ID PLCE1_HUMAN Reviewed; 2302 AA. AC Q9P212; A6NGW0; A6NLA1; A7MBN7; A8K1D7; B9EIJ6; Q1X6H8; Q5VWL4; Q5VWL5; AC Q9H9X8; Q9HBX6; Q9HC53; Q9UHV3; DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 31-OCT-2006, sequence version 3. DT 24-JAN-2024, entry version 193. DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 {ECO:0000305}; DE EC=3.1.4.11 {ECO:0000269|PubMed:11022047, ECO:0000269|PubMed:11022048}; DE AltName: Full=Pancreas-enriched phospholipase C; 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|HGNC:HGNC:17175}; GN Synonyms=KIAA1516, PLCE, PPLC; 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), TISSUE SPECIFICITY, CATALYTIC RP ACTIVITY, COFACTOR, INTERACTION WITH HRAS AND RAP1A, SUBCELLULAR LOCATION, RP ACTIVITY REGULATION, AND VARIANTS ILE-1777 AND ARG-1927. RC TISSUE=Fetal brain; RX PubMed=11022048; DOI=10.1074/jbc.m008324200; RA Song C., Hu C.-D., Masago M., Kariya K., Yamawaki-Kataoka Y., RA Shibatohge M., Wu D., Satoh T., Kataoka T.; RT "Regulation of a novel human phospholipase C, PLCepsilon, through membrane RT targeting by Ras."; RL J. Biol. Chem. 276:2752-2757(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, RP SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND RP MUTAGENESIS OF HIS-1452. RC TISSUE=Heart; RX PubMed=11022047; DOI=10.1074/jbc.m008119200; RA Lopez I., Mak E.C., Ding J., Hamm H.E., Lomasney J.W.; RT "A novel bifunctional phospholipase C that is regulated by Galpha 12 and RT stimulates the Ras/mitogen-activated protein kinase pathway."; RL J. Biol. Chem. 276:2758-2765(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-1927. RC TISSUE=Brain; RX PubMed=10819331; DOI=10.1093/dnares/7.2.143; RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:143-150(2000). RN [4] RP SEQUENCE REVISION. RA Ohara O., Nagase T., Kikuno R.; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-1927. 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 [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1098-2302 (ISOFORMS 1/2), AND VARIANTS RP ILE-1777 AND ARG-1927. RC TISSUE=Pancreas; RA Kawasaki H., Chen E.J., Springett G.M., Graybiel A.M., Housman D.E.; RT "A novel phospholipase C enriched in pancreas."; RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1383 (ISOFORM 2), AND RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1475-2302 (ISOFORMS 1/2). RC TISSUE=Brain, and Teratocarcinoma; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1987-2302 (ISOFORMS 1/2). RC TISSUE=Brain; RA Buessow K.; RT "Sequence of cDNA clone MPMGp800D13530."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=11395506; DOI=10.1074/jbc.m103530200; RA Jin T.-G., Satoh T., Liao Y., Song C., Gao X., Kariya K., Hu C.