PK3CG_MOUSE
ID PK3CG_MOUSE Reviewed; 1102 AA.
AC Q9JHG7; Q80V09;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform;
DE Short=PI3-kinase subunit gamma;
DE Short=PI3K-gamma;
DE Short=PI3Kgamma;
DE Short=PtdIns-3-kinase subunit gamma;
DE EC=2.7.1.137 {ECO:0000269|PubMed:11054537};
DE EC=2.7.1.153 {ECO:0000250|UniProtKB:P48736};
DE EC=2.7.1.154 {ECO:0000250|UniProtKB:P48736};
DE AltName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma;
DE Short=PtdIns-3-kinase subunit p110-gamma;
DE Short=p110gamma;
DE AltName: Full=Phosphoinositide-3-kinase catalytic gamma polypeptide;
DE AltName: Full=Serine/threonine protein kinase PIK3CG {ECO:0000250|UniProtKB:P48736};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P48736};
DE AltName: Full=p120-PI3K;
GN Name=Pik3cg; Synonyms=Pi3kg1;
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 [GENOMIC DNA / MRNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP ACTIVITY REGULATION.
RX PubMed=11054537; DOI=10.1016/s0378-1119(00)00328-0;
RA Hirsch E., Wymann M.P., Patrucco E., Tolosano E., Bulgarelli-Leva G.,
RA Marengo S., Rocchi M., Altruda F.;
RT "Analysis of the murine phosphoinositide 3-kinase gamma gene.";
RL Gene 256:69-81(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N-3; TISSUE=Mammary tumor;
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 [3]
RP PROTEIN SEQUENCE OF 1060-1065, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [4]
RP FUNCTION ON INFLAMMATION AND CHEMOTACTIC RESPONSE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=10669416; DOI=10.1126/science.287.5455.1040;
RA Sasaki T., Irie-Sasaki J., Jones R.G., Oliveira-dos-Santos A.J.,
RA Stanford W.L., Bolon B., Wakeham A., Itie A., Bouchard D., Kozieradzki I.,
RA Joza N., Mak T.W., Ohashi P.S., Suzuki A., Penninger J.M.;
RT "Function of PI3Kgamma in thymocyte development, T cell activation, and
RT neutrophil migration.";
RL Science 287:1040-1046(2000).
RN [5]
RP FUNCTION ON INFLAMMATION AND CHEMOTACTIC RESPONSE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=10669418; DOI=10.1126/science.287.5455.1049;
RA Hirsch E., Katanaev V.L., Garlanda C., Azzolino O., Pirola L., Silengo L.,
RA Sozzani S., Mantovani A., Altruda F., Wymann M.P.;
RT "Central role for G protein-coupled phosphoinositide 3-kinase gamma in
RT inflammation.";
RL Science 287:1049-1053(2000).
RN [6]
RP INTERACTION WITH EPHA8.
RX PubMed=11416136; DOI=10.1128/mcb.21.14.4579-4597.2001;
RA Gu C., Park S.;
RT "The EphA8 receptor regulates integrin activity through p110gamma
RT phosphatidylinositol-3 kinase in a tyrosine kinase activity-independent
RT manner.";
RL Mol. Cell. Biol. 21:4579-4597(2001).
RN [7]
RP FUNCTION ON CARDIAC CONTRACTILITY, AND DISRUPTION PHENOTYPE.
RX PubMed=12297047; DOI=10.1016/s0092-8674(02)00969-8;
RA Crackower M.A., Oudit G.Y., Kozieradzki I., Sarao R., Sun H., Sasaki T.,
RA Hirsch E., Suzuki A., Shioi T., Irie-Sasaki J., Sah R., Cheng H.-Y.M.,
RA Rybin V.O., Lembo G., Fratta L., Oliveira-dos-Santos A.J., Benovic J.L.,
RA Kahn C.R., Izumo S., Steinberg S.F., Wymann M.P., Backx P.H.,
RA Penninger J.M.;
RT "Regulation of myocardial contractility and cell size by distinct PI3K-PTEN
RT signaling pathways.";
RL Cell 110:737-749(2002).
RN [8]
RP FUNCTION, INTERACTION WITH PDE3B, AND DISRUPTION PHENOTYPE.
RX PubMed=15294162; DOI=10.1016/j.cell.2004.07.017;
RA Patrucco E., Notte A., Barberis L., Selvetella G., Maffei A.,
RA Brancaccio M., Marengo S., Russo G., Azzolino O., Rybalkin S.D.,
RA Silengo L., Altruda F., Wetzker R., Wymann M.P., Lembo G., Hirsch E.;
RT "PI3Kgamma modulates the cardiac response to chronic pressure overload by
RT distinct kinase-dependent and -independent effects.";
RL Cell 118:375-387(2004).
RN [9]
RP FUNCTION ON IMMUNE RESPONSE, AND DISRUPTION PHENOTYPE.
RX PubMed=15318168; DOI=10.1038/sj.emboj.7600361;
RA Del Prete A., Vermi W., Dander E., Otero K., Barberis L., Luini W.,
RA Bernasconi S., Sironi M., Santoro A., Garlanda C., Facchetti F.,
RA Wymann M.P., Vecchi A., Hirsch E., Mantovani A., Sozzani S.;
RT "Defective dendritic cell migration and activation of adaptive immunity in
RT PI3Kgamma-deficient mice.";
RL EMBO J. 23:3505-3515(2004).
RN [10]
RP FUNCTION IN T-CELL DEVELOPMENT.
RX PubMed=16116162; DOI=10.4049/jimmunol.175.5.2783;
RA Webb L.M.C., Vigorito E., Wymann M.P., Hirsch E., Turner M.;
RT "T cell development requires the combined activities of the p110gamma and
RT p110delta catalytic isoforms of phosphatidylinositol 3-kinase.";
RL J. Immunol. 175:2783-2787(2005).
RN [11]
RP FUNCTION ON INFLAMMATION AND CHEMOTACTIC RESPONSE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=16127437; DOI=10.1038/nm1284;
RA Camps M., Rueckle T., Ji H., Ardissone V., Rintelen F., Shaw J.,
RA Ferrandi C., Chabert C., Gillieron C., Francon B., Martin T., Gretener D.,
RA Perrin D., Leroy D., Vitte P.-A., Hirsch E., Wymann M.P., Cirillo R.,
RA Schwarz M.K., Rommel C.;
RT "Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse
RT models of rheumatoid arthritis.";
RL Nat. Med. 11:936-943(2005).
RN [12]
RP FUNCTION ON PLATELET AGGREGATION, AND DISRUPTION PHENOTYPE.
RX PubMed=17673465; DOI=10.1074/jbc.m704358200;
RA Schoenwaelder S.M., Ono A., Sturgeon S., Chan S.M., Mangin P.,
RA Maxwell M.J., Turnbull S., Mulchandani M., Anderson K., Kauffenstein G.,
RA Rewcastle G.W., Kendall J., Gachet C., Salem H.H., Jackson S.P.;
RT "Identification of a unique co-operative phosphoinositide 3-kinase
RT signaling mechanism regulating integrin alpha IIb beta 3 adhesive function
RT in platelets.";
RL J. Biol. Chem. 282:28648-28658(2007).
RN [13]
RP FUNCTION IN NATURAL KILLER CELL MIGRATION, AND ACTIVITY REGULATION.
RX PubMed=19297623; DOI=10.1073/pnas.0808594106;
RA Saudemont A., Garcon F., Yadi H., Roche-Molina M., Kim N.,
RA Segonds-Pichon A., Martin-Fontecha A., Okkenhaug K., Colucci F.;
RT "p110gamma and p110delta isoforms of phosphoinositide 3-kinase
RT differentially regulate natural killer cell migration in health and
RT disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:5795-5800(2009).
RN [14]
RP INTERACTION WITH HRAS.
RX PubMed=19906996; DOI=10.1073/pnas.0905506106;
RA Kurig B., Shymanets A., Bohnacker T., Prajwal X., Brock C., Ahmadian M.R.,
RA Schaefer M., Gohla A., Harteneck C., Wymann M.P., Jeanclos E., Nurnberg B.;
RT "Ras is an indispensable coregulator of the class IB phosphoinositide 3-
RT kinase p87/p110gamma.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:20312-20317(2009).
RN [15]
RP FUNCTION ON CARDIAC CONTRACTILITY, AND PHOSPHORYLATION AT THR-1024.
