ECHM_HUMAN
ID ECHM_HUMAN Reviewed; 290 AA.
AC P30084; O00739; Q5VWY1; Q96H54;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 4.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=Enoyl-CoA hydratase, mitochondrial {ECO:0000305};
DE Short=mECH;
DE Short=mECH1;
DE EC=4.2.1.17 {ECO:0000269|PubMed:26251176};
DE EC=5.3.3.8 {ECO:0000250|UniProtKB:P14604};
DE AltName: Full=Enoyl-CoA hydratase 1;
DE Short=ECHS1 {ECO:0000303|PubMed:25125611, ECO:0000303|PubMed:26251176};
DE AltName: Full=Short-chain enoyl-CoA hydratase {ECO:0000303|PubMed:25125611};
DE Short=SCEH;
DE Flags: Precursor;
GN Name=ECHS1 {ECO:0000312|HGNC:HGNC:3151};
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], AND VARIANTS ALA-11 AND ILE-75.
RC TISSUE=Liver;
RX PubMed=8012501; DOI=10.1159/000468650;
RA Kanazawa M., Ohtake A., Abe H., Yamamoto S., Satoh Y., Takayanagi M.,
RA Niimi H., Mori M., Hashimoto T.;
RT "Molecular cloning and sequence analysis of the cDNA for human
RT mitochondrial short-chain enoyl-CoA hydratase.";
RL Enzyme Protein 47:9-13(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-11 AND ILE-75.
RX PubMed=9073515; DOI=10.1006/geno.1996.4597;
RA Janssen U., Davis E.M., le Beau M.M., Stoffel W.;
RT "Human mitochondrial enoyl-CoA hydratase gene (ECHS1): structural
RT organization and assignment to chromosome 10q26.2-q26.3.";
RL Genomics 40:470-475(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-75.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-75.
RC TISSUE=Placenta;
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 [6]
RP PROTEIN SEQUENCE OF 28-37.
RC TISSUE=Liver;
RX PubMed=1286669; DOI=10.1002/elps.11501301201;
RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R.,
RA Appel R.D., Hughes G.J.;
RT "Human liver protein map: a reference database established by
RT microsequencing and gel comparison.";
RL Electrophoresis 13:992-1001(1992).
RN [7]
RP PROTEIN SEQUENCE OF 44-56; 102-115; 158-178; 186-197; 242-257 AND 262-273,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 57-63; 75-92 AND 158-178, VARIANT ILE-75, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=11271497;
RX DOI=10.1002/1522-2683(200011)21:17<3785::aid-elps3785>3.0.co;2-2;
RA Hubbard M.J., McHugh N.J.;
RT "Human ERp29: isolation, primary structural characterisation and two-
RT dimensional gel mapping.";
RL Electrophoresis 21:3785-3796(2000).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-118, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP INVOLVEMENT IN ECHS1D, VARIANT ECHS1D ASP-158, AND PATHWAY.
RX PubMed=25125611; DOI=10.1093/brain/awu216;
RA Peters H., Buck N., Wanders R., Ruiter J., Waterham H., Koster J.,
RA Yaplito-Lee J., Ferdinandusse S., Pitt J.;
RT "ECHS1 mutations in Leigh disease: a new inborn error of metabolism
RT affecting valine metabolism.";
RL Brain 137:2903-2908(2014).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-46 AND SER-114, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP INVOLVEMENT IN ECHS1D, AND VARIANT ECHS1D VAL-2.
RX PubMed=25393721; DOI=10.1002/humu.22730;
RA Sakai C., Yamaguchi S., Sasaki M., Miyamoto Y., Matsushima Y., Goto Y.;
RT "ECHS1 mutations cause combined respiratory chain deficiency resulting in
RT Leigh syndrome.";
RL Hum. Mutat. 36:232-239(2015).
RN [14]
RP CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER PHE-27, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 24-290 IN COMPLEX WITH CROTONYL
RP COENZYME A, AND SUBUNIT.
RG Structural genomics consortium (SGC);
RT "The crystal structure of human enoyl-coenzyme A (CoA) hydratase short
RT chain 1, ECHS1.";
RL Submitted (AUG-2006) to the PDB data bank.
RN [16]
RP VARIANTS ECHS1D SER-33; HIS-54; SER-59; THR-66; GLN-77; ARG-90; THR-132;
RP GLY-150; ARG-159; SER-195; ARG-225 AND GLU-273.
