PK3CG_HUMAN
ID PK3CG_HUMAN Reviewed; 1102 AA.
AC P48736; A4D0Q6; Q8IV23; Q9BZC8;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 3.
DT 03-AUG-2022, entry version 215.
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:11277933, ECO:0000269|PubMed:16123124};
DE EC=2.7.1.153 {ECO:0000269|PubMed:15135396, ECO:0000269|PubMed:16123124};
DE EC=2.7.1.154 {ECO:0000269|PubMed:16123124};
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:0000305|PubMed:12502714};
DE EC=2.7.11.1 {ECO:0000269|PubMed:12502714, ECO:0000269|PubMed:16094730};
DE AltName: Full=p120-PI3K;
GN Name=PIK3CG;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=7624799; DOI=10.1126/science.7624799;
RA Stoyanov B., Volinia S., Hanck T., Rubio I., Loubtchenkov M., Malek D.,
RA Stoyanova S., Vanhaesebroeck B., Dhand R., Nuernberg B., Gierschik P.,
RA Seedorf K., Hsuan J.J., Waterfield M.D., Wetzker R.;
RT "Cloning and characterization of a G protein-activated human
RT phosphoinositide-3 kinase.";
RL Science 269:690-693(1995).
RN [2]
RP SEQUENCE REVISION.
RA Waterfield M.D.;
RL Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Michalke M., Schaefer M., Stoyanov B., Wetzker R., Nuernberg B.;
RT "Regulation of a G-protein-activated phosphoinositide-3-kinase.";
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=11277933; DOI=10.1046/j.1432-1327.2001.02089.x;
RA Suer S., Sickmann A., Meyer H.E., Herberg F.W., Heilmeyer L.M.G. Jr.;
RT "Human phosphatidylinositol 4-kinase isoform PI4K92. Expression of the
RT recombinant enzyme and determination of multiple phosphorylation sites.";
RL Eur. J. Biochem. 268:2099-2106(2001).
RN [9]
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 [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH GRK2.
RX PubMed=12163475; DOI=10.1083/jcb.200202113;
RA Naga Prasad S.V., Laporte S.A., Chamberlain D., Caron M.G., Barak L.,
RA Rockman H.A.;
RT "Phosphoinositide 3-kinase regulates beta2-adrenergic receptor endocytosis
RT by AP-2 recruitment to the receptor/beta-arrestin complex.";
RL J. Cell Biol. 158:563-575(2002).
RN [11]
RP CATALYTIC ACTIVITY, PHOSPHORYLATION AT SER-1101, AND MUTAGENESIS OF
RP SER-1101.
RX PubMed=12502714; DOI=10.1074/jbc.m210351200;
RA Czupalla C., Culo M., Muller E.C., Brock C., Reusch H.P., Spicher K.,
RA Krause E., Nurnberg B.;
RT "Identification and characterization of the autophosphorylation sites of
RT phosphoinositide 3-kinase isoforms beta and gamma.";
RL J. Biol. Chem. 278:11536-11545(2003).
RN [12]
RP FUNCTION IN CARDIAC CONTRACTILITY, AND MUTAGENESIS OF LYS-833.
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 [13]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=15135396; DOI=10.1016/j.pep.2003.12.010;
RA Meier T.I., Cook J.A., Thomas J.E., Radding J.A., Horn C., Lingaraj T.,
RA Smith M.C.;
RT "Cloning, expression, purification, and characterization of the human Class
RT Ia phosphoinositide 3-kinase isoforms.";
RL Protein Expr. Purif. 35:218-224(2004).
RN [14]
RP INTERACTION WITH PIK3R5.
RX PubMed=15797027; DOI=10.1016/j.cub.2005.02.020;
RA Suire S., Coadwell J., Ferguson G.J., Davidson K., Hawkins P., Stephens L.;
RT "p84, a new Gbetagamma-activated regulatory subunit of the type IB
RT phosphoinositide 3-kinase p110gamma.";
RL Curr. Biol. 15:566-570(2005).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH GRK2 AND TPM2, AND
RP MUTAGENESIS OF LYS-833 AND ARG-947.
RX PubMed=16094730; DOI=10.1038/ncb1278;
RA Naga Prasad S.V., Jayatilleke A., Madamanchi A., Rockman H.A.;
RT "Protein kinase activity of phosphoinositide 3-kinase regulates beta-
RT adrenergic receptor endocytosis.";
RL Nat. Cell Biol. 7:785-796(2005).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=16123124; DOI=10.1073/pnas.0506184102;
RA Resnick A.C., Snowman A.M., Kang B.N., Hurt K.J., Snyder S.H., Saiardi A.;
RT "Inositol polyphosphate multikinase is a nuclear PI3-kinase with
RT transcriptional regulatory activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:12783-12788(2005).
RN [17]
RP REVIEW ON FUNCTION.
RX PubMed=17290298; DOI=10.1038/nri2036;
RA Rommel C., Camps M., Ji H.;
RT "PI3K delta and PI3K gamma: partners in crime in inflammation in rheumatoid
RT arthritis and beyond?";
RL Nat. Rev. Immunol. 7:191-201(2007).
