ECE1_RAT
ID ECE1_RAT Reviewed; 762 AA.
AC P42893; Q9WUY8; Q9WUY9;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Endothelin-converting enzyme 1;
DE Short=ECE-1;
DE EC=3.4.24.71;
GN Name=Ece1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C).
RC TISSUE=Endothelial cell;
RX PubMed=8034569; DOI=10.1016/s0021-9258(17)32298-6;
RA Shimada K., Takahashi M., Tanzawa K.;
RT "Cloning and functional expression of endothelin-converting enzyme from rat
RT endothelial cells.";
RL J. Biol. Chem. 269:18275-18278(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-116, ALTERNATIVE SPLICING, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Smooth muscle;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-109 (ISOFORM A).
RC STRAIN=Sprague-Dawley; TISSUE=Lung;
RX PubMed=7672114; DOI=10.1016/0014-5793(95)00886-e;
RA Shimada K., Takahashi M., Ikeda M., Tanzawa K.;
RT "Identification and characterization of two isoforms of an endothelin-
RT converting enzyme-1.";
RL FEBS Lett. 371:140-144(1995).
RN [4]
RP SUBUNIT, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-420; GLU-600; GLU-659
RP AND HIS-724.
RX PubMed=8645169; DOI=10.1042/bj3150863;
RA Shimada K., Takahashi M., Turner A.J., Tanzawa K.;
RT "Rat endothelin-converting enzyme-1 forms a dimer through Cys412 with a
RT similar catalytic mechanism and a distinct substrate binding mechanism
RT compared with neutral endopeptidase-24.11.";
RL Biochem. J. 315:863-867(1996).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Converts big endothelin-1 to endothelin-1.
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; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by phosphoramidon. {ECO:0000250}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:8645169). Interacts with
CC PPP1R16B (By similarity). {ECO:0000250|UniProtKB:P42891,
CC ECO:0000269|PubMed:8645169}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10491078,
CC ECO:0000269|PubMed:8645169}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:10491078, ECO:0000269|PubMed:8645169}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=A;
CC IsoId=P42893-1; Sequence=Displayed;
CC Name=B;
CC IsoId=P42893-2; Sequence=VSP_005505;
CC Name=C;
CC IsoId=P42893-3; Sequence=VSP_005506;
CC Name=D;
CC IsoId=P42893-4; Sequence=VSP_005507;
CC -!- TISSUE SPECIFICITY: All isoforms are expressed in aortic endothelial
CC cells. Isoform A is also expressed in liver; isoform B in smooth muscle
CC cells and fibroblasts; isoform C in aortic endothelial cells, smooth
CC muscle cells, fibroblasts, liver and lung, and isoform D in smooth
CC muscle cells. {ECO:0000269|PubMed:10491078}.
CC -!- SIMILARITY: Belongs to the peptidase M13 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01233, ECO:0000305}.
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DR EMBL; D29683; BAA06152.1; -; mRNA.
DR EMBL; AJ130826; CAB46528.1; -; mRNA.
DR EMBL; AJ130827; CAB46529.1; -; mRNA.
DR EMBL; D63795; BAA09864.1; -; mRNA.
DR PIR; A53679; A53679.
DR PIR; S66530; S66530.
DR AlphaFoldDB; P42893; -.
DR SMR; P42893; -.
DR STRING; 10116.ENSRNOP00000062928; -.
DR BindingDB; P42893; -.
DR ChEMBL; CHEMBL2676; -.
DR GuidetoPHARMACOLOGY; 1615; -.
DR MEROPS; M13.002; -.
DR GlyGen; P42893; 10 sites.
DR PaxDb; P42893; -.
DR RGD; 620293; Ece1.
DR eggNOG; KOG3624; Eukaryota.
DR InParanoid; P42893; -.
DR PhylomeDB; P42893; -.
DR BRENDA; 3.4.24.71; 5301.
DR Reactome; R-RNO-375276; Peptide ligand-binding receptors.
DR PRO; PR:P42893; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:RGD.
DR GO; GO:0005769; C:early endosome; IDA:RGD.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0030141; C:secretory granule; IDA:RGD.
DR GO; GO:0031982; C:vesicle; IDA:BHF-UCL.
DR GO; GO:0033093; C:Weibel-Palade body; ISO:RGD.
DR GO; GO:0004175; F:endopeptidase activity; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; IMP:RGD.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; IMP:RGD.
DR GO; GO:0060385; P:axonogenesis involved in innervation; ISO:RGD.
DR GO; GO:0097746; P:blood vessel diameter maintenance; IMP:RGD.
DR GO; GO:0010815; P:bradykinin catabolic process; ISO:RGD.
DR GO; GO:0010816; P:calcitonin catabolic process; ISO:RGD.
DR GO; GO:0043583; P:ear development; ISO:RGD.
DR GO; GO:0042733; P:embryonic digit morphogenesis; ISO:RGD.
DR GO; GO:0035050; P:embryonic heart tube development; ISO:RGD.
