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Q920F5 (DCMC_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 82. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Malonyl-CoA decarboxylase, mitochondrial

Short name=MCD
EC=4.1.1.9
Gene names
Name:Mlycd
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length492 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the conversion of malonyl-CoA to acetyl-CoA. In the fatty acid biosynthesis MCD selectively removes malonyl-CoA and thus assures that methyl-malonyl-CoA is the only chain elongating substrate for fatty acid synthase and that fatty acids with multiple methyl side chains are produced. In peroxisomes it may be involved in degrading intraperoxisomal malonyl-CoA, which is generated by the peroxisomal beta-oxidation of odd chain-length dicarboxylic fatty acids. Plays a role in the metabolic balance between glucose and lipid oxidation in muscle independent of alterations in insulin signaling. May play a role in controlling the extent of ischemic injury by promoting glucose oxidation. Ref.2 Ref.6 Ref.7

Catalytic activity

Malonyl-CoA = acetyl-CoA + CO2. Ref.1 Ref.3 Ref.7

Enzyme regulation

Malonyl-CoA decarboxylase activity does not require any cofactors or divalent metal ions By similarity.

Pathway

Metabolic intermediate biosynthesis; acetyl-CoA biosynthesis; acetyl-CoA from malonyl-CoA: step 1/1.

Subunit structure

Homotetramer. Dimer of dimers. The two subunits within a dimer display conformational differences suggesting that at any given moment, only one of the two subunits is competent for malonyl-CoA binding and catalytic activity. Under oxidizing conditions, can form disulfide-linked homotetramers (in vitro). Associates with the peroxisomal targeting signal receptor PEX5 By similarity.

Subcellular location

Cytoplasm. Mitochondrion matrix. Peroxisome By similarity. Peroxisome matrix. Note: Enzymatically active in all three subcellular compartments. Ref.5 Ref.7

Tissue specificity

Expressed in liver, heart, skeletal muscles and adipose tissues (at protein level). Ubiquitous. Strongly expressed in liver, kidney, heart, skeletal muscle and adipose tissues. Weakly expressed in brain. Ref.1 Ref.2 Ref.3 Ref.5

Post-translational modification

Acetylation at Lys-471 activates malonyl-CoA decarboxylase activity. Deacetylation at Lys-471 by SIRT4 represses activity, leading to promote lipogenesis By similarity.

Interchain disulfide bonds may form in peroxisomes Potential. Interchain disulfide bonds are not expected to form in the reducing environment of the cytoplasm and mitochondria.

Biophysicochemical properties

Kinetic parameters:

KM=0.36 mM for malonyl-CoA Ref.3

Ontologies

Keywords
   Biological processFatty acid biosynthesis
Fatty acid metabolism
Lipid biosynthesis
Lipid metabolism
   Cellular componentCytoplasm
Mitochondrion
Peroxisome
   Coding sequence diversityAlternative initiation
   DomainTransit peptide
   Molecular functionDecarboxylase
Lyase
   PTMAcetylation
Disulfide bond
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processacetyl-CoA biosynthetic process

Inferred from direct assay PubMed 17316539. Source: RGD

fatty acid biosynthetic process

Inferred from mutant phenotype Ref.6. Source: UniProtKB

fatty acid oxidation

Inferred from direct assay PubMed 17316539. Source: RGD

malonyl-CoA catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of fatty acid oxidation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of fatty acid beta-oxidation

Inferred from direct assay PubMed 10516138. Source: RGD

regulation of fatty acid oxidation

Inferred from mutant phenotype Ref.6. Source: RGD

regulation of glucose metabolic process

Inferred from mutant phenotype Ref.6. Source: UniProtKB

response to ischemia

Inferred from mutant phenotype Ref.6. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay Ref.5Ref.7. Source: UniProtKB

cytosol

Inferred from direct assay Ref.7. Source: RGD

mitochondrial matrix

Inferred from direct assay Ref.7. Source: UniProtKB

mitochondrion

Inferred from direct assay Ref.7. Source: RGD

peroxisomal matrix

Inferred from direct assay Ref.7. Source: UniProtKB

peroxisome

Inferred from direct assay Ref.5. Source: UniProtKB

   Molecular_functionmalonyl-CoA decarboxylase activity

Inferred from direct assay PubMed 12065578Ref.7PubMed 17316539. Source: RGD

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]