RX PubMed=26000322; DOI=10.1002/acn3.189;
RA Haack T.B., Jackson C.B., Murayama K., Kremer L.S., Schaller A.,
RA Kotzaeridou U., de Vries M.C., Schottmann G., Santra S., Buechner B.,
RA Wieland T., Graf E., Freisinger P., Eggimann S., Ohtake A., Okazaki Y.,
RA Kohda M., Kishita Y., Tokuzawa Y., Sauer S., Memari Y., Kolb-Kokocinski A.,
RA Durbin R., Hasselmann O., Cremer K., Albrecht B., Wieczorek D., Engels H.,
RA Hahn D., Zink A.M., Alston C.L., Taylor R.W., Rodenburg R.J., Trollmann R.,
RA Sperl W., Strom T.M., Hoffmann G.F., Mayr J.A., Meitinger T., Bolognini R.,
RA Schuelke M., Nuoffer J.M., Koelker S., Prokisch H., Klopstock T.;
RT "Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac
RT involvement.";
RL Ann. Clin. Transl. Neurol. 2:492-509(2015).
RN [17]
RP VARIANTS ECHS1D SER-59 AND VAL-138, FUNCTION, BIOPHYSICOCHEMICAL
RP PROPERTIES, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=26251176; DOI=10.1136/jmedgenet-2015-103231;
RA Yamada K., Aiba K., Kitaura Y., Kondo Y., Nomura N., Nakamura Y.,
RA Fukushi D., Murayama K., Shimomura Y., Pitt J., Yamaguchi S., Yokochi K.,
RA Wakamatsu N.;
RT "Clinical, biochemical and metabolic characterisation of a mild form of
RT human short-chain enoyl-CoA hydratase deficiency: significance of increased
RT N-acetyl-S-(2-carboxypropyl)cysteine excretion.";
RL J. Med. Genet. 52:691-698(2015).
RN [18]
RP VARIANT ECHS1D GLY-281.
RX PubMed=27221955; DOI=10.1007/s11011-016-9842-x;
RA Nair P., Hamzeh A.R., Mohamed M., Malik E.M., Al-Ali M.T., Bastaki F.;
RT "Novel ECHS1 mutation in an Emirati neonate with severe metabolic
RT acidosis.";
RL Metab. Brain Dis. 31:1189-1192(2016).
RN [19]
RP VARIANTS ECHS1D SER-33; SER-59 AND ARG-159.
RX PubMed=26741492; DOI=10.1371/journal.pgen.1005679;
RA Kohda M., Tokuzawa Y., Kishita Y., Nyuzuki H., Moriyama Y., Mizuno Y.,
RA Hirata T., Yatsuka Y., Yamashita-Sugahara Y., Nakachi Y., Kato H.,
RA Okuda A., Tamaru S., Borna N.N., Banshoya K., Aigaki T., Sato-Miyata Y.,
RA Ohnuma K., Suzuki T., Nagao A., Maehata H., Matsuda F., Higasa K.,
RA Nagasaki M., Yasuda J., Yamamoto M., Fushimi T., Shimura M.,
RA Kaiho-Ichimoto K., Harashima H., Yamazaki T., Mori M., Murayama K.,
RA Ohtake A., Okazaki Y.;
RT "A comprehensive genomic analysis reveals the genetic landscape of
RT mitochondrial respiratory chain complex deficiencies.";
RL PLoS Genet. 12:E1005679-E1005679(2016).
CC -!- FUNCTION: Converts unsaturated trans-2-enoyl-CoA species ((2E)-enoyl-
CC CoA) to the corresponding (3S)-3hydroxyacyl-CoA species through
CC addition of a water molecule to the double bond (PubMed:25125611,
CC PubMed:26251176). Catalyzes the hydration of medium- and short-chained
CC fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16
CC (PubMed:26251176). Has high substrate specificity for crotonyl-CoA
CC ((2E)-butenoyl-CoA) and moderate specificity for acryloyl-CoA, 3-
CC methylcrotonyl-CoA (3-methyl-(2E)-butenoyl-CoA) and methacrylyl-CoA
CC ((2E)-2-methylpropenoyl-CoA) (PubMed:26251176). Can bind tiglyl-CoA (2-
CC methylcrotonoyl-CoA), but hydrates only a small amount of this
CC substrate (PubMed:26251176). Plays a key role in the beta-oxidation
CC spiral of short- and medium-chain fatty acid oxidation
CC (PubMed:25125611, PubMed:26251176). At a lower rate than the hydratase
CC reaction, catalyzes the isomerase reaction of trans-3-enoyl-CoA species
CC (such as (3E)-hexenoyl-CoA) to trans-2-enoyl-CoA species (such as (2E)-
CC hexenoyl-CoA), which are subsequently hydrated to 3(S)-3-hydroxyacyl-
CC CoA species (such as (3S)-hydroxyhexanoyl-CoA) (By similarity).
