ECEL1_HUMAN
ID ECEL1_HUMAN Reviewed; 775 AA.
AC O95672; Q45UD9; Q53RF9; Q6UW86; Q86TH4; Q9NY95;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 3.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Endothelin-converting enzyme-like 1;
DE EC=3.4.24.-;
DE AltName: Full=Xce protein;
GN Name=ECEL1; Synonyms=XCE; ORFNames=UNQ2431/PRO4991;
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 1), AND VARIANT TYR-328.
RC TISSUE=Caudate nucleus, and Spinal cord;
RX PubMed=9931490; DOI=10.1016/s0169-328x(98)00321-0;
RA Valdenaire O., Richards J.G., Faull R.L.M., Schweizer A.;
RT "XCE, a new member of the endothelin-converting enzyme and neutral
RT endopeptidase family, is preferentially expressed in the CNS.";
RL Brain Res. Mol. Brain Res. 64:211-221(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT TYR-328.
RX PubMed=10698686; DOI=10.1042/bj3460611;
RA Valdenaire O., Rohrbacher E., Langeveld A., Schweizer A., Meijers C.;
RT "Organization and chromosomal localization of the human ECEL1 (XCE) gene
RT encoding a zinc metallopeptidase involved in the nervous control of
RT respiration.";
RL Biochem. J. 346:611-616(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT TYR-328.
RA Lin L., Nong W., Zhou G., Ke R., Shen C., Zhong G., Zheng Z., Liang M.,
RA Huang B., Li H., Yang S.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT TYR-328.
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=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT TYR-328.
RC TISSUE=PNS;
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 VARIANT DA5D SER-418.
RX PubMed=23261301; DOI=10.1016/j.ajhg.2012.11.014;
RG University of Washington Center for Mendelian Genomics;
RA McMillin M.J., Below J.E., Shively K.M., Beck A.E., Gildersleeve H.I.,
RA Pinner J., Gogola G.R., Hecht J.T., Grange D.K., Harris D.J., Earl D.L.,
RA Jagadeesh S., Mehta S.G., Robertson S.P., Swanson J.M., Faustman E.M.,
RA Mefford H.C., Shendure J., Nickerson D.A., Bamshad M.J.;
RT "Mutations in ECEL1 cause distal arthrogryposis type 5D.";
RL Am. J. Hum. Genet. 92:150-156(2013).
RN [8]
RP VARIANT DA5D SER-607.
RX PubMed=23808592; DOI=10.1111/cge.12224;
RA Shaaban S., Duzcan F., Yildirim C., Chan W.M., Andrews C., Akarsu N.,
RA Engle E.;
RT "Expanding the phenotypic spectrum of ECEL1-related congenital contracture
RT syndromes.";
RL Clin. Genet. 85:562-567(2014).
RN [9]
RP VARIANT DA5D CYS-404.
RX PubMed=23829171; DOI=10.1111/cge.12226;
RA Shaheen R., Al-Owain M., Khan A., Zaki M., Hossni H., Al-Tassan R.,
RA Eyaid W., Alkuraya F.;
RT "Identification of three novel ECEL1 mutations in three families with
RT distal arthrogryposis type 5D.";
RL Clin. Genet. 85:568-572(2014).
RN [10]
RP VARIANT DA5D ARG-760.
RX PubMed=23236030; DOI=10.1093/hmg/dds514;
RA Dieterich K., Quijano-Roy S., Monnier N., Zhou J., Faure J., Smirnow D.A.,
RA Carlier R., Laroche C., Marcorelles P., Mercier S., Megarbane A., Odent S.,
RA Romero N., Sternberg D., Marty I., Estournet B., Jouk P.S., Melki J.,
RA Lunardi J.;
RT "The neuronal endopeptidase ECEL1 is associated with a distinct form of
RT recessive distal arthrogryposis.";
RL Hum. Mol. Genet. 22:1483-1492(2013).
CC -!- FUNCTION: May contribute to the degradation of peptide hormones and be
CC involved in the inactivation of neuronal peptides.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type II
CC membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O95672-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95672-2; Sequence=VSP_017544;
CC -!- TISSUE SPECIFICITY: Highly expressed in the CNS, in particular in
CC putamen, spinal cord, medulla and subthalamic nucleus. A strong signal
CC was also detected in uterine subepithelial cells and around renal blood
CC vessels. Detected at lower levels in amygdala, caudate, thalamus,
CC pancreas and skeletal muscle. Detected at very low levels in substantia
CC nigra, cerebellum, cortex, corpus callosum and hippocampus.
CC -!- PTM: N-glycosylated.