-D., RA Kataoka T.; RT "Role of the CDC25 homology domain of phospholipase Cepsilon in RT amplification of Rap1-dependent signaling."; RL J. Biol. Chem. 276:30301-30307(2001). RN [12] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=11715024; DOI=10.1038/ncb1101-1020; RA Schmidt M., Evellin S., Weernink P.A.O., von Dorp F., Rehmann H., RA Lomasney J.W., Jakobs K.H.; RT "A new phospholipase-C-calcium signalling pathway mediated by cyclic AMP RT and a Rap GTPase."; RL Nat. Cell Biol. 3:1020-1024(2001). RN [13] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=11877431; DOI=10.1074/jbc.m112024200; RA Evellin S., Nolte J., Tysack K., vom Dorp F., Thiel M., Weernink P.A.O., RA Jakobs K.H., Webb E.J., Lomasney J.W., Schmidt M.; RT "Stimulation of phospholipase C-epsilon by the M3 muscarinic acetylcholine RT receptor mediated by cyclic AMP and the GTPase Rap2B."; RL J. Biol. Chem. 277:16805-16813(2002). RN [14] RP INTERACTION WITH RAP1A; RAP2A AND RAP2B. RX PubMed=12444546; DOI=10.1038/sj.onc.1206003; RA Song C., Satoh T., Edamatsu H., Wu D., Tadano M., Gao X., Kataoka T.; RT "Differential roles of Ras and Rap1 in growth factor-dependent activation RT of phospholipase C epsilon."; RL Oncogene 21:8105-8113(2002). RN [15] 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 [16] RP ACTIVITY REGULATION. RX PubMed=15157671; DOI=10.1016/j.cellsig.2004.01.009; RA vom Dorp F., Sari A.Y., Sanders H., Keiper M., Oude Weernink P.A., RA Jakobs K.H., Schmidt M.; RT "Inhibition of phospholipase C-epsilon by Gi-coupled receptors."; RL Cell. Signal. 16:921-928(2004). RN [17] RP 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 [18] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=15558028; DOI=10.1038/sj.onc.1208168; RA Sorli S.C., Bunney T.D., Sugden P.H., Paterson H.F., Katan M.; RT "Signaling properties and expression in normal and tumor tissues of two RT phospholipase C epsilon splice variants."; RL Oncogene 24:90-100(2005). RN [19] RP FUNCTION, INTERACTION WITH RRAS, AND ACTIVITY REGULATION. RX PubMed=16537651; DOI=10.1242/jcs.02835; RA Ada-Nguema A.S., Xenias H., Sheetz M.P., Keely P.J.; RT "The small GTPase R-Ras regulates organization of actin and drives membrane RT protrusions through the activity of PLCepsilon."; RL J. Cell Sci. 119:1307-1319(2006). RN [20] RP SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH AVIL, AND TISSUE RP SPECIFICITY. RX PubMed=29058690; DOI=10.1172/jci94138; RA Rao J., Ashraf S., Tan W., van der Ven A.T., Gee H.Y., Braun D.A., RA Feher K., George S.P., Esmaeilniakooshkghazi A., Choi W.I., RA Jobst-Schwan T., Schneider R., Schmidt J.M., Widmeier E., Warejko J.K., RA Hermle T., Schapiro D., Lovric S., Shril S., Daga A., Nayir A., Shenoy M., RA Tse Y., Bald M., Helmchen U., Mir S., Berdeli A., Kari J.A., El Desoky S., RA Soliman N.A., Bagga A., Mane S., Jairajpuri M.A., Lifton R.P., Khurana S., RA Martins J.C., Hildebrandt F.; RT "Advillin acts upstream of phospholipase C 1 in steroid-resistant nephrotic RT syndrome."; RL J. Clin. Invest. 