DR GO; GO:0034959; P:endothelin maturation; ISO:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0042447; P:hormone catabolic process; ISO:RGD.
DR GO; GO:0031175; P:neuron projection development; ISO:RGD.
DR GO; GO:0016486; P:peptide hormone processing; ISO:RGD.
DR GO; GO:0060037; P:pharyngeal system development; ISO:RGD.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; IMP:RGD.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IMP:RGD.
DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; IMP:RGD.
DR GO; GO:0001921; P:positive regulation of receptor recycling; IMP:RGD.
DR GO; GO:0016485; P:protein processing; IDA:RGD.
DR GO; GO:0008217; P:regulation of blood pressure; IMP:RGD.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IMP:RGD.
DR GO; GO:0046686; P:response to cadmium ion; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IDA:RGD.
DR GO; GO:0035994; P:response to muscle stretch; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:1902287; P:semaphorin-plexin signaling pathway involved in axon guidance; ISO:RGD.
DR GO; GO:0010814; P:substance P catabolic process; ISO:RGD.
DR GO; GO:0097492; P:sympathetic neuron axon guidance; ISO:RGD.
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 Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Hydrolase; Membrane; Metal-binding; Metalloprotease; Protease;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW Zinc.
FT CHAIN 1..762
FT /note="Endothelin-converting enzyme 1"
FT /id="PRO_0000078221"
FT TOPO_DOM 1..60
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 61..81
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 82..762
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 90..762
FT /note="Peptidase M13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT ACT_SITE 600
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT ACT_SITE 663
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT BINDING 599
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 603
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 659
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 179
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 262
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 308
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 354
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 375
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 531
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 624
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 643
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 91..96
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 114..747
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 122..707
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 177..427
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 636..759
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT VAR_SEQ 1..36
FT /note="MGSLRPPQGLGLQWSSFFLGKKGPGLTVSLPLLASS -> MRTVWPPLRAAL
FT AALGMSSYKRATLDEEDLVDSLSEGDVYPNG (in isoform B)"
FT /evidence="ECO:0000305"
FT /id="VSP_005505"
FT VAR_SEQ 1..36
FT /note="MGSLRPPQGLGLQWSSFFLGKKGPGLTVSLPLLASS -> MMSSYKRATLDE
FT EDLVDSLSEGDVYPNG (in isoform C)"
FT /evidence="ECO:0000303|PubMed:8034569"
FT /id="VSP_005506"
FT VAR_SEQ 1..36
FT /note="MGSLRPPQGLGLQWSSFFLGKKGPGLTVSLPLLASS -> METLRESVLHLA
FT LQMSSYKRATLDEEDLVDSLSEGDVYPNG (in isoform D)"
FT /evidence="ECO:0000305"
FT /id="VSP_005507"
FT MUTAGEN 420
FT /note="C->S: Loss of dimerization."
FT /evidence="ECO:0000269|PubMed:8645169"
FT MUTAGEN 600
FT /note="E->Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:8645169"
FT MUTAGEN 659
FT /note="E->Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:8645169"
FT MUTAGEN 724
FT /note="H->Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:8645169"
SQ SEQUENCE 762 AA; 86126 MW; D6B8253BC67CCAD8 CRC64;
MGSLRPPQGL GLQWSSFFLG KKGPGLTVSL PLLASSLQVN FRSPRSGQRC WAARTSVEKR
LVVLVTLLAA GLVACLAALG IQYRTRTPPV CLTEACVSVT SSILNSMDPT VDPCQDFFSY
ACGGWIKANP VPDGHSRWGT FSNLWEHNQA IIKHLLENST ASASEAEKKA QVYYRACMNE
TRIEELRAKP LMELIEKLGG WNITGPWAKD NFQDTLQVVT AHYRTSPFFS VYVSADSKNS
NSNVIQVDQS GLGLPSRDYY LNKTENEKVL TGYLNYMVQL GKLLGGGDED SIRPQMQQIL
DFETALANIT IPQEKRRDEE LIYHKVTAAE LQTLAPAINW LPFLNAIFYP VEINESEPIV
VYDKEYLRQV STLINSTDKC LLNNYMMWNL VRKTSSFLDQ RFQDADEKFM EVMYGTKKTC
LPRWKFCVSD TENNLGFALG PMFVKATFAE DSKNIASEII LEIKKAFEES LSTLKWMDED
TRRSAKEKAD AIYNMIGYPN FIMDPKELDK VFNDYTAVPD LYFENAMRFF NFSLRVTADQ
LRKAPNRDQW SMTPPMVNAY YSPTKNEIVF PAGILQAPFY TRSSPNALNF GGIGVVVGHE
LTHAFDDQGR EYDKDGNLRP WWKNSSVEAF KQQTECMVQQ YNNYSVNGEP VNGRHTLGEN
IADNGGLKAA YRAYQNWVKK NGAEQILPTL GLTSNQLFFL GFAQVWCSVR TPESSHEGLI
TDPHSPSRFR VIGSLSNSKE FSEHFRCPLG SPMNPRHKCE VW
