ID PLCE1_MOUSE Reviewed; 2282 AA. AC Q8K4S1; B9EHS1; E9Q5G0; Q3TS68; Q80TC4; Q8BZF3; Q9JKM2; DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 3. DT 27-MAR-2024, entry version 168. DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 {ECO:0000305}; DE EC=3.1.4.11 {ECO:0000269|PubMed:12752375}; DE AltName: Full=Phosphoinositide phospholipase C-epsilon-1; DE AltName: Full=Phospholipase C-epsilon-1; DE Short=PLC-epsilon-1; GN Name=Plce1 {ECO:0000312|MGI:MGI:1921305}; Synonyms=Kiaa1516, Plce; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, DEVELOPMENTAL STAGE, AND RP INDUCTION. RC TISSUE=Embryo; RX PubMed=12752375; DOI=10.1046/j.1460-9568.2003.02591.x; RA Wu D., Tadano M., Edamatsu H., Masago-Toda M., Yamawaki-Kataoka Y., RA Terashima T., Mizoguchi A., Minami Y., Satoh T., Kataoka T.; RT "Neuronal lineage-specific induction of phospholipase Cepsilon expression RT in the developing mouse brain."; RL Eur. J. Neurosci. 17:1571-1580(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 919-2282. RC TISSUE=Brain; RX PubMed=12693553; DOI=10.1093/dnares/10.1.35; RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., RA Nakajima D., Nagase T., Ohara O., Koga H.; RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II. RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs RT identified by screening of terminal sequences of cDNA clones randomly RT sampled from size-fractionated libraries."; RL DNA Res. 10:35-48(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1166-2282. RC STRAIN=C57BL/6J; TISSUE=Egg, and Urinary bladder; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1661-2282. RX PubMed=11146508; RX DOI=10.1002/1097-0177(2000)9999:9999<::aid-dvdy1089>3.0.co;2-x; RA Tidhar A., Reichenstein M., Cohen D., Faerman A., Copeland N.G., RA Gilbert D.J., Jenkins N.A., Shani M.; RT "A novel transgenic marker for migrating limb muscle precursors and for RT vascular smooth muscle cells."; RL Dev. Dyn. 220:60-73(2001). RN [7] RP FUNCTION. RX PubMed=12721365; DOI=10.1073/pnas.1031494100; RA Czyzyk J., Brogdon J.L., Badou A., Henegariu O., Preston Hurlburt P., RA Flavell R., Bottomly K.; RT "Activation of CD4 T cells by Raf-independent effectors of Ras."; RL Proc. Natl. Acad. Sci. U.S.A. 100:6003-6008(2003). RN [8] RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. RX PubMed=15604236; DOI=10.1158/0008-5472.can-04-3143; RA Bai Y., Edamatsu H., Maeda S., Saito H., Suzuki N., Satoh T., Kataoka T.; RT "Crucial role of phospholipase Cepsilon in chemical carcinogen-induced skin RT tumor development."; RL Cancer Res. 64:8808-8810(2004). RN [9] RP FUNCTION, AND INDUCTION. RX PubMed=16293787; DOI=10.1161/01.res.0000196578.15385.bb; RA Wang H., Oestreich E.A., Maekawa N., Bullard T.A., Vikstrom K.L., RA Dirksen R.T., Kelley G.G., Blaxall B.C., Smrcka A.V.; RT "Phospholipase C epsilon modulates beta-adrenergic receptor-dependent RT cardiac contraction and inhibits cardiac hypertrophy."; RL Circ. Res. 97:1305-1313(2005). RN [10] RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. RX