127:4257-4269(2017). RN [21] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 2131-2246 OF MUTANT LEU-2176 IN RP COMPLEX WITH HRAS, STRUCTURE BY NMR OF 2006-2114 AND 2131-2246, AND RP MUTAGENESIS OF GLN-2140; GLN-2148; ARG-2150; LYS-2171 AND TYR-2174. RX PubMed=16483931; DOI=10.1016/j.molcel.2006.01.008; RA Bunney T.D., Harris R., Gandarillas N.L., Josephs M.B., Roe S.M., RA Sorli S.C., Paterson H.F., Rodrigues-Lima F., Esposito D., Ponting C.P., RA Gierschik P., Pearl L.H., Driscoll P.C., Katan M.; RT "Structural and mechanistic insights into ras association domains of RT phospholipase C epsilon."; RL Mol. Cell 21:495-507(2006). RN [22] RP VARIANT NPHS3 LEU-1484, FUNCTION, AND 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 [23] RP VARIANT NPHS3 1020-GLN--GLN-2302 DEL, AND VARIANT ARG-2173. RX PubMed=23595123; DOI=10.1038/jhg.2013.27; RA Al-Hamed M.H., Al-Sabban E., Al-Mojalli H., Al-Harbi N., Faqeih E., RA Al Shaya H., Alhasan K., Al-Hissi S., Rajab M., Edwards N., Al-Abbad A., RA Al-Hassoun I., Sayer J.A., Meyer B.F.; RT "A molecular genetic analysis of childhood nephrotic syndrome in a cohort RT of Saudi Arabian families."; RL J. Hum. Genet. 58:480-489(2013). 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 (PubMed:29058690). {ECO:0000269|PubMed:11022047, CC ECO:0000269|PubMed:11395506, ECO:0000269|PubMed:11715024, CC ECO:0000269|PubMed:11877431, ECO:0000269|PubMed:12721365, CC ECO:0000269|PubMed:16537651, ECO:0000269|PubMed:17086182, CC ECO:0000269|PubMed:29058690}. 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:11022047, ECO:0000269|PubMed:11022048}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:11022048}; 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. {ECO:0000269|PubMed:11022047, CC ECO:0000269|PubMed:11022048, ECO:0000269|PubMed:11715024, CC ECO:0000269|PubMed:11877431, ECO:0000269|PubMed:15157671, CC ECO:0000269|PubMed:16537651}. CC -!- SUBUNIT: Interacts with RHOA (By similarity). Interacts with GTP-bound CC HRAS, RAP1A, RAP2A, RAP2B and RRAS (PubMed:11022048, PubMed:12444546, CC PubMed:16483931, PubMed:16537651). Interacts with AVIL CC (PubMed:29058690). Interacts with IQGAP1 (PubMed:17086182). CC {ECO:0000250|UniProtKB:Q99P84, ECO:0000269|PubMed:11022048, CC ECO:0000269|PubMed:12444546, ECO:0000269|PubMed:16483931, CC ECO:0000269|PubMed:16537651, ECO:0000269|PubMed:17086182, CC ECO:0000269|PubMed:29058690}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Cell membrane. Golgi CC apparatus membrane. Cell projection, lamellipodium CC {ECO:0000269|PubMed:29058690}. 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 -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=PLCepsilon1a; CC IsoId=Q9P212-1; Sequence=Displayed; CC Name=2; Synonyms=PLCepsilon1b; CC IsoId=Q9P212-2; Sequence=VSP_021335, VSP_021336; CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in podocytes CC (PubMed:29058690). {ECO:0000269|PubMed:15558028, CC ECO:0000269|PubMed:29058690}. CC -!- TISSUE SPECIFICITY: [Isoform 1]: Broadly expressed and only absent in CC peripheral blood leukocytes. {ECO:0000269|PubMed:11022048, CC ECO:0000269|PubMed:15558028}. CC -!