Methylcrotonoyl-CoA Carboxylase Beta Chain

MCCC2 encodes the beta subunit of methylcrotonoyl-CoA carboxylase (MCCase), a mitochondrial carboxyltransferase that catalyzes the conversion of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA during leucine and isovaleric acid catabolism (UniProt: Q9HCC0). The protein is 563 amino acids long with a mass of 61.3 kDa.

Mutations in MCCC2 cause 3-methylcrotonoyl-CoA carboxylase 2 deficiency (MCC2D, MIM 210210), an autosomal recessive mitochondrial metabolic disorder with variable severity ranging from neonatal neurological disease to asymptomatic presentation, typically accompanied by characteristic organic aciduria and secondary carnitine deficiency (UniProt: Q9HCC0).

In Alzheimer's disease, MCCC2 expression is upregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change = 0.8032; Chaparral AD proteomics). This modest elevation was detected via TMT-labeled, data-dependent acquisition proteomics across subcellular fractions from human brain tissue, suggesting altered leucine metabolism may accompany neurodegeneration.