UniProt functional annotation for O95822



	UniProt functional annotation for O95822

UniProt code: O95822.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. {ECO:0000269|PubMed:10455107, ECO:0000269|PubMed:15003260, ECO:0000269|PubMed:18314420, ECO:0000269|PubMed:23482565}.

Catalytic activity: Reaction=H(+) + malonyl-CoA = acetyl-CoA + CO2; Xref=Rhea:RHEA:18781, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57288, ChEBI:CHEBI:57384; EC=4.1.1.9; Evidence={ECO:0000269|PubMed:10417274, ECO:0000269|PubMed:10455107, ECO:0000269|PubMed:15003260, ECO:0000269|PubMed:23482565, ECO:0000269|PubMed:9869665}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18782; Evidence={ECO:0000305|PubMed:23482565};

Activity 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). {ECO:0000269|PubMed:15003260, ECO:0000269|PubMed:23482565}.

Biophysicochemical properties: Kinetic parameters: KM=0.36 mM for malonyl-CoA (Malonyl-CoA decarboxylase mitochondrial form) {ECO:0000269|PubMed:15003260}; KM=0.83 mM for malonyl-CoA (Malonyl-CoA decarboxylase mitochondrial form) {ECO:0000269|PubMed:23482565}; KM=0.22 mM for malonyl-CoA (Malonyl-CoA decarboxylase cytoplasmic+peroxisomal form) {ECO:0000269|PubMed:10455107}; KM=0.33 mM for malonyl-CoA (Malonyl-CoA decarboxylase cytoplasmic+peroxisomal form) {ECO:0000269|PubMed:15003260}; Note=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). {ECO:0000269|PubMed:15003260};

Pathway: Metabolic intermediate biosynthesis; acetyl-CoA biosynthesis; acetyl-CoA from malonyl-CoA: step 1/1.

Subunit: 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. {ECO:0000269|PubMed:23482565, ECO:0000269|PubMed:23791943}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:10417274}. Mitochondrion matrix {ECO:0000269|PubMed:10417274}. Peroxisome {ECO:0000269|PubMed:10417274}. Peroxisome matrix {ECO:0000250|UniProtKB:Q920F5}. Note=Enzymatically active in all three subcellular compartments. {ECO:0000250|UniProtKB:Q920F5}.

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. {ECO:0000269|PubMed:10455107, ECO:0000269|PubMed:18314420}.

Ptm: Acetylation at Lys-472 activates malonyl-CoA decarboxylase activity. Deacetylation at Lys-472 by SIRT4 represses activity, leading to promote lipogenesis (By similarity). {ECO:0000250|UniProtKB:Q99J39}.

Ptm: 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. {ECO:0000305}.

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. {ECO:0000269|PubMed:10417274}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform Cytoplasmic+peroxisomal]: May be produced by alternative initiation at Met-40 of isoform mitochondrial. Alternatively, represents a proteolytic processed form of the mitochondrial form. {ECO:0000305}.

Sequence caution: Sequence=AAD16177.2; Type=Frameshift; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. {ECO:0000269\|PubMed:10455107, ECO:0000269\|PubMed:15003260, ECO:0000269\|PubMed:18314420, ECO:0000269\|PubMed:23482565}.


Catalytic activity:		Reaction=H(+) + malonyl-CoA = acetyl-CoA + CO2; Xref=Rhea:RHEA:18781, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57288, ChEBI:CHEBI:57384; EC=4.1.1.9; Evidence={ECO:0000269\|PubMed:10417274, ECO:0000269\|PubMed:10455107, ECO:0000269\|PubMed:15003260, ECO:0000269\|PubMed:23482565, ECO:0000269\|PubMed:9869665}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18782; Evidence={ECO:0000305\|PubMed:23482565};
Activity 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). {ECO:0000269\|PubMed:15003260, ECO:0000269\|PubMed:23482565}.
Biophysicochemical properties:		Kinetic parameters: KM=0.36 mM for malonyl-CoA (Malonyl-CoA decarboxylase mitochondrial form) {ECO:0000269\|PubMed:15003260}; KM=0.83 mM for malonyl-CoA (Malonyl-CoA decarboxylase mitochondrial form) {ECO:0000269\|PubMed:23482565}; KM=0.22 mM for malonyl-CoA (Malonyl-CoA decarboxylase cytoplasmic+peroxisomal form) {ECO:0000269\|PubMed:10455107}; KM=0.33 mM for malonyl-CoA (Malonyl-CoA decarboxylase cytoplasmic+peroxisomal form) {ECO:0000269\|PubMed:15003260}; Note=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). {ECO:0000269\|PubMed:15003260};
Pathway:		Metabolic intermediate biosynthesis; acetyl-CoA biosynthesis; acetyl-CoA from malonyl-CoA: step 1/1.
Subunit:		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. {ECO:0000269\|PubMed:23482565, ECO:0000269\|PubMed:23791943}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:10417274}. Mitochondrion matrix {ECO:0000269\|PubMed:10417274}. Peroxisome {ECO:0000269\|PubMed:10417274}. Peroxisome matrix {ECO:0000250\|UniProtKB:Q920F5}. Note=Enzymatically active in all three subcellular compartments. {ECO:0000250\|UniProtKB:Q920F5}.
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. {ECO:0000269\|PubMed:10455107, ECO:0000269\|PubMed:18314420}.
Ptm:		Acetylation at Lys-472 activates malonyl-CoA decarboxylase activity. Deacetylation at Lys-472 by SIRT4 represses activity, leading to promote lipogenesis (By similarity). {ECO:0000250\|UniProtKB:Q99J39}.
Ptm:		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. {ECO:0000305}.
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. {ECO:0000269\|PubMed:10417274}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform Cytoplasmic+peroxisomal]: May be produced by alternative initiation at Met-40 of isoform mitochondrial. Alternatively, represents a proteolytic processed form of the mitochondrial form. {ECO:0000305}.
Sequence caution:		Sequence=AAD16177.2; Type=Frameshift; Evidence={ECO:0000305};