UniProtKB - O95822 (DCMC_HUMAN)
Malonyl-CoA decarboxylase, mitochondrial
MLYCD
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 PublicationsCatalytic activityi
Activity regulationi
Kineticsi
- KM=0.36 mM for malonyl-CoA (Malonyl-CoA decarboxylase mitochondrial form)1 Publication
- KM=0.83 mM for malonyl-CoA (Malonyl-CoA decarboxylase mitochondrial form)1 Publication
- KM=0.22 mM for malonyl-CoA (Malonyl-CoA decarboxylase cytoplasmic+peroxisomal form)1 Publication
- KM=0.33 mM for malonyl-CoA (Malonyl-CoA decarboxylase cytoplasmic+peroxisomal form)1 Publication
: acetyl-CoA biosynthesis Pathwayi
This protein is involved in step 1 of the subpathway that synthesizes acetyl-CoA from malonyl-CoA. 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 211 | Essential for catalytic activityBy similarity | 1 | |
Active sitei | 329 | Proton acceptor1 Publication | 1 | |
Binding sitei | 329 | Malonyl-CoACurated | 1 | |
Active sitei | 423 | Proton donor1 Publication | 1 | |
Binding sitei | 423 | Malonyl-CoACurated | 1 |
GO - Molecular functioni
- identical protein binding Source: IntAct
- malonyl-CoA decarboxylase activity Source: UniProtKB
GO - Biological processi
- acetyl-CoA biosynthetic process Source: UniProtKB
- acyl-CoA metabolic process Source: Reactome
- fatty acid biosynthetic process Source: UniProtKB
- fatty acid oxidation Source: Ensembl
- malonyl-CoA catabolic process Source: UniProtKB
- positive regulation of fatty acid oxidation Source: UniProtKB
- regulation of fatty acid beta-oxidation Source: Ensembl
- regulation of glucose metabolic process Source: UniProtKB
- response to ischemia Source: UniProtKB
Keywordsi
Molecular function | Decarboxylase, Lyase |
Biological process | Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism |
Enzyme and pathway databases
BRENDAi | 4.1.1.9, 2681 |
PathwayCommonsi | O95822 |
Reactomei | R-HSA-390247, Beta-oxidation of very long chain fatty acids [O95822-2] R-HSA-9033241, Peroxisomal protein import [O95822-2] |
SABIO-RKi | O95822 |
SignaLinki | O95822 |
UniPathwayi | UPA00340;UER00710 |
Chemistry databases
SwissLipidsi | SLP:000000251 |
Names & Taxonomyi
Protein namesi | Recommended name: Malonyl-CoA decarboxylase, mitochondrialCurated (EC:4.1.1.95 Publications)Short name: MCD |
Gene namesi | Name:MLYCDImported |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:7150, MLYCD |
MIMi | 606761, gene |
neXtProti | NX_O95822 |
VEuPathDBi | HostDB:ENSG00000103150 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Peroxisome
- Peroxisome 1 Publication
- Peroxisome matrix By similarity
Mitochondrion
- Mitochondrion matrix 1 Publication
Note: Enzymatically active in all three subcellular compartments.By similarity
Cytosol
- cytosol Source: Reactome
Mitochondrion
- mitochondrial matrix Source: UniProtKB
- mitochondrion Source: UniProtKB
Peroxisome
- peroxisomal matrix Source: UniProtKB
- peroxisome Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, Mitochondrion, PeroxisomePathology & Biotechi
Involvement in diseasei
Malonyl-CoA decarboxylase deficiency (MLYCD deficiency)1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 206 | C → S: Abolishes formation of disulfide-linked homotetramers. Abolishes the cooperative enzyme kinetics that are seen under oxidative conditions. 1 Publication | 1 | |
Mutagenesisi | 243 | C → S: Does not abolish formation of disulfide-linked homotetramers. No effect on development of cooperative enzyme kinetics in response to oxidative conditions. 1 Publication | 1 | |
Mutagenesisi | 290 | S → F: 2-fold reduction in catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 302 | E → G: Decreases catalytic activity. Increases affinity for malonyl-CoA. 1 Publication | 1 | |
Mutagenesisi | 329 | S → A: 110-fold reduction in catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 423 | H → N: 7-fold reduction in catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 456 | Y → S: 3.5-fold reduction in catalytic activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 23417 |
MalaCardsi | MLYCD |
MIMi | 248360, phenotype |
OpenTargetsi | ENSG00000103150 |
Orphaneti | 943, Malonic aciduria |
PharmGKBi | PA30861 |
Miscellaneous databases
Pharosi | O95822, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4698 |
GuidetoPHARMACOLOGYi | 1275 |
Genetic variation databases
BioMutai | MLYCD |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 39 | MitochondrionSequence analysisAdd BLAST | 39 | |
ChainiPRO_0000021088 | 40 – 493 | Malonyl-CoA decarboxylase, mitochondrialAdd BLAST | 454 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 59 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 168 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 168 | N6-succinyllysine; alternateBy similarity | 1 | |
Disulfide bondi | 206 | InterchainSequence analysis | ||
Modified residuei | 211 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 222 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 389 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 472 | N6-acetyllysineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Disulfide bondProteomic databases
EPDi | O95822 |
jPOSTi | O95822 |
MassIVEi | O95822 |
MaxQBi | O95822 |
PaxDbi | O95822 |
PeptideAtlasi | O95822 |
PRIDEi | O95822 |
ProteomicsDBi | 51071 [O95822-1] |
PTM databases
iPTMneti | O95822 |
PhosphoSitePlusi | O95822 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000103150, Expressed in heart left ventricle and 201 other tissues |
ExpressionAtlasi | O95822, baseline and differential |
Genevisiblei | O95822, HS |
Organism-specific databases
HPAi | ENSG00000103150, Tissue enhanced (tongue) |
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 PublicationsBinary interactionsi
O95822
With | #Exp. | IntAct |
---|---|---|
itself | 4 | EBI-10714916,EBI-10714916 |
Isoform Cytoplasmic+peroxisomal [O95822-2]
With | #Exp. | IntAct |
---|---|---|
RBM5 [P52756] | 4 | EBI-13315321,EBI-714003 |
UBALD1 [Q8TB05] | 3 | EBI-13315321,EBI-725656 |
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 116989, 26 interactors |
DIPi | DIP-60405N |
IntActi | O95822, 17 interactors |
STRINGi | 9606.ENSP00000262430 |
Chemistry databases
BindingDBi | O95822 |
Miscellaneous databases
RNActi | O95822, protein |
Structurei
Secondary structure
3D structure databases
SMRi | O95822 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 40 – 190 | Alpha-helical domainAdd BLAST | 151 | |
Regioni | 191 – 493 | Catalytic domainAdd BLAST | 303 | |
Regioni | 299 – 305 | Malonyl-CoA bindingCurated | 7 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 491 – 493 | Microbody targeting signalSequence analysis | 3 |
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG3018, Eukaryota |
GeneTreei | ENSGT00390000005410 |
HOGENOMi | CLU_023433_0_0_1 |
InParanoidi | O95822 |
OMAi | PIDWSTP |
OrthoDBi | 1436590at2759 |
PhylomeDBi | O95822 |
TreeFami | TF312959 |
Family and domain databases
Gene3Di | 1.20.140.90, 1 hit 3.40.630.150, 1 hit |
InterProi | View protein in InterPro IPR038917, Malonyl_CoA_deC IPR007956, Malonyl_CoA_deC_C IPR042303, Malonyl_CoA_deC_C_sf IPR035372, MCD_N IPR038351, MCD_N_sf |
PANTHERi | PTHR28641, PTHR28641, 1 hit |
Pfami | View protein in Pfam PF05292, MCD, 1 hit PF17408, MCD_N, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative initiation. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
The sequence of this isoform differs from the canonical sequence as follows:
1-39: Missing.
