ECE1_HUMAN
ID ECE1_HUMAN Reviewed; 770 AA.
AC P42892; A8K3P1; B4E291; Q14217; Q17RN5; Q2Z2K8; Q58GE7; Q5THM5; Q5THM7;
AC Q5THM8; Q9UJQ6; Q9UPF4; Q9UPM4; Q9Y501;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Endothelin-converting enzyme 1;
DE Short=ECE-1;
DE EC=3.4.24.71;
GN Name=ECE1;
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 B).
RX PubMed=7695628; DOI=10.1006/bbrc.1995.1397;
RA Yorimitsu K., Moroi K., Inagaki N., Saito T., Masuda Y., Masaki T.,
RA Seino S., Kimura S.;
RT "Cloning and sequencing of a human endothelin converting enzyme in renal
RT adenocarcinoma (ACHN) cells producing endothelin-2.";
RL Biochem. Biophys. Res. Commun. 208:721-727(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RX PubMed=7864876; DOI=10.1006/bbrc.1995.1258;
RA Shimada K., Matsushita Y., Wakabayashi K., Takahashi M., Matsubara A.,
RA Iijima Y., Tanzawa K.;
RT "Cloning and functional expression of human endothelin-converting enzyme
RT cDNA.";
RL Biochem. Biophys. Res. Commun. 207:807-812(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A AND B).
RC TISSUE=Placenta;
RX PubMed=8530372; DOI=10.1074/jbc.270.50.29794;
RA Valdenaire O., Rohrbacher E., Mattei M.-G.;
RT "Organization of the gene encoding the human endothelin-converting enzyme
RT (ECE-1).";
RL J. Biol. Chem. 270:29794-29798(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C).
RC TISSUE=Umbilical vein endothelial cell;
RA Takayanagi R.;
RT "Human endothelin-converting enzyme-1c.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC TISSUE=Trachea;
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ILE-341.
RG NIEHS SNPs program;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
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 [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-132 (ISOFORM D), AND TISSUE SPECIFICITY.
RX PubMed=10491078; DOI=10.1046/j.1432-1327.1999.00602.x;
RA Valdenaire O., Lepailleur-Enouf D., Egidy G., Thouard A., Barret A.,
RA Vranckx R., Tougard C., Michel J.-B.;
RT "A fourth isoform of endothelin-converting enzyme (ECE-1) is generated from
RT an additional promoter.";
RL Eur. J. Biochem. 264:341-349(1999).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-103 (ISOFORM C), FUNCTION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Umbilical vein endothelial cell;
RX PubMed=9396733; DOI=10.1042/bj3280871;
RA Schweizer A., Valdenaire O., Nelboeck P., Deuschle U.,
RA Dumas Milne Edwards J.B., Stumpf J.G., Loeffler B.-M.;
RT "Human endothelin-converting enzyme (ECE-1): three isoforms with distinct
RT subcellular localizations.";
RL Biochem. J. 328:871-877(1997).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 7-770 (ISOFORM B).
RC TISSUE=Placenta;
RX PubMed=7805846; DOI=10.1016/0014-5793(94)01277-6;
RA Schmidt M., Kroeger B., Jacob E., Seulberger H., Subkowski T., Otter R.,
RA Meyer T., Schmalzing G., Hillen H.;
RT "Molecular characterization of human and bovine endothelin converting
RT enzyme (ECE-1).";
RL FEBS Lett. 356:238-243(1994).
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 713-770.
RA Flowers M.A., Tai S.C., Baluyut C.A., Cheung A.H., Kau C.L., Wong G.K.T.,
RA Marsden P.A.;
RT "Characterization of the human endothelin converting enzyme-1 gene (ECE-1):
RT genomic structure and chromosomal localization.";
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [15]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-210.
RC TISSUE=Platelet;
RX PubMed=16263699; DOI=10.1074/mcp.m500324-mcp200;
RA Lewandrowski U., Moebius J., Walter U., Sickmann A.;
RT "Elucidation of N-glycosylation sites on human platelet proteins: a
RT glycoproteomic approach.";
RL Mol. Cell. Proteomics 5:226-233(2006).