- TISSUE SPECIFICITY: [Isoform 2]: Specifically expressed in placenta, CC lung and spleen. {ECO:0000269|PubMed:11022047, CC ECO:0000269|PubMed:15558028}. CC -!- INDUCTION: Overexpressed during heart failure. 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. CC -!- DOMAIN: The Ras-GEF domain has a GEF activity towards HRAS and RAP1A. CC Mediates activation of the mitogen-activated protein kinase pathway. CC -!- DISEASE: Nephrotic syndrome 3 (NPHS3) [MIM:610725]: A form of nephrotic CC syndrome, a renal disease clinically characterized by severe CC proteinuria, resulting in complications such as hypoalbuminemia, CC hyperlipidemia and edema. Kidney biopsies show non-specific histologic CC changes such as focal segmental glomerulosclerosis and diffuse CC mesangial proliferation. Some affected individuals have an inherited CC steroid-resistant form and progress to end-stage renal failure. Most CC patients with NPHS3 show diffuse mesangial sclerosis on renal biopsy, CC which is a pathologic entity characterized by mesangial matrix CC expansion with no mesangial hypercellularity, hypertrophy of the CC podocytes, vacuolized podocytes, thickened basement membranes, and CC diminished patency of the capillary lumen. CC {ECO:0000269|PubMed:17086182, ECO:0000269|PubMed:23595123}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAF22005.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAG17145.2; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAA96040.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB14090.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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; AF190642; AAG17145.2; ALT_FRAME; mRNA. DR EMBL; AF170071; AAG28341.1; -; mRNA. DR EMBL; AB040949; BAA96040.2; ALT_INIT; mRNA. DR EMBL; AL139118; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL139124; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL365510; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL389885; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471066; EAW50042.1; -; Genomic_DNA. DR EMBL; CH471066; EAW50043.1; -; Genomic_DNA. DR EMBL; BC140705; AAI40706.1; -; mRNA. DR EMBL; BC151854; AAI51855.1; -; mRNA. DR EMBL; AF117948; AAF22005.1; ALT_FRAME; mRNA. DR EMBL; AK022543; BAB14090.1; ALT_INIT; mRNA. DR EMBL; AK289852; BAF82541.1; -; mRNA. DR EMBL; AY995135; AAY45890.1; -; mRNA. DR CCDS; CCDS41552.1; -. [Q9P212-1] DR CCDS; CCDS53555.1; -. [Q9P212-2] DR RefSeq; NP_001159451.1; NM_001165979.2. [Q9P212-2] DR RefSeq; NP_001275918.1; NM_001288989.1. DR RefSeq; NP_057425.3; NM_016341.3. [Q9P212-1] DR PDB; 2BYE; NMR; -; A=2006-2114. DR PDB; 2BYF; NMR; -; A=2131-2246. DR PDB; 2C5L; X-ray; 1.90 A; C/D=2131-2246. DR PDBsum; 2BYE; -. DR PDBsum; 2BYF; -. DR PDBsum; 2C5L; -. DR AlphaFoldDB; Q9P212; -. DR BMRB; Q9P212; -. DR SMR; Q9P212; -. DR BioGRID; 119370; 16. DR IntAct; Q9P212; 6. DR STRING; 9606.ENSP00000360431; -. DR SwissLipids; SLP:000000663; -. DR GlyCosmos; Q9P212; 1 site, 1 glycan. DR