DCMC_MOUSE
ID DCMC_MOUSE Reviewed; 492 AA.
AC Q99J39; Q7TNL6;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Malonyl-CoA decarboxylase, mitochondrial {ECO:0000305};
DE Short=MCD;
DE EC=4.1.1.9 {ECO:0000269|PubMed:17030679};
DE Flags: Precursor;
GN Name=Mlycd {ECO:0000312|MGI:MGI:1928485};
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=Cerebellum;
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=129, C57BL/6J, and 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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-175.
RC STRAIN=129S6/SvEvTac;
RA Kim N.H., Lee G.Y., Kim Y.S.;
RT "Mouse malonyl-CoA decarboxylase: genome structure, cDNA cloning,
RT expression and promoter study.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=17030679; DOI=10.1161/circulationaha.106.642009;
RA Dyck J.R., Hopkins T.A., Bonnet S., Michelakis E.D., Young M.E.,
RA Watanabe M., Kawase Y., Jishage K., Lopaschuk G.D.;
RT "Absence of malonyl coenzyme A decarboxylase in mice increases cardiac
RT glucose oxidation and protects the heart from ischemic injury.";
RL Circulation 114:1721-1728(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen,
RC 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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, ACETYLATION AT LYS-58; LYS-167; LYS-210;
RP LYS-316; LYS-388; LYS-441 AND LYS-471, AND MUTAGENESIS OF LYS-471.
RX PubMed=23746352; DOI=10.1016/j.molcel.2013.05.012;
RA Laurent G., German N.J., Saha A.K., de Boer V.C., Davies M., Koves T.R.,
RA Dephoure N., Fischer F., Boanca G., Vaitheesvaran B., Lovitch S.B.,
RA Sharpe A.H., Kurland I.J., Steegborn C., Gygi S.P., Muoio D.M.,
RA Ruderman N.B., Haigis M.C.;
RT "SIRT4 coordinates the balance between lipid synthesis and catabolism by
RT repressing malonyl CoA decarboxylase.";
RL Mol. Cell 50:686-698(2013).
RN [7]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-167; LYS-221 AND LYS-385, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-385, AND IDENTIFICATION BY MASS
RP 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).
CC -!- FUNCTION: Catalyzes the conversion of malonyl-CoA to acetyl-CoA. In the
CC fatty acid biosynthesis MCD selectively removes malonyl-CoA and thus
CC assures that methyl-malonyl-CoA is the only chain elongating substrate
CC for fatty acid synthase and that fatty acids with multiple methyl side
CC chains are produced. In peroxisomes it may be involved in degrading
CC intraperoxisomal malonyl-CoA, which is generated by the peroxisomal
CC beta-oxidation of odd chain-length dicarboxylic fatty acids. Plays a
CC role in the metabolic balance between glucose and lipid oxidation in
CC muscle independent of alterations in insulin signaling. Plays a role in
CC controlling the extent of ischemic injury by promoting glucose
CC oxidation. {ECO:0000269|PubMed:17030679, ECO:0000269|PubMed:23746352}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + malonyl-CoA = acetyl-CoA + CO2; Xref=Rhea:RHEA:18781,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:57384; EC=4.1.1.9;
CC Evidence={ECO:0000269|PubMed:17030679};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18782;
CC Evidence={ECO:0000305};
CC -!- ACTIVITY REGULATION: Malonyl-CoA decarboxylase activity does not
CC require any cofactors or divalent metal ions.
CC {ECO:0000250|UniProtKB:O95822}.
CC -!- PATHWAY: Metabolic intermediate biosynthesis; acetyl-CoA biosynthesis;
CC acetyl-CoA from malonyl-CoA: step 1/1.
CC -!- SUBUNIT: Homotetramer. Dimer of dimers. The two subunits within a dimer
CC display conformational differences suggesting that at any given moment,
CC only one of the two subunits is competent for malonyl-CoA binding and
CC catalytic activity. Under oxidizing conditions, can form disulfide-
CC linked homotetramers (in vitro). Associates with the peroxisomal
CC targeting signal receptor PEX5 (By similarity).
CC {ECO:0000250|UniProtKB:O95822}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O95822}.
