MECR_HUMAN
ID MECR_HUMAN Reviewed; 373 AA.
AC Q9BV79; B3KT72; Q5SYU0; Q5SYU1; Q5SYU2; Q6IBU9; Q9Y373;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 31-MAY-2011, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Enoyl-[acyl-carrier-protein] reductase, mitochondrial {ECO:0000305};
DE EC=1.3.1.104 {ECO:0000305|PubMed:12654921, ECO:0000305|PubMed:18479707};
DE AltName: Full=2-enoyl thioester reductase {ECO:0000303|PubMed:12654921, ECO:0000303|PubMed:18479707};
DE AltName: Full=Nuclear receptor-binding factor 1;
DE Short=HsNrbf-1;
DE Short=NRBF-1;
DE Flags: Precursor;
GN Name=MECR; Synonyms=NBRF1; ORFNames=CGI-63;
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 [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-96.
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT LEU-96.
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-96.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT LEU-96.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-96.
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 [7]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12654921; DOI=10.1074/jbc.m302851200;
RA Miinalainen I.J., Chen Z.-J., Torkko J.M., Pirilae P.L., Sormunen R.T.,
RA Bergmann U., Qin Y.-M., Hiltunen J.K.;
RT "Characterization of 2-enoyl thioester reductase from mammals: an ortholog
RT of Ybr026p/Mrf1'p of the yeast mitochondrial fatty acid synthesis type
RT II.";
RL J. Biol. Chem. 278:20154-20161(2003).
RN [8]
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 [9]
RP SUBCELLULAR LOCATION (ISOFORM 2).
RX PubMed=25031892; DOI=10.3803/enm.2014.29.2.185;
RA Kim D.G., Yoo J.C., Kim E., Lee Y.S., Yarishkin O.V., Lee da Y., Lee K.H.,
RA Hong S.G., Hwang E.M., Park J.Y.;
RT "A novel cytosolic isoform of mitochondrial Trans-2-Enoyl-CoA reductase
RT enhances peroxisome proliferator-activated receptor alpha activity.";
RL Endocrinol. Metab. 29:185-194(2014).
RN [10]
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 [11]
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 [12]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 40-373.
RG Structural genomics consortium (SGC);
RT "The structure of human mitochondrial 2-enoyl thioester reductase (CGI-
RT 63).";
RL Submitted (JUN-2005) to the PDB data bank.
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.41 ANGSTROMS) OF 31-373, FUNCTION, CATALYTIC
RP ACTIVITY, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF
RP SER-85; TYR-94; ILE-129; GLY-165; THR-170; TRP-311 AND PHE-324.
RX PubMed=18479707; DOI=10.1016/j.jmb.2008.04.041;
RA Chen Z.J., Pudas R., Sharma S., Smart O.S., Juffer A.H., Hiltunen J.K.,
RA Wierenga R.K., Haapalainen A.M.;
RT "Structural enzymological studies of 2-enoyl thioester reductase of the
RT human mitochondrial FAS II pathway: new insights into its substrate
RT recognition properties.";
RL J. Mol. Biol. 379:830-844(2008).
RN [14]
RP INVOLVEMENT IN DYTOABG, VARIANTS DYTOABG GLU-232; TRP-258; 285-TYR--MET-373
RP DEL AND CYS-285, CHARACTERIZATION OF VARIANTS DYTOABG GLU-232 AND
RP 285-TYR--MET-373 DEL, AND FUNCTION.
RX PubMed=27817865; DOI=10.1016/j.ajhg.2016.09.021;
RG University of Washington Center for Mendelian Genomics;
RA Heimer G., Keraetaer J.M., Riley L.G., Balasubramaniam S., Eyal E.,
RA Pietikaeinen L.P., Hiltunen J.K., Marek-Yagel D., Hamada J., Gregory A.,
RA Rogers C., Hogarth P., Nance M.A., Shalva N., Veber A., Tzadok M.,
RA Nissenkorn A., Tonduti D., Renaldo F., Kraoua I., Panteghini C.,
RA Valletta L., Garavaglia B., Cowley M.J., Gayevskiy V., Roscioli T.,
RA Silberstein J.M., Hoffmann C., Raas-Rothschild A., Tiranti V., Anikster Y.,
RA Christodoulou J., Kastaniotis A.J., Ben-Zeev B., Hayflick S.J.;
RT "MECR mutations cause childhood-onset dystonia and optic atrophy, a
RT mitochondrial fatty acid synthesis disorder.";
RL Am. J. Hum. Genet. 99:1229-1244(2016).
