PLCG2_HUMAN
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 03-AUG-2022, entry version 240.
DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 {ECO:0000305};
DE EC=3.1.4.11 {ECO:0000269|PubMed:23000145};
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 {ECO:0000312|HGNC:HGNC:9066};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 human
RT 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 across
RT 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., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., 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., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 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 project:
RT 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 BY
RP 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 from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-753; TYR-759 AND TYR-1217,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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., Buerckstuemmer T.,
RA 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., Ho J.,
RA Cruse G., Jung M.Y., Gilfillan A.M., Metcalfe D.D., Nelson C., O'Brien M.,
RA Wisch L., Stone K., Douek D.C., Gandhi C., Wanderer A.A., Lee H.,
RA Nelson S.F., Shianna K.V., Cirulli E.T., Goldstein D.B., Long E.O.,
RA Moir S., Meffre E., Holland S.M., Kastner D.L., Katan M., Hoffman H.M.,
RA 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, CATALYTIC ACTIVITY, FUNCTION, AND CHARACTERIZATION
RP OF 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., Martins M.S.,
RA Bunney T.D., Santich B.H., Moir S., Kuhns D.B., Long Priel D.A.,
RA Ombrello A., Stone D., Ombrello M.J., Khan J., Milner J.D., Kastner D.L.,
RA Aksentijevich I.;
RT "A hypermorphic missense mutation in PLCG2, encoding phospholipase Cgamma2,
RT 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., Ruppert A.S.,
RA Xue L., Li D.H., Steggerda S.M., Versele M., Dave S.S., Zhang J.,
RA Yilmaz A.S., Jaglowski S.M., Blum K.A., Lozanski A., Lozanski G.,
RA James D.F., Barrientos J.C., Lichter P., Stilgenbauer S., Buggy J.J.,
RA 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 mediated
CC by activated phosphatidylinositol-specific phospholipase C enzymes. It
CC is a crucial enzyme in transmembrane signaling.
CC {ECO:0000269|PubMed:23000145}.
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 1,2-
CC diacyl-sn-glycerol + H(+); Xref=Rhea:RHEA:33179, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17815, ChEBI:CHEBI:58456,
CC ChEBI:CHEBI:203600; EC=3.1.4.11;
CC Evidence={ECO:0000269|PubMed:23000145};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33180;
CC Evidence={ECO:0000305|PubMed:23000145};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC -!- SUBUNIT: Interacts (via SH2 domain) with CSF1R (tyrosine
CC phosphorylated). Interacts constitutively with THEMIS2.
CC {ECO:0000250|UniProtKB:Q8CIH5}.
CC -!- INTERACTION:
CC P16885; P10275: AR; NbExp=6; IntAct=EBI-617403, EBI-608057;
CC P16885; P00533: EGFR; NbExp=6; IntAct=EBI-617403, EBI-297353;
CC P16885; P19235: EPOR; NbExp=3; IntAct=EBI-617403, EBI-617321;
CC P16885; P04626: ERBB2; NbExp=3; IntAct=EBI-617403, EBI-641062;
CC P16885; O95073-2: FSBP; NbExp=2; IntAct=EBI-617403, EBI-10696047;
CC P16885; Q13480: GAB1; NbExp=15; IntAct=EBI-617403, EBI-517684;
CC P16885; P10721: KIT; NbExp=8; IntAct=EBI-617403, EBI-1379503;
CC P16885; O43242: PSMD3; NbExp=2; IntAct=EBI-617403, EBI-357622;
CC P16885; 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-induced
CC activation of a variety of growth factor receptors and immune system
CC receptors. Phosphorylation leads to increased phospholipase activity.
CC {ECO:0000250|UniProtKB:Q8CIH5, 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 by
CC the development of cutaneous urticaria, erythema, and pruritis in
CC 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 caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Autoinflammation, antibody deficiency, and immune
CC dysregulation (APLAID) [MIM:614878]: An autosomal dominant systemic
CC disorder characterized by recurrent blistering skin lesions with a
CC dense inflammatory infiltrate and variable involvement of other
CC tissues, including joints, the eye, and the gastrointestinal tract.
CC Affected individuals have a mild humoral immune deficiency associated
CC with recurrent sinopulmonary infections, but no evidence of circulating
CC autoantibodies. {ECO:0000269|PubMed:23000145}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA60112.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAQ76815.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAD92151.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA32194.1; Type=Frameshift; 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 AlphaFoldDB; P16885; -.
DR BMRB; P16885; -.
DR SMR; P16885; -.
DR BioGRID; 111352; 69.
DR CORUM; P16885; -.
DR IntAct; P16885; 68.
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 Antibodypedia; 3797; 1047 antibodies from 43 providers.
DR DNASU; 5336; -.
DR Ensembl; ENST00000564138.6; ENSP00000482457.1; ENSG00000197943.11.
DR GeneID; 5336; -.
DR KEGG; hsa:5336; -.
DR MANE-Select; ENST00000564138.6; ENSP00000482457.1; NM_002661.5; NP_002652.2.
DR UCSC; uc002fgt.4; human.
