ID PLCG2_HUMAN Reviewed; 1265 AA. AC P16885; D3DUL3; Q3ZTS2; Q59H45; Q969T5; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 4. DT 18-SEP-2019, entry version 224. DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2; DE EC=3.1.4.11; DE AltName: Full=Phosphoinositide phospholipase C-gamma-2; DE AltName: Full=Phospholipase C-IV; DE Short=PLC-IV; DE AltName: Full=Phospholipase C-gamma-2; DE Short=PLC-gamma-2; 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 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 GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] 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 [7] RP PHOSPHORYLATION AT TYR-753 AND TYR-759. RX PubMed=11606584; DOI=10.1074/jbc.m107577200; RA Rodriguez R., Matsuda M., Perisic O., Bravo J., Paul A., Jones N.P., RA Light Y., Swann K., Williams R.L., Katan M.; RT "Tyrosine residues in phospholipase Cgamma 2 essential for the enzyme RT function in B-cell signaling."; RL J. Biol. Chem. 276:47982-47992(2001). RN [8] RP PHOSPHORYLATION AT TYR-753 AND TYR-759. RX 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 [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1245, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic 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 [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-753; TYR-759 AND RP TYR-1217, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [12] RP INVOLVEMENT IN FCAS3. RX PubMed=22236196; DOI=10.1056/nejmoa1102140; RA Ombrello M.J., Remmers E.F., Sun G., Freeman A.F., Datta S., RA Torabi-Parizi P., Subramanian N., Bunney T.D., Baxendale R.W., RA Martins M.S., Romberg N., Komarow H., Aksentijevich I., Kim H.S., RA Ho J., Cruse G., Jung M.Y., Gilfillan A.M., Metcalfe D.D., Nelson C., RA O'Brien M., Wisch L., Stone K., Douek D.C., Gandhi C., Wanderer A.A., RA Lee H., Nelson S.F., Shianna K.V., Cirulli E.T., Goldstein D.B., RA Long E.O., Moir S., Meffre E., Holland S.M., Kastner D.L., Katan M., RA Hoffman H.M., Milner J.D.; RT "Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 RT deletions."; RL N. Engl. J. Med. 366:330-338(2012). RN [13] RP VARIANT APLAID TYR-707. RX PubMed=23000145; DOI=10.1016/j.ajhg.2012.08.006; RA Zhou Q., Lee G.S., Brady J., Datta S., Katan M., Sheikh A., RA Martins M.S., Bunney T.D., Santich B.H., Moir S., Kuhns D.B., RA Long Priel D.A., Ombrello A., Stone D., Ombrello M.J., Khan J., RA Milner J.D., Kastner D.L., Aksentijevich I.; RT "A hypermorphic missense mutation in PLCG2, encoding phospholipase RT Cgamma2, causes a dominantly inherited autoinflammatory disease with RT immunodeficiency."; RL Am. J. Hum. Genet. 91:713-720(2012). RN [14] RP VARIANTS TRP-665 AND PHE-845. RX PubMed=24869598; DOI=10.1056/nejmoa1400029; RA Woyach J.A., Furman R.R., Liu T.M., Ozer H.G., Zapatka M., RA Ruppert A.S., Xue L., Li D.H., Steggerda S.M., Versele M., Dave S.S., RA Zhang J., Yilmaz A.S., Jaglowski S.M., Blum K.A., Lozanski A., RA Lozanski G., James D.F., Barrientos J.C., Lichter P., Stilgenbauer S., RA Buggy J.J., Chang B.Y., Johnson A.J., Byrd J.C.; RT "Resistance mechanisms for the Bruton's tyrosine kinase inhibitor RT ibrutinib."; RL N. Engl. J. Med. 370:2286-2294(2014). 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: CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5- CC bisphosphate) + H2O = 1D-myo-inositol 1,4,5-trisphosphate + a CC 1,2-diacyl-sn-glycerol + H(+); Xref=Rhea:RHEA:33179, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17815, CC ChEBI:CHEBI:58456, ChEBI:CHEBI:203600; EC=3.1.4.11; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC -!- SUBUNIT: Interacts (via SH2 domain) with CSF1R (tyrosine CC phosphorylated). {ECO:0000250}. CC -!