ID   PLCG2_HUMAN             Reviewed;        1265 AA.
AC   P16885; Q3ZTS2; Q59H45; Q969T5;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   25-NOV-2008, sequence version 4.
DT   16-DEC-2008, entry version 108.
DE   RecName: Full=1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-2;
DE            EC=3.1.4.11;
DE   AltName: Full=Phosphoinositide phospholipase C;
DE   AltName: Full=Phospholipase C-gamma-2;
DE            Short=PLC-gamma-2;
DE   AltName: Full=PLC-IV;
GN   Name=PLCG2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Lymphoblast;
RX   MEDLINE=89078616; PubMed=2849563; DOI=10.1016/0014-5793(88)80979-7;
RA   Ohta S., Matsui A., Nazawa Y., Kagawa Y.;
RT   "Complete cDNA encoding a putative phospholipase C from transformed
RT   human lymphocytes.";
RL   FEBS Lett. 242:31-35(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Spleen;
RA   Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA   Ohara O., Nagase T., Kikuno R.F.;
RL   Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=16533400; DOI=10.1186/1471-2164-7-48;
RA   Kemmer D., Podowski R.M., Arenillas D., Lim J., Hodges E., Roth P.,
RA   Sonnhammer E.L.L., Hoeoeg C., Wasserman W.W.;
RT   "NovelFam3000 -- uncharacterized human protein domains conserved
RT   across model organisms.";
RL   BMC Genomics 7:48-48(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15616553; DOI=10.1038/nature03187;
RA   Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA   Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA   Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA   Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA   Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA   Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA   Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA   Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA   Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA   Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA   Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA   Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA   Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA   Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA   Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA   Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA   Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA   Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA   Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA   Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA   Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA   Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA   Rubin E.M., Pennacchio L.A.;
RT   "The sequence and analysis of duplication-rich human chromosome 16.";
RL   Nature 432:988-994(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-244 AND
RP   TYR-883.
RC   TISSUE=Lymph;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   PHOSPHORYLATION AT TYR-753 AND TYR-759.
RX   MEDLINE=22169270; PubMed=12181444; DOI=10.1124/mol.62.3.672;
RA   Ozdener F., Dangelmaier C., Ashby B., Kunapuli S.P., Daniel J.L.;
RT   "Activation of phospholipase Cgamma2 by tyrosine phosphorylation.";
RL   Mol. Pharmacol. 62:672-679(2002).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1245, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=T-cell;
RX   PubMed=15144186; DOI=10.1021/ac035352d;
RA   Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA   Peters E.C.;
RT   "Robust phosphoproteomic profiling of tyrosine phosphorylation sites
RT   from human T cells using immobilized metal affinity chromatography and
RT   tandem mass spectrometry.";
RL   Anal. Chem. 76:2763-2772(2004).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-733, AND MASS
RP   SPECTROMETRY.
RX   PubMed=18083107; DOI=10.1016/j.cell.2007.11.025;
RA   Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,
RA   Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,
RA   Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,
RA   Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,
RA   Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
RT   "Global survey of phosphotyrosine signaling identifies oncogenic
RT   kinases in lung cancer.";
RL   Cell 131:1190-1203(2007).
CC   -!- FUNCTION: The production of the second messenger molecules
CC       diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is
CC       mediated by activated phosphatidylinositol-specific phospholipase
CC       C enzymes. It is a crucial enzyme in transmembrane signaling.
CC   -!- CATALYTIC ACTIVITY: 1-phosphatidyl-1D-myo-inositol 4,5-
CC       bisphosphate + H(2)O = 1D-myo-inositol 1,4,5-trisphosphate +
CC       diacylglycerol.
CC   -!- COFACTOR: Calcium.
CC   -!- INTERACTION:
CC       P19235:EPOR; NbExp=3; IntAct=EBI-617403, EBI-617321;
CC       P62993:GRB2; NbExp=1; IntAct=EBI-617403, EBI-401755;
CC       P27986:PIK3R1; NbExp=1; IntAct=EBI-617403, EBI-79464;
CC   -!- PTM: Phosphorylated on tyrosine residues; upon ligand-induced
CC       activation of a variety of growth factor receptors and immune
CC       system receptors. Increases phospholipase activity.
CC   -!- SIMILARITY: Contains 1 C2 domain.
CC   -!- SIMILARITY: Contains 1 PH domain.
CC   -!- SIMILARITY: Contains 1 PI-PLC X-box domain.
CC   -!- SIMILARITY: Contains 1 PI-PLC Y-box domain.
CC   -!- SIMILARITY: Contains 2 SH2 domains.
CC   -!- SIMILARITY: Contains 1 SH3 domain.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA60112.1; Type=Frameshift; Positions=1242;
CC       Sequence=AAQ76815.1; Type=Frameshift; Positions=1242;
CC       Sequence=CAA32194.1; Type=Frameshift; Positions=1242;
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DR   EMBL; M37238; AAA60112.1; ALT_FRAME; mRNA.
DR   EMBL; X14034; CAA32194.1; ALT_FRAME; mRNA.