CC {ECO:0000250|UniProtKB:P14604, ECO:0000269|PubMed:25125611,
CC ECO:0000269|PubMed:26251176}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3S)-3-hydroxyacyl-CoA = a (2E)-enoyl-CoA + H2O;
CC Xref=Rhea:RHEA:16105, ChEBI:CHEBI:15377, ChEBI:CHEBI:57318,
CC ChEBI:CHEBI:58856; EC=4.2.1.17;
CC Evidence={ECO:0000269|PubMed:26251176};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16107;
CC Evidence={ECO:0000305|PubMed:26251176};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3E)-enoyl-CoA = a 4-saturated (2E)-enoyl-CoA;
CC Xref=Rhea:RHEA:45228, ChEBI:CHEBI:58521, ChEBI:CHEBI:85097;
CC EC=5.3.3.8; Evidence={ECO:0000250|UniProtKB:P14604};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45229;
CC Evidence={ECO:0000250|UniProtKB:P14604};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3E)-hexenoyl-CoA = (2E)-hexenoyl-CoA; Xref=Rhea:RHEA:45736,
CC ChEBI:CHEBI:62077, ChEBI:CHEBI:84790;
CC Evidence={ECO:0000250|UniProtKB:P14604};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45737;
CC Evidence={ECO:0000250|UniProtKB:P14604};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-3-hydroxybutanoyl-CoA = (2E)-butenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:26558, ChEBI:CHEBI:15377, ChEBI:CHEBI:57316,
CC ChEBI:CHEBI:57332; Evidence={ECO:0000269|PubMed:26251176};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:26560;
CC Evidence={ECO:0000305|PubMed:26251176};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-hydroxyisovaleryl-CoA = 3-methyl-(2E)-butenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:31079, ChEBI:CHEBI:15377, ChEBI:CHEBI:57344,
CC ChEBI:CHEBI:62555; Evidence={ECO:0000269|PubMed:26251176};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31081;
CC Evidence={ECO:0000305|PubMed:26251176};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-hydroxypropanoyl-CoA = acryloyl-CoA + H2O;
CC Xref=Rhea:RHEA:26518, ChEBI:CHEBI:15377, ChEBI:CHEBI:57367,
CC ChEBI:CHEBI:58528; Evidence={ECO:0000269|PubMed:26251176};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:26520;
CC Evidence={ECO:0000305|PubMed:26251176};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-hydroxybutanoyl-CoA = (2E)-butenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:45584, ChEBI:CHEBI:15377, ChEBI:CHEBI:57332,
CC ChEBI:CHEBI:78611; Evidence={ECO:0000269|PubMed:26251176};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:45586;
CC Evidence={ECO:0000305|PubMed:26251176};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-2-methylpropenoyl-CoA + H2O = (S)-3-hydroxyisobutanoyl-
CC CoA; Xref=Rhea:RHEA:31175, ChEBI:CHEBI:15377, ChEBI:CHEBI:62500,
CC ChEBI:CHEBI:62611; Evidence={ECO:0000269|PubMed:26251176};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31176;
CC Evidence={ECO:0000305|PubMed:26251176};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexanoyl-CoA = (2E)-hexenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:30547, ChEBI:CHEBI:15377, ChEBI:CHEBI:62075,
CC ChEBI:CHEBI:62077; Evidence={ECO:0000250|UniProtKB:P14604};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:30549;
CC Evidence={ECO:0000250|UniProtKB:P14604};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxydecanoyl-CoA = (2E)-decenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:31191, ChEBI:CHEBI:15377, ChEBI:CHEBI:61406,
CC ChEBI:CHEBI:62616; Evidence={ECO:0000250|UniProtKB:P14604};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31193;
CC Evidence={ECO:0000250|UniProtKB:P14604};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=12.75 uM for crotonyl-CoA ((2E)-butenoyl-CoA)
CC {ECO:0000269|PubMed:26251176};
CC KM=34.04 uM for acryloyl-CoA {ECO:0000269|PubMed:26251176};
CC KM=45.83 uM for 3-Methylcrotonyl-CoA (3-methyl-(2E)-butenoyl-CoA)
CC {ECO:0000269|PubMed:26251176};
CC KM=57.87 uM for tiglyl-CoA (2-methylcrotonoyl-CoA)
CC {ECO:0000269|PubMed:26251176};
CC Vmax=54.64 umol/min/mg enzyme toward crotonyl-CoA
CC {ECO:0000269|PubMed:26251176};
CC Vmax=42.92 umol/min/mg enzyme toward acryloyl-CoA
CC {ECO:0000269|PubMed:26251176};
CC Vmax=49.02 umol/min/mg enzyme toward 3-Methylcrotonyl-CoA
CC {ECO:0000269|PubMed:26251176};
CC Vmax=6.66 umol/min/mg enzyme toward tiglyl-CoA
CC {ECO:0000269|PubMed:26251176};
CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC {ECO:0000269|PubMed:25125611, ECO:0000269|PubMed:26251176}.
