MMACHC

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; OMA:MMACHC - orthologs
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 116,559,476 bp [2] End 116,565,603 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver muscle of thigh stromal cell of endometrium ventricular zone mucosa of transverse colon testicle right auricle left ventricle prefrontal cortex right adrenal gland Top expressed in myocardium of ventricle sternocleidomastoid muscle soleus muscle digastric muscle temporal muscle tibialis anterior muscle triceps brachii muscle vastus lateralis muscle extraocular muscle gastrocnemius muscle More reference expression data BioGPS n/a
Gene ontology Molecular function cobalamin binding 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 glutathione metabolic process cobalamin biosynthetic process 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: 116.56 – 116.57 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

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 combined homocystinuria and methylmalonic acidemia. ^{[5] [10] [11] [12] [13]}

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.
13. Sloan, Jennifer L.; Carrillo, Nuria; Adams, David; Venditti, Charles P. (1993), Adam, Margaret P.; Feldman, Jerry; Mirzaa, Ghayda M.; Pagon, Roberta A. (eds.), "Disorders of Intracellular Cobalamin Metabolism", GeneReviews®, Seattle (WA): University of Washington, Seattle, PMID   20301503 , retrieved 2024-02-24

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