RN [16]
RP IDENTIFICATION BY MASS 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 [17]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-166; ASN-210; ASN-270 AND
RP ASN-316.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [18]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-166; ASN-210; ASN-362 AND
RP ASN-383.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-25, AND IDENTIFICATION BY
RP 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 [20]
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 [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [22]
RP ACTIVITY REGULATION.
RX PubMed=26931059; DOI=10.1038/srep22413;
RA Smith A.I., Rajapakse N.W., Kleifeld O., Lomonte B., Sikanyika N.L.,
RA Spicer A.J., Hodgson W.C., Conroy P.J., Small D.H., Kaye D.M.,
RA Parkington H.C., Whisstock J.C., Kuruppu S.;
RT "N-terminal domain of Bothrops asper Myotoxin II enhances the activity of
RT endothelin converting enzyme-1 and neprilysin.";
RL Sci. Rep. 6:22413-22413(2016).
RN [23]
RP ERRATUM OF PUBMED:26931059.
RX PubMed=27102936; DOI=10.1038/srep24333;
RA Smith A.I., Rajapakse N.W., Kleifeld O., Lomonte B., Sikanyika N.L.,
RA Spicer A.J., Hodgson W.C., Conroy P.J., Small D.H., Kaye D.M.,
RA Parkington H.C., Whisstock J.C., Kuruppu S.;
RT "Corrigendum: N-terminal domain of Bothrops asper Myotoxin II enhances the
RT activity of endothelin converting enzyme-1 and neprilysin.";
RL Sci. Rep. 6:24333-24333(2016).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.38 ANGSTROMS) OF 101-770 OF MUTANT SER-428 IN
RP COMPLEX WITH ZINC IONS AND PHOSPHORAMIDON, COFACTOR, SUBUNIT, AND
RP MUTAGENESIS OF CYS-428.
RX PubMed=18992253; DOI=10.1016/j.jmb.2008.10.052;
RA Schulz H., Dale G.E., Karimi-Nejad Y., Oefner C.;
RT "Structure of human endothelin-converting enzyme I complexed with
RT phosphoramidon.";
RL J. Mol. Biol. 385:178-187(2009).
RN [25]
RP VARIANT HCAD CYS-754.
RX PubMed=9915973; DOI=10.1086/302184;
RA Hofstra R.M.W., Valdenaire O., Arch E., Osinga J., Kroes H., Loffler B.-M.,
RA Hamosh A., Meijers C., Buys C.H.C.M.;
RT "A loss-of-function mutation in the endothelin-converting enzyme 1 (ECE-1)
RT associated with Hirschsprung disease, cardiac defects, and autonomic
RT dysfunction.";
RL Am. J. Hum. Genet. 64:304-308(1999).
CC -!- FUNCTION: Converts big endothelin-1 to endothelin-1.
CC {ECO:0000269|PubMed:9396733}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of the 21-Trp-|-Val-22 bond in big endothelin to
CC form endothelin 1.; EC=3.4.24.71;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:18992253};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:18992253};
CC -!- ACTIVITY REGULATION: Inhibited by phosphoramidon (PubMed:18992253).
CC Activated by K49-P1-20, a twenty-residue synthetic peptide shortened
CC from the snake B.asper myotoxin II (PubMed:26931059).
CC {ECO:0000269|PubMed:26931059}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:18992253). Interacts with
CC PPP1R16B (By similarity). {ECO:0000250|UniProtKB:P42891,
CC ECO:0000269|PubMed:18992253}.
