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Protein

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

Gene

Pik3cg

Organism
Mus musculus (Mouse)
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 GRK2 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. Contribute 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 (By similarity).By similarity10 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 subunit PIK3R5 leading to the translocation from the cytosol to the plasma membrane and to kinase activation; the respective activation involving PIK3R6 requires HRAS for membrane recruitment. Wortmannin sensitive in nM range. Inhibited by AS252424.2 Publications

Pathwayi: 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)DescriptionActionsGraphical viewLength
Nucleotide bindingi829 – 838ATPBy similarity10
Nucleotide bindingi864 – 872ATPBy similarity9
Nucleotide bindingi961 – 969ATPBy similarity9

GO - Molecular functioni

GO - Biological processi

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

BRENDAi2.7.1.153. 3474.
ReactomeiR-MMU-114604. GPVI-mediated activation cascade.
R-MMU-1660499. Synthesis of PIPs at the plasma membrane.
R-MMU-392451. G beta:gamma signalling through PI3Kgamma.
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
Synonyms:Pi3kg1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:1353576. Pik3cg.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Disruption phenotypei

Viable and fertile. Display abnormalities when the immune system is stressed. Reduced leukocyte migration in response to chemotactic agents and towards the site of inflammation. Reduced neutrophil oxidative burst in response to chemotactic agents. Reduced thymocyte survival and defective T lymphocyte activation. Protected from leukocyte infiltration of synovia in a model of rheumatoid arthritis. Dendritic cell showed reduced response to chemokines and migration to draining lymph nodes under inflammatory conditions. Platelets have defects in thrombus formation. Increased cardiac contractility. Display myocardial damage after transverse aortic constriction.7 Publications

Chemistry databases

ChEMBLiCHEMBL2189158.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000887931 – 1102Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoformAdd BLAST1102

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1024Phosphothreonine; by PKA1 Publication1
Modified residuei1101Phosphoserine; by autocatalysisBy similarity1

Post-translational modificationi

Phosphorylated at Thr-1024 by PKA. Phosphorylation inhibits lipid kinase activity.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9JHG7.
MaxQBiQ9JHG7.
PaxDbiQ9JHG7.
PRIDEiQ9JHG7.

PTM databases

iPTMnetiQ9JHG7.
PhosphoSitePlusiQ9JHG7.

Expressioni

Gene expression databases

BgeeiENSMUSG00000020573.
GenevisibleiQ9JHG7. MM.

Interactioni

Subunit structurei

Heterodimer of a catalytic subunit PIK3CG and a PIK3R5 or PIK3R6 regulatory subunit. Interacts with GRK2 through the PIK helical domain (By similarity). Interaction with GRK2 is required for targeting to agonist-occupied receptor. Interacts with PDE3B. Interacts with TPM2 (By similarity). 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 similarity3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi206031. 2 interactors.
DIPiDIP-41862N.
IntActiQ9JHG7. 6 interactors.
MINTiMINT-1612546.
STRINGi10090.ENSMUSP00000062864.

Chemistry databases

BindingDBiQ9JHG7.

Structurei

3D structure databases

ProteinModelPortaliQ9JHG7.
SMRiQ9JHG7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini34 – 141PI3K-ABDPROSITE-ProRule annotationAdd BLAST108
Domaini217 – 309PI3K-RBDPROSITE-ProRule annotationAdd BLAST93
Domaini357 – 521C2 PI3K-typePROSITE-ProRule annotationAdd BLAST165
Domaini541 – 723PIK helicalPROSITE-ProRule annotationAdd BLAST183
Domaini828 – 1073PI3K/PI4KPROSITE-ProRule annotationAdd BLAST246

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi18 – 22Poly-Arg5

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

eggNOGiKOG0904. Eukaryota.
COG5032. LUCA.
GeneTreeiENSGT00760000119110.
HOGENOMiHOG000252912.
HOVERGENiHBG101026.
InParanoidiQ9JHG7.
KOiK00922.
OMAiFTEEVLW.
OrthoDBiEOG091G027R.
PhylomeDBiQ9JHG7.
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.

Q9JHG7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MELENYEQPV VLREDNLRRR RRMKPRSAAG SLSSMELIPI EFVLPTSQRI
60 70 80 90 100
SKTPETALLH VAGHGNVEQM KAQVWLRALE TSVAAEFYHR LGPDQFLLLY
110 120 130 140 150
QKKGQWYEIY DRYQVVQTLD CLHYWKLMHK SPGQIHVVQR HVPSEETLAF
160 170 180 190 200
QKQLTSLIGY DVTDISNVHD DELEFTRRRL VTPRMAEVAG RDAKLYAMHP
210 220 230 240 250
WVTSKPLPDY LSKKIANNCI FIVIHRGTTS QTIKVSADDT PGTILQSFFT
260 270 280 290 300
KMAKKKSLMN ISESQSEQDF VLRVCGRDEY LVGETPLKNF QWVRQCLKNG
310 320 330 340 350
DEIHLVLDTP PDPALDEVRK EEWPLVDDCT GVTGYHEQLT IHGKDHESVF
360 370 380 390 400
TVSLWDCDRK FRVKIRGIDI PVLPRNTDLT VFVEANIQHG QQVLCQRRTS
410 420 430 440 450
PKPFAEEVLW NVWLEFGIKI KDLPKGALLN LQIYCCKTPS LSSKASAETP
460 470 480 490 500
GSESKGKAQL LYYVNLLLID HRFLLRHGDY VLHMWQISGK AEEQGSFNAD
510 520 530 540 550
KLTSATNPDK ENSMSISILL DNYCHPIALP KHRPTPDPEG DRVRAEMPNQ
560 570 580 590 600
LRKQLEAIIA TDPLNPLTAE DKELLWHFRY ESLKHPKAYP KLFSSVKWGQ
610 620 630 640 650
QEIVAKTYQL LARREIWDQS ALDVGLTMQL LDCNFSDENV RAIAVQKLES
660 670 680 690 700
LEDDDVLHYL LQLVQAVKFE PYHDSALARF LLKRGLRNKR IGHFLFWFLR
710 720 730 740 750
SEIAQSRHYQ QRFAVILEAY LRGCGTAMLQ DFTQQVHVIE MLQKVTIDIK
760 770 780 790 800
SLSAEKYDVS SQVISQLKQK LESLQNSNLP ESFRVPYDPG LKAGTLVIEK
810 820 830 840 850
CKVMASKKKP LWLEFKCADP TVLSNETIGI IFKHGDDLRQ DMLILQILRI
860 870 880 890 900
MESIWETESL DLCLLPYGCI STGDKIGMIE IVKDATTIAQ IQQSTVGNTG
910 920 930 940 950
AFKDEVLNHW LKEKCPIEEK FQAAVERFVY SCAGYCVATF VLGIGDRHND
960 970 980 990 1000
NIMISETGNL FHIDFGHILG NYKSFLGINK ERVPFVLTPD FLFVMGSSGK
1010 1020 1030 1040 1050
KTSPHFQKFQ DVCVRAYLAL RHHTNLLIIL FSMMLMTGMP QLTSKEDIEY
1060 1070 1080 1090 1100
IRDALTVGKS EEDAKKYFLD QIEVCRDKGW TVQFNWFLHL VLGIKQGEKH

