DCMC_RAT
ID DCMC_RAT Reviewed; 492 AA.
AC Q920F5; Q9WUY2;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Malonyl-CoA decarboxylase, mitochondrial {ECO:0000305};
DE Short=MCD;
DE EC=4.1.1.9 {ECO:0000269|PubMed:10229677, ECO:0000269|PubMed:12297032, ECO:0000269|PubMed:16298369};
DE Flags: Precursor;
GN Name=Mlycd {ECO:0000312|RGD:620234};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MITOCHONDRIAL), CATALYTIC ACTIVITY, AND
RP TISSUE SPECIFICITY.
RX PubMed=10229677; DOI=10.1042/bj3400213;
RA Voilley N., Roduit R., Vicaretti R., Bonny C., Waeber G., Dyck J.R.,
RA Lopaschuk G.D., Prentki M.;
RT "Cloning and expression of rat pancreatic beta-cell malonyl-CoA
RT decarboxylase.";
RL Biochem. J. 340:213-217(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MITOCHONDRIAL), PARTIAL PROTEIN
RP SEQUENCE, FUNCTION, PROTEOLYTIC PROCESSING, AND TISSUE SPECIFICITY.
RX PubMed=10947976; DOI=10.1042/bj3500599;
RA Dyck J.R., Berthiaume L.G., Thomas P.D., Kantor P.F., Barr A.J., Barr R.,
RA Singh D., Hopkins T.A., Voilley N., Prentki M., Lopaschuk G.D.;
RT "Characterization of rat liver malonyl-CoA decarboxylase and the study of
RT its role in regulating fatty acid metabolism.";
RL Biochem. J. 350:599-608(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MITOCHONDRIAL), CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=12297032; DOI=10.5483/bmbrep.2002.35.2.213;
RA Lee G.Y., Bahk Y.Y., Kim Y.S.;
RT "Rat malonyl-CoA decarboxylase; cloning, expression in E. coli and its
RT biochemical characterization.";
RL J. Biochem. Mol. Biol. 35:213-219(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MITOCHONDRIAL).
RC TISSUE=Prostate;
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 [5]
RP SUBCELLULAR LOCATION (ISOFORM CYTOPLASMIC+PEROXISOMAL), AND TISSUE
RP SPECIFICITY.
RX PubMed=10455107; DOI=10.1074/jbc.274.35.24461;
RA Sacksteder K.A., Morrell J.C., Wanders R.J.A., Matalon R., Gould S.J.;
RT "MCD encodes peroxisomal and cytoplasmic forms of malonyl-CoA decarboxylase
RT and is mutated in malonyl-CoA decarboxylase deficiency.";
RL J. Biol. Chem. 274:24461-24468(1999).
RN [6]
RP FUNCTION.
RX PubMed=15105298; DOI=10.1161/01.res.0000129255.19569.8f;
RA Dyck J.R., Cheng J.F., Stanley W.C., Barr R., Chandler M.P., Brown S.,
RA Wallace D., Arrhenius T., Harmon C., Yang G., Nadzan A.M., Lopaschuk G.D.;
RT "Malonyl coenzyme a decarboxylase inhibition protects the ischemic heart by
RT inhibiting fatty acid oxidation and stimulating glucose oxidation.";
RL Circ. Res. 94:E78-E84(2004).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=16298369; DOI=10.1016/j.febslet.2005.10.050;
RA Joly E., Bendayan M., Roduit R., Saha A.K., Ruderman N.B., Prentki M.;
RT "Malonyl-CoA decarboxylase is present in the cytosolic, mitochondrial and
RT peroxisomal compartments of rat hepatocytes.";
RL FEBS Lett. 579:6581-6586(2005).
RN [8]
RP ACETYLATION AT LYS-58; LYS-167; LYS-210; LYS-316; LYS-388 AND LYS-441, AND
RP MUTAGENESIS OF LYS-210; LYS-308 AND LYS-388.