- INTERACTION: CC P10275:AR; NbExp=6; IntAct=EBI-617403, EBI-608057; CC P00533:EGFR; NbExp=5; IntAct=EBI-617403, EBI-297353; CC P19235:EPOR; NbExp=3; IntAct=EBI-617403, EBI-617321; CC P04626:ERBB2; NbExp=3; IntAct=EBI-617403, EBI-641062; CC O95073-2:FSBP; NbExp=2; IntAct=EBI-617403, EBI-10696047; CC Q13480:GAB1; NbExp=15; IntAct=EBI-617403, EBI-517684; CC P10721:KIT; NbExp=8; IntAct=EBI-617403, EBI-1379503; CC P27986:PIK3R1; NbExp=2; IntAct=EBI-617403, EBI-79464; CC O43242:PSMD3; NbExp=2; IntAct=EBI-617403, EBI-357622; CC O14796:SH2D1B; NbExp=2; IntAct=EBI-617403, EBI-3923013; CC -!- PTM: Phosphorylated on tyrosine residues by CSF1R (By similarity). CC Phosphorylated on tyrosine residues by BTK and SYK; upon ligand- CC induced activation of a variety of growth factor receptors and CC immune system receptors. Phosphorylation leads to increased CC phospholipase activity. {ECO:0000250, ECO:0000269|PubMed:11606584, CC ECO:0000269|PubMed:12181444}. CC -!- DISEASE: Familial cold autoinflammatory syndrome 3 (FCAS3) CC [MIM:614468]: An autosomal dominant immune disorder characterized CC by the development of cutaneous urticaria, erythema, and pruritis CC in response to cold exposure. Affected individuals have variable CC additional immunologic defects, including antibody deficiency, CC decreased numbers of B-cells, defective B-cells, increased CC susceptibility to infection, and increased risk of autoimmune CC disorders. {ECO:0000269|PubMed:22236196}. Note=The disease is CC caused by mutations affecting the gene represented in this entry. CC -!- DISEASE: Autoinflammation, antibody deficiency, and immune CC dysregulation PLCG2-associated (APLAID) [MIM:614878]: An autosomal CC dominant systemic disorder characterized by recurrent blistering CC skin lesions with a dense inflammatory infiltrate and variable CC involvement of other tissues, including joints, the eye, and the CC gastrointestinal tract. Affected individuals have a mild humoral CC immune deficiency associated with recurrent sinopulmonary CC infections, but no evidence of circulating autoantibodies. CC {ECO:0000269|PubMed:23000145}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAA60112.1; Type=Frameshift; Positions=1242; Evidence={ECO:0000305}; CC Sequence=AAQ76815.1; Type=Frameshift; Positions=1242; Evidence={ECO:0000305}; CC Sequence=BAD92151.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC Sequence=CAA32194.1; Type=Frameshift; Positions=1242; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; CH471114; EAW95524.1; -; Genomic_DNA. DR EMBL; CH471114; EAW95525.1; -; 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 CCDS; CCDS42204.1; -. DR PIR; S02004; S02004. DR RefSeq; NP_002652.2; NM_002661.4. DR PDB; 2K2J; NMR; -; A=471-514, A=841-913. DR PDB; 2W2W; X-ray; 2.80 A; A/B/C/D/E/F/G/H/I/J/K/L=471-514, A/B/C/D/E/F/G/H/I/J/K/L=841-913. DR PDB; 2W2X; X-ray; 2.30 A; C/D=471-514, C/D=841-913. DR PDBsum; 2K2J; -. DR PDBsum; 2W2W; -. DR PDBsum; 2W2X; -. DR SMR; P16885; -. DR BioGrid; 111352; 49. DR CORUM; P16885; -. DR IntAct; P16885; 38. DR MINT; P16885; -. DR STRING; 9606.ENSP00000482457; -. DR BindingDB; P16885; -. DR ChEMBL; CHEMBL4100; -. DR GuidetoPHARMACOLOGY; 1408; -. DR SwissLipids; SLP:000000647; -. DR MoonDB; P16885; Predicted. DR iPTMnet; P16885; -. DR PhosphoSitePlus; P16885; -. DR BioMuta; PLCG2; -. DR DMDM; 215274231; -. DR EPD; P16885; -. DR jPOST; P16885; -. DR MassIVE; P16885; -. DR MaxQB; P16885; -. DR PaxDb; P16885; -. DR PeptideAtlas; P16885; -. DR PRIDE; P16885; -. DR ProteomicsDB; 53400; -. DR DNASU; 5336; -. DR GeneID; 5336; -. DR KEGG; hsa:5336; -. DR UCSC; uc002fgt.4; human. DR CTD; 5336; -. DR DisGeNET; 5336; -. DR GeneCards; PLCG2; -. DR HGNC; HGNC:9066; PLCG2. DR HPA; CAB004280; -. DR HPA; HPA020099; -. DR HPA; HPA020100; -. DR MalaCards; PLCG2; -. DR MIM; 600220; gene. DR MIM; 614468; phenotype. DR MIM; 614878; phenotype. DR neXtProt; NX_P16885; -. DR OpenTargets; ENSG00000197943; -. DR Orphanet; 324530; Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation. DR Orphanet; 300359; PLCG2-associated antibody deficiency and immune dysregulation. DR