CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-008079
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform 
Protein Synonyms/Alias
 PI3-kinase subunit gamma; PI3K-gamma; PI3Kgamma; PtdIns-3-kinase subunit gamma; Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma; PtdIns-3-kinase subunit p110-gamma; p110gamma; Phosphoinositide-3-kinase catalytic gamma polypeptide; Serine/threonine protein kinase PIK3CG; p120-PI3K 
Gene Name
 PIK3CG 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
7*MELENYKQPVVLREubiquitination[1]
255FFTKMAKKKSLMDIPubiquitination[1]
256FTKMAKKKSLMDIPEubiquitination[1]
288LVGETPIKNFQWVRHubiquitination[1]
597PKLFSSVKWGQQEIVubiquitination[1]
606GQQEIVAKTYQLLARubiquitination[1]
792VPYDPGLKAGALAIEubiquitination[1]
903VGNTGAFKDEVLNHWubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 34 141 PI3K-ABD.
 DOMAIN 217 309 PI3K-RBD.
 DOMAIN 357 521 C2 PI3K-type.
 DOMAIN 541 723 PIK helical.
 DOMAIN 828 1073 PI3K/PI4K.
 NP_BIND 829 838 ATP (By similarity).
 NP_BIND 864 872 ATP (By similarity).
 NP_BIND 961 969 ATP (By similarity).
 MOD_RES 1024 1024 Phosphothreonine; by PKA (By similarity).
 MOD_RES 1101 1101 Phosphoserine; by autocatalysis.  
Keyword
 3D-structure; Angiogenesis; ATP-binding; Cell membrane; Chemotaxis; Complete proteome; Cytoplasm; Endocytosis; Immunity; Inflammatory response; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1102 AA 
Protein Sequence
MELENYKQPV VLREDNCRRR RRMKPRSAAA SLSSMELIPI EFVLPTSQRK CKSPETALLH 60
VAGHGNVEQM KAQVWLRALE TSVAADFYHR LGPHHFLLLY QKKGQWYEIY DKYQVVQTLD 120
CLRYWKATHR SPGQIHLVQR HPPSEESQAF QRQLTALIGY DVTDVSNVHD DELEFTRRGL 180
VTPRMAEVAS RDPKLYAMHP WVTSKPLPEY LWKKIANNCI FIVIHRSTTS QTIKVSPDDT 240
PGAILQSFFT KMAKKKSLMD IPESQSEQDF VLRVCGRDEY LVGETPIKNF QWVRHCLKNG 300
EEIHVVLDTP PDPALDEVRK EEWPLVDDCT GVTGYHEQLT IHGKDHESVF TVSLWDCDRK 360
FRVKIRGIDI PVLPRNTDLT VFVEANIQHG QQVLCQRRTS PKPFTEEVLW NVWLEFSIKI 420
KDLPKGALLN LQIYCGKAPA LSSKASAESP SSESKGKVQL LYYVNLLLID HRFLLRRGEY 480
VLHMWQISGK GEDQGSFNAD KLTSATNPDK ENSMSISILL DNYCHPIALP KHQPTPDPEG 540
DRVRAEMPNQ LRKQLEAIIA TDPLNPLTAE DKELLWHFRY ESLKHPKAYP KLFSSVKWGQ 600
QEIVAKTYQL LARREVWDQS ALDVGLTMQL LDCNFSDENV RAIAVQKLES LEDDDVLHYL 660
LQLVQAVKFE PYHDSALARF LLKRGLRNKR IGHFLFWFLR SEIAQSRHYQ QRFAVILEAY 720
LRGCGTAMLH DFTQQVQVIE MLQKVTLDIK SLSAEKYDVS SQVISQLKQK LENLQNSQLP 780
ESFRVPYDPG LKAGALAIEK CKVMASKKKP LWLEFKCADP TALSNETIGI IFKHGDDLRQ 840
DMLILQILRI MESIWETESL DLCLLPYGCI STGDKIGMIE IVKDATTIAK IQQSTVGNTG 900
AFKDEVLNHW LKEKSPTEEK FQAAVERFVY SCAGYCVATF VLGIGDRHND NIMITETGNL 960
FHIDFGHILG NYKSFLGINK ERVPFVLTPD FLFVMGTSGK KTSPHFQKFQ DICVKAYLAL 1020
RHHTNLLIIL FSMMLMTGMP QLTSKEDIEY IRDALTVGKN EEDAKKYFLD QIEVCRDKGW 1080
TVQFNWFLHL VLGIKQGEKH SA 1102 
Gene Ontology
 GO:0005944; C:1-phosphatidylinositol-4-phosphate 3-kinase, class IB complex; IDA:UniProtKB.