CC Mitochondrion matrix {ECO:0000269|PubMed:23746352}. Peroxisome
CC {ECO:0000250|UniProtKB:O95822}. Peroxisome matrix
CC {ECO:0000250|UniProtKB:Q920F5}. Note=Enzymatically active in all three
CC subcellular compartments. {ECO:0000250|UniProtKB:Q920F5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Comment=A single transcription start site has been demonstrated in
CC Rat.;
CC Name=Mitochondrial;
CC IsoId=Q99J39-1; Sequence=Displayed;
CC Name=Cytoplasmic+peroxisomal;
CC IsoId=Q99J39-2; Sequence=VSP_018817;
CC -!- PTM: Interchain disulfide bonds may form in peroxisomes (Potential).
CC Interchain disulfide bonds are not expected to form in the reducing
CC environment of the cytoplasm and mitochondria. {ECO:0000305}.
CC -!- PTM: Acetylation at Lys-471 activates malonyl-CoA decarboxylase
CC activity. Deacetylation at Lys-471 by SIRT4 represses activity, leading
CC to promote lipogenesis. {ECO:0000269|PubMed:23746352}.
CC -!- DISRUPTION PHENOTYPE: Mice show an increased expression of genes
CC regulating fatty acid utilization and likely contributes to the absence
CC of changes in energy metabolism in the aerobic heart. Display a
CC preference for glucose utilization after ischemia and improve
CC functional recovery of the heart. {ECO:0000269|PubMed:17030679}.
CC -!- MISCELLANEOUS: [Isoform Cytoplasmic+peroxisomal]: May be produced by
CC alternative initiation at Met-39 of isoform mitochondrial.
CC Alternatively, represents a proteolytic processed form of the
CC mitochondrial form. {ECO:0000305}.
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DR EMBL; AK082479; BAC38505.1; -; mRNA.
DR EMBL; BC004764; AAH04764.1; -; mRNA.
DR EMBL; AY331094; AAP93335.2; -; Genomic_DNA.
DR CCDS; CCDS22703.1; -. [Q99J39-1]
DR RefSeq; NP_064350.2; NM_019966.2. [Q99J39-1]
DR AlphaFoldDB; Q99J39; -.
DR SMR; Q99J39; -.
DR IntAct; Q99J39; 1.
DR STRING; 10090.ENSMUSP00000095970; -.
DR BindingDB; Q99J39; -.
DR ChEMBL; CHEMBL1255162; -.
DR iPTMnet; Q99J39; -.
DR PhosphoSitePlus; Q99J39; -.
DR SwissPalm; Q99J39; -.
DR EPD; Q99J39; -.
DR jPOST; Q99J39; -.
DR MaxQB; Q99J39; -.
DR PaxDb; Q99J39; -.
DR PeptideAtlas; Q99J39; -.
DR PRIDE; Q99J39; -.
DR ProteomicsDB; 279501; -. [Q99J39-1]
DR ProteomicsDB; 279502; -. [Q99J39-2]
DR Antibodypedia; 30519; 109 antibodies from 21 providers.
DR DNASU; 56690; -.
DR Ensembl; ENSMUST00000098367; ENSMUSP00000095970; ENSMUSG00000074064. [Q99J39-1]
DR GeneID; 56690; -.
DR KEGG; mmu:56690; -.
DR UCSC; uc009npn.1; mouse. [Q99J39-1]
DR CTD; 23417; -.
DR MGI; MGI:1928485; Mlycd.
DR VEuPathDB; HostDB:ENSMUSG00000074064; -.
DR eggNOG; KOG3018; Eukaryota.
DR GeneTree; ENSGT00390000005410; -.
DR HOGENOM; CLU_023433_0_0_1; -.
DR InParanoid; Q99J39; -.
DR OMA; PIDWSTP; -.
DR OrthoDB; 1436590at2759; -.
DR PhylomeDB; Q99J39; -.
DR TreeFam; TF312959; -.
DR BRENDA; 4.1.1.9; 3474.
DR Reactome; R-MMU-390247; Beta-oxidation of very long chain fatty acids.
DR Reactome; R-MMU-9033241; Peroxisomal protein import.
DR UniPathway; UPA00340; UER00710.
DR BioGRID-ORCS; 56690; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Mlycd; mouse.
DR PRO; PR:Q99J39; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q99J39; protein.
DR Bgee; ENSMUSG00000074064; Expressed in hindlimb stylopod muscle and 208 other tissues.
DR Genevisible; Q99J39; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005782; C:peroxisomal matrix; ISS:UniProtKB.
DR GO; GO:0005777; C:peroxisome; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0050080; F:malonyl-CoA decarboxylase activity; IDA:UniProtKB.
