MCCC2

Methylcrotonoyl-CoA carboxylase subunit beta is an enzyme that in humans is encoded by the MCCC2 gene.

Function

MCCC2 encodes the β-subunit of the mitochondrial enzyme methylcrotonoyl-CoA carboxylase (MCC), which catalyzes the biotin-dependent carboxylation of 3-methylcrotonoyl-CoA to 3-methylglutaconyl-CoA in the catabolic pathway of the branched-chain amino acid leucine. The β-subunit encoded by MCCC2 contains the carboxyltransferase domain that forms active sites at the interface of β-subunit dimers within the MCC α6β6 holoenzyme.

Clinical significance

Pathogenic variants in MCCC2 cause 3-methylcrotonyl-CoA carboxylase deficiency, an autosomal recessive inborn error of leucine metabolism that can manifest with metabolic acidosis, developmental delay, or remain clinically asymptomatic. Beyond its metabolic role, MCCC2 has been implicated in tumorigenesis through modulation of mitochondrial dynamics, apoptosis, and energy metabolism, promoting cell proliferation and migration in prostate and colorectal cancers via pathways such as GLUD1–p38 MAPK signaling.