CC -!- INTERACTION:
CC P42892; P49760: CLK2; NbExp=6; IntAct=EBI-2859983, EBI-750020;
CC P42892; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-2859983, EBI-3867333;
CC P42892; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-2859983, EBI-11749135;
CC P42892; P60370: KRTAP10-5; NbExp=3; IntAct=EBI-2859983, EBI-10172150;
CC P42892; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-2859983, EBI-10171774;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=B;
CC IsoId=P42892-1; Sequence=Displayed;
CC Name=A;
CC IsoId=P42892-2; Sequence=VSP_005502;
CC Name=C;
CC IsoId=P42892-3; Sequence=VSP_005504;
CC Name=D;
CC IsoId=P42892-4; Sequence=VSP_005503;
CC -!- TISSUE SPECIFICITY: All isoforms are expressed in umbilical vein
CC endothelial cells, polynuclear neutrophils, fibroblasts, atrium
CC cardiomyocytes and ventricles. Isoforms A, B and C are also expressed
CC in placenta, lung, heart, adrenal gland and phaeochromocytoma; isoforms
CC A and C in liver, testis and small intestine; isoform B, C and D in
CC endothelial cells and umbilical vein smooth muscle cells; isoforms C
CC and D in saphenous vein cells, and isoform C in kidney.
CC {ECO:0000269|PubMed:10491078, ECO:0000269|PubMed:9396733}.
CC -!- DISEASE: Hirschsprung disease, cardiac defects, and autonomic
CC dysfunction (HCAD) [MIM:613870]: A disorder characterized by skip-
CC lesions Hirschsprung disease, craniofacial abnormalities and other
CC dysmorphic features, cardiac defects including ductus arteriosus, small
CC subaortic ventricular septal defect, small atrial septal defect, and
CC autonomic dysfunction. {ECO:0000269|PubMed:9915973}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase M13 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01233, ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAX35820.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAA84548.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ece1/";
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; D49471; BAA08442.1; -; mRNA.
DR EMBL; D43698; BAA07800.1; -; mRNA.
DR EMBL; X91922; CAA63015.1; -; Genomic_DNA.
DR EMBL; X91923; CAA63015.1; JOINED; Genomic_DNA.
DR EMBL; X91924; CAA63015.1; JOINED; Genomic_DNA.
DR EMBL; X91925; CAA63015.1; JOINED; Genomic_DNA.
DR EMBL; X91926; CAA63015.1; JOINED; Genomic_DNA.
DR EMBL; X91927; CAA63015.1; JOINED; Genomic_DNA.
DR EMBL; X91928; CAA63015.1; JOINED; Genomic_DNA.
DR EMBL; X91929; CAA63015.1; JOINED; Genomic_DNA.
DR EMBL; X91930; CAA63015.1; JOINED; Genomic_DNA.
DR EMBL; X91931; CAA63015.1; JOINED; Genomic_DNA.
DR EMBL; X91932; CAA63015.1; JOINED; Genomic_DNA.
DR EMBL; X91933; CAA63015.1; JOINED; Genomic_DNA.
DR EMBL; X91934; CAA63015.1; JOINED; Genomic_DNA.
DR EMBL; X91935; CAA63015.1; JOINED; Genomic_DNA.
DR EMBL; X91936; CAA63015.1; JOINED; Genomic_DNA.
DR EMBL; X91937; CAA63015.1; JOINED; Genomic_DNA.
DR EMBL; X91938; CAA63015.1; JOINED; Genomic_DNA.
DR EMBL; X91939; CAA63015.1; JOINED; Genomic_DNA.
DR EMBL; X91923; CAA63016.1; -; Genomic_DNA.
DR EMBL; X91924; CAA63016.1; JOINED; Genomic_DNA.
DR EMBL; X91925; CAA63016.1; JOINED; Genomic_DNA.
DR EMBL; X91926; CAA63016.1; JOINED; Genomic_DNA.
DR EMBL; X91927; CAA63016.1; JOINED; Genomic_DNA.
DR EMBL; X91928; CAA63016.1; JOINED; Genomic_DNA.
DR EMBL; X91929; CAA63016.1; JOINED; Genomic_DNA.
DR EMBL; X91930; CAA63016.1; JOINED; Genomic_DNA.
DR EMBL; X91931; CAA63016.1; JOINED; Genomic_DNA.
DR EMBL; X91932; CAA63016.1; JOINED; Genomic_DNA.
DR EMBL; X91933; CAA63016.1; JOINED; Genomic_DNA.
DR EMBL; X91934; CAA63016.1; JOINED; Genomic_DNA.
DR EMBL; X91935; CAA63016.1; JOINED; Genomic_DNA.
DR EMBL; X91936; CAA63016.1; JOINED; Genomic_DNA.
DR EMBL; X91937; CAA63016.1; JOINED; Genomic_DNA.
DR EMBL; X91938; CAA63016.1; JOINED; Genomic_DNA.
DR EMBL; X91939; CAA63016.1; JOINED; Genomic_DNA.
DR EMBL; AB031742; BAA83687.1; -; mRNA.
DR EMBL; AK290656; BAF83345.1; -; mRNA.
DR EMBL; AK304167; BAG65053.1; -; mRNA.
DR EMBL; AY953519; AAX35820.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL031005; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL031728; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471134; EAW94959.1; -; Genomic_DNA.
DR EMBL; CH471134; EAW94964.1; -; Genomic_DNA.
DR EMBL; BC117256; AAI17257.1; -; mRNA.
DR EMBL; BC126257; AAI26258.1; -; mRNA.
DR EMBL; AJ130828; CAB46443.1; -; mRNA.
DR EMBL; X98272; CAA66922.1; -; mRNA.
DR EMBL; Z35307; CAA84548.1; ALT_INIT; mRNA.
DR EMBL; AF018034; AAD21221.1; -; Genomic_DNA.
DR CCDS; CCDS215.1; -. [P42892-1]
DR CCDS; CCDS44081.1; -. [P42892-3]
DR CCDS; CCDS44082.1; -. [P42892-4]
DR CCDS; CCDS44083.1; -. [P42892-2]
DR PIR; JC2521; JC2521.
DR PIR; JC4136; JC4136.
DR RefSeq; NP_001106818.1; NM_001113347.1. [P42892-2]
DR RefSeq; NP_001106819.1; NM_001113348.1. [P42892-3]
DR RefSeq; NP_001106820.1; NM_001113349.1. [P42892-4]
DR RefSeq; NP_001388.1; NM_001397.2. [P42892-1]
DR RefSeq; XP_006710461.1; XM_006710398.2.
DR RefSeq; XP_011539175.1; XM_011540873.2.
DR RefSeq; XP_016856000.1; XM_017000511.1.
DR PDB; 3DWB; X-ray; 2.38 A; A=101-770.
DR PDBsum; 3DWB; -.
DR AlphaFoldDB; P42892; -.
DR SMR; P42892; -.
DR BioGRID; 108218; 134.
DR IntAct; P42892; 30.
DR MINT; P42892; -.
DR STRING; 9606.ENSP00000364028; -.
DR BindingDB; P42892; -.
DR ChEMBL; CHEMBL4791; -.
DR DrugBank; DB07171; 5-(2-hydroxyethyl)nonane-1,9-diol.
DR DrugCentral; P42892; -.
DR GuidetoPHARMACOLOGY; 1615; -.
DR MEROPS; M13.002; -.
DR GlyConnect; 1207; 13 N-Linked glycans (7 sites).
DR GlyGen; P42892; 14 sites, 13 N-linked glycans (7 sites).
DR iPTMnet; P42892; -.
DR PhosphoSitePlus; P42892; -.
DR SwissPalm; P42892; -.
DR BioMuta; ECE1; -.
DR DMDM; 1706563; -.
DR EPD; P42892; -.
DR jPOST; P42892; -.
DR MassIVE; P42892; -.
DR MaxQB; P42892; -.
DR PaxDb; P42892; -.
DR PeptideAtlas; P42892; -.
DR PRIDE; P42892; -.
DR ProteomicsDB; 55562; -. [P42892-1]
DR ProteomicsDB; 55563; -. [P42892-2]
DR ProteomicsDB; 55564; -. [P42892-3]
DR ProteomicsDB; 55565; -. [P42892-4]
DR Antibodypedia; 772; 417 antibodies from 34 providers.
DR DNASU; 1889; -.
DR Ensembl; ENST00000264205.10; ENSP00000264205.6; ENSG00000117298.16. [P42892-4]
DR Ensembl; ENST00000357071.8; ENSP00000349581.4; ENSG00000117298.16. [P42892-2]
DR Ensembl; ENST00000374893.11; ENSP00000364028.6; ENSG00000117298.16. [P42892-1]
DR Ensembl; ENST00000415912.6; ENSP00000405088.2; ENSG00000117298.16. [P42892-3]
DR GeneID; 1889; -.
DR KEGG; hsa:1889; -.
DR MANE-Select; ENST00000374893.11; ENSP00000364028.6; NM_001397.3; NP_001388.1.
DR UCSC; uc001bei.3; human. [P42892-1]
DR CTD; 1889; -.
DR DisGeNET; 1889; -.
DR GeneCards; ECE1; -.
DR HGNC; HGNC:3146; ECE1.
DR HPA; ENSG00000117298; Low tissue specificity.
DR MalaCards; ECE1; -.
DR MIM; 600423; gene.
DR MIM; 613870; phenotype.
DR neXtProt; NX_P42892; -.
DR OpenTargets; ENSG00000117298; -.
DR Orphanet; 388; Hirschsprung disease.
DR PharmGKB; PA27594; -.
DR VEuPathDB; HostDB:ENSG00000117298; -.
DR eggNOG; KOG3624; Eukaryota.
DR GeneTree; ENSGT00940000156050; -.
DR HOGENOM; CLU_006187_8_0_1; -.
DR InParanoid; P42892; -.
DR OMA; DQRFFMN; -.
DR OrthoDB; 282463at2759; -.
DR PhylomeDB; P42892; -.
DR TreeFam; TF315192; -.
DR BRENDA; 3.4.24.71; 2681.
DR PathwayCommons; P42892; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR SignaLink; P42892; -.
DR SIGNOR; P42892; -.
DR BioGRID-ORCS; 1889; 4 hits in 1081 CRISPR screens.
DR ChiTaRS; ECE1; human.
DR EvolutionaryTrace; P42892; -.
DR GeneWiki; Endothelin_converting_enzyme_1; -.
DR GenomeRNAi; 1889; -.
DR Pharos; P42892; Tchem.
DR PRO; PR:P42892; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P42892; protein.
DR Bgee; ENSG00000117298; Expressed in stromal cell of endometrium and 191 other tissues.
DR ExpressionAtlas; P42892; baseline and differential.
DR Genevisible; P42892; HS.
DR GO; GO:0005769; C:early endosome; IDA:BHF-UCL.
DR GO; GO:0005768; C:endosome; IDA:BHF-UCL.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:BHF-UCL.
DR GO; GO:0031302; C:intrinsic component of endosome membrane; TAS:BHF-UCL.
DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0031982; C:vesicle; ISS:BHF-UCL.
DR GO; GO:0033093; C:Weibel-Palade body; IDA:BHF-UCL.
DR GO; GO:0004175; F:endopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:BHF-UCL.
DR GO; GO:0017046; F:peptide hormone binding; IC:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0060385; P:axonogenesis involved in innervation; IEA:Ensembl.
DR GO; GO:0010815; P:bradykinin catabolic process; IDA:BHF-UCL.
DR GO; GO:0010816; P:calcitonin catabolic process; IDA:BHF-UCL.
DR GO; GO:0043583; P:ear development; IMP:BHF-UCL.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IMP:BHF-UCL.
DR GO; GO:0035050; P:embryonic heart tube development; IEA:Ensembl.
DR GO; GO:0034959; P:endothelin maturation; IDA:BHF-UCL.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007507; P:heart development; IMP:BHF-UCL.
DR GO; GO:0042447; P:hormone catabolic process; IDA:BHF-UCL.
DR GO; GO:0016486; P:peptide hormone processing; IDA:BHF-UCL.
DR GO; GO:0060037; P:pharyngeal system development; IEA:Ensembl.
DR GO; GO:0001921; P:positive regulation of receptor recycling; IMP:BHF-UCL.
DR GO; GO:0016485; P:protein processing; IDA:BHF-UCL.
DR GO; GO:0003100; P:regulation of systemic arterial blood pressure by endothelin; IC:BHF-UCL.
DR GO; GO:0019229; P:regulation of vasoconstriction; IC:BHF-UCL.
DR GO; GO:1902287; P:semaphorin-plexin signaling pathway involved in axon guidance; IEA:Ensembl.
DR GO; GO:0010814; P:substance P catabolic process; IDA:BHF-UCL.
DR GO; GO:0097492; P:sympathetic neuron axon guidance; IEA:Ensembl.
DR CDD; cd08662; M13; 1.
DR Gene3D; 1.10.1380.10; -; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR029734; ECE1.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR000718; Peptidase_M13.
DR InterPro; IPR018497; Peptidase_M13_C.
DR InterPro; IPR042089; Peptidase_M13_dom_2.
DR InterPro; IPR008753; Peptidase_M13_N.
DR PANTHER; PTHR11733; PTHR11733; 1.
DR PANTHER; PTHR11733:SF130; PTHR11733:SF130; 1.
DR Pfam; PF01431; Peptidase_M13; 1.
DR Pfam; PF05649; Peptidase_M13_N; 1.
DR PRINTS; PR00786; NEPRILYSIN.
DR PROSITE; PS51885; NEPRILYSIN; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disease variant;
KW Disulfide bond; Glycoprotein; Hirschsprung disease; Hydrolase; Membrane;
KW Metal-binding; Metalloprotease; Phosphoprotein; Protease;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW Zinc.
FT CHAIN 1..770
FT /note="Endothelin-converting enzyme 1"
FT /id="PRO_0000078220"
FT TOPO_DOM 1..68
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 69..89
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 90..770
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 98..770
FT /note="Peptidase M13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT ACT_SITE 608
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000305|PubMed:18992253"
FT ACT_SITE 671
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000305|PubMed:18992253"
FT BINDING 607
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000269|PubMed:18992253"
FT BINDING 611
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000269|PubMed:18992253"
FT BINDING 667
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000269|PubMed:18992253"
FT MOD_RES 25
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:19349973"
FT CARBOHYD 187
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 210
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16263699,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19349973"
FT CARBOHYD 270
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 316
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 362
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 383
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 539
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 632
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 651
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 99..104
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 122..755
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 130..715
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 185..435
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 644..767
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT VAR_SEQ 1..44
FT /note="MRGVWPPPVSALLSALGMSTYKRATLDEEDLVDSLSEGDAYPNG -> MPLQ
FT GLGLQRNPFLQGKRGPGLTSSPPLLPPS (in isoform A)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7864876"
FT /id="VSP_005502"
FT VAR_SEQ 1..17
FT /note="MRGVWPPPVSALLSALG -> M (in isoform C)"
FT /evidence="ECO:0000303|PubMed:9396733, ECO:0000303|Ref.4"
FT /id="VSP_005504"
FT VAR_SEQ 1..17
FT /note="MRGVWPPPVSALLSALG -> MEALRESVLHLALQ (in isoform D)"
FT /evidence="ECO:0000303|PubMed:10491078"
FT /id="VSP_005503"
FT VARIANT 341
FT /note="T -> I (in dbSNP:rs1076669)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_011972"
FT VARIANT 754
FT /note="R -> C (in HCAD; dbSNP:rs3026906)"
FT /evidence="ECO:0000269|PubMed:9915973"
FT /id="VAR_026747"
FT MUTAGEN 428
FT /note="C->S: Abolishes dimerization."