CC -!- FUNCTION: Catalyzes the NADPH-dependent reduction of trans-2-enoyl
CC thioesters in mitochondrial fatty acid synthesis (fatty acid synthesis
CC type II). Fatty acid chain elongation in mitochondria uses acyl carrier
CC protein (ACP) as an acyl group carrier, but the enzyme accepts both ACP
CC and CoA thioesters as substrates in vitro. Displays a preference for
CC medium-chain over short- and long-chain substrates (PubMed:18479707,
CC PubMed:12654921, PubMed:27817865). May provide the octanoyl chain used
CC for lipoic acid biosynthesis, regulating protein lipoylation and
CC mitochondrial respiratory activity particularly in Purkinje cells (By
CC similarity). {ECO:0000250|UniProtKB:Q9DCS3,
CC ECO:0000269|PubMed:12654921, ECO:0000269|PubMed:18479707,
CC ECO:0000269|PubMed:27817865}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2,3-saturated acyl-[ACP] + NADP(+) = a (2E)-enoyl-[ACP] +
CC H(+) + NADPH; Xref=Rhea:RHEA:22564, Rhea:RHEA-COMP:9925, Rhea:RHEA-
CC COMP:9926, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78784, ChEBI:CHEBI:78785; EC=1.3.1.104;
CC Evidence={ECO:0000305|PubMed:12654921, ECO:0000305|PubMed:18479707};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22566;
CC Evidence={ECO:0000305|PubMed:12654921, ECO:0000305|PubMed:18479707};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-butenoyl-[ACP] + H(+) + NADPH = butanoyl-[ACP] + NADP(+);
CC Xref=Rhea:RHEA:41812, Rhea:RHEA-COMP:9627, Rhea:RHEA-COMP:9628,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78453, ChEBI:CHEBI:78454;
CC Evidence={ECO:0000305|PubMed:18479707};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41813;
CC Evidence={ECO:0000305|PubMed:18479707};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-hexenoyl-[ACP] + H(+) + NADPH = hexanoyl-[ACP] + NADP(+);
CC Xref=Rhea:RHEA:41832, Rhea:RHEA-COMP:9631, Rhea:RHEA-COMP:9632,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78458, ChEBI:CHEBI:78459;
CC Evidence={ECO:0000305|PubMed:18479707};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41833;
CC Evidence={ECO:0000305|PubMed:18479707};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-octenoyl-[ACP] + H(+) + NADPH = NADP(+) + octanoyl-[ACP];
CC Xref=Rhea:RHEA:41848, Rhea:RHEA-COMP:9635, Rhea:RHEA-COMP:9636,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78462, ChEBI:CHEBI:78463;
CC Evidence={ECO:0000305|PubMed:18479707};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41849;
CC Evidence={ECO:0000305|PubMed:18479707};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-decenoyl-[ACP] + H(+) + NADPH = decanoyl-[ACP] + NADP(+);
CC Xref=Rhea:RHEA:41864, Rhea:RHEA-COMP:9639, Rhea:RHEA-COMP:9640,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78467, ChEBI:CHEBI:78468;
CC Evidence={ECO:0000305|PubMed:12654921, ECO:0000305|PubMed:18479707};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41865;
CC Evidence={ECO:0000305|PubMed:18479707};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-dodecenoyl-[ACP] + H(+) + NADPH = dodecanoyl-[ACP] +
CC NADP(+); Xref=Rhea:RHEA:41880, Rhea:RHEA-COMP:9643, Rhea:RHEA-
CC COMP:9644, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:65264, ChEBI:CHEBI:78472;
CC Evidence={ECO:0000305|PubMed:18479707};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41881;
