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P48736

- PK3CG_HUMAN

UniProt

P48736 - PK3CG_HUMAN

Protein

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

Gene

PIK3CG

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 151 (01 Oct 2014)
      Sequence version 3 (04 Apr 2006)
      Previous versions | rss
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    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 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.5 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 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-605240.2 Publications

    Pathwayi

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi829 – 83810ATPBy similarity
    Nucleotide bindingi864 – 8729ATPBy similarity
    Nucleotide bindingi961 – 9699ATPBy similarity

    GO - Molecular functioni

    1. 1-phosphatidylinositol-3-kinase activity Source: RefGenome
    2. 1-phosphatidylinositol-4-phosphate 3-kinase activity Source: RefGenome
    3. ATP binding Source: UniProtKB-KW
    4. ephrin receptor binding Source: UniProtKB
    5. phosphatidylinositol 3-kinase activity Source: UniProtKB
    6. phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: RefGenome
    7. protein binding Source: IntAct
    8. protein kinase activity Source: UniProtKB
    9. protein serine/threonine kinase activity Source: UniProtKB-KW

    GO - Biological processi

    1. adaptive immune response Source: UniProtKB
    2. angiogenesis Source: UniProtKB-KW
    3. blood coagulation Source: Reactome
    4. cytokine production Source: UniProtKB
    5. dendritic cell chemotaxis Source: UniProtKB
    6. endocytosis Source: UniProtKB-KW
    7. G-protein coupled receptor signaling pathway Source: UniProtKB
    8. hepatocyte apoptotic process Source: Ensembl
    9. inflammatory response Source: UniProtKB
    10. innate immune response Source: UniProtKB
    11. mast cell degranulation Source: UniProtKB
    12. natural killer cell chemotaxis Source: UniProtKB
    13. negative regulation of cardiac muscle contraction Source: UniProtKB
    14. negative regulation of fibroblast apoptotic process Source: Ensembl
    15. negative regulation of triglyceride catabolic process Source: Ensembl
    16. neutrophil chemotaxis Source: UniProtKB
    17. neutrophil extravasation Source: UniProtKB
    18. phosphatidylinositol 3-kinase signaling Source: UniProtKB
    19. phosphatidylinositol biosynthetic process Source: Reactome
    20. phospholipid metabolic process Source: Reactome
    21. platelet activation Source: Reactome
    22. platelet aggregation Source: UniProtKB
    23. positive regulation of acute inflammatory response Source: Ensembl
    24. positive regulation of cytosolic calcium ion concentration Source: Ensembl
    25. positive regulation of MAP kinase activity Source: UniProtKB
    26. positive regulation of protein kinase B signaling Source: UniProtKB
    27. regulation of cell adhesion mediated by integrin Source: UniProtKB
    28. respiratory burst involved in defense response Source: UniProtKB
    29. secretory granule localization Source: Ensembl
    30. small molecule metabolic process Source: Reactome
    31. T cell activation Source: UniProtKB
    32. T cell chemotaxis Source: UniProtKB
    33. T cell proliferation Source: UniProtKB

    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

    BioCyciMetaCyc:HS02818-MONOMER.
    BRENDAi2.7.1.137. 2681.
    ReactomeiREACT_121025. Synthesis of PIPs at the plasma membrane.
    REACT_1695. GPVI-mediated activation cascade.
    REACT_19290. G beta:gamma signalling through PI3Kgamma.
    SignaLinkiP48736.
    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
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:8978. PIK3CG.

    Subcellular locationi

    Cytoplasm 1 Publication. Cell membrane 1 Publication

    GO - Cellular componenti

    1. 1-phosphatidylinositol-4-phosphate 3-kinase, class IB complex Source: UniProtKB
    2. cytoplasm Source: UniProtKB
    3. cytosol Source: Reactome
    4. mast cell granule Source: GOC
    5. membrane Source: UniProtKB
    6. plasma membrane Source: RefGenome

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi833 – 8331K → R: Reduced inflammatory reactions but no alterations in cardiac contractility. 1 Publication
    Mutagenesisi947 – 9471R → P: Abolishes protein and lipid kinase activity. Does not abolishes interaction with ADRBK1. 1 Publication

    Organism-specific databases

    PharmGKBiPA33311.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11021102Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoformPRO_0000088792Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1024 – 10241Phosphothreonine; by PKABy similarity
    Modified residuei1101 – 11011Phosphoserine; by autocatalysis1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP48736.
    PaxDbiP48736.
    PRIDEiP48736.

