MECR_MOUSE
ID MECR_MOUSE Reviewed; 373 AA.
AC Q9DCS3; Q99L39;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Enoyl-[acyl-carrier-protein] reductase, mitochondrial;
DE EC=1.3.1.104 {ECO:0000250|UniProtKB:Q9BV79};
DE AltName: Full=2-enoyl thioester reductase;
DE AltName: Full=Nuclear receptor-binding factor 1;
DE Short=NRBF-1;
DE Flags: Precursor;
GN Name=Mecr; Synonyms=Nrbf1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-267, SUCCINYLATION [LARGE SCALE
RP ANALYSIS] AT LYS-61; LYS-252; LYS-267 AND LYS-316, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast, and Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-61 AND LYS-252, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=28369354; DOI=10.1093/hmg/ddx105;
RA Nair R.R., Keraetaer J.M., Autio K.J., Masud A.J., Finnilae M.A.J.,
RA Autio-Harmainen H.I., Miinalainen I.J., Nieminen P.A., Hiltunen J.K.,
RA Kastaniotis A.J.;
RT "Genetic modifications of Mecr reveal a role for mitochondrial 2-enoyl-
RT CoA/ACP reductase in placental development in mice.";
RL Hum. Mol. Genet. 26:2104-2117(2017).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=30266742; DOI=10.1523/jneurosci.3514-17.2018;
RA Nair R.R., Koivisto H., Jokivarsi K., Miinalainen I.J., Autio K.J.,
RA Manninen A., Poutiainen P., Tanila H., Hiltunen J.K., Kastaniotis A.J.;
RT "Impaired Mitochondrial Fatty Acid Synthesis Leads to Neurodegeneration in
RT Mice.";
RL J. Neurosci. 38:9781-9800(2018).
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 (By similarity). May
CC provide the octanoyl chain used for lipoic acid biosynthesis,
CC regulating protein lipoylation and mitochondrial respiratory activity
CC particularly in Purkinje cells (PubMed:30266742).
CC {ECO:0000250|UniProtKB:Q9BV79, ECO:0000269|PubMed:30266742}.
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:0000250|UniProtKB:Q9BV79};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22566;
CC Evidence={ECO:0000250|UniProtKB:Q9BV79};
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:0000250|UniProtKB:Q9BV79};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41813;
CC Evidence={ECO:0000250|UniProtKB:Q9BV79};
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:0000250|UniProtKB:Q9BV79};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41833;
CC Evidence={ECO:0000250|UniProtKB:Q9BV79};
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:0000250|UniProtKB:Q9BV79};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41849;
CC Evidence={ECO:0000250|UniProtKB:Q9BV79};
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:0000250|UniProtKB:Q9BV79};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41865;
CC Evidence={ECO:0000250|UniProtKB:Q9BV79};
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:0000250|UniProtKB:Q9BV79};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41881;
CC Evidence={ECO:0000250|UniProtKB:Q9BV79};
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:0000250|UniProtKB:Q9BV79};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41897;
CC Evidence={ECO:0000250|UniProtKB:Q9BV79};
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:0000250|UniProtKB:Q9BV79};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41913;
CC Evidence={ECO:0000250|UniProtKB:Q9BV79};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q9BV79}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q9BV79}.
CC -!- TISSUE SPECIFICITY: Expressed in Purkinje cells (at protein level).
CC {ECO:0000269|PubMed:30266742}.
CC -!- DISRUPTION PHENOTYPE: Homozygous deficiency causes placental
CC insufficiency and embryonic lethality between 9.5 and 11.5 dpc.
CC {ECO:0000269|PubMed:28369354}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. Quinone oxidoreductase subfamily. {ECO:0000305}.
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DR EMBL; AK002533; BAB22169.1; -; mRNA.
DR EMBL; BC003864; AAH03864.1; -; mRNA.
DR CCDS; CCDS18715.1; -.
DR RefSeq; NP_079573.2; NM_025297.2.
DR AlphaFoldDB; Q9DCS3; -.
DR SMR; Q9DCS3; -.
DR BioGRID; 205066; 7.
DR STRING; 10090.ENSMUSP00000030742; -.
DR iPTMnet; Q9DCS3; -.
DR PhosphoSitePlus; Q9DCS3; -.
DR SwissPalm; Q9DCS3; -.
DR EPD; Q9DCS3; -.
DR jPOST; Q9DCS3; -.
DR MaxQB; Q9DCS3; -.
DR PaxDb; Q9DCS3; -.
DR PeptideAtlas; Q9DCS3; -.
DR PRIDE; Q9DCS3; -.
DR ProteomicsDB; 293449; -.
DR Antibodypedia; 16646; 179 antibodies from 26 providers.
DR DNASU; 26922; -.
DR Ensembl; ENSMUST00000030742; ENSMUSP00000030742; ENSMUSG00000028910.
DR GeneID; 26922; -.
DR KEGG; mmu:26922; -.
DR UCSC; uc008vae.2; mouse.
DR CTD; 51102; -.
DR MGI; MGI:1349441; Mecr.
DR VEuPathDB; HostDB:ENSMUSG00000028910; -.
DR eggNOG; KOG0025; Eukaryota.
DR GeneTree; ENSGT00940000156592; -.
DR HOGENOM; CLU_026673_17_1_1; -.
DR InParanoid; Q9DCS3; -.
DR OMA; HQLCRAW; -.
DR OrthoDB; 1269870at2759; -.
DR PhylomeDB; Q9DCS3; -.
DR TreeFam; TF312886; -.
DR Reactome; R-MMU-77346; Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA.
DR BioGRID-ORCS; 26922; 28 hits in 71 CRISPR screens.
DR ChiTaRS; Mecr; mouse.
DR PRO; PR:Q9DCS3; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q9DCS3; protein.
DR Bgee; ENSMUSG00000028910; Expressed in brown adipose tissue and 255 other tissues.
DR ExpressionAtlas; Q9DCS3; baseline and differential.
DR Genevisible; Q9DCS3; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0016922; F:nuclear receptor binding; ISO:MGI.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IEA:UniProt.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0019166; F:trans-2-enoyl-CoA reductase (NADPH) activity; ISO:MGI.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006631; P:fatty acid metabolic process; ISO:MGI.
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 Acetylation; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; Mitochondrion; NADP; Oxidoreductase;
KW 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_0000000889"
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:0007744|PubMed:23576753"
FT MOD_RES 61
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 252
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 252
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 267
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 267
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 316
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 69
FT /note="E -> K (in Ref. 1; BAB22169)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 373 AA; 40343 MW; EBA9A61A46386AEE CRC64;
MLVSQRVTGA RARAPQLAGL LEAWYRHGRT TSSYSALSEP SRVRALVYGN HGDPAKVVQL
KNLELTAVEG SDVHVRMLAA PINPSDINMI QGNYGLLPKL PAVGGNEGVG QVIAVGSSVS
ALKPGDWVIP ANAGLGTWRT EAVFSEEALI GIPKDIPLQS AATLGVNPCT AYRMLVDFEQ
LQPGDSVIQN ASNSGVGQAV IQIASALRLK TINVVRDRPD IKKLTDRLKD LGADYVLTEE
ELRMPETKTI FKDLPLPRLA LNCVGGKSST ELLRHLAPGG TMVTYGGMAK QPVTASVSLL
IFKDLKLRGF WLSQWKKNHS PDEFKELILT LCNLIRQGRL TAPSCSEVPL QGYQQALEAS
MKPFVSSKQI LTM
