EFCE2_MOUSE
ID EFCE2_MOUSE Reviewed; 881 AA.
AC P0DPD9; E9QKA6; Q14BY3; Q80Z59; Q80Z60; Q9D8Q9; Q9D928;
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=EEF1AKMT4-ECE2 readthrough transcript protein {ECO:0000250|UniProtKB:P0DPD8};
DE EC=3.4.24.71 {ECO:0000250|UniProtKB:P0DPE2};
DE Includes:
DE RecName: Full=Methyltransferase-like region {ECO:0000305};
DE EC=2.1.1.-;
DE Includes:
DE RecName: Full=Endothelin-converting enzyme 2 region {ECO:0000305};
DE EC=3.4.24.71;
GN Name=Eef1akmt4-Ece2 {ECO:0000250|UniProtKB:P0DPD8};
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 [MRNA] OF 58-881 (ISOFORMS EEF1AKMT4-ECE2-1 AND
RP EEF1AKMT4-ECE2-2).
RX PubMed=12054617; DOI=10.1016/s0006-291x(02)00252-8;
RA Ikeda S., Emoto N., Alimsardjono H., Yokoyama M., Matsuo M.;
RT "Molecular isolation and characterization of novel four subisoforms of ECE-
RT 2.";
RL Biochem. Biophys. Res. Commun. 293:421-426(2002).
RN [3]
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND 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-174 (ISOFORM
RP EEF1AKMT4-ECE2-2), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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. May also have
CC methyltransferase activity (By similarity). May play a role in amyloid-
CC beta processing (PubMed:12464614). {ECO:0000250|UniProtKB:P0DPE2,
CC 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:P0DPE2};
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 -!- ACTIVITY REGULATION: Inhibited by phosphoramidon.
CC {ECO:0000250|UniProtKB:P0DPE2}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:P0DPE2}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:P0DPE2}. Cytoplasmic vesicle, secretory vesicle
CC membrane {ECO:0000250|UniProtKB:P0DPE2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=Eef1akmt4-Ece2-1; Synonyms=ECE-2a-1 {ECO:0000303|PubMed:12054617};
CC IsoId=P0DPD9-1, Q80Z60-1;
CC Sequence=Displayed;
CC Name=Eef1akmt4-Ece2-2; Synonyms=ECE-2a-2 {ECO:0000303|PubMed:12054617};
CC IsoId=P0DPD9-2, Q80Z60-2;
CC Sequence=VSP_029335;
CC Name=Eef1akmt4-1;
CC IsoId=P0DPE0-1, Q80Z60-3;
CC Sequence=External;
CC Name=Ece2-1;
CC IsoId=B2RQR8-1; Sequence=External;
CC Name=Ece2-2;
CC IsoId=B2RQR8-2; Sequence=External;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in central nervous system.
CC Expressed in adrenal glands, ovary and uterus, and at low levels in
CC heart. {ECO:0000269|PubMed:10811845}.
CC -!- DEVELOPMENTAL STAGE: Weakly expressed in mesenchyme and parts of neural
CC tube at 10.5 dpc. At 13.5 dpc, expressed in anterior part of neural
CC tube, dorsal root ganglia, bilateral sympathetic trunk and heart.
CC {ECO:0000269|PubMed:10811845}.
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 -!- MISCELLANEOUS: [Isoform Eef1akmt4-Ece2-1]: Based on a naturally
CC occurring readthrough transcript which produces an Eef1akmt4-Ece2
CC fusion protein. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform Eef1akmt4-Ece2-2]: Based on a naturally
CC occurring readthrough transcript which produces an Eef1akmt4-Ece2
CC fusion protein. {ECO:0000305}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the methyltransferase
CC superfamily. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the peptidase M13
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO72356.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAO72357.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AC087898; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF489569; AAO72356.1; ALT_INIT; mRNA.
DR EMBL; AF489570; AAO72357.1; ALT_INIT; mRNA.
DR RefSeq; NP_808809.1; NM_177940.1. [P0DPD9-1]
DR RefSeq; NP_808810.1; NM_177941.1. [P0DPD9-2]
DR AlphaFoldDB; P0DPD9; -.
DR SMR; P0DPD9; -.
DR STRING; 10090.ENSMUSP00000113475; -.
DR GlyGen; P0DPD9; 9 sites.
DR iPTMnet; P0DPD9; -.
DR PhosphoSitePlus; P0DPD9; -.
DR MaxQB; P0DPD9; -.
DR PRIDE; P0DPD9; -.
DR Ensembl; ENSMUST00000079600; ENSMUSP00000078550; ENSMUSG00000115293. [P0DPD9-1]
DR Ensembl; ENSMUST00000120394; ENSMUSP00000113475; ENSMUSG00000115293. [P0DPD9-2]
DR GeneID; 110599584; -.
DR KEGG; mmu:110599584; -.
DR MGI; MGI:1101356; Eef1akmt4-Ece2.
DR VEuPathDB; HostDB:ENSMUSG00000115293; -.
DR GeneTree; ENSGT00940000156921; -.
DR OMA; FGWAQVW; -.
DR Reactome; R-MMU-375276; Peptide ligand-binding receptors.
DR BioGRID-ORCS; 107522; 5 hits in 70 CRISPR screens.
DR ChiTaRS; Ece2; mouse.
DR PRO; PR:P0DPD9; -.
DR Proteomes; UP000000589; Chromosome 16.
