ECE2_HUMAN
ID ECE2_HUMAN Reviewed; 811 AA.
AC P0DPD6; A5PLK8; O60344; Q6NTG7; Q6UW36; Q8NFD7; Q96NX3; Q96NX4; Q9BRZ8;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 28-FEB-2018, sequence version 1.
DT 03-AUG-2022, entry version 29.
DE RecName: Full=Endothelin-converting enzyme 2 {ECO:0000303|PubMed:11718899};
DE Short=ECE-2;
DE EC=3.4.24.71 {ECO:0000269|PubMed:12560336};
GN Name=ECE2 {ECO:0000312|HGNC:HGNC:13275};
GN Synonyms=KIAA0604 {ECO:0000303|PubMed:9628581};
GN ORFNames=UNQ403/PRO740 {ECO:0000303|PubMed:12975309};
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] (ISOFORMS ECE2-2 AND ECE2-3), AND ALTERNATIVE
RP SPLICING.
RX PubMed=11718899; DOI=10.1016/s0167-4781(01)00283-4;
RA Lorenzo M.-N., Khan R.Y., Wang Y., Tai S.C., Chan G.C., Cheung A.H.,
RA Marsden P.A.;
RT "Human endothelin converting enzyme-2 (ECE2): characterization of mRNA
RT species and chromosomal localization.";
RL Biochim. Biophys. Acta 1522:46-52(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ECE2-1).
RC TISSUE=Thalamus;
RA Funke-Kaiser H., Scheuch K., Behrouzi T., Synowitz M., Draheim N.,
RA Schwaneberg B., Thomas A., Zollmann F.S., Paul M., Orzechowski H.D.;
RT "Human endothelin-converting enzyme-2C (ECE-2C): a new ECE-2 variant.";
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ECE2-2).
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ECE2-3).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ECE2-3).
RC TISSUE=Lung, and Ovary;
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 [7]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND CATALYTIC ACTIVITY.
RX PubMed=12560336; DOI=10.1074/jbc.m211242200;
RA Mzhavia N., Pan H., Che F.-Y., Fricker L.D., Devi L.A.;
RT "Characterization of endothelin-converting enzyme-2. Implication for a role
RT in the nonclassical processing of regulatory peptides.";
RL J. Biol. Chem. 278:14704-14711(2003).
CC -!- FUNCTION: Converts big endothelin-1 to endothelin-1. Also involved in
CC the processing of various neuroendocrine peptides, including
CC neurotensin, angiotensin I, substance P, proenkephalin-derived
CC peptides, and prodynorphin-derived peptides. May play a role in
CC amyloid-beta processing (By similarity). {ECO:0000250|UniProtKB:B2RQR8,
CC ECO:0000269|PubMed:12560336}.
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 Evidence={ECO:0000269|PubMed:12560336};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P42892};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P42892};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.4 uM for big ET-1 {ECO:0000269|PubMed:12560336};
CC KM=1.4 uM for peptide E {ECO:0000269|PubMed:12560336};
CC KM=27.4 uM for bradykinin {ECO:0000269|PubMed:12560336};
CC KM=48.4 uM for dynorphin B {ECO:0000269|PubMed:12560336};
CC pH dependence:
CC Optimum pH is 5.0-5.5. Inactive at neutral pH.
CC {ECO:0000269|PubMed:12560336};
CC -!- INTERACTION:
CC P0DPD6-3; P19397: CD53; NbExp=3; IntAct=EBI-19128181, EBI-6657396;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:F1N476}; Single-pass type II membrane protein
CC {ECO:0000305}. Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000250|UniProtKB:F1N476}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=ECE2-1; Synonyms=ECE2-2C {ECO:0000303|Ref.2};
CC IsoId=P0DPD6-4, O60344-5;
CC Sequence=Displayed;
CC Name=ECE2-2; Synonyms=ECE-2B {ECO:0000303|PubMed:11718899};
CC IsoId=P0DPD6-2, O60344-2;
CC Sequence=VSP_059325;
CC Name=ECE2-3;
CC IsoId=P0DPD6-3, O60344-3;
CC Sequence=VSP_059324;
CC Name=EEF1AKMT4-ECE2-1; Synonyms=ECE-2A {ECO:0000303|PubMed:11718899};
CC IsoId=P0DPD8-1, O60344-1;
CC Sequence=External;
CC -!- SIMILARITY: Belongs to the peptidase M13 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01233, ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA25530.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF428264; AAL30387.1; -; mRNA.
