAP12 signaling.
DR Reactome; R-RNO-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-RNO-388841; Costimulation by the CD28 family.
DR Reactome; R-RNO-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-RNO-416476; G alpha (q) signalling events.
DR Reactome; R-RNO-430116; GP1b-IX-V activation signalling.
DR Reactome; R-RNO-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-RNO-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-RNO-5654689; PI-3K cascade:FGFR1.
DR Reactome; R-RNO-5654695; PI-3K cascade:FGFR2.
DR Reactome; R-RNO-5654710; PI-3K cascade:FGFR3.
DR Reactome; R-RNO-5654720; PI-3K cascade:FGFR4.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-RNO-8851907; MET activates PI3K/AKT signaling.
DR Reactome; R-RNO-8853659; RET signaling.
DR Reactome; R-RNO-8980692; RHOA GTPase cycle.
DR Reactome; R-RNO-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-RNO-9013026; RHOB GTPase cycle.
DR Reactome; R-RNO-9013106; RHOC GTPase cycle.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR Reactome; R-RNO-9013404; RAC2 GTPase cycle.
DR Reactome; R-RNO-9013405; RHOD GTPase cycle.
DR Reactome; R-RNO-9013408; RHOG GTPase cycle.
DR Reactome; R-RNO-9013409; RHOJ GTPase cycle.
DR Reactome; R-RNO-9013420; RHOU GTPase cycle.
DR Reactome; R-RNO-9013423; RAC3 GTPase cycle.
DR Reactome; R-RNO-9013424; RHOV GTPase cycle.
DR Reactome; R-RNO-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR Reactome; R-RNO-9035034; RHOF GTPase cycle.
DR Reactome; R-RNO-912526; Interleukin receptor SHC signaling.
DR Reactome; R-RNO-912631; Regulation of signaling by CBL.
DR Reactome; R-RNO-9607240; FLT3 Signaling.
DR Reactome; R-RNO-9696264; RND3 GTPase cycle.
DR Reactome; R-RNO-9696270; RND2 GTPase cycle.
DR Reactome; R-RNO-9696273; RND1 GTPase cycle.
DR Reactome; R-RNO-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR EvolutionaryTrace; Q63787; -.
DR PRO; PR:Q63787; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005911; C:cell-cell junction; ISO:RGD.
DR GO; GO:0005801; C:cis-Golgi network; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:1990578; C:perinuclear endoplasmic reticulum membrane; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IDA:RGD.
DR GO; GO:0005943; C:phosphatidylinositol 3-kinase complex, class IA; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; TAS:RGD.
DR GO; GO:0046935; F:1-phosphatidylinositol-3-kinase regulator activity; IDA:RGD.
DR GO; GO:0051117; F:ATPase binding; IPI:RGD.
DR GO; GO:0005516; F:calmodulin binding; IPI:RGD.
DR GO; GO:0043125; F:ErbB-3 class receptor binding; ISS:UniProtKB.
DR GO; GO:0043559; F:insulin binding; ISO:RGD.
DR GO; GO:0005158; F:insulin receptor binding; ISS:UniProtKB.
DR GO; GO:0043560; F:insulin receptor substrate binding; IPI:RGD.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; ISS:UniProtKB.
DR GO; GO:0005168; F:neurotrophin TRKA receptor binding; ISO:RGD.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; IPI:RGD.
DR GO; GO:0035014; F:phosphatidylinositol 3-kinase regulator activity; ISS:UniProtKB.
DR GO; GO:0036312; F:phosphatidylinositol 3-kinase regulatory subunit binding; ISO:RGD.
DR GO; GO:0051219; F:phosphoprotein binding; IPI:RGD.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:RGD.
DR GO; GO:0005161; F:platelet-derived growth factor receptor binding; IPI:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; IDA:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:RGD.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:RGD.
DR GO; GO:0005102; F:signaling receptor binding; IPI:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0030183; P:B cell differentiation; ISO:RGD.