CC Evidence={ECO:0000305|PubMed:18479707};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-tetradecenoyl-[ACP] + H(+) + NADPH = NADP(+) +
CC tetradecanoyl-[ACP]; Xref=Rhea:RHEA:41896, Rhea:RHEA-COMP:9647,
CC Rhea:RHEA-COMP:9648, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:78475, ChEBI:CHEBI:78477;
CC Evidence={ECO:0000305|PubMed:18479707};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41897;
CC Evidence={ECO:0000305|PubMed:18479707};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-hexadecenoyl-[ACP] + H(+) + NADPH = hexadecanoyl-[ACP] +
CC NADP(+); Xref=Rhea:RHEA:41912, Rhea:RHEA-COMP:9651, Rhea:RHEA-
CC COMP:9652, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78481, ChEBI:CHEBI:78483;
CC Evidence={ECO:0000305|PubMed:18479707};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41913;
CC Evidence={ECO:0000305|PubMed:18479707};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=74.2 uM for (2E)-butenoyl-CoA {ECO:0000269|PubMed:18479707};
CC KM=63.5 uM for (2E)-hexenoyl-CoA {ECO:0000269|PubMed:18479707};
CC KM=10.2 uM for (2E)-octenoyl-CoA {ECO:0000269|PubMed:18479707};
CC KM=10.4 uM for (2E)-decenoyl-CoA {ECO:0000269|PubMed:18479707};
CC KM=3.6 uM for (2E)-dodecenoyl-CoA {ECO:0000269|PubMed:18479707};
CC KM=4.3 uM for (2E)-tetradecenoyl-CoA {ECO:0000269|PubMed:18479707};
CC KM=6.6 uM for (2E)-hexadecenoyl-CoA {ECO:0000269|PubMed:18479707};
CC KM=37 uM for (2E)-hexenoyl-CoA {ECO:0000269|PubMed:12654921};
CC KM=7.1 uM for (2E)-decenoyl-CoA {ECO:0000269|PubMed:12654921};
CC -!- SUBUNIT: Homodimer (PubMed:12654921, PubMed:18479707). Isoform 2
CC interacts with PPARA in the nucleus and increases its activity (By
CC similarity). {ECO:0000250|UniProtKB:Q9Z311,
CC ECO:0000269|PubMed:12654921, ECO:0000269|PubMed:18479707}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion
CC {ECO:0000269|PubMed:12654921}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:25031892}. Nucleus {ECO:0000269|PubMed:25031892}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BV79-1; Sequence=Displayed;
CC Name=2; Synonyms=cMECR;
CC IsoId=Q9BV79-2; Sequence=VSP_041131;
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal and heart muscle.
CC Expressed at lower level in placenta, liver, kidney and pancreas.
CC Weakly or not expressed in lung. {ECO:0000269|PubMed:12654921}.
CC -!- DISEASE: Dystonia, childhood-onset, with optic atrophy and basal
CC ganglia abnormalities (DYTOABG) [MIM:617282]: An autosomal recessive
CC neurologic disorder characterized by childhood-onset dystonia, basal
CC ganglia degeneration and optic atrophy with decreased visual acuity.
CC Dystonia is defined by the presence of sustained involuntary muscle
CC contraction, often leading to abnormal postures. DYTOABG severity is
CC variable, and some patients lose independent ambulation.
CC {ECO:0000269|PubMed:27817865}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. Quinone oxidoreductase subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD34058.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF151821; AAD34058.1; ALT_FRAME; mRNA.
DR EMBL; AK095099; BAG52984.1; -; mRNA.
DR EMBL; CR456703; CAG32984.1; -; mRNA.
DR EMBL; AL590729; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07655.1; -; Genomic_DNA.
DR EMBL; BC001419; AAH01419.1; -; mRNA.