RN [18]
RP REVIEW ON FUNCTION IN LEUKOCYTES AND ENDOTHELIAL CELLS, AND REVIEW ON
RP ANTINFLAMMATORY THERAPY TARGET.
RX PubMed=18278175; DOI=10.1160/th07-10-0632;
RA Barberis L., Hirsch E.;
RT "Targeting phosphoinositide 3-kinase gamma to fight inflammation and
RT more.";
RL Thromb. Haemost. 99:279-285(2008).
RN [19]
RP REVIEW ON FUNCTION IN CARDIAC CONTRACTILITY.
RX PubMed=19147653; DOI=10.1093/cvr/cvp014;
RA Oudit G.Y., Penninger J.M.;
RT "Cardiac regulation by phosphoinositide 3-kinases and PTEN.";
RL Cardiovasc. Res. 82:250-260(2009).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP FUNCTION.
RX PubMed=21393242; DOI=10.1074/jbc.m110.217026;
RA Wilson L.S., Baillie G.S., Pritchard L.M., Umana B., Terrin A., Zaccolo M.,
RA Houslay M.D., Maurice D.H.;
RT "A phosphodiesterase 3B-based signaling complex integrates exchange protein
RT activated by cAMP 1 and phosphatidylinositol 3-kinase signals in human
RT arterial endothelial cells.";
RL J. Biol. Chem. 286:16285-16296(2011).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 144-1102.
RX PubMed=10580505; DOI=10.1038/46319;
RA Walker E.H., Perisic O., Ried C., Stephens L., Williams R.L.;
RT "Structural insights into phosphoinositide 3-kinase catalysis and
RT signalling.";
RL Nature 402:313-320(1999).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 144-1101 IN A COMPLEX WITH
RP AS-604850 AND AS-605240, AND ACTIVITY REGULATION.
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).
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. Contributes 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. {ECO:0000269|PubMed:11277933,
CC ECO:0000269|PubMed:12163475, ECO:0000269|PubMed:15135396,
CC ECO:0000269|PubMed:15294162, ECO:0000269|PubMed:16094730,
CC ECO:0000269|PubMed:16123124, ECO:0000269|PubMed:21393242,
CC ECO:0000269|PubMed:7624799}.
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:11277933,
CC ECO:0000269|PubMed:16123124};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710;
CC Evidence={ECO:0000305|PubMed:11277933};
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:0000269|PubMed:15135396, ECO:0000269|PubMed:16123124};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21293;
CC Evidence={ECO:0000305|PubMed:15135396};
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:0000269|PubMed:16123124};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18374;
CC Evidence={ECO:0000305|PubMed:16123124};
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:0000269|PubMed:12502714, ECO:0000269|PubMed:16094730};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000305|PubMed:12502714};
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 subunits (PIK3R5 or
CC PIK3R6) leading to the translocation from the cytosol to the plasma
CC membrane and to kinase activation. Inhibited by AS-604850 and AS-
CC 605240. {ECO:0000269|PubMed:16127437, ECO:0000269|PubMed:7624799}.
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylinositol phosphate
CC biosynthesis. {ECO:0000305|PubMed:11277933,
CC ECO:0000305|PubMed:15135396, ECO:0000305|PubMed:16123124}.
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. Interaction with GRK2 is required for targeting to agonist-
CC occupied receptor. Interacts with PDE3B; regulates PDE3B activity and
CC thereby cAMP levels in cells (By similarity). Interacts with TPM2.
CC Interacts with EPHA8; regulates integrin-mediated cell adhesion to
CC substrate. Interacts with HRAS; the interaction is required for
CC membrane recruitment and beta-gamma G protein dimer-dependent
CC activation of the PI3K gamma complex PIK3CG:PIK3R6 (By similarity).
CC {ECO:0000250|UniProtKB:Q9JHG7, ECO:0000269|PubMed:11416136,
CC ECO:0000269|PubMed:12163475, ECO:0000269|PubMed:15797027,
CC ECO:0000269|PubMed:16094730}.
CC -!- INTERACTION:
CC P48736; P05067: APP; NbExp=3; IntAct=EBI-1030384, EBI-77613;
CC P48736; Q13370: PDE3B; NbExp=3; IntAct=EBI-1030384, EBI-6172856;
CC P48736; P48736: PIK3CG; NbExp=2; IntAct=EBI-1030384, EBI-1030384;
CC P48736; O02696: PIK3R5; Xeno; NbExp=6; IntAct=EBI-1030384, EBI-6172343;
CC P48736; Q3U6Q4: Pik3r6; Xeno; NbExp=6; IntAct=EBI-1030384, EBI-4303950;
CC P48736; P68404-2: Prkcb; Xeno; NbExp=2; IntAct=EBI-1030384, EBI-16063464;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12163475}. Cell
CC membrane {ECO:0000269|PubMed:12163475}.
CC -!- TISSUE SPECIFICITY: Pancreas, skeletal muscle, liver and heart.
CC {ECO:0000269|PubMed:7624799}.
CC -!- PTM: Autophosphorylation at Ser-1101 has no effect on the
CC phosphatidylinositol-4,5-bisphosphate 3-kinase activity.
CC {ECO:0000269|PubMed:12502714}.
CC -!- MISCELLANEOUS: Candidate target in therapy for inflammatory diseases.
CC Selective inhibitors and protein ablation are anti-inflammatory in
CC multiple disease models such as asthma, rheumatoid arthritis, allergy,
CC systemic lupus erythematosus, airway inflammation, lung injury and
CC pancreatitis (PubMed:18278175). {ECO:0000305|PubMed:18278175}.
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; X83368; CAA58284.1; -; mRNA.
DR EMBL; AF327656; AAG61115.1; -; mRNA.
DR EMBL; AC005018; AAQ96873.1; -; Genomic_DNA.
DR EMBL; CH236947; EAL24396.1; -; Genomic_DNA.
DR EMBL; CH471070; EAW83387.1; -; Genomic_DNA.
DR EMBL; BC035683; AAH35683.1; -; mRNA.
DR CCDS; CCDS5739.1; -.
DR RefSeq; NP_001269355.1; NM_001282426.1.
DR RefSeq; NP_001269356.1; NM_001282427.1.
DR RefSeq; NP_002640.2; NM_002649.3.
DR RefSeq; XP_005250500.1; XM_005250443.3.
DR PDB; 1E8Y; X-ray; 2.00 A; A=144-1102.
DR PDB; 1E8Z; X-ray; 2.40 A; A=144-1102.
DR PDB; 1HE8; X-ray; 3.00 A; A=144-1102.
DR PDB; 2A4Z; X-ray; 2.90 A; A=144-1102.
DR PDB; 2A5U; X-ray; 2.70 A; A=144-1102.
DR PDB; 2CHW; X-ray; 2.60 A; A=144-1102.
DR PDB; 2CHX; X-ray; 2.50 A; A=144-1102.
DR PDB; 2CHZ; X-ray; 2.60 A; A=144-1102.
DR PDB; 2V4L; X-ray; 2.50 A; A=144-1102.
DR PDB; 3APC; X-ray; 2.54 A; A=144-1102.
DR PDB; 3APD; X-ray; 2.55 A; A=144-1102.
DR PDB; 3APF; X-ray; 2.82 A; A=144-1102.
DR PDB; 3CSF; X-ray; 2.80 A; A=144-1102.
DR PDB; 3CST; X-ray; 3.20 A; A=144-1102.
DR PDB; 3DBS; X-ray; 2.80 A; A=144-1102.
DR PDB; 3DPD; X-ray; 2.85 A; A=144-1102.
DR PDB; 3ENE; X-ray; 2.40 A; A=144-1102.
DR PDB; 3IBE; X-ray; 2.80 A; A=144-1102.
DR PDB; 3L08; X-ray; 2.70 A; A=144-1102.
DR PDB; 3L13; X-ray; 3.00 A; A=144-1102.
DR PDB; 3L16; X-ray; 2.90 A; A=144-1102.
DR PDB; 3L17; X-ray; 3.00 A; A=144-1102.
DR PDB; 3L54; X-ray; 2.30 A; A=144-1102.
DR PDB; 3LJ3; X-ray; 2.43 A; A=144-1102.
DR PDB; 3MJW; X-ray; 2.87 A; A=144-1102.
DR PDB; 3ML8; X-ray; 2.70 A; A=144-1102.
DR PDB; 3ML9; X-ray; 2.55 A; A=144-1102.
DR PDB; 3NZS; X-ray; 2.75 A; A=147-1094.
DR PDB; 3NZU; X-ray; 2.60 A; A=147-1094.
DR PDB; 3OAW; X-ray; 2.75 A; A=144-1102.
DR PDB; 3P2B; X-ray; 3.20 A; A=144-1102.
DR PDB; 3PRE; X-ray; 2.91 A; A=144-1102.
DR PDB; 3PRZ; X-ray; 2.60 A; A=144-1102.
DR PDB; 3PS6; X-ray; 2.60 A; A=144-1102.
DR PDB; 3QAQ; X-ray; 2.90 A; A=144-1102.
DR PDB; 3QAR; X-ray; 2.65 A; A=144-1102.
DR PDB; 3QJZ; X-ray; 2.90 A; A=144-1102.
DR PDB; 3QK0; X-ray; 2.85 A; A=144-1102.
DR PDB; 3R7Q; X-ray; 2.50 A; A=144-1102.
DR PDB; 3R7R; X-ray; 2.90 A; A=144-1102.
DR PDB; 3S2A; X-ray; 2.55 A; A=144-1102.
DR PDB; 3SD5; X-ray; 3.20 A; A=144-1102.
DR PDB; 3T8M; X-ray; 2.50 A; A=144-1102.
DR PDB; 3TJP; X-ray; 2.70 A; A=144-1102.
DR PDB; 3TL5; X-ray; 2.79 A; A=144-1102.
DR PDB; 3ZVV; X-ray; 2.50 A; A=144-1102.
DR PDB; 3ZW3; X-ray; 2.80 A; A=144-1102.
DR PDB; 4ANU; X-ray; 2.81 A; A=144-1102.
DR PDB; 4ANV; X-ray; 2.13 A; A=144-1102.
DR PDB; 4ANW; X-ray; 2.31 A; A=144-1102.