GlyGen; Q9P212; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9P212; -. DR PhosphoSitePlus; Q9P212; -. DR BioMuta; PLCE1; -. DR DMDM; 118595723; -. DR EPD; Q9P212; -. DR jPOST; Q9P212; -. DR MassIVE; Q9P212; -. DR MaxQB; Q9P212; -. DR PaxDb; 9606-ENSP00000360431; -. DR PeptideAtlas; Q9P212; -. DR ProteomicsDB; 83705; -. [Q9P212-1] DR ProteomicsDB; 83706; -. [Q9P212-2] DR Antibodypedia; 2889; 51 antibodies from 15 providers. DR DNASU; 51196; -. DR Ensembl; ENST00000371375.2; ENSP00000360426.1; ENSG00000138193.17. [Q9P212-2] DR Ensembl; ENST00000371380.8; ENSP00000360431.2; ENSG00000138193.17. [Q9P212-1] DR Ensembl; ENST00000675218.1; ENSP00000501910.1; ENSG00000138193.17. [Q9P212-2] DR GeneID; 51196; -. DR KEGG; hsa:51196; -. DR MANE-Select; ENST00000371380.8; ENSP00000360431.2; NM_016341.4; NP_057425.3. DR UCSC; uc001kjk.4; human. [Q9P212-1] DR AGR; HGNC:17175; -. DR CTD; 51196; -. DR DisGeNET; 51196; -. DR GeneCards; PLCE1; -. DR HGNC; HGNC:17175; PLCE1. DR HPA; ENSG00000138193; Low tissue specificity. DR MalaCards; PLCE1; -. DR MIM; 608414; gene. DR MIM; 610725; phenotype. DR neXtProt; NX_Q9P212; -. DR OpenTargets; ENSG00000138193; -. DR Orphanet; 656; Genetic steroid-resistant nephrotic syndrome. DR PharmGKB; PA33391; -. DR VEuPathDB; HostDB:ENSG00000138193; -. DR eggNOG; KOG0169; Eukaryota. DR GeneTree; ENSGT00940000157356; -. DR HOGENOM; CLU_001158_0_0_1; -. DR InParanoid; Q9P212; -. DR OMA; KKNYMAY; -. DR OrthoDB; 2900494at2759; -. DR PhylomeDB; Q9P212; -. DR TreeFam; TF314432; -. DR BioCyc; MetaCyc:HS06473-MONOMER; -. DR BRENDA; 3.1.4.11; 2681. DR PathwayCommons; Q9P212; -. DR Reactome; R-HSA-1855204; Synthesis of IP3 and IP4 in the cytosol. DR SignaLink; Q9P212; -. DR SIGNOR; Q9P212; -. DR BioGRID-ORCS; 51196; 26 hits in 1155 CRISPR screens. DR ChiTaRS; PLCE1; human. DR EvolutionaryTrace; Q9P212; -. DR GeneWiki; PLCE1; -. DR GenomeRNAi; 51196; -. DR Pharos; Q9P212; Tbio. DR PRO; PR:Q9P212; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q9P212; Protein. DR Bgee; ENSG00000138193; Expressed in renal glomerulus and 191 other cell types or tissues. DR ExpressionAtlas; Q9P212; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; TAS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; IDA:UniProtKB. DR GO; GO:0004629; F:phospholipase C activity; IDA:UniProtKB. DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB. DR GO; GO:0019722; P:calcium-mediated signaling; NAS:UniProtKB. DR GO; GO:0006651; P:diacylglycerol biosynthetic process; IMP:UniProtKB. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0032835; P:glomerulus development; IMP:HGNC-UCL. DR GO; GO:0035556; P:intracellular signal transduction; IDA: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; IDA:UniProtKB. DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IMP:UniProtKB. DR GO; GO:0007265; P:Ras protein signal transduction; IDA:UniProtKB. 