MBD4

Methyl-CpG binding domain protein 4
PDB rendering based on 1ngn.
Available structures PDB 1ngn
Identifiers
Symbols	MBD4; MED1
External IDs	OMIM: 603574 MGI: 1333850 HomoloGene: 2916 GeneCards: MBD4 Gene
Gene Ontology Molecular function • DNA binding • satellite DNA binding • endodeoxyribonuclease activity • protein binding • hydrolase activity • DNA N-glycosylase activity Cellular component • chromatin • nucleus • nucleoplasm • nucleolus • cytoplasm Biological process • DNA repair • base-excision repair • base-excision repair, AP site formation • DNA damage response, signal transduction resulting in induction of apoptosis • response to radiation • depyrimidination Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8930	17193
Ensembl	ENSG00000129071	ENSMUSG00000030322
UniProt	O95243	Q3TU27
RefSeq (mRNA)	NM_003925	NM_010774.2
RefSeq (protein)	NP_003916	NP_034904.2
Location (UCSC)	Chr 3: 129.15 – 129.16 Mb	Chr 6: 115.79 – 115.8 Mb
PubMed search	[1]	[2]

Methyl-CpG-binding domain protein 4 is a protein that in humans is encoded by the MBD4 gene.

DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MBD4 may function to mediate the biological consequences of the methylation signal. In addition, MBD4 has protein sequence similarity to bacterial DNA repair enzymes and thus may have some function in DNA repair. Further, MBD4 gene mutations are detected in tumors with primary microsatellite-instability (MSI), a form of genomic instability associated with defective DNA mismatch repair, and MBD4 gene meets 4 of 5 criteria of a bona fide MIS target gene.

Interactions

MBD4 has been shown to interact with MLH1 and FADD.

Further reading

• Boland CR, Thibodeau SN, Hamilton SR et al (1998). "A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer". Cancer Res. 58 (22): 5248–57. PMID 9823339. 
• Hendrich B, Abbott C, McQueen H et al (1999). "Genomic structure and chromosomal mapping of the murine and human Mbd1, Mbd2, Mbd3, and Mbd4 genes". Mamm. Genome 10 (9): 906–12. doi:10.1007/s003359901112. PMID 10441743. 
• Hendrich B, Hardeland U, Ng HH et al (1999). "The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites". Nature 401 (6750): 301–4. doi:10.1038/45843. PMID 10499592. 
• Riccio A, Aaltonen LA, Godwin AK et al (1999). "The DNA repair gene MBD4 (MED1) is mutated in human carcinomas with microsatellite instability". Nat. Genet. 23 (3): 266–8. doi:10.1038/15443. PMID 10545939. 
• Petronzelli F, Riccio A, Markham GD et al (2000). "Biphasic kinetics of the human DNA repair protein MED1 (MBD4), a mismatch-specific DNA N-glycosylase". J. Biol. Chem. 275 (42): 32422–9. doi:10.1074/jbc.M004535200. PMID 10930409. 
• Petronzelli F, Riccio A, Markham GD et al (2000). "Investigation of the substrate spectrum of the human mismatch-specific DNA N-glycosylase MED1 (MBD4): fundamental role of the catalytic domain". J. Cell. Physiol. 185 (3): 473–80. doi:10.1002/1097-4652(200012)185:3<473::AID-JCP19>3.0.CO;2-#. PMID 11056019. 
• Schlegel J, Güneysu S, Mennel HD (2002). "Expression of the genes of methyl-binding domain proteins in human gliomas". Oncol. Rep. 9 (2): 393–5. PMID 11836615. 
• Jost JP, Thiry S, Siegmann M (2002). "Estradiol receptor potentiates, in vitro, the activity of 5-methylcytosine DNA glycosylase". FEBS Lett. 527 (1–3): 63–6. doi:10.1016/S0014-5793(02)03166-6. PMID 12220634. 
• Yamada T, Koyama T, Ohwada S et al (2002). "Frameshift mutations in the MBD4/MED1 gene in primary gastric cancer with high-frequency microsatellite instability". Cancer Lett. 181 (1): 115–20. doi:10.1016/S0304-3835(02)00043-5. PMID 12430186. 
• Strausberg RL, Feingold EA, Grouse LH et al (2003). "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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Screaton RA, Kiessling S, Sansom OJ et al (2003). "Fas-associated death domain protein interacts with methyl-CpG binding domain protein 4: A potential link between genome surveillance and apoptosis". Proc. Natl. Acad. Sci. U.S.A. 100 (9): 5211–6. doi:10.1073/pnas.0431215100. PMC 154324. PMID 12702765. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=154324. 
• Evertson S, Wallin A, Arbman G et al (2003). "Microsatellite instability and MBD4 mutation in unselected colorectal cancer". Anticancer Res. 23 (4): 3569–74. PMID 12926109. 
• Lehner B, Semple JI, Brown SE et al (2004). "Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region". Genomics 83 (1): 153–67. doi:10.1016/S0888-7543(03)00235-0. PMID 14667819. 
• 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928. 
• Kondo E, Gu Z, Horii A, Fukushige S (2005). "The Thymine DNA Glycosylase MBD4 Represses Transcription and Is Associated with Methylated p16INK4a and hMLH1 Genes". Mol. Cell. Biol. 25 (11): 4388–96. doi:10.1128/MCB.25.11.4388-4396.2005. PMC 1140624. PMID 15899845. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1140624. 
• Zhang X, Krutchinsky A, Fukuda A et al (2005). "MED1/TRAP220 exists predominantly in a TRAP/ Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription". Mol. Cell 19 (1): 89–100. doi:10.1016/j.molcel.2005.05.015. PMID 15989967. 
• Rual JF, Venkatesan K, Hao T et al (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.