Biology:MBD3

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Methyl-CpG-binding domain protein 3 is a protein that in humans is encoded by the MBD3 gene.

Function

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). However, unlike the other family members, MBD3 is not capable of binding to methylated DNA but instead binds to hydroxymethylated DNA. The predicted MBD3 protein shares 71% and 94% identity with MBD2 (isoform 1) and mouse Mbd3. MBD3 is a subunit of the NuRD, a multisubunit complex containing nucleosome remodeling and histone deacetylase activities. MBD3 mediates the association of metastasis-associated protein 2 (MTA2) with the core histone deacetylase complex.

MBD3 also contains the coiled‐coil domain common to all three MBD3 isoforms. The coiled‐coil domain, but not the MBD domain, helps to maintain pluripotency of embryonic stem cells via the recruitment of polycomb repressive complex 2 to a subset of genes linked to development and organogenesis, thus establishing stable transcriptional repression.

Interactions

MBD3 has been shown to interact with:

• AURKA,
• GATAD2B,
• HDAC1,
• MTA2, and
• MBD2.

Further reading

• "5-Hydroxymethylcytosine: generation, fate, and genomic distribution". Current Opinion in Cell Biology 25 (3): 289–96. June 2013. doi:10.1016/j.ceb.2013.02.017. PMID 23498661. 
• "Soluble bovine galactose-binding lectin. cDNA cloning reveals the complete amino acid sequence and an antigenic relationship with the major encephalitogenic domain of myelin basic protein". The Biochemical Journal 259 (1): 283–90. April 1989. doi:10.1042/bj2590283. PMID 2470348. 
• "The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities". Cell 95 (2): 279–89. October 1998. doi:10.1016/S0092-8674(00)81758-4. PMID 9790534. 
• "Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex". Nature 395 (6705): 917–21. October 1998. doi:10.1038/27699. PMID 9804427. Bibcode: 1998Natur.395..917T. 
• "Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation". Genes & Development 13 (15): 1924–35. August 1999. doi:10.1101/gad.13.15.1924. PMID 10444591. 
• "Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation". Nature Genetics 23 (1): 62–6. September 1999. doi:10.1038/12664. PMID 10471500. 
• "MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase". Genes to Cells 5 (8): 677–88. August 2000. doi:10.1046/j.1365-2443.2000.00359.x. PMID 10947852. 
• "Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1". The Journal of Biological Chemistry 276 (9): 6817–24. March 2001. doi:10.1074/jbc.M007372200. PMID 11102443. 
• "Sharp, an inducible cofactor that integrates nuclear receptor repression and activation". Genes & Development 15 (9): 1140–51. May 2001. doi:10.1101/gad.871201. PMID 11331609. 
• "Identification and functional characterization of the p66/p68 components of the MeCP1 complex". Molecular and Cellular Biology 22 (2): 536–46. January 2002. doi:10.1128/MCB.22.2.536-546.2002. PMID 11756549. 
• "Expression of the genes of methyl-binding domain proteins in human gliomas". Oncology Reports 9 (2): 393–5. 2002. doi:10.3892/or.9.2.393. PMID 11836615. 
• "The mCpG-binding domain of human MBD3 does not bind to mCpG but interacts with NuRD/Mi2 components HDAC1 and MTA2". The Journal of Biological Chemistry 277 (38): 35434–9. September 2002. doi:10.1074/jbc.M203455200. PMID 12124384. 
• "Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3". The Journal of Biological Chemistry 277 (43): 40958–66. October 2002. doi:10.1074/jbc.M207467200. PMID 12183469. 
• "MBD3 and HDAC1, two components of the NuRD complex, are localized at Aurora-A-positive centrosomes in M phase". The Journal of Biological Chemistry 277 (50): 48714–23. December 2002. doi:10.1074/jbc.M208461200. PMID 12354758. 
• "MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer". Cell 113 (2): 207–19. April 2003. doi:10.1016/S0092-8674(03)00234-4. PMID 12705869. 
• "MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation". Cell 119 (1): 75–86. October 2004. doi:10.1016/j.cell.2004.09.014. PMID 15454082.