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O02697

- PK3CG_PIG

UniProt

O02697 - PK3CG_PIG

Protein

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

Gene

PIK3CG

Organism
Sus scrofa (Pig)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 111 (01 Oct 2014)
      Sequence version 2 (15 Dec 1998)
      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. 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.By similarity

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

    Pathwayi

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi829 – 83810ATP1 Publication
    Nucleotide bindingi864 – 8729ATP1 Publication
    Nucleotide bindingi961 – 9699ATP1 Publication

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: UniProtKB-EC
    3. protein serine/threonine kinase activity Source: UniProtKB-KW

    GO - Biological processi

    1. angiogenesis Source: UniProtKB-KW
    2. chemotaxis Source: UniProtKB-KW
    3. endocytosis Source: UniProtKB-KW
    4. immune system process Source: UniProtKB-KW
    5. inflammatory response Source: UniProtKB-KW
    6. phosphatidylinositol-mediated signaling Source: InterPro

    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

    BRENDAi2.7.1.137. 6170.
    ReactomeiREACT_208233. Synthesis of PIPs at the plasma membrane.
    REACT_208923. G beta:gamma signalling through PI3Kgamma.
    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
    OrganismiSus scrofa (Pig)
    Taxonomic identifieri9823 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
    ProteomesiUP000008227: Unplaced

    Subcellular locationi

    Cytoplasm By similarity. Cell membrane By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11021102Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoformPRO_0000088794Add
    BLAST

    Amino acid modifications

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

    Keywords - PTMi

    Phosphoprotein

    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. 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

    Protein-protein interaction databases

    IntActiO02697. 2 interactions.

    Structurei

    Secondary structure

    1
    1102
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi145 – 15814
    Beta strandi169 – 1713
    Helixi172 – 19019
    Helixi193 – 1986
    Helixi209 – 2124
    Helixi213 – 2153
    Beta strandi216 – 22813
    Beta strandi230 – 2367
    Helixi241 – 25111
    Beta strandi271 – 2744
    Beta strandi283 – 2853
    Helixi287 – 2893
    Helixi291 – 2999
    Beta strandi303 – 3086
    Helixi313 – 3164
    Beta strandi359 – 36911
    Beta strandi379 – 38911
    Beta strandi392 – 3987
    Beta strandi406 – 41914
    Helixi420 – 4223
    Beta strandi428 – 43710
    Beta strandi460 – 46910
    Beta strandi473 – 4753
    Beta strandi478 – 4836
    Helixi499 – 5024
    Turni510 – 5123
    Beta strandi515 – 5206
    Helixi549 – 55911
    Beta strandi563 – 5653
    Helixi569 – 5779
    Helixi579 – 5824
    Helixi586 – 5883
    Helixi589 – 5935
    Helixi601 – 61212
    Helixi615 – 6195
    Helixi624 – 6296
    Helixi638 – 64811
    Helixi653 – 66614
    Helixi667 – 6693
    Beta strandi671 – 6744
    Helixi676 – 68712
    Helixi689 – 70517
    Turni707 – 7093
    Helixi710 – 72112
    Helixi726 – 74823
    Helixi750 – 7534
    Beta strandi754 – 7563
    Helixi761 – 77616
    Beta strandi783 – 7853
    Beta strandi788 – 7969
    Helixi798 – 8003
    Beta strandi805 – 8084
    Beta strandi811 – 8188
    Beta strandi828 – 8369
    Helixi839 – 85719
    Beta strandi869 – 8735
    Beta strandi876 – 8805
    Beta strandi883 – 8875
    Helixi888 – 8958
    Beta strandi898 – 9003
    Helixi906 – 9149
    Helixi918 – 94124
    Helixi949 – 9513
    Beta strandi952 – 9554
    Beta strandi960 – 9623
    Helixi989 – 9946
    Beta strandi998 – 10014
    Helixi1004 – 102118
    Helixi1024 – 103714
    Beta strandi1039 – 10413
    Helixi1045 – 105410
    Turni1055 – 10584
    Helixi1061 – 107818
    Helixi1081 – 109010

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1E7UX-ray2.00A144-1102[»]
    1E7VX-ray2.40A144-1102[»]
    1E8WX-ray2.50A144-1102[»]
    1E8XX-ray2.20A144-1094[»]
    1E90X-ray2.70A144-1102[»]
    ProteinModelPortaliO02697.
    SMRiO02697. Positions 144-1094.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO02697.

    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 biasi17 – 226Poly-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

    HOVERGENiHBG101026.
    KOiK00922.

    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.

