P48736 (PK3CG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
Short name=PI3-kinase subunit gamma
Short name=PI3K-gamma
Short name=PI3Kgamma
Short name=PtdIns-3-kinase subunit gamma
EC=2.7.1.153

Alternative name(s):
Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma
Short name=PtdIns-3-kinase subunit p110-gamma
Short name=p110gamma
Phosphoinositide-3-kinase catalytic gamma polypeptide
Serine/threonine protein kinase PIK3CG
EC=2.7.11.1
p120-PI3K

Gene names

Name:

PIK3CG

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1102 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to ADRBK1 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis. Ref.1 Ref.9 Ref.11 Ref.13 Ref.18
Catalytic activity	ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate. ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Activated by both the alpha and the beta-gamma G proteins following stimulation of G protein-coupled receptors (GPCRs). Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation. Inhibited by AS-604850 and AS-605240. Ref.1 Ref.20
Pathway	Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis.
Subunit structure	Heterodimer of a catalytic subunit PIK3CG and a PIK3R5 or PIK3R6 regulatory subunit. Interacts with ADRBK1 through the PIK helical domain. Interaction with ADRBK1 is required for targeting to agonist-occupied receptor. Interacts with PDE3B By similarity. Interacts with TPM2. Interacts with EPHA8; regulates integrin-mediated cell adhesion to substrate. Interacts with HRAS1; the interaction is required for membrane recruitment and beta-gamma G protein dimer-dependent activation of the PI3K gamma complex PIK3CG:PIK3R6 By similarity. Ref.8 Ref.9 Ref.12 Ref.13
Subcellular location	Cytoplasm. Cell membrane Ref.9.
Tissue specificity	Pancreas, skeletal muscle, liver and heart. Ref.1
Miscellaneous	Candidate target in therapy for inflammatory diseases. Selective inhibitors and protein ablation are anti-inflammatory in multiple disease models such as asthma, rheumatoid arthritis, allergy, systemic lupus erythematosus, airway inflammation, lung injury and pancreatitis (Ref.15).
Sequence similarities	Belongs to the PI3/PI4-kinase family. Contains 1 C2 PI3K-type domain. Contains 1 PI3K-ABD domain. Contains 1 PI3K-RBD domain. Contains 1 PI3K/PI4K domain. Contains 1 PIK helical domain.

Ontologies

Keywords
Biological process	Angiogenesis Chemotaxis Endocytosis Immunity Inflammatory response
Cellular component	Cell membrane Cytoplasm Membrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway Inferred from direct assay PubMed 12507995. Source: UniProtKB T cell chemotaxis Traceable author statement Ref.15. Source: UniProtKB T cell proliferation Traceable author statement PubMed 19075988. Source: UniProtKB adaptive immune response Traceable author statement Ref.14. Source: UniProtKB angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW cytokine production Traceable author statement PubMed 19075988. Source: UniProtKB dendritic cell chemotaxis Traceable author statement Ref.15. Source: UniProtKB elevation of cytosolic calcium ion concentration Inferred from electronic annotation. Source: Compara endocytosis Inferred from electronic annotation. Source: UniProtKB-KW hepatocyte apoptotic process Inferred from electronic annotation. Source: Compara inflammatory response Traceable author statement Ref.14. Source: UniProtKB innate immune response Traceable author statement Ref.14. Source: UniProtKB mast cell degranulation Traceable author statement Ref.14. Source: UniProtKB natural killer cell chemotaxis Traceable author statement Ref.15. Source: UniProtKB negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of cardiac muscle contraction Traceable author statement Ref.16. Source: UniProtKB negative regulation of triglyceride catabolic process Inferred from electronic annotation. Source: Compara neutrophil chemotaxis Traceable author statement Ref.14. Source: UniProtKB neutrophil extravasation Traceable author statement Ref.15. Source: UniProtKB phosphatidylinositol 3-kinase cascade Inferred from direct assay PubMed 12507995. Source: UniProtKB platelet aggregation Traceable author statement PubMed 21035500. Source: UniProtKB positive regulation of MAP kinase activity Inferred from direct assay PubMed 12507995. Source: UniProtKB positive regulation of acute inflammatory response Inferred from electronic annotation. Source: Compara positive regulation of protein kinase B signaling cascade Inferred from direct assay PubMed 12507995. Source: UniProtKB regulation of cell adhesion mediated by integrin Traceable author statement Ref.15. Source: UniProtKB respiratory burst involved in defense response Traceable author statement PubMed 19075988. Source: UniProtKB secretory granule localization Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	1-phosphatidylinositol-4-phosphate 3-kinase, class IB complex Inferred from direct assay PubMed 12507995. Source: UniProtKB plasma membrane Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	1-phosphatidylinositol-3-kinase activity Inferred from Biological aspect of Ancestor. Source: RefGenome 1-phosphatidylinositol-4-phosphate 3-kinase activity Inferred from Biological aspect of Ancestor. Source: RefGenome ATP binding Inferred from electronic annotation. Source: UniProtKB-KW phosphatidylinositol-4,5-bisphosphate 3-kinase activity Inferred from Biological aspect of Ancestor. Source: RefGenome protein kinase activity Traceable author statement PubMed 19376709. Source: UniProtKB protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PDE3B	Q13370	3	EBI-1030384,EBI-6172856
PIK3R5	O02696	6	EBI-1030384,EBI-6172343	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1102