CC -!- SUBUNIT: Homohexamer; dimer of trimers. {ECO:0000269|Ref.15}.
CC -!- INTERACTION:
CC P30084; Q5S007: LRRK2; NbExp=4; IntAct=EBI-719602, EBI-5323863;
CC P30084; P40763: STAT3; NbExp=3; IntAct=EBI-719602, EBI-518675;
CC P30084; P42227: Stat3; Xeno; NbExp=3; IntAct=EBI-719602, EBI-602878;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- TISSUE SPECIFICITY: Liver, fibroblast, muscle. Barely detectable in
CC spleen and kidney.
CC -!- DISEASE: Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency
CC (ECHS1D) [MIM:616277]: A severe, autosomal recessive inborn error
CC affecting valine metabolism. Disease features include brain lesions in
CC the basal ganglia, neurodegeneration, delayed psychomotor development,
CC hypotonia, spasticity, and increased lactic acid in serum and cerebral
CC serum fluid. {ECO:0000269|PubMed:25125611, ECO:0000269|PubMed:25393721,
CC ECO:0000269|PubMed:26000322, ECO:0000269|PubMed:26251176,
CC ECO:0000269|PubMed:26741492, ECO:0000269|PubMed:27221955}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the enoyl-CoA hydratase/isomerase family.
CC {ECO:0000305}.
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DR EMBL; D13900; BAA03001.1; -; mRNA.
DR EMBL; X98126; CAA66808.1; -; Genomic_DNA.
DR EMBL; X98127; CAA66808.1; JOINED; Genomic_DNA.
DR EMBL; X98128; CAA66808.1; JOINED; Genomic_DNA.
DR EMBL; X98129; CAA66808.1; JOINED; Genomic_DNA.
DR EMBL; BT007123; AAP35787.1; -; mRNA.
DR EMBL; AL360181; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008906; AAH08906.1; -; mRNA.
DR CCDS; CCDS7681.1; -.
DR RefSeq; NP_004083.3; NM_004092.3.
DR PDB; 2HW5; X-ray; 2.55 A; A/B/C/D/E/F=28-290.
DR PDBsum; 2HW5; -.
DR AlphaFoldDB; P30084; -.
DR SMR; P30084; -.
DR BioGRID; 108221; 201.
DR IntAct; P30084; 50.
DR MINT; P30084; -.
DR STRING; 9606.ENSP00000357535; -.
DR ChEMBL; CHEMBL4523211; -.
DR DrugBank; DB04117; 4-(N,N-Dimethylamino)cinnamoyl-CoA.
DR DrugBank; DB03059; Acetoacetyl-CoA.
DR DrugBank; DB02563; Hexanoyl-CoA.
DR DrugBank; DB02910; Octanoyl-Coenzyme A.
DR DrugBank; DB09568; Omega-3-carboxylic acids.
DR SwissLipids; SLP:000001471; -.
DR iPTMnet; P30084; -.
DR MetOSite; P30084; -.
DR PhosphoSitePlus; P30084; -.
DR SwissPalm; P30084; -.
DR BioMuta; ECHS1; -.
DR DMDM; 62906863; -.
DR DOSAC-COBS-2DPAGE; P30084; -.
DR REPRODUCTION-2DPAGE; IPI00024993; -.