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; SM00314; RA; 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; Q9P212; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Cell membrane; KW Cell projection; Cytoplasm; Disease variant; 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..2302 FT /note="1-phosphatidylinositol 4,5-bisphosphate FT phosphodiesterase epsilon-1" FT /id="PRO_0000256238" FT DOMAIN 531..790 FT /note="Ras-GEF" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168" FT DOMAIN 1392..1540 FT /note="PI-PLC X-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT DOMAIN 1730..1846 FT /note="PI-PLC Y-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00271" FT DOMAIN 1851..1976 FT /note="C2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT DOMAIN 2012..2114 FT /note="Ras-associating 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166" FT DOMAIN 2135..2238 FT /note="Ras-associating 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166" FT REGION 1053..1192 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1567..1591 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1683..1743 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1686..1764 FT /note="Required for activation by RHOA, RHOB, GNA12, GNA13 FT and G-beta gamma" FT /evidence="ECO:0000250" FT REGION 2260..2302 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1057..1084 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1088..1125 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1146..1192 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1702..1743 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 1407 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT ACT_SITE 1452 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT MOD_RES 1096 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8K4S1" FT VAR_SEQ 1..308 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11022047, FT ECO:0000303|PubMed:14702039" FT /id="VSP_021335" FT VAR_SEQ 309..402 FT /note="DVEEDAFKSKKERSTLLVRRFCKNDREVKKSVYTGTRAIVRTLPSGHIGLTA FT WSYIDQKRNGPLLPCGRVMEPPSTVEIRQDGSQRLSEAQWYP -> MVSEGSAAGRDFA FT GMEEVRQLHVRFCKGIKIWHQAWFLCSLLGREPQEREAGCQLWLCTLSAVLKVGWLFPL FT SEVPNFTLLKDGCGCWRLKEDQ (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11022047, FT ECO:0000303|PubMed:14702039" FT /id="VSP_021336" FT VARIANT 469 FT /note="S -> T (in dbSNP:rs17508082)" FT /id="VAR_031843" FT VARIANT 548 FT /note="R -> L (in dbSNP:rs17417407)" FT /id="VAR_031844" FT VARIANT 1020..2302 FT /note="Missing (in NPHS3)" FT /evidence="ECO:0000269|PubMed:23595123" FT /id="VAR_087600" FT VARIANT 1484 FT /note="S -> L (in NPHS3; gives rise to focal segmental FT glomerulosclerosis rather than diffuse mesangial sclerosis; FT dbSNP:rs121912605)" FT /evidence="ECO:0000269|PubMed:17086182" FT /id="VAR_029883" FT VARIANT 1575 FT /note="R -> P (in dbSNP:rs2274224)" FT /id="VAR_031845" FT VARIANT 1777 FT /note="T -> I (in dbSNP:rs3765524)" FT /evidence="ECO:0000269|PubMed:11022048, ECO:0000269|Ref.8" FT /id="VAR_031846" FT VARIANT 1927 FT /note="H -> R (in dbSNP:rs2274223)" FT /evidence="ECO:0000269|PubMed:10819331, FT ECO:0000269|PubMed:11022048, ECO:0000269|PubMed:15489334, FT ECO:0000269|Ref.8" FT /id="VAR_031847" FT VARIANT 2173 FT /note="K -> R (in dbSNP:rs111929795)" FT /evidence="ECO:0000269|PubMed:23595123" FT /id="VAR_087601" FT MUTAGEN 1452 FT /note="H->L: Loss of the phospholipase C enzymatic FT activity. Still activates HRAS and the MAP kinase pathway." FT /evidence="ECO:0000269|PubMed:11022047" FT MUTAGEN 2140 FT /note="Q->E: Increases 2.8-fold the affinity for HRAS." FT /evidence="ECO:0000269|PubMed:16483931" FT MUTAGEN 2148 FT /note="Q->E: Decreases 17.5-fold the affinity for HRAS." FT /evidence="ECO:0000269|PubMed:16483931" FT MUTAGEN 2148 FT /note="Q->K: Increases 1.4-fold the affinity for HRAS." FT /evidence="ECO:0000269|PubMed:16483931" FT MUTAGEN 2150 FT /note="R->L: Abolishes interaction with HRAS." FT /evidence="ECO:0000269|PubMed:16483931" FT MUTAGEN 2171 FT /note="K->L: No effect on HRAS-binding." FT /evidence="ECO:0000269|PubMed:16483931" FT MUTAGEN 2174 FT /note="Y->L: Reduces HRAS-binding." FT /evidence="ECO:0000269|PubMed:16483931" FT CONFLICT 502 FT /note="G -> S (in Ref. 2; AAG28341)" FT /evidence="ECO:0000305" FT CONFLICT 703 FT /note="V -> F (in Ref. 2; AAG28341)" FT /evidence="ECO:0000305" FT CONFLICT 1133 FT /note="E -> K (in Ref. 2; AAG28341)" FT /evidence="ECO:0000305" FT CONFLICT 1229..1230 FT /note="SR -> QA (in Ref. 8; AAF22005)" FT /evidence="ECO:0000305" FT CONFLICT 1456 FT /note="L -> P (in Ref. 1; AAG17145)" FT /evidence="ECO:0000305" FT CONFLICT 1571 FT /note="N -> D (in Ref. 9; BAB14090)" FT /evidence="ECO:0000305" FT CONFLICT 1575 FT /note="R -> Q (in Ref. 2; AAG28341)" FT /evidence="ECO:0000305" FT CONFLICT 1672 FT /note="C -> R (in Ref. 1; AAG17145)" FT /evidence="ECO:0000305" FT CONFLICT 1705 FT /note="P -> L (in Ref. 9; BAB14090)" FT /evidence="ECO:0000305" FT CONFLICT 2125 FT /note="D -> G (in Ref. 9; BAB14090)" FT /evidence="ECO:0000305" FT STRAND 2015..2020 FT /evidence="ECO:0007829|PDB:2BYE" FT STRAND 2022..2031 FT /evidence="ECO:0007829|PDB:2BYE" FT HELIX 2038..2046 FT /evidence="ECO:0007829|PDB:2BYE" FT STRAND 2049..2052 FT /evidence="ECO:0007829|PDB:2BYE" FT STRAND 2058..2064 FT /evidence="ECO:0007829|PDB:2BYE" FT STRAND 2069..2072 FT /evidence="ECO:0007829|PDB:2BYE" FT STRAND 2081..2084 FT /evidence="ECO:0007829|PDB:2BYE" FT STRAND 2086..2088 FT /evidence="ECO:0007829|PDB:2BYE" FT HELIX 2090..2096 FT /evidence="ECO:0007829|PDB:2BYE" FT TURN 2099..2103 FT /evidence="ECO:0007829|PDB:2BYE" FT STRAND 2107..2112 FT /evidence="ECO:0007829|PDB:2BYE" FT STRAND 2136..2143 FT /evidence="ECO:0007829|PDB:2C5L" FT STRAND 2150..2156 FT /evidence="ECO:0007829|PDB:2C5L" FT HELIX 2161..2171 FT /evidence="ECO:0007829|PDB:2C5L" FT TURN 2172..2174 FT /evidence="ECO:0007829|PDB:2C5L" FT HELIX 2176..2180 FT /evidence="ECO:0007829|PDB:2C5L" FT HELIX 2184..2186 FT /evidence="ECO:0007829|PDB:2C5L" FT STRAND 2187..2194 FT /evidence="ECO:0007829|PDB:2C5L" FT