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O95822 (DCMC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length493 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 Ref.9

Catalytic activity

Malonyl-CoA = acetyl-CoA + CO2. Ref.1 Ref.2 Ref.3 Ref.6 Ref.9

Enzyme regulation

Malonyl-CoA decarboxylase activity does not require any cofactors or divalent metal ions. Formation of interchain disulfide bonds leads to positive cooperativity between active sites and increases the affinity for malonyl-CoA and the catalytic efficiency (in vitro). Ref.6 Ref.9

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. Ref.9

Subcellular location

Cytoplasm. Mitochondrion matrix. Peroxisome. Peroxisome matrix By similarity. Note: Enzymatically active in all three subcellular compartments By similarity. Ref.1

Tissue specificity

Expressed in fibroblasts and hepatoblastoma cells (at protein level). Expressed strongly in heart, liver, skeletal muscle, kidney and pancreas. Expressed in myotubes. Expressed weakly in brain, placenta, spleen, thymus, testis, ovary and small intestine. Ref.2 Ref.7

Post-translational modification

Acetylation at Lys-472 activates malonyl-CoA decarboxylase activity. Deacetylation at Lys-472 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.

Involvement in disease

Malonyl-CoA decarboxylase deficiency (MLYCD deficiency) [MIM:248360]: Autosomal recessive disease characterized by abdominal pain, chronic constipation, episodic vomiting, metabolic acidosis and malonic aciduria.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Biophysicochemical properties

Kinetic parameters:

kcat is 19 sec(-1) with malonyl-CoA for malonyl-CoA decarboxylase mitochondrial form, Ref.6. kcat is 28 sec(-1) with malonyl-CoA for Malonyl-CoA decarboxylase cytoplasmic+peroxisomal form, Ref.6. The catalytic efficiency for malonyl-CoA is at least 1.09-fold higher with the malonyl-CoA decarboxylase cytoplasmic+peroxisomal form, Ref.6.

KM=0.36 mM for malonyl-CoA (Malonyl-CoA decarboxylase mitochondrial form), Ref.6 Ref.2 Ref.6 Ref.9

KM=0.83 mM for malonyl-CoA (Malonyl-CoA decarboxylase mitochondrial form), Ref.9

KM=0.22 mM for malonyl-CoA (Malonyl-CoA decarboxylase cytoplasmic+peroxisomal form), Ref.2

KM=0.33 mM for malonyl-CoA (Malonyl-CoA decarboxylase cytoplasmic+peroxisomal form), Ref.6

Sequence caution

The sequence AAD16177.2 differs from that shown. Reason: Frameshift at positions 23, 28, 297 and 308.

Ontologies

Keywords
   Biological processFatty acid biosynthesis
Fatty acid metabolism
Lipid biosynthesis
Lipid metabolism
   Cellular componentCytoplasm
Mitochondrion
Peroxisome
   Coding sequence diversityAlternative initiation
Alternative splicing
   DomainTransit peptide
   Molecular functionDecarboxylase
Lyase
   PTMAcetylation
Disulfide bond
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processacetyl-CoA biosynthetic process

Inferred from direct assay Ref.1Ref.2Ref.3. Source: UniProtKB

cellular lipid metabolic process

Traceable author statement. Source: Reactome

fatty acid biosynthetic process

Inferred from direct assay Ref.6. Source: UniProtKB

malonyl-CoA catabolic process

Inferred from direct assay Ref.1Ref.2Ref.6. Source: UniProtKB

positive regulation of fatty acid oxidation

Inferred from mutant phenotype Ref.7. Source: UniProtKB

regulation of glucose metabolic process

Inferred from mutant phenotype Ref.7. Source: UniProtKB

response to ischemia

Inferred from sequence or structural similarity. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay Ref.2. Source: UniProtKB

mitochondrial matrix

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrion

Inferred from direct assay Ref.1. Source: UniProtKB

peroxisomal matrix

Inferred from sequence or structural similarity. Source: UniProtKB

peroxisome

Inferred from direct assay Ref.1Ref.2. Source: UniProtKB

   Molecular_functionmalonyl-CoA decarboxylase activity

Inferred from direct assay Ref.1Ref.2Ref.6Ref.3. Source: UniProtKB

receptor binding

Inferred from physical interaction Ref.8. 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: O95822-1)

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: O95822-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-39: Missing.
Note: May be produced by alternative initiation at Met-40 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
Chain? – 493Malonyl-CoA decarboxylase, mitochondrialPRO_0000021088

Regions

Region299 – 3057Malonyl-CoA binding Probable
Motif491 – 4933Microbody targeting signal Potential

Sites

Binding site3291Malonyl-CoA Probable
Binding site4231Malonyl-CoA Probable

Amino acid modifications

Modified residue591N6-acetyllysine By similarity
Modified residue1681N6-acetyllysine; alternate By similarity
Modified residue1681N6-succinyllysine; alternate By similarity
Modified residue2111N6-acetyllysine By similarity
Modified residue2221N6-succinyllysine By similarity
Modified residue3891N6-acetyllysine By similarity
Modified residue4721N6-acetyllysine By similarity
Disulfide bond206Interchain Potential

Natural variations

Alternative sequence1 – 3939Missing in isoform Cytoplasmic+peroxisomal.
VSP_047649

Experimental info

Mutagenesis2061C → S: Abolishes formation of disulfide-linked homotetramers. Abolishes the cooperative enzyme kinetics that are seen under oxidative conditions. Ref.9
Mutagenesis2431C → S: Does not abolish formation of disulfide-linked homotetramers. No effect on development of cooperative enzyme kinetics in response to oxidative conditions. Ref.9
Mutagenesis3021E → G: Decreases catalytic activity. Increases affinity for malonyl-CoA. Ref.9
Sequence conflict821A → D in AAD16177. Ref.1
Sequence conflict1191A → S in AAD48994. Ref.3
Sequence conflict1271D → V in AAD48994. Ref.3
Sequence conflict1921S → P in AAD34631. Ref.2

Secondary structure

........................................................................ 493
Helix Strand Turn

Details...

Sequences

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

Last modified December 1, 2000. Version 3.
Checksum: 8F061CA38908E8FC

FASTA49355,003
        10         20         30         40         50         60 
MRGFGPGLTA RRLLPLRLPP RPPGPRLASG QAAGALERAM DELLRRAVPP TPAYELREKT 

        70         80         90        100        110        120 
PAPAEGQCAD FVSFYGGLAE TAQRAELLGR LARGFGVDHG QVAEQSAGVL HLRQQQREAA 

       130        140        150        160        170        180 
VLLQAEDRLR YALVPRYRGL FHHISKLDGG VRFLVQLRAD LLEAQALKLV EGPDVREMNG 

       190        200        210        220        230        240 
VLKGMLSEWF SSGFLNLERV TWHSPCEVLQ KISEAEAVHP VKNWMDMKRR VGPYRRCYFF 

       250        260        270        280        290        300 
SHCSTPGEPL VVLHVALTGD ISSNIQAIVK EHPPSETEEK NKITAAIFYS ISLTQQGLQG 

       310        320        330        340        350        360 
VELGTFLIKR VVKELQREFP HLGVFSSLSP IPGFTKWLLG LLNSQTKEHG RNELFTDSEC 

       370        380        390        400        410        420 
KEISEITGGP INETLKLLLS SSEWVQSEKL VRALQTPLMR LCAWYLYGEK HRGYALNPVA 

       430        440        450        460        470        480 
NFHLQNGAVL WRINWMADVS LRGITGSCGL MANYRYFLEE TGPNSTSYLG SKIIKASEQV 

       490 
LSLVAQFQKN SKL 

« Hide

Isoform Cytoplasmic+peroxisomal [UniParc].

