MBD3

MBD3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2MB7
Identifiers
Aliases	MBD3
External IDs	MGI: 1333812 HomoloGene: 2917 GeneCards: MBD3
Gene ontology Molecular function • methyl-CpG binding • DNA binding • nucleosomal DNA binding • RNA polymerase II distal enhancer sequence-specific DNA binding • protein binding • RNA polymerase II core promoter proximal region sequence-specific DNA binding • chromatin binding • histone deacetylase activity Cellular component • nucleus • nucleoplasm • protein complex • nuclear chromatin • heterochromatin • chromosome • NuRD complex • cytoplasm • chromatin Biological process • response to estradiol • tissue development • embryonic organ development • regulation of DNA methylation • in utero embryonic development • response to organic cyclic compound • regulation of transcription, DNA-templated • ATP-dependent chromatin remodeling • heart development • methylation-dependent chromatin silencing • histone acetylation • negative regulation of transcription from RNA polymerase II promoter • aging • brain development • response to nutrient levels • transcription, DNA-templated • regulation of signal transduction by p53 class mediator • histone deacetylation Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	53615	17192
Ensembl	ENSG00000071655	ENSMUSG00000035478
UniProt	O95983	Q9Z2D8
RefSeq (mRNA)	NM_003926 NM_001281453 NM_001281454	NM_013595 NM_001306143
RefSeq (protein)	NP_001268382.1 NP_001268383.1	NP_001293072.1 NP_038623.1
Location (UCSC)	Chr 19: 1.57 – 1.59 Mb	Chr 10: 80.39 – 80.4 Mb
PubMed search	[1]	[2]
Wikidata

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Methyl-CpG-binding domain protein 3 is a protein that in humans is encoded by the MBD3 gene.^[3][4][5]

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.^[5]

Interactions

MBD3 has been shown to interact with:

• AURKA,^[6]
• GATAD2B,^[7][8]
• HDAC1,^[6][9][10]
• MTA2,^[6][9][10] and
• MBD2.^[9][11]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Hendrich B, Bird A (Nov 1998). "Identification and characterization of a family of mammalian methyl-CpG binding proteins". Mol Cell Biol. 18 (11): 6538–47. PMC 109239. PMID 9774669.
4. Hendrich B, Abbott C, McQueen H, Chambers D, Cross S, Bird A (Sep 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.
5. "Entrez Gene: MBD3 methyl-CpG binding domain protein 3".
6. Sakai H, Urano T, Ookata K, Kim MH, Hirai Y, Saito M, Nojima Y, Ishikawa F (2002). "MBD3 and HDAC1, two components of the NuRD complex, are localized at Aurora-A-positive centrosomes in M phase". J. Biol. Chem. 277 (50): 48714–23. doi:10.1074/jbc.M208461200. PMID 12354758.
7. Brackertz M, Boeke J, Zhang R, Renkawitz R (2002). "Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3". J. Biol. Chem. 277 (43): 40958–66. doi:10.1074/jbc.M207467200. PMID 12183469.
8. Feng Q, Cao R, Xia L, Erdjument-Bromage H, Tempst P, Zhang Y (2002). "Identification and functional characterization of the p66/p68 components of the MeCP1 complex". Mol. Cell. Biol. 22 (2): 536–46. doi:10.1128/MCB.22.2.536-546.2002. PMC 139742. PMID 11756549.
9. Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D (1999). "Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation". Genes Dev. 13 (15): 1924–35. doi:10.1101/gad.13.15.1924. PMC 316920. PMID 10444591.
10. Saito M, Ishikawa F (2002). "The mCpG-binding domain of human MBD3 does not bind to mCpG but interacts with NuRD/Mi2 components HDAC1 and MTA2". J. Biol. Chem. 277 (38): 35434–9. doi:10.1074/jbc.M203455200. PMID 12124384.
11. Jiang CL, Jin SG, Pfeifer GP (2004). "MBD3L1 is a transcriptional repressor that interacts with methyl-CpG-binding protein 2 (MBD2) and components of the NuRD complex". J. Biol. Chem. 279 (50): 52456–64. doi:10.1074/jbc.M409149200. PMID 15456747.