DR CCDS; CCDS30659.1; -. [Q9BV79-1]
DR CCDS; CCDS30660.1; -. [Q9BV79-2]
DR RefSeq; NP_001019903.2; NM_001024732.2. [Q9BV79-2]
DR RefSeq; NP_057095.3; NM_016011.3. [Q9BV79-1]
DR RefSeq; XP_005245944.1; XM_005245887.2.
DR RefSeq; XP_016856902.1; XM_017001413.1. [Q9BV79-2]
DR RefSeq; XP_016856903.1; XM_017001414.1.
DR RefSeq; XP_016856904.1; XM_017001415.1.
DR PDB; 1ZSY; X-ray; 1.75 A; A=40-373.
DR PDB; 2VCY; X-ray; 2.41 A; A/B=31-373.
DR PDBsum; 1ZSY; -.
DR PDBsum; 2VCY; -.
DR AlphaFoldDB; Q9BV79; -.
DR SMR; Q9BV79; -.
DR BioGRID; 119291; 28.
DR IntAct; Q9BV79; 4.
DR STRING; 9606.ENSP00000263702; -.
DR SwissLipids; SLP:000001054; -.
DR iPTMnet; Q9BV79; -.
DR PhosphoSitePlus; Q9BV79; -.
DR BioMuta; MECR; -.
DR DMDM; 334302832; -.
DR EPD; Q9BV79; -.
DR jPOST; Q9BV79; -.
DR MassIVE; Q9BV79; -.
DR MaxQB; Q9BV79; -.
DR PaxDb; Q9BV79; -.
DR PeptideAtlas; Q9BV79; -.
DR PRIDE; Q9BV79; -.
DR ProteomicsDB; 79177; -. [Q9BV79-1]
DR ProteomicsDB; 79178; -. [Q9BV79-2]
DR Antibodypedia; 16646; 179 antibodies from 26 providers.
DR DNASU; 51102; -.
DR Ensembl; ENST00000263702.11; ENSP00000263702.6; ENSG00000116353.16. [Q9BV79-1]
DR Ensembl; ENST00000373791.7; ENSP00000362896.3; ENSG00000116353.16. [Q9BV79-2]
DR GeneID; 51102; -.
DR KEGG; hsa:51102; -.
DR MANE-Select; ENST00000263702.11; ENSP00000263702.6; NM_016011.5; NP_057095.4.
DR UCSC; uc001brp.3; human. [Q9BV79-1]
DR CTD; 51102; -.
DR DisGeNET; 51102; -.
DR GeneCards; MECR; -.
DR GeneReviews; MECR; -.
DR HGNC; HGNC:19691; MECR.
DR HPA; ENSG00000116353; Tissue enhanced (skeletal).
DR MalaCards; MECR; -.
DR MIM; 608205; gene.
DR MIM; 617282; phenotype.
DR neXtProt; NX_Q9BV79; -.
DR OpenTargets; ENSG00000116353; -.
DR Orphanet; 508093; MEPAN syndrome.
DR PharmGKB; PA142671471; -.
DR VEuPathDB; HostDB:ENSG00000116353; -.
DR eggNOG; KOG0025; Eukaryota.
DR GeneTree; ENSGT00940000156592; -.
DR HOGENOM; CLU_026673_17_1_1; -.
DR InParanoid; Q9BV79; -.
DR OMA; HQLCRAW; -.
DR OrthoDB; 1269870at2759; -.
DR PhylomeDB; Q9BV79; -.
DR TreeFam; TF312886; -.
DR BioCyc; MetaCyc:HS04010-MON; -.
DR PathwayCommons; Q9BV79; -.
DR Reactome; R-HSA-77346; Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA.
DR SABIO-RK; Q9BV79; -.
DR SignaLink; Q9BV79; -.
DR BioGRID-ORCS; 51102; 93 hits in 1082 CRISPR screens.
DR ChiTaRS; MECR; human.
DR EvolutionaryTrace; Q9BV79; -.
DR GeneWiki; MECR; -.
DR GenomeRNAi; 51102; -.