CC -!- DISEASE: Arthrogryposis, distal, 5D (DA5D) [MIM:615065]: An autosomal
CC recessive form of distal arthrogryposis, a disease characterized by
CC congenital joint contractures that mainly involve two or more distal
CC parts of the limbs, in the absence of a primary neurological or muscle
CC disease. DA5D is characterized by severe camptodactyly of the hands,
CC mild camptodactyly of the toes, clubfoot and/or a calcaneovalgus
CC deformity, extension contractures of the knee, unilateral ptosis or
CC ptosis that is more severe on one side, a round-shaped face, arched
CC eyebrows, a bulbous upturned nose, and micrognathia. Patients do not
CC have ophthalmoplegia. {ECO:0000269|PubMed:23236030,
CC ECO:0000269|PubMed:23261301, ECO:0000269|PubMed:23808592,
CC ECO:0000269|PubMed:23829171}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. ECEL1 mutations have also
CC been found in patients with arthrogryposis, significant
CC ophthalmoplegia, and refractive errors (PubMed:23808592).
CC {ECO:0000269|PubMed:23808592}.
CC -!- SIMILARITY: Belongs to the peptidase M13 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01233, ECO:0000305}.
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DR EMBL; Y16187; CAA76113.1; -; mRNA.
DR EMBL; AJ130734; CAB86601.1; -; Genomic_DNA.
DR EMBL; DQ114476; AAZ22338.1; -; mRNA.
DR EMBL; AY358923; AAQ89282.1; -; mRNA.
DR EMBL; AC092165; AAY24101.1; -; Genomic_DNA.
DR EMBL; BC050453; AAH50453.2; -; mRNA.
DR CCDS; CCDS2493.1; -. [O95672-1]
DR CCDS; CCDS77540.1; -. [O95672-2]
DR RefSeq; NP_001277716.1; NM_001290787.1. [O95672-2]
DR RefSeq; NP_004817.2; NM_004826.3. [O95672-1]
DR AlphaFoldDB; O95672; -.
DR SMR; O95672; -.
DR BioGRID; 114820; 149.
DR IntAct; O95672; 9.
DR STRING; 9606.ENSP00000302051; -.
DR MEROPS; M13.007; -.
DR GlyGen; O95672; 3 sites.
DR iPTMnet; O95672; -.
DR PhosphoSitePlus; O95672; -.
DR BioMuta; ECEL1; -.
DR EPD; O95672; -.
DR MassIVE; O95672; -.
DR MaxQB; O95672; -.
DR PaxDb; O95672; -.
DR PeptideAtlas; O95672; -.
DR PRIDE; O95672; -.
DR ProteomicsDB; 50986; -. [O95672-1]
DR ProteomicsDB; 50987; -. [O95672-2]
DR Antibodypedia; 47689; 53 antibodies from 13 providers.
DR DNASU; 9427; -.
DR Ensembl; ENST00000304546.6; ENSP00000302051.1; ENSG00000171551.12. [O95672-1]
DR Ensembl; ENST00000409941.1; ENSP00000386333.1; ENSG00000171551.12. [O95672-2]
DR GeneID; 9427; -.
DR KEGG; hsa:9427; -.
DR MANE-Select; ENST00000304546.6; ENSP00000302051.1; NM_004826.4; NP_004817.2.
DR UCSC; uc002vsv.3; human. [O95672-1]
DR CTD; 9427; -.
DR DisGeNET; 9427; -.
DR GeneCards; ECEL1; -.
DR HGNC; HGNC:3147; ECEL1.
DR HPA; ENSG00000171551; Group enriched (brain, ovary, pituitary gland).
DR MalaCards; ECEL1; -.
DR MIM; 605896; gene.
DR MIM; 615065; phenotype.
DR neXtProt; NX_O95672; -.
DR OpenTargets; ENSG00000171551; -.
DR Orphanet; 329457; Distal arthrogryposis type 5D.
DR PharmGKB; PA27595; -.
DR VEuPathDB; HostDB:ENSG00000171551; -.
DR eggNOG; KOG3624; Eukaryota.
DR GeneTree; ENSGT00940000157673; -.
DR HOGENOM; CLU_006187_8_0_1; -.
DR InParanoid; O95672; -.
DR OMA; MHKVSDL; -.
DR OrthoDB; 282463at2759; -.
DR PhylomeDB; O95672; -.
DR TreeFam; TF315192; -.
DR PathwayCommons; O95672; -.
DR SignaLink; O95672; -.
DR BioGRID-ORCS; 9427; 10 hits in 1068 CRISPR screens.
DR GeneWiki; ECEL1; -.
DR GenomeRNAi; 9427; -.
DR Pharos; O95672; Tbio.
DR PRO; PR:O95672; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O95672; protein.
DR Bgee; ENSG00000171551; Expressed in left ovary and 102 other tissues.
DR ExpressionAtlas; O95672; baseline and differential.
DR Genevisible; O95672; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008237; F:metallopeptidase activity; TAS:ProtInc.
DR GO; GO:0007218; P:neuropeptide signaling pathway; TAS:ProtInc.
DR GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR GO; GO:0003016; P:respiratory system process; ISS:UniProtKB.
DR CDD; cd08662; M13; 1.
DR Gene3D; 1.10.1380.10; -; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR029736; ECEL1.
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:SF195; PTHR11733:SF195; 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; Disease variant; Disulfide bond; Glycoprotein;
KW Hydrolase; Membrane; Metal-binding; Metalloprotease; Protease;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW Zinc.