    PTM databases

    PhosphoSiteiP48736.

    Expressioni

    Tissue specificityi

    Pancreas, skeletal muscle, liver and heart.1 Publication

    Gene expression databases

    ArrayExpressiP48736.
    BgeeiP48736.
    CleanExiHS_PIK3CG.
    GenevestigatoriP48736.

    Interactioni

    Subunit structurei

    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:PIK3R6 By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    PDE3BQ133703EBI-1030384,EBI-6172856
    PIK3R5O026966EBI-1030384,EBI-6172343From a different organism.

    Protein-protein interaction databases

    BioGridi111312. 18 interactions.
    DIPiDIP-37781N.
    IntActiP48736. 14 interactions.
    MINTiMINT-155782.
    STRINGi9606.ENSP00000352121.

    Structurei

    Secondary structure

    1
    1102
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi145 – 15814
    Helixi165 – 1673
    Beta strandi169 – 1713
    Helixi172 – 1798
    Helixi181 – 19010
    Helixi193 – 1986
    Helixi209 – 2124
    Helixi213 – 2153
    Beta strandi216 – 2183
    Beta strandi220 – 2267
    Beta strandi229 – 2357
    Helixi241 – 2433
    Helixi246 – 2527
    Helixi256 – 2594
    Beta strandi263 – 2653
    Beta strandi271 – 2744
    Beta strandi283 – 2853
    Helixi287 – 2893
    Helixi291 – 2988
    Beta strandi303 – 3086
    Helixi313 – 3164
    Helixi354 – 3563
    Beta strandi359 – 36911
    Beta strandi375 – 3773
    Beta strandi380 – 39112
    Beta strandi393 – 3986
    Beta strandi406 – 41914
    Helixi420 – 4223
    Beta strandi428 – 4347
    Beta strandi462 – 4698
    Beta strandi473 – 4753
    Beta strandi478 – 4836
    Helixi499 – 5024
    Beta strandi511 – 5133
    Beta strandi515 – 5206
    Helixi549 – 56012
    Beta strandi563 – 5653
    Helixi569 – 5779
    Helixi579 – 5824
    Helixi586 – 5883
    Helixi589 – 5935
    Helixi601 – 61212
    Helixi615 – 6184
    Helixi624 – 6307
    Beta strandi632 – 6343
    Helixi638 – 64811
    Helixi653 – 66614
    Helixi667 – 6693
    Beta strandi671 – 6744
    Helixi676 – 68712
    Helixi689 – 70517
    Turni707 – 7093
    Helixi710 – 72112
    Turni722 – 7243
    Helixi726 – 75126
    Beta strandi755 – 7573
    Helixi761 – 77414
    Turni775 – 7784
    Beta strandi783 – 7853
    Beta strandi788 – 7969
    Helixi798 – 8003
    Beta strandi806 – 8083
    Beta strandi811 – 8188
    Beta strandi828 – 8369
    Helixi838 – 85619
    Turni857 – 8593
    Beta strandi869 – 8735
    Beta strandi876 – 8805
    Beta strandi885 – 8873
    Helixi888 – 8958
    Beta strandi898 – 9003
    Helixi906 – 9149
    Beta strandi915 – 9173
    Helixi918 – 94124
    Helixi949 – 9513
    Beta strandi952 – 9554
    Turni956 – 9583
    Beta strandi960 – 9623
    Helixi965 – 9706
    Helixi989 – 9946
    Turni998 – 10003
    Helixi1004 – 102118
    Helixi1024 – 103815
    Beta strandi1039 – 10413
    Turni1042 – 10454
    Helixi1046 – 10549
    Turni1055 – 10584
    Helixi1061 – 107818
    Helixi1081 – 10855
    Turni1086 – 10905
    Turni1091 – 10933