DR   EMBL; AB208914; BAD92151.1; ALT_INIT; mRNA.
DR   EMBL; AY364256; AAQ76815.1; ALT_FRAME; mRNA.
DR   EMBL; AC092142; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC098966; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC099524; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC007565; AAH07565.1; -; mRNA.
DR   EMBL; BC011772; AAH11772.1; -; mRNA.
DR   EMBL; BC014561; AAH14561.1; -; mRNA.
DR   EMBL; BC018646; AAH18646.1; -; mRNA.
DR   PIR; S02004; S02004.
DR   RefSeq; NP_002652.2; -.
DR   UniGene; Hs.413111; -.
DR   HSSP; P08487; 2PLD.
DR   IntAct; P16885; 3.
DR   PhosphoSite; P16885; -.
DR   PRIDE; P16885; -.
DR   Ensembl; ENSG00000197943; Homo sapiens.
DR   GeneID; 5336; -.
DR   KEGG; hsa:5336; -.
DR   GeneCards; GC16P080370; -.
DR   H-InvDB; HIX0013277; -.
DR   HGNC; HGNC:9066; PLCG2.
DR   HPA; CAB004280; -.
DR   MIM; 600220; gene.
DR   PharmGKB; PA33393; -.
DR   HOGENOM; P16885; -.
DR   HOVERGEN; P16885; -.
DR   Reactome; REACT_604; Hemostasis.
DR   NextBio; 20668; -.
DR   ArrayExpress; P16885; -.
DR   CleanEx; HS_PLCG2; -.
DR   GermOnline; ENSG00000197943; Homo sapiens.
DR   GO; GO:0005886; C:plasma membrane; EXP:Reactome.
DR   GO; GO:0005509; F:calcium ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004435; F:phosphoinositide phospholipase C activity; IEA:InterPro.
DR   GO; GO:0005515; F:protein binding; IPI:IntAct.
DR   GO; GO:0004871; F:signal transducer activity; IEA:InterPro.
DR   GO; GO:0007242; P:intracellular signaling cascade; IEA:InterPro.
DR   GO; GO:0009395; P:phospholipid catabolic process; IEA:InterPro.
DR   InterPro; IPR000008; C2_Ca-dep.
DR   InterPro; IPR001849; PH.
DR   InterPro; IPR011993; PH_type.
DR   InterPro; IPR001192; Phospholipase_C_Pinositol-sp_C.
DR   InterPro; IPR000909; Phospholipase_C_Pinositol-sp_X.
DR   InterPro; IPR001711; Phospholipase_C_Pinositol-sp_Y.
DR   InterPro; IPR016279; PLC-gamma.
DR   InterPro; IPR000980; SH2.
DR   InterPro; IPR001452; SH3.
DR   Gene3D; G3DSA:2.30.29.30; PH_type; 1.
DR   Pfam; PF00168; C2; 1.
DR   Pfam; PF00169; PH; 1.
DR   Pfam; PF00388; PI-PLC-X; 1.
DR   Pfam; PF00387; PI-PLC-Y; 1.
DR   Pfam; PF00017; SH2; 2.
DR   Pfam; PF00018; SH3_1; 1.
DR   PIRSF; PIRSF000952; PLC-gamma; 1.
DR   PRINTS; PR00390; PHPHLIPASEC.
DR   PRINTS; PR00401; SH2DOMAIN.
DR   PRINTS; PR00452; SH3DOMAIN.
DR   ProDom; PD001202; PI_PLC_Y; 2.
DR   ProDom; PD000093; SH2; 2.
DR   ProDom; PD000066; SH3; 1.
DR   SMART; SM00239; C2; 1.
DR   SMART; SM00233; PH; 2.
DR   SMART; SM00148; PLCXc; 1.
DR   SMART; SM00149; PLCYc; 1.
DR   SMART; SM00252; SH2; 2.
DR   SMART; SM00326; SH3; 1.
DR   PROSITE; PS50004; C2; 1.
DR   PROSITE; PS50003; PH_DOMAIN; 1.
DR   PROSITE; PS50007; PIPLC_X_DOMAIN; 1.
DR   PROSITE; PS50008; PIPLC_Y_DOMAIN; 1.
DR   PROSITE; PS50001; SH2; 2.
DR   PROSITE; PS50002; SH3; 1.
PE   1: Evidence at protein level;
KW   Calcium; Hydrolase; Lipid degradation; Phosphoprotein; Polymorphism;
KW   Repeat; SH2 domain; SH3 domain; Transducer.
FT   CHAIN         1   1265       1-phosphatidylinositol-4,5-bisphosphate
FT                                phosphodiesterase gamma-2.
FT                                /FTId=PRO_0000088501.
FT   DOMAIN       20    131       PH.
FT   DOMAIN      312    456       PI-PLC X-box.
FT   DOMAIN      532    635       SH2 1.
FT   DOMAIN      646    735       SH2 2.
FT   DOMAIN      769    829       SH3.
FT   DOMAIN      930   1044       PI-PLC Y-box.
FT   DOMAIN     1059   1152       C2.
FT   ACT_SITE    327    327       By similarity.
FT   ACT_SITE    372    372       By similarity.
FT   MOD_RES     733    733       Phosphotyrosine.
FT   MOD_RES     753    753       Phosphotyrosine.
FT   MOD_RES     759    759       Phosphotyrosine.
FT   MOD_RES    1245   1245       Phosphotyrosine.
FT   VARIANT     244    244       H -> R (in dbSNP:rs11548656).
FT                                /FTId=VAR_031560.
FT   VARIANT     268    268       R -> W (in dbSNP:rs17537869).
FT                                /FTId=VAR_031561.
FT   VARIANT     541    541       T -> A (in dbSNP:rs11548657).
FT                                /FTId=VAR_047427.
FT   VARIANT     883    883       D -> Y (in dbSNP:rs17856213).
FT                                /FTId=VAR_047428.
FT   CONFLICT    606    610       TFSSI -> RFRRM (in Ref. 1; CAA32194/
FT                                AAA60112 and 3; AAQ76815).
FT   CONFLICT    623    623       R -> P (in Ref. 1; AAA60112/CAA32194 and
FT                                3; AAQ76815).
FT   CONFLICT    745    745       M -> T (in Ref. 1; AAA60112/CAA32194 and
FT                                3; AAQ76815).
FT   CONFLICT    880    880       Q -> E (in Ref. 1; AAA60112/CAA32194 and
FT                                3; AAQ76815).
FT   CONFLICT    912    912       T -> S (in Ref. 1; AAA60112/CAA32194 and
FT                                3; AAQ76815).
FT   CONFLICT   1095   1095       D -> G (in Ref. 1; AAA60112/CAA32194 and
FT                                3; AAQ76815).
SQ   SEQUENCE   1265 AA;  147870 MW;  1D56BCBF51D7A0D3 CRC64;
     MSTTVNVDSL AEYEKSQIKR ALELGTVMTV FSFRKSTPER RTVQVIMETR QVAWSKTADK
     IEGFLDIMEI KEIRPGKNSK DFERAKAVRQ KEDCCFTILY GTQFVLSTLS LAADSKEDAV
     NWLSGLKILH QEAMNASTPT IIESWLRKQI YSVDQTRRNS ISLRELKTIL PLINFKVSSA
     KFLKDKFVEI GAHKDELSFE QFHLFYKKLM FEQQKSILDE FKKDSSVFIL GNTDRPDASA
     VYLHDFQRFL IHEQQEHWAQ DLNKVRERMT KFIDDTMRET AEPFLFVDEF LTYLFSRENS
     IWDEKYDAVD MQDMNNPLSH YWISSSHNTY LTGDQLRSES SPEAYIRCLR MGCRCIELDC
     WDGPDGKPVI YHGWTRTTKI KFDDVVQAIK DHAFVTSSFP VILSIEEHCS VEQQRHMAKA
     FKEVFGDLLL TKPTEASADQ LPSPSQLREK IIIKHKKLGP RGDVDVNMED KKDEHKQQGE
     LYMWDSIDQK WTRHYCAIAD AKLSFSDDIE QTMEEEVPQD IPPTELHFGE KWFHKKVEKR
     TSAEKLLQEY CMETGGKDGT FLVRESETFP NDYTLSFWRS GRVQHCRIRS TMEGGTLKYY
     LTDNLTFSSI YALIQHYRET HLRCAEFELR LTDPVPNPNP HESKPWYYDS LSRGEAEDML
     MRIPRDGAFL IRKREGSDSY AITFRARGKV KHCRINRDGR HFVLGTSAYF ESLVELVSYY
     EKHSLYRKMR LRYPVTPELL ERYNMERDIN SLYDVSRMYV DPSEINPSMP QRTVKALYDY
     KAKRSDELSF CRGALIHNVS KEPGGWWKGD YGTRIQQYFP SNYVEDISTA DFEELEKQII
     EDNPLGSLCR GILDLNTYNV VKAPQGKNQK SFVFILEPKQ QGDPPVEFAT DRVEELFEWF
     QSIREITWKI DTKENNMKYW EKNQSIAIEL SDLVVYCKPT SKTKDNLENP DFREIRSFVE
     TKADSIIRQK PVDLLKYNQK GLTRVYPKGQ RVDSSNYDPF RLWLCGSQMV ALNFQTADKY
     MQMNHALFSL NGRTGYVLQP ESMRTEKYDP MPPESQRKIL MTLTVKVLGA RHLPKLGRSI
     ACPFVEVEIC GAEYDNNKFK TTVVNDNGLS PIWAPTQEKV TFEIYDPNLA FLRFVVYEED
     MFSDPNFLAH ATYPIKAVKS GFRSVPLKNG YSEDIELASL LVFCEMRPVL ESEEELYSSC
     RQLRRRQEEL NNQLFLYDTH QNLRNANRDA LVKEFSVNEN QLQLYQEKCN KRLREKRVSN
     SKFYS
//