1102

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform

PRO_0000088792

Regions

Domain

34 – 141

108

PI3K-ABD

Domain

217 – 309

93

PI3K-RBD

Domain

357 – 521

165

C2 PI3K-type

Domain

541 – 723

183

PIK helical

Domain

828 – 1073

246

PI3K/PI4K

Nucleotide binding

829 – 838

10

ATP By similarity

Nucleotide binding

864 – 872

9

ATP By similarity

Nucleotide binding

961 – 969

9

ATP By similarity

Compositional bias

19 – 23

5

Poly-Arg

Amino acid modifications

Modified residue

1024

1

Phosphothreonine; by PKA By similarity

Modified residue

1101

1

Phosphoserine; by autocatalysis Ref.10

Experimental info

Mutagenesis

833

1

K → R: Reduced inflammatory reactions but no alterations in cardiac contractility. Ref.11

Mutagenesis

947

1

R → P: Abolishes protein and lipid kinase activity. Does not abolishes interaction with ADRBK1. Ref.13

Sequence conflict

30

1

Missing in CAA58284. Ref.1

Sequence conflict

459

1

Q → R Ref.1

Sequence conflict

459

1

Q → R Ref.3

Secondary structure

1

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1102

Helix Strand Turn

Details...

Helix

145 – 158

14

Helix

165 – 167

3

Beta strand

169 – 171

3

Helix

172 – 179

8

Helix

181 – 190

10

Helix

193 – 198

6

Helix

209 – 212

4

Helix

213 – 215

3

Beta strand

216 – 218

3

Beta strand

220 – 226

7

Beta strand

229 – 235

7

Helix

241 – 243

3

Helix

246 – 252

7

Helix

256 – 259

4

Beta strand

263 – 265

3

Beta strand

271 – 274

4

Beta strand

283 – 285

3

Helix

287 – 289

3

Helix

291 – 298

8

Beta strand

303 – 308

6

Helix

313 – 316

4

Helix

354 – 356

3

Beta strand

359 – 369

11

Beta strand

375 – 377

3

Beta strand

380 – 391

12

Beta strand

393 – 398

6

Beta strand

406 – 419

14

Helix

420 – 422

3

Beta strand

428 – 434

7

Beta strand

462 – 469

8

Beta strand

473 – 475

3

Beta strand

478 – 483

6

Helix

499 – 502

4

Beta strand

511 – 513

3

Beta strand

515 – 520

6

Helix

549 – 560

12

Beta strand

563 – 565

3

Helix

569 – 577

9

Helix

579 – 582

4

Helix

586 – 588

3

Helix

589 – 593

5

Helix

601 – 612

12

Helix

615 – 618

4

Helix

624 – 630

7

Beta strand

632 – 634

3

Helix

638 – 648

11

Helix

653 – 666

14

Helix

667 – 669

3

Beta strand

671 – 674

4

Helix

676 – 687

12

Helix

689 – 705

17

Turn

707 – 709

3

Helix

710 – 721

12

Turn

722 – 724

3

Helix

726 – 751

26

Beta strand

755 – 757

3

Helix

761 – 774

14

Turn

775 – 778

4

Beta strand

783 – 785

3

Beta strand

788 – 796

9

Helix

798 – 800

3

Beta strand

806 – 808

3

Beta strand

811 – 818

8

Beta strand

828 – 836

9

Helix

838 – 856

19

Turn

857 – 859

3

Beta strand

869 – 873

5

Beta strand

876 – 880

5

Beta strand

885 – 887

3

Helix

888 – 895

8

Beta strand

898 – 900

3

Helix

906 – 914

9

Beta strand

915 – 917

3

Helix

918 – 941

24

Helix

949 – 951

3

Beta strand

952 – 955

4

Turn

956 – 958

3

Beta strand

960 – 962

3

Helix

965 – 970

6

Helix

989 – 994

6

Turn

998 – 1000

3

Helix

1004 – 1021

18

Helix

1024 – 1038

15

Beta strand

1039 – 1041

3

Turn

1042 – 1045

4

Helix

1046 – 1054

9

Turn

1055 – 1058

4

Helix

1061 – 1078

18

Helix

1081 – 1085

5

Turn

1086 – 1090

5

Turn

1091 – 1093

3

Sequences

	Sequence		Length	Mass (Da)
	P48736 [UniParc]. Last modified April 4, 2006. Version 3. Checksum: EF2B1A0E1CBEF406	FASTA	1,102	126,454
	10 20 30 40 50 60 MELENYKQPV VLREDNCRRR RRMKPRSAAA SLSSMELIPI EFVLPTSQRK CKSPETALLH 70 80 90 100 110 120 VAGHGNVEQM KAQVWLRALE TSVAADFYHR LGPHHFLLLY QKKGQWYEIY DKYQVVQTLD 130 140 150 160 170 180 CLRYWKATHR SPGQIHLVQR HPPSEESQAF QRQLTALIGY DVTDVSNVHD DELEFTRRGL 190 200 210 220 230 240 VTPRMAEVAS RDPKLYAMHP WVTSKPLPEY LWKKIANNCI FIVIHRSTTS QTIKVSPDDT 250 260 270 280 290 300 PGAILQSFFT KMAKKKSLMD IPESQSEQDF VLRVCGRDEY LVGETPIKNF QWVRHCLKNG 310 320 330 340 350 360 EEIHVVLDTP PDPALDEVRK EEWPLVDDCT GVTGYHEQLT IHGKDHESVF TVSLWDCDRK 370 380 390 400 410 420 FRVKIRGIDI PVLPRNTDLT VFVEANIQHG QQVLCQRRTS PKPFTEEVLW NVWLEFSIKI 430 440 450 460 470 480 KDLPKGALLN LQIYCGKAPA LSSKASAESP SSESKGKVQL LYYVNLLLID HRFLLRRGEY 490 500 510 520 530 540 VLHMWQISGK GEDQGSFNAD KLTSATNPDK ENSMSISILL DNYCHPIALP KHQPTPDPEG 550 560 570 580 590 600 DRVRAEMPNQ LRKQLEAIIA TDPLNPLTAE DKELLWHFRY ESLKHPKAYP KLFSSVKWGQ 610 620 630 640 650 660 QEIVAKTYQL LARREVWDQS ALDVGLTMQL LDCNFSDENV RAIAVQKLES LEDDDVLHYL 670 680 690 700 710 720 LQLVQAVKFE PYHDSALARF LLKRGLRNKR IGHFLFWFLR SEIAQSRHYQ QRFAVILEAY 730 740 750 760 770 780 LRGCGTAMLH DFTQQVQVIE MLQKVTLDIK SLSAEKYDVS SQVISQLKQK LENLQNSQLP 790 800 810 820 830 840 ESFRVPYDPG LKAGALAIEK CKVMASKKKP LWLEFKCADP TALSNETIGI IFKHGDDLRQ 850 860 870 880 890 900 DMLILQILRI MESIWETESL DLCLLPYGCI STGDKIGMIE IVKDATTIAK IQQSTVGNTG 910 920 930 940 950 960 AFKDEVLNHW LKEKSPTEEK FQAAVERFVY SCAGYCVATF VLGIGDRHND NIMITETGNL 970 980 990 1000 1010 1020 FHIDFGHILG NYKSFLGINK ERVPFVLTPD FLFVMGTSGK KTSPHFQKFQ DICVKAYLAL 1030 1040 1050 1060 1070 1080 RHHTNLLIIL FSMMLMTGMP QLTSKEDIEY IRDALTVGKN EEDAKKYFLD QIEVCRDKGW 1090 1100 TVQFNWFLHL VLGIKQGEKH SA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of a G protein-activated human phosphoinositide-3 kinase." Stoyanov B., Volinia S., Hanck T., Rubio I., Loubtchenkov M., Malek D., Stoyanova S., Vanhaesebroeck B., Dhand R., Nuernberg B., Gierschik P., Seedorf K., Hsuan J.J., Waterfield M.D., Wetzker R. Science 269:690-693(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ENZYME REGULATION, TISSUE SPECIFICITY.
[2]	Waterfield M.D. Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"Regulation of a G-protein-activated phosphoinositide-3-kinase." Michalke M., Schaefer M., Stoyanov B., Wetzker R., Nuernberg B. Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[8]	"The EphA8 receptor regulates integrin activity through p110gamma phosphatidylinositol-3 kinase in a tyrosine kinase activity-independent manner." Gu C., Park S. Mol. Cell. Biol. 21:4579-4597(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EPHA8.
[9]	"Phosphoinositide 3-kinase regulates beta2-adrenergic receptor endocytosis by AP-2 recruitment to the receptor/beta-arrestin complex." Naga Prasad S.V., Laporte S.A., Chamberlain D., Caron M.G., Barak L., Rockman H.A. J. Cell Biol. 158:563-575(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ADRBK1.
[10]	"Identification and characterization of the autophosphorylation sites of phosphoinositide 3-kinase isoforms beta and gamma." Czupalla C., Culo M., Muller E.C., Brock C., Reusch H.P., Spicher K., Krause E., Nurnberg B. J. Biol. Chem. 278:11536-11545(2003) [PubMed] [Europe PMC] [Abstract] Cited for: AUTOPHOSPHORYLATION AT SER-1101.