PharmGKB; PA33393; -. DR eggNOG; KOG1264; Eukaryota. DR eggNOG; ENOG410XPXE; LUCA. DR GeneTree; ENSGT00940000157517; -. DR HOGENOM; HOG000230864; -. DR InParanoid; P16885; -. DR KO; K05859; -. DR OMA; PWYYDGL; -. DR OrthoDB; 368239at2759; -. DR PhylomeDB; P16885; -. DR TreeFam; TF313216; -. DR BioCyc; MetaCyc:HS06773-MONOMER; -. DR BRENDA; 3.1.4.11; 2681. DR Reactome; R-HSA-114604; GPVI-mediated activation cascade. DR Reactome; R-HSA-166016; Toll Like Receptor 4 (TLR4) Cascade. DR Reactome; R-HSA-1855204; Synthesis of IP3 and IP4 in the cytosol. DR Reactome; R-HSA-2029485; Role of phospholipids in phagocytosis. DR Reactome; R-HSA-2424491; DAP12 signaling. DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation. DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization. DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling. DR Reactome; R-HSA-5621480; Dectin-2 family. DR Reactome; R-HSA-9027277; Erythropoietin activates Phospholipase C gamma (PLCG). DR Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers. DR SignaLink; P16885; -. DR SIGNOR; P16885; -. DR EvolutionaryTrace; P16885; -. DR GeneWiki; PLCG2; -. DR GenomeRNAi; 5336; -. DR Pharos; P16885; -. DR PRO; PR:P16885; -. DR Proteomes; UP000005640; Chromosome 16. DR Bgee; ENSG00000197943; Expressed in 204 organ(s), highest expression level in renal glomerulus. DR ExpressionAtlas; P16885; baseline and differential. DR Genevisible; P16885; HS. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; IDA:UniProtKB. DR GO; GO:0004629; F:phospholipase C activity; TAS:Reactome. DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:CAFA. DR GO; GO:0032237; P:activation of store-operated calcium channel activity; IEA:Ensembl. DR GO; GO:0030183; P:B cell differentiation; ISS:UniProtKB. DR GO; GO:0050853; P:B cell receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0019722; P:calcium-mediated signaling; NAS:UniProtKB. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome. DR GO; GO:0002316; P:follicular B cell differentiation; IEA:Ensembl. DR GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome. DR GO; GO:0032959; P:inositol trisphosphate biosynthetic process; IBA:GO_Central. DR GO; GO:0043069; P:negative regulation of programmed cell death; IEA:Ensembl. DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; IDA:UniProtKB. DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IBA:GO_Central. DR GO; GO:0009395; P:phospholipid catabolic process; IEA:InterPro. DR GO; GO:0030168; P:platelet activation; TAS:Reactome. DR GO; GO:0002092; P:positive regulation of receptor internalization; IEA:Ensembl. DR GO; GO:0032481; P:positive regulation of type I interferon production; IEA:Ensembl. DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl. DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IDA:UniProtKB. DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; TAS:Reactome. DR GO; GO:0050852; P:T cell receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0016055; P:Wnt signaling pathway; TAS:UniProtKB. DR CDD; cd09932; SH2_C-SH2_PLC_gamma_like; 1. DR CDD; cd10341; SH2_N-SH2_PLC_gamma_like; 1. DR CDD; cd11969; SH3_PLCgamma2; 1. DR Gene3D; 2.30.29.30; -; 2. DR Gene3D; 2.60.40.150; -; 1. DR Gene3D; 3.20.20.190; -; 2. DR Gene3D; 3.30.505.10; -; 2. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR InterPro; IPR001192; PI-PLC_fam. DR InterPro; IPR016279; PLC-gamma. DR InterPro; IPR028381; PLC-gamma2. DR InterPro; IPR035023; PLC-gamma_C-SH2. DR InterPro; IPR035024; PLC-gamma_N-SH2. DR InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl. DR InterPro; IPR035723; PLCgamma2_SH3. DR InterPro; IPR000909; PLipase_C_PInositol-sp_X_dom. DR InterPro; IPR001711; PLipase_C_Pinositol-sp_Y. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR PANTHER; PTHR10336; PTHR10336; 1. DR PANTHER; PTHR10336:SF25; PTHR10336:SF25; 1. DR Pfam; PF00168; C2; 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 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 SUPFAM; SSF47473; SSF47473; 1. DR SUPFAM; SSF50044; SSF50044; 1. DR SUPFAM; SSF51695; SSF51695; 1. DR SUPFAM; SSF55550; SSF55550; 2. 