GenomeNet

Database: UniProt
Entry: P48736
LinkDB: P48736
Original site: P48736 
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   01-OCT-2014, entry version 151.
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   PHOSPHORYLATION 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. {ECO:0000269|PubMed:12163475,
CC       ECO:0000269|PubMed:15294162, ECO:0000269|PubMed:16094730,
CC       ECO:0000269|PubMed:21393242, ECO:0000269|PubMed:7624799}.
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. {ECO:0000269|PubMed:16127437,
CC       ECO:0000269|PubMed:7624799}.
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 HRAS;
CC       the interaction is required for membrane recruitment and beta-
CC       gamma G protein dimer-dependent activation of the PI3K gamma
CC       complex PIK3CG:PIK3R6 (By similarity). {ECO:0000250}.
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 {ECO:0000269|PubMed:12163475}.
CC       Cell membrane {ECO:0000269|PubMed:12163475}.
CC   -!- TISSUE SPECIFICITY: Pancreas, skeletal muscle, liver and heart.
CC       {ECO:0000269|PubMed:7624799}.
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       {ECO:0000305|PubMed:18278175}.
CC   -!- SIMILARITY: Belongs to the PI3/PI4-kinase family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00877, ECO:0000255|PROSITE-
CC       ProRule:PRU00879, ECO:0000255|PROSITE-ProRule:PRU00880}.
CC   -!- SIMILARITY: Contains 1 C2 PI3K-type domain. {ECO:0000255|PROSITE-
CC       ProRule:PRU00880}.
CC   -!- SIMILARITY: Contains 1 PI3K-ABD domain. {ECO:0000255|PROSITE-
CC       ProRule:PRU00877}.
CC   -!- SIMILARITY: Contains 1 PI3K-RBD domain. {ECO:0000255|PROSITE-
CC       ProRule:PRU00879}.
CC   -!- SIMILARITY: Contains 1 PI3K/PI4K domain. {ECO:0000255|PROSITE-
CC       ProRule:PRU00269}.
CC   -!- SIMILARITY: Contains 1 PIK helical domain. {ECO:0000255|PROSITE-
CC       ProRule:PRU00878}.
CC   -----------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution-NoDerivs 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_005250443.1.
DR   UniGene; Hs.32942; -.
DR   UniGene; Hs.561747; -.
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   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   ProteinModelPortal; P48736; -.
DR   SMR; P48736; 144-1089.
DR   BioGrid; 111312; 18.
DR   DIP; DIP-37781N; -.
DR   IntAct; P48736; 14.
DR   MINT; MINT-155782; -.
DR   STRING; 9606.ENSP00000352121; -.
DR   BindingDB; P48736; -.
DR   ChEMBL; CHEMBL3267; -.
DR   GuidetoPHARMACOLOGY; 2156; -.
DR   PhosphoSite; P48736; -.
DR   DMDM; 92090623; -.
DR   MaxQB; P48736; -.
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; YHEQLTI; -.
DR   OrthoDB; EOG70CR65; -.
DR   PhylomeDB; P48736; -.
DR   TreeFam; TF102031; -.
DR   BioCyc; MetaCyc:HS02818-MONOMER; -.
DR   BRENDA; 2.7.1.137; 2681.
DR   Reactome; REACT_121025; Synthesis of PIPs at the plasma membrane.
DR   Reactome; REACT_1695; GPVI-mediated activation cascade.
DR   Reactome; REACT_19290; G beta:gamma signalling through PI3Kgamma.
DR   SignaLink; P48736; -.
DR   UniPathway; UPA00220; -.
DR   EvolutionaryTrace; P48736; -.
DR   GeneWiki; PIK3CG; -.
DR   GenomeRNAi; 5294; -.
DR   NextBio; 20458; -.
DR   PRO; PR:P48736; -.
DR   ArrayExpress; P48736; -.
DR   Bgee; P48736; -.
DR   CleanEx; HS_PIK3CG; -.
DR   Genevestigator; P48736; -.
DR   GO; GO:0005944; C:1-phosphatidylinositol-4-phosphate 3-kinase, class IB complex; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0042629; C:mast cell granule; TAS:GOC.
DR   GO; GO:0016020; C:membrane; 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:0046875; F:ephrin receptor binding; IPI:UniProtKB.
DR   GO; GO:0035004; F:phosphatidylinositol 3-kinase activity; TAS:UniProtKB.
DR   GO; GO:0046934; F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity; IBA:RefGenome.
DR   GO; GO:0005515; F:protein binding; IPI:IntAct.
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:0007596; P:blood coagulation; TAS:Reactome.
DR   GO; GO:0001816; P:cytokine production; TAS:UniProtKB.
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: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:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR   GO; GO:0006644; P:phospholipid metabolic process; TAS:Reactome.
DR   GO; GO:0030168; P:platelet activation; TAS:Reactome.
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:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl.
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: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:0044281; P:small molecule metabolic process; TAS:Reactome.
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; IPR000008; C2_dom.
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   InterPro; IPR029071; Ubiquitin-rel_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; SSF48371; 1.
DR   SUPFAM; SSF49562; SSF49562; 1.
DR   SUPFAM; SSF54236; SSF54236; 1.
DR   SUPFAM; SSF56112; SSF56112; 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. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00877}.
FT   DOMAIN      217    309       PI3K-RBD. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00879}.
FT   DOMAIN      357    521       C2 PI3K-type. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00880}.
FT   DOMAIN      541    723       PIK helical. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00878}.
FT   DOMAIN      828   1073       PI3K/PI4K. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00269}.
FT   NP_BIND     829    838       ATP. {ECO:0000250}.
FT   NP_BIND     864    872       ATP. {ECO:0000250}.
FT   NP_BIND     961    969       ATP. {ECO:0000250}.
FT   COMPBIAS     19     23       Poly-Arg.
FT   MOD_RES    1024   1024       Phosphothreonine; by PKA. {ECO:0000250}.
FT   MOD_RES    1101   1101       Phosphoserine; by autocatalysis.
FT                                {ECO:0000269|PubMed:12502714}.
FT   MUTAGEN     833    833       K->R: Reduced inflammatory reactions but
FT                                no alterations in cardiac contractility.
FT                                {ECO:0000269|PubMed:15294162}.
FT   MUTAGEN     947    947       R->P: Abolishes protein and lipid kinase
FT                                activity. Does not abolishes interaction
FT                                with ADRBK1.
FT                                {ECO:0000269|PubMed:16094730}.
FT   CONFLICT     30     30       Missing (in Ref. 1; CAA58284).
FT                                {ECO:0000305}.
FT   CONFLICT    459    459       Q -> R (in Ref. 1; CAA58284 and 3;
FT                                AAG61115). {ECO:0000305}.
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
//
DBGET integrated database retrieval system