DR CTD; 5336; -.
DR DisGeNET; 5336; -.
DR GeneCards; PLCG2; -.
DR HGNC; HGNC:9066; PLCG2.
DR HPA; ENSG00000197943; Group enriched (brain, choroid plexus).
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 VEuPathDB; HostDB:ENSG00000197943; -.
DR eggNOG; KOG1264; Eukaryota.
DR GeneTree; ENSGT00940000157517; -.
DR HOGENOM; CLU_002738_5_1_1; -.
DR InParanoid; P16885; -.
DR OMA; QQRYMAR; -.
DR OrthoDB; 368239at2759; -.
DR PhylomeDB; P16885; -.
DR TreeFam; TF313216; -.
DR BioCyc; MetaCyc:HS06773-MON; -.
DR BRENDA; 3.1.4.11; 2681.
DR PathwayCommons; P16885; -.
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-202433; Generation of second messenger molecules.
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-9664323; FCGR3A-mediated IL10 synthesis.
DR Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR SignaLink; P16885; -.
DR SIGNOR; P16885; -.
DR BioGRID-ORCS; 5336; 10 hits in 1078 CRISPR screens.
DR ChiTaRS; PLCG2; human.
DR EvolutionaryTrace; P16885; -.
DR GeneWiki; PLCG2; -.
DR GenomeRNAi; 5336; -.
DR Pharos; P16885; Tchem.
DR PRO; PR:P16885; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P16885; protein.
DR Bgee; ENSG00000197943; Expressed in renal glomerulus and 159 other tissues.
DR ExpressionAtlas; P16885; baseline and differential.
DR Genevisible; P16885; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:ARUK-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0097708; C:intracellular vesicle; IDA:ARUK-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IDA:ARUK-UCL.
DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; IDA:UniProtKB.
DR GO; GO:0004629; F:phospholipase C activity; TAS:Reactome.
DR GO; GO:0140031; F:phosphorylation-dependent protein binding; IEA:Ensembl.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:CAFA.
DR GO; GO:0019901; F:protein kinase binding; IPI:ARUK-UCL.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IPI:ARUK-UCL.
DR GO; GO:0097110; F:scaffold protein binding; IPI:ARUK-UCL.
DR GO; GO:0032237; P:activation of store-operated calcium channel activity; IEA:Ensembl.
DR GO; GO:0061760; P:antifungal innate immune response; ISS:ARUK-UCL.
DR GO; GO:0030183; P:B cell differentiation; ISS:UniProtKB.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IDA:ARUK-UCL.
DR GO; GO:0019722; P:calcium-mediated signaling; IMP:ARUK-UCL.
DR GO; GO:0001775; P:cell activation; ISS:ARUK-UCL.
DR GO; GO:0071277; P:cellular response to calcium ion; IMP:ARUK-UCL.
DR GO; GO:1990858; P:cellular response to lectin; ISS:ARUK-UCL.
DR GO; GO:0071396; P:cellular response to lipid; IMP:ARUK-UCL.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0002316; P:follicular B cell differentiation; IEA:Ensembl.
DR GO; GO:0032959; P:inositol trisphosphate biosynthetic process; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:ARUK-UCL.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IMP:ARUK-UCL.
DR GO; GO:0002281; P:macrophage activation involved in immune response; ISS:ARUK-UCL.
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:0009395; P:phospholipid catabolic process; IEA:InterPro.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; ISS:ARUK-UCL.
DR GO; GO:1902808; P:positive regulation of cell cycle G1/S phase transition; ISS:ARUK-UCL.
DR GO; GO:0002732; P:positive regulation of dendritic cell cytokine production; ISS:ARUK-UCL.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISS:ARUK-UCL.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IBA:GO_Central.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:1903721; P:positive regulation of I-kappaB phosphorylation; ISS:ARUK-UCL.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISS:ARUK-UCL.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISS:ARUK-UCL.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; ISS:ARUK-UCL.
DR GO; GO:0032747; P:positive regulation of interleukin-23 production; ISS:ARUK-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:ARUK-UCL.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; ISS:ARUK-UCL.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:ARUK-UCL.
DR GO; GO:0150078; P:positive regulation of neuroinflammatory response; IMP:ARUK-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:ARUK-UCL.
DR GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; IMP:ARUK-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:ARUK-UCL.
DR GO; GO:0060100; P:positive regulation of phagocytosis, engulfment; IMP:ARUK-UCL.
DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; ISS:ARUK-UCL.
DR GO; GO:0002092; P:positive regulation of receptor internalization; IEA:Ensembl.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:ARUK-UCL.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IEA:Ensembl.
DR GO; GO:0012501; P:programmed cell death; IEA:Ensembl.
DR GO; GO:0070884; P:regulation of calcineurin-NFAT signaling cascade; ISS:ARUK-UCL.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; ISS:ARUK-UCL.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IMP:ARUK-UCL.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IDA:UniProtKB.
DR GO; GO:0048678; P:response to axon injury; IMP:ARUK-UCL.
DR GO; GO:0001878; P:response to yeast; ISS:ARUK-UCL.
DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; ISS:ARUK-UCL.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; ISS:ARUK-UCL.
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; -; 1.
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; SSF49562; SSF49562; 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; Disease variant; Hydrolase; Lipid degradation;
KW Lipid metabolism; Phosphoprotein; Reference proteome; Repeat; SH2 domain;
KW SH3 domain; Transducer.
FT CHAIN 1..1265
FT /note="1-phosphatidylinositol 4,5-bisphosphate
FT phosphodiesterase gamma-2"
FT /id="PRO_0000088501"
FT DOMAIN 20..131
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 312..456
FT /note="PI-PLC X-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270"
FT DOMAIN 532..635
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 646..735
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 769..829
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 930..1044
FT /note="PI-PLC Y-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00271"
FT DOMAIN 1038..1169
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT ACT_SITE 327
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270"
FT ACT_SITE 372
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270"
FT MOD_RES 753
FT /note="Phosphotyrosine; by BTK"
FT /evidence="ECO:0000269|PubMed:11606584,
FT ECO:0000269|PubMed:12181444, ECO:0007744|PubMed:19690332"
FT MOD_RES 759
FT /note="Phosphotyrosine; by BTK"
FT /evidence="ECO:0000269|PubMed:11606584,
FT ECO:0000269|PubMed:12181444, ECO:0007744|PubMed:19690332"
FT MOD_RES 1197
FT /note="Phosphotyrosine; by BTK"
FT /evidence="ECO:0000250|UniProtKB:P24135"
FT MOD_RES 1217
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 1245
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15144186"
FT VARIANT 244
FT /note="H -> R (in dbSNP:rs11548656)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_031560"
FT VARIANT 268
FT /note="R -> W (in dbSNP:rs1143687)"
FT /id="VAR_031561"
FT VARIANT 541
FT /note="T -> A (in dbSNP:rs11548657)"
FT /id="VAR_047427"
FT VARIANT 665
FT /note="R -> W (found in patients with chronic lymphocytic
FT leukemia; associated with BTK mutation S-481; unknown
FT pathological significance; results in resistance to
FT ibrutinib therapy; dbSNP:rs1057519831)"
FT /evidence="ECO:0000269|PubMed:24869598"
FT /id="VAR_074310"
FT VARIANT 707
FT /note="S -> Y (in APLAID; results in increased epidermal
FT growth factor-stimulated production of intracellular IP3
FT and increased intracellular calcium release; is a
FT hypermorphic mutation; dbSNP:rs397514562)"
FT /evidence="ECO:0000269|PubMed:23000145"
FT /id="VAR_069211"
FT VARIANT 845
FT /note="L -> F (found in patients with chronic lymphocytic
FT leukemia; associated with BTK mutation S-481; unknown
FT pathological significance; results in resistance to
FT ibrutinib therapy; dbSNP:rs1057519832)"
FT /evidence="ECO:0000269|PubMed:24869598"
FT /id="VAR_074311"
FT VARIANT 883
FT /note="D -> Y (in dbSNP:rs17856213)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_047428"
FT CONFLICT 606..610
FT /note="TFSSI -> RFRRM (in Ref. 1; CAA32194/AAA60112 and 3;
FT AAQ76815)"
FT /evidence="ECO:0000305"
FT CONFLICT 623
FT /note="R -> P (in Ref. 1; AAA60112/CAA32194 and 3;
FT AAQ76815)"
FT /evidence="ECO:0000305"
FT CONFLICT 745
FT /note="M -> T (in Ref. 1; AAA60112/CAA32194 and 3;
FT AAQ76815)"
FT /evidence="ECO:0000305"
FT CONFLICT 880
FT /note="Q -> E (in Ref. 1; AAA60112/CAA32194 and 3;
FT AAQ76815)"
FT /evidence="ECO:0000305"
FT CONFLICT 912
FT /note="T -> S (in Ref. 1; AAA60112/CAA32194 and 3;
FT AAQ76815)"
FT /evidence="ECO:0000305"
FT CONFLICT 1095
FT /note="D -> G (in Ref. 1; AAA60112/CAA32194 and 3;
FT AAQ76815)"
FT /evidence="ECO:0000305"
FT TURN 815..817
FT /evidence="ECO:0007829|PDB:2W2X"
FT STRAND 818..825
FT /evidence="ECO:0007829|PDB:2W2X"
FT STRAND 828..831
FT /evidence="ECO:0007829|PDB:2W2X"
FT HELIX 835..840
FT /evidence="ECO:0007829|PDB:2W2X"
FT STRAND 850..854
FT /evidence="ECO:0007829|PDB:2W2X"
FT HELIX 855..857
FT /evidence="ECO:0007829|PDB:2W2X"
FT STRAND 858..862
FT /evidence="ECO:0007829|PDB:2W2X"
FT STRAND 867..869
FT /evidence="ECO:0007829|PDB:2K2J"
FT STRAND 870..882
FT /evidence="ECO:0007829|PDB:2W2X"
FT STRAND 886..892
FT /evidence="ECO:0007829|PDB:2W2X"
FT HELIX 893..907
FT /evidence="ECO:0007829|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
