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Protein

Malonyl-CoA decarboxylase, mitochondrial

Gene

Mlycd

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

Malonyl-CoA = acetyl-CoA + CO2.1 Publication

Enzyme regulationi

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

Pathway: acetyl-CoA biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes acetyl-CoA from malonyl-CoA.
Proteins known to be involved in this subpathway in this organism are:
  1. Malonyl-CoA decarboxylase, mitochondrial (Mlycd)
This subpathway is part of the pathway acetyl-CoA biosynthesis, which is itself part of Metabolic intermediate biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes acetyl-CoA from malonyl-CoA, the pathway acetyl-CoA biosynthesis and in Metabolic intermediate biosynthesis.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei210 – 2101Essential for catalytic activityBy similarity
Active sitei328 – 3281Proton acceptorBy similarity
Binding sitei328 – 3281Malonyl-CoABy similarity
Active sitei422 – 4221Proton donorBy similarity
Binding sitei422 – 4221Malonyl-CoABy similarity

GO - Molecular functioni

  • malonyl-CoA decarboxylase activity Source: UniProtKB
  • receptor binding Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Decarboxylase, Lyase

Keywords - Biological processi

Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism

Enzyme and pathway databases

ReactomeiREACT_337309. Peroxisomal lipid metabolism.
UniPathwayiUPA00340; UER00710.

Names & Taxonomyi

Protein namesi
Recommended name:
Malonyl-CoA decarboxylase, mitochondrial (EC:4.1.1.9)
Short name:
MCD
Gene namesi
Name:Mlycd
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1928485. Mlycd.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Ensembl
  • mitochondrial matrix Source: UniProtKB
  • mitochondrion Source: MGI
  • peroxisomal matrix Source: UniProtKB
  • peroxisome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Peroxisome

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi471 – 4711K → Q: Mimicks constitutive acetylation, leading to increased malonyl-CoA decarboxylase activity. 1 Publication
Mutagenesisi471 – 4711K → R: Decreased acetylation, leading to reduced malonyl-CoA decarboxylase activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 3838MitochondrionSequence AnalysisAdd
BLAST
Chaini39 – 492454Malonyl-CoA decarboxylase, mitochondrialPRO_0000021090Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei58 – 581N6-acetyllysine1 Publication
Modified residuei167 – 1671N6-acetyllysine; alternate1 Publication
Modified residuei167 – 1671N6-succinyllysine; alternate1 Publication
Disulfide bondi205 – 205InterchainSequence Analysis
Modified residuei210 – 2101N6-acetyllysine1 Publication
Modified residuei221 – 2211N6-succinyllysine1 Publication
Modified residuei316 – 3161N6-acetyllysine1 Publication
Modified residuei385 – 3851N6-acetyllysine; alternate1 Publication
Modified residuei385 – 3851N6-succinyllysine; alternate1 Publication
Modified residuei388 – 3881N6-acetyllysine1 Publication
Modified residuei441 – 4411N6-acetyllysine1 Publication
Modified residuei471 – 4711N6-acetyllysine1 Publication

Post-translational modificationi

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.Curated
Acetylation at Lys-471 activates malonyl-CoA decarboxylase activity. Deacetylation at Lys-471 by SIRT4 represses activity, leading to promote lipogenesis.1 Publication

Keywords - PTMi

Acetylation, Disulfide bond

Proteomic databases

MaxQBiQ99J39.
PaxDbiQ99J39.
PRIDEiQ99J39.

PTM databases

PhosphoSiteiQ99J39.

Expressioni

Gene expression databases

BgeeiQ99J39.
CleanExiMM_MLYCD.
GenevisibleiQ99J39. MM.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

MINTiMINT-1861916.
STRINGi10090.ENSMUSP00000095970.

Structurei

3D structure databases

ProteinModelPortaliQ99J39.
SMRiQ99J39. Positions 38-492.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni39 – 189151Alpha-helical domainBy similarityAdd
BLAST
Regioni190 – 492303Catalytic domainBy similarityAdd
BLAST
Regioni298 – 3047Malonyl-CoA bindingBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi490 – 4923Microbody targeting signalSequence Analysis

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG1593.
GeneTreeiENSGT00390000005410.
HOGENOMiHOG000141409.
HOVERGENiHBG000825.
InParanoidiQ99J39.
KOiK01578.
OMAiLDEGREQ.
OrthoDBiEOG76X5ZZ.
PhylomeDBiQ99J39.
TreeFamiTF312959.

Family and domain databases

InterProiIPR007956. Malonyl_CoA_deC.
[Graphical view]
PfamiPF05292. MCD. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

Note: A single transcription start site has been demonstrated in Rat.