SA
Length:1,102
Mass (Da):126,400
Last modified:July 27, 2011 - v2
Checksum:i7675848792D76734
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti262S → P in CAB89686 (PubMed:11054537).Curated1
Sequence conflicti262S → P in CAB89851 (PubMed:11054537).Curated1
Sequence conflicti350F → V in CAB89686 (PubMed:11054537).Curated1
Sequence conflicti350F → V in CAB89851 (PubMed:11054537).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ249280 mRNA. Translation: CAB89686.1.
AJ249413
, AJ249414, AJ249415, AJ249416, AJ249417, AJ249418, AJ249419, AJ249420 Genomic DNA. Translation: CAB89851.1.
BC051246 mRNA. Translation: AAH51246.1.
CCDSiCCDS25870.1.
RefSeqiNP_001139672.1. NM_001146200.1.
NP_001139673.1. NM_001146201.1.
NP_064668.2. NM_020272.2.
XP_006515175.1. XM_006515112.3.
UniGeneiMm.101369.
Mm.404021.

Genome annotation databases

EnsembliENSMUST00000053215; ENSMUSP00000062864; ENSMUSG00000020573.
ENSMUST00000085469; ENSMUSP00000082596; ENSMUSG00000020573.
ENSMUST00000156904; ENSMUSP00000123539; ENSMUSG00000020573.
GeneIDi30955.
KEGGimmu:30955.
UCSCiuc007nib.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ249280 mRNA. Translation: CAB89686.1.
AJ249413
, AJ249414, AJ249415, AJ249416, AJ249417, AJ249418, AJ249419, AJ249420 Genomic DNA. Translation: CAB89851.1.
BC051246 mRNA. Translation: AAH51246.1.
CCDSiCCDS25870.1.
RefSeqiNP_001139672.1. NM_001146200.1.
NP_001139673.1. NM_001146201.1.
NP_064668.2. NM_020272.2.
XP_006515175.1. XM_006515112.3.
UniGeneiMm.101369.
Mm.404021.

3D structure databases

ProteinModelPortaliQ9JHG7.
SMRiQ9JHG7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi206031. 2 interactors.
DIPiDIP-41862N.
IntActiQ9JHG7. 6 interactors.
MINTiMINT-1612546.
STRINGi10090.ENSMUSP00000062864.

Chemistry databases

BindingDBiQ9JHG7.
ChEMBLiCHEMBL2189158.

PTM databases

iPTMnetiQ9JHG7.
PhosphoSitePlusiQ9JHG7.

Proteomic databases

EPDiQ9JHG7.
MaxQBiQ9JHG7.
PaxDbiQ9JHG7.
PRIDEiQ9JHG7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000053215; ENSMUSP00000062864; ENSMUSG00000020573.
ENSMUST00000085469; ENSMUSP00000082596; ENSMUSG00000020573.
ENSMUST00000156904; ENSMUSP00000123539; ENSMUSG00000020573.
GeneIDi30955.
KEGGimmu:30955.
UCSCiuc007nib.2. mouse.

Organism-specific databases

CTDi5294.
MGIiMGI:1353576. Pik3cg.

Phylogenomic databases

eggNOGiKOG0904. Eukaryota.
COG5032. LUCA.
GeneTreeiENSGT00760000119110.
HOGENOMiHOG000252912.
HOVERGENiHBG101026.
InParanoidiQ9JHG7.
KOiK00922.
OMAiFTEEVLW.
OrthoDBiEOG091G027R.
PhylomeDBiQ9JHG7.
TreeFamiTF102031.

Enzyme and pathway databases

UniPathwayiUPA00220.
BRENDAi2.7.1.153. 3474.
ReactomeiR-MMU-114604. GPVI-mediated activation cascade.
R-MMU-1660499. Synthesis of PIPs at the plasma membrane.
R-MMU-392451. G beta:gamma signalling through PI3Kgamma.

Miscellaneous databases

ChiTaRSiPik3cg. mouse.
PROiQ9JHG7.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020573.
GenevisibleiQ9JHG7. MM.

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...

Entry informationi

Entry nameiPK3CG_MOUSE
AccessioniPrimary (citable) accession number: Q9JHG7
Secondary accession number(s): Q80V09
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families

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 one 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.