MCCC1

Methylcrotonoyl-CoA carboxylase subunit alpha is an enzyme that in humans is encoded by the MCCC1 gene.

MCCC1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2EJM
Identifiers
Aliases	MCCC1, MCC-B, MCCA, methylcrotonoyl-CoA carboxylase 1, methylcrotonyl-CoA carboxylase subunit 1, MCCCalpha
External IDs	OMIM: 609010; MGI: 1919289; HomoloGene: 10603; GeneCards: MCCC1; OMA:MCCC1 - orthologs
Gene location (Human) Chr. Chromosome 3 (human) Band 3q27.1 Start 183,015,218 bp End 183,116,075 bp
Gene location (Mouse) Chr. Chromosome 3 (mouse) Band 3|3 B Start 36,013,461 bp End 36,054,827 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in body of pancreas right lobe of liver right lung right adrenal cortex epithelium of colon human kidney right uterine tube left ovary left adrenal cortex body of stomach Top expressed in brown adipose tissue right kidney right ventricle proximal tubule Epithelium of choroid plexus epithelium of stomach white adipose tissue tunica adventitia of aorta human kidney myocardium of ventricle More reference expression data BioGPS n/a
Gene ontology Molecular function biotin binding nucleotide binding methylcrotonoyl-CoA carboxylase activity ligase activity protein binding ATP binding metal ion binding biotin carboxylase activity Cellular component cytosol mitochondrion mitochondrial matrix methylcrotonoyl-CoA carboxylase complex 3-methylcrotonyl-CoA carboxylase complex, mitochondrial Biological process biotin metabolic process protein heterooligomerization leucine catabolic process branched-chain amino acid catabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 56922 72039 Ensembl ENSG00000078070 ENSMUSG00000027709 UniProt Q96RQ3 Q99MR8 RefSeq (mRNA) NM_001293273 NM_020166 NM_001363880 NM_023644 RefSeq (protein) NP_001280202 NP_064551 NP_001350809 NP_076133 Location (UCSC) Chr 3: 183.02 – 183.12 Mb Chr 3: 36.01 – 36.05 Mb PubMed search
Wikidata
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Function

MCCC1 encodes the α-subunit of the mitochondrial enzyme methylcrotonyl-CoA carboxylase (MCC), which catalyzes a key carboxylation step in the catabolic pathway of the branched-chain amino acid leucine. The MCC holoenzyme forms a dodecameric α6β6 complex in which MCCC1-derived α subunits contain the biotin-binding and carboxylation domains essential for enzymatic activity.

Clinical significance

Pathogenic variants in MCCC1 cause 3-methylcrotonyl-CoA carboxylase deficiency, an autosomal recessive metabolic disorder characterized by impaired leucine degradation and accumulation of organic acid intermediates.

Beyond its metabolic role, MCCC1 has been implicated in immune regulation, where it enhances antiviral signaling through MAVS-mediated activation of NF-κB and interferon pathways, and in neurodegenerative disease genetics, with intronic variants such as rs12637471 associated with altered gene expression and Parkinson’s disease susceptibility.