DR REPRODUCTION-2DPAGE; P30084; -.
DR SWISS-2DPAGE; P30084; -.
DR UCD-2DPAGE; P30084; -.
DR EPD; P30084; -.
DR jPOST; P30084; -.
DR MassIVE; P30084; -.
DR MaxQB; P30084; -.
DR PaxDb; P30084; -.
DR PeptideAtlas; P30084; -.
DR PRIDE; P30084; -.
DR ProteomicsDB; 54632; -.
DR TopDownProteomics; P30084; -.
DR Antibodypedia; 19426; 248 antibodies from 26 providers.
DR DNASU; 1892; -.
DR Ensembl; ENST00000368547.4; ENSP00000357535.3; ENSG00000127884.5.
DR GeneID; 1892; -.
DR KEGG; hsa:1892; -.
DR MANE-Select; ENST00000368547.4; ENSP00000357535.3; NM_004092.4; NP_004083.3.
DR UCSC; uc001lmu.4; human.
DR CTD; 1892; -.
DR DisGeNET; 1892; -.
DR GeneCards; ECHS1; -.
DR GeneReviews; ECHS1; -.
DR HGNC; HGNC:3151; ECHS1.
DR HPA; ENSG00000127884; Tissue enhanced (liver).
DR MalaCards; ECHS1; -.
DR MIM; 602292; gene.
DR MIM; 616277; phenotype.
DR neXtProt; NX_P30084; -.
DR OpenTargets; ENSG00000127884; -.
DR Orphanet; 255241; Leigh syndrome with leukodystrophy.
DR PharmGKB; PA27597; -.
DR VEuPathDB; HostDB:ENSG00000127884; -.
DR eggNOG; KOG1680; Eukaryota.
DR GeneTree; ENSGT00940000157609; -.
DR HOGENOM; CLU_009834_7_6_1; -.
DR InParanoid; P30084; -.
DR OMA; IFKQTDA; -.
DR OrthoDB; 1221604at2759; -.
DR PhylomeDB; P30084; -.
DR TreeFam; TF314497; -.
DR BioCyc; MetaCyc:HS05132-MON; -.
DR BRENDA; 4.2.1.17; 2681.
DR PathwayCommons; P30084; -.
DR Reactome; R-HSA-70895; Branched-chain amino acid catabolism.
DR Reactome; R-HSA-77310; Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA.
DR Reactome; R-HSA-77346; Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA.
DR Reactome; R-HSA-77348; Beta oxidation of octanoyl-CoA to hexanoyl-CoA.
DR Reactome; R-HSA-77350; Beta oxidation of hexanoyl-CoA to butanoyl-CoA.
DR Reactome; R-HSA-77352; Beta oxidation of butanoyl-CoA to acetyl-CoA.
DR SABIO-RK; P30084; -.
DR SignaLink; P30084; -.
DR UniPathway; UPA00659; -.
DR BioGRID-ORCS; 1892; 22 hits in 1070 CRISPR screens.
DR ChiTaRS; ECHS1; human.
DR EvolutionaryTrace; P30084; -.
DR GeneWiki; ECHS1; -.
DR GenomeRNAi; 1892; -.
DR Pharos; P30084; Tbio.
DR PRO; PR:P30084; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P30084; protein.
DR Bgee; ENSG00000127884; Expressed in right lobe of liver and 208 other tissues.
DR Genevisible; P30084; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0043956; F:3-hydroxypropionyl-CoA dehydratase activity; IEA:RHEA.
DR GO; GO:0120092; F:crotonyl-CoA hydratase activity; IEA:RHEA.
DR GO; GO:0004165; F:delta(3)-delta(2)-enoyl-CoA isomerase activity; IEA:RHEA.
DR GO; GO:0004300; F:enoyl-CoA hydratase activity; IDA:UniProtKB.
DR GO; GO:0009083; P:branched-chain amino acid catabolic process; TAS:Reactome.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IDA:UniProtKB.
DR Gene3D; 1.10.12.10; -; 1.
DR InterPro; IPR029045; ClpP/crotonase-like_dom_sf.
DR InterPro; IPR018376; Enoyl-CoA_hyd/isom_CS.
DR InterPro; IPR001753; Enoyl-CoA_hydra/iso.
DR InterPro; IPR014748; Enoyl-CoA_hydra_C.
DR Pfam; PF00378; ECH_1; 1.
DR SUPFAM; SSF52096; SSF52096; 1.
DR PROSITE; PS00166; ENOYL_COA_HYDRATASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Disease variant;
KW Fatty acid metabolism; Isomerase; Lipid metabolism; Lyase; Mitochondrion;
KW Neurodegeneration; Phosphoprotein; Reference proteome; Transit peptide.
FT TRANSIT 1..27
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:1286669,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 28..290
FT /note="Enoyl-CoA hydratase, mitochondrial"
FT /id="PRO_0000007411"
FT BINDING 98..101
FT /ligand="substrate"
FT BINDING 141
FT /ligand="substrate"
FT SITE 164
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250"
FT MOD_RES 46
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 101
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BH95"
FT MOD_RES 101
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BH95"
FT MOD_RES 114
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 115
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BH95"
FT MOD_RES 115
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BH95"
FT MOD_RES 118
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 204
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BH95"
FT MOD_RES 211
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BH95"
FT VARIANT 2
FT /note="A -> V (in ECHS1D; dbSNP:rs587776498)"
FT /evidence="ECO:0000269|PubMed:25393721"
FT /id="VAR_073373"
FT VARIANT 11
FT /note="V -> A (in dbSNP:rs10466126)"
FT /evidence="ECO:0000269|PubMed:8012501,
FT ECO:0000269|PubMed:9073515"
FT /id="VAR_022273"
FT VARIANT 33
FT /note="F -> S (in ECHS1D)"
FT /evidence="ECO:0000269|PubMed:26000322,
FT ECO:0000269|PubMed:26741492"
FT /id="VAR_076185"
FT VARIANT 54
FT /note="R -> H (in ECHS1D; dbSNP:rs375266808)"
FT /evidence="ECO:0000269|PubMed:26000322"
FT /id="VAR_076186"
FT VARIANT 59
FT /note="N -> S (in ECHS1D; decreases significantly enoyl-CoA
FT hydratase activity; decreases significantly protein
FT expression; dbSNP:rs201865375)"
FT /evidence="ECO:0000269|PubMed:26000322,
FT ECO:0000269|PubMed:26251176, ECO:0000269|PubMed:26741492"
FT /id="VAR_076187"
FT VARIANT 66
FT /note="I -> T (in ECHS1D; dbSNP:rs371063211)"
FT /evidence="ECO:0000269|PubMed:26000322"
FT /id="VAR_076188"
FT VARIANT 75
FT /note="T -> I (in dbSNP:rs1049951)"
FT /evidence="ECO:0000269|PubMed:11271497,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:8012501,
FT ECO:0000269|PubMed:9073515, ECO:0000269|Ref.3"
FT /id="VAR_022274"
FT VARIANT 77
FT /note="E -> Q (in ECHS1D; dbSNP:rs1426014295)"
FT /evidence="ECO:0000269|PubMed:26000322"
FT /id="VAR_076189"
FT VARIANT 90
FT /note="G -> R (in ECHS1D; unknown pathological
FT significance; dbSNP:rs1085307550)"
FT /evidence="ECO:0000269|PubMed:26000322"
FT /id="VAR_076190"
FT VARIANT 132
FT /note="A -> T (in ECHS1D; dbSNP:rs770931871)"
FT /evidence="ECO:0000269|PubMed:26000322"
FT /id="VAR_076191"
FT VARIANT 138
FT /note="A -> V (in ECHS1D; decreases enoyl-CoA hydratase
FT activity of 70%; decreases significantly protein
FT expression; dbSNP:rs864309656)"
FT /evidence="ECO:0000269|PubMed:26251176"
FT /id="VAR_076479"
FT VARIANT 150
FT /note="D -> G (in ECHS1D)"
FT /evidence="ECO:0000269|PubMed:26000322"