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1E8YX-ray2.00A144-1102[»]
    1E8ZX-ray2.40A144-1102[»]
    1HE8X-ray3.00A144-1102[»]
    2A4ZX-ray2.90A144-1102[»]
    2A5UX-ray2.70A144-1102[»]
    2CHWX-ray2.60A144-1102[»]
    2CHXX-ray2.50A144-1102[»]
    2CHZX-ray2.60A144-1102[»]
    2V4LX-ray2.50A144-1102[»]
    3APCX-ray2.54A144-1102[»]
    3APDX-ray2.55A144-1102[»]
    3APFX-ray2.82A144-1102[»]
    3CSFX-ray2.80A144-1102[»]
    3CSTX-ray3.20A144-1102[»]
    3DBSX-ray2.80A144-1102[»]
    3DPDX-ray2.85A144-1102[»]
    3ENEX-ray2.40A144-1102[»]
    3IBEX-ray2.80A144-1102[»]
    3L08X-ray2.70A144-1102[»]
    3L13X-ray3.00A144-1102[»]
    3L16X-ray2.90A144-1102[»]
    3L17X-ray3.00A144-1102[»]
    3L54X-ray2.30A144-1102[»]
    3LJ3X-ray2.43A144-1102[»]
    3MJWX-ray2.87A144-1102[»]
    3ML8X-ray2.70A144-1102[»]
    3ML9X-ray2.55A144-1102[»]
    3NZSX-ray2.75A147-1094[»]
    3NZUX-ray2.60A147-1094[»]
    3OAWX-ray2.75A144-1102[»]
    3P2BX-ray3.20A144-1102[»]
    3PREX-ray2.91A144-1102[»]
    3PRZX-ray2.60A144-1102[»]
    3PS6X-ray2.60A144-1102[»]
    3QAQX-ray2.90A144-1102[»]
    3QARX-ray2.65A144-1102[»]
    3QJZX-ray2.90A144-1102[»]
    3QK0X-ray2.85A144-1102[»]
    3R7QX-ray2.50A144-1102[»]
    3R7RX-ray2.90A144-1102[»]
    3S2AX-ray2.55A144-1102[»]
    3SD5X-ray3.20A144-1102[»]
    3T8MX-ray2.50A144-1102[»]
    3TJPX-ray2.70A144-1102[»]
    3TL5X-ray2.79A144-1102[»]
    3ZVVX-ray2.50A144-1102[»]
    3ZW3X-ray2.80A144-1102[»]
    4ANUX-ray2.81A144-1102[»]
    4ANVX-ray2.13A144-1102[»]
    4ANWX-ray2.31A144-1102[»]
    4ANXX-ray2.73A144-1102[»]
    4AOFX-ray3.30A144-1102[»]
    4DK5X-ray2.95A144-1102[»]
    4EZJX-ray2.67A144-1102[»]
    4EZKX-ray2.80A144-1102[»]
    4EZLX-ray2.94A144-1102[»]
    4F1SX-ray3.00A144-1102[»]
    4FA6X-ray2.70A144-1102[»]
    4FADX-ray2.70A144-1102[»]
    4FHJX-ray2.60A144-1102[»]
    4FHKX-ray3.00A144-1102[»]
    4FJYX-ray2.90A144-1102[»]
    4FJZX-ray3.00A144-1102[»]
    4FLHX-ray2.60A144-1102[»]
    4FULX-ray2.47A144-1102[»]
    4G11X-ray3.40A144-1102[»]
    4GB9X-ray2.44A144-1102[»]
    4HLEX-ray2.78A144-1102[»]
    4HVBX-ray2.35A144-1102[»]
    4J6IX-ray2.90A144-1102[»]
    4KZ0X-ray2.87A144-1102[»]
    4KZCX-ray3.25A144-1102[»]
    4PS3X-ray2.90A144-1102[»]
    4PS7X-ray2.69A144-1102[»]
    4PS8X-ray2.99A144-1102[»]
    ProteinModelPortaliP48736.
    SMRiP48736. Positions 144-1089.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP48736.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini34 – 141108PI3K-ABDPROSITE-ProRule annotationAdd
    BLAST
    Domaini217 – 30993PI3K-RBDPROSITE-ProRule annotationAdd
    BLAST
    Domaini357 – 521165C2 PI3K-typePROSITE-ProRule annotationAdd
    BLAST
    Domaini541 – 723183PIK helicalPROSITE-ProRule annotationAdd
    BLAST
    Domaini828 – 1073246PI3K/PI4KPROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi19 – 235Poly-Arg

    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

    eggNOGiCOG5032.
    HOGENOMiHOG000252912.
    HOVERGENiHBG101026.
    InParanoidiP48736.
    KOiK00922.
    OMAiYHEQLTI.
    OrthoDBiEOG70CR65.
    PhylomeDBiP48736.
    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.

