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Protein

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

Gene

PIK3CG

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.5 Publications

Catalytic activityi

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 regulationi

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-605240.2 Publications

Pathway: phosphatidylinositol phosphate biosynthesis

This protein is involved in the pathway phosphatidylinositol phosphate biosynthesis, which is part of Phospholipid metabolism.
View all proteins of this organism that are known to be involved in the pathway phosphatidylinositol phosphate biosynthesis and in Phospholipid metabolism.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi829 – 83810ATPBy similarity
Nucleotide bindingi864 – 8729ATPBy similarity
Nucleotide bindingi961 – 9699ATPBy similarity

GO - Molecular functioni

  • 1-phosphatidylinositol-3-kinase activity Source: ProtInc
  • 1-phosphatidylinositol-4-phosphate 3-kinase activity Source: GO_Central
  • ATP binding Source: UniProtKB-KW
  • ephrin receptor binding Source: UniProtKB
  • phosphatidylinositol 3-kinase activity Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: UniProtKB-EC
  • protein kinase activity Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB-KW

GO - Biological processi

  • adaptive immune response Source: UniProtKB
  • angiogenesis Source: UniProtKB-KW
  • blood coagulation Source: Reactome
  • cytokine production Source: UniProtKB
  • dendritic cell chemotaxis Source: UniProtKB
  • endocytosis Source: UniProtKB-KW
  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • hepatocyte apoptotic process Source: Ensembl
  • inflammatory response Source: UniProtKB
  • innate immune response Source: UniProtKB
  • mast cell degranulation Source: UniProtKB
  • natural killer cell chemotaxis Source: UniProtKB
  • negative regulation of cardiac muscle contraction Source: UniProtKB
  • negative regulation of fibroblast apoptotic process Source: Ensembl
  • negative regulation of triglyceride catabolic process Source: Ensembl
  • neutrophil chemotaxis Source: UniProtKB
  • neutrophil extravasation Source: UniProtKB
  • phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • phosphatidylinositol-3-phosphate biosynthetic process Source: GO_Central
  • phosphatidylinositol biosynthetic process Source: Reactome
  • phosphatidylinositol phosphorylation Source: GO_Central
  • phospholipid metabolic process Source: Reactome
  • platelet activation Source: GO_Central
  • platelet aggregation Source: UniProtKB
  • positive regulation of acute inflammatory response Source: Ensembl
  • positive regulation of cytosolic calcium ion concentration Source: Ensembl
  • positive regulation of MAP kinase activity Source: UniProtKB
  • positive regulation of protein kinase B signaling Source: UniProtKB
  • protein phosphorylation Source: GO_Central
  • regulation of cell adhesion mediated by integrin Source: UniProtKB
  • respiratory burst involved in defense response Source: UniProtKB
  • secretory granule localization Source: Ensembl
  • small molecule metabolic process Source: Reactome
  • T cell activation Source: UniProtKB
  • T cell chemotaxis Source: UniProtKB
  • T cell proliferation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Angiogenesis, Chemotaxis, Endocytosis, Immunity, Inflammatory response

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS02818-MONOMER.
BRENDAi2.7.1.137. 2681.
2.7.1.153. 2681.
ReactomeiREACT_121025. Synthesis of PIPs at the plasma membrane.
REACT_1695. GPVI-mediated activation cascade.
REACT_19290. G beta:gamma signalling through PI3Kgamma.
SignaLinkiP48736.
UniPathwayiUPA00220.

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (EC:2.7.1.153)
Short name:
PI3-kinase subunit gamma
Short name:
PI3K-gamma
Short name:
PI3Kgamma
Short name:
PtdIns-3-kinase subunit gamma
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 namesi
Name:PIK3CG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:8978. PIK3CG.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • mast cell granule Source: GOC
  • membrane Source: UniProtKB
  • phosphatidylinositol 3-kinase complex, class IB Source: UniProtKB
  • plasma membrane Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi833 – 8331K → R: Reduced inflammatory reactions but no alterations in cardiac contractility. 1 Publication
Mutagenesisi947 – 9471R → P: Abolishes protein and lipid kinase activity. Does not abolishes interaction with ADRBK1. 1 Publication

Organism-specific databases

PharmGKBiPA33311.

Polymorphism and mutation databases

BioMutaiPIK3CG.
DMDMi92090623.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11021102Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoformPRO_0000088792Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1024 – 10241Phosphothreonine; by PKABy similarity
Modified residuei1101 – 11011Phosphoserine; by autocatalysis1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP48736.
PaxDbiP48736.
PRIDEiP48736.

PTM databases

PhosphoSiteiP48736.

Expressioni

Tissue specificityi

Pancreas, skeletal muscle, liver and heart.1 Publication

Gene expression databases

BgeeiP48736.
CleanExiHS_PIK3CG.
ExpressionAtlasiP48736. baseline and differential.
GenevisibleiP48736. HS.

Interactioni

Subunit structurei

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 HRAS; the interaction is required for membrane recruitment and beta-gamma G protein dimer-dependent activation of the PI3K gamma complex PIK3CG:PIK3R6 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
PDE3BQ133703EBI-1030384,EBI-6172856
PIK3R5O026966EBI-1030384,EBI-6172343From a different organism.

Protein-protein interaction databases

BioGridi111312. 19 interactions.
DIPiDIP-37781N.
IntActiP48736. 14 interactions.
MINTiMINT-155782.
STRINGi9606.ENSP00000352121.

Structurei

Secondary structure

1
1102
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi145 – 15814Combined sources
Helixi165 – 1673Combined sources
Beta strandi169 – 1713Combined sources
Helixi172 – 1798Combined sources
Helixi181 – 19010Combined sources
Helixi193 – 1986Combined sources
Helixi209 – 2124Combined sources
Helixi213 – 2153Combined sources
Beta strandi216 – 2183Combined sources
Beta strandi220 – 2267Combined sources
Beta strandi229 – 2357Combined sources
Helixi241 – 2433Combined sources
Helixi246 – 2527Combined sources
Helixi256 – 2594Combined sources
Beta strandi263 – 2653Combined sources
Beta strandi271 – 2744Combined sources
Beta strandi283 – 2853Combined sources
Helixi287 – 2893Combined sources
Helixi291 – 2988Combined sources
Beta strandi303 – 3086Combined sources
Helixi313 – 3164Combined sources
Helixi354 – 3563Combined sources
Beta strandi359 – 36911Combined sources
Beta strandi375 – 3773Combined sources
Beta strandi380 – 39112Combined sources
Beta strandi393 – 3986Combined sources
Beta strandi406 – 41914Combined sources
Helixi420 – 4223Combined sources
Beta strandi428 – 4347Combined sources
Beta strandi462 – 4698Combined sources
Beta strandi473 – 4753Combined sources
Beta strandi478 – 4836Combined sources
Helixi499 – 5024Combined sources
Beta strandi511 – 5133Combined sources
Beta strandi515 – 5206Combined sources
Helixi549 – 56012Combined sources
Beta strandi563 – 5653Combined sources
Helixi569 – 5779Combined sources
Helixi579 – 5824Combined sources
Helixi586 – 5883Combined sources
Helixi589 – 5935Combined sources
Helixi601 – 61212Combined sources
Helixi615 – 6184Combined sources
Helixi624 – 6307Combined sources
Beta strandi632 – 6343Combined sources
Helixi638 – 64811Combined sources
Helixi653 – 66614Combined sources
Helixi667 – 6693Combined sources
Beta strandi671 – 6744Combined sources
Helixi676 – 68712Combined sources
Helixi689 – 70517Combined sources
Turni707 – 7093Combined sources
Helixi710 – 72112Combined sources
Turni722 – 7243Combined sources
Helixi726 – 75126Combined sources
Beta strandi755 – 7573Combined sources
Helixi761 – 77414Combined sources
Turni775 – 7784Combined sources
Beta strandi783 – 7853Combined sources
Beta strandi788 – 7969Combined sources
Helixi798 – 8003Combined sources
Beta strandi806 – 8083Combined sources
Beta strandi811 – 8188Combined sources
