ECE2_MOUSE
ID ECE2_MOUSE Reviewed; 763 AA.
AC B2RQR8; E9Q896;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Endothelin-converting enzyme 2 {ECO:0000305};
DE Short=ECE-2;
DE EC=3.4.24.71 {ECO:0000250|UniProtKB:P0DPD6};
GN Name=Ece2 {ECO:0000312|MGI:MGI:1101356};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ECE2-2).
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 [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=10811845; DOI=10.1172/jci7447;
RA Yanagisawa H., Hammer R.E., Richardson J.A., Emoto N., Williams S.C.,
RA Takeda S., Clouthier D.E., Yanagisawa M.;
RT "Disruption of ECE-1 and ECE-2 reveals a role for endothelin-converting
RT enzyme-2 in murine cardiac development.";
RL J. Clin. Invest. 105:1373-1382(2000).
RN [4]
RP FUNCTION.
RX PubMed=12464614; DOI=10.1074/jbc.c200642200;
RA Eckman E.A., Watson M., Marlow L., Sambamurti K., Eckman C.B.;
RT "Alzheimer's disease beta-amyloid peptide is increased in mice deficient in
RT endothelin-converting enzyme.";
RL J. Biol. Chem. 278:2081-2084(2003).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: 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 (By similarity). May play a
CC role in amyloid-beta processing (PubMed:12464614).
CC {ECO:0000250|UniProtKB:P0DPD6, ECO:0000269|PubMed:12464614}.
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:0000250|UniProtKB:P0DPD6};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
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;
CC IsoId=B2RQR8-1; Sequence=Displayed;
CC Name=Ece2-2;
CC IsoId=B2RQR8-2; Sequence=VSP_059326;
CC Name=Eef1akmt4-Ece2-1; Synonyms=ECE-2a-1;
CC IsoId=P0DPD9-1, Q80Z60-1;
CC Sequence=External;
CC Name=Eef1akmt4-Ece2-2; Synonyms=ECE-2a-2;
CC IsoId=P0DPD9-2, Q80Z60-2;
CC Sequence=External;
CC -!- DISRUPTION PHENOTYPE: Eef1akmt4-Ece2 and Ece2 double mutant mice are
CC fertile and healthy, and do not display any abnormality in terms of
CC growth or aging. {ECO:0000269|PubMed:10811845}.
CC -!- SIMILARITY: Belongs to the peptidase M13 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01233, 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; AC087898; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC138052; AAI38053.1; -; mRNA.
DR EMBL; BC138053; AAI38054.1; -; mRNA.
DR CCDS; CCDS28052.1; -. [B2RQR8-1]
DR CCDS; CCDS49796.1; -. [B2RQR8-2]
DR RefSeq; NP_647454.2; NM_139293.2. [B2RQR8-1]
DR AlphaFoldDB; B2RQR8; -.
DR SMR; B2RQR8; -.
DR MEROPS; M13.003; -.
DR iPTMnet; B2RQR8; -.
DR PhosphoSitePlus; B2RQR8; -.
DR MaxQB; B2RQR8; -.
DR PRIDE; B2RQR8; -.
DR DNASU; 107522; -.
DR Ensembl; ENSMUST00000003898; ENSMUSP00000003898; ENSMUSG00000022842. [B2RQR8-1]
DR Ensembl; ENSMUST00000133344; ENSMUSP00000119693; ENSMUSG00000022842. [B2RQR8-2]
DR GeneID; 107522; -.
DR KEGG; mmu:107522; -.
DR UCSC; uc007yqm.1; mouse. [B2RQR8-1]
DR CTD; 9718; -.
DR MGI; MGI:1101356; Ece2.
DR VEuPathDB; HostDB:ENSMUSG00000022842; -.
DR GeneTree; ENSGT00940000156921; -.
DR OMA; FRVRTEC; -.
DR BioGRID-ORCS; 107522; 5 hits in 70 CRISPR screens.
DR ChiTaRS; Ece2; mouse.
DR PRO; PR:B2RQR8; -.
DR Proteomes; UP000000589; Chromosome 16.
DR Bgee; ENSMUSG00000022842; Expressed in hypothalamus and 57 other tissues.
DR ExpressionAtlas; B2RQR8; baseline and differential.
DR Genevisible; E9Q896; MM.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; ISO:MGI.
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:0005802; C:trans-Golgi network; ISS:MGI.
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; ISO:MGI.
DR GO; GO:0016486; P:peptide hormone processing; ISS:MGI.
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 Phosphoprotein; Protease; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix; Zinc.
FT CHAIN 1..763
FT /note="Endothelin-converting enzyme 2"
FT /id="PRO_0000443294"
FT TOPO_DOM 1..60
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 61..81
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000305"
FT TOPO_DOM 82..763
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT DOMAIN 91..763
FT /note="Peptidase M13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT ACT_SITE 601
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT ACT_SITE 664
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT BINDING 600
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 604
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 660
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT MOD_RES 27
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 159
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 163
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 264
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 376
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 532
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 625
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 633
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 92..97
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 115..748
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 123..708
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 179..428
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 637..760
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT VAR_SEQ 14..42
FT /note="Missing (in isoform Ece2-2)"
FT /id="VSP_059326"
SQ SEQUENCE 763 AA; 86231 MW; 10FB30AFEF8AE9E2 CRC64;
MNVALHELGG GGSMVEYKRA KLRDEESPEI TVEGRATRDS LEVGFQKRTR QLFGSHTQLE
LVLAGLILVL AALLLGCLVA LWVHRDPAHS TCVTEACIRV AGKILESLDR GVSPCQDFYQ
FSCGGWIRRN PLPNGRSRWN TFNSLWDQNQ AILKHLLENT TFNSSSEAER KTRSFYLSCL
QSERIEKLGA KPLRDLIDKI GGWNITGPWD EDSFMDVLKA VAGTYRATPF FTVYVSADSK
SSNSNIIQVD QSGLFLPSRD YYLNRTANEK VLTAYLDYMV ELGVLLGGQP TSTREQMQQV
LELEIQLANI TVPQDQRRDE EKIYHKMSIS ELQALAPAVD WLEFLSFLLS PLELGDSEPV
VVYGTEYLQQ VSELINRTEP SILNNYLIWN LVQKTTSSLD QRFETAQEKL LETLYGTKKS
CTPRWQTCIS NTDDALGFAL GSLFVKATFD RQSKEIAEGM INEIRSAFEE TLGDLVWMDE
KTRLAAKEKA DAIYDMIGFP DFILEPKELD DVYDGYEVSE DSFFQNMLNL YNFSAKVMAD
QLRKPPSRDQ WSMTPQTVNA YYLPTKNEIV FPAGILQAPF YAHNHPKALN FGGIGVVMGH
ELTHAFDDQG REYDKEGNLR PWWQNESLTA FQNHTACMEE QYSQYQVNGE RLNGLQTLGE
NIADNGGLKA AYNAYKAWLR KHGEEQPLPA VGLTNHQLFF VGFAQVWCSV RTPESSHEGL
VTDPHSPARF RVLGTLSNSR DFLRHFGCPV GSPMNPGQLC EVW