Isoform Mitochondrial (identifier: Q99J39-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MRGLGPGLRA RRLLPLRSPP RPPGPRGRRL CGGLAASAMD ELLRRAVPPT
60 70 80 90 100
PAYELREKTP APAEGQCADF VSFYGGLAEA SQRAELLGRL AQGFGVDHGQ
110 120 130 140 150
VAEQSAGVLQ LRQQAREAAV LLQAEDRLRY ALVPRYRGLF HHISKLDGGV
160 170 180 190 200
RFLVQLRADL LEAQALKLVE GPHVREMNGV LKSMLSEWFS SGFLNLERVT
210 220 230 240 250
WHSPCEVLQK ISECEAVHPV KNWMDMKRRV GPYRRCYFFS HCSTPGEPLV
260 270 280 290 300
VLHVALTGDI SNNIQGIVKE CPPTETEERN RIAAAIFYSI SLTQQGLQGV
310 320 330 340 350
ELGTFLIKRV VKELQKEFPQ LGAFSSLSPI PGFTKWLLGL LNVQGKEHGR
360 370 380 390 400
NELFTDSECQ EISAVTGNPV HESLKGFLSS GEWVKSEKLT QALQGPLMRL
410 420 430 440 450
CAWYLYGEKH RGYALNPVAN FHLQNGAVMW RINWMADSSL KGLTSSCGLM
460 470 480 490
VNYRYYLEET GPNSISYLGS KNIKASEQIL SLVAQFQNNS KL
Length:492
Mass (Da):54,736
Last modified:June 1, 2001 - v1
Checksum:iCEBDA62714A21DC1
GO
Isoform Cytoplasmic+peroxisomal (identifier: Q99J39-2) [UniParc]FASTAAdd to basket

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.
Show »
Length:454
Mass (Da):50,766
Checksum:i233693B9C1BF74CA
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 3838Missing in isoform Cytoplasmic+peroxisomal. CuratedVSP_018817Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK082479 mRNA. Translation: BAC38505.1.
BC004764 mRNA. Translation: AAH04764.1.
AY331094 Genomic DNA. Translation: AAP93335.2.
CCDSiCCDS22703.1. [Q99J39-1]
RefSeqiNP_064350.2. NM_019966.2. [Q99J39-1]
UniGeneiMm.423037.

Genome annotation databases

EnsembliENSMUST00000098367; ENSMUSP00000095970; ENSMUSG00000074064. [Q99J39-1]
GeneIDi56690.
KEGGimmu:56690.
UCSCiuc009npn.1. mouse. [Q99J39-1]

Keywords - Coding sequence diversityi

Alternative initiation

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK082479 mRNA. Translation: BAC38505.1.
BC004764 mRNA. Translation: AAH04764.1.
AY331094 Genomic DNA. Translation: AAP93335.2.
CCDSiCCDS22703.1. [Q99J39-1]
RefSeqiNP_064350.2. NM_019966.2. [Q99J39-1]
UniGeneiMm.423037.

3D structure databases

ProteinModelPortaliQ99J39.
SMRiQ99J39. Positions 38-492.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-1861916.
STRINGi10090.ENSMUSP00000095970.

Chemistry

BindingDBiQ99J39.
ChEMBLiCHEMBL1255162.

PTM databases

PhosphoSiteiQ99J39.

Proteomic databases

MaxQBiQ99J39.
PaxDbiQ99J39.
PRIDEiQ99J39.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000098367; ENSMUSP00000095970; ENSMUSG00000074064. [Q99J39-1]
GeneIDi56690.
KEGGimmu:56690.
UCSCiuc009npn.1. mouse. [Q99J39-1]

Organism-specific databases

CTDi23417.
MGIiMGI:1928485. Mlycd.

Phylogenomic databases

eggNOGiCOG1593.
GeneTreeiENSGT00390000005410.
HOGENOMiHOG000141409.
HOVERGENiHBG000825.
InParanoidiQ99J39.
KOiK01578.
OMAiLDEGREQ.
OrthoDBiEOG76X5ZZ.
PhylomeDBiQ99J39.
TreeFamiTF312959.

Enzyme and pathway databases

UniPathwayiUPA00340; UER00710.
ReactomeiREACT_337309. Peroxisomal lipid metabolism.

Miscellaneous databases

NextBioi313103.
PROiQ99J39.
SOURCEiSearch...

Gene expression databases

BgeeiQ99J39.
CleanExiMM_MLYCD.
GenevisibleiQ99J39. MM.

Family and domain databases

InterProiIPR007956. Malonyl_CoA_deC.
[Graphical view]
PfamiPF05292. MCD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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.

Entry informationi

Entry nameiDCMC_MOUSE
AccessioniPrimary (citable) accession number: Q99J39
Secondary accession number(s): Q7TNL6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: June 1, 2001
Last modified: June 24, 2015
This is version 105 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.