DR EMBL; AF192531; AAG28399.1; -; mRNA.
DR EMBL; AF521189; AAM77664.1; -; mRNA.
DR EMBL; AB011176; BAA25530.2; ALT_INIT; mRNA.
DR EMBL; AY359003; AAQ89362.1; -; mRNA.
DR EMBL; AC061705; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC078797; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC142950; AAI42951.1; -; mRNA.
DR CCDS; CCDS33899.1; -. [P0DPD6-3]
DR CCDS; CCDS43179.1; -.
DR CCDS; CCDS46969.1; -. [P0DPD6-2]
DR RefSeq; NP_001032401.1; NM_001037324.2. [P0DPD6-3]
DR RefSeq; NP_001093590.1; NM_001100120.1. [P0DPD6-4]
DR RefSeq; NP_001093591.1; NM_001100121.1. [P0DPD6-2]
DR RefSeq; NP_055508.3; NM_014693.3.
DR AlphaFoldDB; P0DPD6; -.
DR SMR; P0DPD6; -.
DR IntAct; P0DPD6; 6.
DR ChEMBL; CHEMBL5890; -.
DR GuidetoPHARMACOLOGY; 1616; -.
DR GlyGen; P0DPD6; 10 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P0DPD6; -.
DR PhosphoSitePlus; P0DPD6; -.
DR MassIVE; P0DPD6; -.
DR MaxQB; P0DPD6; -.
DR PeptideAtlas; P0DPD6; -.
DR PRIDE; P0DPD6; -.
DR Antibodypedia; 33804; 114 antibodies from 25 providers.
DR DNASU; 9718; -.
DR Ensembl; ENST00000357474.9; ENSP00000350066.5; ENSG00000145194.19. [P0DPD6-4]
DR Ensembl; ENST00000359140.8; ENSP00000352052.4; ENSG00000145194.19. [P0DPD6-3]
DR Ensembl; ENST00000404464.8; ENSP00000385846.3; ENSG00000145194.19. [P0DPD6-2]
DR GeneID; 110599583; -.
DR GeneID; 9718; -.
DR KEGG; hsa:110599583; -.
DR KEGG; hsa:9718; -.
DR MANE-Select; ENST00000404464.8; ENSP00000385846.3; NM_001100121.2; NP_001093591.1. [P0DPD6-2]
DR CTD; 110599583; -.
DR CTD; 9718; -.
DR DisGeNET; 110599583; -.
DR DisGeNET; 9718; -.
DR GeneCards; ECE2; -.
DR HGNC; HGNC:13275; ECE2.
DR HPA; ENSG00000145194; Tissue enhanced (brain, pancreas, pituitary gland).
DR MIM; 610145; gene.
DR neXtProt; NX_P0DPD6; -.
DR OpenTargets; ENSG00000145194; -.
DR VEuPathDB; HostDB:ENSG00000145194; -.
DR GeneTree; ENSGT00940000156921; -.
DR OMA; FRVRTEC; -.
DR OrthoDB; 282463at2759; -.
DR PathwayCommons; P0DPD6; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR SignaLink; P0DPD6; -.
DR Pharos; P0DPD6; Tchem.
DR PRO; PR:P0DPD6; -.
DR Proteomes; UP000005640; Chromosome 3.