    P48736-1 [UniParc]FASTAAdd to Basket

    « Hide

    MELENYKQPV VLREDNCRRR RRMKPRSAAA SLSSMELIPI EFVLPTSQRK     50
    CKSPETALLH VAGHGNVEQM KAQVWLRALE TSVAADFYHR LGPHHFLLLY 100
    QKKGQWYEIY DKYQVVQTLD CLRYWKATHR SPGQIHLVQR HPPSEESQAF 150
    QRQLTALIGY DVTDVSNVHD DELEFTRRGL VTPRMAEVAS RDPKLYAMHP 200
    WVTSKPLPEY LWKKIANNCI FIVIHRSTTS QTIKVSPDDT PGAILQSFFT 250
    KMAKKKSLMD IPESQSEQDF VLRVCGRDEY LVGETPIKNF QWVRHCLKNG 300
    EEIHVVLDTP PDPALDEVRK EEWPLVDDCT GVTGYHEQLT IHGKDHESVF 350
    TVSLWDCDRK FRVKIRGIDI PVLPRNTDLT VFVEANIQHG QQVLCQRRTS 400
    PKPFTEEVLW NVWLEFSIKI KDLPKGALLN LQIYCGKAPA LSSKASAESP 450
    SSESKGKVQL LYYVNLLLID HRFLLRRGEY VLHMWQISGK GEDQGSFNAD 500
    KLTSATNPDK ENSMSISILL DNYCHPIALP KHQPTPDPEG DRVRAEMPNQ 550
    LRKQLEAIIA TDPLNPLTAE DKELLWHFRY ESLKHPKAYP KLFSSVKWGQ 600
    QEIVAKTYQL LARREVWDQS ALDVGLTMQL LDCNFSDENV RAIAVQKLES 650
    LEDDDVLHYL LQLVQAVKFE PYHDSALARF LLKRGLRNKR IGHFLFWFLR 700
    SEIAQSRHYQ QRFAVILEAY LRGCGTAMLH DFTQQVQVIE MLQKVTLDIK 750
    SLSAEKYDVS SQVISQLKQK LENLQNSQLP ESFRVPYDPG LKAGALAIEK 800
    CKVMASKKKP LWLEFKCADP TALSNETIGI IFKHGDDLRQ DMLILQILRI 850
    MESIWETESL DLCLLPYGCI STGDKIGMIE IVKDATTIAK IQQSTVGNTG 900
    AFKDEVLNHW LKEKSPTEEK FQAAVERFVY SCAGYCVATF VLGIGDRHND 950
    NIMITETGNL FHIDFGHILG NYKSFLGINK ERVPFVLTPD FLFVMGTSGK 1000
    KTSPHFQKFQ DICVKAYLAL RHHTNLLIIL FSMMLMTGMP QLTSKEDIEY 1050
    IRDALTVGKN EEDAKKYFLD QIEVCRDKGW TVQFNWFLHL VLGIKQGEKH 1100
    SA 1102
    Length:1,102
    Mass (Da):126,454
    Last modified:April 4, 2006 - v3
    Checksum:iEF2B1A0E1CBEF406
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti30 – 301Missing in CAA58284. (PubMed:7624799)Curated
    Sequence conflicti459 – 4591Q → R in CAA58284. (PubMed:7624799)Curated
    Sequence conflicti459 – 4591Q → R in AAG61115. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X83368 mRNA. Translation: CAA58284.1.
    AF327656 mRNA. Translation: AAG61115.1.
    AC005018 Genomic DNA. Translation: AAQ96873.1.
    CH236947 Genomic DNA. Translation: EAL24396.1.
    CH471070 Genomic DNA. Translation: EAW83387.1.
    BC035683 mRNA. Translation: AAH35683.1.
    CCDSiCCDS5739.1.
    RefSeqiNP_001269355.1. NM_001282426.1.
    NP_001269356.1. NM_001282427.1.
    NP_002640.2. NM_002649.3.
    XP_005250500.1. XM_005250443.1.
    UniGeneiHs.32942.
    Hs.561747.

    Genome annotation databases

    EnsembliENST00000359195; ENSP00000352121; ENSG00000105851.
    ENST00000440650; ENSP00000392258; ENSG00000105851.
    ENST00000496166; ENSP00000419260; ENSG00000105851.
    GeneIDi5294.
    KEGGihsa:5294.
    UCSCiuc003vdu.3. human.

