Gene/Proteome Database (LMPD)

LMPD ID
LMP000468
Gene ID
5294
Species
Homo sapiens (Human)
Gene Name
phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma
Gene Symbol
PIK3CG
Synonyms
PI3CG; PI3K; PI3Kgamma; PIK3; p110gamma; p120-PI3K
Alternate Names
phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform; PI3-kinase subunit gamma; ptdIns-3-kinase subunit gamma; 1-phosphatidylinositol 3-kinase; ptdIns-3-kinase subunit p110-gamma; serine/threonine protein kinase PIK3CG; phosphatidylinositol 3 kinase gamma, p110 gamma; phosphoinositide-3-kinase gamma catalytic subunit; phosphatidylinositol 3-kinase catalytic 110-kD gamma; phosphatidylinositol-4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
Chromosome
7
Map Location
7q22.3
EC Number
2.7.1.153
Summary
This gene encodes a protein that belongs to the pi3/pi4-kinase family of proteins. The gene product is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. It is an important modulator of extracellular signals, including those elicited by E-cadherin-mediated cell-cell adhesion, which plays an important role in maintenance of the structural and functional integrity of epithelia. In addition to its role in promoting assembly of adherens junctions, the protein is thought to play a pivotal role in the regulation of cytotoxicity in NK cells. The gene is located in a commonly deleted segment of chromosome 7 previously identified in myeloid leukemias. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2013]
Orthologs
View orthologs and multiple alignments for PIK3CG

Proteins

phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
Refseq ID NP_002640
Protein GI 21237725
UniProt ID P48736
mRNA ID NM_002649
Length 1102
RefSeq Status REVIEWED
MELENYKQPVVLREDNCRRRRRMKPRSAAASLSSMELIPIEFVLPTSQRKCKSPETALLHVAGHGNVEQMKAQVWLRALETSVAADFYHRLGPHHFLLLYQKKGQWYEIYDKYQVVQTLDCLRYWKATHRSPGQIHLVQRHPPSEESQAFQRQLTALIGYDVTDVSNVHDDELEFTRRGLVTPRMAEVASRDPKLYAMHPWVTSKPLPEYLWKKIANNCIFIVIHRSTTSQTIKVSPDDTPGAILQSFFTKMAKKKSLMDIPESQSEQDFVLRVCGRDEYLVGETPIKNFQWVRHCLKNGEEIHVVLDTPPDPALDEVRKEEWPLVDDCTGVTGYHEQLTIHGKDHESVFTVSLWDCDRKFRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNVWLEFSIKIKDLPKGALLNLQIYCGKAPALSSKASAESPSSESKGKVQLLYYVNLLLIDHRFLLRRGEYVLHMWQISGKGEDQGSFNADKLTSATNPDKENSMSISILLDNYCHPIALPKHQPTPDPEGDRVRAEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARREVWDQSALDVGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSRHYQQRFAVILEAYLRGCGTAMLHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLKAGALAIEKCKVMASKKKPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIAKIQQSTVGNTGAFKDEVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSPHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKNEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLVLGIKQGEKHSA
phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
Refseq ID NP_001269356
Protein GI 539846764
UniProt ID P48736
mRNA ID NM_001282427
Length 1102
RefSeq Status REVIEWED
Protein sequence is identical to GI:21237725 (mRNA isoform)
phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
Refseq ID NP_001269355
Protein GI 539846630
UniProt ID P48736
mRNA ID NM_001282426
Length 1102
RefSeq Status REVIEWED
Protein sequence is identical to GI:21237725 (mRNA isoform)

Gene Information

Entrez Gene ID
5294
Gene Name
phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma
Gene Symbol
PIK3CG
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005737 IDA:UniProtKB C cytoplasm
GO:0005829 TAS:Reactome C cytosol
GO:0042629 TAS:GOC C mast cell granule
GO:0016020 IDA:UniProtKB C membrane
GO:0005944 IDA:UniProtKB C phosphatidylinositol 3-kinase complex, class IB
GO:0005886 IBA:RefGenome C plasma membrane
GO:0016303 IBA:RefGenome F 1-phosphatidylinositol-3-kinase activity
GO:0035005 IBA:RefGenome F 1-phosphatidylinositol-4-phosphate 3-kinase activity
GO:0005524 IEA:UniProtKB-KW F ATP binding
GO:0046875 IPI:UniProtKB F ephrin receptor binding
GO:0035004 TAS:UniProtKB F phosphatidylinositol 3-kinase activity
GO:0046934 IBA:RefGenome F phosphatidylinositol-4,5-bisphosphate 3-kinase activity
GO:0004672 TAS:UniProtKB F protein kinase activity
GO:0004674 IEA:UniProtKB-KW F protein serine/threonine kinase activity
GO:0007186 IDA:UniProtKB P G-protein coupled receptor signaling pathway
GO:0042110 TAS:UniProtKB P T cell activation
GO:0010818 TAS:UniProtKB P T cell chemotaxis
GO:0042098 TAS:UniProtKB P T cell proliferation
GO:0002250 TAS:UniProtKB P adaptive immune response
GO:0001525 IEA:UniProtKB-KW P angiogenesis
GO:0007596 TAS:Reactome P blood coagulation
GO:0001816 TAS:UniProtKB P cytokine production
GO:0002407 TAS:UniProtKB P dendritic cell chemotaxis
GO:0006897 IEA:UniProtKB-KW P endocytosis
GO:0097284 IEA:Ensembl P hepatocyte apoptotic process
GO:0006954 TAS:UniProtKB P inflammatory response
GO:0045087 TAS:UniProtKB P innate immune response
GO:0043303 TAS:UniProtKB P mast cell degranulation
GO:0035747 TAS:UniProtKB P natural killer cell chemotaxis
GO:0055118 TAS:UniProtKB P negative regulation of cardiac muscle contraction
GO:2000270 IEA:Ensembl P negative regulation of fibroblast apoptotic process
GO:0010897 IEA:Ensembl P negative regulation of triglyceride catabolic process
GO:0030593 TAS:UniProtKB P neutrophil chemotaxis
GO:0072672 TAS:UniProtKB P neutrophil extravasation
GO:0014065 IDA:UniProtKB P phosphatidylinositol 3-kinase signaling
GO:0006661 TAS:Reactome P phosphatidylinositol biosynthetic process
GO:0006644 TAS:Reactome P phospholipid metabolic process
GO:0030168 TAS:Reactome P platelet activation
GO:0070527 TAS:UniProtKB P platelet aggregation
GO:0043406 IDA:UniProtKB P positive regulation of MAP kinase activity
GO:0002675 IEA:Ensembl P positive regulation of acute inflammatory response
GO:0007204 IEA:Ensembl P positive regulation of cytosolic calcium ion concentration
GO:0051897 IDA:UniProtKB P positive regulation of protein kinase B signaling
GO:0033628 TAS:UniProtKB P regulation of cell adhesion mediated by integrin
GO:0002679 TAS:UniProtKB P respiratory burst involved in defense response
GO:0032252 IEA:Ensembl P secretory granule localization
GO:0044281 TAS:Reactome P small molecule metabolic process

