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Gene Review

MBD4  -  methyl-CpG binding domain protein 4

Homo sapiens

Synonyms: MED1, Methyl-CpG-binding domain protein 4, Methyl-CpG-binding endonuclease 1, Methyl-CpG-binding protein MBD4, Mismatch-specific DNA N-glycosylase
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Disease relevance of MBD4


High impact information on MBD4


Chemical compound and disease context of MBD4


Biological context of MBD4


Anatomical context of MBD4

  • Reduced expression of DNA repair protein, MBD4, was significantly correlated with poorer tumor differentiation and involvement of portal vein [13].
  • During an analysis of MBD4 expression in HeLa cells we noted the presence of an unexpectedly short reverse transcribed product [14].

Associations of MBD4 with chemical compounds

  • Back-up UDG activities such as SMUG, TDG and MBD4 were not found, underlying the importance of the TcUNG enzyme in protection against uracil in DNA and as a potential target for drug therapy [15].
  • A spectrum of deaminated cis-syn cyclobutane pyrimidine dimers in the supF gene was determined using the mismatch glycosylase activities of MBD4 protein in combination with ligation-mediated PCR [16].
  • The MBD4 gene is involved in the repair of mutation at methyl-CpG dinucleotides [4].
  • Among the methyl CpG binding proteins, MBD2 and MBD4 specifically associated with the methylated promoter and inhibited its activity [17].
  • 5-Methylcytosine DNA glycosylase activity is also present in the human MBD4 (G/T mismatch glycosylase) and in a related avian sequence [18].

Physical interactions of MBD4


Other interactions of MBD4

  • MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1 [12].
  • Expression of MBD2 and MBD4 tagged with green fluorescent protein in mouse cells shows that both proteins colocalize with foci of heavily methylated satellite DNA [9].
  • MBD3 and MBD4/MED1, however, showed a correlation of expression with the grade of malignancy [20].
  • TDG and MBD4 may have specialized roles in the repair of U and T in mismatches in CpG contexts [21].
  • The adjusted odd ratios were 1.25 [95% confidence interval (CI) 1.02-1.53] for the ADPRT 762Ala allele, 1.25 (95% CI 1.02-1.53) for the MBD4 346 Lys allele, 0.78 (95% CI 0.63-0.97) for the LIG3 3704G allele, and 1.38 (95% CI 1.01-1.89) for the XRCC1-77C allele [22].