STRAND 2198..2204 FT /evidence="ECO:0007829|PDB:2BYF" FT STRAND 2207..2211 FT /evidence="ECO:0007829|PDB:2C5L" FT HELIX 2218..2223 FT /evidence="ECO:0007829|PDB:2C5L" FT STRAND 2229..2235 FT /evidence="ECO:0007829|PDB:2C5L" FT TURN 2236..2238 FT /evidence="ECO:0007829|PDB:2C5L" FT CONFLICT Q9P212-2:69 FT /note="L -> P (in Ref. 2; AAG28341)" FT /evidence="ECO:0000305" SQ SEQUENCE 2302 AA; 258715 MW; 71DDE446277077A3 CRC64; MTSEEMTASV LIPVTQRKVV SAQSAADESS EKVSDINISK AHTVRRSGET SHTISQLNKL KEEPSGSNLP KILSIAREKI VSDENSNEKC WEKIMPDSAK NLNINCNNIL RNHQHGLPQR QFYEMYNSVA EEDLCLETGI PSPLERKVFP GIQLELDRPS MGISPLGNQS VIIETGRAHP DSRRAVFHFH YEVDRRMSDT FCTLSENLIL DDCGNCVPLP GGEEKQKKNY VAYTCKLMEL AKNCDNKNEQ LQCDHCDTLN DKYFCFEGSC EKVDMVYSGD SFCRKDFTDS QAAKTFLSHF EDFPDNCDDV EEDAFKSKKE RSTLLVRRFC KNDREVKKSV YTGTRAIVRT LPSGHIGLTA WSYIDQKRNG PLLPCGRVME PPSTVEIRQD GSQRLSEAQW YPIYNAVRRE ETENTVGSLL HFLTKLPASE TAHGRISVGP CLKQCVRDTV CEYRATLQRT SISQYITGSL LEATTSLGAR SGLLSTFGGS TGRMMLKERQ PGPSVANSNA LPSSSAGISK ELIDLQPLIQ FPEEVASILM EQEQTIYRRV LPVDYLCFLT RDLGTPECQS SLPCLKASIS ASILTTQNGE HNALEDLVMR FNEVSSWVTW LILTAGSMEE KREVFSYLVH VAKCCWNMGN YNAVMEFLAG LRSRKVLKMW QFMDQSDIET MRSLKDAMAQ HESSCEYRKV VTRALHIPGC KVVPFCGVFL KELCEVLDGA SGLMKLCPRY NSQEETLEFV ADYSGQDNFL QRVGQNGLKN SEKESTVNSI FQVIRSCNRS LETDEEDSPS EGNSSRKSSL KDKSRWQFII GDLLDSDNDI FEQSKEYDSH GSEDSQKAFD HGTELIPWYV LSIQADVHQF LLQGATVIHY DQDTHLSARC FLQLQPDNST LTWVKPTTAS PASSKAKLGV LNNTAEPGKF PLLGNAGLSS LTEGVLDLFA VKAVYMGHPG IDIHTVCVQN KLGSMFLSET GVTLLYGLQT TDNRLLHFVA PKHTAKMLFS GLLELTRAVR KMRKFPDQRQ QWLRKQYVSL YQEDGRYEGP TLAHAVELFG GRRWSARNPS PGTSAKNAEK PNMQRNNTLG ISTTKKKKKI LMRGESGEVT DDEMATRKAK MHKECRSRSG SDPQDINEQE ESEVNAIANP PNPLPSRRAH SLTTAGSPNL AAGTSSPIRP VSSPVLSSSN KSPSSAWSSS SWHGRIKGGM KGFQSFMVSD SNMSFVEFVE LFKSFSVRSR KDLKDLFDVY AVPCNRSGSE SAPLYTNLTI DENTSDLQPD LDLLTRNVSD LGLFIKSKQQ LSDNQRQISD AIAAASIVTN GTGIESTSLG IFGVGILQLN DFLVNCQGEH CTYDEILSII QKFEPSISMC HQGLMSFEGF ARFLMDKENF ASKNDESQEN IKELQLPLSY YYIESSHNTY LTGHQLKGES SVELYSQVLL QGCRSVELDC WDGDDGMPII YHGHTLTTKI PFKEVVEAID RSAFINSDLP IIISIENHCS LPQQRKMAEI FKTVFGEKLV TKFLFETDFS DDPMLPSPDQ LRKKVLLKNK KLKAHQTPVD ILKQKAHQLA SMQVQAYNGG NANPRPANNE EEEDEEDEYD YDYESLSDDN ILEDRPENKS CNDKLQFEYN EEIPKRIKKA DNSACNKGKV YDMELGEEFY LDQNKKESRQ IAPELSDLVI YCQAVKFPGL STLNASGSSR GKERKSRKSI FGNNPGRMSP GETASFNKTS GKSSCEGIRQ TWEESSSPLN PTTSLSAIIR TPKCYHISSL NENAAKRLCR RYSQKLTQHT ACQLLRTYPA ATRIDSSNPN PLMFWLHGIQ LVALNYQTDD LPLHLNAAMF EANGGCGYVL KPPVLWDKNC PMYQKFSPLE RDLDSMDPAV YSLTIVSGQN VCPSNSMGSP CIEVDVLGMP LDSCHFRTKP IHRNTLNPMW NEQFLFHVHF EDLVFLRFAV VENNSSAVTA QRIIPLKALK RGYRHLQLRN LHNEVLEISS LFINSRRMEE NSSGNTMSAS SMFNTEERKC LQTHRVTVHG VPGPEPFTVF TINGGTKAKQ LLQQILTNEQ DIKPVTTDYF LMEEKYFISK EKNECRKQPF QRAIGPEEEI MQILSSWFPE EGYMGRIVLK TQQENLEEKN IVQDDKEVIL SSEEESFFVQ VHDVSPEQPR TVIKAPRVST AQDVIQQTLC KAKYSYSILS NPNPSDYVLL EEVVKDTTNK KTTTPKSSQR VLLDQECVFQ AQSKWKGAGK FILKLKEQVQ ASREDKKKGI SFASELKKLT KSTKQPRGLT SPSQLLTSES IQTKEEKPVG GLSSSDTMDY RQ //