FT /id="VAR_076192"
FT VARIANT 158
FT /note="A -> D (in ECHS1D; dbSNP:rs786204001)"
FT /evidence="ECO:0000269|PubMed:25125611"
FT /id="VAR_073374"
FT VARIANT 159
FT /note="Q -> R (in ECHS1D; dbSNP:rs375032130)"
FT /evidence="ECO:0000269|PubMed:26000322,
FT ECO:0000269|PubMed:26741492"
FT /id="VAR_076193"
FT VARIANT 195
FT /note="G -> S (in ECHS1D; dbSNP:rs761989177)"
FT /evidence="ECO:0000269|PubMed:26000322"
FT /id="VAR_076194"
FT VARIANT 225
FT /note="C -> R (in ECHS1D; dbSNP:rs769429279)"
FT /evidence="ECO:0000269|PubMed:26000322"
FT /id="VAR_076195"
FT VARIANT 273
FT /note="K -> E (in ECHS1D; dbSNP:rs565090080)"
FT /evidence="ECO:0000269|PubMed:26000322"
FT /id="VAR_076196"
FT VARIANT 281
FT /note="E -> G (in ECHS1D; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:27221955"
FT /id="VAR_076480"
FT CONFLICT 84
FT /note="A -> G (in Ref. 1; BAA03001)"
FT /evidence="ECO:0000305"
FT CONFLICT 121
FT /note="D -> G (in Ref. 1; BAA03001)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="A -> P (in Ref. 1; BAA03001)"
FT /evidence="ECO:0000305"
FT CONFLICT 188..189
FT /note="AM -> EL (in Ref. 1; BAA03001)"
FT /evidence="ECO:0000305"
FT CONFLICT 197
FT /note="R -> A (in Ref. 1; BAA03001)"
FT /evidence="ECO:0000305"
FT STRAND 34..42
FT /evidence="ECO:0007829|PDB:2HW5"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:2HW5"
FT STRAND 47..52
FT /evidence="ECO:0007829|PDB:2HW5"
FT HELIX 55..57
FT /evidence="ECO:0007829|PDB:2HW5"
FT HELIX 63..78
FT /evidence="ECO:0007829|PDB:2HW5"
FT STRAND 84..88
FT /evidence="ECO:0007829|PDB:2HW5"
FT STRAND 91..95
FT /evidence="ECO:0007829|PDB:2HW5"
FT HELIX 100..103
FT /evidence="ECO:0007829|PDB:2HW5"
FT HELIX 108..113
FT /evidence="ECO:0007829|PDB:2HW5"
FT TURN 114..117
FT /evidence="ECO:0007829|PDB:2HW5"
FT HELIX 119..125
FT /evidence="ECO:0007829|PDB:2HW5"
FT STRAND 130..134
FT /evidence="ECO:0007829|PDB:2HW5"
FT STRAND 136..139
FT /evidence="ECO:0007829|PDB:2HW5"
FT HELIX 141..147
FT /evidence="ECO:0007829|PDB:2HW5"
FT STRAND 149..155
FT /evidence="ECO:0007829|PDB:2HW5"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:2HW5"
FT HELIX 163..167
FT /evidence="ECO:0007829|PDB:2HW5"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:2HW5"
FT TURN 175..177
FT /evidence="ECO:0007829|PDB:2HW5"
FT HELIX 178..183
FT /evidence="ECO:0007829|PDB:2HW5"
FT HELIX 185..194
FT /evidence="ECO:0007829|PDB:2HW5"
FT HELIX 200..205
FT /evidence="ECO:0007829|PDB:2HW5"
FT STRAND 210..213
FT /evidence="ECO:0007829|PDB:2HW5"
FT TURN 215..217
FT /evidence="ECO:0007829|PDB:2HW5"
FT HELIX 218..231
FT /evidence="ECO:0007829|PDB:2HW5"
FT HELIX 234..245
FT /evidence="ECO:0007829|PDB:2HW5"
FT HELIX 246..248
FT /evidence="ECO:0007829|PDB:2HW5"
FT HELIX 252..266
FT /evidence="ECO:0007829|PDB:2HW5"
FT HELIX 270..280
FT /evidence="ECO:0007829|PDB:2HW5"
SQ SEQUENCE 290 AA; 31387 MW; 0CCD0C7F891B1704 CRC64;
MAALRVLLSC VRGPLRPPVR CPAWRPFASG ANFEYIIAEK RGKNNTVGLI QLNRPKALNA
LCDGLIDELN QALKTFEEDP AVGAIVLTGG DKAFAAGADI KEMQNLSFQD CYSSKFLKHW
DHLTQVKKPV IAAVNGYAFG GGCELAMMCD IIYAGEKAQF AQPEILIGTI PGAGGTQRLT
RAVGKSLAME MVLTGDRISA QDAKQAGLVS KICPVETLVE EAIQCAEKIA SNSKIVVAMA
KESVNAAFEM TLTEGSKLEK KLFYSTFATD DRKEGMTAFV EKRKANFKDQ