FT CHAIN 1..775
FT /note="Endothelin-converting enzyme-like 1"
FT /id="PRO_0000078224"
FT TOPO_DOM 1..59
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 60..82
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 83..775
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 98..775
FT /note="Peptidase M13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT ACT_SITE 613
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT ACT_SITE 676
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT BINDING 612
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 616
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 672
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT CARBOHYD 255
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 656
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 123..760
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 131..720
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 187..441
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT DISULFID 649..772
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT VAR_SEQ 561..562
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_017544"
FT VARIANT 10
FT /note="H -> Q (in dbSNP:rs2741281)"
FT /id="VAR_012813"
FT VARIANT 328
FT /note="H -> Y (in dbSNP:rs1529874)"
FT /evidence="ECO:0000269|PubMed:10698686,
FT ECO:0000269|PubMed:12975309, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9931490, ECO:0000269|Ref.3"
FT /id="VAR_012814"
FT VARIANT 404
FT /note="R -> C (in DA5D; dbSNP:rs532757890)"
FT /evidence="ECO:0000269|PubMed:23829171"
FT /id="VAR_069993"
FT VARIANT 418
FT /note="R -> S (in DA5D; dbSNP:rs587776919)"
FT /evidence="ECO:0000269|PubMed:23261301"
FT /id="VAR_069747"
FT VARIANT 607
FT /note="G -> S (in DA5D; patients have ophthalmoplegia)"
FT /evidence="ECO:0000269|PubMed:23808592"
FT /id="VAR_069994"
FT VARIANT 760
FT /note="C -> R (in DA5D; dbSNP:rs587777129)"
FT /evidence="ECO:0000269|PubMed:23236030"
FT /id="VAR_069995"
FT CONFLICT 45
FT /note="A -> V (in Ref. 4; AAQ89282)"
FT /evidence="ECO:0000305"
FT CONFLICT 124
FT /note="Q -> R (in Ref. 3; AAZ22338)"
FT /evidence="ECO:0000305"
FT CONFLICT 152
FT /note="A -> T (in Ref. 3; AAZ22338)"
FT /evidence="ECO:0000305"
FT CONFLICT 163
FT /note="R -> C (in Ref. 3; AAZ22338)"
FT /evidence="ECO:0000305"
FT CONFLICT 286
FT /note="I -> V (in Ref. 1; CAA76113)"
FT /evidence="ECO:0000305"
FT CONFLICT 293
FT /note="F -> L (in Ref. 3; AAZ22338)"
FT /evidence="ECO:0000305"
FT CONFLICT 544
FT /note="R -> P (in Ref. 4; AAQ89282)"
FT /evidence="ECO:0000305"
FT CONFLICT 679
FT /note="G -> V (in Ref. 4; AAQ89282)"
FT /evidence="ECO:0000305"
FT CONFLICT 757..758
FT /note="AF -> VL (in Ref. 1; CAA76113)"
FT /evidence="ECO:0000305"
FT CONFLICT 763
FT /note="D -> V (in Ref. 1; CAA76113)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 775 AA; 87791 MW; C4ED98DE848BE822 CRC64;
MEPPYSLTAH YDEFQEVKYV SRCGAGGARG ASLPPGFPLG AARSATGARS GLPRWNRREV
CLLSGLVFAA GLCAILAAML ALKYLGPVAA GGGACPEGCP ERKAFARAAR FLAANLDASI
DPCQDFYSFA CGGWLRRHAI PDDKLTYGTI AAIGEQNEER LRRLLARPGG GPGGAAQRKV
RAFFRSCLDM REIERLGPRP MLEVIEDCGG WDLGGAEERP GVAARWDLNR LLYKAQGVYS
AAALFSLTVS LDDRNSSRYV IRIDQDGLTL PERTLYLAQD EDSEKILAAY RVFMERVLSL
LGADAVEQKA QEILQVEQQL ANITVSEHDD LRRDVSSMYN KVTLGQLQKI TPHLRWKWLL
DQIFQEDFSE EEEVVLLATD YMQQVSQLIR STPHRVLHNY LVWRVVVVLS EHLSPPFREA
LHELAQEMEG SDKPQELARV CLGQANRHFG MALGALFVHE HFSAASKAKV QQLVEDIKYI
LGQRLEELDW MDAETRAAAR AKLQYMMVMV GYPDFLLKPD AVDKEYEFEV HEKTYFKNIL
NSIRFSIQLS VKKIRQEVDK STWLLPPQAL NAYYLPNKNQ MVFPAGILQP TLYDPDFPQS
LNYGGIGTII GHELTHGYDD WGGQYDRSGN LLHWWTEASY SRFLRKAECI VRLYDNFTVY
NQRVNGKHTL GENIADMGGL KLAYHAYQKW VREHGPEHPL PRLKYTHDQL FFIAFAQNWC
IKRRSQSIYL QVLTDKHAPE HYRVLGSVSQ FEEFGRAFHC PKDSPMNPAH KCSVW
