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 29-MAY-2013, entry version 136.
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=2.7.1.153;
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;
DE EC=2.7.11.1;
DE AltName: Full=p120-PI3K;
GN Name=PIK3CG;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ENZYME REGULATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=7624799; DOI=10.1126/science.7624799;
RA Stoyanov B., Volinia S., Hanck T., Rubio I., Loubtchenkov M.,
RA Malek D., Stoyanova S., Vanhaesebroeck B., Dhand R., Nuernberg B.,
RA Gierschik P., 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.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA 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.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., 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.,
RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA 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.,
RA Mural R.J., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
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-
RT independent manner.";
RL Mol. Cell. Biol. 21:4579-4597(2001).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ADRBK1.
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
RT endocytosis by AP-2 recruitment to the receptor/beta-arrestin
RT complex.";
RL J. Cell Biol. 158:563-575(2002).
RN [10]
RP AUTOPHOSPHORYLATION AT 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
RT of phosphoinositide 3-kinase isoforms beta and gamma.";
RL J. Biol. Chem. 278:11536-11545(2003).
RN [11]
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
RT by distinct kinase-dependent and -independent effects.";
RL Cell 118:375-387(2004).
RN [12]
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.,
RA 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 [13]
RP FUNCTION AS A PROTEIN KINASE, INTERACTION WITH ADRBK1 AND TPM2, AND
RP MUTAGENESIS OF 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 [14]
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
RT rheumatoid arthritis and beyond?";
RL Nat. Rev. Immunol. 7:191-201(2007).
RN [15]
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 [16]
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 [17]
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.,
RA Buerckstuemmer T., 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 [18]
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.,
RA Zaccolo M., Houslay M.D., Maurice D.H.;
RT "A phosphodiesterase 3B-based signaling complex integrates exchange
RT protein activated by cAMP 1 and phosphatidylinositol 3-kinase signals
RT in human arterial endothelial cells.";
RL J. Biol. Chem. 286:16285-16296(2011).
RN [19]
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 [20]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 144-1101 IN A COMPLEX WITH
RP AS-604850 AND AS-605240, AND ENZYME 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.,
RA Gretener D., Perrin D., Leroy D., Vitte P.-A., Hirsch E., Wymann M.P.,
RA Cirillo R., Schwarz M.K., Rommel C.;
RT "Blockade of PI3Kgamma suppresses joint inflammation and damage in
RT mouse 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
CC role by recruiting PH domain-containing proteins to the membrane,
CC including AKT1 and PDPK1, activating signaling cascades involved
CC in cell growth, survival, proliferation, motility and morphology.
CC Links G-protein coupled receptor activation to PIP3 production.
CC Involved in immune, inflammatory and allergic responses. Modulates
CC leukocyte chemotaxis to inflammatory sites and in response to
CC chemoattractant agents. May control leukocyte polarization and
CC migration by regulating the spatial accumulation of PIP3 and by
CC regulating the organization of F-actin formation and integrin-
CC based adhesion at the leading edge. Controls motility of dendritic
CC cells. Together with PIK3CD is involved in natural killer (NK)
CC cell development and migration towards the sites of inflammation.
CC Participates in T-lymphocyte migration. Regulates T-lymphocyte
CC proliferation and cytokine production. Together with PIK3CD
CC participates in T-lymphocyte development. Required for B-
CC lymphocyte development and signaling. Together with PIK3CD
CC participates in neutrophil respiratory burst. Together with PIK3CD
CC is involved in neutrophil chemotaxis and extravasation. Together
CC with PIK3CB promotes platelet aggregation and thrombosis.