PubMed=15743817; DOI=10.1128/mcb.25.6.2191-2199.2005; RA Tadano M., Edamatsu H., Minamisawa S., Yokoyama U., Ishikawa Y., Suzuki N., RA Saito H., Wu D., Masago-Toda M., Yamawaki-Kataoka Y., Setsu T., RA Terashima T., Maeda S., Satoh T., Kataoka T.; RT "Congenital semilunar valvulogenesis defect in mice deficient in RT phospholipase C epsilon."; RL Mol. Cell. Biol. 25:2191-2199(2005). RN [11] RP INTERACTION WITH IQGAP1. RX PubMed=17086182; DOI=10.1038/ng1918; RA Hinkes B., Wiggins R.C., Gbadegesin R., Vlangos C.N., Seelow D., RA Nuernberg G., Garg P., Verma R., Chaib H., Hoskins B.E., Ashraf S., RA Becker C., Hennies H.C., Goyal M., Wharram B.L., Schachter A.D., RA Mudumana S., Drummond I., Kerjaschki D., Waldherr R., Dietrich A., RA Ozaltin F., Bakkaloglu A., Cleper R., Basel-Vanagaite L., Pohl M., RA Griebel M., Tsygin A.N., Soylu A., Mueller D., Sorli C.S., Bunney T.D., RA Katan M., Liu J., Attanasio M., O'toole J.F., Hasselbacher K., Mucha B., RA Otto E.A., Airik R., Kispert A., Kelley G.G., Smrcka A.V., Gudermann T., RA Holzman L.B., Nuernberg P., Hildebrandt F.; RT "Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic RT syndrome variant that may be reversible."; RL Nat. Genet. 38:1397-1405(2006). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1093, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Heart, Kidney, Lung, and Spleen; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). CC -!- FUNCTION: The production of the second messenger molecules CC diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated CC by activated phosphatidylinositol-specific phospholipase C enzymes. CC PLCE1 is a bifunctional enzyme which also regulates small GTPases of CC the Ras superfamily through its Ras guanine-exchange factor (RasGEF) CC activity. As an effector of heterotrimeric and small G-protein, it may CC play a role in cell survival, cell growth, actin organization and T- CC cell activation. In podocytes, is involved in the regulation of CC lamellipodia formation. Acts downstream of AVIL to allow ARP2/3 complex CC assembly (By similarity). {ECO:0000250|UniProtKB:Q9P212, CC ECO:0000269|PubMed:12721365, ECO:0000269|PubMed:15604236, CC ECO:0000269|PubMed:15743817, ECO:0000269|PubMed:16293787}. 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:12752375}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: Activated by the heterotrimeric G-protein subunits CC GNA12, GNA13 and GNB1-GNG2. Activated by HRAS, RAP1A, RHOA, RHOB, RHOC, CC RRAS and RRAS2. Activated by the G(s)-coupled GPCRs ADRB2, PTGER1 and CC CHRM3 through cyclic-AMP formation and RAP2B activation. Inhibited by CC G(i)-coupled GPCRs (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Interacts with RHOA (By similarity). Interacts with IQGAP1, CC HRAS, RAP1A, RAP2A, RAP2B and RRAS (By similarity). Interacts with CC IQGAP1 (PubMed:17086182). Interacts with AVIL (By similarity). CC {ECO:0000250|UniProtKB:Q99P84, ECO:0000250|UniProtKB:Q9P212, CC ECO:0000269|PubMed:17086182}. CC -!