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Protein

Malonyl-CoA decarboxylase, mitochondrial

Gene

MLYCD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. May play a role in controlling the extent of ischemic injury by promoting glucose oxidation.4 Publications

Catalytic activityi

Malonyl-CoA = acetyl-CoA + CO2.5 Publications

Activity regulationi

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).2 Publications

Kineticsi

kcat is 19 sec(-1) with malonyl-CoA for malonyl-CoA decarboxylase mitochondrial form (PubMed:15003260). kcat is 28 sec(-1) with malonyl-CoA for Malonyl-CoA decarboxylase cytoplasmic+peroxisomal form (PubMed:15003260). The catalytic efficiency for malonyl-CoA is at least 1.09-fold higher with the malonyl-CoA decarboxylase cytoplasmic+peroxisomal form (PubMed:15003260).1 Publication
  1. KM=0.36 mM for malonyl-CoA (Malonyl-CoA decarboxylase mitochondrial form)1 Publication
  2. KM=0.83 mM for malonyl-CoA (Malonyl-CoA decarboxylase mitochondrial form)1 Publication
  3. KM=0.22 mM for malonyl-CoA (Malonyl-CoA decarboxylase cytoplasmic+peroxisomal form)1 Publication
  4. KM=0.33 mM for malonyl-CoA (Malonyl-CoA decarboxylase cytoplasmic+peroxisomal form)1 Publication

    Pathwayi: 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)DescriptionActionsGraphical viewLength
    Sitei211Essential for catalytic activityBy similarity1
    Active sitei329Proton acceptor1 Publication1
    Binding sitei329Malonyl-CoACurated1
    Active sitei423Proton donor1 Publication1
    Binding sitei423Malonyl-CoACurated1

    GO - Molecular functioni

    • identical protein binding Source: IntAct
    • malonyl-CoA decarboxylase activity Source: UniProtKB
    • signaling receptor binding Source: UniProtKB

    GO - Biological processi

    Keywordsi

    Molecular functionDecarboxylase, Lyase
    Biological processFatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism

    Enzyme and pathway databases

    BRENDAi4.1.1.9 2681
    ReactomeiR-HSA-390247 Beta-oxidation of very long chain fatty acids
    R-HSA-9033241 Peroxisomal protein import
    SABIO-RKiO95822
    UniPathwayi
    UPA00340;UER00710

    Chemistry databases

    SwissLipidsiSLP:000000251

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Malonyl-CoA decarboxylase, mitochondrial (EC:4.1.1.9)
    Short name:
    MCD
    Gene namesi
    Name:MLYCD
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 16

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000103150.5
    HGNCiHGNC:7150 MLYCD
    MIMi606761 gene
    neXtProtiNX_O95822

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm, Mitochondrion, Peroxisome

    Pathology & Biotechi

    Involvement in diseasei

    Malonyl-CoA decarboxylase deficiency (MLYCD deficiency)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionAutosomal recessive disease characterized by abdominal pain, chronic constipation, episodic vomiting, metabolic acidosis and malonic aciduria.
    See also OMIM:248360

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi206C → S: Abolishes formation of disulfide-linked homotetramers. Abolishes the cooperative enzyme kinetics that are seen under oxidative conditions. 1 Publication1
    Mutagenesisi243C → S: Does not abolish formation of disulfide-linked homotetramers. No effect on development of cooperative enzyme kinetics in response to oxidative conditions. 1 Publication1
    Mutagenesisi290S → F: 2-fold reduction in catalytic activity. 1 Publication1
    Mutagenesisi302E → G: Decreases catalytic activity. Increases affinity for malonyl-CoA. 1 Publication1
    Mutagenesisi329S → A: 110-fold reduction in catalytic activity. 1 Publication1
    Mutagenesisi423H → N: 7-fold reduction in catalytic activity. 1 Publication1
    Mutagenesisi456Y → S: 3.5-fold reduction in catalytic activity. 1 Publication1

    Organism-specific databases

    DisGeNETi23417
    MalaCardsiMLYCD
    MIMi248360 phenotype
    OpenTargetsiENSG00000103150
    Orphaneti943 Malonic aciduria
    PharmGKBiPA30861

    Chemistry databases

    ChEMBLiCHEMBL4698
    GuidetoPHARMACOLOGYi1275

    Polymorphism and mutation databases

    BioMutaiMLYCD

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Transit peptidei1 – 39MitochondrionSequence analysisAdd BLAST39
    ChainiPRO_000002108840 – 493Malonyl-CoA decarboxylase, mitochondrialAdd BLAST454