Note: According to PubMed:10229677, a single transcription start site has been demonstrated.
Isoform Mitochondrial (identifier: Q920F5-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Cytoplasmic+peroxisomal (identifier: Q920F5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: Missing.
Note: May be produced by alternative initiation at Met-39 of isoform mitochondrial. Alternatively, represents a proteolytic processed form of the mitochondrial form (PubMed:10947976).

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – ?Mitochondrion Potential
Chain? – 492Malonyl-CoA decarboxylase, mitochondrialPRO_0000021092

Regions

Region298 – 3047Malonyl-CoA binding By similarity
Motif490 – 4923Microbody targeting signal Potential

Sites

Binding site3281Malonyl-CoA By similarity
Binding site4221Malonyl-CoA By similarity

Amino acid modifications

Modified residue581N6-acetyllysine By similarity
Modified residue1671N6-acetyllysine; alternate By similarity
Modified residue1671N6-succinyllysine; alternate By similarity
Modified residue2101N6-acetyllysine By similarity
Modified residue2211N6-succinyllysine By similarity
Modified residue3161N6-acetyllysine By similarity
Modified residue3851N6-acetyllysine; alternate By similarity
Modified residue3851N6-succinyllysine; alternate By similarity
Modified residue3881N6-acetyllysine By similarity
Modified residue4411N6-acetyllysine By similarity
Modified residue4711N6-acetyllysine By similarity
Disulfide bond205Interchain Potential

Natural variations

Alternative sequence1 – 3838Missing in isoform Cytoplasmic+peroxisomal.
VSP_018818

Experimental info

Sequence conflict2131E → D in CAB46681. Ref.1
Sequence conflict2181H → Q in CAB46681. Ref.1
Sequence conflict3011E → G in CAB46681. Ref.1
Sequence conflict4121Missing in CAB46681. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform Mitochondrial [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: D1FB65533B5A582E

FASTA49254,762
        10         20         30         40         50         60 
MRGLGPSLRA RRLLPLRYPP RPPGPRGPRL CSGLTASAMD ELLRRAVPPT PAYELREKTP 

        70         80         90        100        110        120 
APAEGQCADF VSFYGGLAEA AQRAELLGRL AQGFGVDHGQ VAEQSAGVLQ LRQQSREAAV 

       130        140        150        160        170        180 
LLQAEDRLRY ALVPRYRGLF HHISKLDGGV RFLVQLRADL LEAQALKLVE GPHVREMNGV 

       190        200        210        220        230        240 
LKSMLSEWFS SGFLNLERVT WHSPCEVLQK ISECEAVHPV KNWMDMKRRV GPYRRCYFFS 

       250        260        270        280        290        300 
HCSTPGDPLV VLHVALTGDI SNNIQSIVKE CPPSETEEKN RIAAAVFYSI SLTQQGLQGV 

       310        320        330        340        350        360 
ELGTFLIKRV VKELQKEFPH LGAFSSLSPI PGFTKWLLGL LNVQGKEYGR NELFTDSECK 

       370        380        390        400        410        420 
EIAEVTGDPV HESLKGLLSS GEWAKSEKLA QALQGPLMRL CAWYLYGEKH RGYALNPVAN 

       430        440        450        460        470        480 
FHLQNGAVMW RINWMADSSL KGLTSSCGLM VNYRYYLEET GPNSISYLGS KNIKASEQIL 

       490 
SLVAQFQSNS KL 

« Hide

Isoform Cytoplasmic+peroxisomal [UniParc].

