PLCG1_HUMAN
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 03-AUG-2022, entry version 254.
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).
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. {ECO:0000250|UniProtKB:Q62077,
CC ECO:0000269|PubMed:10488157, ECO:0000269|PubMed:10747847,
CC ECO:0000269|PubMed:10873601, ECO:0000269|PubMed:15102829,
CC ECO:0000269|PubMed:15270728, ECO:0000269|PubMed:15488758,
CC ECO:0000269|PubMed:1656221, ECO:0000269|PubMed:16844695,
CC ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:17620338,
CC ECO:0000269|PubMed:19286672, ECO:0000269|PubMed:20494825,
CC ECO:0000269|PubMed:21765395, ECO:0000269|PubMed:22561606,
CC ECO:0000269|PubMed:7518429, ECO:0000269|PubMed:8657103,
CC ECO:0000269|PubMed:9038210, ECO:0000269|PubMed:9178760,
CC 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=9; 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; P09619: PDGFRB; NbExp=6; 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/";
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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; 176.
DR CORUM; P19174; -.
DR DIP; DIP-100N; -.
DR IntAct; P19174; 137.
DR MINT; P19174; -.
DR STRING; 9606.ENSP00000244007; -.
DR BindingDB; P19174; -.
DR ChEMBL; CHEMBL3964; -.
DR MoonDB; P19174; Predicted.
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; P19174; -.
DR PeptideAtlas; P19174; -.
DR PRIDE; P19174; -.
DR ProteomicsDB; 53635; -. [P19174-1]
DR ProteomicsDB; 53636; -. [P19174-2]
DR ABCD; P19174; 1 sequenced antibody.
DR Antibodypedia; 3796; 1181 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 CTD; 5335; -.
DR DisGeNET; 5335; -.
DR GeneCards; PLCG1; -.
DR HGNC; HGNC:9065; PLCG1.
DR HPA; ENSG00000124181; Low tissue specificity.
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; FNPVPFW; -.
DR OrthoDB; 368239at2759; -.
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; 23 hits in 1084 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 186 other tissues.
DR ExpressionAtlas; P19174; baseline and differential.
DR Genevisible; P19174; HS.
DR GO; GO:0042995; C:cell projection; IDA:BHF-UCL.
DR GO; GO:0008180; C:COP9 signalosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
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:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0050429; F:calcium-dependent phospholipase C 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: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: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: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:0050852; P:T cell receptor signaling pathway; TAS:Reactome.
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; 2.30.29.30; -; 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; 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; IPR028380; PLC-gamma1.
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; PTHR10336; 1.
DR PANTHER; PTHR10336:SF173; PTHR10336:SF173; 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 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; 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; 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.
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