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei59N6-acetyllysineBy similarity1
    Modified residuei168N6-acetyllysine; alternateBy similarity1
    Modified residuei168N6-succinyllysine; alternateBy similarity1
    Disulfide bondi206InterchainSequence analysis
    Modified residuei211N6-acetyllysineBy similarity1
    Modified residuei222N6-succinyllysineBy similarity1
    Modified residuei389N6-acetyllysineBy similarity1
    Modified residuei472N6-acetyllysineBy similarity1

    Post-translational modificationi

    Acetylation at Lys-472 activates malonyl-CoA decarboxylase activity. Deacetylation at Lys-472 by SIRT4 represses activity, leading to promote lipogenesis (By similarity).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.Curated

    Keywords - PTMi

    Acetylation, Disulfide bond

    Proteomic databases

    EPDiO95822
    MaxQBiO95822
    PaxDbiO95822
    PeptideAtlasiO95822
    PRIDEiO95822
    ProteomicsDBi51071

    PTM databases

    iPTMnetiO95822
    PhosphoSitePlusiO95822

    Expressioni

    Tissue specificityi

    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.2 Publications

    Gene expression databases

    BgeeiENSG00000103150 Expressed in 186 organ(s), highest expression level in muscle organ
    CleanExiHS_MLYCD
    GenevisibleiO95822 HS

    Organism-specific databases

    HPAiHPA031625

    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 PEX5.2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself4EBI-10714916,EBI-10714916

    GO - Molecular functioni

    Protein-protein interaction databases

    BioGridi116989, 19 interactors
    DIPiDIP-60405N
    IntActiO95822, 6 interactors
    STRINGi9606.ENSP00000262430

    Chemistry databases

    BindingDBiO95822

    Structurei

    Secondary structure

    1493
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliO95822
    SMRiO95822
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni40 – 190Alpha-helical domainAdd BLAST151
    Regioni191 – 493Catalytic domainAdd BLAST303
    Regioni299 – 305Malonyl-CoA bindingCurated7

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi491 – 493Microbody targeting signalSequence analysis3

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiKOG3018 Eukaryota
    COG1593 LUCA
    GeneTreeiENSGT00390000005410
    HOGENOMiHOG000141409
    HOVERGENiHBG000825
    InParanoidiO95822
    KOiK01578
    OMAiTGSCGLM
    OrthoDBiEOG091G07WG
    PhylomeDBiO95822
    TreeFamiTF312959

    Family and domain databases

    Gene3Di1.20.140.90, 1 hit
    InterProiView protein in InterPro
    IPR038917 Malonyl_CoA_deC
    IPR007956 Malonyl_CoA_deC_C
    IPR035372 MCD_N
    IPR038351 MCD_N_sf
    PANTHERiPTHR28641 PTHR28641, 1 hit
    PfamiView protein in Pfam
    PF05292 MCD, 1 hit
    PF17408 MCD_N, 1 hit

    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: O95822-1) [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
    MRGFGPGLTA RRLLPLRLPP RPPGPRLASG QAAGALERAM DELLRRAVPP
    60 70 80 90 100
    TPAYELREKT PAPAEGQCAD FVSFYGGLAE TAQRAELLGR LARGFGVDHG
    110 120 130 140 150
    QVAEQSAGVL HLRQQQREAA VLLQAEDRLR YALVPRYRGL FHHISKLDGG
    160 170 180 190 200
    VRFLVQLRAD LLEAQALKLV EGPDVREMNG VLKGMLSEWF SSGFLNLERV
    210 220 230 240 250
    TWHSPCEVLQ KISEAEAVHP VKNWMDMKRR VGPYRRCYFF SHCSTPGEPL
    260 270 280 290 300
    VVLHVALTGD ISSNIQAIVK EHPPSETEEK NKITAAIFYS ISLTQQGLQG
    310 320 330 340 350
    VELGTFLIKR VVKELQREFP HLGVFSSLSP IPGFTKWLLG LLNSQTKEHG
    360 370 380 390 400
    RNELFTDSEC KEISEITGGP INETLKLLLS SSEWVQSEKL VRALQTPLMR
    410 420 430 440 450
    LCAWYLYGEK HRGYALNPVA NFHLQNGAVL WRINWMADVS LRGITGSCGL
    460 470 480 490
    MANYRYFLEE TGPNSTSYLG SKIIKASEQV LSLVAQFQKN SKL
    Length:493
    Mass (Da):55,003
    Last modified:December 1, 2000 - v3
    Checksum:i8F061CA38908E8FC
    GO
    Isoform Cytoplasmic+peroxisomal (identifier: O95822-2) [UniParc]FASTAAdd to basket

