PK3CA_MOUSE
ID PK3CA_MOUSE Reviewed; 1068 AA.
AC P42337; Q0VGQ5;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform;
DE Short=PI3-kinase subunit alpha;
DE Short=PI3K-alpha;
DE Short=PI3Kalpha;
DE Short=PtdIns-3-kinase subunit alpha;
DE EC=2.7.1.137 {ECO:0000250|UniProtKB:P42336};
DE EC=2.7.1.153 {ECO:0000250|UniProtKB:P42336};
DE AltName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha;
DE Short=PtdIns-3-kinase subunit p110-alpha;
DE Short=p110alpha;
DE AltName: Full=Phosphoinositide-3-kinase catalytic alpha polypeptide;
DE AltName: Full=Serine/threonine protein kinase PIK3CA;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P32871};
GN Name=Pik3ca;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBUNIT.
RC STRAIN=BALB/cJ;
RX PubMed=8139567; DOI=10.1128/mcb.14.4.2675-2685.1994;
RA Klippel A., Escobedo J.A., Hirano M., Williams L.T.;
RT "The interaction of small domains between the subunits of
RT phosphatidylinositol 3-kinase determines enzyme activity.";
RL Mol. Cell. Biol. 14:2675-2685(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH IRS1.
RX PubMed=15197263; DOI=10.1073/pnas.0403328101;
RA Drakas R., Tu X., Baserga R.;
RT "Control of cell size through phosphorylation of upstream binding factor 1
RT by nuclear phosphatidylinositol 3-kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:9272-9276(2004).
RN [5]
RP FUNCTION.
RX PubMed=16647110; DOI=10.1016/j.cell.2006.03.035;
RA Knight Z.A., Gonzalez B., Feldman M.E., Zunder E.R., Goldenberg D.D.,
RA Williams O., Loewith R., Stokoe D., Balla A., Toth B., Balla T.,
RA Weiss W.A., Williams R.L., Shokat K.M.;
RT "A pharmacological map of the PI3-K family defines a role for p110alpha in
RT insulin signaling.";
RL Cell 125:733-747(2006).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ASP-933.
RX PubMed=16625210; DOI=10.1038/nature04694;
RA Foukas L.C., Claret M., Pearce W., Okkenhaug K., Meek S., Peskett E.,
RA Sancho S., Smith A.J.H., Withers D.J., Vanhaesebroeck B.;
RT "Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and
RT metabolic regulation.";
RL Nature 441:366-370(2006).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17060635; DOI=10.1073/pnas.0607899103;
RA Zhao J.J., Cheng H., Jia S., Wang L., Gjoerup O.V., Mikami A.,
RA Roberts T.M.;
RT "The p110alpha isoform of PI3K is essential for proper growth factor
RT signaling and oncogenic transformation.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:16296-16300(2006).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH HRAS AND KRAS, AND
RP MUTAGENESIS OF THR-208 AND LYS-227.
RX PubMed=17540175; DOI=10.1016/j.cell.2007.03.051;
RA Gupta S., Ramjaun A.R., Haiko P., Wang Y., Warne P.H., Nicke B., Nye E.,
RA Stamp G., Alitalo K., Downward J.;
RT "Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-
RT driven tumorigenesis in mice.";
RL Cell 129:957-968(2007).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18449193; DOI=10.1038/nature06892;
RA Graupera M., Guillermet-Guibert J., Foukas L.C., Phng L.-K., Cain R.J.,
RA Salpekar A., Pearce W., Meek S., Millan J., Cutillas P.R., Smith A.J.H.,
RA Ridley A.J., Ruhrberg C., Gerhardt H., Vanhaesebroeck B.;
RT "Angiogenesis selectively requires the p110alpha isoform of PI3K to control
RT endothelial cell migration.";
RL Nature 453:662-666(2008).
RN [10]
RP FUNCTION.
RX PubMed=19604150; DOI=10.1042/bj20090687;
RA Tamura N., Hazeki K., Okazaki N., Kametani Y., Murakami H., Takaba Y.,
RA Ishikawa Y., Nigorikawa K., Hazeki O.;
RT "Specific role of phosphoinositide 3-kinase p110alpha in the regulation of
RT phagocytosis and pinocytosis in macrophages.";
RL Biochem. J. 423:99-108(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [12]
RP FUNCTION IN CARDIOMYOGENESIS, AND FUNCTION IN VASCULOGENESIS.
RX PubMed=21540297; DOI=10.1242/jcs.077594;
RA Bekhite M.M., Finkensieper A., Binas S., Mueller J., Wetzker R.,
RA Figulla H.-R., Sauer H., Wartenberg M.;
RT "VEGF-mediated PI3K class IA and PKC signaling in cardiomyogenesis and
RT vasculogenesis of mouse embryonic stem cells.";
RL J. Cell Sci. 124:1819-1830(2011).
CC -!- FUNCTION: Phosphoinositide-3-kinase (PI3K) phosphorylates
CC phosphatidylinositol (PI) and its phosphorylated derivatives at
CC position 3 of the inositol ring to produce 3-phosphoinositides. Uses
CC ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to
CC generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a
CC key role by recruiting PH domain-containing proteins to the membrane,
CC including AKT1 and PDPK1, activating signaling cascades involved in
CC cell growth, survival, proliferation, motility and morphology.
CC Participates in cellular signaling in response to various growth
CC factors. Involved in the activation of AKT1 upon stimulation by
CC receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and
CC PDGF. Involved in signaling via insulin-receptor substrate (IRS)
CC proteins. Essential in endothelial cell migration during vascular
CC development through VEGFA signaling, possibly by regulating RhoA
CC activity. Required for lymphatic vasculature development, possibly by
CC binding to RAS and by activation by EGF and FGF2, but not by PDGF.
CC Regulates invadopodia formation through the PDPK1-AKT1 pathway.
CC Participates in cardiomyogenesis in embryonic stem cells through a AKT1
CC pathway. Participates in vasculogenesis in embryonic stem cells through
CC PDK1 and protein kinase C pathway. Also has serine-protein kinase
CC activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1
CC and HRAS. Plays a role in the positive regulation of phagocytosis and
CC pinocytosis (PubMed:19604150). {ECO:0000269|PubMed:16625210,
CC ECO:0000269|PubMed:16647110, ECO:0000269|PubMed:17060635,
CC ECO:0000269|PubMed:17540175, ECO:0000269|PubMed:18449193,
CC ECO:0000269|PubMed:19604150, ECO:0000269|PubMed:21540297}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3,4,5-trisphosphate) + ADP + H(+); Xref=Rhea:RHEA:21292,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57836,
CC ChEBI:CHEBI:58456, ChEBI:CHEBI:456216; EC=2.7.1.153;
CC Evidence={ECO:0000250|UniProtKB:P42336};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21293;
CC Evidence={ECO:0000250|UniProtKB:P42336};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a
CC 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP +
CC H(+); Xref=Rhea:RHEA:12709, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57880, ChEBI:CHEBI:58088, ChEBI:CHEBI:456216;
CC EC=2.7.1.137; Evidence={ECO:0000250|UniProtKB:P42336};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710;
CC Evidence={ECO:0000250|UniProtKB:P42336};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:P32871};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000250|UniProtKB:P32871};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC bisphosphate) + ATP = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3,4,5-trisphosphate) + ADP + H(+); Xref=Rhea:RHEA:55632,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:83416,
CC ChEBI:CHEBI:83419, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P42336};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55633;
CC Evidence={ECO:0000250|UniProtKB:P42336};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-
CC 3-phospho-1D-myo-inositol 4,5-bisphosphate + ATP = 1-octadecanoyl-2-
CC (5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-
CC inositol 3,4,5-triphosphate) + ADP + H(+); Xref=Rhea:RHEA:43396,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77137,
CC ChEBI:CHEBI:83243, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P42336};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43397;
CC Evidence={ECO:0000250|UniProtKB:P42336};
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylinositol phosphate
CC biosynthesis. {ECO:0000250|UniProtKB:P42336}.
CC -!- SUBUNIT: Heterodimer of a catalytic subunit PIK3CA and a p85 regulatory
CC subunit (PIK3R1, PIK3R2 or PIK3R3) (PubMed:8139567). Interacts with
CC IRS1 in nuclear extracts (PubMed:15197263). Interacts with RUFY3.
CC Interacts with RASD2. Interacts with APPL1 (By similarity). Interacts
CC with HRAS and KRAS (PubMed:17540175). Interaction with HRAS/KRAS is
CC required for PI3K pathway signaling and cell proliferation stimulated
CC by EGF and FGF2 (PubMed:17540175). Interacts with FAM83B; activates the
CC PI3K/AKT signaling cascade (By similarity).
CC {ECO:0000250|UniProtKB:P42336, ECO:0000269|PubMed:15197263,
CC ECO:0000269|PubMed:17540175, ECO:0000269|PubMed:8139567}.
CC -!- INTERACTION:
CC P42337; P41241: Csk; NbExp=2; IntAct=EBI-641748, EBI-2553183;
CC P42337; P26450: Pik3r1; NbExp=7; IntAct=EBI-641748, EBI-641764;
CC P42337; P01112: HRAS; Xeno; NbExp=2; IntAct=EBI-641748, EBI-350145;
CC -!- DOMAIN: The PI3K-ABD domain and the PI3K-RBD domain interact with the
CC PI3K/PI4K kinase domain. The C2 PI3K-type domain may facilitate the
CC recruitment to the plasma membrane. The inhibitory interactions with
CC PIK3R1 are mediated by the PI3K-ABD domain and the C2 PI3K-type domain
CC with the iSH2 (inter-SH2) region of PIK3R1, and the C2 PI3K-type
CC domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with
CC the nSH2 (N-terminal SH2) region of PIK3R1.
CC {ECO:0000250|UniProtKB:P42336}.
CC -!- DISRUPTION PHENOTYPE: Lethal. Embryonic fibroblasts cells are resistant
CC to oncogenic transformation induced by oncogenic receptor tyrosine
CC kinases (RTKs), are unable to differentiate into adipocytes and
CC deficient in cellular signaling in response to various growth factors.
CC Defective responsiveness to insulin led to reduced somatic growth,
CC hyperinsulinemia, glucose intolerance, hyperphagia and increased
CC adiposity. {ECO:0000269|PubMed:16625210, ECO:0000269|PubMed:17060635,
CC ECO:0000269|PubMed:17540175, ECO:0000269|PubMed:18449193}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU00877, ECO:0000255|PROSITE-ProRule:PRU00879,
CC ECO:0000255|PROSITE-ProRule:PRU00880}.
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DR EMBL; U03279; AAA18334.1; -; mRNA.
DR EMBL; CH466530; EDL34990.1; -; Genomic_DNA.
DR EMBL; BC089038; AAH89038.1; -; mRNA.
DR EMBL; BC130228; AAI30229.1; -; mRNA.
DR CCDS; CCDS38409.1; -.
DR RefSeq; NP_032865.2; NM_008839.2.
DR RefSeq; XP_006535472.1; XM_006535409.3.
DR RefSeq; XP_006535473.1; XM_006535410.3.
DR PDB; 4A55; X-ray; 3.50 A; A=1-1068.
DR PDBsum; 4A55; -.
DR AlphaFoldDB; P42337; -.
DR SMR; P42337; -.
DR BioGRID; 202160; 11.
DR CORUM; P42337; -.
DR DIP; DIP-32095N; -.
DR IntAct; P42337; 10.
DR MINT; P42337; -.
DR STRING; 10090.ENSMUSP00000029201; -.
DR BindingDB; P42337; -.
DR ChEMBL; CHEMBL2499; -.
DR iPTMnet; P42337; -.
DR PhosphoSitePlus; P42337; -.
DR EPD; P42337; -.
DR MaxQB; P42337; -.
DR PaxDb; P42337; -.
DR PRIDE; P42337; -.
DR ProteomicsDB; 289599; -.
DR Antibodypedia; 1374; 754 antibodies from 43 providers.
DR DNASU; 18706; -.
DR Ensembl; ENSMUST00000029201; ENSMUSP00000029201; ENSMUSG00000027665.
DR Ensembl; ENSMUST00000108243; ENSMUSP00000103878; ENSMUSG00000027665.
DR GeneID; 18706; -.
DR KEGG; mmu:18706; -.
DR UCSC; uc008owd.2; mouse.
DR CTD; 5290; -.
DR MGI; MGI:1206581; Pik3ca.
DR VEuPathDB; HostDB:ENSMUSG00000027665; -.
DR eggNOG; KOG0904; Eukaryota.
DR GeneTree; ENSGT00940000155531; -.
DR HOGENOM; CLU_002191_1_1_1; -.
DR InParanoid; P42337; -.
DR OMA; EHANWTV; -.
DR OrthoDB; 204282at2759; -.
DR PhylomeDB; P42337; -.
DR TreeFam; TF102031; -.
DR BRENDA; 2.7.1.137; 3474.
DR BRENDA; 2.7.1.153; 3474.
DR Reactome; R-MMU-109704; PI3K Cascade.
DR Reactome; R-MMU-112399; IRS-mediated signalling.
DR Reactome; R-MMU-114604; GPVI-mediated activation cascade.
DR Reactome; R-MMU-1250342; PI3K events in ERBB4 signaling.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-1433557; Signaling by SCF-KIT.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-MMU-180292; GAB1 signalosome.
DR Reactome; R-MMU-186763; Downstream signal transduction.
DR Reactome; R-MMU-1963642; PI3K events in ERBB2 signaling.
DR Reactome; R-MMU-198203; PI3K/AKT activation.
DR Reactome; R-MMU-201556; Signaling by ALK.
DR Reactome; R-MMU-202424; Downstream TCR signaling.
DR Reactome; R-MMU-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-MMU-210993; Tie2 Signaling.
DR Reactome; R-MMU-2424491; DAP12 signaling.
DR Reactome; R-MMU-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-MMU-388841; Costimulation by the CD28 family.
DR Reactome; R-MMU-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-MMU-416476; G alpha (q) signalling events.
DR Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-MMU-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-MMU-5654689; PI-3K cascade:FGFR1.
DR Reactome; R-MMU-5654695; PI-3K cascade:FGFR2.
DR Reactome; R-MMU-5654710; PI-3K cascade:FGFR3.
DR Reactome; R-MMU-5654720; PI-3K cascade:FGFR4.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-8851907; MET activates PI3K/AKT signaling.
DR Reactome; R-MMU-8853659; RET signaling.
DR Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013404; RAC2 GTPase cycle.
DR Reactome; R-MMU-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR Reactome; R-MMU-912526; Interleukin receptor SHC signaling.
DR Reactome; R-MMU-912631; Regulation of signaling by CBL.
DR Reactome; R-MMU-9607240; FLT3 Signaling.
DR UniPathway; UPA00220; -.
DR BioGRID-ORCS; 18706; 5 hits in 77 CRISPR screens.
DR ChiTaRS; Pik3ca; mouse.
DR PRO; PR:P42337; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P42337; protein.
DR Bgee; ENSMUSG00000027665; Expressed in rostral migratory stream and 253 other tissues.
DR ExpressionAtlas; P42337; baseline and differential.
DR Genevisible; P42337; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0014704; C:intercalated disc; IDA:BHF-UCL.
DR GO; GO:0030027; C:lamellipodium; IDA:MGI.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IPI:MGI.
DR GO; GO:0005943; C:phosphatidylinositol 3-kinase complex, class IA; ISO:MGI.
DR GO; GO:0005944; C:phosphatidylinositol 3-kinase complex, class IB; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IDA:MGI.
DR GO; GO:0035005; F:1-phosphatidylinositol-4-phosphate 3-kinase activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043560; F:insulin receptor substrate binding; IPI:MGI.
DR GO; GO:0016301; F:kinase activity; ISO:MGI.
DR GO; GO:0052742; F:phosphatidylinositol kinase activity; IBA:GO_Central.
DR GO; GO:0052812; F:phosphatidylinositol-3,4-bisphosphate 5-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0046934; F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity; TAS:Reactome.
DR GO; GO:0030295; F:protein kinase activator activity; IDA:BHF-UCL.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0030036; P:actin cytoskeleton organization; IMP:BHF-UCL.
DR GO; GO:0060612; P:adipose tissue development; IMP:MGI.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0086003; P:cardiac muscle cell contraction; IMP:BHF-UCL.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IMP:MGI.
DR GO; GO:0071464; P:cellular response to hydrostatic pressure; IMP:BHF-UCL.
DR GO; GO:0097009; P:energy homeostasis; IMP:MGI.
DR GO; GO:0006006; P:glucose metabolic process; IMP:MGI.
DR GO; GO:0044029; P:hypomethylation of CpG island; IDA:BHF-UCL.
DR GO; GO:0001889; P:liver development; IMP:MGI.
DR GO; GO:0030835; P:negative regulation of actin filament depolymerization; IMP:BHF-UCL.
DR GO; GO:2000811; P:negative regulation of anoikis; ISO:MGI.
DR GO; GO:2000270; P:negative regulation of fibroblast apoptotic process; IDA:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI.
DR GO; GO:0006909; P:phagocytosis; IEA:UniProtKB-KW.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IMP:BHF-UCL.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; ISO:MGI.
DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; ISO:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0043491; P:protein kinase B signaling; IMP:MGI.
DR GO; GO:0110053; P:regulation of actin filament organization; IMP:BHF-UCL.
DR GO; GO:0043457; P:regulation of cellular respiration; IMP:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:2000653; P:regulation of genetic imprinting; IDA:BHF-UCL.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IMP:MGI.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IDA:MGI.
DR GO; GO:0055119; P:relaxation of cardiac muscle; IMP:BHF-UCL.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR GO; GO:1903544; P:response to butyrate; IEA:Ensembl.
DR GO; GO:0071548; P:response to dexamethasone; IEA:Ensembl.
DR GO; GO:0043201; P:response to leucine; IEA:Ensembl.
DR GO; GO:0014870; P:response to muscle inactivity; IEA:Ensembl.
DR GO; GO:0035994; P:response to muscle stretch; IMP:BHF-UCL.
DR GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; ISO:MGI.
DR CDD; cd05175; PI3Kc_IA_alpha; 1.
DR DisProt; DP02792; -.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.25.40.70; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR InterPro; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR002420; PI3K-type_C2_dom.
DR InterPro; IPR003113; PI3K_ABD.
DR InterPro; IPR001263; PI3K_accessory_dom.
DR InterPro; IPR042236; PI3K_accessory_sf.
DR InterPro; IPR000341; PI3K_Ras-bd_dom.
DR InterPro; IPR037704; PI3Kalpha_dom.
DR InterPro; IPR015433; PI_Kinase.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR10048; PTHR10048; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF00792; PI3K_C2; 1.
DR Pfam; PF02192; PI3K_p85B; 1.
DR Pfam; PF00794; PI3K_rbd; 1.
DR Pfam; PF00613; PI3Ka; 1.
DR SMART; SM00142; PI3K_C2; 1.
DR SMART; SM00143; PI3K_p85B; 1.
DR SMART; SM00144; PI3K_rbd; 1.
DR SMART; SM00145; PI3Ka; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51547; C2_PI3K; 1.
DR PROSITE; PS00915; PI3_4_KINASE_1; 1.
DR PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
DR PROSITE; PS51544; PI3K_ABD; 1.
DR PROSITE; PS51546; PI3K_RBD; 1.
DR PROSITE; PS51545; PIK_HELICAL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Angiogenesis; ATP-binding; Kinase; Nucleotide-binding;
KW Phagocytosis; Proto-oncogene; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..1068
FT /note="Phosphatidylinositol 4,5-bisphosphate 3-kinase
FT catalytic subunit alpha isoform"
FT /id="PRO_0000088786"
FT DOMAIN 16..105
FT /note="PI3K-ABD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00877"
FT DOMAIN 187..289
FT /note="PI3K-RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00879"
FT DOMAIN 330..487
FT /note="C2 PI3K-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00880"
FT DOMAIN 517..694
FT /note="PIK helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00878"
FT DOMAIN 765..1051
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 771..777
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 912..920
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 931..957
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT MUTAGEN 208
FT /note="T->D: Abolishes binding to HRAS and KRAS; does not
FT affect kinase activity; displays defective development of
FT the lymphatic vasculature, resulting in perinatal
FT appearance of chylous ascites and is highly resistant to
FT endogenous Ras oncogene-induced tumorigenesis; when
FT associated with A-227."
FT /evidence="ECO:0000269|PubMed:17540175"
FT MUTAGEN 227
FT /note="K->A: Abolishes binding to HRAS and KRAS; does not
FT affect kinase activity; displays defective development of
FT the lymphatic vasculature, resulting in perinatal
FT appearance of chylous ascites and is highly resistant to
FT endogenous Ras oncogene-induced tumorigenesis; when
FT associated with D-208."
FT /evidence="ECO:0000269|PubMed:17540175"
FT MUTAGEN 933
FT /note="D->A: Loss of kinase activity; displays early
FT embryonic lethality at 10-11 dpc and severe defects in
FT angiogenic sprouting and vascular remodeling. Heterozygous
FT mice yield adult mice with markedly impaired insulin
FT signaling and reduced activation of effector pathways such
FT as Akt/PKB."
FT /evidence="ECO:0000269|PubMed:16625210"
FT CONFLICT 399
FT /note="A -> L (in Ref. 1; AAA18334)"
FT /evidence="ECO:0000305"
FT STRAND 8..12
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 18..25
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 31..37
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 42..52
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:4A55"
FT TURN 57..60
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 69..74
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 77..81
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 90..92
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 94..102
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 109..112
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 117..121
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 125..129
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 134..142
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 144..153
FT /evidence="ECO:0007829|PDB:4A55"
FT TURN 154..157
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 158..165
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 179..182
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 189..196
FT /evidence="ECO:0007829|PDB:4A55"
FT TURN 199..202
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 205..212
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 217..230
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 236..246
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 250..254
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 267..269
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 271..279
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 284..289
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 290..295
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 324..327
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 332..340
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 348..350
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 354..364
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 378..380
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 382..392
FT /evidence="ECO:0007829|PDB:4A55"
FT TURN 393..395
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 401..408
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 423..430
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 434..436
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 439..444
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 454..456
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 458..460
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 468..470
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 472..477
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 481..485
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 489..499
FT /evidence="ECO:0007829|PDB:4A55"
FT TURN 529..535
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 545..553
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 555..558
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 562..564
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 565..569
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 578..588
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 595..598
FT /evidence="ECO:0007829|PDB:4A55"
FT TURN 599..602
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 609..621
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 625..630
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 632..636
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 639..641
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 643..646
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 648..659
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 661..673
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 678..694
FT /evidence="ECO:0007829|PDB:4A55"
FT TURN 695..697
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 698..720
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 728..738
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 742..747
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 749..752
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 759..761
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 779..784
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 790..792
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 795..805
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 808..827
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 838..842
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 845..849
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 854..856
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 857..860
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 876..884
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 887..889
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 890..911
FT /evidence="ECO:0007829|PDB:4A55"
FT TURN 918..920
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 921..924
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 929..931
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 941..945
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 957..964
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 965..967
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 975..993
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 995..1004
FT /evidence="ECO:0007829|PDB:4A55"
FT STRAND 1013..1015
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 1016..1025
FT /evidence="ECO:0007829|PDB:4A55"
FT HELIX 1032..1043
FT /evidence="ECO:0007829|PDB:4A55"
FT TURN 1046..1049
FT /evidence="ECO:0007829|PDB:4A55"
FT TURN 1057..1059
FT /evidence="ECO:0007829|PDB:4A55"
SQ SEQUENCE 1068 AA; 124412 MW; D593283B416ABFD0 CRC64;
MPPRPSSGEL WGIHLMPPRI LVECLLPNGM IVTLECLREA TLVTIKHELF REARKYPLHQ
LLQDETSYIF VSVTQEAERE EFFDETRRLC DLRLFQPFLK VIEPVGNREE KILNREIGFV
IGMPVCEFDM VKDPEVQDFR RNILNVCKEA VDLRDLNSPH SRAMYVYPPN VESSPELPKH
IYNKLDKGQI IVVIWVIVSP NNDKQKYTLK INHDCVPEQV IAEAIRKKTR SMLLSSEQLK
LCVLEYQGKY ILKVCGCDEY FLEKYPLSQY KYIRSCIMLG RMPNLMLMAK ESLYSQLPID
SFTMPSYSRR ISTATPYMNG ETSTKSLWVI NSALRIKILC ATYVNVNIRD IDKIYVRTGI
YHGGEPLCDN VNTQRVPCSN PRWNEWLNYD IYIPDLPRAA RLCLSICSVK GRKGAKEEHC
PLAWGNINLF DYTDTLVSGK MALNLWPVPH GLEDLLNPIG VTGSNPNKET PCLELEFDWF
SSVVKFPDMS VIEEHANWSV SREAGFSYSH TGLSNRLARD NELRENDKEQ LRALCTRDPL
SEITEQEKDF LWSHRHYCVT IPEILPKLLL SVKWNSRDEV AQMYCLVKDW PPIKPEQAME
LLDCNYPDPM VRSFAVRCLE KYLTDDKLSQ YLIQLVQVLK YEQYLDNLLV RFLLKKALTN
QRIGHFFFWH LKSEMHNKTV SQRFGLLLES YCRACGMYLK HLNRQVEAME KLINLTDILK
QEKKDETQKV QMKFLVEQMR QPDFMDALQG FLSPLNPAHQ LGNLRLEECR IMSSAKRPLW
LNWENPDIMS ELLFQNNEII FKNGDDLRQD MLTLQIIRIM ENIWQNQGLD LRMLPYGCLS
IGDCVGLIEV VRNSHTIMQI QCKGGLKGAL QFNSHTLHQW LKDKNKGEIY DAAIDLFTRS
CAGYCVATFI LGIGDRHNSN IMVKDDGQLF HIDFGHFLDH KKKKFGYKRE RVPFVLTQDF
LIVISKGAQE YTKTREFERF QEMCYKAYLA IRQHANLFIN LFSMMLGSGM PELQSFDDIA
YIRKTLALDK TEQEALEYFT KQMNDAHHGG WTTKMDWIFH TIKQHALN
