Methyl-CpG-binding domain protein 2

Methyl-CpG-binding domain protein 2 is a protein that in humans is encoded by the MBD2 gene.[5][6]

MBD2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2L2L
Identifiers
Aliases	MBD2, DMTase, NY-CO-41, methyl-CpG binding domain protein 2
External IDs	OMIM: 603547 MGI: 1333813 HomoloGene: 2918 GeneCards: MBD2
Gene location (Human) Chr. Chromosome 18 (human)[1] Band 18q21.2 Start 54,151,606 bp[1] End 54,224,669 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18 E2|18 44.54 cM Start 70,568,189 bp[2] End 70,626,131 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • DNA binding • protein domain specific binding • methyl-CpG binding • C2H2 zinc finger domain binding • chromatin binding • GO:0001948 protein binding • siRNA binding • nucleosomal DNA binding • satellite DNA binding • mRNA binding Cellular component • cytoplasm • histone deacetylase complex • heterochromatin • chromatin • cell nucleus • nuclear chromatin • nucleoplasm • cytosol • macromolecular complex Biological process • regulation of transcription, DNA-templated • negative regulation of transcription from RNA polymerase II promoter • transcription, DNA-templated • ATP-dependent chromatin remodeling • positive regulation of Wnt signaling pathway • regulation of cell proliferation • maternal behavior • negative regulation of transcription, DNA-templated • aging • response to mechanical stimulus • response to estradiol • cellular response to organic cyclic compound • response to nutrient levels • response to organic cyclic compound • positive regulation of chromatin binding • heart development • embryonic organ development • chromatin silencing at rDNA • regulation of DNA methylation • methylation-dependent chromatin silencing • cellular macromolecular complex assembly Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	8932	17191
Ensembl	ENSG00000134046	ENSMUSG00000024513
UniProt	Q9UBB5	Q9Z2E1
RefSeq (mRNA)	NM_015832 NM_003927	NM_010773 NM_001311071
RefSeq (protein)	NP_003918 NP_056647 NP_056647.1	NP_001298000 NP_034903
Location (UCSC)	Chr 18: 54.15 – 54.22 Mb	Chr 18: 70.57 – 70.63 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1, and MBD2 can also repress transcription from methylated gene promoters. The protein encoded by these genes may function as a mediator of the biological consequences of the methylation signal. It is also reported that MBD2 and MBD3 recruit the NuRD complex to regions of DNA depending on their selective binding of methylated CpG sites. Therefore, MBD2/NuRD and MBD3/NuRD define two distinct protein complexes with different biochemical and functional properties.[7]

Interactions

Methyl-CpG-binding domain protein 2 has been shown to interact with:

• GATAD2B,[8][9]
• HDAC1,[8][10][11]
• Histone deacetylase 2,[8][10][11]
• MBD3[11][12]
• MIZF,[13] and
• SIN3A.[14]

References

1. GRCh38: Ensembl release 89: ENSG00000134046 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000024513 - 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. Hendrich B, Bird A (November 1998). "Identification and Characterization of a Family of Mammalian Methyl-CpG Binding Proteins". Mol Cell Biol. 18 (11): 6538–47. doi:10.1128/mcb.18.11.6538. PMC 109239. PMID 9774669.
6. Hendrich B, Abbott C, McQueen H, Chambers D, Cross S, Bird A (September 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.
7. Guezennec, Xavier (2006). "MBD2/NuRD and MBD3/NuRD, Two Distinct Complexes with Different Biochemical and Functional Properties". Molecular and Cellular Biology. 26 (3): 843–851. doi:10.1128/MCB.26.3.843-851.2006. PMC 1347035. PMID 16428440.
8. Brackertz M, Boeke J, Zhang R, Renkawitz R (October 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.
9. Feng Q, Cao R, Xia L, Erdjument-Bromage H, Tempst P, Zhang Y (January 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.
10. Ng HH, Zhang Y, Hendrich B, Johnson CA, Turner BM, Erdjument-Bromage H, Tempst P, Reinberg D, Bird A (September 1999). "MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex". Nat. Genet. 23 (1): 58–61. doi:10.1038/12659. hdl:1842/684. PMID 10471499.
11. Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D (August 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.
12. Jiang CL, Jin SG, Pfeifer GP (December 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.
13. Sekimata M, Takahashi A, Murakami-Sekimata A, Homma Y (November 2001). "Involvement of a novel zinc finger protein, MIZF, in transcriptional repression by interacting with a methyl-CpG-binding protein, MBD2". J. Biol. Chem. 276 (46): 42632–8. doi:10.1074/jbc.M107048200. PMID 11553631.
14. Boeke J, Ammerpohl O, Kegel S, Moehren U, Renkawitz R (November 2000). "The minimal repression domain of MBD2b overlaps with the methyl-CpG-binding domain and binds directly to Sin3A". J. Biol. Chem. 275 (45): 34963–7. doi:10.1074/jbc.M005929200. PMID 10950960.