 GO:0005886; C:plasma membrane; IBA:RefGenome.
 GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IBA:RefGenome.
 GO:0035005; F:1-phosphatidylinositol-4-phosphate 3-kinase activity; IBA:RefGenome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0046934; F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity; IBA:RefGenome.
 GO:0004672; F:protein kinase activity; TAS:UniProtKB.
 GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
 GO:0002250; P:adaptive immune response; TAS:UniProtKB.
 GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
 GO:0001816; P:cytokine production; TAS:UniProtKB.
 GO:0002407; P:dendritic cell chemotaxis; TAS:UniProtKB.
 GO:0007204; P:elevation of cytosolic calcium ion concentration; IEA:Compara.
 GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
 GO:0007186; P:G-protein coupled receptor signaling pathway; IDA:UniProtKB.
 GO:0097284; P:hepatocyte apoptotic process; IEA:Compara.
 GO:0006954; P:inflammatory response; TAS:UniProtKB.
 GO:0045087; P:innate immune response; TAS:UniProtKB.
 GO:0043303; P:mast cell degranulation; TAS:UniProtKB.
 GO:0035747; P:natural killer cell chemotaxis; TAS:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; IEA:Compara.
 GO:0055118; P:negative regulation of cardiac muscle contraction; TAS:UniProtKB.
 GO:0010897; P:negative regulation of triglyceride catabolic process; IEA:Compara.
 GO:0030593; P:neutrophil chemotaxis; TAS:UniProtKB.
 GO:0072672; P:neutrophil extravasation; TAS:UniProtKB.
 GO:0014065; P:phosphatidylinositol 3-kinase cascade; IDA:UniProtKB.
 GO:0070527; P:platelet aggregation; TAS:UniProtKB.
 GO:0002675; P:positive regulation of acute inflammatory response; IEA:Compara.
 GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB.
 GO:0051897; P:positive regulation of protein kinase B signaling cascade; IDA:UniProtKB.
 GO:0033628; P:regulation of cell adhesion mediated by integrin; TAS:UniProtKB.
 GO:0002679; P:respiratory burst involved in defense response; TAS:UniProtKB.
 GO:0032252; P:secretory granule localization; IEA:Compara.
 GO:0044281; P:small molecule metabolic process; TAS:Reactome.
 GO:0010818; P:T cell chemotaxis; TAS:UniProtKB.
 GO:0042098; P:T cell proliferation; TAS:UniProtKB. 
Interpro
 IPR016024; ARM-type_fold.
 IPR008973; C2_Ca/lipid-bd_dom_CaLB.
 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. 
Pfam
 PF00454; PI3_PI4_kinase
 PF00792; PI3K_C2
 PF00794; PI3K_rbd
 PF00613; PI3Ka 
SMART
 SM00142; PI3K_C2
 SM00144; PI3K_rbd
 SM00145; PI3Ka
 SM00146; PI3Kc 
PROSITE
 PS00915; PI3_4_KINASE_1
 PS00916; PI3_4_KINASE_2
 PS50290; PI3_4_KINASE_3
 PS51544; PI3K_ABD
 PS51547; PI3K_C2
 PS51546; PI3K_RBD
 PS51545; PIK_HELICAL 
PRINTS