DR PDB; 4ANX; X-ray; 2.73 A; A=144-1102.
DR PDB; 4AOF; X-ray; 3.30 A; A=144-1102.
DR PDB; 4DK5; X-ray; 2.95 A; A=144-1102.
DR PDB; 4EZJ; X-ray; 2.67 A; A=144-1102.
DR PDB; 4EZK; X-ray; 2.80 A; A=144-1102.
DR PDB; 4EZL; X-ray; 2.94 A; A=144-1102.
DR PDB; 4F1S; X-ray; 3.00 A; A=144-1102.
DR PDB; 4FA6; X-ray; 2.70 A; A=144-1102.
DR PDB; 4FAD; X-ray; 2.70 A; A=144-1102.
DR PDB; 4FHJ; X-ray; 2.60 A; A=144-1102.
DR PDB; 4FHK; X-ray; 3.00 A; A=144-1102.
DR PDB; 4FJY; X-ray; 2.90 A; A=144-1102.
DR PDB; 4FJZ; X-ray; 3.00 A; A=144-1102.
DR PDB; 4FLH; X-ray; 2.60 A; A=144-1102.
DR PDB; 4FUL; X-ray; 2.47 A; A=144-1102.
DR PDB; 4G11; X-ray; 3.40 A; A=144-1102.
DR PDB; 4GB9; X-ray; 2.44 A; A=144-1102.
DR PDB; 4HLE; X-ray; 2.78 A; A=144-1102.
DR PDB; 4HVB; X-ray; 2.35 A; A=144-1102.
DR PDB; 4J6I; X-ray; 2.90 A; A=144-1102.
DR PDB; 4KZ0; X-ray; 2.87 A; A=144-1102.
DR PDB; 4KZC; X-ray; 3.25 A; A=144-1102.
DR PDB; 4PS3; X-ray; 2.90 A; A=144-1102.
DR PDB; 4PS7; X-ray; 2.69 A; A=144-1102.
DR PDB; 4PS8; X-ray; 2.99 A; A=144-1102.
DR PDB; 4URK; X-ray; 2.90 A; A=144-1102.
DR PDB; 4WWN; X-ray; 2.70 A; A=144-1102.
DR PDB; 4WWO; X-ray; 2.30 A; A=144-1102.
DR PDB; 4WWP; X-ray; 2.40 A; A=144-1102.
DR PDB; 4XX5; X-ray; 2.76 A; A=144-1102.
DR PDB; 4XZ4; X-ray; 2.60 A; A=144-1102.
DR PDB; 5EDS; X-ray; 2.80 A; A=144-1102.
DR PDB; 5G2N; X-ray; 2.68 A; A=144-1102.
DR PDB; 5G55; X-ray; 2.45 A; A=144-1102.
DR PDB; 5JHA; X-ray; 2.51 A; A=144-1102.
DR PDB; 5JHB; X-ray; 2.48 A; A=144-1102.
DR PDB; 5KAE; X-ray; 2.65 A; A=144-1102.
DR PDB; 5OQ4; X-ray; 2.70 A; A=144-1102.
DR PDB; 5T23; X-ray; 2.78 A; A=144-1102.
DR PDB; 6AUD; X-ray; 2.02 A; A=144-1102.
DR PDB; 6C1S; X-ray; 2.31 A; A=144-1102.
DR PDB; 6FH5; X-ray; 2.84 A; A=144-1102.
DR PDB; 6GQ7; X-ray; 2.84 A; A=144-1102.
DR PDB; 6T3B; X-ray; 3.01 A; A=144-1102.
DR PDB; 6T3C; X-ray; 2.62 A; A=144-1102.
DR PDB; 6XRL; X-ray; 2.99 A; A=144-1091.
DR PDB; 6XRM; X-ray; 2.88 A; A=144-1091.
DR PDB; 6XRN; X-ray; 2.96 A; A=144-1091.
DR PDB; 7JWE; X-ray; 2.55 A; A=144-1102.
DR PDB; 7JWZ; X-ray; 2.65 A; A=144-1102.
DR PDB; 7JX0; X-ray; 3.15 A; A=144-1102.
DR PDB; 7KKE; X-ray; 2.81 A; A=144-1102.
DR PDB; 7MEZ; EM; 2.89 A; A=1-1102.
DR PDBsum; 1E8Y; -.
DR PDBsum; 1E8Z; -.
DR PDBsum; 1HE8; -.
DR PDBsum; 2A4Z; -.
DR PDBsum; 2A5U; -.
DR PDBsum; 2CHW; -.
DR PDBsum; 2CHX; -.
DR PDBsum; 2CHZ; -.
DR PDBsum; 2V4L; -.
DR PDBsum; 3APC; -.
DR PDBsum; 3APD; -.
DR PDBsum; 3APF; -.
DR PDBsum; 3CSF; -.
DR PDBsum; 3CST; -.
DR PDBsum; 3DBS; -.
DR PDBsum; 3DPD; -.
DR PDBsum; 3ENE; -.
DR PDBsum; 3IBE; -.
DR PDBsum; 3L08; -.
DR PDBsum; 3L13; -.
DR PDBsum; 3L16; -.
DR PDBsum; 3L17; -.
DR PDBsum; 3L54; -.
DR PDBsum; 3LJ3; -.
DR PDBsum; 3MJW; -.
DR PDBsum; 3ML8; -.
DR PDBsum; 3ML9; -.
DR PDBsum; 3NZS; -.
DR PDBsum; 3NZU; -.
DR PDBsum; 3OAW; -.
DR PDBsum; 3P2B; -.
DR PDBsum; 3PRE; -.
DR PDBsum; 3PRZ; -.
DR PDBsum; 3PS6; -.
DR PDBsum; 3QAQ; -.
DR PDBsum; 3QAR; -.
DR PDBsum; 3QJZ; -.
DR PDBsum; 3QK0; -.
DR PDBsum; 3R7Q; -.
DR PDBsum; 3R7R; -.
DR PDBsum; 3S2A; -.
DR PDBsum; 3SD5; -.
DR PDBsum; 3T8M; -.
DR PDBsum; 3TJP; -.
DR PDBsum; 3TL5; -.
DR PDBsum; 3ZVV; -.
DR PDBsum; 3ZW3; -.
DR PDBsum; 4ANU; -.
DR PDBsum; 4ANV; -.
DR PDBsum; 4ANW; -.
DR PDBsum; 4ANX; -.
DR PDBsum; 4AOF; -.
DR PDBsum; 4DK5; -.
DR PDBsum; 4EZJ; -.
DR PDBsum; 4EZK; -.
DR PDBsum; 4EZL; -.
DR PDBsum; 4F1S; -.
DR PDBsum; 4FA6; -.
DR PDBsum; 4FAD; -.
DR PDBsum; 4FHJ; -.
DR PDBsum; 4FHK; -.
DR PDBsum; 4FJY; -.
DR PDBsum; 4FJZ; -.
DR PDBsum; 4FLH; -.
DR PDBsum; 4FUL; -.
DR PDBsum; 4G11; -.
DR PDBsum; 4GB9; -.
DR PDBsum; 4HLE; -.
DR PDBsum; 4HVB; -.
DR PDBsum; 4J6I; -.
DR PDBsum; 4KZ0; -.
DR PDBsum; 4KZC; -.
DR PDBsum; 4PS3; -.
DR PDBsum; 4PS7; -.
DR PDBsum; 4PS8; -.
DR PDBsum; 4URK; -.
DR PDBsum; 4WWN; -.
DR PDBsum; 4WWO; -.
DR PDBsum; 4WWP; -.
DR PDBsum; 4XX5; -.
DR PDBsum; 4XZ4; -.
DR PDBsum; 5EDS; -.
DR PDBsum; 5G2N; -.
DR PDBsum; 5G55; -.
DR PDBsum; 5JHA; -.
DR PDBsum; 5JHB; -.
DR PDBsum; 5KAE; -.
DR PDBsum; 5OQ4; -.
DR PDBsum; 5T23; -.
DR PDBsum; 6AUD; -.
DR PDBsum; 6C1S; -.
DR PDBsum; 6FH5; -.
DR PDBsum; 6GQ7; -.
DR PDBsum; 6T3B; -.
DR PDBsum; 6T3C; -.
DR PDBsum; 6XRL; -.
DR PDBsum; 6XRM; -.
DR PDBsum; 6XRN; -.
DR PDBsum; 7JWE; -.
DR PDBsum; 7JWZ; -.
DR PDBsum; 7JX0; -.
DR PDBsum; 7KKE; -.
DR PDBsum; 7MEZ; -.
DR AlphaFoldDB; P48736; -.
DR SMR; P48736; -.
DR BioGRID; 111312; 45.
DR ComplexPortal; CPX-5986; Phosphatidylinositol 3-kinase complex class IB, p110gamma/p101.
DR ComplexPortal; CPX-5987; Phosphatidylinositol 3-kinase complex class IB, p110gamma/p87.
DR DIP; DIP-37781N; -.
DR IntAct; P48736; 20.
DR MINT; P48736; -.
DR STRING; 9606.ENSP00000352121; -.
DR BindingDB; P48736; -.
DR ChEMBL; CHEMBL3267; -.
DR DrugBank; DB07503; (5E)-5-[(2,2-DIFLUORO-1,3-BENZODIOXOL-5-YL)METHYLENE]-1,3-THIAZOLIDINE-2,4-DIONE.
DR DrugBank; DB08300; 1-methyl-3-naphthalen-2-yl-1H-pyrazolo[3,4-d]pyrimidin-4-amine.
DR DrugBank; DB06831; 2-((9H-PURIN-6-YLTHIO)METHYL)-5-CHLORO-3-(2-METHOXYPHENYL)QUINAZOLIN-4(3H)-ONE.
DR DrugBank; DB07335; 3-[4-AMINO-1-(1-METHYLETHYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-3-YL]PHENOL.
DR DrugBank; DB07073; 5,5-dimethyl-2-morpholin-4-yl-5,6-dihydro-1,3-benzothiazol-7(4H)-one.
DR DrugBank; DB04769; 5-QUINOXALIN-6-YLMETHYLENE-THIAZOLIDINE-2,4-DIONE.