    Polymorphism databases

    DMDMi92090623.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X83368 mRNA. Translation: CAA58284.1 .
    AF327656 mRNA. Translation: AAG61115.1 .
    AC005018 Genomic DNA. Translation: AAQ96873.1 .
    CH236947 Genomic DNA. Translation: EAL24396.1 .
    CH471070 Genomic DNA. Translation: EAW83387.1 .
    BC035683 mRNA. Translation: AAH35683.1 .
    CCDSi CCDS5739.1.
    RefSeqi NP_001269355.1. NM_001282426.1.
    NP_001269356.1. NM_001282427.1.
    NP_002640.2. NM_002649.3.
    XP_005250500.1. XM_005250443.1.
    UniGenei Hs.32942.
    Hs.561747.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1E8Y X-ray 2.00 A 144-1102 [» ]
    1E8Z X-ray 2.40 A 144-1102 [» ]
    1HE8 X-ray 3.00 A 144-1102 [» ]
    2A4Z X-ray 2.90 A 144-1102 [» ]
    2A5U X-ray 2.70 A 144-1102 [» ]
    2CHW X-ray 2.60 A 144-1102 [» ]
    2CHX X-ray 2.50 A 144-1102 [» ]
    2CHZ X-ray 2.60 A 144-1102 [» ]
    2V4L X-ray 2.50 A 144-1102 [» ]
    3APC X-ray 2.54 A 144-1102 [» ]
    3APD X-ray 2.55 A 144-1102 [» ]
    3APF X-ray 2.82 A 144-1102 [» ]
    3CSF X-ray 2.80 A 144-1102 [» ]
    3CST X-ray 3.20 A 144-1102 [» ]
    3DBS X-ray 2.80 A 144-1102 [» ]
    3DPD X-ray 2.85 A 144-1102 [» ]
    3ENE X-ray 2.40 A 144-1102 [» ]
    3IBE X-ray 2.80 A 144-1102 [» ]
    3L08 X-ray 2.70 A 144-1102 [» ]
    3L13 X-ray 3.00 A 144-1102 [» ]
    3L16 X-ray 2.90 A 144-1102 [» ]
    3L17 X-ray 3.00 A 144-1102 [» ]
    3L54 X-ray 2.30 A 144-1102 [» ]
    3LJ3 X-ray 2.43 A 144-1102 [» ]
    3MJW X-ray 2.87 A 144-1102 [» ]
    3ML8 X-ray 2.70 A 144-1102 [» ]
    3ML9 X-ray 2.55 A 144-1102 [» ]
    3NZS X-ray 2.75 A 147-1094 [» ]
    3NZU X-ray 2.60 A 147-1094 [» ]
    3OAW X-ray 2.75 A 144-1102 [» ]
    3P2B X-ray 3.20 A 144-1102 [» ]
    3PRE X-ray 2.91 A 144-1102 [» ]
    3PRZ X-ray 2.60 A 144-1102 [» ]
    3PS6 X-ray 2.60 A 144-1102 [» ]
    3QAQ X-ray 2.90 A 144-1102 [» ]
    3QAR X-ray 2.65 A 144-1102 [» ]
    3QJZ X-ray 2.90 A 144-1102 [» ]
    3QK0 X-ray 2.85 A 144-1102 [» ]
    3R7Q X-ray 2.50 A 144-1102 [» ]
    3R7R X-ray 2.90 A 144-1102 [» ]
    3S2A X-ray 2.55 A 144-1102 [» ]
    3SD5 X-ray 3.20 A 144-1102 [» ]
    3T8M X-ray 2.50 A 144-1102 [» ]
    3TJP X-ray 2.70 A 144-1102 [» ]
    3TL5 X-ray 2.79 A 144-1102 [» ]
    3ZVV X-ray 2.50 A 144-1102 [» ]
    3ZW3 X-ray 2.80 A 144-1102 [» ]
    4ANU X-ray 2.81 A 144-1102 [» ]
    4ANV X-ray 2.13 A 144-1102 [» ]
    4ANW X-ray 2.31 A 144-1102 [» ]
    4ANX X-ray 2.73 A 144-1102 [» ]
    4AOF X-ray 3.30 A 144-1102 [» ]
    4DK5 X-ray 2.95 A 144-1102 [» ]
    4EZJ X-ray 2.67 A 144-1102 [» ]
    4EZK X-ray 2.80 A 144-1102 [» ]
    4EZL X-ray 2.94 A 144-1102 [» ]
    4F1S X-ray 3.00 A 144-1102 [» ]
    4FA6 X-ray 2.70 A 144-1102 [» ]
    4FAD X-ray 2.70 A 144-1102 [» ]
    4FHJ X-ray 2.60 A 144-1102 [» ]
    4FHK X-ray 3.00 A 144-1102 [» ]
    4FJY X-ray 2.90 A 144-1102 [» ]
    4FJZ X-ray 3.00 A 144-1102 [» ]
    4FLH X-ray 2.60 A 144-1102 [» ]
    4FUL X-ray 2.47 A 144-1102 [» ]
    4G11 X-ray 3.40 A 144-1102 [» ]
    4GB9 X-ray 2.44 A 144-1102 [» ]
    4HLE X-ray 2.78 A 144-1102 [» ]
    4HVB X-ray 2.35 A 144-1102 [» ]
    4J6I X-ray 2.90 A 144-1102 [» ]
    4KZ0 X-ray 2.87 A 144-1102 [» ]
    4KZC X-ray 3.25 A 144-1102 [» ]
    4PS3 X-ray 2.90 A 144-1102 [» ]
    4PS7 X-ray 2.69 A 144-1102 [» ]
    4PS8 X-ray 2.99 A 144-1102 [» ]
    ProteinModelPortali P48736.
    SMRi P48736. Positions 144-1089.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111312. 18 interactions.
    DIPi DIP-37781N.
    IntActi P48736. 14 interactions.
    MINTi MINT-155782.
    STRINGi 9606.ENSP00000352121.

    Chemistry

    BindingDBi P48736.
    ChEMBLi CHEMBL3267.
    GuidetoPHARMACOLOGYi 2156.

    PTM databases

    PhosphoSitei P48736.

    Polymorphism databases

    DMDMi 92090623.

    Proteomic databases

    MaxQBi P48736.
    PaxDbi P48736.
    PRIDEi P48736.

    Protocols and materials databases

    DNASUi 5294.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000359195 ; ENSP00000352121 ; ENSG00000105851 .
    ENST00000440650 ; ENSP00000392258 ; ENSG00000105851 .
    ENST00000496166 ; ENSP00000419260 ; ENSG00000105851 .
    GeneIDi 5294.
    KEGGi hsa:5294.
    UCSCi uc003vdu.3. human.

    Organism-specific databases

    CTDi 5294.
    GeneCardsi GC07P106505.
    HGNCi HGNC:8978. PIK3CG.
    MIMi 601232. gene.
    neXtProti NX_P48736.
    PharmGKBi PA33311.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5032.
    HOGENOMi HOG000252912.
    HOVERGENi HBG101026.
    InParanoidi P48736.
    KOi K00922.
    OMAi YHEQLTI.
    OrthoDBi EOG70CR65.
    PhylomeDBi P48736.
    TreeFami TF102031.

    Enzyme and pathway databases

    UniPathwayi UPA00220 .
    BioCyci MetaCyc:HS02818-MONOMER.
    BRENDAi 2.7.1.137. 2681.
    Reactomei REACT_121025. Synthesis of PIPs at the plasma membrane.
    REACT_1695. GPVI-mediated activation cascade.
    REACT_19290. G beta:gamma signalling through PI3Kgamma.
    SignaLinki P48736.

    Miscellaneous databases

    EvolutionaryTracei P48736.
    GeneWikii PIK3CG.
    GenomeRNAii 5294.
    NextBioi 20458.
    PROi P48736.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P48736.
    Bgeei P48736.
    CleanExi HS_PIK3CG.
    Genevestigatori P48736.