DR GO; GO:0001678; P:cellular glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0071398; P:cellular response to fatty acid; IEP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0034644; P:cellular response to UV; ISO:RGD.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; ISO:RGD.
DR GO; GO:0006006; P:glucose metabolic process; IMP:RGD.
DR GO; GO:0060396; P:growth hormone receptor signaling pathway; ISO:RGD.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP:RGD.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IMP:RGD.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0045776; P:negative regulation of blood pressure; IMP:RGD.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISO:RGD.
DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; IMP:RGD.
DR GO; GO:0001953; P:negative regulation of cell-matrix adhesion; ISO:RGD.
DR GO; GO:0010459; P:negative regulation of heart rate; IMP:RGD.
DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; IMP:RGD.
DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; ISO:RGD.
DR GO; GO:0045861; P:negative regulation of proteolysis; IMP:RGD.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0051497; P:negative regulation of stress fiber assembly; ISO:RGD.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; ISO:RGD.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:RGD.
DR GO; GO:1900103; P:positive regulation of endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR GO; GO:0051491; P:positive regulation of filopodium assembly; ISO:RGD.
DR GO; GO:0120183; P:positive regulation of focal adhesion disassembly; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; ISO:RGD.
DR GO; GO:0045663; P:positive regulation of myoblast differentiation; IMP:RGD.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:RGD.
DR GO; GO:0033120; P:positive regulation of RNA splicing; ISS:UniProtKB.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IDA:CACAO.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0006606; P:protein import into nucleus; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; ISO:RGD.
DR GO; GO:0043551; P:regulation of phosphatidylinositol 3-kinase activity; IDA:RGD.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; ISO:RGD.
DR GO; GO:0051492; P:regulation of stress fiber assembly; ISO:RGD.
DR GO; GO:0043200; P:response to amino acid; IEP:RGD.
DR GO; GO:0051591; P:response to cAMP; IDA:RGD.
DR GO; GO:0071548; P:response to dexamethasone; IEP:RGD.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0070542; P:response to fatty acid; IEP:RGD.
DR GO; GO:0009750; P:response to fructose; IEP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IDA:RGD.
DR GO; GO:0070848; P:response to growth factor; IEP:RGD.
DR GO; GO:0032868; P:response to insulin; IDA:RGD.
DR GO; GO:0010040; P:response to iron(II) ion; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0032570; P:response to progesterone; IEP:RGD.
DR GO; GO:0033574; P:response to testosterone; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0001878; P:response to yeast; IEP:RGD.
DR CDD; cd12924; iSH2_PIK3R1; 1.
DR CDD; cd09930; SH2_cSH2_p85_like; 1.
DR CDD; cd09942; SH2_nSH2_p85_like; 1.
DR CDD; cd11910; SH3_PI3K_p85alpha; 1.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 3.30.505.10; -; 2.
DR IDEAL; IID50255; -.
DR InterPro; IPR044124; ISH2_PIK3R1.
DR InterPro; IPR032498; PI3K_P85_iSH2.
DR InterPro; IPR035591; PI3K_p85alpha_SH3.
DR InterPro; IPR035020; PI3kinase_P85_cSH2.
DR InterPro; IPR035022; PI3kinase_P85_nSH2.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR000198; RhoGAP_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF16454; PI3K_P85_iSH2; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR Pfam; PF00017; SH2; 2.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00324; RhoGAP; 1.
DR SMART; SM00252; SH2; 2.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 2.
DR PROSITE; PS50238; RHOGAP; 1.