Beta strandi828 – 8369Combined sources
Helixi838 – 85619Combined sources
Turni857 – 8593Combined sources
Beta strandi869 – 8735Combined sources
Beta strandi876 – 8805Combined sources
Beta strandi885 – 8873Combined sources
Helixi888 – 8958Combined sources
Beta strandi898 – 9003Combined sources
Helixi906 – 9149Combined sources
Beta strandi915 – 9173Combined sources
Helixi918 – 94124Combined sources
Helixi949 – 9513Combined sources
Beta strandi952 – 9554Combined sources
Turni956 – 9583Combined sources
Beta strandi960 – 9623Combined sources
Helixi965 – 9706Combined sources
Helixi989 – 9946Combined sources
Turni998 – 10003Combined sources
Helixi1004 – 102118Combined sources
Helixi1024 – 103815Combined sources
Beta strandi1039 – 10413Combined sources
Turni1042 – 10454Combined sources
Helixi1046 – 10549Combined sources
Turni1055 – 10584Combined sources
Helixi1061 – 107818Combined sources
Helixi1081 – 10855Combined sources
Turni1086 – 10905Combined sources
Turni1091 – 10933Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1E8YX-ray2.00A144-1102[»]
1E8ZX-ray2.40A144-1102[»]
1HE8X-ray3.00A144-1102[»]
2A4ZX-ray2.90A144-1102[»]
2A5UX-ray2.70A144-1102[»]
2CHWX-ray2.60A144-1102[»]
2CHXX-ray2.50A144-1102[»]
2CHZX-ray2.60A144-1102[»]
2V4LX-ray2.50A144-1102[»]
3APCX-ray2.54A144-1102[»]
3APDX-ray2.55A144-1102[»]
3APFX-ray2.82A144-1102[»]
3CSFX-ray2.80A144-1102[»]
3CSTX-ray3.20A144-1102[»]
3DBSX-ray2.80A144-1102[»]
3DPDX-ray2.85A144-1102[»]
3ENEX-ray2.40A144-1102[»]
3IBEX-ray2.80A144-1102[»]
3L08X-ray2.70A144-1102[»]
3L13X-ray3.00A144-1102[»]
3L16X-ray2.90A144-1102[»]
3L17X-ray3.00A144-1102[»]
3L54X-ray2.30A144-1102[»]
3LJ3X-ray2.43A144-1102[»]
3MJWX-ray2.87A144-1102[»]
3ML8X-ray2.70A144-1102[»]
3ML9X-ray2.55A144-1102[»]
3NZSX-ray2.75A147-1094[»]
3NZUX-ray2.60A147-1094[»]
3OAWX-ray2.75A144-1102[»]
3P2BX-ray3.20A144-1102[»]
3PREX-ray2.91A144-1102[»]
3PRZX-ray2.60A144-1102[»]
3PS6X-ray2.60A144-1102[»]
3QAQX-ray2.90A144-1102[»]
3QARX-ray2.65A144-1102[»]
3QJZX-ray2.90A144-1102[»]
3QK0X-ray2.85A144-1102[»]
3R7QX-ray2.50A144-1102[»]
3R7RX-ray2.90A144-1102[»]
3S2AX-ray2.55A144-1102[»]
3SD5X-ray3.20A144-1102[»]
3T8MX-ray2.50A144-1102[»]
3TJPX-ray2.70A144-1102[»]
3TL5X-ray2.79A144-1102[»]
3ZVVX-ray2.50A144-1102[»]
3ZW3X-ray2.80A144-1102[»]
4ANUX-ray2.81A144-1102[»]
4ANVX-ray2.13A144-1102[»]
4ANWX-ray2.31A144-1102[»]
4ANXX-ray2.73A144-1102[»]
4AOFX-ray3.30A144-1102[»]
4DK5X-ray2.95A144-1102[»]
4EZJX-ray2.67A144-1102[»]
4EZKX-ray2.80A144-1102[»]
4EZLX-ray2.94A144-1102[»]
4F1SX-ray3.00A144-1102[»]
4FA6X-ray2.70A144-1102[»]
4FADX-ray2.70A144-1102[»]
4FHJX-ray2.60A144-1102[»]
4FHKX-ray3.00A144-1102[»]
4FJYX-ray2.90A144-1102[»]
4FJZX-ray3.00A144-1102[»]
4FLHX-ray2.60A144-1102[»]
4FULX-ray2.47A144-1102[»]
4G11X-ray3.40A144-1102[»]
4GB9X-ray2.44A144-1102[»]
4HLEX-ray2.78A144-1102[»]
4HVBX-ray2.35A144-1102[»]
4J6IX-ray2.90A144-1102[»]
4KZ0X-ray2.87A144-1102[»]
4KZCX-ray3.25A144-1102[»]
4PS3X-ray2.90A144-1102[»]
4PS7X-ray2.69A144-1102[»]
4PS8X-ray2.99A144-1102[»]
4URKX-ray2.90A144-1102[»]
4WWNX-ray2.70A144-1102[»]
4WWOX-ray2.30A144-1102[»]
4WWPX-ray2.40A144-1102[»]
ProteinModelPortaliP48736.
SMRiP48736. Positions 144-1089.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP48736.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini34 – 141108PI3K-ABDPROSITE-ProRule annotationAdd
BLAST
Domaini217 – 30993PI3K-RBDPROSITE-ProRule annotationAdd
BLAST
Domaini357 – 521165C2 PI3K-typePROSITE-ProRule annotationAdd
BLAST
Domaini541 – 723183PIK helicalPROSITE-ProRule annotationAdd
BLAST
Domaini828 – 1073246PI3K/PI4KPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi19 – 235Poly-Arg

