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 27-MAR-2024, entry version 224. 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). RN [24] RP VARIANT IMD97 PRO-1021, CHARACTERIZATION OF VARIANT IMD97 PRO-1021, RP INVOLVEMENT IN IMD97, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=31554793; DOI=10.1038/s41467-019-12311-5; RA Takeda A.J., Maher T.J., Zhang Y., Lanahan S.M., Bucklin M.L., RA Compton S.R., Tyler P.M., Comrie W.A., Matsuda M., Olivier K.N., RA Pittaluga S., McElwee J.J., Long Priel D.A., Kuhns D.B., Williams R.L., RA Mustillo P.J., Wymann M.P., Koneti Rao V., Lucas C.L.; RT "Human PI3Kgamma deficiency and its microbiota-dependent mouse model reveal RT immunodeficiency and tissue immunopathology."; RL Nat. Commun. 10:4364-4364(2019). RN [25] RP VARIANTS IMD97 SER-49 AND SER-1085, CHARACTERIZATION OF VARIANTS IMD97 RP SER-49 AND SER-1085, INVOLVEMENT IN IMD97, AND FUNCTION. RX PubMed=33054089; DOI=10.3324/haematol.2019.231399; RA Thian M., Hoeger B., Kamnev A., Poyer F., Koestel Bal S., Caldera M., RA Jimenez-Heredia R., Huemer J., Pickl W.F., Gross M., Ehl S., Lucas C.L., RA Menche J., Hutter C., Attarbaschi A., Dupre L., Boztug K.; RT "Germline biallelic PIK3CG mutations in a multifaceted immunodeficiency RT with immune dysregulation."; RL Haematologica 105:e488-e488(2020). 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, activation, and cytokine production. Together CC with PIK3CD participates in T-lymphocyte development. Required for B- CC lymphocyte development and signaling. Together with PIK3CD participates CC in 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:31554793, ECO:0000269|PubMed:33054089, 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 ECO:0000269|PubMed:31554793}; 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 -!- DISEASE: Immunodeficiency 97 with autoinflammation (IMD97) CC [MIM:619802]: An autosomal recessive disorder with variable features. CC Affected individuals have childhood-onset antibody defects, cytopenias, CC and T lymphocytic pneumonitis and colitis. Some patients may have CC features of hemophagocytic lymphohistiocytosis. CC {ECO:0000269|PubMed:31554793, ECO:0000269|PubMed:33054089}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 PDB; 7Z61; X-ray; 2.74 A; A=144-1102. DR PDB; 8DP0; EM; 2.96 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 PDBsum; 7Z61; -. DR PDBsum; 8DP0; -. DR AlphaFoldDB; P48736; -. DR EMDB; EMD-23808; -. DR EMDB; EMD-27627; -. DR EMDB; EMD-34271; -. DR EMDB; EMD-34272; -. DR EMDB; EMD-34273; -. 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.ENSP00000419260; -. 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 CPTAC; CPTAC-3150; -. DR CPTAC; CPTAC-3151; -. DR CPTAC; CPTAC-3152; -. DR EPD; P48736; -. DR jPOST; P48736; -. DR MassIVE; P48736; -. DR MaxQB; P48736; -. DR PaxDb; 9606-ENSP00000352121; -. DR PeptideAtlas; P48736; -. DR ProteomicsDB; 55933; -. DR Pumba; P48736; -. DR Antibodypedia; 4141; 1124 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 AGR; HGNC:8978; -. DR CTD; 5294; -. DR DisGeNET; 5294; -. DR GeneCards; PIK3CG; -. DR HGNC; HGNC:8978; PIK3CG. DR HPA; ENSG00000105851; Group enriched (bone marrow, lymphoid tissue). DR MalaCards; PIK3CG; -. DR MIM; 601232; gene. DR MIM; 619802; phenotype. 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; WDCDRRF; -. DR OrthoDB; 10350at2759; -. DR PhylomeDB; P48736; -. DR TreeFam; TF102031; -. DR BioCyc; MetaCyc:HS02818-MONOMER; -. 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 Reactome; R-HSA-9680350; Signaling by CSF1 (M-CSF) in myeloid cells. DR SignaLink; P48736; -. DR SIGNOR; P48736; -. DR UniPathway; UPA00220; -. DR BioGRID-ORCS; 5294; 21 hits in 1160 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 131 other cell types or tissues. DR ExpressionAtlas; P48736; baseline and differential. 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:0005943; C:phosphatidylinositol 3-kinase complex, class IA; EXP:ComplexPortal. 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:0046934; F:1-phosphatidylinositol-4,5-bisphosphate 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: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: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; NAS: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:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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: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 phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProtKB. DR GO; GO:0035022; P:positive regulation of Rac protein signal transduction; IMP:BHF-UCL. DR GO; GO:0045765; P:regulation of angiogenesis; IMP:UniProt. 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 CDD; cd08399; C2_PI3K_class_I_gamma; 1. DR CDD; cd00872; PI3Ka_I; 1. DR CDD; cd00894; PI3Kc_IB_gamma; 1. DR Gene3D; 3.10.20.770; -; 1. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 1.10.1070.11; Phosphatidylinositol 3-/4-kinase, catalytic domain; 1. DR Gene3D; 1.25.40.70; Phosphatidylinositol 3-kinase, accessory domain (PIK); 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:SF34; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT GAMMA ISOFORM; 1. DR PANTHER; PTHR10048; PHOSPHATIDYLINOSITOL KINASE; 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; ARM repeat; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF54236; Ubiquitin-like; 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. DR Genevisible; P48736; HS. PE 1: Evidence at protein level; KW 3D-structure; Angiogenesis; ATP-binding; Cell membrane; Chemotaxis; KW Cytoplasm; Disease variant; 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_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 VARIANT 49 FT /note="R -> S (in IMD97; loss-of-function variant unable to FT rescue reduced T-cell activation when expressed in Jurkat FT PIK3CG-deficient cells)" FT /evidence="ECO:0000269|PubMed:33054089" FT /id="VAR_087092" FT VARIANT 1021 FT /note="R -> P (in IMD97; loss of FT phosphatidylinositol-3,4-bisphosphate 5-kinase activity)" FT /evidence="ECO:0000269|PubMed:31554793" FT /id="VAR_087093" FT VARIANT 1085 FT /note="N -> S (in IMD97; loss-of-function variant unable to FT rescue reduced T-cell activation when expressed in Jurkat FT PIK3CG-deficient cells)" FT /evidence="ECO:0000269|PubMed:33054089" FT /id="VAR_087094" 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 abolish 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 //