[11]	"PI3Kgamma modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and -independent effects." Patrucco E., Notte A., Barberis L., Selvetella G., Maffei A., Brancaccio M., Marengo S., Russo G., Azzolino O., Rybalkin S.D., Silengo L., Altruda F., Wetzker R., Wymann M.P., Lembo G., Hirsch E. Cell 118:375-387(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CARDIAC CONTRACTILITY, MUTAGENESIS OF LYS-833.
[12]	"p84, a new Gbetagamma-activated regulatory subunit of the type IB phosphoinositide 3-kinase p110gamma." Suire S., Coadwell J., Ferguson G.J., Davidson K., Hawkins P., Stephens L. Curr. Biol. 15:566-570(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PIK3R5.
[13]	"Protein kinase activity of phosphoinositide 3-kinase regulates beta-adrenergic receptor endocytosis." Naga Prasad S.V., Jayatilleke A., Madamanchi A., Rockman H.A. Nat. Cell Biol. 7:785-796(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A PROTEIN KINASE, INTERACTION WITH ADRBK1 AND TPM2, MUTAGENESIS OF ARG-947.
[14]	"PI3K delta and PI3K gamma: partners in crime in inflammation in rheumatoid arthritis and beyond?" Rommel C., Camps M., Ji H. Nat. Rev. Immunol. 7:191-201(2007) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[15]	"Targeting phosphoinositide 3-kinase gamma to fight inflammation and more." Barberis L., Hirsch E. Thromb. Haemost. 99:279-285(2008) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION IN LEUKOCYTES AND ENDOTHELIAL CELLS, REVIEW ON ANTINFLAMMATORY THERAPY TARGET.
[16]	"Cardiac regulation by phosphoinositide 3-kinases and PTEN." Oudit G.Y., Penninger J.M. Cardiovasc. Res. 82:250-260(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION IN CARDIAC CONTRACTILITY.
[17]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]	"A phosphodiesterase 3B-based signaling complex integrates exchange protein activated by cAMP 1 and phosphatidylinositol 3-kinase signals in human arterial endothelial cells." Wilson L.S., Baillie G.S., Pritchard L.M., Umana B., Terrin A., Zaccolo M., Houslay M.D., Maurice D.H. J. Biol. Chem. 286:16285-16296(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[19]	"Structural insights into phosphoinositide 3-kinase catalysis and signalling." Walker E.H., Perisic O., Ried C., Stephens L., Williams R.L. Nature 402:313-320(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 144-1102.
[20]	"Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis." Camps M., Rueckle T., Ji H., Ardissone V., Rintelen F., Shaw J., Ferrandi C., Chabert C., Gillieron C., Francon B., Martin T., Gretener D., Perrin D., Leroy D., Vitte P.-A., Hirsch E., Wymann M.P., Cirillo R., Schwarz M.K., Rommel C. Nat. Med. 11:936-943(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 144-1101 IN A COMPLEX WITH AS-604850 AND AS-605240, ENZYME REGULATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X83368 mRNA. Translation: CAA58284.1.
AF327656 mRNA. Translation: AAG61115.1.
AC005018 Genomic DNA. Translation: AAQ96873.1.
CH236947 Genomic DNA. Translation: EAL24396.1.
CH471070 Genomic DNA. Translation: EAW83387.1.
BC035683 mRNA. Translation: AAH35683.1.

IPI

IPI00292690.

RefSeq

NP_002640.2. NM_002649.2.

UniGene

Hs.32942.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1E8Y	X-ray	2.00	A	144-1102	[»]
1E8Z	X-ray	2.40	A	144-1102	[»]
1HE8	X-ray	3.00	A	144-1102	[»]
2A4Z	X-ray	2.90	A	144-1101	[»]
2A5U	X-ray	2.70	A	144-1101	[»]
2CHW	X-ray	2.60	A	144-1101	[»]
2CHX	X-ray	2.50	A	144-1101	[»]
2CHZ	X-ray	2.60	A	144-1101	[»]
2V4L	X-ray	2.50	A	144-1102	[»]
3APC	X-ray	2.54	A	144-1102	[»]
3APD	X-ray	2.55	A	144-1102	[»]
3APF	X-ray	2.82	A	144-1102	[»]
3CSF	X-ray	2.80	A	144-1102	[»]
3CST	X-ray	3.20	A	144-1102	[»]
3DBS	X-ray	2.80	A	144-1102	[»]
3DPD	X-ray	2.85	A	144-1102	[»]
3ENE	X-ray	2.40	A	144-1102	[»]
3IBE	X-ray	2.80	A	144-1102	[»]
3L08	X-ray	2.70	A	144-1102	[»]
3L13	X-ray	3.00	A	144-1102	[»]
3L16	X-ray	2.90	A	144-1102	[»]
3L17	X-ray	3.00	A	144-1102	[»]
3L54	X-ray	2.30	A	144-1102	[»]
3LJ3	X-ray	2.43	A	144-1102	[»]
3MJW	X-ray	2.87	A	144-1102	[»]
3ML8	X-ray	2.70	A	144-1102	[»]
3ML9	X-ray	2.55	A	144-1102	[»]
3NZS	X-ray	2.75	A	147-1094	[»]
3NZU	X-ray	2.60	A	147-1094	[»]
3OAW	X-ray	2.75	A	144-1102	[»]
3P2B	X-ray	3.20	A	144-1102	[»]
3PRE	X-ray	2.91	A	144-1102	[»]
3PRZ	X-ray	2.60	A	144-1102	[»]
3PS6	X-ray	2.60	A	144-1102	[»]
3QAQ	X-ray	2.90	A	144-1102	[»]
3QAR	X-ray	2.65	A	144-1102	[»]
3QJZ	X-ray	2.90	A	144-1102	[»]
3QK0	X-ray	2.85	A	144-1102	[»]
3R7Q	X-ray	2.50	A	144-1102	[»]
3R7R	X-ray	2.90	A	144-1102	[»]
3S2A	X-ray	2.55	A	144-1102	[»]
3SD5	X-ray	3.20	A	144-1102	[»]
3T8M	X-ray	2.50	A	144-1102	[»]
3TJP	X-ray	2.70	A	144-1102	[»]
3TL5	X-ray	2.79	A	144-1102	[»]
3ZVV	X-ray	2.50	A	144-1102	[»]
3ZW3	X-ray	2.80	A	144-1102	[»]
4ANU	X-ray	2.81	A	144-1102	[»]
4ANV	X-ray	2.13	A	144-1102	[»]
4ANW	X-ray	2.31	A	144-1102	[»]
4ANX	X-ray	2.73	A	144-1102	[»]
4AOF	X-ray	3.30	A	144-1102	[»]
4DK5	X-ray	2.95	A	144-1102	[»]
4F1S	X-ray	3.00	A	144-1102	[»]
4FA6	X-ray	2.70	A	144-1102	[»]
4FAD	X-ray	2.70	A	144-1102	[»]
4FHJ	X-ray	2.60	A	144-1102	[»]
4FHK	X-ray	3.00	A	144-1102	[»]
4FJY	X-ray	2.90	A	144-1102	[»]
4FJZ	X-ray	3.00	A	144-1102	[»]
4FLH	X-ray	2.60	A	144-1102	[»]
4FUL	X-ray	2.47	A	144-1102	[»]
4G11	X-ray	3.40	A	144-1102	[»]
4GB9	X-ray	2.44	A	144-1102	[»]
4HLE	X-ray	2.78	A	144-1102	[»]

ProteinModelPortal

P48736.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-37781N.