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A087X1B8 | A0A087X1B8_HUMAN | Malonyl-CoA decarboxylase, mitochon... | MLYCD | 175 | Annotation score: | ||
V9GY18 | V9GY18_HUMAN | Malonyl-CoA decarboxylase, mitochon... | MLYCD | 98 | Annotation score: | ||
V9GYW3 | V9GYW3_HUMAN | Malonyl-CoA decarboxylase, mitochon... | MLYCD | 91 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 82 | A → D in AAD16177 (PubMed:10417274).Curated | 1 | |
Sequence conflicti | 119 | A → S in AAD48994 (PubMed:9869665).Curated | 1 | |
Sequence conflicti | 127 | D → V in AAD48994 (PubMed:9869665).Curated | 1 | |
Sequence conflicti | 192 | S → P in AAD34631 (PubMed:10455107).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_047649 | 1 – 39 | Missing in isoform Cytoplasmic+peroxisomal. 3 PublicationsAdd BLAST | 39 |
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 |
CCDSi | CCDS42206.1 [O95822-1] |
RefSeqi | NP_036345.2, NM_012213.2 [O95822-1] |
Genome annotation databases
Ensembli | ENST00000262430; ENSP00000262430; ENSG00000103150 |
GeneIDi | 23417 |
KEGGi | hsa:23417 |
MANE-Selecti | ENST00000262430.6; ENSP00000262430.4; NM_012213.3; NP_036345.2 |
UCSCi | uc002fgz.4, human [O95822-1] |
Keywords - Coding sequence diversityi
Alternative initiationSimilar 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 |
CCDSi | CCDS42206.1 [O95822-1] |
RefSeqi | NP_036345.2, NM_012213.2 [O95822-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2YGW | X-ray | 2.80 | A/B | 40-490 | [»] | |
4F0X | X-ray | 3.29 | A/B/C/D/E/F/G/H | 39-493 | [»] | |
SMRi | O95822 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 116989, 26 interactors |
DIPi | DIP-60405N |
IntActi | O95822, 17 interactors |
STRINGi | 9606.ENSP00000262430 |
Chemistry databases
BindingDBi | O95822 |
ChEMBLi | CHEMBL4698 |
GuidetoPHARMACOLOGYi | 1275 |
SwissLipidsi | SLP:000000251 |
PTM databases
iPTMneti | O95822 |
PhosphoSitePlusi | O95822 |
Genetic variation databases
BioMutai | MLYCD |
Proteomic databases
EPDi | O95822 |
jPOSTi | O95822 |
MassIVEi | O95822 |
MaxQBi | O95822 |
PaxDbi | O95822 |
PeptideAtlasi | O95822 |
PRIDEi | O95822 |
ProteomicsDBi | 51071 [O95822-1] |
Protocols and materials databases
Antibodypediai | 30519, 111 antibodies from 22 providers |
DNASUi | 23417 |
Genome annotation databases
Ensembli | ENST00000262430; ENSP00000262430; ENSG00000103150 |
GeneIDi | 23417 |
KEGGi | hsa:23417 |
MANE-Selecti | ENST00000262430.6; ENSP00000262430.4; NM_012213.3; NP_036345.2 |
UCSCi | uc002fgz.4, human [O95822-1] |
Organism-specific databases
CTDi | 23417 |
DisGeNETi | 23417 |
GeneCardsi | MLYCD |
HGNCi | HGNC:7150, MLYCD |
HPAi | ENSG00000103150, Tissue enhanced (tongue) |
MalaCardsi | MLYCD |
MIMi | 248360, phenotype 606761, gene |
neXtProti | NX_O95822 |
OpenTargetsi | ENSG00000103150 |
Orphaneti | 943, Malonic aciduria |
PharmGKBi | PA30861 |
VEuPathDBi | HostDB:ENSG00000103150 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3018, Eukaryota |
GeneTreei | ENSGT00390000005410 |
HOGENOMi | CLU_023433_0_0_1 |
InParanoidi | O95822 |
OMAi | PIDWSTP |
OrthoDBi | 1436590at2759 |
PhylomeDBi | O95822 |
TreeFami | TF312959 |
Enzyme and pathway databases
UniPathwayi | UPA00340;UER00710 |
BRENDAi | 4.1.1.9, 2681 |
PathwayCommonsi | O95822 |
Reactomei | R-HSA-390247, Beta-oxidation of very long chain fatty acids [O95822-2] R-HSA-9033241, Peroxisomal protein import [O95822-2] |
SABIO-RKi | O95822 |
SignaLinki | O95822 |
Miscellaneous databases
BioGRID-ORCSi | 23417, 5 hits in 1047 CRISPR screens |
ChiTaRSi | MLYCD, human |
GenomeRNAii | 23417 |
Pharosi | O95822, Tchem |
PROi | PR:O95822 |
RNActi | O95822, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000103150, Expressed in heart left ventricle and 201 other tissues |
ExpressionAtlasi | O95822, baseline and differential |
Genevisiblei | O95822, HS |
Family and domain databases
Gene3Di | 1.20.140.90, 1 hit 3.40.630.150, 1 hit |
InterProi | View protein in InterPro IPR038917, Malonyl_CoA_deC IPR007956, Malonyl_CoA_deC_C IPR042303, Malonyl_CoA_deC_C_sf IPR035372, MCD_N IPR038351, MCD_N_sf |
PANTHERi | PTHR28641, PTHR28641, 1 hit |
Pfami | View protein in Pfam PF05292, MCD, 1 hit PF17408, MCD_N, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | DCMC_HUMAN | |
Accessioni | O95822Primary (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: | February 23, 2022 | |
This is version 182 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references