DR Bgee; ENSMUSG00000115293; Expressed in ventricular zone and 29 other tissues.
DR Genevisible; E9QKA6; MM.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; ISS: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: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; ISS:UniProtKB.
DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; IEA:UniProt.
DR GO; GO:0007420; P:brain development; ISS:ARUK-UCL.
DR GO; GO:0010002; P:cardioblast differentiation; ISS:ARUK-UCL.
DR GO; GO:0007507; P:heart development; ISS:ARUK-UCL.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0016486; P:peptide hormone processing; ISS: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 Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR041698; Methyltransf_25.
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 InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR11733; PTHR11733; 1.
DR Pfam; PF13649; Methyltransf_25; 1.
DR Pfam; PF01431; Peptidase_M13; 1.
DR Pfam; PF05649; Peptidase_M13_N; 1.
DR PRINTS; PR00786; NEPRILYSIN.
DR SUPFAM; SSF53335; SSF53335; 1.
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; Phosphoprotein; Protease;
KW Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix; Zinc.
FT CHAIN 1..881
FT /note="EEF1AKMT4-ECE2 readthrough transcript protein"
FT /id="PRO_0000310760"
FT TOPO_DOM 1..178
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 179..199
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 200..881
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT DOMAIN 209..881
FT /note="Peptidase M13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT REGION 1..160
FT /note="Methyltransferase-like region"
FT /evidence="ECO:0000305"
FT ACT_SITE 719
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT ACT_SITE 782
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT BINDING 26
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P0DPD7"
FT BINDING 30
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P0DPD7"
FT BINDING 41
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P0DPD7"
FT BINDING 66
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P0DPD7"
FT BINDING 88..89
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P0DPD7"
FT BINDING 113..114
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P0DPD7"
FT BINDING 130
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P0DPD7"
FT BINDING 718
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 722
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 778
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT MOD_RES 39
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P0DPD8"
FT CARBOHYD 277
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 281
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 322
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 382
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 427
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 494
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 650
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 743
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 751
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 210..215
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 233..866
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 241..826
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 297..546
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 755..878
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT VAR_SEQ 159
FT /note="S -> SEMVEYKRAKLRDEESPEITVEGRATRDSL (in isoform
FT Eef1akmt4-Ece2-2)"
FT /evidence="ECO:0000303|PubMed:12054617"
FT /id="VSP_029335"
FT CONFLICT 359..365
FT /note="SSNSNII -> RSYSNIT (in Ref. 2; AAO72356/AAO72357)"
FT /evidence="ECO:0000305"
FT CONFLICT 483..484
FT /note="TE -> MS (in Ref. 2; AAO72356/AAO72357)"
FT /evidence="ECO:0000305"
FT CONFLICT 632
FT /note="D -> Y (in Ref. 2; AAO72356/AAO72357)"
FT /evidence="ECO:0000305"
FT CONFLICT 696
FT /note="A -> P (in Ref. 2; AAO72356/AAO72357)"
FT /evidence="ECO:0000305"
FT CONFLICT 717
FT /note="G -> D (in Ref. 2; AAO72356/AAO72357)"
FT /evidence="ECO:0000305"
FT MOD_RES P0DPD9-2:174
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 881 AA; 99480 MW; 43F512214E293D89 CRC64;
MASPRTPVSP PELPEKNFQY RQVQYWDQRY KDAADSGPYE WFGDFASFRA LLEPELCPED
RILVLGCGNS ALSYELFLGG FPNVTSVDYS PVVVAAMQVR YAHVPSLRWE TMDVRALDFP
SGSFDVVLEK GTLDAMLAGE PDPWNVSSEG VHTVDQVLSE VGFQKRTRQL FGSHTQLELV
LAGLILVLAA LLLGCLVALW VHRDPAHSTC VTEACIRVAG KILESLDRGV SPCQDFYQFS
CGGWIRRNPL PNGRSRWNTF NSLWDQNQAI LKHLLENTTF NSSSEAERKT RSFYLSCLQS
ERIEKLGAKP LRDLIDKIGG WNITGPWDED SFMDVLKAVA GTYRATPFFT VYVSADSKSS
NSNIIQVDQS GLFLPSRDYY LNRTANEKVL TAYLDYMVEL GVLLGGQPTS TREQMQQVLE
LEIQLANITV PQDQRRDEEK IYHKMSISEL QALAPAVDWL EFLSFLLSPL ELGDSEPVVV
YGTEYLQQVS ELINRTEPSI LNNYLIWNLV QKTTSSLDQR FETAQEKLLE TLYGTKKSCT
PRWQTCISNT DDALGFALGS LFVKATFDRQ SKEIAEGMIN EIRSAFEETL GDLVWMDEKT
RLAAKEKADA IYDMIGFPDF ILEPKELDDV YDGYEVSEDS FFQNMLNLYN FSAKVMADQL
RKPPSRDQWS MTPQTVNAYY LPTKNEIVFP AGILQAPFYA HNHPKALNFG GIGVVMGHEL
THAFDDQGRE YDKEGNLRPW WQNESLTAFQ NHTACMEEQY SQYQVNGERL NGLQTLGENI
ADNGGLKAAY NAYKAWLRKH GEEQPLPAVG LTNHQLFFVG FAQVWCSVRT PESSHEGLVT
DPHSPARFRV LGTLSNSRDF LRHFGCPVGS PMNPGQLCEV W