    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.
    Show »
    Length:454
    Mass (Da):50,946
    Checksum:i41C79B2AC6DB3554
    GO

    Sequence cautioni

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

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti82A → D in AAD16177 (PubMed:10417274).Curated1
    Sequence conflicti119A → S in AAD48994 (PubMed:9869665).Curated1
    Sequence conflicti127D → V in AAD48994 (PubMed:9869665).Curated1
    Sequence conflicti192S → P in AAD34631 (PubMed:10455107).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0476491 – 39Missing in isoform Cytoplasmic+peroxisomal. 3 PublicationsAdd BLAST39

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    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
    CCDSiCCDS42206.1 [O95822-1]
    RefSeqiNP_036345.2, NM_012213.2 [O95822-1]
    UniGeneiHs.644610

    Genome annotation databases

    EnsembliENST00000262430; ENSP00000262430; ENSG00000103150 [O95822-1]
    GeneIDi23417
    KEGGihsa:23417
    UCSCiuc002fgz.4 human [O95822-1]

    Keywords - Coding sequence diversityi

    Alternative initiation

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    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
    CCDSiCCDS42206.1 [O95822-1]
    RefSeqiNP_036345.2, NM_012213.2 [O95822-1]
    UniGeneiHs.644610

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2YGWX-ray2.80A/B40-490[»]
    4F0XX-ray3.29A/B/C/D/E/F/G/H39-493[»]
    ProteinModelPortaliO95822
    SMRiO95822
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi116989, 19 interactors
    DIPiDIP-60405N
    IntActiO95822, 6 interactors
    STRINGi9606.ENSP00000262430

    Chemistry databases

    BindingDBiO95822
    ChEMBLiCHEMBL4698
    GuidetoPHARMACOLOGYi1275
    SwissLipidsiSLP:000000251

    PTM databases

    iPTMnetiO95822
    PhosphoSitePlusiO95822

    Polymorphism and mutation databases

    BioMutaiMLYCD

    Proteomic databases

    EPDiO95822
    MaxQBiO95822
    PaxDbiO95822
    PeptideAtlasiO95822
    PRIDEiO95822
    ProteomicsDBi51071

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000262430; ENSP00000262430; ENSG00000103150 [O95822-1]
    GeneIDi23417
    KEGGihsa:23417
    UCSCiuc002fgz.4 human [O95822-1]

    Organism-specific databases

    CTDi23417
    DisGeNETi23417
    EuPathDBiHostDB:ENSG00000103150.5
    GeneCardsiMLYCD
    H-InvDBiHIX0173296
    HGNCiHGNC:7150 MLYCD
    HPAiHPA031625
    MalaCardsiMLYCD
    MIMi248360 phenotype
    606761 gene
    neXtProtiNX_O95822
    OpenTargetsiENSG00000103150
    Orphaneti943 Malonic aciduria
    PharmGKBiPA30861
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3018 Eukaryota
    COG1593 LUCA
    GeneTreeiENSGT00390000005410
    HOGENOMiHOG000141409
    HOVERGENiHBG000825
    InParanoidiO95822
    KOiK01578
    OMAiTGSCGLM
    OrthoDBiEOG091G07WG
    PhylomeDBiO95822
    TreeFamiTF312959

    Enzyme and pathway databases

    UniPathwayi
    UPA00340;UER00710

    BRENDAi4.1.1.9 2681
    ReactomeiR-HSA-390247 Beta-oxidation of very long chain fatty acids
    R-HSA-9033241 Peroxisomal protein import
    SABIO-RKiO95822

    Miscellaneous databases

    ChiTaRSiMLYCD human
    GenomeRNAii23417
    PROiPR:O95822
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000103150 Expressed in 186 organ(s), highest expression level in muscle organ
    CleanExiHS_MLYCD
    GenevisibleiO95822 HS

    Family and domain databases

    Gene3Di1.20.140.90, 1 hit
    InterProiView protein in InterPro
    IPR038917 Malonyl_CoA_deC
    IPR007956 Malonyl_CoA_deC_C
    IPR035372 MCD_N
    IPR038351 MCD_N_sf
    PANTHERiPTHR28641 PTHR28641, 1 hit
    PfamiView protein in Pfam
    PF05292 MCD, 1 hit
    PF17408 MCD_N, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiDCMC_HUMAN
    AccessioniPrimary (citable) accession number: O95822
    Secondary accession number(s): Q9UNU5, Q9Y3F2
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: December 1, 2000
    Last modified: October 10, 2018
    This is version 161 of the entry and version 3 of the sequence. See complete history.
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    4. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

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