ID PLCG1_HUMAN Reviewed; 1290 AA. AC P19174; B7ZLY7; B9EGH4; E1P5W4; Q2V575; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1990, sequence version 1. DT 27-MAR-2024, entry version 263. DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 {ECO:0000305}; DE EC=3.1.4.11 {ECO:0000250|UniProtKB:P10686}; DE AltName: Full=PLC-148; DE AltName: Full=Phosphoinositide phospholipase C-gamma-1; DE AltName: Full=Phospholipase C-II; DE Short=PLC-II; DE AltName: Full=Phospholipase C-gamma-1; DE Short=PLC-gamma-1; GN Name=PLCG1 {ECO:0000312|HGNC:HGNC:9065}; Synonyms=PLC1; 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] (ISOFORM 1), AND PHOSPHORYLATION. RC TISSUE=Brain, and Vein; RX PubMed=2167438; DOI=10.1128/mcb.10.9.4770-4777.1990; RA Burgess W.H., Dionne C.A., Kaplow J.M., Mudd R., Friesel R., RA Zilberstein A., Schlessinger J., Jaye M.; RT "Characterization and cDNA cloning of phospholipase C-gamma, a major RT substrate for heparin-binding growth factor 1 (acidic fibroblast growth RT factor)-activated tyrosine kinase."; RL Mol. Cell. Biol. 10:4770-4777(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASN-209; GLY-279; THR-739 RP AND THR-813. RG NIEHS SNPs program; RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP THR-813. RC TISSUE=Brain, and Testis; 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 [6] RP INTERACTION WITH FGFR1. RX PubMed=1656221; DOI=10.1128/mcb.11.10.5068-5078.1991; RA Mohammadi M., Honegger A.M., Rotin D., Fischer R., Bellot F., Li W., RA Dionne C.A., Jaye M., Rubinstein M., Schlessinger J.; RT "A tyrosine-phosphorylated carboxy-terminal peptide of the fibroblast RT growth factor receptor (Flg) is a binding site for the SH2 domain of RT phospholipase C-gamma 1."; RL Mol. Cell. Biol. 11:5068-5078(1991). RN [7] RP PHOSPHORYLATION AT SER-1248. RX PubMed=1370476; DOI=10.1016/s0021-9258(18)45973-x; RA Park D.J., Min H.K., Rhee S.G.; RT "Inhibition of CD3-linked phospholipase C by phorbol ester and by cAMP is RT associated with decreased phosphotyrosine and increased phosphoserine RT contents of PLC-gamma 1."; RL J. Biol. Chem. 267:1496-1501(1992). RN [8] RP INTERACTION WITH FGFR4. RX PubMed=7518429; DOI=10.1016/s0021-9258(17)32309-8; RA Vainikka S., Joukov V., Wennstrom S., Bergman M., Pelicci P.G., Alitalo K.; RT "Signal transduction by fibroblast growth factor receptor-4 (FGFR-4). RT Comparison with FGFR-1."; RL J. Biol. Chem. 269:18320-18326(1994). RN [9] RP PHOSPHORYLATION AT TYR-771 AND TYR-783 BY SYK, AND INTERACTION WITH SYK. RX PubMed=8657103; DOI=10.1128/mcb.16.4.1305; RA Law C.L., Chandran K.A., Sidorenko S.P., Clark E.A.; RT "Phospholipase C-gamma1 interacts with conserved phosphotyrosyl residues in RT the linker region of Syk and is a substrate for Syk."; RL Mol. Cell. Biol. 16:1305-1315(1996). RN [10] RP INTERACTION WITH KIT. RX PubMed=9038210; DOI=10.1074/jbc.272.9.5915; RA Price D.J., Rivnay B., Fu Y., Jiang S., Avraham S., Avraham H.; RT "Direct association of Csk homologous kinase (CHK) with the RT diphosphorylated site Tyr568/570 of the activated c-KIT in RT megakaryocytes."; RL J. Biol. Chem. 272:5915-5920(1997). RN [11] RP INTERACTION WITH AXL. RX PubMed=9178760; DOI=10.1038/sj.onc.1201123; RA Braunger J., Schleithoff L., Schulz A.S., Kessler H., Lammers R., RA Ullrich A., Bartram C.R., Janssen J.W.; RT "Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is RT mediated mainly by a multi-substrate docking-site."; RL Oncogene 14:2619-2631(1997). RN [12] RP INTERACTION WITH LAT. RX PubMed=9489702; DOI=10.1016/s0092-8674(00)80901-0; RA Zhang W., Sloan-Lancaster J., Kitchen J., Trible R.P., Samelson L.E.; RT "LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to RT cellular activation."; RL Cell 92:83-92(1998). RN [13] RP INTERACTION WITH SHB. RX PubMed=10488157; DOI=10.1074/jbc.274.39.28050; RA Lindholm C.K., Gylfe E., Zhang W., Samelson L.E., Welsh M.; RT "Requirement of the Src homology 2 domain protein Shb for T cell receptor- RT dependent activation of the interleukin-2 gene nuclear factor for RT activation of T cells element in Jurkat T cells."; RL J. Biol. Chem. 274:28050-28057(1999). RN [14] RP PHOSPHORYLATION BY KDR. RX PubMed=10102632; DOI=10.1038/sj.onc.1202478; RA Dougher M., Terman B.I.; RT "Autophosphorylation of KDR in the kinase domain is required for maximal RT VEGF-stimulated kinase activity and receptor internalization."; RL Oncogene 18:1619-1627(1999). RN [15] RP INTERACTION WITH TNK1. RX PubMed=10873601; DOI=10.1006/bbrc.2000.2887; RA Felschow D.M., Civin C.I., Hoehn G.T.; RT "Characterization of the tyrosine kinase Tnk1 and its binding with RT phospholipase C-gamma1."; RL Biochem. Biophys. Res. Commun. 273:294-301(2000). RN [16] RP INTERACTION WITH HEPATITIS E VIRUS/HEV PROTEIN ORF3 (MICROBIAL INFECTION). RX PubMed=11518702; DOI=10.1074/jbc.m101546200; RA Korkaya H., Jameel S., Gupta D., Tyagi S., Kumar R., Zafrullah M., RA Mazumdar M., Lal S.K., Xiaofang L., Sehgal D., Das S.R., Sahal D.; RT "The ORF3 protein of hepatitis E virus binds to Src homology 3 domains and RT activates MAPK."; RL J. Biol. Chem. 276:42389-42400(2001). RN [17] RP INTERACTION WITH RALGPS1. RX PubMed=10747847; DOI=10.1074/jbc.c000085200; RA Rebhun J.F., Chen H., Quilliam L.A.; RT "Identification and characterization of a new family of guanine nucleotide RT exchange factors for the ras-related GTPase Ral."; RL J. Biol. Chem. 275:13406-13410(2000). RN [18] RP PROBABLE DEPHOSPHORYLATION BY PTPRJ. RX PubMed=11259588; DOI=10.1128/mcb.21.7.2393-2403.2001; RA Baker J.E., Majeti R., Tangye S.G., Weiss A.; RT "Protein tyrosine phosphatase CD148-mediated inhibition of T-cell receptor RT signal transduction is associated with reduced LAT and phospholipase RT Cgamma1 phosphorylation."; RL Mol. Cell. Biol. 21:2393-2403(2001). RN [19] RP PHOSPHORYLATION AT TYR-783, AND SUBCELLULAR LOCATION. RX PubMed=11564877; DOI=10.1128/mcb.21.20.6939-6950.2001; RA Veri M.C., DeBell K.E., Seminario M.C., DiBaldassarre A., Reischl I., RA Rawat R., Graham L., Noviello C., Rellahan B.L., Miscia S., Wange R.L., RA Bonvini E.; RT "Membrane raft-dependent regulation of phospholipase Cgamma-1 activation in RT T lymphocytes."; RL Mol. Cell. Biol. 21:6939-6950(2001). RN [20] RP PROBABLE DEPHOSPHORYLATION BY PTPRJ. RX PubMed=12913111; DOI=10.1083/jcb.200303040; RA Lin J., Weiss A.; RT "The tyrosine phosphatase CD148 is excluded from the immunologic synapse RT and down-regulates prolonged T cell signaling."; RL J. Cell Biol. 162:673-682(2003). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-771 AND TYR-1253, AND RP IDENTIFICATION 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 from RT human T cells using immobilized metal affinity chromatography and tandem RT mass spectrometry."; RL Anal. Chem. 76:2763-2772(2004). RN [22] RP INTERACTION WITH NTRK1. RX PubMed=15488758; DOI=10.1016/j.ccr.2004.09.011; RA Tacconelli A., Farina A.R., Cappabianca L., Desantis G., Tessitore A., RA Vetuschi A., Sferra R., Rucci N., Argenti B., Screpanti I., Gulino A., RA Mackay A.R.; RT "TrkA alternative splicing: a regulated tumor-promoting switch in human RT neuroblastoma."; RL Cancer Cell 6:347-360(2004). RN [23] RP REVIEW ON INTERACTION WITH KIT AND ROLE IN KIT SIGNALING. RX PubMed=15526160; DOI=10.1007/s00018-004-4189-6; RA Ronnstrand L.; RT "Signal transduction via the stem cell factor receptor/c-Kit."; RL Cell. Mol. Life Sci. 61:2535-2548(2004). RN [24] RP INTERACTION WITH BLNK; VAV1; GRB2 AND NCK1. RX PubMed=15270728; DOI=10.1111/j.1365-2567.2004.01918.x; RA Taguchi T., Kiyokawa N., Takenouch H., Matsui J., Tang W.-R., Nakajima H., RA Suzuki K., Shiozawa Y., Saito M., Katagiri Y.U., Takahashi T., RA Karasuyama H., Matsuo Y., Okita H., Fujimoto J.; RT "Deficiency of BLNK hampers PLC-gamma2 phosphorylation and Ca2+ influx RT induced by the pre-B-cell receptor in human pre-B cells."; RL Immunology 112:575-582(2004). RN [25] RP INTERACTION WITH FLT4. RX PubMed=15102829; DOI=10.1074/jbc.m314015200; RA Wang J.F., Zhang X., Groopman J.E.; RT "Activation of vascular endothelial growth factor receptor-3 and its RT downstream signaling promote cell survival under oxidative stress."; RL J. Biol. Chem. 279:27088-27097(2004). RN [26] RP PHOSPHORYLATION AT TYR-783 IN RESPONSE TO KDR ACTIVATION. RX PubMed=15215251; DOI=10.1074/jbc.m401538200; RA Jia H., Bagherzadeh A., Bicknell R., Duchen M.R., Liu D., Zachary I.; RT "Vascular endothelial growth factor (VEGF)-D and VEGF-A differentially RT regulate KDR-mediated signaling and biological function in vascular RT endothelial cells."; RL J. Biol. Chem. 279:36148-36157(2004). RN [27] RP PHOSPHORYLATION BY ITK. RX PubMed=16081816; DOI=10.4049/jimmunol.175.4.2449; RA Houtman J.C., Houghtling R.A., Barda-Saad M., Toda Y., Samelson L.E.; RT "Early phosphorylation kinetics of proteins involved in proximal TCR- RT mediated signaling pathways."; RL J. Immunol. 175:2449-2458(2005). RN [28] RP INTERACTION WITH FGFR2, AND PHOSPHORYLATION. RX PubMed=16844695; DOI=10.1074/jbc.m600448200; RA Hatch N.E., Hudson M., Seto M.L., Cunningham M.L., Bothwell M.; RT "Intracellular retention, degradation, and signaling of glycosylation- RT deficient FGFR2 and craniosynostosis syndrome-associated FGFR2C278F."; RL J. Biol. Chem. 281:27292-27305(2006). RN [29] RP FUNCTION, INTERACTION WITH VIL1, AND SUBCELLULAR LOCATION. RX PubMed=17229814; DOI=10.1152/ajpcell.00420.2006; RA Wang Y., Tomar A., George S.P., Khurana S.; RT "Obligatory role for phospholipase C-gamma(1) in villin-induced epithelial RT cell migration."; RL Am. J. Physiol. 292:C1775-C1786(2007). RN [30] RP PHOSPHORYLATION BY FGFR3. RX PubMed=17561467; DOI=10.1016/j.bone.2006.11.030; RA Harada D., Yamanaka Y., Ueda K., Nishimura R., Morishima T., Seino Y., RA Tanaka H.; RT "Sustained phosphorylation of mutated FGFR3 is a crucial feature of genetic RT dwarfism and induces apoptosis in the ATDC5 chondrogenic cell line via RT PLCgamma-activated STAT1."; RL Bone 41:273-281(2007). RN [31] RP INTERACTION WITH PDGFRB. RX PubMed=17620338; DOI=10.1074/jbc.m701797200; RA Reddi A.L., Ying G., Duan L., Chen G., Dimri M., Douillard P., Druker B.J., RA Naramura M., Band V., Band H.; RT "Binding of Cbl to a phospholipase Cgamma1-docking site on platelet-derived RT growth factor receptor beta provides a dual mechanism of negative RT regulation."; RL J. Biol. Chem. 282:29336-29347(2007). RN [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1221, PHOSPHORYLATION [LARGE RP SCALE ANALYSIS] AT SER-1222 (ISOFORM 2), AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [33] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [34] RP INTERACTION WITH FGFR3. RX PubMed=19286672; DOI=10.1093/hmg/ddp116; RA Salazar L., Kashiwada T., Krejci P., Muchowski P., Donoghue D., RA Wilcox W.R., Thompson L.M.; RT "A novel interaction between fibroblast growth factor receptor 3 and the RT p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation RT of ERK by p85 in multiple myeloma cells."; RL Hum. Mol. Genet. 18:1951-1961(2009). RN [35] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-771; TYR-775; TYR-783 AND RP SER-1221, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1222 (ISOFORM 2), 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 [36] RP INTERACTION WITH PDGFRB, AND PHOSPHORYLATION AT TYR-771. RX PubMed=20494825; DOI=10.1016/j.cellsig.2010.05.004; RA Wardega P., Heldin C.H., Lennartsson J.; RT "Mutation of tyrosine residue 857 in the PDGF beta-receptor affects cell RT proliferation but not migration."; RL Cell. Signal. 22:1363-1368(2010). RN [37] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1221 AND TYR-1253, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [38] 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 [39] RP INTERACTION WITH FGFR1, AND PHOSPHORYLATION BY FGFR1. RX PubMed=21765395; DOI=10.1038/emboj.2011.234; RA Persaud A., Alberts P., Hayes M., Guettler S., Clarke I., Sicheri F., RA Dirks P., Ciruna B., Rotin D.; RT "Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis RT and function."; RL EMBO J. 30:3259-3273(2011). RN [40] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1222 (ISOFORM 2), AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [41] RP INTERACTION WITH TESPA1. RC TISSUE=Thymocyte; RX PubMed=22561606; DOI=10.1038/ni.2301; RA Wang D., Zheng M., Lei L., Ji J., Yao Y., Qiu Y., Ma L., Lou J., Ouyang C., RA Zhang X., He Y., Chi J., Wang L., Kuang Y., Wang J., Cao X., Lu L.; RT "Tespa1 is involved in late thymocyte development through the regulation of RT TCR-mediated signaling."; RL Nat. Immunol. 13:560-568(2012). RN [42] RP REVIEW ON ROLE IN FGF-ACTIVATED SIGNALING PATHWAYS. RX PubMed=15863030; DOI=10.1016/j.cytogfr.2005.01.001; RA Eswarakumar V.P., Lax I., Schlessinger J.; RT "Cellular signaling by fibroblast growth factor receptors."; RL Cytokine Growth Factor Rev. 16:139-149(2005). RN [43] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1221; SER-1227; SER-1233 AND RP SER-1263, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [44] RP STRUCTURE BY NMR OF SH3 DOMAIN. RX PubMed=7681365; DOI=10.1016/0092-8674(93)90583-c; RA Kohda D., Hatanaka H., Odaka M., Mandiyan V., Ullrich A., Schlessinger J., RA Inagaki F.; RT "Solution structure of the SH3 domain of phospholipase C-gamma."; RL Cell 72:953-960(1993). CC -!- FUNCTION: Mediates the production of the second messenger molecules CC diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an CC important role in the regulation of intracellular signaling cascades. CC Becomes activated in response to ligand-mediated activation of CC receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, EGFR, FGFR1, CC FGFR2, FGFR3 and FGFR4 (By similarity). Plays a role in actin CC reorganization and cell migration (PubMed:17229814). Guanine nucleotide CC exchange factor that binds the GTPase DNM1 and catalyzes the CC dissociation of GDP, allowing a GTP molecule to bind in its place, CC therefore enhancing DNM1-dependent endocytosis (By similarity). CC {ECO:0000250|UniProtKB:P10686, ECO:0000269|PubMed:17229814}. 