DR Pharos; Q9BV79; Tbio.
DR PRO; PR:Q9BV79; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9BV79; protein.
DR Bgee; ENSG00000116353; Expressed in apex of heart and 175 other tissues.
DR ExpressionAtlas; Q9BV79; baseline and differential.
DR Genevisible; Q9BV79; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0019166; F:trans-2-enoyl-CoA reductase (NADPH) activity; IDA:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006631; P:fatty acid metabolic process; IDA:UniProtKB.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR013154; ADH_N.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Disease variant; Dystonia; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; Mitochondrion; NADP; Nucleus;
KW Oxidoreductase; Reference proteome; Transit peptide.
FT TRANSIT 1..53
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 54..373
FT /note="Enoyl-[acyl-carrier-protein] reductase,
FT mitochondrial"
FT /id="PRO_0000000888"
FT ACT_SITE 94
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q8WZM3"
FT BINDING 167
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8WZM3"
FT BINDING 193..196
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8WZM3"
FT BINDING 216..218
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8WZM3"
FT BINDING 285..288
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8WZM3"
FT BINDING 310..312
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8WZM3"
FT BINDING 368
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8WZM3"
FT MOD_RES 61
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DCS3"
FT MOD_RES 61
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DCS3"
FT MOD_RES 252
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DCS3"
FT MOD_RES 252
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DCS3"
FT MOD_RES 267
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DCS3"
FT MOD_RES 267
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DCS3"
FT MOD_RES 316
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DCS3"
FT VAR_SEQ 1..76
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041131"
FT VARIANT 96
FT /note="F -> L (in dbSNP:rs1128400)"
FT /evidence="ECO:0000269|PubMed:10810093,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.3, ECO:0000269|Ref.5"
FT /id="VAR_027935"
FT VARIANT 227
FT /note="R -> K (in dbSNP:rs11544658)"
FT /id="VAR_055486"
FT VARIANT 232
FT /note="G -> E (in DYTOABG; probably decreased protein
FT abundance; dbSNP:rs762913101)"
FT /evidence="ECO:0000269|PubMed:27817865"
FT /id="VAR_077997"
FT VARIANT 258
FT /note="R -> L (in dbSNP:rs34835902)"
FT /id="VAR_055487"
FT VARIANT 258
FT /note="R -> W (in DYTOABG; dbSNP:rs145192716)"
FT /evidence="ECO:0000269|PubMed:27817865"
FT /id="VAR_077998"
FT VARIANT 285..373
FT /note="Missing (in DYTOABG; probably decreased protein
FT abundance)"
FT /evidence="ECO:0000269|PubMed:27817865"
FT /id="VAR_077999"
FT VARIANT 285
FT /note="Y -> C (in DYTOABG; dbSNP:rs759218713)"
FT /evidence="ECO:0000269|PubMed:27817865"
FT /id="VAR_078000"
FT MUTAGEN 85
FT /note="S->A: Reduces catalytic activity by 68%."
FT /evidence="ECO:0000269|PubMed:18479707"
FT MUTAGEN 94
FT /note="Y->F: Reduces catalytic activity by 95%. Strongly
FT reduces affinity for trans-oct-2-enoyl-CoA."
FT /evidence="ECO:0000269|PubMed:18479707"
FT MUTAGEN 129
FT /note="I->M: Strongly increases activity with trans-oct-2-
FT enoyl-CoA. No effect on activity with trans-tetradec-2-
FT enoyl-CoA. Decreases activity with trans-hexadec-2-enoyl-
FT CoA by 20%."
FT /evidence="ECO:0000269|PubMed:18479707"
FT MUTAGEN 165
FT /note="G->S: Strongly increases activity with trans-oct-2-
FT enoyl-CoA. Decreases activity with trans-tetradec-2-enoyl-
FT CoA by 73%. Decreases activity with trans-hexadec-2-enoyl-
FT CoA by 80%."
FT /evidence="ECO:0000269|PubMed:18479707"
FT MUTAGEN 170
FT /note="T->A: Reduces catalytic activity by 69%."