RX PubMed=16739991; DOI=10.1021/pr050487g;
RA Nam H.W., Lee G.Y., Kim Y.S.;
RT "Mass spectrometric identification of K210 essential for rat malonyl-CoA
RT decarboxylase catalysis.";
RL J. Proteome Res. 5:1398-1406(2006).
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. May play a role
CC in controlling the extent of ischemic injury by promoting glucose
CC oxidation. {ECO:0000269|PubMed:10947976, ECO:0000269|PubMed:15105298,
CC ECO:0000269|PubMed:16298369}.
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; Evidence={ECO:0000269|PubMed:10229677,
CC ECO:0000269|PubMed:12297032, ECO:0000269|PubMed:16298369};
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.36 mM for malonyl-CoA {ECO:0000269|PubMed:12297032};
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:0000269|PubMed:16298369}.
CC Mitochondrion matrix {ECO:0000269|PubMed:16298369}. Peroxisome
CC {ECO:0000250}. Peroxisome matrix {ECO:0000269|PubMed:16298369}.
CC Note=Enzymatically active in all three subcellular compartments.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Comment=According to PubMed:10229677, a single transcription start
CC site has been demonstrated.;
CC Name=Mitochondrial;
CC IsoId=Q920F5-1; Sequence=Displayed;
CC Name=Cytoplasmic+peroxisomal;
CC IsoId=Q920F5-2; Sequence=VSP_018818;
CC -!- TISSUE SPECIFICITY: Expressed in liver, heart, skeletal muscles and
CC adipose tissues (at protein level). Ubiquitous. Strongly expressed in
CC liver, kidney, heart, skeletal muscle and adipose tissues. Weakly
CC expressed in brain. {ECO:0000269|PubMed:10229677,
CC ECO:0000269|PubMed:10455107, ECO:0000269|PubMed:10947976,
CC ECO:0000269|PubMed:12297032}.
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 (By similarity). {ECO:0000250|UniProtKB:Q99J39}.
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 -!- 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 (PubMed:10947976). {ECO:0000305|PubMed:10947976}.
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DR EMBL; AJ007704; CAB46681.1; -; mRNA.
DR EMBL; AF304865; AAL09352.1; -; mRNA.
DR EMBL; BC061845; AAH61845.1; -; mRNA.
DR RefSeq; NP_445929.1; NM_053477.1. [Q920F5-1]
DR AlphaFoldDB; Q920F5; -.
DR SMR; Q920F5; -.
DR IntAct; Q920F5; 1.
DR STRING; 10116.ENSRNOP00000019923; -.
DR iPTMnet; Q920F5; -.
DR PhosphoSitePlus; Q920F5; -.
DR jPOST; Q920F5; -.
DR PaxDb; Q920F5; -.
DR PRIDE; Q920F5; -.
DR ABCD; Q920F5; 4 sequenced antibodies.
DR Ensembl; ENSRNOT00000019923; ENSRNOP00000019923; ENSRNOG00000014522. [Q920F5-1]
DR GeneID; 85239; -.
DR KEGG; rno:85239; -.
DR UCSC; RGD:620234; rat. [Q920F5-1]
DR CTD; 23417; -.
DR RGD; 620234; Mlycd.
DR eggNOG; KOG3018; Eukaryota.
DR GeneTree; ENSGT00390000005410; -.
DR HOGENOM; CLU_023433_0_0_1; -.
DR InParanoid; Q920F5; -.
DR OMA; PIDWSTP; -.
DR OrthoDB; 1436590at2759; -.
DR PhylomeDB; Q920F5; -.
DR TreeFam; TF312959; -.
DR BRENDA; 4.1.1.9; 5301.
DR Reactome; R-RNO-390247; Beta-oxidation of very long chain fatty acids.
DR Reactome; R-RNO-9033241; Peroxisomal protein import.
DR SABIO-RK; Q920F5; -.
