Methylcrotonoyl-CoA carboxylase subunit beta is an enzyme that in humans is encoded by the MCCC2 gene .[ 5]
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 .[ 6]
Clinical significance [ edit ] 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.[ 7] [ 8] [ 9] [ 10] mitochondrial dynamics, apoptosis , and energy metabolism, promoting cell proliferation and migration in prostate and colorectal cancers [ 11] GLUD1 –p38 MAPK signaling.[ 12]
^ a b c ENSG00000281742, ENSG00000275300 GRCh38: Ensembl release 89: ENSG00000131844, ENSG00000281742, ENSG00000275300 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021646 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "MCCC2 gene: MedlinePlus Genetics" . MedlinePlus Genetics . U.S. National Library of Medicine, National Institutes of Health. Retrieved October 20, 2025 .^ Plaza-Pegueroles A, Aphasizheva I, Aphasizhev R, Fernández-Tornero C, Ruiz FM (July 2024). "The cryo-EM structure of trypanosome 3-methylcrotonyl-CoA carboxylase provides mechanistic and dynamic insights into its enzymatic function" . Structure . 32 (7): 930–940.e3. doi :10.1016/j.str.2024.03.010 . PMC 11246232 PMID 38593794 . ^ Grünert SC, Stucki M, Morscher RJ, Suormala T, Bürer C, Burda P, et al. (May 2012). "3-methylcrotonyl-CoA carboxylase deficiency: clinical, biochemical, enzymatic and molecular studies in 88 individuals" . Orphanet Journal of Rare Diseases . 7 31. doi :10.1186/1750-1172-7-31 PMC 3495011 PMID 22642865 . ^ "3-methylcrotonyl-CoA carboxylase deficiency" . Orphanet . INSERM US14, Université de Lyon, France. Retrieved October 20, 2025 .^ "3-methylcrotonyl-CoA carboxylase deficiency – MedlinePlus Genetics" . MedlinePlus Genetics . U.S. National Library of Medicine, National Institutes of Health. October 1, 2008. Retrieved October 20, 2025 .^ Baumgartner MR, Almashanu S, Suormala T, Obie C, Cole RN, Packman S, et al. (February 2001). "The molecular basis of human 3-methylcrotonyl-CoA carboxylase deficiency" . The Journal of Clinical Investigation . 107 (4): 495– 504. doi :10.1172/JCI11948 . PMC 199271 PMID 11181649 . ^ Liu W, Chen S, Xie W, Wang Q, Luo Q, Huang M, et al. (October 2023). "MCCC2 is a novel mediator between mitochondria and telomere and functions as an oncogene in colorectal cancer" . Cellular & Molecular Biology Letters . 28 (1) 80. doi :10.1186/s11658-023-00487-0 PMC 10571261 PMID 37828426 . ^ He J, Mao Y, Huang W, Li M, Zhang H, Qing Y, et al. (2020). "Methylcrotonoyl-CoA Carboxylase 2 Promotes Proliferation, Migration and Invasion and Inhibits Apoptosis of Prostate Cancer Cells Through Regulating GLUD1-P38 MAPK Signaling Pathway" . OncoTargets and Therapy . 13 : 7317– 7327. doi :10.2147/OTT.S249906 PMC 7395692 PMID 32801758 .