DR GO; GO:0006085; P:acetyl-CoA biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0019395; P:fatty acid oxidation; ISO:MGI.
DR GO; GO:2001294; P:malonyl-CoA catabolic process; IDA:UniProtKB.
DR GO; GO:0046321; P:positive regulation of fatty acid oxidation; IDA:UniProtKB.
DR GO; GO:0031998; P:regulation of fatty acid beta-oxidation; ISO:MGI.
DR GO; GO:0046320; P:regulation of fatty acid oxidation; ISO:MGI.
DR GO; GO:0010906; P:regulation of glucose metabolic process; ISS:UniProtKB.
DR GO; GO:0002931; P:response to ischemia; ISS:UniProtKB.
DR Gene3D; 1.20.140.90; -; 1.
DR Gene3D; 3.40.630.150; -; 1.
DR InterPro; IPR038917; Malonyl_CoA_deC.
DR InterPro; IPR007956; Malonyl_CoA_deC_C.
DR InterPro; IPR042303; Malonyl_CoA_deC_C_sf.
DR InterPro; IPR035372; MCD_N.
DR InterPro; IPR038351; MCD_N_sf.
DR PANTHER; PTHR28641; PTHR28641; 1.
DR Pfam; PF05292; MCD; 1.
DR Pfam; PF17408; MCD_N; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative initiation; Cytoplasm; Decarboxylase;
KW Disulfide bond; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; Lyase; Mitochondrion; Peroxisome;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..38
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 39..492
FT /note="Malonyl-CoA decarboxylase, mitochondrial"
FT /id="PRO_0000021090"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 39..189
FT /note="Alpha-helical domain"
FT /evidence="ECO:0000250"
FT REGION 190..492
FT /note="Catalytic domain"
FT /evidence="ECO:0000250"
FT MOTIF 490..492
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 328
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 422
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 298..304
FT /ligand="malonyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57384"
FT /evidence="ECO:0000250"
FT BINDING 328
FT /ligand="malonyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57384"
FT /evidence="ECO:0000250"
FT BINDING 422
FT /ligand="malonyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57384"
FT /evidence="ECO:0000250"
FT SITE 210
FT /note="Essential for catalytic activity"
FT /evidence="ECO:0000250"
FT MOD_RES 58
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23746352"
FT MOD_RES 167
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:23746352"
FT MOD_RES 167
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 210
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23746352"
FT MOD_RES 221
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 316
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23746352"
FT MOD_RES 385
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 385
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 388
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23746352"
FT MOD_RES 441
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23746352"
FT MOD_RES 471
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23746352"
FT DISULFID 205
FT /note="Interchain"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..38
FT /note="Missing (in isoform Cytoplasmic+peroxisomal)"
FT /evidence="ECO:0000305"
FT /id="VSP_018817"
FT MUTAGEN 471
FT /note="K->Q: Mimicks constitutive acetylation, leading to
FT increased malonyl-CoA decarboxylase activity."
FT /evidence="ECO:0000269|PubMed:23746352"
FT MUTAGEN 471
FT /note="K->R: Decreased acetylation, leading to reduced
FT malonyl-CoA decarboxylase activity."
FT /evidence="ECO:0000269|PubMed:23746352"
SQ SEQUENCE 492 AA; 54736 MW; CEBDA62714A21DC1 CRC64;
MRGLGPGLRA RRLLPLRSPP RPPGPRGRRL CGGLAASAMD ELLRRAVPPT PAYELREKTP
APAEGQCADF VSFYGGLAEA SQRAELLGRL AQGFGVDHGQ VAEQSAGVLQ LRQQAREAAV
LLQAEDRLRY ALVPRYRGLF HHISKLDGGV RFLVQLRADL LEAQALKLVE GPHVREMNGV
LKSMLSEWFS SGFLNLERVT WHSPCEVLQK ISECEAVHPV KNWMDMKRRV GPYRRCYFFS
HCSTPGEPLV VLHVALTGDI SNNIQGIVKE CPPTETEERN RIAAAIFYSI SLTQQGLQGV
ELGTFLIKRV VKELQKEFPQ LGAFSSLSPI PGFTKWLLGL LNVQGKEHGR NELFTDSECQ
EISAVTGNPV HESLKGFLSS GEWVKSEKLT QALQGPLMRL CAWYLYGEKH RGYALNPVAN
FHLQNGAVMW RINWMADSSL KGLTSSCGLM VNYRYYLEET GPNSISYLGS KNIKASEQIL
SLVAQFQNNS KL