Sequence similaritiesi

Belongs to the PI3/PI4-kinase family.PROSITE-ProRule annotation
Contains 1 C2 PI3K-type domain.PROSITE-ProRule annotation
Contains 1 PI3K-ABD domain.PROSITE-ProRule annotation
Contains 1 PI3K-RBD domain.PROSITE-ProRule annotation
Contains 1 PI3K/PI4K domain.PROSITE-ProRule annotation
Contains 1 PIK helical domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG5032.
GeneTreeiENSGT00760000119110.
HOGENOMiHOG000252912.
HOVERGENiHBG101026.
InParanoidiP48736.
KOiK00922.
OMAiFTEEVLW.
OrthoDBiEOG70CR65.
PhylomeDBiP48736.
TreeFamiTF102031.

Family and domain databases

Gene3Di1.10.1070.11. 1 hit.
1.25.40.70. 1 hit.
2.60.40.150. 1 hit.
InterProiIPR016024. ARM-type_fold.
IPR000008. C2_dom.
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.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERiPTHR10048. PTHR10048. 1 hit.
PfamiPF00454. PI3_PI4_kinase. 1 hit.
PF00792. PI3K_C2. 1 hit.
PF00794. PI3K_rbd. 1 hit.
PF00613. PI3Ka. 1 hit.
[Graphical view]
SMARTiSM00142. PI3K_C2. 1 hit.
SM00144. PI3K_rbd. 1 hit.
SM00145. PI3Ka. 1 hit.
SM00146. PI3Kc. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 1 hit.
SSF49562. SSF49562. 1 hit.
SSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00915. 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]

Sequencei

Sequence statusi: Complete.

P48736-1 [UniParc]FASTAAdd to basket

« Hide

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

SA
Length:1,102
Mass (Da):126,454
Last modified:April 4, 2006 - v3
Checksum:iEF2B1A0E1CBEF406
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti30 – 301Missing in CAA58284 (PubMed:7624799).Curated
Sequence conflicti459 – 4591Q → R in CAA58284 (PubMed:7624799).Curated
Sequence conflicti459 – 4591Q → R in AAG61115 (Ref. 3) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5739.1.
RefSeqiNP_001269355.1. NM_001282426.1.
NP_001269356.1. NM_001282427.1.
NP_002640.2. NM_002649.3.
XP_005250500.1. XM_005250443.2.
UniGeneiHs.32942.
Hs.561747.