DR UniPathway; UPA00340; UER00710.
DR PRO; PR:Q920F5; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000014522; Expressed in heart and 20 other tissues.
DR Genevisible; Q920F5; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005782; C:peroxisomal matrix; IDA:UniProtKB.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0050080; F:malonyl-CoA decarboxylase activity; IDA:RGD.
DR GO; GO:0006085; P:acetyl-CoA biosynthetic process; IDA:RGD.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0019395; P:fatty acid oxidation; IDA:RGD.
DR GO; GO:2001294; P:malonyl-CoA catabolic process; ISS:UniProtKB.
DR GO; GO:0046321; P:positive regulation of fatty acid oxidation; ISS:UniProtKB.
DR GO; GO:0031998; P:regulation of fatty acid beta-oxidation; IDA:RGD.
DR GO; GO:0046320; P:regulation of fatty acid oxidation; IMP:RGD.
DR GO; GO:0010906; P:regulation of glucose metabolic process; IMP:UniProtKB.
DR GO; GO:0002931; P:response to ischemia; IMP: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 Direct protein sequencing; Disulfide bond; Fatty acid biosynthesis;
KW Fatty acid metabolism; Lipid biosynthesis; Lipid metabolism; Lyase;
KW Mitochondrion; Peroxisome; 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_0000021092"
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 MOD_RES 58
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:16739991"
FT MOD_RES 167
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99J39"
FT MOD_RES 167
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99J39"
FT MOD_RES 210
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:16739991"
FT MOD_RES 221
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99J39"
FT MOD_RES 316
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:16739991"
FT MOD_RES 385
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99J39"
FT MOD_RES 385
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99J39"
FT MOD_RES 388
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:16739991"
FT MOD_RES 441
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:16739991"
FT MOD_RES 471
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99J39"
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_018818"
FT MUTAGEN 210
FT /note="K->M: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:16739991"
FT MUTAGEN 308
FT /note="K->M: 40% reduction in catalytic activity."
FT /evidence="ECO:0000269|PubMed:16739991"
FT MUTAGEN 388
FT /note="K->M: 40% reduction in catalytic activity."
FT /evidence="ECO:0000269|PubMed:16739991"
FT CONFLICT 213
FT /note="E -> D (in Ref. 1; CAB46681)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="H -> Q (in Ref. 1; CAB46681)"
FT /evidence="ECO:0000305"
FT CONFLICT 301
FT /note="E -> G (in Ref. 1; CAB46681)"
FT /evidence="ECO:0000305"
FT CONFLICT 412
FT /note="Missing (in Ref. 1; CAB46681)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 492 AA; 54762 MW; D1FB65533B5A582E CRC64;
MRGLGPSLRA RRLLPLRYPP RPPGPRGPRL CSGLTASAMD ELLRRAVPPT PAYELREKTP
APAEGQCADF VSFYGGLAEA AQRAELLGRL AQGFGVDHGQ VAEQSAGVLQ LRQQSREAAV
LLQAEDRLRY ALVPRYRGLF HHISKLDGGV RFLVQLRADL LEAQALKLVE GPHVREMNGV
LKSMLSEWFS SGFLNLERVT WHSPCEVLQK ISECEAVHPV KNWMDMKRRV GPYRRCYFFS
HCSTPGDPLV VLHVALTGDI SNNIQSIVKE CPPSETEEKN RIAAAVFYSI SLTQQGLQGV
ELGTFLIKRV VKELQKEFPH LGAFSSLSPI PGFTKWLLGL LNVQGKEYGR NELFTDSECK
EIAEVTGDPV HESLKGLLSS GEWAKSEKLA QALQGPLMRL CAWYLYGEKH RGYALNPVAN
FHLQNGAVMW RINWMADSSL KGLTSSCGLM VNYRYYLEET GPNSISYLGS KNIKASEQIL
SLVAQFQSNS KL