RX PubMed=21474070; DOI=10.1016/j.molcel.2011.01.030;
RA Perino A., Ghigo A., Ferrero E., Morello F., Santulli G., Baillie G.S.,
RA Damilano F., Dunlop A.J., Pawson C., Walser R., Levi R., Altruda F.,
RA Silengo L., Langeberg L.K., Neubauer G., Heymans S., Lembo G., Wymann M.P.,
RA Wetzker R., Houslay M.D., Iaccarino G., Scott J.D., Hirsch E.;
RT "Integrating cardiac PIP3 and cAMP signaling through a PKA anchoring
RT function of p110gamma.";
RL Mol. Cell 42:84-95(2011).
CC -!- FUNCTION: Phosphoinositide-3-kinase (PI3K) that phosphorylates
CC PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate
CC phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role
CC by recruiting PH domain-containing proteins to the membrane, including
CC AKT1 and PDPK1, activating signaling cascades involved in cell growth,
CC survival, proliferation, motility and morphology. Links G-protein
CC coupled receptor activation to PIP3 production. Involved in immune,
CC inflammatory and allergic responses. Modulates leukocyte chemotaxis to
CC inflammatory sites and in response to chemoattractant agents. May
CC control leukocyte polarization and migration by regulating the spatial
CC accumulation of PIP3 and by regulating the organization of F-actin
CC formation and integrin-based adhesion at the leading edge. Controls
CC motility of dendritic cells. Together with PIK3CD is involved in
CC natural killer (NK) cell development and migration towards the sites of
CC inflammation. Participates in T-lymphocyte migration. Regulates T-
CC lymphocyte proliferation and cytokine production. Together with PIK3CD
CC participates in T-lymphocyte development. Required for B-lymphocyte
CC development and signaling. Together with PIK3CD participates in
CC neutrophil respiratory burst. Together with PIK3CD is involved in
CC neutrophil chemotaxis and extravasation. Together with PIK3CB promotes
CC platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3
CC integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of
CC P2Y12 through a lipid kinase activity-independent mechanism. May have
CC also a lipid kinase activity-dependent function in platelet
CC aggregation. Involved in endothelial progenitor cell migration.
CC Negative regulator of cardiac contractility. Modulates cardiac
CC contractility by anchoring protein kinase A (PKA) and PDE3B activation,
CC reducing cAMP levels. Regulates cardiac contractility also by promoting
CC beta-adrenergic receptor internalization by binding to GRK2 and by non-
CC muscle tropomyosin phosphorylation. Also has serine/threonine protein
CC kinase activity: both lipid and protein kinase activities are required
CC for beta-adrenergic receptor endocytosis. May also have a scaffolding
CC role in modulating cardiac contractility. Contribute to cardiac
CC hypertrophy under pathological stress. Through simultaneous binding of
CC PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in
CC which the PI3K gamma complex is activated by RAPGEF3 and which is
CC involved in angiogenesis (By similarity).
CC {ECO:0000250|UniProtKB:P48736, ECO:0000269|PubMed:10669416,
CC ECO:0000269|PubMed:10669418, ECO:0000269|PubMed:11054537,
CC ECO:0000269|PubMed:12297047, ECO:0000269|PubMed:15294162,
CC ECO:0000269|PubMed:15318168, ECO:0000269|PubMed:16116162,
CC ECO:0000269|PubMed:16127437, ECO:0000269|PubMed:17673465,
CC ECO:0000269|PubMed:19297623, ECO:0000269|PubMed:21474070}.
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:0000269|PubMed:11054537};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710;
CC Evidence={ECO:0000305|PubMed:11054537};
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:P48736};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21293;
CC Evidence={ECO:0000250|UniProtKB:P48736};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-
CC phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3,4-bisphosphate) + ADP + H(+); Xref=Rhea:RHEA:18373,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57658,
CC ChEBI:CHEBI:58178, ChEBI:CHEBI:456216; EC=2.7.1.154;
CC Evidence={ECO:0000250|UniProtKB:P48736};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18374;
CC Evidence={ECO:0000250|UniProtKB:P48736};
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:P48736};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000250|UniProtKB:P48736};
CC -!- ACTIVITY REGULATION: Activated by both the alpha and the beta-gamma G
CC proteins following stimulation of G protein-coupled receptors (GPCRs).