DR DrugBank; DB11952; Duvelisib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB02656; LY-294002.
DR DrugBank; DB02375; Myricetin.
DR DrugBank; DB06836; N-(5-{4-Chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl}-4-methyl-1,3-thiazol-2-yl)acetamide.
DR DrugBank; DB04216; Quercetin.
DR DrugBank; DB02010; Staurosporine.
DR DrugBank; DB05552; TG100-115.
DR DrugBank; DB08059; Wortmannin.
DR DrugBank; DB05241; XL765.
DR DrugCentral; P48736; -.
DR GuidetoPHARMACOLOGY; 2156; -.
DR SwissLipids; SLP:000000909; -.
DR iPTMnet; P48736; -.
DR PhosphoSitePlus; P48736; -.
DR BioMuta; PIK3CG; -.
DR DMDM; 92090623; -.
DR EPD; P48736; -.
DR jPOST; P48736; -.
DR MassIVE; P48736; -.
DR MaxQB; P48736; -.
DR PaxDb; P48736; -.
DR PeptideAtlas; P48736; -.
DR PRIDE; P48736; -.
DR ProteomicsDB; 55933; -.
DR Antibodypedia; 4141; 1009 antibodies from 40 providers.
DR DNASU; 5294; -.
DR Ensembl; ENST00000359195.3; ENSP00000352121.3; ENSG00000105851.11.
DR Ensembl; ENST00000440650.6; ENSP00000392258.2; ENSG00000105851.11.
DR Ensembl; ENST00000496166.6; ENSP00000419260.1; ENSG00000105851.11.
DR GeneID; 5294; -.
DR KEGG; hsa:5294; -.
DR MANE-Select; ENST00000496166.6; ENSP00000419260.1; NM_001282426.2; NP_001269355.1.
DR UCSC; uc003vdu.5; human.
DR CTD; 5294; -.
DR DisGeNET; 5294; -.
DR GeneCards; PIK3CG; -.
DR HGNC; HGNC:8978; PIK3CG.
DR HPA; ENSG00000105851; Group enriched (bone marrow, lymphoid tissue).
DR MIM; 601232; gene.
DR neXtProt; NX_P48736; -.
DR OpenTargets; ENSG00000105851; -.
DR PharmGKB; PA33311; -.
DR VEuPathDB; HostDB:ENSG00000105851; -.
DR eggNOG; KOG0904; Eukaryota.
DR GeneTree; ENSGT00940000156858; -.
DR HOGENOM; CLU_002191_1_0_1; -.
DR InParanoid; P48736; -.
DR OMA; RGCGMAM; -.
DR OrthoDB; 204282at2759; -.
DR PhylomeDB; P48736; -.
DR TreeFam; TF102031; -.
DR BioCyc; MetaCyc:HS02818-MON; -.
DR BRENDA; 2.7.1.137; 2681.
DR BRENDA; 2.7.1.153; 2681.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; P48736; -.
DR Reactome; R-HSA-114604; GPVI-mediated activation cascade.
DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-HSA-392451; G beta:gamma signalling through PI3Kgamma.
DR Reactome; R-HSA-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR SignaLink; P48736; -.
DR SIGNOR; P48736; -.
DR UniPathway; UPA00220; -.
DR BioGRID-ORCS; 5294; 18 hits in 1078 CRISPR screens.
DR ChiTaRS; PIK3CG; human.
DR EvolutionaryTrace; P48736; -.
DR GeneWiki; PIK3CG; -.
DR GenomeRNAi; 5294; -.
DR Pharos; P48736; Tclin.
DR PRO; PR:P48736; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P48736; protein.
DR Bgee; ENSG00000105851; Expressed in bone marrow and 129 other tissues.
DR ExpressionAtlas; P48736; baseline and differential.
DR Genevisible; P48736; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
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; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IDA:UniProtKB.
DR GO; GO:0035005; F:1-phosphatidylinositol-4-phosphate 3-kinase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046875; F:ephrin receptor binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016301; F:kinase activity; IDA:MGI.
DR GO; GO:0035004; F:phosphatidylinositol 3-kinase activity; TAS:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; TAS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IDA:UniProtKB.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0002250; P:adaptive immune response; TAS:UniProtKB.
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; IEA:Ensembl.
DR GO; GO:0002407; P:dendritic cell chemotaxis; TAS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0097284; P:hepatocyte apoptotic process; IEA:Ensembl.
DR GO; GO:0006955; P:immune response; IC:ComplexPortal.
DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; TAS:UniProtKB.
DR GO; GO:0043303; P:mast cell degranulation; TAS:UniProtKB.
DR GO; GO:0035747; P:natural killer cell chemotaxis; TAS:UniProtKB.
DR GO; GO:0055118; P:negative regulation of cardiac muscle contraction; TAS:UniProtKB.
DR GO; GO:2000270; P:negative regulation of fibroblast apoptotic process; IEA:Ensembl.
DR GO; GO:0010897; P:negative regulation of triglyceride catabolic process; IEA:Ensembl.
DR GO; GO:0030593; P:neutrophil chemotaxis; TAS:UniProtKB.