CC Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive
CC function in platelets downstream of P2Y12 through a lipid kinase
CC activity-independent mechanism. May have also a lipid kinase
CC activity-dependent function in platelet aggregation. Involved in
CC endothelial progenitor cell migration. Negative regulator of
CC cardiac contractility. Modulates cardiac contractility by
CC anchoring protein kinase A (PKA) and PDE3B activation, reducing
CC cAMP levels. Regulates cardiac contractility also by promoting
CC beta-adrenergic receptor internalization by binding to ADRBK1 and
CC by non-muscle tropomyosin phosphorylation. Also has
CC serine/threonine protein kinase activity: both lipid and protein
CC kinase activities are required for beta-adrenergic receptor
CC endocytosis. May also have a scaffolding role in modulating
CC cardiac contractility. Contributes to cardiac hypertrophy under
CC pathological stress. Through simultaneous binding of PDE3B to
CC RAPGEF3 and PIK3R6 is assembled in a signaling complex in which
CC the PI3K gamma complex is activated by RAPGEF3 and which is
CC involved in angiogenesis.
CC -!- CATALYTIC ACTIVITY: ATP + 1-phosphatidyl-1D-myo-inositol 4,5-
CC bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-
CC trisphosphate.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- ENZYME REGULATION: Activated by both the alpha and the beta-gamma
CC G proteins following stimulation of G protein-coupled receptors
CC (GPCRs). Activation by GPCRs is assisted by the regulatory
CC subunits (PIK3R5 or PIK3R6) leading to the translocation from the
CC cytosol to the plasma membrane and to kinase activation. Inhibited
CC by AS-604850 and AS-605240.
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylinositol phosphate
CC biosynthesis.
CC -!- SUBUNIT: Heterodimer of a catalytic subunit PIK3CG and a PIK3R5 or
CC PIK3R6 regulatory subunit. Interacts with ADRBK1 through the PIK
CC helical domain. Interaction with ADRBK1 is required for targeting
CC to agonist-occupied receptor. Interacts with PDE3B (By
CC similarity). Interacts with TPM2. Interacts with EPHA8; regulates
CC integrin-mediated cell adhesion to substrate. Interacts with
CC HRAS1; the interaction is required for membrane recruitment and
CC beta-gamma G protein dimer-dependent activation of the PI3K gamma
CC complex PIK3CG:PIK3R6 (By similarity).
CC -!- INTERACTION:
CC Q13370:PDE3B; NbExp=3; IntAct=EBI-1030384, EBI-6172856;
CC O02696:PIK3R5 (xeno); NbExp=6; IntAct=EBI-1030384, EBI-6172343;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane.
CC -!- TISSUE SPECIFICITY: Pancreas, skeletal muscle, liver and heart.
CC -!- MISCELLANEOUS: Candidate target in therapy for inflammatory
CC diseases. Selective inhibitors and protein ablation are anti-
CC inflammatory in multiple disease models such as asthma, rheumatoid
CC arthritis, allergy, systemic lupus erythematosus, airway
CC inflammation, lung injury and pancreatitis (PubMed:18278175).
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family.
CC -!- SIMILARITY: Contains 1 C2 PI3K-type domain.
CC -!- SIMILARITY: Contains 1 PI3K-ABD domain.
CC -!- SIMILARITY: Contains 1 PI3K-RBD domain.
CC -!- SIMILARITY: Contains 1 PI3K/PI4K domain.
CC -!- SIMILARITY: Contains 1 PIK helical domain.
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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 IPI; IPI00292690; -.
DR RefSeq; NP_002640.2; NM_002649.2.
DR UniGene; Hs.32942; -.
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=144-1101.
DR PDB; 2A5U; X-ray; 2.70 A; A=144-1101.
DR PDB; 2CHW; X-ray; 2.60 A; A=144-1101.
DR PDB; 2CHX; X-ray; 2.50 A; A=144-1101.
DR PDB; 2CHZ; X-ray; 2.60 A; A=144-1101.
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; 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 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; 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 ProteinModelPortal; P48736; -.
DR DIP; DIP-37781N; -.
DR IntAct; P48736; 11.
DR MINT; MINT-155782; -.
DR STRING; 9606.ENSP00000352121; -.
DR PhosphoSite; P48736; -.
DR DMDM; 92090623; -.
DR PaxDb; P48736; -.
DR PRIDE; P48736; -.
DR DNASU; 5294; -.
DR Ensembl; ENST00000359195; ENSP00000352121; ENSG00000105851.
DR Ensembl; ENST00000440650; ENSP00000392258; ENSG00000105851.
DR Ensembl; ENST00000496166; ENSP00000419260; ENSG00000105851.
DR GeneID; 5294; -.
DR KEGG; hsa:5294; -.
DR UCSC; uc003vdu.3; human.
DR CTD; 5294; -.
DR GeneCards; GC07P106505; -.
DR HGNC; HGNC:8978; PIK3CG.
DR MIM; 601232; gene.
DR neXtProt; NX_P48736; -.
DR PharmGKB; PA33311; -.
DR eggNOG; COG5032; -.
DR HOGENOM; HOG000252912; -.
DR HOVERGEN; HBG101026; -.
DR InParanoid; P48736; -.
DR KO; K00922; -.
DR OMA; WYEIYDK; -.
DR OrthoDB; EOG4T4CTN; -.
DR PhylomeDB; P48736; -.
DR BioCyc; MetaCyc:HS02818-MONOMER; -.
DR BRENDA; 2.7.1.137; 2681.
DR Pathway_Interaction_DB; pi3kcipathway; Class I PI3K signaling events.
DR Pathway_Interaction_DB; pi3kcibpathway; Class IB PI3K non-lipid kinase events.
DR Pathway_Interaction_DB; epha_fwdpathway; EPHA forward signaling.
DR Pathway_Interaction_DB; txa2pathway; Thromboxane A2 receptor signaling.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_604; Hemostasis.
DR SignaLink; P48736; -.
DR UniPathway; UPA00220; -.
DR BindingDB; P48736; -.
DR ChEMBL; CHEMBL3267; -.
DR EvolutionaryTrace; P48736; -.
DR GenomeRNAi; 5294; -.
DR NextBio; 20458; -.
DR ArrayExpress; P48736; -.
DR Bgee; P48736; -.
DR CleanEx; HS_PIK3CG; -.
DR Genevestigator; P48736; -.
DR GermOnline; ENSG00000105851; Homo sapiens.
DR GO; GO:0005944; C:1-phosphatidylinositol-4-phosphate 3-kinase, class IB complex; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:RefGenome.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IBA:RefGenome.
DR GO; GO:0035005; F:1-phosphatidylinositol-4-phosphate 3-kinase activity; IBA:RefGenome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046934; F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity; IBA:RefGenome.
DR GO; GO:0004672; F:protein kinase activity; TAS: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:0001816; P:cytokine production; TAS:UniProtKB.
DR GO; GO:0002407; P:dendritic cell chemotaxis; TAS:UniProtKB.
DR GO; GO:0007204; P:elevation of cytosolic calcium ion concentration; IEA:Compara.
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:Compara.
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:0043066; P:negative regulation of apoptotic process; IEA:Compara.
DR GO; GO:0055118; P:negative regulation of cardiac muscle contraction; TAS:UniProtKB.
DR GO; GO:0010897; P:negative regulation of triglyceride catabolic process; IEA:Compara.
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 cascade; IDA:UniProtKB.
DR GO; GO:0070527; P:platelet aggregation; TAS:UniProtKB.
DR GO; GO:0002675; P:positive regulation of acute inflammatory response; IEA:Compara.
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 cascade; IDA:UniProtKB.
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:Compara.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
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 InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR008973; C2_Ca/lipid-bd_dom_CaLB.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR003113; PI3K_adapt-bd_dom.
DR InterPro; IPR002420; PI3K_C2_dom.
DR InterPro; IPR000341; PI3K_Ras-bd_dom.
DR InterPro; IPR015433; PI_Kinase.
DR InterPro; IPR001263; PInositide-3_kin_accessory_dom.
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 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-type_fold; 1.
DR SUPFAM; SSF49562; C2_CaLB; 1.
DR SUPFAM; SSF56112; Kinase_like; 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; PS51547; PI3K_C2; 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 Complete proteome; Cytoplasm; Endocytosis; Immunity;
KW Inflammatory response; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1 1102 Phosphatidylinositol 4,5-bisphosphate 3-
FT kinase catalytic subunit gamma isoform.
FT /FTId=PRO_0000088792.
FT DOMAIN 34 141 PI3K-ABD.
FT DOMAIN 217 309 PI3K-RBD.
FT DOMAIN 357 521 C2 PI3K-type.
FT DOMAIN 541 723 PIK helical.
FT DOMAIN 828 1073 PI3K/PI4K.
FT NP_BIND 829 838 ATP (By similarity).
FT NP_BIND 864 872 ATP (By similarity).
FT NP_BIND 961 969 ATP (By similarity).
FT COMPBIAS 19 23 Poly-Arg.
FT MOD_RES 1024 1024 Phosphothreonine; by PKA (By similarity).
FT MOD_RES 1101 1101 Phosphoserine; by autocatalysis.
FT MUTAGEN 833 833 K->R: Reduced inflammatory reactions but
FT no alterations in cardiac contractility.
FT MUTAGEN 947 947 R->P: Abolishes protein and lipid kinase
FT activity. Does not abolishes interaction
FT with ADRBK1.
FT CONFLICT 30 30 Missing (in Ref. 1; CAA58284).
FT CONFLICT 459 459 Q -> R (in Ref. 1 and 3).
FT HELIX 145 158
FT HELIX 165 167
FT STRAND 169 171
FT HELIX 172 179
FT HELIX 181 190
FT HELIX 193 198
FT HELIX 209 212
FT HELIX 213 215
FT STRAND 216 218
FT STRAND 220 226
FT STRAND 229 235
FT HELIX 241 243
FT HELIX 246 252
FT HELIX 256 259
FT STRAND 263 265
FT STRAND 271 274
FT STRAND 283 285
FT HELIX 287 289
FT HELIX 291 298
FT STRAND 303 308
FT HELIX 313 316
FT HELIX 354 356
FT STRAND 359 369
FT STRAND 375 377
FT STRAND 380 391
FT STRAND 393 398
FT STRAND 406 419
FT HELIX 420 422
FT STRAND 428 434
FT STRAND 462 469
FT STRAND 473 475
FT STRAND 478 483
FT HELIX 499 502
FT STRAND 511 513
FT STRAND 515 520
FT HELIX 549 560
FT STRAND 563 565
FT HELIX 569 577
FT HELIX 579 582
FT HELIX 586 588
FT HELIX 589 593
FT HELIX 601 612
FT HELIX 615 618
FT HELIX 624 630
FT STRAND 632 634
FT HELIX 638 648
FT HELIX 653 666
FT HELIX 667 669
FT STRAND 671 674
FT HELIX 676 687
FT HELIX 689 705
FT TURN 707 709
FT HELIX 710 721
FT TURN 722 724
FT HELIX 726 751
FT STRAND 755 757
FT HELIX 761 774
FT TURN 775 778
FT STRAND 783 785
FT STRAND 788 796
FT HELIX 798 800
FT STRAND 806 808
FT STRAND 811 818
FT STRAND 828 836
FT HELIX 838 856
FT TURN 857 859
FT STRAND 869 873
FT STRAND 876 880
FT STRAND 885 887
FT HELIX 888 895
FT STRAND 898 900
FT HELIX 906 914
FT STRAND 915 917
FT HELIX 918 941
FT HELIX 949 951
FT STRAND 952 955
FT TURN 956 958
FT STRAND 960 962
FT HELIX 965 970
FT HELIX 989 994
FT TURN 998 1000
FT HELIX 1004 1021
FT HELIX 1024 1038
FT STRAND 1039 1041
FT TURN 1042 1045
FT HELIX 1046 1054
FT TURN 1055 1058
FT HELIX 1061 1078
FT HELIX 1081 1085
FT TURN 1086 1090
FT TURN 1091 1093
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
//