DR PROSITE; PS50001; SH2; 2.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Phosphoprotein;
KW Protein transport; Reference proteome; Repeat; SH2 domain; SH3 domain;
KW Stress response; Transport; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P27986"
FT CHAIN 2..724
FT /note="Phosphatidylinositol 3-kinase regulatory subunit
FT alpha"
FT /id="PRO_0000080760"
FT DOMAIN 3..79
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 113..301
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT DOMAIN 333..428
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 624..718
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 80..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 84..98
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P27986"
FT MOD_RES 154
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27986"
FT MOD_RES 279
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27986"
FT MOD_RES 467
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P26450"
FT MOD_RES 580
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P27986"
FT MOD_RES 608
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23727"
FT VAR_SEQ 1..300
FT /note="Missing (in isoform p50-alpha)"
FT /evidence="ECO:0000303|PubMed:8921377,
FT ECO:0000303|PubMed:9065454"
FT /id="VSP_004711"
FT VAR_SEQ 1..270
FT /note="Missing (in isoform p55-alpha)"
FT /evidence="ECO:0000303|PubMed:8621382"
FT /id="VSP_004709"
FT VAR_SEQ 271..304
FT /note="VLFRFPAASSDNTEHLIKAVELLISAEWSERQPA -> MYTTVWTMEDLDLE
FT CAKTDINCGTDLMFYIEMDP (in isoform p55-alpha)"
FT /evidence="ECO:0000303|PubMed:8621382"
FT /id="VSP_004710"
FT VAR_SEQ 301..306
FT /note="RQPAPA -> MHNLQT (in isoform p50-alpha)"
FT /evidence="ECO:0000303|PubMed:8921377,
FT ECO:0000303|PubMed:9065454"
FT /id="VSP_004712"
FT STRAND 324..327
FT /evidence="ECO:0007829|PDB:1FU5"
FT HELIX 340..346
FT /evidence="ECO:0007829|PDB:1FU5"
FT STRAND 347..349
FT /evidence="ECO:0007829|PDB:1FU5"
FT STRAND 358..360
FT /evidence="ECO:0007829|PDB:1FU6"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:1FU6"
FT STRAND 371..374
FT /evidence="ECO:0007829|PDB:1FU6"
FT STRAND 377..380
FT /evidence="ECO:0007829|PDB:1FU6"
FT STRAND 385..393
FT /evidence="ECO:0007829|PDB:1FU5"
FT HELIX 403..407
FT /evidence="ECO:0007829|PDB:1FU5"
FT STRAND 408..411
FT /evidence="ECO:0007829|PDB:1FU5"
FT STRAND 415..417
FT /evidence="ECO:0007829|PDB:1FU5"
SQ SEQUENCE 724 AA; 83531 MW; 95C65CF612873B84 CRC64;
MSAEGYQYRA LYDYKKEREE DIDLHLGDIL TVNKGSLVAL GFSDGQEARP EDIGWLNGYN
ETTGERGDFP GTYVEYIGRK RISPPTPKPR PPRPLPVAPG SSKTEADTEQ PVLTLPDLAE
QFAPPDVAPP LLIKLLEAIE KKGLECSTLY RTQSSSNPAE LRQLLDCDPP SVDLDVFDEH
VLADAFKRYL ADLPNPVIPV AVYNEMMSLA QEVPSSEDYI QLLKKLIRSP NIPHQYWLTL
QYLLKHFFKL SQASSKNLLN ARALSEIFSH VLFRFPAASS DNTEHLIKAV ELLISAEWSE
RQPAPALPPK PPKPTSIANN SMNNNMSLQD AEWYWGDISR EEVNEKLRDT ADGTFLVRDA
STKMHGDYTL TLRKGGNNKL IKIFHRDGKY GFSDPLTFNS VVELINHYRN ESLAQYNPKL
DVKLLYPVSK YQQDQVVKED NIEAVGKKLH EYNTQFQEKS REYDRLYEEY TRTSQEIQMK
RTAIEAFNDT IKIFEEQCHP QERYSKDYIE KFKREGNEKE IQRIMHNHDK LKSRISEIID
SRRRLEEDLK KQAAEYREID KRMNSIKPDL IQLRKTRDQY LMWLTQKGVR QKKLNEWLGN
ENTEDQYSLV DDDEDLPHHD EKTWNVGSSN RNKAENLLRG KRDGTFLVRE SSKQGCYACS
VVVDGEVKHC VINKTATGYG FAEPYNLYSS LKELVLHYQH TSLVQHNDSL NVTLAYPVYA
QQRR
