General Information of Drug Therapeutic Target (DTT) (ID: TTHXGLJ)

DTT Name HUMAN PI3-kinase gamma (PIK3CG)
Synonyms
p120-PI3K; p110gamma; Serine/threonine protein kinase PIK3CG; PtdIns-3-kinase subunit p110-gamma; PtdIns-3-kinase subunit gamma; PtdIns-3-kinase p110; Phosphoinositol-3 kinase; Phosphoinositide-3-kinase catalytic gamma polypeptide; Phosphoinositide 3-Kinase gamma; Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit, gamma isoform; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform; Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma; PI3Kgamma; PI3K-gamma; PI3K; PI3-kinase subunit gamma; PI3-kinase p110 subunit gamma
Gene Name PIK3CG
BioChemical Class
Kinase
UniProt ID
PK3CG_HUMAN
TTD ID
T94131
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.7.1.153
Sequence
MELENYKQPVVLREDNCRRRRRMKPRSAAASLSSMELIPIEFVLPTSQRKCKSPETALLH
VAGHGNVEQMKAQVWLRALETSVAADFYHRLGPHHFLLLYQKKGQWYEIYDKYQVVQTLD
CLRYWKATHRSPGQIHLVQRHPPSEESQAFQRQLTALIGYDVTDVSNVHDDELEFTRRGL
VTPRMAEVASRDPKLYAMHPWVTSKPLPEYLWKKIANNCIFIVIHRSTTSQTIKVSPDDT
PGAILQSFFTKMAKKKSLMDIPESQSEQDFVLRVCGRDEYLVGETPIKNFQWVRHCLKNG
EEIHVVLDTPPDPALDEVRKEEWPLVDDCTGVTGYHEQLTIHGKDHESVFTVSLWDCDRK
FRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNVWLEFSIKI
KDLPKGALLNLQIYCGKAPALSSKASAESPSSESKGKVQLLYYVNLLLIDHRFLLRRGEY
VLHMWQISGKGEDQGSFNADKLTSATNPDKENSMSISILLDNYCHPIALPKHQPTPDPEG
DRVRAEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQ
QEIVAKTYQLLARREVWDQSALDVGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYL
LQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSRHYQQRFAVILEAY
LRGCGTAMLHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLP
ESFRVPYDPGLKAGALAIEKCKVMASKKKPLWLEFKCADPTALSNETIGIIFKHGDDLRQ
DMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIAKIQQSTVGNTG
AFKDEVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNL
FHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSPHFQKFQDICVKAYLAL
RHHTNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKNEEDAKKYFLDQIEVCRDKGW
TVQFNWFLHLVLGIKQGEKHSA
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 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. 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.
KEGG Pathway
Inositol phosphate metabolism (hsa00562 )
Metabolic pathways (hsa01100 )
cGMP-PKG signaling pathway (hsa04022 )
Chemokine signaling pathway (hsa04062 )
Phospholipase D signaling pathway (hsa04072 )
PI3K-Akt signaling pathway (hsa04151 )
Adrenergic signaling in cardiomyocytes (hsa04261 )
Apelin signaling pathway (hsa04371 )
Platelet activation (hsa04611 )
Cholinergic synapse (hsa04725 )
Oxytocin signaling pathway (hsa04921 )
Salmonella infection (hsa05132 )
Toxoplasmosis (hsa05145 )
Kaposi sarcoma-associated herpesvirus infection (hsa05167 )
Reactome Pathway
Synthesis of PIPs at the plasma membrane (R-HSA-1660499 )
G beta (R-HSA-392451 )
Erythropoietin activates Phosphoinositide-3-kinase (PI3K) (R-HSA-9027276 )
GPVI-mediated activation cascade (R-HSA-114604 )
BioCyc Pathway
MetaCyc:HS02818-MON

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Drugs in Phase 2 Trial Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Duvelisib DM7USVA Follicular lymphoma 2A80 Phase 2 Trial [1]
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References

1 ClinicalTrials.gov (NCT04372602) Duvelisib to Combat COVID-19. U.S. National Institutes of Health.