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:0000250|UniProtKB:P10686}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33180; CC Evidence={ECO:0000250|UniProtKB:P10686}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + H2O = CC 1D-myo-inositol 1-phosphate + a 1,2-diacyl-sn-glycerol + H(+); CC Xref=Rhea:RHEA:43484, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17815, ChEBI:CHEBI:57880, ChEBI:CHEBI:58433; CC Evidence={ECO:0000250|UniProtKB:P10686}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43485; CC Evidence={ECO:0000250|UniProtKB:P10686}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000250|UniProtKB:P10686}; CC -!- ACTIVITY REGULATION: Activated by phosphorylation on tyrosine residues. CC {ECO:0000269|PubMed:1370476}. CC -!- SUBUNIT: Interacts with AGAP2 via its SH3 domain. Interacts (via SH2 CC domain) with RET. Interacts with FLT1 (tyrosine-phosphorylated) (By CC similarity). Interacts (via SH2 domain) with FGFR1, FGFR2, FGFR3 and CC FGFR4 (phosphorylated). Interacts with LAT (phosphorylated) upon TCR CC activation. Interacts (via SH3 domain) with the Pro-rich domain of CC TNK1. Associates with BLNK, VAV1, GRB2 and NCK1 in a B-cell antigen CC receptor-dependent fashion. Interacts with CBLB in activated T-cells; CC which inhibits phosphorylation. Interacts with SHB. Interacts (via SH3 CC domain) with the Arg/Gly-rich-flanked Pro-rich domains of CC KHDRBS1/SAM68. This interaction is selectively regulated by arginine CC methylation of KHDRBS1/SAM68. Interacts with INPP5D/SHIP1, THEMIS and CC CLNK (By similarity). Interacts with AXL, FLT4 and KIT. Interacts with CC RALGPS1. Interacts (via the SH2 domains) with VIL1 (phosphorylated at CC C-terminus tyrosine phosphorylation sites). Interacts (via SH2 domain) CC with PDGFRA and PDGFRB (tyrosine phosphorylated). Interacts with CC PIP5K1C (By similarity). Interacts with NTRK1 and NTRK2 (phosphorylated CC upon ligand-binding). Interacts with SYK; activates PLCG1. Interacts CC with GRB2, LAT and THEMIS upon TCR activation in thymocytes (By CC similarity). Interacts with TESPA1; the association is increased with CC prolonged stimulation of the TCR and may facilitate the assembly of the CC LAT signalosome. Interacts (via C-terminal proline-rich domain (PRD)) CC with PLCG1 (via SH3 domain); this interaction leads to guanine CC nucleotide exchange from PlCG1 to DNM1 and enhances DNM1-dependent CC endocytosis (By similarity). {ECO:0000250|UniProtKB:P10686, CC ECO:0000250|UniProtKB:Q62077, ECO:0000269|PubMed:10488157, CC ECO:0000269|PubMed:10747847, ECO:0000269|PubMed:10873601, CC ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:15270728, CC ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:1656221, CC ECO:0000269|PubMed:16844695, ECO:0000269|PubMed:17229814, CC ECO:0000269|PubMed:17620338, ECO:0000269|PubMed:19286672, CC ECO:0000269|PubMed:20494825, ECO:0000269|PubMed:21765395, CC ECO:0000269|PubMed:22561606, ECO:0000269|PubMed:7518429, CC ECO:0000269|PubMed:8657103, ECO:0000269|PubMed:9038210, CC ECO:0000269|PubMed:9178760, ECO:0000269|PubMed:9489702}. CC -!- SUBUNIT: (Microbial infection) Interacts (via SH3 domain) with HEV ORF3 CC protein. {ECO:0000269|PubMed:11518702}. CC -!- INTERACTION: CC P19174; P42684: ABL2; NbExp=4; IntAct=EBI-79387, EBI-1102694; CC P19174; P31749: AKT1; NbExp=9; IntAct=EBI-79387, EBI-296087; CC P19174; P10275: AR; NbExp=22; IntAct=EBI-79387, EBI-608057; CC P19174; Q9ULH1: ASAP1; NbExp=3; IntAct=EBI-79387, EBI-346622; CC P19174; O43150: ASAP2; NbExp=3; IntAct=EBI-79387, EBI-310968; CC P19174; Q03135: CAV1; NbExp=2; IntAct=EBI-79387, EBI-603614; CC P19174; P20273: CD22; NbExp=2; IntAct=EBI-79387, EBI-78277; CC P19174; Q9BZW8: CD244; NbExp=2; IntAct=EBI-79387, EBI-1580565; CC P19174; Q9H1R2: DUSP15; NbExp=2; IntAct=EBI-79387, EBI-1752795; CC P19174; P00533: EGFR; NbExp=6; IntAct=EBI-79387, EBI-297353; CC P19174; P04626: ERBB2; NbExp=5; IntAct=EBI-79387, EBI-641062; CC P19174; P21860: ERBB3; NbExp=4; IntAct=EBI-79387, EBI-720706; CC P19174; P31994: FCGR2B; NbExp=2; IntAct=EBI-79387, EBI-724784; CC P19174; P11362: FGFR1; NbExp=11; IntAct=EBI-79387, EBI-1028277; CC P19174; P21802-1: FGFR2; NbExp=9; IntAct=EBI-79387, EBI-15489960; CC P19174; Q13480: GAB1; NbExp=36; IntAct=EBI-79387, EBI-517684; CC P19174; P62993: GRB2; NbExp=2; IntAct=EBI-79387, EBI-401755; CC P19174; P06213: INSR; NbExp=9; IntAct=EBI-79387, EBI-475899; CC P19174; Q07666: KHDRBS1; NbExp=3; IntAct=EBI-79387, EBI-1364; CC P19174; P10721: KIT; NbExp=31; IntAct=EBI-79387, EBI-1379503; CC P19174; O43561: LAT; NbExp=7; IntAct=EBI-79387, EBI-1222766; CC P19174; Q13094: LCP2; NbExp=3; IntAct=EBI-79387, EBI-346946; CC P19174; Q92918: MAP4K1; NbExp=6; IntAct=EBI-79387, EBI-881; CC P19174; P08581: MET; NbExp=10; IntAct=EBI-79387, EBI-1039152; CC P19174; P04629: NTRK1; NbExp=4; IntAct=EBI-79387, EBI-1028226; CC P19174; P09619: PDGFRB; NbExp=7; IntAct=EBI-79387, EBI-641237; CC P19174; P63000: RAC1; NbExp=7; IntAct=EBI-79387, EBI-413628; CC P19174; Q8TB24: RIN3; NbExp=3; IntAct=EBI-79387, EBI-1570523; CC P19174; Q8WTV0-3: SCARB1; NbExp=2; IntAct=EBI-79387, EBI-20819026; CC P19174; O14796: SH2D1B; NbExp=2; IntAct=EBI-79387, EBI-3923013; CC P19174; Q9UPX8: SHANK2; NbExp=4; IntAct=EBI-79387, EBI-1570571; CC P19174; Q9BYB0: SHANK3; NbExp=2; IntAct=EBI-79387, EBI-1752330; CC P19174; Q15036: SNX17; NbExp=2; IntAct=EBI-79387, EBI-1752620; CC P19174; Q07889: SOS1; NbExp=3; IntAct=EBI-79387, EBI-297487; CC P19174; Q07890: SOS2; NbExp=4; IntAct=EBI-79387, EBI-298181; CC P19174; P43405: SYK; NbExp=4; IntAct=EBI-79387, EBI-78302; CC P19174; Q8N1K5-1: THEMIS; NbExp=3; IntAct=EBI-79387, EBI-15102259; CC P19174; P09327: VIL1; NbExp=5; IntAct=EBI-79387, EBI-746958; CC P19174; Q71V39: EEF1A2; Xeno; NbExp=3; IntAct=EBI-79387, EBI-7645815; CC -!- SUBCELLULAR LOCATION: Cell projection, lamellipodium CC {ECO:0000269|PubMed:17229814}. Cell projection, ruffle CC {ECO:0000269|PubMed:17229814}. Note=Rapidly redistributed to ruffles CC and lamellipodia structures in response to epidermal growth factor CC (EGF) treatment. {ECO:0000269|PubMed:17229814}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P19174-1; Sequence=Displayed; CC Name=2; CC IsoId=P19174-2; Sequence=VSP_038692; CC -!- DOMAIN: The SH3 domain mediates interaction with CLNK (By similarity). CC The SH3 domain also mediates interaction with RALGPS1 CC (PubMed:10747847). {ECO:0000250|UniProtKB:Q62077, CC ECO:0000269|PubMed:10747847}. CC -!- PTM: Tyrosine phosphorylated in response to signaling via activated CC FLT3, KIT and PDGFRA (By similarity). Tyrosine phosphorylated by CC activated FGFR1, FGFR2, FGFR3 and FGFR4. Tyrosine phosphorylated by CC activated FLT1 and KDR. Tyrosine phosphorylated by activated PDGFRB. CC The receptor-mediated activation of PLCG1 involves its phosphorylation CC by tyrosine kinases, in response to ligation of a variety of growth CC factor receptors and immune system receptors. For instance, SYK CC phosphorylates and activates PLCG1 in response to ligation of the B- CC cell receptor. May be dephosphorylated by PTPRJ. Phosphorylated by ITK CC and TXK on Tyr-783 upon TCR activation in T-cells. {ECO:0000250, CC ECO:0000269|PubMed:10102632, ECO:0000269|PubMed:11564877, CC ECO:0000269|PubMed:1370476, ECO:0000269|PubMed:15215251, CC ECO:0000269|PubMed:16081816, ECO:0000269|PubMed:16844695, CC ECO:0000269|PubMed:17561467, ECO:0000269|PubMed:20494825, CC ECO:0000269|PubMed:2167438, ECO:0000269|PubMed:21765395, CC ECO:0000269|PubMed:8657103}. CC -!- PTM: Ubiquitinated by CBLB in activated T-cells. CC {ECO:0000250|UniProtKB:Q62077}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/plcg1/"; 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; M34667; AAA36452.1; -; mRNA. DR EMBL; DQ297143; ABB84466.1; -; Genomic_DNA. DR EMBL; AL022394; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471077; EAW75991.1; -; Genomic_DNA. DR EMBL; CH471077; EAW75992.1; -; Genomic_DNA. DR EMBL; BC136466; AAI36467.1; -; mRNA. DR EMBL; BC144136; AAI44137.1; -; mRNA. DR CCDS; CCDS13313.1; -. [P19174-2] DR CCDS; CCDS13314.1; -. [P19174-1] DR PIR; A36466; A36466. DR RefSeq; NP_002651.2; NM_002660.2. [P19174-2] DR RefSeq; NP_877963.1; NM_182811.1. [P19174-1] DR PDB; 1HSQ; NMR; -; A=790-851. DR PDB; 2HSP; NMR; -; A=790-851. DR PDB; 4EY0; X-ray; 2.80 A; A/B/C/D=545-790. DR PDB; 4FBN; X-ray; 2.40 A; A=545-790. DR PDB; 7NXE; X-ray; 2.10 A; A=545-772. DR PDBsum; 1HSQ; -. DR PDBsum; 2HSP; -. DR PDBsum; 4EY0; -. DR PDBsum; 4FBN; -. DR PDBsum; 7NXE; -. DR AlphaFoldDB; P19174; -. DR SMR; P19174; -. DR BioGRID; 111351; 224. DR CORUM; P19174; -. DR DIP; DIP-100N; -. DR IntAct; P19174; 145. DR MINT; P19174; -. DR STRING; 9606.ENSP00000244007; -. DR BindingDB; P19174; -. DR ChEMBL; CHEMBL3964; -. DR MoonDB; P19174; Predicted. DR GlyCosmos; P19174; 1 site, 1 glycan. DR GlyGen; P19174; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P19174; -. DR PhosphoSitePlus; P19174; -. DR BioMuta; PLCG1; -. DR DMDM; 130225; -. DR CPTAC; CPTAC-1738; -. DR EPD; P19174; -. DR jPOST; P19174; -. DR MassIVE; P19174; -. DR MaxQB; P19174; -. DR PaxDb; 9606-ENSP00000244007; -. DR PeptideAtlas; P19174; -. DR ProteomicsDB; 53635; -. [P19174-1] DR ProteomicsDB; 53636; -. [P19174-2] DR