FT /evidence="ECO:0000269|PubMed:18479707"
FT MUTAGEN 311
FT /note="W->A: Reduces catalytic activity by 98%. Strongly
FT reduces affinity for trans-oct-2-enoyl-CoA."
FT /evidence="ECO:0000269|PubMed:18479707"
FT MUTAGEN 311
FT /note="W->L: Reduces catalytic activity by 87%. Strongly
FT reduces affinity for trans-oct-2-enoyl-CoA."
FT /evidence="ECO:0000269|PubMed:18479707"
FT MUTAGEN 324
FT /note="F->Y: Strongly increases activity with trans-oct-2-
FT enoyl-CoA. Decreases activity with trans-tetradec-2-enoyl-
FT CoA by 25%. Decreases activity with trans-hexadec-2-enoyl-
FT CoA by 68%."
FT /evidence="ECO:0000269|PubMed:18479707"
FT CONFLICT 45..46
FT /note="AL -> GV (in Ref. 1; AAD34058)"
FT /evidence="ECO:0000305"
FT CONFLICT 373
FT /note="M -> I (in Ref. 2; CAG32984)"
FT /evidence="ECO:0000305"
FT STRAND 43..52
FT /evidence="ECO:0007829|PDB:1ZSY"
FT HELIX 54..57
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 58..63
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 72..81
FT /evidence="ECO:0007829|PDB:1ZSY"
FT HELIX 84..91
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 100..103
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 109..115
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 138..145
FT /evidence="ECO:0007829|PDB:1ZSY"
FT HELIX 146..148
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 149..152
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:1ZSY"
FT HELIX 158..163
FT /evidence="ECO:0007829|PDB:1ZSY"
FT HELIX 167..177
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 186..191
FT /evidence="ECO:0007829|PDB:1ZSY"
FT HELIX 195..207
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 210..215
FT /evidence="ECO:0007829|PDB:1ZSY"
FT HELIX 221..230
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 234..238
FT /evidence="ECO:0007829|PDB:1ZSY"
FT HELIX 239..243
FT /evidence="ECO:0007829|PDB:1ZSY"
FT HELIX 245..249
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 258..264
FT /evidence="ECO:0007829|PDB:1ZSY"
FT HELIX 266..273
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 281..284
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 293..295
FT /evidence="ECO:0007829|PDB:2VCY"
FT HELIX 297..302
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 306..309
FT /evidence="ECO:0007829|PDB:1ZSY"
FT HELIX 312..318
FT /evidence="ECO:0007829|PDB:1ZSY"
FT HELIX 321..336
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 345..349
FT /evidence="ECO:0007829|PDB:1ZSY"
FT HELIX 350..352
FT /evidence="ECO:0007829|PDB:1ZSY"
FT HELIX 353..360
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 362..364
FT /evidence="ECO:0007829|PDB:1ZSY"
FT STRAND 366..372
FT /evidence="ECO:0007829|PDB:1ZSY"
SQ SEQUENCE 373 AA; 40462 MW; DB13F6B0ED54A823 CRC64;
MWVCSTLWRV RTPARQWRGL LPASGCHGPA ASSYSASAEP ARVRALVYGH HGDPAKVVEL
KNLELAAVRG SDVRVKMLAA PINPSDINMI QGNYGFLPEL PAVGGNEGVA QVVAVGSNVT
GLKPGDWVIP ANAGLGTWRT EAVFSEEALI QVPSDIPLQS AATLGVNPCT AYRMLMDFEQ
LQPGDSVIQN ASNSGVGQAV IQIAAALGLR TINVVRDRPD IQKLSDRLKS LGAEHVITEE
ELRRPEMKNF FKDMPQPRLA LNCVGGKSST ELLRQLARGG TMVTYGGMAK QPVVASVSLL
IFKDLKLRGF WLSQWKKDHS PDQFKELILT LCDLIRRGQL TAPACSQVPL QDYQSALEAS
MKPFISSKQI LTM