    O02697-1 [UniParc]FASTAAdd to Basket

    « Hide

    MELENYEQPV VLREDNRRRR RRMKPRSTAA SLSSMELIPI EFVLPTSQRN     50
    TKTPETALLH VAGHGNVEQM KAQVWLRALE TSVSADFYHR LGPDHFLLLY 100
    QKKGQWYEIY DKYQVVQTLD CLRYWKVLHR SPGQIHVVQR HAPSEETLAF 150
    QRQLNALIGY DVTDVSNVHD DELEFTRRRL VTPRMAEVAG RDPKLYAMHP 200
    WVTSKPLPEY LLKKITNNCV FIVIHRSTTS QTIKVSADDT PGTILQSFFT 250
    KMAKKKSLMD IPESQNERDF VLRVCGRDEY LVGETPIKNF QWVRQCLKNG 300
    EEIHLVLDTP PDPALDEVRK EEWPLVDDCT GVTGYHEQLT IHGKDHESVF 350
    TVSLWDCDRK FRVKIRGIDI PVLPRTADLT VFVEANIQYG QQVLCQRRTS 400
    PKPFTEEVLW NVWLEFSIKI KDLPKGALLN LQIYCGKAPA LSGKTSAEMP 450
    SPESKGKAQL LYYVNLLLID HRFLLRHGEY VLHMWQLSGK GEDQGSFNAD 500
    KLTSRTNPDK ENSMSISILL DNYCHPIALP KHRPTPDPEG DRVRAEMPNQ 550
    LRKQLEAIIA TDPLNPLTAE DKELLWHFRY ESLKDPKAYP KLFSSVKWGQ 600
    QEIVAKTYQL LAKREVWDQS ALDVGLTMQL LDCNFSDENV RAIAVQKLES 650
    LEDDDVLHYL LQLVQAVKFE PYHDSALARF LLKRGLRNKR IGHFLFWFLR 700
    SEIAQSRHYQ QRFAVILEAY LRGCGTAMLH DFTQQVQVID MLQKVTIDIK 750
    SLSAEKYDVS SQVISQLKQK LENLQNLNLP QSFRVPYDPG LKAGALVIEK 800
    CKVMASKKKP LWLEFKCADP TALSNETIGI IFKHGDDLRQ DMLILQILRI 850
    MESIWETESL DLCLLPYGCI STGDKIGMIE IVKDATTIAK IQQSTVGNTG 900
    AFKDEVLSHW LKEKCPIEEK FQAAVERFVY SCAGYCVATF VLGIGDRHND 950
    NIMISETGNL FHIDFGHILG NYKSFLGINK ERVPFVLTPD FLFVMGTSGK 1000
    KTSLHFQKFQ DVCVKAYLAL RHHTNLLIIL FSMMLMTGMP QLTSKEDIEY 1050
    IRDALTVGKS EEDAKKYFLD QIEVCRDKGW TVQFNWFLHL VLGIKQGEKH 1100
    SA 1102
    Length:1,102
    Mass (Da):126,658
    Last modified:December 15, 1998 - v2
    Checksum:i9E7D4211FD626DFC
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y10743 mRNA. Translation: CAA71731.1.
    RefSeqiNP_999104.1. NM_213939.1.
    UniGeneiSsc.82467.

    Genome annotation databases

    GeneIDi396979.
    KEGGissc:396979.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y10743 mRNA. Translation: CAA71731.1 .
    RefSeqi NP_999104.1. NM_213939.1.
    UniGenei Ssc.82467.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1E7U X-ray 2.00 A 144-1102 [» ]
    1E7V X-ray 2.40 A 144-1102 [» ]
    1E8W X-ray 2.50 A 144-1102 [» ]
    1E8X X-ray 2.20 A 144-1094 [» ]
    1E90 X-ray 2.70 A 144-1102 [» ]
    ProteinModelPortali O02697.
    SMRi O02697. Positions 144-1094.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi O02697. 2 interactions.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 396979.
    KEGGi ssc:396979.

    Organism-specific databases

    CTDi 5294.

    Phylogenomic databases

    HOVERGENi HBG101026.
    KOi K00922.

    Enzyme and pathway databases

    UniPathwayi UPA00220 .
    BRENDAi 2.7.1.137. 6170.
    Reactomei REACT_208233. Synthesis of PIPs at the plasma membrane.
    REACT_208923. G beta:gamma signalling through PI3Kgamma.

    Miscellaneous databases

    EvolutionaryTracei O02697.

    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. "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.

    Entry informationi

    Entry nameiPK3CG_PIG
    AccessioniPrimary (citable) accession number: O02697
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: December 15, 1998
    Last modified: October 1, 2014
    This is version 111 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3