- INTERACTION: CC Q8K4S1; E9Q401: Ryr2; NbExp=2; IntAct=EBI-6902760, EBI-643628; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:Q9P212}. Cell membrane CC {ECO:0000250|UniProtKB:Q9P212}. Golgi apparatus membrane CC {ECO:0000250|UniProtKB:Q9P212}. Cell projection, lamellipodium CC {ECO:0000250|UniProtKB:Q9P212}. Note=Recruited to plasma membrane by CC activated HRAS and RAP2. Recruited to perinuclear membrane by activated CC RAP1A. Isoform 1 and isoform 2 associates with Golgi membranes. CC {ECO:0000250|UniProtKB:Q9P212}. CC -!- TISSUE SPECIFICITY: Highly expressed in neurons and to a lower extent CC in skin, skeletal muscle and heart (at protein level). Expressed in the CC epidermis. {ECO:0000269|PubMed:15604236, ECO:0000269|PubMed:15743817}. CC -!- DEVELOPMENTAL STAGE: Specifically expressed in cells committed to the CC neuronal lineage (at protein level). Weakly expressed at 7 dpc, CC expression strongly increases at later embryonic stages. Expressed CC abundantly in almost all neural tissues at 12.5 dpc and also detected CC in tongue muscles, genital tubercle and hand plate. At 15.5 dpc a CC strong expression in skeletal muscles is detected together with the CC strong expression in neural tissues. {ECO:0000269|PubMed:12752375}. CC -!- INDUCTION: Up-regulated during the differentiation of neural precursor CC cells into neurons but not glial cells. Up-regulated in heart upon CC induced hypertrophy. {ECO:0000269|PubMed:12752375, CC ECO:0000269|PubMed:16293787}. CC -!- DOMAIN: The Ras-associating domain 1 is degenerated and may not bind CC HRAS. The Ras-associating domain 2 mediates interaction with GTP-bound CC HRAS, RAP1A, RAP2A and RAP2B and recruitment of HRAS to the cell CC membrane (By similarity). {ECO:0000250}. CC -!- DOMAIN: The Ras-GEF domain has a GEF activity towards HRAS and RAP1A. CC Mediates activation of the mitogen-activated protein kinase pathway (By CC similarity). {ECO:0000250}. CC -!- DISRUPTION PHENOTYPE: Mice exhibit delayed onset and markedly reduced CC incidence of chemically induced skin squamous tumors. They also display CC cardiac malformations which mainly affects aortic and pulmonary valves CC and enhanced susceptibility to cardiac hypertrophy and fibrosis in CC response to chronic stress. {ECO:0000269|PubMed:15604236, CC ECO:0000269|PubMed:15743817}. CC -!- SEQUENCE CAUTION: CC Sequence=BAC29099.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB076247; BAC00906.1; -; mRNA. DR EMBL; AC111023; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC158905; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC138349; AAI38350.1; -; mRNA. DR EMBL; BC138350; AAI38351.1; -; mRNA. DR EMBL; AK122521; BAC65803.1; -; mRNA. DR EMBL; AK035546; BAC29099.1; ALT_SEQ; mRNA. DR EMBL; AK162236; BAE36807.1; -; mRNA. DR EMBL; AF233885; AAF40208.1; -; mRNA. DR CCDS; CCDS37973.1; -. DR RefSeq; NP_062534.2; NM_019588.2. DR RefSeq; XP_011245682.1; XM_011247380.1. DR AlphaFoldDB; Q8K4S1; -. DR SMR; Q8K4S1; -. DR BioGRID; 216456; 2. DR DIP; DIP-60738N; -. DR IntAct; Q8K4S1; 3. DR STRING; 10090.ENSMUSP00000130604; -. DR GlyGen; Q8K4S1; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8K4S1; -. DR PhosphoSitePlus; Q8K4S1; -. DR MaxQB; Q8K4S1; -. DR PaxDb; 10090-ENSMUSP00000130604; -. DR ProteomicsDB; 289677; -. DR Antibodypedia; 2889; 51 antibodies from 15 providers. DR DNASU; 74055; -. DR Ensembl; ENSMUST00000169713.9; ENSMUSP00000130604.2; ENSMUSG00000024998.18. DR Ensembl; ENSMUST00000182481.8; ENSMUSP00000138360.2; ENSMUSG00000024998.18. DR GeneID; 74055; -. DR KEGG; mmu:74055; -. DR UCSC; uc008hjp.1; mouse. DR AGR; MGI:1921305; -. DR CTD; 51196; -. DR MGI; MGI:1921305; Plce1. DR VEuPathDB; HostDB:ENSMUSG00000024998; -. DR eggNOG; KOG0169; Eukaryota. DR GeneTree; ENSGT00940000157356; -. DR InParanoid; Q8K4S1; -. DR OrthoDB; 2900494at2759; -. DR TreeFam; TF314432; -. DR BRENDA; 3.1.4.11; 3474. DR Reactome; R-MMU-1855204; Synthesis of IP3 and IP4 in the cytosol. DR BioGRID-ORCS; 74055; 5 hits in 79 CRISPR screens. DR ChiTaRS; Plce1; mouse. DR PRO; PR:Q8K4S1; -. DR Proteomes; UP000000589; Chromosome 19. DR RNAct; Q8K4S1; Protein. DR Bgee; ENSMUSG00000024998; Expressed in pigmented layer of retina and 228 other cell types or tissues. DR ExpressionAtlas; Q8K4S1; baseline and differential. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0019899; F:enzyme binding; ISS:UniProtKB. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; ISS:UniProtKB. DR GO; GO:0004629; F:phospholipase C activity; ISS:UniProtKB. DR GO; GO:0031267; F:small GTPase binding; ISO:MGI. DR GO; GO:0006651; P:diacylglycerol biosynthetic process; ISS:UniProtKB. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI. DR GO; GO:0032835; P:glomerulus development; ISO:MGI. DR GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB. DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW. DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IBA:GO_Central. DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; ISS:UniProtKB. DR GO; GO:0007265; P:Ras protein signal transduction; ISO:MGI. DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IBA:GO_Central. DR CDD; cd00275; C2_PLC_like; 1. DR CDD; cd16203; EFh_PI-PLCepsilon; 1. DR CDD; cd08596; PI-PLCc_epsilon; 1. DR CDD; cd17229; RA1_PLC-epsilon; 1. DR CDD; cd01780; RA2_PLC-epsilon; 1. 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; 1. DR Gene3D; 1.10.840.10; Ras guanine-nucleotide exchange factors catalytic domain; 1. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR001192; PI-PLC_fam. DR InterPro; IPR046973; PLC-epsilon1_cat. DR InterPro; IPR028398; PLC-epsilon1_RA2. DR InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl. DR InterPro; IPR015359; PLC_EF-hand-like. DR InterPro; IPR046974; PLC_epsilon1_EF. DR InterPro; IPR000909; PLipase_C_PInositol-sp_X_dom. DR InterPro; IPR001711; PLipase_C_Pinositol-sp_Y. DR InterPro; IPR000159; RA_dom. DR InterPro; IPR023578; Ras_GEF_dom_sf. DR InterPro; IPR001895; RASGEF_cat_dom. DR InterPro; IPR036964; RASGEF_cat_dom_sf. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR PANTHER; PTHR10336:SF6; 1-PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE PHOSPHODIESTERASE EPSILON-1; 1. DR PANTHER; PTHR10336; PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C FAMILY PROTEIN; 1. DR Pfam; PF00168; C2; 1. DR Pfam; PF09279; EF-hand_like; 1. DR Pfam; PF00388; PI-PLC-X; 1. DR Pfam; PF00387; PI-PLC-Y; 1. DR Pfam; PF00788; RA; 1. DR Pfam; PF00617; RasGEF; 1. DR PRINTS; PR00390; PHPHLIPASEC. DR SMART; SM00239; C2; 1. DR SMART; SM00148; PLCXc; 1. DR SMART; SM00149; PLCYc; 1. DR SMART; SM00147; RasGEF; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF47473; EF-hand; 1. DR SUPFAM; SSF51695; PLC-like phosphodiesterases; 1. DR SUPFAM; SSF48366; Ras GEF; 1. DR SUPFAM; SSF54236; Ubiquitin-like; 2. DR PROSITE; PS50004; C2; 1. DR PROSITE; PS50007; PIPLC_X_DOMAIN; 1. DR PROSITE; PS50008; PIPLC_Y_DOMAIN; 1. DR PROSITE; PS50200; RA; 1. DR PROSITE; PS50009; RASGEF_CAT; 1. DR Genevisible; Q8K4S1; MM. PE 1: Evidence at protein level; KW Calcium; Cell membrane; Cell projection; Cytoplasm; Golgi apparatus; KW Guanine-nucleotide releasing factor; Hydrolase; Lipid degradation; KW Lipid metabolism; Membrane; Metal-binding; Phosphoprotein; KW Reference proteome; Repeat; Transducer. FT CHAIN 1..2282 FT /note="1-phosphatidylinositol 4,5-bisphosphate FT phosphodiesterase epsilon-1" FT /id="PRO_0000256239" FT DOMAIN 528..781 FT /note="Ras-GEF" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168" FT DOMAIN 1373..1521 FT /note="PI-PLC X-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT DOMAIN 1710..1826 FT /note="PI-PLC Y-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00271" FT DOMAIN 1831..1956 FT /note="C2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT DOMAIN 1992..2094 FT /note="Ras-associating 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166" FT DOMAIN 2115..2218 FT /note="Ras-associating 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166" FT REGION 31..52 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 84..114 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 157..179 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1050..1146 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1548..1572 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1663..1718 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1667..1744 FT /note="Required for activation by RHOA, RHOB, GNA12, GNA13 FT and G-beta gamma" FT /evidence="ECO:0000250" FT REGION 2239..2282 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 100..114 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1054..1081 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1085..1122 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1127..1146 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 1388 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT ACT_SITE 1433 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT MOD_RES 1093 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT CONFLICT 295 FT /note="N -> S (in Ref. 1; BAC00906 and 3; FT AAI38350/AAI38351)" FT /evidence="ECO:0000305" FT CONFLICT 1798 FT /note="T -> A (in Ref. 6; AAF40208)" FT /evidence="ECO:0000305" FT CONFLICT 1829 FT /note="S -> N (in Ref. 6; AAF40208)" FT /evidence="ECO:0000305" FT CONFLICT 2215..2217 FT /note="LKE -> VKD (in Ref. 5; BAC29099)" FT /evidence="ECO:0000305" FT CONFLICT 2233 FT /note="A -> G (in Ref. 5; BAC29099)" FT /evidence="ECO:0000305" FT CONFLICT 2236 FT /note="L -> V (in Ref. 5; BAC29099)" FT /evidence="ECO:0000305" FT CONFLICT 2239 FT /note="L -> V (in Ref. 5; BAC29099)" FT /evidence="ECO:0000305" FT CONFLICT 2275 FT /note="S -> T (in Ref. 5; BAC29099)" FT /evidence="ECO:0000305" SQ SEQUENCE 2282 AA; 255047 MW; AA288A76304E43ED CRC64; MTSEEMAASV LIPVTQRKVA SAQSVAEERS VKVSDAGIPR ARAGRQGALI PPTISQWNKH KEESSRSDLS KVFSIARGEL VCDENSNEEG WEENAPDSPE NHAMNGNSLV QSHQHQFPRS QLCEARDSVT EDPCLQPGIP SPLERKVLPG IQLEMEDSPM DVSPAGSQPR IMESSGPHSD RNTAVFHFHY EADRTMSDAF HTLSENLILD DCANCVTLPG GQQNKNCMAY ACKLVELTRT CGSKNGQVQC EHCTSLRDEY LCFESSCSKA DEVCSGGGFC EDGFAHGPAA KTFLNPLEDF SDNCEDVDDF FKSKKERSTL LVRRFCKNDR EVKKSVYTGT RAIMRTLPSG CIGPAAWNYV DQKKAGLLWP CGNVMGTLSA MDIRQSGSQR LSEAQWCLIY SAVRRGEEIE DTVGSLLHCS TQLPNSETAH GRIEDGPCLK QCVRDTECEF RATLQRTSIA QYITGSLLEA TTSLGARSGL LSSFGGSTGR IMLKERQLGT SMANSNPVPS SSAGISKELI DLQPLIQFPE EVASILTEQE QNIYRRVLPM DYLCFLTRDL SSPECQRSLP RLKASISESI LTSQSGEHNA LEDLVMRFNE VSSWVTWLIL TAGSMEEKRE VFSYLVHVAK CCWNMGNYNA VMEFLAGLRS RKVLKMWQFM DQSDIETMRS LKDAMAQHES SVEYKKVVTR ALHIPGCKVV PFCGVFLKEL CEVLDGASGL LKLCPRYSSQ EEALEFVADY SGQDNFLQRV GQNGLKNSEK ELTVNSIFQV IRSCSRSLEM EEEDSASEGS GSRKNSLKDK ARWQFIIGDL LDSENDIFEK SKECDPHGSE ESQKAFDHGT ELIPWYVLSI QADVHQFLLQ GATVIHYDQD THLSARCFLQ LQPDNSTLTW MKPPTASPAG ARPKLGVLSN MAEPGKFPSP GNAGVSGLAE GILDLFSVKA VYMGHPGIDI HTVCVQNKLS SMLLSETGVT LLYGLQTTDN RLLHFVAPKH TAEMLFSGLL ELTTAVRKIR RFPDQRQQWL RKQYVSLYQE DGRYEGPTLA HAVELFGGRR WSTRNPSPGM SAKNAEKPNM QRNNTLGIST TKKKKKMLMR GESGEVTDDE MATRKAKMYR ECRSRSGSDP QDVNEQEESE ANVITNPPNP LHSRRAYSLT TAGSPNLATG MSSPISAWSS SSWHGRIRGG MQGFQSFMVS DSNMSFVEFV ELFKSFSIRS RKDLKDIFDI YSVPCNRSAS ESAPLYTNLT IEENTSDLQP DLDLLTRNVS DLGLFIKSKQ QLSDNQRQIS DAIAAASIVT NGTGIESTSL GIFGVGILQL NDFLVNCQGE HCTYDEILSI IQKFEPSVSM CHQGLLSFEG FARFLMDKDN FASKNDESRE NKKELQLPLS YYYIESSHNT YLTGHQLKGE SSVELYSQVL LQGCRSIELD CWDGDDGMPI IYHGHTLTTK IPFKEVVEAI DRSAFITSDL PIIISIENHC SLPQQRKMAE IFKSVFGEKL VAKFLFETDF SDDPMLPSPD QLRRKVLLKN KKLKAHQTPV DILKQKAHQL ASMQAQAFTG GNANPPPASN EEEEDEEDEY DYDYESLSDD NILEDRPENK SCADKLQFEY NEEVPKRIKK ADNSSGNKGK VYDMELGEEF YLPQNKKESR QIAPELSDLV IYCQAVKFPG LSTLNSSGSS RGKERKSRKS IFGNNPGRMS PGETAPFNRT SGKGSCEGMR HTWEESSPLS PSTSLSAIIR TPKCYHISSL NENAAKRLCR RGSQKLIQHT AYQLLRTYPA ATRIDSSNPN PIMFWLHGIQ LVALNYQTDD LPLHLNAAMF EANGGCGYVL KPPVLWDKSC PMYQKFSPLE RDLDNLDPAI YSLTIISGQN VCPSNSTGSP CIEVDVLGMP LDSCHFRTKP IHRNTLNPMW NEQFLFRVHF EDLVFLRFAV VENNSSAITA QRIIPLRALK RGYRHLQLRN LHNEILEISS LFINSRRMEE NPSGSSMPAS LMFNTEERKC SQTHKVTVHG VPGPEPFAVF TINEGTKAKQ LLQQVLAVDQ DTKCTATDYF LMEEKHFISK EKNECRKQPF QRAVGPEEDI VQILNSWFPE EGYVGRIVLK PQQETLEEKS IVFDDKEVIL SSEEESFFVQ VHDVSPEQPR TVIKAPRVST AQDVIQQTLC KAKYSYSILN NPNPCDYVLL EEVLKDAANK KSSTPKSSQR ILLDQECVFQ AQSKWKGAGK FILKLKEQVQ ASREDKRRGI SFASELKKLT KSTKQSRGLP SPPQLVASES VQSKEEKPVG ALSSSDTVGY QQ //