ID PLCG1_RAT Reviewed; 1290 AA. AC P10686; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 27-MAR-2024, entry version 233. DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 {ECO:0000305}; DE EC=3.1.4.11 {ECO:0000269|PubMed:7531435}; DE AltName: Full=Phosphoinositide phospholipase C-gamma-1; DE AltName: Full=Phospholipase C-gamma-1; DE Short=PLC-gamma-1; GN Name=Plcg1 {ECO:0000312|RGD:3347}; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2840660; DOI=10.1073/pnas.85.15.5419; RA Suh P.-G., Ryu S.H., Moon K.H., Suh H.W., Rhee S.G.; RT "Inositol phospholipid-specific phospholipase C: complete cDNA and protein RT sequences and sequence homology to tyrosine kinase-related oncogene RT products."; RL Proc. Natl. Acad. Sci. U.S.A. 85:5419-5423(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-29. RX PubMed=8392838; DOI=10.1006/bbrc.1993.1818; RA Lee S.J., Ryu S.H., Suh P.G.; RT "Promoter region of the rat phospholipase C-gamma 1 gene."; RL Biochem. Biophys. Res. Commun. 194:294-300(1993). RN [3] RP INTERACTION WITH FGFR4, AND PHOSPHORYLATION. 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 [4] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=7531435; DOI=10.1042/bj3050745; RA Koblan K.S., Schaber M.D., Edwards G., Gibbs J.B., Pompliano D.L.; RT "src-homology 2 (SH2) domain ligation as an allosteric regulator: RT modulation of phosphoinositide-specific phospholipase C gamma 1 structure RT and activity."; RL Biochem. J. 305:745-751(1995). RN [5] RP INTERACTION WITH AGAP2, AND MUTAGENESIS OF PRO-842. RX PubMed=11823862; DOI=10.1038/415541a; RA Ye K., Aghdasi B., Luo H.R., Moriarity J.L., Wu F.Y., Hong J.J., Hurt K.J., RA Bae S.S., Suh P.-G., Snyder S.H.; RT "Phospholipase C gamma 1 is a physiological guanine nucleotide exchange RT factor for the nuclear GTPase PIKE."; RL Nature 415:541-544(2002). RN [6] RP FUNCTION, AND INTERACTION WITH DNM1. RX PubMed=15252117; DOI=10.1242/jcs.01220; RA Choi J.H., Park J.B., Bae S.S., Yun S., Kim H.S., Hong W.P., Kim I.S., RA Kim J.H., Han M.Y., Ryu S.H., Patterson R.L., Snyder S.H., Suh P.G.; RT "Phospholipase C-gamma1 is a guanine nucleotide exchange factor for RT dynamin-1 and enhances dynamin-1-dependent epidermal growth factor receptor RT endocytosis."; RL J. Cell Sci. 117:3785-3795(2004). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1221 AND SER-1248, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). RN [8] RP STRUCTURE BY NMR OF 489-553 AND 663-759. RX PubMed=16500902; DOI=10.1074/jbc.m600336200; RA Wen W., Yan J., Zhang M.; RT "Structural characterization of the split pleckstrin homology domain in RT phospholipase C-gamma1 and its interaction with TRPC3."; RL J. Biol. Chem. 281:12060-12068(2006). CC -!- FUNCTION: Mediates the production of the second messenger molecules CC diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) CC (PubMed:7531435). Plays an important role in the regulation of CC intracellular signaling cascades. Becomes activated in response to CC ligand-mediated activation of receptor-type tyrosine kinases, such as CC PDGFRA, PDGFRB, EGFR, FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:7531435). CC Plays a role in actin reorganization and cell migration (By CC similarity). Guanine nucleotide exchange factor that binds the GTPase CC DNM1 and catalyzes the dissociation of GDP, allowing a GTP molecule to CC bind in its place, therefore enhancing DNM1-dependent endocytosis CC (PubMed:15252117). {ECO:0000250|UniProtKB:P19174, CC ECO:0000250|UniProtKB:Q62077, ECO:0000269|PubMed:15252117, CC ECO:0000269|PubMed:7531435}. 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:7531435}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33180; CC Evidence={ECO:0000305|PubMed:7531435}; 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:0000269|PubMed:7531435}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43485; CC Evidence={ECO:0000305|PubMed:7531435}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:7531435}; CC -!- ACTIVITY REGULATION: Activated by phosphorylation on tyrosine residues. CC {ECO:0000250|UniProtKB:P19174}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC Vmax=13.8 umol/min/mg enzyme toward phosphatidylinositol CC {ECO:0000269|PubMed:7531435}; CC Vmax=0.6 umol/min/mg enzyme toward CC 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) CC {ECO:0000269|PubMed:7531435}; CC pH dependence: CC Optimum pH is 5. {ECO:0000269|PubMed:7531435}; 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 (By similarity). Interacts (via C-terminal proline-rich CC domain (PRD)) with PLCG1 (via SH3 domain); this interaction leads to CC guanine nucleotide exchange from PlCG1 to DNM1 and enhances DNM1- CC dependent endocytosis (PubMed:15252117). {ECO:0000250|UniProtKB:P19174, CC ECO:0000250|UniProtKB:Q62077, ECO:0000269|PubMed:15252117}. CC -!- INTERACTION: CC P10686; Q04589: Fgfr1; NbExp=2; IntAct=EBI-520788, EBI-2480918; CC P10686; P11362: FGFR1; Xeno; NbExp=4; IntAct=EBI-520788, EBI-1028277; CC P10686; Q08881: ITK; Xeno; NbExp=2; IntAct=EBI-520788, EBI-968552; CC P10686; Q62120: Jak2; Xeno; NbExp=3; IntAct=EBI-520788, EBI-646604; CC P10686; Q60749: Khdrbs1; Xeno; NbExp=2; IntAct=EBI-520788, EBI-519077; CC P10686; Q9WU01: Khdrbs2; Xeno; NbExp=2; IntAct=EBI-520788, EBI-8339046; CC P10686; P18031: PTPN1; Xeno; NbExp=4; IntAct=EBI-520788, EBI-968788; CC P10686; Q13507: TRPC3; Xeno; NbExp=2; IntAct=EBI-520788, EBI-520807; CC -!- SUBCELLULAR LOCATION: Cell projection, lamellipodium CC {ECO:0000250|UniProtKB:P19174}. Cell projection, ruffle CC {ECO:0000250|UniProtKB:P19174}. Note=Rapidly redistributed to ruffles CC and lamellipodia structures in response to epidermal growth factor CC (EGF) treatment. {ECO:0000250|UniProtKB:P19174}. CC -!- DOMAIN: The SH3 domain mediates interaction with CLNK (By similarity). CC The SH3 domain also mediates interaction with RALGPS1 (By similarity). CC {ECO:0000250|UniProtKB:P19174, ECO:0000250|UniProtKB:Q62077}. CC -!- PTM: Ubiquitinated by CBLB in activated T-cells. CC {ECO:0000250|UniProtKB:Q62077}. 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 (By similarity). CC {ECO:0000250|UniProtKB:P19174, ECO:0000250|UniProtKB:Q62077}. 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; J03806; AAA41921.1; -; mRNA. DR EMBL; L14476; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR PIR; A31317; A31317. DR RefSeq; NP_037319.1; NM_013187.1. DR PDB; 1Y0M; X-ray; 1.20 A; A=791-851. DR PDB; 1YWO; X-ray; 1.81 A; A=790-851. DR PDB; 1YWP; X-ray; 1.60 A; A=790-851. DR PDB; 2FJL; NMR; -; A=489-547, A=851-933. DR PDB; 3GQI; X-ray; 2.50 A; B=545-770. DR PDB; 4K44; X-ray; 1.70 A; A/B=664-766. DR PDB; 4K45; X-ray; 1.50 A; A=664-766, B=770-787. DR PDB; 5EG3; X-ray; 2.61 A; B=661-773. DR PDB; 6PBC; X-ray; 2.46 A; A=21-200, A=791-1215. DR PDB; 7T8T; EM; 3.68 A; A=20-1215. DR PDB; 7Z3J; X-ray; 2.00 A; A=20-765, A=791-1215. DR PDBsum; 1Y0M; -. DR PDBsum; 1YWO; -. DR PDBsum; 1YWP; -. DR PDBsum; 2FJL; -. DR PDBsum; 3GQI; -. DR PDBsum; 4K44; -. DR PDBsum; 4K45; -. DR PDBsum; 5EG3; -. DR PDBsum; 6PBC; -. DR PDBsum; 7T8T; -. DR PDBsum; 7Z3J; -. DR AlphaFoldDB; P10686; -. DR SMR; P10686; -. DR BioGRID; 247766; 5. DR CORUM; P10686; -. DR DIP; DIP-2863N; -. DR IntAct; P10686; 27. DR MINT; P10686; -. DR STRING; 10116.ENSRNOP00000069822; -. DR BindingDB; P10686; -. DR ChEMBL; CHEMBL5188; -. DR SwissLipids; SLP:000000960; -. DR iPTMnet; P10686; -. DR PhosphoSitePlus; P10686; -. DR PaxDb; 10116-ENSRNOP00000022276; -. DR GeneID; 25738; -. DR KEGG; rno:25738; -. DR UCSC; RGD:3347; rat. DR AGR; RGD:3347; -. DR CTD; 5335; -. DR RGD; 3347; Plcg1. DR eggNOG; KOG1264; Eukaryota. DR InParanoid; P10686; -. DR OrthoDB; 2900494at2759; -. DR PhylomeDB; P10686; -. DR BRENDA; 3.1.4.11; 5301. DR Reactome; R-RNO-1169408; ISG15 antiviral mechanism. DR Reactome; R-RNO-1855204; Synthesis of IP3 and IP4 in the cytosol. DR Reactome; R-RNO-186763; Downstream signal transduction. DR Reactome; R-RNO-201556; Signaling by ALK. DR Reactome; R-RNO-202433; Generation of second messenger molecules. DR Reactome; R-RNO-2029485; Role of phospholipids in phagocytosis. DR Reactome; R-RNO-210990; PECAM1 interactions. DR Reactome; R-RNO-212718; EGFR interacts with phospholipase C-gamma. DR Reactome; R-RNO-2424491; DAP12 signaling. DR Reactome; R-RNO-2871796; FCERI mediated MAPK activation. DR Reactome; R-RNO-2871809; FCERI mediated Ca+2 mobilization. DR Reactome; R-RNO-5218921; VEGFR2 mediated cell proliferation. DR Reactome; R-RNO-5654219; Phospholipase C-mediated cascade: FGFR1. DR Reactome; R-RNO-5654221; Phospholipase C-mediated cascade, FGFR2. DR Reactome; R-RNO-5654227; Phospholipase C-mediated cascade, FGFR3. DR Reactome; R-RNO-5654228; Phospholipase C-mediated cascade, FGFR4. DR Reactome; R-RNO-8853659; RET signaling. DR Reactome; R-RNO-9026527; Activated NTRK2 signals through PLCG1. DR Reactome; R-RNO-9034793; Activated NTRK3 signals through PLCG1. DR EvolutionaryTrace; P10686; -. DR PRO; PR:P10686; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0042995; C:cell projection; ISO:RGD. DR GO; GO:0005911; C:cell-cell junction; ISO:RGD. DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:RGD. DR GO; GO:0008180; C:COP9 signalosome; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005829; C:cytosol; ISO:RGD. DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD. DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISO:RGD. DR GO; GO:0001726; C:ruffle; ISS:UniProtKB. DR GO; GO:0032587; C:ruffle membrane; ISO:RGD. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISO:RGD. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0050429; F:calcium-dependent phospholipase C activity; IDA:UniProtKB. DR GO; GO:0035254; F:glutamate receptor binding; ISO:RGD. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB. DR GO; GO:0005158; F:insulin receptor binding; IDA:RGD. DR GO; GO:0005168; F:neurotrophin TRKA receptor binding; ISO:RGD. DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; IDA:UniProtKB. DR GO; GO:0004629; F:phospholipase C activity; ISO:RGD. DR GO; GO:0051219; F:phosphoprotein binding; IPI:RGD. DR GO; GO:0019901; F:protein kinase binding; ISO:RGD. DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:RGD. DR GO; GO:0006816; P:calcium ion transport; IMP:RGD. DR GO; GO:0019722; P:calcium-mediated signaling; ISO:RGD. DR GO; GO:0016477; P:cell migration; ISO:RGD. DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISS:UniProtKB. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD. DR GO; GO:0032959; P:inositol trisphosphate biosynthetic process; IMP:RGD. DR GO; GO:0032957; P:inositol trisphosphate metabolic process; IDA:RGD. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; ISO:RGD. DR GO; GO:0031161; P:phosphatidylinositol catabolic process; IDA:RGD. DR GO; GO:0046488; P:phosphatidylinositol metabolic process; IDA:UniProtKB. DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IBA:GO_Central. DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:RGD. DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; ISO:RGD. DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IMP:RGD. DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; ISO:RGD. DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; ISO:RGD. DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IBA:GO_Central. DR GO; GO:1904643; P:response to curcumin; IDA:RGD. DR GO; GO:0009629; P:response to gravity; IEP:RGD. DR GO; GO:0042542; P:response to hydrogen peroxide; IEP:RGD. DR GO; GO:0010243; P:response to organonitrogen compound; IDA:RGD. DR GO; GO:0050852; P:T cell receptor signaling pathway; ISO:RGD. DR CDD; cd00275; C2_PLC_like; 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 DisProt; DP01851; -. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 1.10.238.10; EF-hand; 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 PRINTS; PR00452; SH3DOMAIN. 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. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Calcium; Cell projection; Hydrolase; KW Lipid degradation; Lipid metabolism; Metal-binding; Phosphoprotein; KW Reference proteome; Repeat; SH2 domain; SH3 domain; Transducer; KW Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P19174" FT CHAIN 2..1290 FT /note="1-phosphatidylinositol 4,5-bisphosphate FT phosphodiesterase gamma-1" FT /id="PRO_0000088500" 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..546 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:0000250|UniProtKB:P19174" 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:0000250|UniProtKB:P08487" FT MOD_RES 775 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P19174" FT MOD_RES 783 FT /note="Phosphotyrosine; by ITK, SYK and TXK" FT /evidence="ECO:0000250|UniProtKB:P19174" 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:22673903" FT MOD_RES 1227 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19174" FT MOD_RES 1233 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19174" FT MOD_RES 1248 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 1253 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P08487" FT MOD_RES 1263 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19174" FT MUTAGEN 842 FT /note="P->L: Inhibits interaction with AGAP2." FT /evidence="ECO:0000269|PubMed:11823862" FT HELIX 20..29 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 33..38 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 42..44 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 47..54 FT /evidence="ECO:0007829|PDB:7Z3J" FT TURN 55..58 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 59..63 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 69..74 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 75..77 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 78..85 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 88..92 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 97..99 FT /evidence="ECO:0007829|PDB:7Z3J" FT TURN 103..105 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 106..111 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 113..116 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 118..123 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 129..146 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 149..161 FT /evidence="ECO:0007829|PDB:7Z3J" FT TURN 166..168 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 169..172 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 175..183 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 210..223 FT /evidence="ECO:0007829|PDB:7Z3J" FT TURN 224..227 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 251..260 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 265..268 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 270..281 FT /evidence="ECO:0007829|PDB:7Z3J" FT TURN 285..288 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 295..302 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 305..307 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 308..310 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 312..315 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 319..322 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 326..328 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 329..336 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 339..341 FT /evidence="ECO:0007829|PDB:7Z3J" FT TURN 343..345 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 350..358 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 363..369 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 377..379 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 390..400 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 409..415 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 419..433 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 434..436 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 453..455 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 459..462 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 490..498 FT /evidence="ECO:0007829|PDB:7Z3J" FT TURN 500..502 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 505..512 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 514..522 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 551..553 FT /evidence="ECO:0007829|PDB:3GQI" FT HELIX 556..558 FT /evidence="ECO:0007829|PDB:3GQI" FT HELIX 559..576 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 583..587 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 589..591 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 595..601 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 604..613 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 615..617 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 620..623 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 628..631 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 632..639 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 644..646 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 649..651 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 665..668 FT /evidence="ECO:0007829|PDB:4K45" FT STRAND 669..672 FT /evidence="ECO:0007829|PDB:4K45" FT HELIX 675..682 FT /evidence="ECO:0007829|PDB:4K45" FT STRAND 690..695 FT /evidence="ECO:0007829|PDB:4K45" FT STRAND 701..708 FT /evidence="ECO:0007829|PDB:4K45" FT STRAND 711..720 FT /evidence="ECO:0007829|PDB:4K45" FT STRAND 723..726 FT /evidence="ECO:0007829|PDB:4K45" FT STRAND 729..733 FT /evidence="ECO:0007829|PDB:4K45" FT HELIX 734..743 FT /evidence="ECO:0007829|PDB:4K45" FT HELIX 758..762 FT /evidence="ECO:0007829|PDB:4K45" FT TURN 763..765 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 796..800 FT /evidence="ECO:0007829|PDB:1Y0M" FT STRAND 817..822 FT /evidence="ECO:0007829|PDB:1Y0M" FT STRAND 825..833 FT /evidence="ECO:0007829|PDB:1Y0M" FT STRAND 836..842 FT /evidence="ECO:0007829|PDB:1Y0M" FT HELIX 843..845 FT /evidence="ECO:0007829|PDB:1Y0M" FT STRAND 846..848 FT /evidence="ECO:0007829|PDB:1Y0M" FT HELIX 852..854 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 859..861 FT /evidence="ECO:0007829|PDB:6PBC" FT HELIX 869..871 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 872..877 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 878..880 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 882..886 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 890..892 FT /evidence="ECO:0007829|PDB:2FJL" FT STRAND 893..900 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 904..906 FT /evidence="ECO:0007829|PDB:2FJL" FT STRAND 908..912 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 916..931 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 951..954 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 967..969 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 979..984 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 985..989 FT /evidence="ECO:0007829|PDB:7Z3J" FT TURN 994..996 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 997..1006 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 1009..1012 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 1026..1029 FT /evidence="ECO:0007829|PDB:7Z3J" FT TURN 1030..1032 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 1034..1038 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 1045..1053 FT /evidence="ECO:0007829|PDB:7Z3J" FT TURN 1054..1058 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 1061..1064 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 1067..1070 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 1071..1073 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 1079..1082 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 1088..1099 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 1103..1106 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 1110..1119 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 1120..1122 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 1124..1127 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 1132..1137 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 1145..1150 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 1154..1164 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 1170..1179 FT /evidence="ECO:0007829|PDB:7Z3J" FT HELIX 1180..1182 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 1186..1193 FT /evidence="ECO:0007829|PDB:7Z3J" FT STRAND 1199..1213 FT /evidence="ECO:0007829|PDB:7Z3J" SQ SEQUENCE 1290 AA; 148548 MW; BB3240C27972CE3B CRC64; MAGVGTPCAN GCGPSAPSEA EVLHLCRSLE VGTVMTLFYS KKSQRPERKT FQVKLETRQI TWSRGADKIE GSIDIREIKE IRPGKTSRDF DRYQEDPAFR PDQSHCFVIL YGMEFRLKTL SLQATSEDEV NMWIKGLTWL MEDTLQAATP LQIERWLRKQ FYSVDRNRED RISAKDLKNM LSQVNYRVPN MRFLRERLTD FEQRSGDITY GQFAQLYRSL MYSAQKTMDL PFLETNTLRT GERPELCQVS LSEFQQFLLE YQGELWAVDR LQVQEFMLSF LRDPLREIEE PYFFLDELVT FLFSKENSVW NSQLDAVCPE TMNNPLSHYW ISSSHNTYLT GDQFSSESSL EAYARCLRMG CRCIELDCWD GPDGMPVIYH GHTLTTKIKF SDVLHTIKEH AFVASEYPVI LSIEDHCSIA QQRNMAQHFR KVLGDTLLTK PVDIAADGLP SPNQLKRKIL IKHKKLAEGS AYEEVPTSVM YSENDISNSI KNGILYLEDP VNHEWYPHYF VLTSSKIYYS EETSSDQGNE DEEEPKEASG STELHSSEKW 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 TFTKSAIIQN VEKQDGGWWR GDYGGKKQLW FPSNYVEEMI NPAILEPERE HLDENSPLGD LLRGVLDVPA CQIAIRPEGK NNRLFVFSIS MPSVAQWSLD VAADSQEELQ DWVKKIREVA QTADARLTEG KMMERRKKIA LELSELVVYC RPVPFDEEKI GTERACYRDM SSFPETKAEK YVNKAKGKKF LQYNRLQLSR IYPKGQRLDS SNYDPLPMWI CGSQLVALNF QTPDKPMQMN QALFMAGGHC GYVLQPSTMR DEAFDPFDKS SLRGLEPCVI CIEVLGARHL PKNGRGIVCP FVEIEVAGAE YDSTKQKTEF VVDNGLNPVW PAKPFHFQIS NPEFAFLRFV VYEEDMFSDQ NFLAQATFPV KGLKTGYRAV PLKNNYSEDL ELASLLIKID IFPAKENGDL SPFSGTSLRE RASDASSQLF HVRAREGSFE ARYQQPFEDF RISQEHLADH FDSRERRAPR RTRVNGDNRL //