Genome annotation databases

EnsembliENST00000359195; ENSP00000352121; ENSG00000105851.
ENST00000440650; ENSP00000392258; ENSG00000105851.
ENST00000496166; ENSP00000419260; ENSG00000105851.
GeneIDi5294.
KEGGihsa:5294.
UCSCiuc003vdu.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5739.1.
RefSeqiNP_001269355.1. NM_001282426.1.
NP_001269356.1. NM_001282427.1.
NP_002640.2. NM_002649.3.
XP_005250500.1. XM_005250443.2.
UniGeneiHs.32942.
Hs.561747.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1E8YX-ray2.00A144-1102[»]
1E8ZX-ray2.40A144-1102[»]
1HE8X-ray3.00A144-1102[»]
2A4ZX-ray2.90A144-1102[»]
2A5UX-ray2.70A144-1102[»]
2CHWX-ray2.60A144-1102[»]
2CHXX-ray2.50A144-1102[»]
2CHZX-ray2.60A144-1102[»]
2V4LX-ray2.50A144-1102[»]
3APCX-ray2.54A144-1102[»]
3APDX-ray2.55A144-1102[»]
3APFX-ray2.82A144-1102[»]
3CSFX-ray2.80A144-1102[»]
3CSTX-ray3.20A144-1102[»]
3DBSX-ray2.80A144-1102[»]
3DPDX-ray2.85A144-1102[»]
3ENEX-ray2.40A144-1102[»]
3IBEX-ray2.80A144-1102[»]
3L08X-ray2.70A144-1102[»]
3L13X-ray3.00A144-1102[»]
3L16X-ray2.90A144-1102[»]
3L17X-ray3.00A144-1102[»]
3L54X-ray2.30A144-1102[»]
3LJ3X-ray2.43A144-1102[»]
3MJWX-ray2.87A144-1102[»]
3ML8X-ray2.70A144-1102[»]
3ML9X-ray2.55A144-1102[»]
3NZSX-ray2.75A147-1094[»]
3NZUX-ray2.60A147-1094[»]
3OAWX-ray2.75A144-1102[»]
3P2BX-ray3.20A144-1102[»]
3PREX-ray2.91A144-1102[»]
3PRZX-ray2.60A144-1102[»]
3PS6X-ray2.60A144-1102[»]
3QAQX-ray2.90A144-1102[»]
3QARX-ray2.65A144-1102[»]
3QJZX-ray2.90A144-1102[»]
3QK0X-ray2.85A144-1102[»]
3R7QX-ray2.50A144-1102[»]
3R7RX-ray2.90A144-1102[»]
3S2AX-ray2.55A144-1102[»]
3SD5X-ray3.20A144-1102[»]
3T8MX-ray2.50A144-1102[»]
3TJPX-ray2.70A144-1102[»]
3TL5X-ray2.79A144-1102[»]
3ZVVX-ray2.50A144-1102[»]
3ZW3X-ray2.80A144-1102[»]
4ANUX-ray2.81A144-1102[»]
4ANVX-ray2.13A144-1102[»]
4ANWX-ray2.31A144-1102[»]
4ANXX-ray2.73A144-1102[»]
4AOFX-ray3.30A144-1102[»]
4DK5X-ray2.95A144-1102[»]
4EZJX-ray2.67A144-1102[»]
4EZKX-ray2.80A144-1102[»]
4EZLX-ray2.94A144-1102[»]
4F1SX-ray3.00A144-1102[»]
4FA6X-ray2.70A144-1102[»]
4FADX-ray2.70A144-1102[»]
4FHJX-ray2.60A144-1102[»]
4FHKX-ray3.00A144-1102[»]
4FJYX-ray2.90A144-1102[»]
4FJZX-ray3.00A144-1102[»]
4FLHX-ray2.60A144-1102[»]
4FULX-ray2.47A144-1102[»]
4G11X-ray3.40A144-1102[»]
4GB9X-ray2.44A144-1102[»]
4HLEX-ray2.78A144-1102[»]
4HVBX-ray2.35A144-1102[»]
4J6IX-ray2.90A144-1102[»]
4KZ0X-ray2.87A144-1102[»]
4KZCX-ray3.25A144-1102[»]
4PS3X-ray2.90A144-1102[»]
4PS7X-ray2.69A144-1102[»]
4PS8X-ray2.99A144-1102[»]
4URKX-ray2.90A144-1102[»]
4WWNX-ray2.70A144-1102[»]
4WWOX-ray2.30A144-1102[»]
4WWPX-ray2.40A144-1102[»]
ProteinModelPortaliP48736.
SMRiP48736. Positions 144-1089.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111312. 19 interactions.
DIPiDIP-37781N.
IntActiP48736. 14 interactions.
MINTiMINT-155782.
STRINGi9606.ENSP00000352121.