DR GO; GO:0072672; P:neutrophil extravasation; TAS:UniProtKB.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IDA:UniProtKB.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IDA:UniProtKB.
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; IDA:MGI.
DR GO; GO:0070527; P:platelet aggregation; TAS:UniProtKB.
DR GO; GO:0002675; P:positive regulation of acute inflammatory response; IEA:Ensembl.
DR GO; GO:0001819; P:positive regulation of cytokine production; TAS:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl.
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; IDA:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:UniProtKB.
DR GO; GO:0035022; P:positive regulation of Rac protein signal transduction; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IEA:Ensembl.
DR GO; GO:1903169; P:regulation of calcium ion transmembrane transport; IEA:Ensembl.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; TAS:UniProtKB.
DR GO; GO:0002679; P:respiratory burst involved in defense response; TAS:UniProtKB.
DR GO; GO:0032252; P:secretory granule localization; IEA:Ensembl.
DR GO; GO:0003376; P:sphingosine-1-phosphate receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0042110; P:T cell activation; TAS:UniProtKB.
DR GO; GO:0010818; P:T cell chemotaxis; TAS:UniProtKB.
DR GO; GO:0042098; P:T cell proliferation; TAS:UniProtKB.
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 3D-structure; Angiogenesis; ATP-binding; Cell membrane; Chemotaxis;
KW Cytoplasm; Endocytosis; Immunity; Inflammatory response; Kinase;
KW 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_0000088792"
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:0000250|UniProtKB:Q9JHG7"
FT MOD_RES 1101
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12502714"
FT MUTAGEN 833
FT /note="K->R: Loss of kinase activity. Loss of
FT autophosphorylation. Reduced inflammatory reactions but no
FT alterations in cardiac contractility."
FT /evidence="ECO:0000269|PubMed:15294162,
FT ECO:0000269|PubMed:16094730"
FT MUTAGEN 947
FT /note="R->P: Abolishes protein and lipid kinase activity.
FT Does not abolishes interaction with GRK2."
FT /evidence="ECO:0000269|PubMed:16094730"
FT MUTAGEN 1101
FT /note="S->A,Q: Loss of autophosphorylation. No effect on
FT phosphatidylinositol-4,5-bisphosphate 3-kinase activity."
FT /evidence="ECO:0000269|PubMed:12502714"
FT CONFLICT 30
FT /note="Missing (in Ref. 1; CAA58284)"
FT /evidence="ECO:0000305"
FT CONFLICT 459
FT /note="Q -> R (in Ref. 1; CAA58284 and 3; AAG61115)"
FT /evidence="ECO:0000305"
FT STRAND 41..44
FT /evidence="ECO:0007829|PDB:7MEZ"
FT STRAND 55..58
FT /evidence="ECO:0007829|PDB:7MEZ"
FT HELIX 70..81
FT /evidence="ECO:0007829|PDB:7MEZ"
FT HELIX 83..89
FT /evidence="ECO:0007829|PDB:7MEZ"
FT STRAND 96..108
FT /evidence="ECO:0007829|PDB:7MEZ"
FT HELIX 115..118
FT /evidence="ECO:0007829|PDB:7MEZ"
FT HELIX 119..128
FT /evidence="ECO:0007829|PDB:7MEZ"
FT STRAND 134..139
FT /evidence="ECO:0007829|PDB:7MEZ"
FT HELIX 145..158
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 165..167
FT /evidence="ECO:0007829|PDB:3APC"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 172..179
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 181..190
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 193..198
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 209..212
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 213..215
FT /evidence="ECO:0007829|PDB:5G2N"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 220..226
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 229..235
FT /evidence="ECO:0007829|PDB:6AUD"
FT HELIX 241..243
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 246..252
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 256..259
FT /evidence="ECO:0007829|PDB:1HE8"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:1HE8"
FT HELIX 267..269
FT /evidence="ECO:0007829|PDB:6XRL"
FT STRAND 271..274
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:6AUD"
FT HELIX 287..289
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 291..298
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 303..308
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 313..316
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 336..339
FT /evidence="ECO:0007829|PDB:7MEZ"
FT STRAND 346..348
FT /evidence="ECO:0007829|PDB:7MEZ"
FT STRAND 351..353
FT /evidence="ECO:0007829|PDB:7MEZ"
FT HELIX 354..356
FT /evidence="ECO:0007829|PDB:4ANV"
FT STRAND 359..369
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 375..377
FT /evidence="ECO:0007829|PDB:4ANW"
FT STRAND 380..391
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 393..398
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 406..419
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 420..422
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 428..434
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 462..469
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 473..475
FT /evidence="ECO:0007829|PDB:4ANV"
FT STRAND 478..483
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 484..486
FT /evidence="ECO:0007829|PDB:5T23"
FT HELIX 499..502
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 511..513
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 515..520
FT /evidence="ECO:0007829|PDB:1E8Y"
FT TURN 537..540
FT /evidence="ECO:0007829|PDB:7MEZ"
FT HELIX 549..560
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 563..565
FT /evidence="ECO:0007829|PDB:7JWE"
FT HELIX 569..577
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 579..582
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 586..588
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 589..593
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 601..612
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 615..618
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 624..630
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 632..634
FT /evidence="ECO:0007829|PDB:1HE8"
FT HELIX 638..648
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 653..666
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 667..669
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 671..674
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 676..687
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 689..705
FT /evidence="ECO:0007829|PDB:1E8Y"
FT TURN 707..709
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 710..721
FT /evidence="ECO:0007829|PDB:1E8Y"
FT TURN 722..724
FT /evidence="ECO:0007829|PDB:3ML8"
FT HELIX 726..751
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 755..757
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 761..774
FT /evidence="ECO:0007829|PDB:1E8Y"
FT TURN 775..778
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 783..785
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 788..796
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 798..800
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 806..808
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 811..818
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 819..821
FT /evidence="ECO:0007829|PDB:6XRM"
FT STRAND 828..836
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 838..856
FT /evidence="ECO:0007829|PDB:1E8Y"
FT TURN 857..859
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 869..873
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 876..880
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 885..887
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 888..895
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 898..900
FT /evidence="ECO:0007829|PDB:3LJ3"
FT HELIX 906..914
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 915..917
FT /evidence="ECO:0007829|PDB:2A4Z"
FT HELIX 918..941
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 949..951
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 952..955
FT /evidence="ECO:0007829|PDB:1E8Y"
FT TURN 956..958
FT /evidence="ECO:0007829|PDB:1HE8"
FT STRAND 960..962
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 965..970
FT /evidence="ECO:0007829|PDB:3L54"
FT TURN 976..979
FT /evidence="ECO:0007829|PDB:7MEZ"
FT HELIX 989..994
FT /evidence="ECO:0007829|PDB:1E8Y"
FT TURN 998..1000
FT /evidence="ECO:0007829|PDB:4ANV"
FT HELIX 1004..1021
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 1024..1038
FT /evidence="ECO:0007829|PDB:1E8Y"
FT STRAND 1039..1041
FT /evidence="ECO:0007829|PDB:1E8Y"
FT TURN 1042..1045
FT /evidence="ECO:0007829|PDB:3PRE"
FT HELIX 1046..1054
FT /evidence="ECO:0007829|PDB:1E8Y"
FT TURN 1055..1058
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 1061..1078
FT /evidence="ECO:0007829|PDB:1E8Y"
FT HELIX 1081..1085
FT /evidence="ECO:0007829|PDB:1E8Y"
FT TURN 1090..1092
FT /evidence="ECO:0007829|PDB:5G55"
SQ SEQUENCE 1102 AA; 126454 MW; EF2B1A0E1CBEF406 CRC64;
MELENYKQPV VLREDNCRRR RRMKPRSAAA SLSSMELIPI EFVLPTSQRK CKSPETALLH
VAGHGNVEQM KAQVWLRALE TSVAADFYHR LGPHHFLLLY QKKGQWYEIY DKYQVVQTLD
CLRYWKATHR SPGQIHLVQR HPPSEESQAF QRQLTALIGY DVTDVSNVHD DELEFTRRGL
VTPRMAEVAS RDPKLYAMHP WVTSKPLPEY LWKKIANNCI FIVIHRSTTS QTIKVSPDDT
PGAILQSFFT KMAKKKSLMD IPESQSEQDF VLRVCGRDEY LVGETPIKNF QWVRHCLKNG
EEIHVVLDTP PDPALDEVRK EEWPLVDDCT GVTGYHEQLT IHGKDHESVF TVSLWDCDRK
FRVKIRGIDI PVLPRNTDLT VFVEANIQHG QQVLCQRRTS PKPFTEEVLW NVWLEFSIKI
KDLPKGALLN LQIYCGKAPA LSSKASAESP SSESKGKVQL LYYVNLLLID HRFLLRRGEY
VLHMWQISGK GEDQGSFNAD KLTSATNPDK ENSMSISILL DNYCHPIALP KHQPTPDPEG
DRVRAEMPNQ LRKQLEAIIA TDPLNPLTAE DKELLWHFRY ESLKHPKAYP KLFSSVKWGQ
QEIVAKTYQL LARREVWDQS ALDVGLTMQL LDCNFSDENV RAIAVQKLES LEDDDVLHYL
LQLVQAVKFE PYHDSALARF LLKRGLRNKR IGHFLFWFLR SEIAQSRHYQ QRFAVILEAY
LRGCGTAMLH DFTQQVQVIE MLQKVTLDIK SLSAEKYDVS SQVISQLKQK LENLQNSQLP
ESFRVPYDPG LKAGALAIEK CKVMASKKKP LWLEFKCADP TALSNETIGI IFKHGDDLRQ
DMLILQILRI MESIWETESL DLCLLPYGCI STGDKIGMIE IVKDATTIAK IQQSTVGNTG
AFKDEVLNHW LKEKSPTEEK FQAAVERFVY SCAGYCVATF VLGIGDRHND NIMITETGNL
FHIDFGHILG NYKSFLGINK ERVPFVLTPD FLFVMGTSGK KTSPHFQKFQ DICVKAYLAL
RHHTNLLIIL FSMMLMTGMP QLTSKEDIEY IRDALTVGKN EEDAKKYFLD QIEVCRDKGW
TVQFNWFLHL VLGIKQGEKH SA