DR Bgee; ENSG00000145194; Expressed in cerebellar hemisphere and 68 other tissues.
DR ExpressionAtlas; P0DPD6; baseline and differential.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0030658; C:transport vesicle membrane; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0007267; P:cell-cell signaling; TAS:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0016486; P:peptide hormone processing; IDA:UniProtKB.
DR GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR CDD; cd08662; M13; 1.
DR Gene3D; 1.10.1380.10; -; 1.
DR Gene3D; 3.40.390.10; -; 1.
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 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; Cytoplasmic vesicle; Disulfide bond; Glycoprotein;
KW Golgi apparatus; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Methyltransferase; Multifunctional enzyme; Protease; Reference proteome;
KW Signal-anchor; Transferase; Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..811
FT /note="Endothelin-converting enzyme 2"
FT /id="PRO_0000443293"
FT TOPO_DOM 1..106
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 107..127
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000305"
FT TOPO_DOM 128..811
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT DOMAIN 139..811
FT /note="Peptidase M13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT REGION 22..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 649
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT ACT_SITE 712
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT BINDING 648
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 652
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 708
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 211
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 252
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 312
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 357
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 424
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 580
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 673
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 681
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 140..145
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 163..796
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 171..756
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 227..476
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 685..808
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT VAR_SEQ 14..88
FT /note="Missing (in isoform ECE2-3)"
FT /id="VSP_059324"
FT VAR_SEQ 43..88
FT /note="Missing (in isoform ECE2-2)"
FT /id="VSP_059325"
FT VARIANT 499
FT /note="R -> Q (in dbSNP:rs35875049)"
FT /id="VAR_037085"
FT CONFLICT 395
FT /note="F -> S (in Ref. 6; AAI42951)"
FT /evidence="ECO:0000305"
FT CONFLICT 711
FT /note="A -> T (in Ref. 4; AAQ89362)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 811 AA; 91211 MW; 7379F7AFEA937FCE CRC64;
MNVALQELGA GSNMVEYKRA TLRDEDAPET PVEGGASPDA MEVGKGASPF SPGPSPGMTP
GTPRSSGLFW RVTCPHLRSI SGLCSRTMVG FQKGTRQLLG SRTQLELVLA GASLLLAALL
LGCLVALGVQ YHRDPSHSTC LTEACIRVAG KILESLDRGV SPCEDFYQFS CGGWIRRNPL
PDGRSRWNTF NSLWDQNQAI LKHLLENTTF NSSSEAEQKT QRFYLSCLQV ERIEELGAQP
LRDLIEKIGG WNITGPWDQD NFMEVLKAVA GTYRATPFFT VYISADSKSS NSNVIQVDQS
GLFLPSRDYY LNRTANEKVL TAYLDYMEEL GMLLGGRPTS TREQMQQVLE LEIQLANITV
PQDQRRDEEK IYHKMSISEL QALAPSMDWL EFLSFLLSPL ELSDSEPVVV YGMDYLQQVS
ELINRTEPSI LNNYLIWNLV QKTTSSLDRR FESAQEKLLE TLYGTKKSCV PRWQTCISNT
DDALGFALGS LFVKATFDRQ SKEIAEGMIS EIRTAFEEAL GQLVWMDEKT RQAAKEKADA
IYDMIGFPDF ILEPKELDDV YDGYEISEDS FFQNMLNLYN FSAKVMADQL RKPPSRDQWS
MTPQTVNAYY LPTKNEIVFP AGILQAPFYA RNHPKALNFG GIGVVMGHEL THAFDDQGRE
YDKEGNLRPW WQNESLAAFR NHTACMEEQY NQYQVNGERL NGRQTLGENI ADNGGLKAAY
NAYKAWLRKH GEEQQLPAVG LTNHQLFFVG FAQVWCSVRT PESSHEGLVT DPHSPARFRV
LGTLSNSRDF LRHFGCPVGS PMNPGQLCEV W
