MMACHC

Methylmalonic aciduria and homocystinuria type C protein (MMACHC) is a protein that in humans is encoded by the MMACHC gene.[5]

MMACHC
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3SBY, 3SBZ, 3SC0, 3SOM
Identifiers
Aliases	MMACHC, cblC, methylmalonic aciduria (cobalamin deficiency) cblC type, with homocystinuria, metabolism of cobalamin associated C
External IDs	OMIM: 609831 MGI: 1914346 HomoloGene: 12082 GeneCards: MMACHC
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p34.1 Start 45,500,300 bp[1] End 45,513,382 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 D1 Start 116,702,279 bp[2] End 116,708,406 bp[2]
Gene ontology Molecular function • cobalamin binding • GO:0001948 protein binding • FAD binding • demethylase activity • protein homodimerization activity • glutathione binding • cyanocobalamin reductase (cyanide-eliminating) activity • oxidoreductase activity Cellular component • cytosol • cytoplasm Biological process • demethylation • oxidation-reduction process • glutathione metabolic process • Cobalamin biosynthesis • cobalamin metabolic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	25974	67096
Ensembl	ENSG00000132763	ENSMUSG00000028690
UniProt	Q9Y4U1	Q9CZD0
RefSeq (mRNA)	NM_015506 NM_001330540	NM_025962
RefSeq (protein)	NP_001317469 NP_056321	NP_080238
Location (UCSC)	Chr 1: 45.5 – 45.51 Mb	Chr 4: 116.7 – 116.71 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The C-terminal region of the product of the MMACHC gene is similar to TonB, a bacterial protein involved in energy transduction for cobalamin uptake.[5] The MMACHC gene product catalyzes the decyanation of cyanocobalamin as well as the dealkylation of alkylcobalamins including methylcobalamin and adenosylcobalamin.[6] This function has also been attributed to cobalamin reductases.[7] The MMACHC gene product and cobalamin reductases enable the interconversion of cyano- and alkylcobalamins.[8][9]

Clinical significance

Mutations are associated with methylmalonic acidemia.[5][10][11][12]

References

1. GRCh38: Ensembl release 89: ENSG00000132763 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028690 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Lerner-Ellis JP, Tirone JC, Pawelek PD, Doré C, Atkinson JL, Watkins D, Morel CF, Fujiwara TM, Moras E, Hosack AR, Dunbar GV, Antonicka H, Forgetta V, Dobson CM, Leclerc D, Gravel RA, Shoubridge EA, Coulton JW, Lepage P, Rommens JM, Morgan K, Rosenblatt DS (January 2006). "Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type". Nat. Genet. 38 (1): 93–100. doi:10.1038/ng1683. PMID 16311595. S2CID 7688576.
6. Luciana Hannibal, Jihoe Kim, Nicola E. Brasch, Sihe Wang, David S. Rosenblatt, Ruma Banerjee, and Donald W. Jacobsen (August 2009). "Processing of alkylcobalamins in mammalian cells: a role for the MMACHC (cblC) gene product". Mol Genet Metab. 2009 Aug; 97(4): 260–266.
7. Watanabe F, Nakano Y. "Purification and characterization of aquacobalamin reductases from mammals". Methods Enzymol. 1997;281;295-305.
8. Quadros EV, Jackson B, Hoffbrand AV, Linnell JC. "Interconversion of cobalamins in human lymphocytes in vitro and the influence of nitrous oxide on the synthesis of cobalamin coenzymes". Vitamin B12, Proceedings of the Third European Symposium on Vitamin B12 and Intrinsic Factor. 1979;1045-1054.
9. Quadros, EV. "Advances in the Understanding of Cobalamin Assimilation and Metabolism". Br J Haematol. 2010 Jan; 148(2): 195–204.
10. Ben-Omran TI, Wong H, Blaser S, Feigenbaum A (May 2007). "Late-onset cobalamin-C disorder: a challenging diagnosis". Am. J. Med. Genet. A. 143A (9): 979–84. doi:10.1002/ajmg.a.31671. PMID 17431913. S2CID 19791175.
11. Morel CF, Lerner-Ellis JP, Rosenblatt DS (August 2006). "Combined methylmalonic aciduria and homocystinuria (cblC): phenotype-genotype correlations and ethnic-specific observations". Mol. Genet. Metab. 88 (4): 315–21. doi:10.1016/j.ymgme.2006.04.001. PMID 16714133.
12. Tsai AC, Morel CF, Scharer G, Yang M, Lerner-Ellis JP, Rosenblatt DS, Thomas JA (October 2007). "Late-onset combined homocystinuria and methylmalonic aciduria (cblC) and neuropsychiatric disturbance". Am. J. Med. Genet. A. 143A (20): 2430–4. doi:10.1002/ajmg.a.31932. PMID 17853453. S2CID 19372503.

Further reading

• Froese DS, Zhang J, Healy S, Gravel RA (2009). "Mechanism of vitamin B12-responsiveness in cblC methylmalonic aciduria with homocystinuria". Mol. Genet. Metab. 98 (4): 338–43. doi:10.1016/j.ymgme.2009.07.014. PMID 19700356.
• Tang H, Hao H, Tang SH, et al. (2009). "[Mutation analysis of the MMACHC gene in a pedigree with methylmalonic aciduria]". Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 26 (1): 62–5. doi:10.3760/cma.j.issn.1003-9406.2009.01.014. PMID 19199254.
• Profitlich LE, Kirmse B, Wasserstein MP, et al. (2009). "High prevalence of structural heart disease in children with cblC-type methylmalonic aciduria and homocystinuria". Mol. Genet. Metab. 98 (4): 344–8. doi:10.1016/j.ymgme.2009.07.017. PMID 19767224.
• Nogueira C, Aiello C, Cerone R, et al. (2008). "Spectrum of MMACHC mutations in Italian and Portuguese patients with combined methylmalonic aciduria and homocystinuria, cblC type". Mol. Genet. Metab. 93 (4): 475–80. doi:10.1016/j.ymgme.2007.11.005. PMID 18164228.
• Gregory SG, Barlow KF, McLay KE, et al. (2006). "The DNA sequence and biological annotation of human chromosome 1". Nature. 441 (7091): 315–21. Bibcode:2006Natur.441..315G. doi:10.1038/nature04727. PMID 16710414. S2CID 4431933.
• Lerner-Ellis JP, Anastasio N, Liu J, et al. (2009). "Spectrum of mutations in MMACHC, allelic expression, and evidence for genotype-phenotype correlations". Hum. Mutat. 30 (7): 1072–81. doi:10.1002/humu.21001. PMID 19370762. S2CID 2767341.
• Hannibal L, Kim J, Brasch NE, et al. (2009). "Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product". Mol. Genet. Metab. 97 (4): 260–6. doi:10.1016/j.ymgme.2009.04.005. PMC 2709701. PMID 19447654.
• Thauvin-Robinet C, Roze E, Couvreur G, et al. (2008). "The adolescent and adult form of cobalamin C disease: clinical and molecular spectrum". J. Neurol. Neurosurg. Psychiatry. 79 (6): 725–8. doi:10.1136/jnnp.2007.133025. PMID 18245139. S2CID 23493993.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Kim J, Hannibal L, Gherasim C, et al. (2009). "A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins". J. Biol. Chem. 284 (48): 33418–24. doi:10.1074/jbc.M109.057877. PMC 2785186. PMID 19801555.
• Richard E, Jorge-Finnigan A, Garcia-Villoria J, et al. (2009). "Genetic and cellular studies of oxidative stress in methylmalonic aciduria (MMA) cobalamin deficiency type C (cblC) with homocystinuria (MMACHC)". Hum. Mutat. 30 (11): 1558–66. doi:10.1002/humu.21107. PMID 19760748. S2CID 42657972.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Loewy AD, Niles KM, Anastasio N, et al. (2009). "Epigenetic modification of the gene for the vitamin B(12) chaperone MMACHC can result in increased tumorigenicity and methionine dependence". Mol. Genet. Metab. 96 (4): 261–7. doi:10.1016/j.ymgme.2008.12.011. PMID 19200761.
• Kim J, Gherasim C, Banerjee R (2008). "Decyanation of vitamin B12 by a trafficking chaperone". Proc. Natl. Acad. Sci. U.S.A. 105 (38): 14551–4. Bibcode:2008PNAS..10514551K. doi:10.1073/pnas.0805989105. PMC 2567227. PMID 18779575.

External links

• GeneReviews/NCBI/NIH/UW entry on Disorders of Intracellular Cobalamin Metabolism