    Family and domain databases

    Gene3Di 1.10.1070.11. 1 hit.
    1.25.40.70. 1 hit.
    2.60.40.150. 1 hit.
    InterProi IPR016024. 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 ]
    PANTHERi PTHR10048. PTHR10048. 1 hit.
    Pfami PF00454. PI3_PI4_kinase. 1 hit.
    PF00792. PI3K_C2. 1 hit.
    PF00794. PI3K_rbd. 1 hit.
    PF00613. PI3Ka. 1 hit.
    [Graphical view ]
    SMARTi SM00142. PI3K_C2. 1 hit.
    SM00144. PI3K_rbd. 1 hit.
    SM00145. PI3Ka. 1 hit.
    SM00146. PI3Kc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48371. SSF48371. 1 hit.
    SSF49562. SSF49562. 1 hit.
    SSF54236. SSF54236. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS00915. 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 ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ENZYME REGULATION, TISSUE SPECIFICITY.
    2. Waterfield M.D.
      Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION.
    3. "Regulation of a G-protein-activated phosphoinositide-3-kinase."
      Michalke M., Schaefer M., Stoyanov B., Wetzker R., Nuernberg B.
      Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "The DNA sequence of human chromosome 7."
      Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L.
      , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
      Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "Human chromosome 7: DNA sequence and biology."
      Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S.
      , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
      Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Pancreas.
    8. "The EphA8 receptor regulates integrin activity through p110gamma phosphatidylinositol-3 kinase in a tyrosine kinase activity-independent manner."
      Gu C., Park S.
      Mol. Cell. Biol. 21:4579-4597(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH EPHA8.
    9. "Phosphoinositide 3-kinase regulates beta2-adrenergic receptor endocytosis by AP-2 recruitment to the receptor/beta-arrestin complex."
      Naga Prasad S.V., Laporte S.A., Chamberlain D., Caron M.G., Barak L., Rockman H.A.
      J. Cell Biol. 158:563-575(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ADRBK1.
    10. "Identification and characterization of the autophosphorylation sites of phosphoinositide 3-kinase isoforms beta and gamma."
      Czupalla C., Culo M., Muller E.C., Brock C., Reusch H.P., Spicher K., Krause E., Nurnberg B.
      J. Biol. Chem. 278:11536-11545(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-1101.
    11. "PI3Kgamma modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and -independent effects."
      Patrucco E., Notte A., Barberis L., Selvetella G., Maffei A., Brancaccio M., Marengo S., Russo G., Azzolino O., Rybalkin S.D., Silengo L., Altruda F., Wetzker R., Wymann M.P., Lembo G., Hirsch E.
      Cell 118:375-387(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CARDIAC CONTRACTILITY, MUTAGENESIS OF LYS-833.
    12. "p84, a new Gbetagamma-activated regulatory subunit of the type IB phosphoinositide 3-kinase p110gamma."
      Suire S., Coadwell J., Ferguson G.J., Davidson K., Hawkins P., Stephens L.
      Curr. Biol. 15:566-570(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PIK3R5.
    13. "Protein kinase activity of phosphoinositide 3-kinase regulates beta-adrenergic receptor endocytosis."
      Naga Prasad S.V., Jayatilleke A., Madamanchi A., Rockman H.A.
      Nat. Cell Biol. 7:785-796(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS A PROTEIN KINASE, INTERACTION WITH ADRBK1 AND TPM2, MUTAGENESIS OF ARG-947.
    14. "PI3K delta and PI3K gamma: partners in crime in inflammation in rheumatoid arthritis and beyond?"
      Rommel C., Camps M., Ji H.
      Nat. Rev. Immunol. 7:191-201(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.
    15. "Targeting phosphoinositide 3-kinase gamma to fight inflammation and more."
      Barberis L., Hirsch E.
      Thromb. Haemost. 99:279-285(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION IN LEUKOCYTES AND ENDOTHELIAL CELLS, REVIEW ON ANTINFLAMMATORY THERAPY TARGET.
    16. "Cardiac regulation by phosphoinositide 3-kinases and PTEN."
      Oudit G.Y., Penninger J.M.
      Cardiovasc. Res. 82:250-260(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION IN CARDIAC CONTRACTILITY.
    17. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    18. "A phosphodiesterase 3B-based signaling complex integrates exchange protein activated by cAMP 1 and phosphatidylinositol 3-kinase signals in human arterial endothelial cells."
      Wilson L.S., Baillie G.S., Pritchard L.M., Umana B., Terrin A., Zaccolo M., Houslay M.D., Maurice D.H.
      J. Biol. Chem. 286:16285-16296(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    19. "Structural insights into phosphoinositide 3-kinase catalysis and signalling."
      Walker E.H., Perisic O., Ried C., Stephens L., Williams R.L.
      Nature 402:313-320(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 144-1102.
    20. Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 144-1101 IN A COMPLEX WITH AS-604850 AND AS-605240, ENZYME REGULATION.

    Entry informationi

    Entry nameiPK3CG_HUMAN
    AccessioniPrimary (citable) accession number: P48736
    Secondary accession number(s): A4D0Q6, Q8IV23, Q9BZC8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: April 4, 2006
    Last modified: October 1, 2014
    This is version 151 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    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).1 Publication

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    4. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    5. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3