Pumba; P19174; -. DR ABCD; P19174; 1 sequenced antibody. DR Antibodypedia; 3796; 1319 antibodies from 42 providers. DR DNASU; 5335; -. DR Ensembl; ENST00000244007.7; ENSP00000244007.3; ENSG00000124181.15. [P19174-2] DR Ensembl; ENST00000373271.5; ENSP00000362368.1; ENSG00000124181.15. [P19174-1] DR Ensembl; ENST00000685551.1; ENSP00000508698.1; ENSG00000124181.15. [P19174-2] DR GeneID; 5335; -. DR KEGG; hsa:5335; -. DR MANE-Select; ENST00000685551.1; ENSP00000508698.1; NM_002660.3; NP_002651.2. [P19174-2] DR UCSC; uc002xjo.2; human. [P19174-1] DR AGR; HGNC:9065; -. DR CTD; 5335; -. DR DisGeNET; 5335; -. DR GeneCards; PLCG1; -. DR HGNC; HGNC:9065; PLCG1. DR HPA; ENSG00000124181; Low tissue specificity. DR MalaCards; PLCG1; -. DR MIM; 172420; gene. DR neXtProt; NX_P19174; -. DR OpenTargets; ENSG00000124181; -. DR PharmGKB; PA33392; -. DR VEuPathDB; HostDB:ENSG00000124181; -. DR eggNOG; KOG1264; Eukaryota. DR GeneTree; ENSGT00940000158901; -. DR HOGENOM; CLU_002738_5_0_1; -. DR InParanoid; P19174; -. DR OMA; YMRNPLY; -. DR OrthoDB; 2900494at2759; -. DR PhylomeDB; P19174; -. DR TreeFam; TF313216; -. DR BRENDA; 3.1.4.11; 2681. DR PathwayCommons; P19174; -. DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism. DR Reactome; R-HSA-1236382; Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants. DR Reactome; R-HSA-1251932; PLCG1 events in ERBB2 signaling. DR Reactome; R-HSA-1489509; DAG and IP3 signaling. DR Reactome; R-HSA-167021; PLC-gamma1 signalling. DR Reactome; R-HSA-1855204; Synthesis of IP3 and IP4 in the cytosol. DR Reactome; R-HSA-186763; Downstream signal transduction. DR Reactome; R-HSA-201556; Signaling by ALK. DR Reactome; R-HSA-202433; Generation of second messenger molecules. DR Reactome; R-HSA-2029485; Role of phospholipids in phagocytosis. DR Reactome; R-HSA-210990; PECAM1 interactions. DR Reactome; R-HSA-212718; EGFR interacts with phospholipase C-gamma. 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-418890; Role of second messengers in netrin-1 signaling. DR Reactome; R-HSA-5218921; VEGFR2 mediated cell proliferation. DR Reactome; R-HSA-5637810; Constitutive Signaling by EGFRvIII. DR Reactome; R-HSA-5654219; Phospholipase C-mediated cascade: FGFR1. DR Reactome; R-HSA-5654221; Phospholipase C-mediated cascade, FGFR2. DR Reactome; R-HSA-5654227; Phospholipase C-mediated cascade, FGFR3. DR Reactome; R-HSA-5654228; Phospholipase C-mediated cascade, FGFR4. DR Reactome; R-HSA-5655253; Signaling by FGFR2 in disease. DR Reactome; R-HSA-5655291; Signaling by FGFR4 in disease. DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease. DR Reactome; R-HSA-5655332; Signaling by FGFR3 in disease. DR Reactome; R-HSA-8853659; RET signaling. DR Reactome; R-HSA-9026527; Activated NTRK2 signals through PLCG1. DR Reactome; R-HSA-9027277; Erythropoietin activates Phospholipase C gamma (PLCG). DR Reactome; R-HSA-9034793; Activated NTRK3 signals through PLCG1. DR Reactome; R-HSA-9664323; FCGR3A-mediated IL10 synthesis. DR Reactome; R-HSA-9664565; Signaling by ERBB2 KD Mutants. DR Reactome; R-HSA-9665348; Signaling by ERBB2 ECD mutants. DR Reactome; R-HSA-9665686; Signaling by ERBB2 TMD/JMD mutants. DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants. DR SignaLink; P19174; -. DR SIGNOR; P19174; -. DR BioGRID-ORCS; 5335; 27 hits in 1168 CRISPR screens. DR ChiTaRS; PLCG1; human. DR EvolutionaryTrace; P19174; -. DR GeneWiki; PLCG1; -. DR GenomeRNAi; 5335; -. DR Pharos; P19174; Tchem. DR PRO; PR:P19174; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; P19174; Protein. DR Bgee; ENSG00000124181; Expressed in right hemisphere of cerebellum and 188 other cell types or tissues. DR ExpressionAtlas; P19174; baseline and differential. DR GO; GO:0042995; C:cell projection; IDA:BHF-UCL. DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl. DR GO; GO:0008180; C:COP9 signalosome; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0001726; C:ruffle; IDA:UniProtKB. DR GO; GO:0032587; C:ruffle membrane; IDA:ARUK-UCL. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0050429; F:calcium-dependent phospholipase C activity; ISS:UniProtKB. DR GO; GO:0035254; F:glutamate receptor binding; IEA:Ensembl. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB. DR GO; GO:0005168; F:neurotrophin TRKA receptor binding; IPI:UniProtKB. DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; IDA:UniProtKB. DR GO; GO:0004629; F:phospholipase C activity; IDA:MGI. DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL. DR GO; GO:0030971; F:receptor tyrosine kinase binding; IEA:Ensembl. DR GO; GO:0019722; P:calcium-mediated signaling; IMP:BHF-UCL. DR GO; GO:0016477; P:cell migration; IMP:BHF-UCL. DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IDA:UniProtKB. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IMP:BHF-UCL. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IEA:Ensembl. DR GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; TAS:Reactome. DR GO; GO:0046488; P:phosphatidylinositol metabolic process; ISS: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:0045766; P:positive regulation of angiogenesis; IDA:DFLAT. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IDA:DFLAT. DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; IMP:BHF-UCL. DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IMP:UniProtKB. DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; IMP:BHF-UCL. DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IMP:BHF-UCL. DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IBA:GO_Central. DR GO; GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome. DR CDD; cd00275; C2_PLC_like; 1. DR CDD; cd16214; EFh_PI-PLCgamma1; 1. DR CDD; cd13362; PH_PLC_gamma; 1. DR CDD; cd13234; PHsplit_PLC_gamma; 1. DR CDD; cd08592; PI-PLCc_gamma; 1. DR CDD; cd09932; SH2_C-SH2_PLC_gamma_like; 1. DR CDD; cd10341; SH2_N-SH2_PLC_gamma_like; 1. DR CDD; cd11970; SH3_PLCgamma1; 1. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 3.20.20.190; Phosphatidylinositol (PI) phosphodiesterase; 2. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 3.30.505.10; SH2 domain; 2. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR018247; EF_Hand_1_Ca_BS. DR InterPro; IPR002048; EF_hand_dom. 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; IPR035023; PLC-gamma_C-SH2. DR InterPro; IPR035024; PLC-gamma_N-SH2. DR InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl. DR InterPro; IPR035724; PLCgamma1_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:SF173; 1-PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE PHOSPHODIESTERASE GAMMA-1; 1. DR PANTHER; PTHR10336; PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C FAMILY PROTEIN; 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 SMART; SM00239; C2; 1. DR SMART; SM00233; PH; 3. DR SMART; SM00148; PLCXc; 1. DR SMART; SM00149; PLCYc; 1. DR SMART; SM00252; SH2; 2. DR SMART; SM00326; SH3; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF47473; EF-hand; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF51695; PLC-like phosphodiesterases; 1. DR SUPFAM; SSF55550; SH2 domain; 2. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS50004; C2; 1. DR PROSITE; PS00018; EF_HAND_1; 1. DR PROSITE; PS50222; EF_HAND_2; 1. DR PROSITE; PS50003; PH_DOMAIN; 2. DR PROSITE; PS50007; PIPLC_X_DOMAIN; 1. DR PROSITE; PS50008; PIPLC_Y_DOMAIN; 1. DR PROSITE; PS50001; SH2; 2. DR PROSITE; PS50002; SH3; 1. DR Genevisible; P19174; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Calcium; Cell projection; KW Host-virus interaction; Hydrolase; Lipid degradation; Lipid metabolism; KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; SH2 domain; KW SH3 domain; Transducer; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330" FT CHAIN 2..1290 FT /note="1-phosphatidylinositol 4,5-bisphosphate FT phosphodiesterase gamma-1" FT /id="PRO_0000088498" FT DOMAIN 27..142 FT /note="PH 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 152..187 FT /note="EF-hand" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 320..464 FT /note="PI-PLC X-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT DOMAIN 489..523 FT /note="PH 2; first part" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 550..657 FT /note="SH2 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 668..756 FT /note="SH2 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 791..851 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 895..931 FT /note="PH 2; second part" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 953..1070 FT /note="PI-PLC Y-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00271" FT DOMAIN 1071..1194 FT /note="C2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT REGION 522..544 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1271..1290 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 335 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT ACT_SITE 380 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT BINDING 165 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 167 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 169 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 171 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 176 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 506 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q62077" FT