Further reading

• Scanlan MJ, Chen YT, Williamson B, Gure AO, Stockert E, Gordan JD, Türeci O, Sahin U, Pfreundschuh M, Old LJ (1998). "Characterization of human colon cancer antigens recognized by autologous antibodies". Int. J. Cancer. 76 (5): 652–8. doi:10.1002/(SICI)1097-0215(19980529)76:5<652::AID-IJC7>3.0.CO;2-P. PMID 9610721.
• 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. Bibcode:1998Natur.395..917T. doi:10.1038/27699. PMID 9804427.
• Bhattacharya SK, Ramchandani S, Cervoni N, Szyf M (1999). "A mammalian protein with specific demethylase activity for mCpG DNA". Nature. 397 (6720): 579–83. Bibcode:1999Natur.397..579B. doi:10.1038/17533. PMID 10050851.
• 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.
• Ng HH, Zhang Y, Hendrich B, Johnson CA, Turner BM, Erdjument-Bromage H, Tempst P, Reinberg D, Bird A (1999). "MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex". Nat. Genet. 23 (1): 58–61. doi:10.1038/12659. hdl:1842/684. PMID 10471499.
• 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.
• Boeke J, Ammerpohl O, Kegel S, Moehren U, Renkawitz R (2001). "The minimal repression domain of MBD2b overlaps with the methyl-CpG-binding domain and binds directly to Sin3A". J. Biol. Chem. 275 (45): 34963–7. doi:10.1074/jbc.M005929200. PMID 10950960.
• 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.
• Feng Q, Zhang Y (2001). "The MeCP1 complex represses transcription through preferential binding, remodeling, and deacetylating methylated nucleosomes". Genes Dev. 15 (7): 827–32. doi:10.1101/gad.876201. PMC 312663. PMID 11297506.
• Sekimata M, Takahashi A, Murakami-Sekimata A, Homma Y (2001). "Involvement of a novel zinc finger protein, MIZF, in transcriptional repression by interacting with a methyl-CpG-binding protein, MBD2". J. Biol. Chem. 276 (46): 42632–8. doi:10.1074/jbc.M107048200. PMID 11553631.
• Müller-Tidow C, Kügler K, Diederichs S, Klümpen S, Möller M, Vogt U, Metzger R, Schneider PM, Berdel WE, Serve H (2001). "Loss of expression of HDAC-recruiting methyl-CpG-binding domain proteins in human cancer". Br. J. Cancer. 85 (8): 1168–74. doi:10.1054/bjoc.2001.2041. PMC 2375156. PMID 11710831.
• 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.
• Bakker J, Lin X, Nelson WG (2002). "Methyl-CpG binding domain protein 2 represses transcription from hypermethylated pi-class glutathione S-transferase gene promoters in hepatocellular carcinoma cells". J. Biol. Chem. 277 (25): 22573–80. doi:10.1074/jbc.M203009200. PMID 11960994.
• 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.
• Detich N, Theberge J, Szyf M (2002). "Promoter-specific activation and demethylation by MBD2/demethylase". J. Biol. Chem. 277 (39): 35791–4. doi:10.1074/jbc.C200408200. PMID 12177048.
• 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.
• Krithivas A, Fujimuro M, Weidner M, Young DB, Hayward SD (2002). "Protein Interactions Targeting the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus to Cell Chromosomes". J. Virol. 76 (22): 11596–604. doi:10.1128/JVI.76.22.11596-11604.2002. PMC 136775. PMID 12388720.