Chemistry

BindingDBiP48736.
ChEMBLiCHEMBL3267.
GuidetoPHARMACOLOGYi2156.

PTM databases

PhosphoSiteiP48736.

Polymorphism and mutation databases

BioMutaiPIK3CG.
DMDMi92090623.

Proteomic databases

MaxQBiP48736.
PaxDbiP48736.
PRIDEiP48736.

Protocols and materials databases

DNASUi5294.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000359195; ENSP00000352121; ENSG00000105851.
ENST00000440650; ENSP00000392258; ENSG00000105851.
ENST00000496166; ENSP00000419260; ENSG00000105851.
GeneIDi5294.
KEGGihsa:5294.
UCSCiuc003vdu.3. human.

Organism-specific databases

CTDi5294.
GeneCardsiGC07P106505.
HGNCiHGNC:8978. PIK3CG.
MIMi601232. gene.
neXtProtiNX_P48736.
PharmGKBiPA33311.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5032.
GeneTreeiENSGT00760000119110.
HOGENOMiHOG000252912.
HOVERGENiHBG101026.
InParanoidiP48736.
KOiK00922.
OMAiFTEEVLW.
OrthoDBiEOG70CR65.
PhylomeDBiP48736.
TreeFamiTF102031.

Enzyme and pathway databases

UniPathwayiUPA00220.
BioCyciMetaCyc:HS02818-MONOMER.
BRENDAi2.7.1.137. 2681.
2.7.1.153. 2681.
ReactomeiREACT_121025. Synthesis of PIPs at the plasma membrane.
REACT_1695. GPVI-mediated activation cascade.
REACT_19290. G beta:gamma signalling through PI3Kgamma.
SignaLinkiP48736.

Miscellaneous databases

EvolutionaryTraceiP48736.
GeneWikiiPIK3CG.
GenomeRNAii5294.
NextBioi20458.
PROiP48736.
SOURCEiSearch...

Gene expression databases

BgeeiP48736.
CleanExiHS_PIK3CG.
ExpressionAtlasiP48736. baseline and differential.
GenevisibleiP48736. HS.

Family and domain databases

Gene3Di1.10.1070.11. 1 hit.
1.25.40.70. 1 hit.
2.60.40.150. 1 hit.
InterProiIPR016024. ARM-type_fold.
IPR000008. C2_dom.
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.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERiPTHR10048. PTHR10048. 1 hit.
PfamiPF00454. PI3_PI4_kinase. 1 hit.
PF00792. PI3K_C2. 1 hit.
PF00794. PI3K_rbd. 1 hit.
PF00613. PI3Ka. 1 hit.
[Graphical view]
SMARTiSM00142. PI3K_C2. 1 hit.
SM00144. PI3K_rbd. 1 hit.
SM00145. PI3Ka. 1 hit.
SM00146. PI3Kc. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 1 hit.
SSF49562. SSF49562. 1 hit.
SSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00915. 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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. 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. 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: PHOSPHORYLATION 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. 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. Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 144-1101 IN A COMPLEX WITH AS-604850 AND AS-605240, ENZYME REGULATION.

Entry informationi

Entry nameiPK3CG_HUMAN
AccessioniPrimary (citable) accession number: P48736
Secondary accession number(s): A4D0Q6, Q8IV23, Q9BZC8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: April 4, 2006
Last modified: June 24, 2015
This is version 159 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

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 (PubMed:18278175).1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.