KEGG Pathway Links

KEGG Pathway ID Description
hsa04152 AMPK signaling pathway
hsa04550 Signaling pathways regulating pluripotency of stem cells
hsa04024 cAMP signaling pathway
hsa04022 cGMP-PKG signaling pathway

Domain Information

InterPro Annotations

Accession Description
IPR016024 Armadillo-type fold
IPR000008 C2 domain
IPR000403 Phosphatidylinositol 3-/4-kinase, catalytic domain
IPR000341 Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain
IPR003113 Phosphatidylinositol 3-kinase adaptor-binding (PI3K ABD) domain
IPR002420 Phosphatidylinositol 3-kinase, C2 domain
IPR018936 Phosphatidylinositol 3/4-kinase, conserved site
IPR015433 Phosphatidylinositol Kinase
IPR001263 Phosphoinositide 3-kinase, accessory (PIK) domain
IPR011009 Protein kinase-like domain
IPR029071 Ubiquitin-related domain

UniProt Annotations

Entry Information

Gene Name
phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma
Protein Entry
PK3CG_HUMAN
UniProt ID
P48736
Species
Human

Comments

Comment Type Description
Catalytic Activity ATP + 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5- trisphosphate.
Catalytic Activity 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. {ECO
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. {ECO
Interaction Q13370:PDE3B; NbExp=3; IntAct=EBI-1030384, EBI-6172856; O02696:PIK3R5 (xeno); NbExp=6; IntAct=EBI-1030384, EBI-6172343;
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).
Pathway Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis.
Similarity Belongs to the PI3/PI4-kinase family. {ECO
Similarity Contains 1 C2 PI3K-type domain. {ECO
Similarity Contains 1 PI3K-ABD domain. {ECO
Similarity Contains 1 PI3K-RBD domain. {ECO
Similarity Contains 1 PI3K/PI4K domain. {ECO
Similarity Contains 1 PIK helical domain. {ECO
Subcellular Location Cytoplasm . Cell membrane .
Subunit 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
Tissue Specificity Pancreas, skeletal muscle, liver and heart.

Identical and Related Proteins

Unique RefSeq proteins for LMP000468 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
21237725 RefSeq NP_002640 1102 phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform

Identical Sequences to LMP000468 proteins

Reference Database Accession Length Protein Name
GI:21237725 GenBank AHD73276.1 1102 Sequence 10344 from patent US 8586006
GI:21237725 GenBank AHL55940.1 1102 Sequence 4 from patent US 8642604
GI:21237725 GenBank AIC62556.1 1102 PIK3CG, partial [synthetic construct]
GI:21237725 RefSeq XP_005250500.1 1102 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X3 [Homo sapiens]
GI:21237725 RefSeq NP_001269355.1 1102 phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [Homo sapiens]
GI:21237725 RefSeq NP_001269356.1 1102 phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [Homo sapiens]

Related Sequences to LMP000468 proteins

Reference Database Accession Length Protein Name
GI:21237725 GenBank AAG61115.1 1102 phosphoinositide-3-kinase gamma catalytic subunit [Homo sapiens]
GI:21237725 GenBank AAX41023.1 1103 phosphoinositide-3-kinase catalytic gamma polypeptide, partial [synthetic construct]
GI:21237725 GenBank AIC54902.1 1102 PIK3CG, partial [synthetic construct]
GI:21237725 RefSeq XP_003811242.1 1102 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [Pan paniscus]
GI:21237725 RefSeq XP_003811243.1 1102 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [Pan paniscus]
GI:21237725 RefSeq XP_003811244.1 1102 PREDICTED: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [Pan paniscus]