IntAct

P48736. 11 interactions.

MINT

MINT-155782.

STRING

9606.ENSP00000352121.

PTM databases

PhosphoSite

P48736.

Polymorphism databases

DMDM

92090623.

Proteomic databases

PaxDb

P48736.

PRIDE

P48736.

Protocols and materials databases

DNASU

5294.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000359195; ENSP00000352121; ENSG00000105851.
ENST00000440650; ENSP00000392258; ENSG00000105851.
ENST00000496166; ENSP00000419260; ENSG00000105851.

GeneID

5294.

KEGG

hsa:5294.

UCSC

uc003vdu.3. human.

Organism-specific databases

CTD

5294.

GeneCards

GC07P106505.

HGNC

HGNC:8978. PIK3CG.

MIM

601232. gene.

neXtProt

NX_P48736.

PharmGKB

PA33311.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5032.

HOGENOM

HOG000252912.

HOVERGEN

HBG101026.

InParanoid

P48736.

KO

K00922.

OMA

WYEIYDK.

OrthoDB

EOG4T4CTN.

PhylomeDB

P48736.

Enzyme and pathway databases

BioCyc

MetaCyc:HS02818-MONOMER.

BRENDA

2.7.1.137. 2681.

Pathway_Interaction_DB

pi3kcipathway. Class I PI3K signaling events.
pi3kcibpathway. Class IB PI3K non-lipid kinase events.
epha_fwdpathway. EPHA forward signaling.
txa2pathway. Thromboxane A2 receptor signaling.

Reactome

REACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_604. Hemostasis.

SignaLink

P48736.

UniPathway

UPA00220.

Gene expression databases

ArrayExpress

P48736.

Bgee

P48736.

CleanEx

HS_PIK3CG.

Genevestigator

P48736.

GermOnline

ENSG00000105851. Homo sapiens.

Family and domain databases

Gene3D

1.10.1070.11. 1 hit.
1.25.40.70. 1 hit.

InterPro

IPR016024. ARM-type_fold.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR011009. Kinase-like_dom.
IPR000403. PI3/4_kinase_cat_dom.
IPR018936. PI3/4_kinase_CS.
IPR003113. PI3K_adapt-bd_dom.
IPR002420. PI3K_C2_dom.
IPR000341. PI3K_Ras-bd_dom.
IPR015433. PI_Kinase.
IPR001263. PInositide-3_kin_accessory_dom.
[Graphical view]

PANTHER

PTHR10048. PTHR10048. 1 hit.

Pfam

PF00454. PI3_PI4_kinase. 1 hit.
PF00792. PI3K_C2. 1 hit.
PF00794. PI3K_rbd. 1 hit.
PF00613. PI3Ka. 1 hit.
[Graphical view]

SMART

SM00142. PI3K_C2. 1 hit.
SM00144. PI3K_rbd. 1 hit.
SM00145. PI3Ka. 1 hit.
SM00146. PI3Kc. 1 hit.
[Graphical view]

SUPFAM

SSF48371. ARM-type_fold. 1 hit.
SSF49562. C2_CaLB. 1 hit.
SSF56112. Kinase_like. 1 hit.

PROSITE

PS00915. PI3_4_KINASE_1. 1 hit.
PS00916. PI3_4_KINASE_2. 1 hit.
PS50290. PI3_4_KINASE_3. 1 hit.
PS51544. PI3K_ABD. 1 hit.
PS51547. PI3K_C2. 1 hit.
PS51546. PI3K_RBD. 1 hit.
PS51545. PIK_HELICAL. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P48736.

ChEMBL

CHEMBL3267.

EvolutionaryTrace

P48736.

GenomeRNAi

5294.

NextBio

20458.

SOURCE

Search...

Entry information

Entry name

PK3CG_HUMAN

Accession

Primary (citable) accession number: P48736
Secondary accession number(s): A4D0Q6, Q8IV23, Q9BZC8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	April 4, 2006
Last modified:	May 29, 2013
This is version 136 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.