CC Activation by GPCRs is assisted by the regulatory subunit PIK3R5
CC leading to the translocation from the cytosol to the plasma membrane
CC and to kinase activation; the respective activation involving PIK3R6
CC requires HRAS for membrane recruitment. Wortmannin sensitive in nM
CC range. Inhibited by AS252424. {ECO:0000269|PubMed:11054537,
CC ECO:0000269|PubMed:19297623}.
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylinositol phosphate
CC biosynthesis.
CC -!- SUBUNIT: Heterodimer of a catalytic subunit PIK3CG and a PIK3R5 or
CC PIK3R6 regulatory subunit. Interacts with GRK2 through the PIK helical
CC domain (By similarity). Interaction with GRK2 is required for targeting
CC to agonist-occupied receptor. Interacts with PDE3B; regulates PDE3B
CC activity and thereby cAMP levels in cells (PubMed:15294162). Interacts
CC with TPM2 (By similarity). Interacts with EPHA8; regulates integrin-
CC mediated cell adhesion to substrate. Interacts with HRAS; the
CC interaction is required for membrane recruitment and beta-gamma G
CC protein dimer-dependent activation of the PI3K gamma complex
CC PIK3CG:PIK3R6. {ECO:0000250|UniProtKB:P48736,
CC ECO:0000269|PubMed:11416136, ECO:0000269|PubMed:15294162,
CC ECO:0000269|PubMed:19906996}.
CC -!- INTERACTION:
CC Q9JHG7; Q3U6Q4: Pik3r6; NbExp=4; IntAct=EBI-644372, EBI-4303950;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P48736}. Cell
CC membrane {ECO:0000250|UniProtKB:P48736}.
CC -!- PTM: Phosphorylated at Thr-1024 by PKA. Phosphorylation inhibits lipid
CC kinase activity. {ECO:0000269|PubMed:21474070}.
CC -!- PTM: Autophosphorylation at Ser-1101 has no effect on the
CC phosphatidylinositol-4,5-bisphosphate 3-kinase activity.
CC {ECO:0000250|UniProtKB:P48736}.
CC -!- DISRUPTION PHENOTYPE: Viable and fertile. Display abnormalities when
CC the immune system is stressed. Reduced leukocyte migration in response
CC to chemotactic agents and towards the site of inflammation. Reduced
CC neutrophil oxidative burst in response to chemotactic agents. Reduced
CC thymocyte survival and defective T lymphocyte activation. Protected
CC from leukocyte infiltration of synovia in a model of rheumatoid
CC arthritis. Dendritic cell showed reduced response to chemokines and
CC migration to draining lymph nodes under inflammatory conditions.
CC Platelets have defects in thrombus formation. Increased cardiac
CC contractility. Display myocardial damage after transverse aortic
CC constriction. {ECO:0000269|PubMed:10669416,
CC ECO:0000269|PubMed:10669418, ECO:0000269|PubMed:12297047,
CC ECO:0000269|PubMed:15294162, ECO:0000269|PubMed:15318168,
CC ECO:0000269|PubMed:16127437, ECO:0000269|PubMed:17673465}.
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; AJ249280; CAB89686.1; -; mRNA.
DR EMBL; AJ249413; CAB89851.1; -; Genomic_DNA.
DR EMBL; AJ249414; CAB89851.1; JOINED; Genomic_DNA.
DR EMBL; AJ249415; CAB89851.1; JOINED; Genomic_DNA.
DR EMBL; AJ249416; CAB89851.1; JOINED; Genomic_DNA.
DR EMBL; AJ249417; CAB89851.1; JOINED; Genomic_DNA.
DR EMBL; AJ249418; CAB89851.1; JOINED; Genomic_DNA.
DR EMBL; AJ249419; CAB89851.1; JOINED; Genomic_DNA.
DR EMBL; AJ249420; CAB89851.1; JOINED; Genomic_DNA.
DR EMBL; BC051246; AAH51246.1; -; mRNA.
DR CCDS; CCDS25870.1; -.
DR RefSeq; NP_001139672.1; NM_001146200.1.
DR RefSeq; NP_001139673.1; NM_001146201.1.
DR RefSeq; NP_064668.2; NM_020272.2.
DR RefSeq; XP_006515175.1; XM_006515112.3.
DR AlphaFoldDB; Q9JHG7; -.
DR SMR; Q9JHG7; -.
DR BioGRID; 206031; 2.
DR CORUM; Q9JHG7; -.
DR DIP; DIP-41862N; -.
DR IntAct; Q9JHG7; 7.
DR STRING; 10090.ENSMUSP00000062864; -.
DR BindingDB; Q9JHG7; -.
DR ChEMBL; CHEMBL2189158; -.
DR iPTMnet; Q9JHG7; -.
DR PhosphoSitePlus; Q9JHG7; -.
DR EPD; Q9JHG7; -.
DR MaxQB; Q9JHG7; -.
DR PaxDb; Q9JHG7; -.
DR PRIDE; Q9JHG7; -.
DR ProteomicsDB; 289437; -.
DR Antibodypedia; 4141; 1009 antibodies from 40 providers.
DR DNASU; 30955; -.
DR Ensembl; ENSMUST00000053215; ENSMUSP00000062864; ENSMUSG00000020573.
DR Ensembl; ENSMUST00000085469; ENSMUSP00000082596; ENSMUSG00000020573.
DR Ensembl; ENSMUST00000156904; ENSMUSP00000123539; ENSMUSG00000020573.
DR Ensembl; ENSMUST00000220366; ENSMUSP00000151400; ENSMUSG00000020573.
DR GeneID; 30955; -.
DR KEGG; mmu:30955; -.
DR UCSC; uc007nib.2; mouse.
DR CTD; 5294; -.
DR MGI; MGI:1353576; Pik3cg.
DR VEuPathDB; HostDB:ENSMUSG00000020573; -.
DR eggNOG; KOG0904; Eukaryota.
DR GeneTree; ENSGT00940000156858; -.
DR HOGENOM; CLU_002191_1_0_1; -.
DR InParanoid; Q9JHG7; -.
DR OMA; RGCGMAM; -.
DR OrthoDB; 204282at2759; -.
DR PhylomeDB; Q9JHG7; -.
DR TreeFam; TF102031; -.
DR BRENDA; 2.7.1.153; 3474.
DR Reactome; R-MMU-114604; GPVI-mediated activation cascade.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-MMU-392451; G beta:gamma signalling through PI3Kgamma.
DR Reactome; R-MMU-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR UniPathway; UPA00220; -.
DR BioGRID-ORCS; 30955; 4 hits in 70 CRISPR screens.
DR ChiTaRS; Pik3cg; mouse.
DR PRO; PR:Q9JHG7; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q9JHG7; protein.
DR Bgee; ENSMUSG00000020573; Expressed in granulocyte and 109 other tissues.
DR ExpressionAtlas; Q9JHG7; baseline and differential.
DR Genevisible; Q9JHG7; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; ISO:MGI.
DR GO; GO:0005943; C:phosphatidylinositol 3-kinase complex, class IA; IBA:GO_Central.
DR GO; GO:0005944; C:phosphatidylinositol 3-kinase complex, class IB; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IDA:UniProtKB.
DR GO; GO:0035005; F:1-phosphatidylinositol-4-phosphate 3-kinase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046875; F:ephrin receptor binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO: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; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; ISS:UniProtKB.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0071320; P:cellular response to cAMP; IMP:MGI.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0097284; P:hepatocyte apoptotic process; ISO:MGI.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:2000270; P:negative regulation of fibroblast apoptotic process; IDA:MGI.
DR GO; GO:0010897; P:negative regulation of triglyceride catabolic process; ISO:MGI.
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:0002675; P:positive regulation of acute inflammatory response; ISO:MGI.
DR GO; GO:0043085; P:positive regulation of catalytic activity; IMP:MGI.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IMP:BHF-UCL.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:0035022; P:positive regulation of Rac protein signal transduction; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:1903169; P:regulation of calcium ion transmembrane transport; IMP:MGI.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IMP:MGI.
DR GO; GO:0032252; P:secretory granule localization; ISO:MGI.
DR GO; GO:0003376; P:sphingosine-1-phosphate receptor signaling pathway; IMP:BHF-UCL.
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; IPR015433; PI_Kinase.
DR InterPro; IPR045580; PIK3CG_ABD.
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; PF00794; PI3K_rbd; 1.
DR Pfam; PF00613; PI3Ka; 1.
DR Pfam; PF19710; PIK3CG_ABD; 1.
DR SMART; SM00142; PI3K_C2; 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 Angiogenesis; ATP-binding; Cell membrane; Chemotaxis; Cytoplasm;
KW Direct protein sequencing; Endocytosis; Immunity; Inflammatory response;
KW Kinase; Lipid metabolism; Membrane; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..1102
FT /note="Phosphatidylinositol 4,5-bisphosphate 3-kinase
FT catalytic subunit gamma isoform"
FT /id="PRO_0000088793"
FT DOMAIN 34..141
FT /note="PI3K-ABD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00877"
FT DOMAIN 217..309
FT /note="PI3K-RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00879"
FT DOMAIN 357..521
FT /note="C2 PI3K-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00880"
FT DOMAIN 541..723
FT /note="PIK helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00878"
FT DOMAIN 797..1080
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 803..809
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 943..951
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 962..988
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT BINDING 829..838
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 864..872
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 961..969
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 1024
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000269|PubMed:21474070"
FT MOD_RES 1101
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P48736"
FT CONFLICT 262
FT /note="S -> P (in Ref. 1; CAB89686/CAB89851)"
FT /evidence="ECO:0000305"
FT CONFLICT 350
FT /note="F -> V (in Ref. 1; CAB89686/CAB89851)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1102 AA; 126400 MW; 7675848792D76734 CRC64;
MELENYEQPV VLREDNLRRR RRMKPRSAAG SLSSMELIPI EFVLPTSQRI SKTPETALLH
VAGHGNVEQM KAQVWLRALE TSVAAEFYHR LGPDQFLLLY QKKGQWYEIY DRYQVVQTLD
CLHYWKLMHK SPGQIHVVQR HVPSEETLAF QKQLTSLIGY DVTDISNVHD DELEFTRRRL
VTPRMAEVAG RDAKLYAMHP WVTSKPLPDY LSKKIANNCI FIVIHRGTTS QTIKVSADDT
PGTILQSFFT KMAKKKSLMN ISESQSEQDF VLRVCGRDEY LVGETPLKNF QWVRQCLKNG
DEIHLVLDTP PDPALDEVRK EEWPLVDDCT GVTGYHEQLT IHGKDHESVF TVSLWDCDRK
FRVKIRGIDI PVLPRNTDLT VFVEANIQHG QQVLCQRRTS PKPFAEEVLW NVWLEFGIKI
KDLPKGALLN LQIYCCKTPS LSSKASAETP GSESKGKAQL LYYVNLLLID HRFLLRHGDY
VLHMWQISGK AEEQGSFNAD KLTSATNPDK ENSMSISILL DNYCHPIALP KHRPTPDPEG
DRVRAEMPNQ LRKQLEAIIA TDPLNPLTAE DKELLWHFRY ESLKHPKAYP KLFSSVKWGQ
QEIVAKTYQL LARREIWDQS ALDVGLTMQL LDCNFSDENV RAIAVQKLES LEDDDVLHYL
LQLVQAVKFE PYHDSALARF LLKRGLRNKR IGHFLFWFLR SEIAQSRHYQ QRFAVILEAY
LRGCGTAMLQ DFTQQVHVIE MLQKVTIDIK SLSAEKYDVS SQVISQLKQK LESLQNSNLP
ESFRVPYDPG LKAGTLVIEK CKVMASKKKP LWLEFKCADP TVLSNETIGI IFKHGDDLRQ
DMLILQILRI MESIWETESL DLCLLPYGCI STGDKIGMIE IVKDATTIAQ IQQSTVGNTG
AFKDEVLNHW LKEKCPIEEK FQAAVERFVY SCAGYCVATF VLGIGDRHND NIMISETGNL
FHIDFGHILG NYKSFLGINK ERVPFVLTPD FLFVMGSSGK KTSPHFQKFQ DVCVRAYLAL
RHHTNLLIIL FSMMLMTGMP QLTSKEDIEY IRDALTVGKS EEDAKKYFLD QIEVCRDKGW
TVQFNWFLHL VLGIKQGEKH SA
