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O02697 (PK3CG_PIG) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismSus scrofa (Pig) [Reference proteome]
Taxonomic identifier9823 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus

Protein attributes

Sequence length1102 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Required for B-lymphocyte development and signaling. Together with other PI3Ks are involved in the oxidative burst produced by neutrophils in response to chemotactic agents. Together with PIK3CD regulate neutrophil 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. 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.

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. When bound to PIK3R5 the PI3K activity of PIK3CG could be activated greater than 100-fold by the beta-gamma G proteins.

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. 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. Ref.1

Subcellular location

Cytoplasm By similarity. Cell membrane By similarity.

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11021102Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
PRO_0000088794

Regions

Domain34 – 141108PI3K-ABD
Domain217 – 30993PI3K-RBD
Domain357 – 521165C2 PI3K-type
Domain541 – 723183PIK helical
Domain828 – 1073246PI3K/PI4K
Nucleotide binding829 – 83810ATP
Nucleotide binding864 – 8729ATP
Nucleotide binding961 – 9699ATP
Compositional bias17 – 226Poly-Arg

Amino acid modifications

Modified residue10241Phosphothreonine; by PKA By similarity
Modified residue11011Phosphoserine; by autocatalysis By similarity

Secondary structure

.......................................................................................................................................... 1102
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O02697 [UniParc].

Last modified December 15, 1998. Version 2.
Checksum: 9E7D4211FD626DFC

FASTA1,102126,658
        10         20         30         40         50         60 
MELENYEQPV VLREDNRRRR RRMKPRSTAA SLSSMELIPI EFVLPTSQRN TKTPETALLH 

        70         80         90        100        110        120 
VAGHGNVEQM KAQVWLRALE TSVSADFYHR LGPDHFLLLY QKKGQWYEIY DKYQVVQTLD 

       130        140        150        160        170        180 
CLRYWKVLHR SPGQIHVVQR HAPSEETLAF QRQLNALIGY DVTDVSNVHD DELEFTRRRL 

       190        200        210        220        230        240 
VTPRMAEVAG RDPKLYAMHP WVTSKPLPEY LLKKITNNCV FIVIHRSTTS QTIKVSADDT 

       250        260        270        280        290        300 
PGTILQSFFT KMAKKKSLMD IPESQNERDF VLRVCGRDEY LVGETPIKNF QWVRQCLKNG 

       310        320        330        340        350        360 
EEIHLVLDTP PDPALDEVRK EEWPLVDDCT GVTGYHEQLT IHGKDHESVF TVSLWDCDRK 

       370        380        390        400        410        420 
FRVKIRGIDI PVLPRTADLT VFVEANIQYG QQVLCQRRTS PKPFTEEVLW NVWLEFSIKI 

       430        440        450        460        470        480 
KDLPKGALLN LQIYCGKAPA LSGKTSAEMP SPESKGKAQL LYYVNLLLID HRFLLRHGEY 

       490        500        510        520        530        540 
VLHMWQLSGK GEDQGSFNAD KLTSRTNPDK ENSMSISILL DNYCHPIALP KHRPTPDPEG 

       550        560        570        580        590        600 
DRVRAEMPNQ LRKQLEAIIA TDPLNPLTAE DKELLWHFRY ESLKDPKAYP KLFSSVKWGQ 

       610        620        630        640        650        660 
QEIVAKTYQL LAKREVWDQS ALDVGLTMQL LDCNFSDENV RAIAVQKLES LEDDDVLHYL 

       670        680        690        700        710        720 
LQLVQAVKFE PYHDSALARF LLKRGLRNKR IGHFLFWFLR SEIAQSRHYQ QRFAVILEAY 

       730        740        750        760        770        780 
LRGCGTAMLH DFTQQVQVID MLQKVTIDIK SLSAEKYDVS SQVISQLKQK LENLQNLNLP 

       790        800        810        820        830        840 
QSFRVPYDPG LKAGALVIEK CKVMASKKKP LWLEFKCADP TALSNETIGI IFKHGDDLRQ 

       850        860        870        880        890        900 
DMLILQILRI MESIWETESL DLCLLPYGCI STGDKIGMIE IVKDATTIAK IQQSTVGNTG 

       910        920        930        940        950        960 
AFKDEVLSHW LKEKCPIEEK FQAAVERFVY SCAGYCVATF VLGIGDRHND NIMISETGNL 

       970        980        990       1000       1010       1020 
FHIDFGHILG NYKSFLGINK ERVPFVLTPD FLFVMGTSGK KTSLHFQKFQ DVCVKAYLAL 

      1030       1040       1050       1060       1070       1080 
RHHTNLLIIL FSMMLMTGMP QLTSKEDIEY IRDALTVGKS EEDAKKYFLD QIEVCRDKGW 

      1090       1100 
TVQFNWFLHL VLGIKQGEKH SA 

« Hide

References

[1]"The G beta gamma sensitivity of a PI3K is dependent upon a tightly associated adaptor, p101."
Stephens L.R., Eguinoa A., Erdjument-Bromage H., Lui M., Cooke F., Coadwell J., Smrcka A.S., Thelen M., Cadwallader K., Tempst P., Hawkins P.T.
Cell 89:105-114(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, INTERACTION WITH PIK3R5.
Tissue: Neutrophil.
[2]Stephens L.R.
Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine."
Walker E.H., Pacold M.E., Perisic O., Stephens L., Hawkins P.T., Wymann M.P., Williams R.L.
Mol. Cell 6:909-919(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 144-1102 IN COMPLEX WITH ATP AND INHIBITORS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y10743 mRNA. Translation: CAA71731.1.
RefSeqNP_999104.1. NM_213939.1.
UniGeneSsc.82467.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1E7UX-ray2.00A144-1102[»]
1E7VX-ray2.40A144-1102[»]
1E8WX-ray2.50A144-1102[»]
1E8XX-ray2.20A144-1094[»]
1E90X-ray2.70A144-1102[»]
ProteinModelPortalO02697.
SMRO02697. Positions 144-1094.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO02697. 2 interactions.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID396979.
KEGGssc:396979.

Organism-specific databases

CTD5294.

Phylogenomic databases

HOVERGENHBG101026.
KOK00922.

Enzyme and pathway databases

BRENDA2.7.1.137. 6170.
UniPathwayUPA00220.

Family and domain databases

Gene3D1.10.1070.11. 1 hit.
1.25.40.70. 1 hit.
2.60.40.150. 1 hit.
InterProIPR016024. 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]
PANTHERPTHR10048. PTHR10048. 1 hit.
PfamPF00454. PI3_PI4_kinase. 1 hit.
PF00792. PI3K_C2. 1 hit.
PF00794. PI3K_rbd. 1 hit.
PF00613. PI3Ka. 1 hit.
[Graphical view]
SMARTSM00142. PI3K_C2. 1 hit.
SM00144. PI3K_rbd. 1 hit.
SM00145. PI3Ka. 1 hit.
SM00146. PI3Kc. 1 hit.
[Graphical view]
SUPFAMSSF48371. SSF48371. 1 hit.
SSF49562. SSF49562. 1 hit.
SSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00915. 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]
ProtoNetSearch...

Other

EvolutionaryTraceO02697.

Entry information

Entry namePK3CG_PIG
AccessionPrimary (citable) accession number: O02697
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: December 15, 1998
Last modified: June 11, 2014
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways