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Q99J39 (DCMC_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 94. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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. Plays a role in controlling the extent of ischemic injury by promoting glucose oxidation. Ref.4 Ref.5

Catalytic activity

Malonyl-CoA = acetyl-CoA + CO2. Ref.4

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

Post-translational modification

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.

Acetylation at Lys-471 activates malonyl-CoA decarboxylase activity. Deacetylation at Lys-471 by SIRT4 represses activity, leading to promote lipogenesis. Ref.5

Disruption phenotype

Mice show an increased expression of genes regulating fatty acid utilization and likely contributes to the absence of changes in energy metabolism in the aerobic heart. Display a preference for glucose utilization after ischemia and improve functional recovery of the heart. Ref.4

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
Reference proteome
Gene Ontology (GO)
   Biological_processacetyl-CoA biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

fatty acid biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

fatty acid oxidation

Inferred from electronic annotation. Source: Ensembl

malonyl-CoA catabolic process

Inferred from direct assay Ref.5. Source: UniProtKB

positive regulation of fatty acid oxidation

Inferred from direct assay Ref.5. Source: UniProtKB

regulation of fatty acid beta-oxidation

Inferred from electronic annotation. Source: Ensembl

regulation of glucose metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

response to ischemia

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Inferred from electronic annotation. Source: Ensembl

mitochondrial matrix

Inferred from direct assay Ref.5. Source: UniProtKB

mitochondrion

Inferred from direct assay PubMed 14651853PubMed 18614015. Source: MGI

peroxisomal matrix

Inferred from sequence or structural similarity. Source: UniProtKB

peroxisome

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionmalonyl-CoA decarboxylase activity

Inferred from direct assay Ref.5. Source: UniProtKB

Complete GO annotation...

Alternative products

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

Note: A single transcription start site has been demonstrated in Rat.
Isoform Mitochondrial (identifier: Q99J39-1)

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: Q99J39-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – ?Mitochondrion Potential
Chain? – 492Malonyl-CoA decarboxylase, mitochondrialPRO_0000021090

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 Ref.5
Modified residue1671N6-acetyllysine; alternate Ref.5
Modified residue1671N6-succinyllysine; alternate Ref.6
Modified residue2101N6-acetyllysine Ref.5
Modified residue2211N6-succinyllysine Ref.6
Modified residue3161N6-acetyllysine Ref.5
Modified residue3851N6-acetyllysine; alternate Ref.7
Modified residue3851N6-succinyllysine; alternate Ref.6
Modified residue3881N6-acetyllysine Ref.5
Modified residue4411N6-acetyllysine Ref.5
Modified residue4711N6-acetyllysine Ref.5
Disulfide bond205Interchain Potential

Natural variations

Alternative sequence1 – 3838Missing in isoform Cytoplasmic+peroxisomal.
VSP_018817

Experimental info

Mutagenesis4711K → Q: Mimicks constitutive acetylation, leading to increased malonyl-CoA decarboxylase activity. Ref.5
Mutagenesis4711K → R: Decreased acetylation, leading to reduced malonyl-CoA decarboxylase activity. Ref.5

Sequences

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

Last modified June 1, 2001. Version 1.
Checksum: CEBDA62714A21DC1

FASTA49254,736
        10         20         30         40         50         60 
MRGLGPGLRA RRLLPLRSPP RPPGPRGRRL CGGLAASAMD ELLRRAVPPT PAYELREKTP 

        70         80         90        100        110        120 
APAEGQCADF VSFYGGLAEA SQRAELLGRL AQGFGVDHGQ VAEQSAGVLQ LRQQAREAAV 

       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 
HCSTPGEPLV VLHVALTGDI SNNIQGIVKE CPPTETEERN RIAAAIFYSI SLTQQGLQGV 

       310        320        330        340        350        360 
ELGTFLIKRV VKELQKEFPQ LGAFSSLSPI PGFTKWLLGL LNVQGKEHGR NELFTDSECQ 

       370        380        390        400        410        420 
EISAVTGNPV HESLKGFLSS GEWVKSEKLT QALQGPLMRL CAWYLYGEKH RGYALNPVAN 

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

       490 
SLVAQFQNNS KL 

« Hide

Isoform Cytoplasmic+peroxisomal [UniParc].

Checksum: 233693B9C1BF74CA
Show »

FASTA45450,766

References

« Hide 'large scale' references
[1]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Cerebellum.
[2]"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].
Strain: 129, C57BL/6J and FVB/N.
Tissue: Mammary tumor.
[3]"Mouse malonyl-CoA decarboxylase: genome structure, cDNA cloning, expression and promoter study."
Kim N.H., Lee G.Y., Kim Y.S.
Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-175.
Strain: 129S6/SvEvTac.
[4]"Absence of malonyl coenzyme A decarboxylase in mice increases cardiac glucose oxidation and protects the heart from ischemic injury."
Dyck J.R., Hopkins T.A., Bonnet S., Michelakis E.D., Young M.E., Watanabe M., Kawase Y., Jishage K., Lopaschuk G.D.
Circulation 114:1721-1728(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE.
[5]"SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase."
Laurent G., German N.J., Saha A.K., de Boer V.C., Davies M., Koves T.R., Dephoure N., Fischer F., Boanca G., Vaitheesvaran B., Lovitch S.B., Sharpe A.H., Kurland I.J., Steegborn C., Gygi S.P., Muoio D.M., Ruderman N.B., Haigis M.C.
Mol. Cell 50:686-698(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, ACETYLATION AT LYS-58; LYS-167; LYS-210; LYS-316; LYS-388; LYS-441 AND LYS-471, MUTAGENESIS OF LYS-471.
[6]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-167; LYS-221 AND LYS-385, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[7]"Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways."
Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B., Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.
Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-385, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK082479 mRNA. Translation: BAC38505.1.
BC004764 mRNA. Translation: AAH04764.1.
AY331094 Genomic DNA. Translation: AAP93335.2.
RefSeqNP_064350.2. NM_019966.2.
UniGeneMm.423037.

3D structure databases

ProteinModelPortalQ99J39.
SMRQ99J39. Positions 38-492.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-1861916.

Chemistry

BindingDBQ99J39.
ChEMBLCHEMBL1255162.

PTM databases

PhosphoSiteQ99J39.

Proteomic databases

PaxDbQ99J39.
PRIDEQ99J39.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000098367; ENSMUSP00000095970; ENSMUSG00000074064. [Q99J39-1]
GeneID56690.
KEGGmmu:56690.
UCSCuc009npn.1. mouse. [Q99J39-1]

Organism-specific databases

CTD23417.
MGIMGI:1928485. Mlycd.

Phylogenomic databases

eggNOGCOG1593.
GeneTreeENSGT00390000005410.
HOGENOMHOG000141409.
HOVERGENHBG000825.
InParanoidQ99J39.
KOK01578.
OMALDEGREQ.
OrthoDBEOG76X5ZZ.
PhylomeDBQ99J39.
TreeFamTF312959.

Enzyme and pathway databases

UniPathwayUPA00340; UER00710.

Gene expression databases

BgeeQ99J39.
CleanExMM_MLYCD.
GenevestigatorQ99J39.

Family and domain databases

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

Other

NextBio313103.
PROQ99J39.
SOURCESearch...

Entry information

Entry nameDCMC_MOUSE
AccessionPrimary (citable) accession number: Q99J39
Secondary accession number(s): Q7TNL6
Entry history
Integrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: June 1, 2001
Last modified: April 16, 2014
This is version 94 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot