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Protein

Malonyl-CoA decarboxylase, mitochondrial

Gene

MLYCD

Organism
Homo sapiens (Human)
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. 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

Enzyme 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. KM=0.36 mM for malonyl-CoA (Malonyl-CoA decarboxylase mitochondrial form), PubMed:150032603 Publications
  2. KM=0.83 mM for malonyl-CoA (Malonyl-CoA decarboxylase mitochondrial form), PubMed:234825653 Publications
  3. KM=0.22 mM for malonyl-CoA (Malonyl-CoA decarboxylase cytoplasmic+peroxisomal form), PubMed:104551073 Publications
  4. KM=0.33 mM for malonyl-CoA (Malonyl-CoA decarboxylase cytoplasmic+peroxisomal form), PubMed:150032603 Publications

    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

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

    GO - Biological processi

    • acetyl-CoA biosynthetic process Source: UniProtKB
    • acyl-CoA metabolic process Source: Reactome
    • fatty acid biosynthetic process Source: UniProtKB
    • malonyl-CoA catabolic process Source: UniProtKB
    • positive regulation of fatty acid oxidation Source: UniProtKB
    • regulation of glucose metabolic process Source: UniProtKB
    • response to ischemia Source: UniProtKB
    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

    BioCyciZFISH:HS02460-MONOMER.
    BRENDAi4.1.1.9. 2681.
    ReactomeiR-HSA-390918. Peroxisomal lipid metabolism.
    SABIO-RKO95822.
    UniPathwayiUPA00340; 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

    HGNCiHGNC:7150. MLYCD.

    Subcellular locationi

    GO - Cellular componenti

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

    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.

    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.
    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

    GO - Molecular functioni

    • receptor binding Source: UniProtKB

    Protein-protein interaction databases

    BioGridi116989. 10 interactors.
    DIPiDIP-60405N.
    IntActiO95822. 1 interactor.
    STRINGi9606.ENSP00000262430.

    Chemistry databases

    BindingDBiO95822.

    Structurei

    Secondary structure

    1493
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi40 – 47Combined sources8
    Helixi54 – 56Combined sources3
    Helixi67 – 76Combined sources10
    Helixi81 – 94Combined sources14
    Helixi99 – 112Combined sources14
    Turni114 – 116Combined sources3
    Helixi119 – 132Combined sources14
    Helixi138 – 145Combined sources8
    Beta strandi147 – 149Combined sources3
    Helixi150 – 166Combined sources17
    Helixi173 – 189Combined sources17
    Helixi192 – 194Combined sources3
    Beta strandi195 – 200Combined sources6
    Helixi206 – 214Combined sources9
    Helixi224 – 230Combined sources7
    Beta strandi235 – 242Combined sources8
    Beta strandi250 – 260Combined sources11
    Helixi266 – 269Combined sources4
    Beta strandi285 – 294Combined sources10
    Helixi296 – 298Combined sources3
    Turni299 – 301Combined sources3
    Helixi303 – 318Combined sources16
    Beta strandi324 – 327Combined sources4
    Helixi334 – 341Combined sources8
    Beta strandi348 – 350Combined sources3
    Helixi357 – 367Combined sources11
    Helixi374 – 379Combined sources6
    Turni380 – 382Combined sources3
    Helixi383 – 386Combined sources4
    Helixi388 – 393Combined sources6
    Helixi395 – 407Combined sources13
    Beta strandi414 – 417Combined sources4
    Helixi418 – 425Combined sources8
    Beta strandi429 – 434Combined sources6
    Helixi441 – 447Combined sources7
    Beta strandi451 – 455Combined sources5
    Helixi458 – 460Combined sources3
    Helixi461 – 471Combined sources11
    Helixi478 – 486Combined sources9

    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...

    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.
    OMAiLDEGREQ.
    OrthoDBiEOG091G07WG.
    PhylomeDBiO95822.
    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: 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, Alternative splicing

    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. 10 interactors.
    DIPiDIP-60405N.
    IntActiO95822. 1 interactor.
    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.

    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.
    GeneCardsiMLYCD.
    H-InvDBHIX0173296.
    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.
    OMAiLDEGREQ.
    OrthoDBiEOG091G07WG.
    PhylomeDBiO95822.
    TreeFamiTF312959.

    Enzyme and pathway databases

    UniPathwayiUPA00340; UER00710.
    BioCyciZFISH:HS02460-MONOMER.
    BRENDAi4.1.1.9. 2681.
    ReactomeiR-HSA-390918. Peroxisomal lipid metabolism.
    SABIO-RKO95822.

    Miscellaneous databases

    ChiTaRSiMLYCD. human.
    GenomeRNAii23417.
    PROiO95822.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000103150.
    CleanExiHS_MLYCD.
    GenevisibleiO95822. HS.

    Family and domain databases

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

    Entry informationi

    Entry nameiDCMC_HUMAN
    AccessioniPrimary (citable) accession number: O95822
    Secondary accession number(s): Q9UNU5, Q9Y3F2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: December 1, 2000
    Last modified: November 2, 2016
    This is version 147 of the entry and version 3 of the sequence. [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. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    4. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references

    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 one 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.