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 27-MAR-2024, entry version 227. 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}. 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; 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; 237. DR IntAct; P30084; 56. 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 GlyGen; P30084; 1 site, 1 O-linked glycan (1 site). 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 EPD; P30084; -. DR jPOST; P30084; -. DR MassIVE; P30084; -. DR MaxQB; P30084; -. DR PaxDb; 9606-ENSP00000357535; -. DR PeptideAtlas; P30084; -. DR PRIDE; P30084; -. DR ProteomicsDB; 54632; -. DR Pumba; P30084; -. DR TopDownProteomics; P30084; -. DR Antibodypedia; 19426; 268 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 AGR; HGNC:3151; -. 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; 653880; Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency. 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; FCDARED; -. DR OrthoDB; 553487at2759; -. DR PhylomeDB; P30084; -. DR TreeFam; TF314497; -. DR BioCyc; MetaCyc:HS05132-MONOMER; -. 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; 31 hits in 1151 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 210 other cell types or tissues. 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; IDA:FlyBase. 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 CDD; cd06558; crotonase-like; 1. DR Gene3D; 1.10.12.10; Lyase 2-enoyl-coa Hydratase, Chain A, domain 2; 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 PANTHER; PTHR11941:SF54; ENOYL-COA HYDRATASE, MITOCHONDRIAL; 1. DR PANTHER; PTHR11941; ENOYL-COA HYDRATASE-RELATED; 1. DR Pfam; PF00378; ECH_1; 1. DR SUPFAM; SSF52096; ClpP/crotonase; 1. DR PROSITE; PS00166; ENOYL_COA_HYDRATASE; 1. DR SWISS-2DPAGE; P30084; -. DR UCD-2DPAGE; P30084; -. DR Genevisible; P30084; HS. 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; uncertain significance; FT 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; uncertain 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 //