MOD_RES 771 FT /note="Phosphotyrosine; by SYK" FT /evidence="ECO:0000269|PubMed:20494825, FT ECO:0000269|PubMed:8657103, ECO:0007744|PubMed:15144186, FT ECO:0007744|PubMed:19690332" FT MOD_RES 775 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 783 FT /note="Phosphotyrosine; by ITK, SYK and TXK" FT /evidence="ECO:0000269|PubMed:11564877, FT ECO:0000269|PubMed:15215251, ECO:0000269|PubMed:8657103, FT ECO:0007744|PubMed:19690332" FT MOD_RES 977 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q62077" FT MOD_RES 1221 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1227 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1233 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1248 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:1370476" FT MOD_RES 1253 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:15144186, FT ECO:0007744|PubMed:20068231" FT MOD_RES 1263 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1215 FT /note="K -> KQ (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_038692" FT VARIANT 209 FT /note="T -> N (in dbSNP:rs2229348)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025213" FT VARIANT 279 FT /note="S -> G (in dbSNP:rs2228246)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_022130" FT VARIANT 739 FT /note="S -> T (in dbSNP:rs34203315)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025214" FT VARIANT 813 FT /note="I -> T (in dbSNP:rs753381)" FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2" FT /id="VAR_011908" FT STRAND 551..554 FT /evidence="ECO:0007829|PDB:7NXE" FT STRAND 556..558 FT /evidence="ECO:0007829|PDB:4EY0" FT HELIX 561..576 FT /evidence="ECO:0007829|PDB:7NXE" FT STRAND 583..587 FT /evidence="ECO:0007829|PDB:7NXE" FT STRAND 589..591 FT /evidence="ECO:0007829|PDB:7NXE" FT STRAND 595..601 FT /evidence="ECO:0007829|PDB:7NXE" FT STRAND 604..612 FT /evidence="ECO:0007829|PDB:7NXE" FT HELIX 615..617 FT /evidence="ECO:0007829|PDB:4FBN" FT STRAND 621..624 FT /evidence="ECO:0007829|PDB:7NXE" FT STRAND 628..631 FT /evidence="ECO:0007829|PDB:7NXE" FT HELIX 632..641 FT /evidence="ECO:0007829|PDB:7NXE" FT STRAND 644..646 FT /evidence="ECO:0007829|PDB:4EY0" FT STRAND 649..651 FT /evidence="ECO:0007829|PDB:4EY0" FT HELIX 662..665 FT /evidence="ECO:0007829|PDB:7NXE" FT STRAND 669..672 FT /evidence="ECO:0007829|PDB:7NXE" FT HELIX 675..683 FT /evidence="ECO:0007829|PDB:7NXE" FT STRAND 690..695 FT /evidence="ECO:0007829|PDB:7NXE" FT STRAND 701..708 FT /evidence="ECO:0007829|PDB:7NXE" FT STRAND 711..720 FT /evidence="ECO:0007829|PDB:7NXE" FT STRAND 723..726 FT /evidence="ECO:0007829|PDB:7NXE" FT STRAND 729..733 FT /evidence="ECO:0007829|PDB:7NXE" FT HELIX 734..741 FT /evidence="ECO:0007829|PDB:7NXE" FT HELIX 758..764 FT /evidence="ECO:0007829|PDB:7NXE" FT STRAND 792..794 FT /evidence="ECO:0007829|PDB:1HSQ" FT STRAND 805..809 FT /evidence="ECO:0007829|PDB:1HSQ" FT STRAND 817..820 FT /evidence="ECO:0007829|PDB:2HSP" FT TURN 825..827 FT /evidence="ECO:0007829|PDB:1HSQ" FT STRAND 834..836 FT /evidence="ECO:0007829|PDB:1HSQ" FT TURN 843..845 FT /evidence="ECO:0007829|PDB:1HSQ" FT MOD_RES P19174-2:1222 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692" SQ SEQUENCE 1290 AA; 148532 MW; AE05ABE2A18EDDAC CRC64; MAGAASPCAN GCGPGAPSDA EVLHLCRSLE VGTVMTLFYS KKSQRPERKT FQVKLETRQI TWSRGADKIE GAIDIREIKE IRPGKTSRDF DRYQEDPAFR PDQSHCFVIL YGMEFRLKTL SLQATSEDEV NMWIKGLTWL MEDTLQAPTP LQIERWLRKQ FYSVDRNRED RISAKDLKNM LSQVNYRVPN MRFLRERLTD LEQRSGDITY GQFAQLYRSL MYSAQKTMDL PFLEASTLRA GERPELCRVS LPEFQQFLLD YQGELWAVDR LQVQEFMLSF LRDPLREIEE PYFFLDEFVT FLFSKENSVW NSQLDAVCPD TMNNPLSHYW ISSSHNTYLT GDQFSSESSL EAYARCLRMG CRCIELDCWD GPDGMPVIYH GHTLTTKIKF SDVLHTIKEH AFVASEYPVI LSIEDHCSIA QQRNMAQYFK KVLGDTLLTK PVEISADGLP SPNQLKRKIL IKHKKLAEGS AYEEVPTSMM YSENDISNSI KNGILYLEDP VNHEWYPHYF VLTSSKIYYS EETSSDQGNE DEEEPKEVSS STELHSNEKW FHGKLGAGRD GRHIAERLLT EYCIETGAPD GSFLVRESET FVGDYTLSFW RNGKVQHCRI HSRQDAGTPK FFLTDNLVFD SLYDLITHYQ QVPLRCNEFE MRLSEPVPQT NAHESKEWYH ASLTRAQAEH MLMRVPRDGA FLVRKRNEPN SYAISFRAEG KIKHCRVQQE GQTVMLGNSE FDSLVDLISY YEKHPLYRKM KLRYPINEEA LEKIGTAEPD YGALYEGRNP GFYVEANPMP TFKCAVKALF DYKAQREDEL TFIKSAIIQN VEKQEGGWWR GDYGGKKQLW FPSNYVEEMV NPVALEPERE HLDENSPLGD LLRGVLDVPA CQIAIRPEGK NNRLFVFSIS MASVAHWSLD VAADSQEELQ DWVKKIREVA QTADARLTEG KIMERRKKIA LELSELVVYC RPVPFDEEKI GTERACYRDM SSFPETKAEK YVNKAKGKKF LQYNRLQLSR IYPKGQRLDS SNYDPLPMWI CGSQLVALNF QTPDKPMQMN QALFMTGRHC GYVLQPSTMR DEAFDPFDKS SLRGLEPCAI SIEVLGARHL PKNGRGIVCP FVEIEVAGAE YDSTKQKTEF VVDNGLNPVW PAKPFHFQIS NPEFAFLRFV VYEEDMFSDQ NFLAQATFPV KGLKTGYRAV PLKNNYSEDL ELASLLIKID IFPAKENGDL SPFSGTSLRE RGSDASGQLF HGRAREGSFE SRYQQPFEDF RISQEHLADH FDSRERRAPR RTRVNGDNRL //