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 3D-structure; Calcium; Complete proteome; Disease mutation; Hydrolase; KW Lipid degradation; Lipid metabolism; Phosphoprotein; Polymorphism; KW Reference proteome; 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. {ECO:0000255|PROSITE- FT ProRule:PRU00145}. FT DOMAIN 312 456 PI-PLC X-box. {ECO:0000255|PROSITE- FT ProRule:PRU00270}. FT DOMAIN 532 635 SH2 1. {ECO:0000255|PROSITE- FT ProRule:PRU00191}. FT DOMAIN 646 735 SH2 2. {ECO:0000255|PROSITE- FT ProRule:PRU00191}. FT DOMAIN 769 829 SH3. {ECO:0000255|PROSITE- FT ProRule:PRU00192}. FT DOMAIN 930 1044 PI-PLC Y-box. {ECO:0000255|PROSITE- FT ProRule:PRU00271}. FT DOMAIN 1059 1152 C2. {ECO:0000255|PROSITE- FT ProRule:PRU00041}. FT ACT_SITE 327 327 {ECO:0000255|PROSITE-ProRule:PRU00270}. FT ACT_SITE 372 372 {ECO:0000255|PROSITE-ProRule:PRU00270}. FT MOD_RES 753 753 Phosphotyrosine; by BTK. FT {ECO:0000244|PubMed:19690332, FT ECO:0000269|PubMed:11606584, FT ECO:0000269|PubMed:12181444}. FT MOD_RES 759 759 Phosphotyrosine; by BTK. FT {ECO:0000244|PubMed:19690332, FT ECO:0000269|PubMed:11606584, FT ECO:0000269|PubMed:12181444}. FT MOD_RES 1197 1197 Phosphotyrosine; by BTK. FT {ECO:0000250|UniProtKB:P24135}. FT MOD_RES 1217 1217 Phosphotyrosine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 1245 1245 Phosphotyrosine. FT {ECO:0000244|PubMed:15144186}. FT VARIANT 244 244 H -> R (in dbSNP:rs11548656). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_031560. FT VARIANT 268 268 R -> W (in dbSNP:rs1143687). FT /FTId=VAR_031561. FT VARIANT 541 541 T -> A (in dbSNP:rs11548657). FT /FTId=VAR_047427. FT VARIANT 665 665 R -> W (found in patients with chronic FT lymphocytic leukemia; associated with BTK FT mutation S-481; unknown pathological FT significance; results in resistance to FT ibrutinib therapy; dbSNP:rs1057519831). FT {ECO:0000269|PubMed:24869598}. FT /FTId=VAR_074310. FT VARIANT 707 707 S -> Y (in APLAID; results in increased FT epidermal growth factor-stimulated FT production of intracellular IP3 and FT increased intracellular calcium release; FT is a hypermorphic mutation; FT dbSNP:rs397514562). FT {ECO:0000269|PubMed:23000145}. FT /FTId=VAR_069211. FT VARIANT 845 845 L -> F (found in patients with chronic FT lymphocytic leukemia; associated with BTK FT mutation S-481; unknown pathological FT significance; results in resistance to FT ibrutinib therapy; dbSNP:rs1057519832). FT {ECO:0000269|PubMed:24869598}. FT /FTId=VAR_074311. FT VARIANT 883 883 D -> Y (in dbSNP:rs17856213). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_047428. FT CONFLICT 606 610 TFSSI -> RFRRM (in Ref. 1; CAA32194/ FT AAA60112 and 3; AAQ76815). {ECO:0000305}. FT CONFLICT 623 623 R -> P (in Ref. 1; AAA60112/CAA32194 and FT 3; AAQ76815). {ECO:0000305}. FT CONFLICT 745 745 M -> T (in Ref. 1; AAA60112/CAA32194 and FT 3; AAQ76815). {ECO:0000305}. FT CONFLICT 880 880 Q -> E (in Ref. 1; AAA60112/CAA32194 and FT 3; AAQ76815). {ECO:0000305}. FT CONFLICT 912 912 T -> S (in Ref. 1; AAA60112/CAA32194 and FT 3; AAQ76815). {ECO:0000305}. FT CONFLICT 1095 1095 D -> G (in Ref. 1; AAA60112/CAA32194 and FT 3; AAQ76815). {ECO:0000305}. FT STRAND 478 485 {ECO:0000244|PDB:2W2X}. FT TURN 815 817 {ECO:0000244|PDB:2W2X}. FT STRAND 818 825 {ECO:0000244|PDB:2W2X}. FT STRAND 828 831 {ECO:0000244|PDB:2W2X}. FT HELIX 835 840 {ECO:0000244|PDB:2W2X}. FT STRAND 850 854 {ECO:0000244|PDB:2W2X}. FT HELIX 855 857 {ECO:0000244|PDB:2W2X}. FT STRAND 858 862 {ECO:0000244|PDB:2W2X}. FT STRAND 867 869 {ECO:0000244|PDB:2K2J}. FT STRAND 870 882 {ECO:0000244|PDB:2W2X}. FT STRAND 886 892 {ECO:0000244|PDB:2W2X}. FT HELIX 893 907 {ECO:0000244|PDB:2W2X}. 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 //