Checksum: 92D3679A358E332B
Show »

FASTA45450,685

References

« Hide 'large scale' references
[1]"Cloning and expression of rat pancreatic beta-cell malonyl-CoA decarboxylase."
Voilley N., Roduit R., Vicaretti R., Bonny C., Waeber G., Dyck J.R., Lopaschuk G.D., Prentki M.
Biochem. J. 340:213-217(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MITOCHONDRIAL), CATALYTIC ACTIVITY, TISSUE SPECIFICITY.
[2]"Characterization of rat liver malonyl-CoA decarboxylase and the study of its role in regulating fatty acid metabolism."
Dyck J.R., Berthiaume L.G., Thomas P.D., Kantor P.F., Barr A.J., Barr R., Singh D., Hopkins T.A., Voilley N., Prentki M., Lopaschuk G.D.
Biochem. J. 350:599-608(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MITOCHONDRIAL), PARTIAL PROTEIN SEQUENCE, FUNCTION, PROTEOLYTIC PROCESSING, TISSUE SPECIFICITY.
[3]"Rat malonyl-CoA decarboxylase; cloning, expression in E. coli and its biochemical characterization."
Lee G.Y., Bahk Y.Y., Kim Y.S.
J. Biochem. Mol. Biol. 35:213-219(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MITOCHONDRIAL), CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
Strain: Sprague-Dawley.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MITOCHONDRIAL).
Tissue: Prostate.
[5]"MCD encodes peroxisomal and cytoplasmic forms of malonyl-CoA decarboxylase and is mutated in malonyl-CoA decarboxylase deficiency."
Sacksteder K.A., Morrell J.C., Wanders R.J.A., Matalon R., Gould S.J.
J. Biol. Chem. 274:24461-24468(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION (ISOFORM CYTOPLASMIC+PEROXISOMAL), TISSUE SPECIFICITY.
[6]"Malonyl coenzyme a decarboxylase inhibition protects the ischemic heart by inhibiting fatty acid oxidation and stimulating glucose oxidation."
Dyck J.R., Cheng J.F., Stanley W.C., Barr R., Chandler M.P., Brown S., Wallace D., Arrhenius T., Harmon C., Yang G., Nadzan A.M., Lopaschuk G.D.
Circ. Res. 94:E78-E84(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Malonyl-CoA decarboxylase is present in the cytosolic, mitochondrial and peroxisomal compartments of rat hepatocytes."
Joly E., Bendayan M., Roduit R., Saha A.K., Ruderman N.B., Prentki M.
FEBS Lett. 579:6581-6586(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ007704 mRNA. Translation: CAB46681.1.
AF304865 mRNA. Translation: AAL09352.1.
BC061845 mRNA. Translation: AAH61845.1.
RefSeqNP_445929.1. NM_053477.1.
UniGeneRn.13468.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000019923.

PTM databases

PhosphoSiteQ920F5.

Proteomic databases

PaxDbQ920F5.
PRIDEQ920F5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000019923; ENSRNOP00000019923; ENSRNOG00000014522. [Q920F5-1]
GeneID85239.
KEGGrno:85239.
UCSCRGD:620234. rat. [Q920F5-1]

Organism-specific databases

CTD23417.
RGD620234. Mlycd.

Phylogenomic databases

eggNOGCOG1593.
GeneTreeENSGT00390000005410.
HOGENOMHOG000141409.
HOVERGENHBG000825.
InParanoidQ920F5.
KOK01578.
OMALDEGREQ.
OrthoDBEOG76X5ZZ.
PhylomeDBQ920F5.
TreeFamTF312959.

Enzyme and pathway databases

SABIO-RKQ920F5.
UniPathwayUPA00340; UER00710.

Gene expression databases

GenevestigatorQ920F5.

Family and domain databases

InterProIPR007956. Malonyl_CoA_deC.
[Graphical view]
PfamPF05292. MCD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio617288.
PROQ920F5.

Entry information

Entry nameDCMC_RAT
AccessionPrimary (citable) accession number: Q920F5
Secondary accession number(s): Q9WUY2
Entry history
Integrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: December 1, 2001
Last modified: April 16, 2014
This is version 82 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

PATHWAY comments

Index of metabolic and biosynthesis pathways