Further reading

• Shen L, Zhang Y (2013). "5-Hydroxymethylcytosine: generation, fate, and genomic distribution". Current Opinion in Cell Biology. 25 (3): 289–96. doi:10.1016/j.ceb.2013.02.017. PMID 23498661.
• Abbott WM, Mellor A, Edwards Y, Feizi T (1989). "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.". Biochem. J. 259 (1): 283–90. PMC 1138502. PMID 2470348.
• Zhang Y, LeRoy G, Seelig HP, Lane WS, Reinberg D (1998). "The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities.". Cell. 95 (2): 279–89. doi:10.1016/S0092-8674(00)81758-4. PMID 9790534.
• Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL (1998). "Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex.". Nature. 395 (6705): 917–21. doi:10.1038/27699. PMID 9804427.
• Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D (1999). "Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation.". Genes Dev. 13 (15): 1924–35. doi:10.1101/gad.13.15.1924. PMC 316920. PMID 10444591.
• Wade PA, Gegonne A, Jones PL, Ballestar E, Aubry F, Wolffe AP (1999). "Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation.". Nat. Genet. 23 (1): 62–6. doi:10.1038/12664. PMID 10471500.
• Tatematsu KI, Yamazaki T, Ishikawa F (2000). "MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase.". Genes Cells. 5 (8): 677–88. doi:10.1046/j.1365-2443.2000.00359.x. PMID 10947852.
• Humphrey GW, Wang Y, Russanova VR, Hirai T, Qin J, Nakatani Y, Howard BH (2001). "Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1.". J. Biol. Chem. 276 (9): 6817–24. doi:10.1074/jbc.M007372200. PMID 11102443.
• Shi Y, Downes M, Xie W, Kao HY, Ordentlich P, Tsai CC, Hon M, Evans RM (2001). "Sharp, an inducible cofactor that integrates nuclear receptor repression and activation.". Genes Dev. 15 (9): 1140–51. doi:10.1101/gad.871201. PMC 312688. PMID 11331609.
• Feng Q, Cao R, Xia L, Erdjument-Bromage H, Tempst P, Zhang Y (2002). "Identification and functional characterization of the p66/p68 components of the MeCP1 complex.". Mol. Cell. Biol. 22 (2): 536–46. doi:10.1128/MCB.22.2.536-546.2002. PMC 139742. PMID 11756549.
• 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. doi:10.3892/or.9.2.393. PMID 11836615.
• Saito M, Ishikawa F (2002). "The mCpG-binding domain of human MBD3 does not bind to mCpG but interacts with NuRD/Mi2 components HDAC1 and MTA2.". J. Biol. Chem. 277 (38): 35434–9. doi:10.1074/jbc.M203455200. PMID 12124384.
• Brackertz M, Boeke J, Zhang R, Renkawitz R (2002). "Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3.". J. Biol. Chem. 277 (43): 40958–66. doi:10.1074/jbc.M207467200. PMID 12183469.
• Sakai H, Urano T, Ookata K, Kim MH, Hirai Y, Saito M, Nojima Y, Ishikawa F (2003). "MBD3 and HDAC1, two components of the NuRD complex, are localized at Aurora-A-positive centrosomes in M phase.". J. Biol. Chem. 277 (50): 48714–23. doi:10.1074/jbc.M208461200. PMID 12354758.
• Fujita N, Jaye DL, Kajita M, Geigerman C, Moreno CS, Wade PA (2003). "MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer.". Cell. 113 (2): 207–19. doi:10.1016/S0092-8674(03)00234-4. PMID 12705869.
• Fujita N, Jaye DL, Geigerman C, Akyildiz A, Mooney MR, Boss JM, Wade PA (2004). "MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation.". Cell. 119 (1): 75–86. doi:10.1016/j.cell.2004.09.014. PMID 15454082.