Analytical, diagnostic and therapeutic context of MBD4


  1. Frequent loss of hMLH1 by promoter hypermethylation leads to microsatellite instability in adenomatous polyps of patients with a single first-degree member affected by colon cancer. Ricciardiello, L., Goel, A., Mantovani, V., Fiorini, T., Fossi, S., Chang, D.K., Lunedei, V., Pozzato, P., Zagari, R.M., De Luca, L., Fuccio, L., Martinelli, G.N., Roda, E., Boland, C.R., Bazzoli, F. Cancer Res. (2003) [Pubmed]
  2. Hyperplastic polyposis syndrome: phenotypic presentations and the role of MBD4 and MYH. Chow, E., Lipton, L., Lynch, E., D'Souza, R., Aragona, C., Hodgkin, L., Brown, G., Winship, I., Barker, M., Buchanan, D., Cowie, S., Nasioulas, S., du Sart, D., Young, J., Leggett, B., Jass, J., Macrae, F. Gastroenterology (2006) [Pubmed]
  3. Somatic frameshift mutations in the MBD4 gene of sporadic colon cancers with mismatch repair deficiency. Bader, S., Walker, M., Hendrich, B., Bird, A., Bird, C., Hooper, M., Wyllie, A. Oncogene (1999) [Pubmed]
  4. Most microsatellite unstable sporadic colorectal carcinomas carry MBD4 mutations. Bader, S., Walker, M., Harrison, D. Br. J. Cancer (2000) [Pubmed]
  5. MBD4 mutations are rare in gastric carcinomas with microsatellite instability. Pinto, M., Wu, Y., Suriano, G., Mensink, R.G., Duval, A., Oliveira, C., Carvalho, B., Hamelin, R., Seruca, R., Hofstra, R.M. Cancer Genet. Cytogenet. (2003) [Pubmed]
  6. The DNA repair gene MBD4 (MED1) is mutated in human carcinomas with microsatellite instability. Riccio, A., Aaltonen, L.A., Godwin, A.K., Loukola, A., Percesepe, A., Salovaara, R., Masciullo, V., Genuardi, M., Paravatou-Petsotas, M., Bassi, D.E., Ruggeri, B.A., Klein-Szanto, A.J., Testa, J.R., Neri, G., Bellacosa, A. Nat. Genet. (1999) [Pubmed]
  7. The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites. Hendrich, B., Hardeland, U., Ng, H.H., Jiricny, J., Bird, A. Nature (1999) [Pubmed]
  8. The thymine DNA glycosylase MBD4 represses transcription and is associated with methylated p16(INK4a) and hMLH1 genes. Kondo, E., Gu, Z., Horii, A., Fukushige, S. Mol. Cell. Biol. (2005) [Pubmed]
  9. Identification and characterization of a family of mammalian methyl-CpG binding proteins. Hendrich, B., Bird, A. Mol. Cell. Biol. (1998) [Pubmed]
  10. MBD3L1 and MBD3L2, two new proteins homologous to the methyl-CpG-binding proteins MBD2 and MBD3: characterization of MBD3L1 as a testis-specific transcriptional repressor. Jiang, C.L., Jin, S.G., Lee, D.H., Lan, Z.J., Xu, X., O'Connor, T.R., Szabó, P.E., Mann, J.R., Cooney, A.J., Pfeifer, G.P. Genomics (2002) [Pubmed]
  11. Sex-specific windows for high mRNA expression of DNA methyltransferases 1 and 3A and methyl-CpG-binding domain proteins 2 and 4 in human fetal gonads. Galetzka, D., Weis, E., Tralau, T., Seidmann, L., Haaf, T. Mol. Reprod. Dev. (2007) [Pubmed]
  12. MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1. Bellacosa, A., Cicchillitti, L., Schepis, F., Riccio, A., Yeung, A.T., Matsumoto, Y., Golemis, E.A., Genuardi, M., Neri, G. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  13. Expression of mRNA for DNA methyltransferases and methyl-CpG-binding proteins and DNA methylation status on CpG islands and pericentromeric satellite regions during human hepatocarcinogenesis. Saito, Y., Kanai, Y., Sakamoto, M., Saito, H., Ishii, H., Hirohashi, S. Hepatology (2001) [Pubmed]
  14. The identification of a novel alternatively spliced form of the MBD4 DNA glycosylase. Owen, R.M., Baker, R.D., Bader, S., Dunlop, M.G., Nicholl, I.D. Oncol. Rep. (2007) [Pubmed]
  15. Trypanosoma cruzi contains a single detectable uracil-DNA glycosylase and repairs uracil exclusively via short patch base excision repair. Peña-Diaz, J., Akbari, M., Sundheim, O., Farez-Vidal, M.E., Andersen, S., Sneve, R., Gonzalez-Pacanowska, D., Krokan, H.E., Slupphaug, G. J. Mol. Biol. (2004) [Pubmed]
  16. Deamination of 5-methylcytosines within cyclobutane pyrimidine dimers is an important component of UVB mutagenesis. Lee, D.H., Pfeifer, G.P. J. Biol. Chem. (2003) [Pubmed]
  17. Epigenetic regulation of metallothionein-i gene expression: differential regulation of methylated and unmethylated promoters by DNA methyltransferases and methyl CpG binding proteins. Majumder, S., Kutay, H., Datta, J., Summers, D., Jacob, S.T., Ghoshal, K. J. Cell. Biochem. (2006) [Pubmed]
  18. 5-Methylcytosine DNA glycosylase activity is also present in the human MBD4 (G/T mismatch glycosylase) and in a related avian sequence. Zhu, B., Zheng, Y., Angliker, H., Schwarz, S., Thiry, S., Siegmann, M., Jost, J.P. Nucleic Acids Res. (2000) [Pubmed]
  19. Human thymine DNA glycosylase (TDG) and methyl-CpG-binding protein 4 (MBD4) excise thymine glycol (Tg) from a Tg:G mispair. Yoon, J.H., Iwai, S., O'Connor, T.R., Pfeifer, G.P. Nucleic Acids Res. (2003) [Pubmed]
  20. Expression of the genes of methyl-binding domain proteins in human gliomas. Schlegel, J., Güneysu, S., Mennel, H.D. Oncol. Rep. (2002) [Pubmed]
  21. Uracil in DNA--occurrence, consequences and repair. Krokan, H.E., Drabløs, F., Slupphaug, G. Oncogene (2002) [Pubmed]
  22. Identification of genetic variants in base excision repair pathway and their associations with risk of esophageal squamous cell carcinoma. Hao, B., Wang, H., Zhou, K., Li, Y., Chen, X., Zhou, G., Zhu, Y., Miao, X., Tan, W., Wei, Q., Lin, D., He, F. Cancer Res. (2004) [Pubmed]
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