FT /evidence="ECO:0000269|PubMed:18992253"
FT HELIX 102..114
FT /evidence="ECO:0007829|PDB:3DWB"
FT TURN 121..123
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 125..136
FT /evidence="ECO:0007829|PDB:3DWB"
FT STRAND 144..147
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 148..164
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 173..186
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 189..194
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 197..205
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 220..229
FT /evidence="ECO:0007829|PDB:3DWB"
FT STRAND 235..244
FT /evidence="ECO:0007829|PDB:3DWB"
FT STRAND 247..256
FT /evidence="ECO:0007829|PDB:3DWB"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 266..269
FT /evidence="ECO:0007829|PDB:3DWB"
FT TURN 270..273
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 277..291
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 297..317
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 321..324
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 327..330
FT /evidence="ECO:0007829|PDB:3DWB"
FT STRAND 332..335
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 336..342
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 348..355
FT /evidence="ECO:0007829|PDB:3DWB"
FT STRAND 366..370
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 372..384
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 387..402
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 403..405
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 408..418
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 434..455
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 458..479
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 487..499
FT /evidence="ECO:0007829|PDB:3DWB"
FT STRAND 501..506
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 508..511
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 513..520
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 530..546
FT /evidence="ECO:0007829|PDB:3DWB"
FT TURN 547..550
FT /evidence="ECO:0007829|PDB:3DWB"
FT STRAND 568..570
FT /evidence="ECO:0007829|PDB:3DWB"
FT TURN 571..574
FT /evidence="ECO:0007829|PDB:3DWB"
FT STRAND 575..579
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 580..582
FT /evidence="ECO:0007829|PDB:3DWB"
FT TURN 585..587
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 594..599
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 601..611
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 617..619
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 632..649
FT /evidence="ECO:0007829|PDB:3DWB"
FT STRAND 653..658
FT /evidence="ECO:0007829|PDB:3DWB"
FT TURN 661..664
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 665..689
FT /evidence="ECO:0007829|PDB:3DWB"
FT STRAND 696..698
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 702..713
FT /evidence="ECO:0007829|PDB:3DWB"
FT STRAND 716..718
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 720..729
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 735..744
FT /evidence="ECO:0007829|PDB:3DWB"
FT HELIX 747..753
FT /evidence="ECO:0007829|PDB:3DWB"
SQ SEQUENCE 770 AA; 87164 MW; DD88A59748B22F80 CRC64;
MRGVWPPPVS ALLSALGMST YKRATLDEED LVDSLSEGDA YPNGLQVNFH SPRSGQRCWA
ARTQVEKRLV VLVVLLAAGL VACLAALGIQ YQTRSPSVCL SEACVSVTSS ILSSMDPTVD
PCHDFFSYAC GGWIKANPVP DGHSRWGTFS NLWEHNQAII KHLLENSTAS VSEAERKAQV
YYRACMNETR IEELRAKPLM ELIERLGGWN ITGPWAKDNF QDTLQVVTAH YRTSPFFSVY
VSADSKNSNS NVIQVDQSGL GLPSRDYYLN KTENEKVLTG YLNYMVQLGK LLGGGDEEAI
RPQMQQILDF ETALANITIP QEKRRDEELI YHKVTAAELQ TLAPAINWLP FLNTIFYPVE
INESEPIVVY DKEYLEQIST LINTTDRCLL NNYMIWNLVR KTSSFLDQRF QDADEKFMEV
MYGTKKTCLP RWKFCVSDTE NNLGFALGPM FVKATFAEDS KSIATEIILE IKKAFEESLS
TLKWMDEETR KSAKEKADAI YNMIGYPNFI MDPKELDKVF NDYTAVPDLY FENAMRFFNF
SWRVTADQLR KAPNRDQWSM TPPMVNAYYS PTKNEIVFPA GILQAPFYTR SSPKALNFGG
IGVVVGHELT HAFDDQGREY DKDGNLRPWW KNSSVEAFKR QTECMVEQYS NYSVNGEPVN
GRHTLGENIA DNGGLKAAYR AYQNWVKKNG AEHSLPTLGL TNNQLFFLGF AQVWCSVRTP
ESSHEGLITD PHSPSRFRVI GSLSNSKEFS EHFRCPPGSP MNPPHKCEVW