Checksum: 41C79B2AC6DB3554
Show »

FASTA45450,946

References

« Hide 'large scale' references
[1]"The molecular basis of malonyl-CoA decarboxylase deficiency."
FitzPatrick D.R., Hill A., Tolmie J.L., Thorburn D.R., Christodoulou J.
Am. J. Hum. Genet. 65:318-326(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYTOPLASMIC+PEROXISOMAL), CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
[2]"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYTOPLASMIC+PEROXISOMAL), FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
Tissue: Heart.
[3]"Cloning and mutational analysis of human malonyl-coenzyme A decarboxylase."
Gao J., Waber L., Bennett M.J., Gibson K.M., Cohen J.C.
J. Lipid Res. 40:178-182(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MITOCHONDRIAL), CATALYTIC ACTIVITY.
[4]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] (ISOFORMS MITOCHONDRIAL AND CYTOPLASMIC+PEROXISOMAL).
Tissue: Eye and Lung.
[6]"Expression, purification, and characterization of human malonyl-CoA decarboxylase."
Zhou D., Yuen P., Chu D., Thon V., McConnell S., Brown S., Tsang A., Pena M., Russell A., Cheng J.F., Nadzan A.M., Barbosa M.S., Dyck J.R., Lopaschuk G.D., Yang G.
Protein Expr. Purif. 34:261-269(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
[7]"Malonyl CoenzymeA decarboxylase regulates lipid and glucose metabolism in human skeletal muscle."
Bouzakri K., Austin R., Rune A., Lassman M.E., Garcia-Roves P.M., Berger J.P., Krook A., Chibalin A.V., Zhang B.B., Zierath J.R.
Diabetes 57:1508-1516(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[8]"A proteome-wide perspective on peroxisome targeting signal 1(PTS1)-Pex5p affinities."
Ghosh D., Berg J.M.
J. Am. Chem. Soc. 132:3973-3979(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION WITH PEX5.
[9]"Structural asymmetry and disulphide bridges among subunits modulate the activity of human Malonyl-CoA Decarboxylase."
Aparicio D., Perez R., Carpena X., Diaz M., Ferrer J.C., Loewen P.C., Fita I.
J. Biol. Chem. 288:11907-11919(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 39-493 IN COMPLEX WITH LIGAND REPRESENTING COENZYME A, CATALYTIC ACTIVITY, FUNCTION, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, DISULFIDE BONDS, MUTAGENESIS OF CYS-206; CYS-243 AND GLU-302, IDENTIFICATION BY MASS SPECTROMETRY.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF097832 mRNA. Translation: AAD16177.2. Frameshift.
AF153679 mRNA. Translation: AAD34631.1.
AF090834 mRNA. Translation: AAD48994.1.
AC009119 Genomic DNA. No translation available.
BC000286 mRNA. Translation: AAH00286.1.
BC052592 mRNA. Translation: AAH52592.1.
RefSeqNP_036345.2. NM_012213.2.
UniGeneHs.644610.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2YGWX-ray2.80A/B40-490[»]
4F0XX-ray3.29A/B/C/D/E/F/G/H39-493[»]
ProteinModelPortalO95822.
SMRO95822. Positions 39-493.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116989. 1 interaction.
DIPDIP-60405N.
STRING9606.ENSP00000262430.

Chemistry

BindingDBO95822.
ChEMBLCHEMBL4698.

PTM databases

PhosphoSiteO95822.

Proteomic databases

PaxDbO95822.
PRIDEO95822.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262430; ENSP00000262430; ENSG00000103150. [O95822-1]
GeneID23417.
KEGGhsa:23417.
UCSCuc002fgz.3. human. [O95822-1]

Organism-specific databases

CTD23417.
GeneCardsGC16P083932.
H-InvDBHIX0173296.
HGNCHGNC:7150. MLYCD.
HPAHPA031625.
MIM248360. phenotype.
606761. gene.
neXtProtNX_O95822.
Orphanet943. Malonic aciduria.
PharmGKBPA30861.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1593.
HOGENOMHOG000141409.
HOVERGENHBG000825.
InParanoidO95822.
KOK01578.
OMALDEGREQ.
OrthoDBEOG76X5ZZ.
PhylomeDBO95822.
TreeFamTF312959.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
SABIO-RKO95822.
UniPathwayUPA00340; UER00710.

Gene expression databases

BgeeO95822.
CleanExHS_MLYCD.
GenevestigatorO95822.

Family and domain databases

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

Other

GenomeRNAi23417.
NextBio45627.
PROO95822.
SOURCESearch...

Entry information

Entry nameDCMC_HUMAN
AccessionPrimary (citable) accession number: O95822
Secondary accession number(s): Q9UNU5, Q9Y3F2
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 1, 2000
Last modified: April 16, 2014
This is version 125 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM