Methyl-CpG-binding domain protein 2

NameMethyl-CpG-binding domain protein 2
Synonyms
  • Demethylase
  • DMTase
  • Methyl-CpG-binding protein MBD2
Gene NameMBD2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0001866|Methyl-CpG-binding domain protein 2
MRAHPGGGRCCPEQEEGESAAGGSGAGGDSAIEQGGQGSALAPSPVSGVRREGARGGGRG
RGRWKQAGRGGGVCGRGRGRGRGRGRGRGRGRGRGRPPSGGSGLGGDGGGCGGGGSGGGG
APRREPVPFPSGSAGPGPRGPRATESGKRMDCPALPPGWKKEEVIRKSGLSAGKSDVYYF
SPSGKKFRSKPQLARYLGNTVDLSSFDFRTGKMMPSKLQKNKQRLRNDPLNQNKGKPDLN
TTLPIRQTASIFKQPVTKVTNHPSNKVKSDPQRMNEQPRQLFWEKRLQGLSASDVTEQII
KTMELPKGLQGVGPGSNDETLLSAVASALHTSSAPITGQVSAAVEKNPAVWLNTSQPLCK
AFIVTDEDIRKQEERVQQVRKKLEEALMADILSRAADTEEMDIEMDSGDEA
Number of residues411
Molecular Weight43254.3
Theoretical pI10.76
GO Classification
Functions
  • C2H2 zinc finger domain binding
  • siRNA binding
  • satellite DNA binding
  • mRNA binding
  • methyl-CpG binding
  • chromatin binding
  • protein domain specific binding
Processes
  • gene expression
  • methylation-dependent chromatin silencing
  • regulation of cell proliferation
  • negative regulation of transcription from RNA polymerase II promoter
  • maternal behavior
  • transcription, DNA-templated
  • negative regulation of transcription, DNA-templated
  • positive regulation of Wnt signaling pathway
  • negative regulation of gene expression, epigenetic
  • regulation of gene expression, epigenetic
  • cellular protein complex assembly
  • ATP-dependent chromatin remodeling
Components
  • heterochromatin
  • nucleoplasm
  • nuclear chromatin
  • cytoplasm
  • protein complex
  • nucleus
  • histone deacetylase complex
General FunctionSirna binding
Specific FunctionBinds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides. Binds hemimethylated DNA as well. Recruits histone deacetylases and DNA methyltransferases. Acts as transcriptional repressor and plays a role in gene silencing. Functions as a scaffold protein, targeting GATAD2A and GATAD2B to chromatin to promote repression. May enhance the activation of some unmethylated cAMP-responsive promoters.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID3800793
UniProtKB IDQ9UBB5
UniProtKB Entry NameMBD2_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0019040|Methyl-CpG-binding domain protein 2 (MBD2)
ATGCGCGCGCACCCGGGGGGAGGCCGCTGCTGCCCGGAGCAGGAGGAGGGGGAGAGTGCG
GCGGGCGGCAGCGGCGCTGGCGGCGACTCCGCCATAGAGCAGGGGGGCCAGGGCAGCGCG
CTCGCCCCGTCCCCGGTGAGCGGCGTGCGCAGGGAAGGCGCTCGGGGCGGCGGCCGTGGC
CGGGGGCGGTGGAAGCAGGCGGGCCGGGGCGGCGGCGTCTGTGGCCGTGGCCGGGGCCGG
GGCCGTGGCCGGGGACGGGGACGGGGCCGGGGCCGGGGCCGCGGCCGTCCCCCGAGTGGC
GGCAGCGGCCTTGGCGGCGACGGCGGCGGCTGCGGCGGCGGCGGCAGCGGTGGCGGCGGC
GCCCCCCGGCGGGAGCCGGTCCCTTTCCCGTCGGGGAGCGCGGGGCCGGGGCCCAGGGGA
CCCCGGGCCACGGAGAGCGGGAAGAGGATGGATTGCCCGGCCCTCCCCCCCGGATGGAAG
AAGGAGGAAGTGATCCGAAAATCTGGGCTAAGTGCTGGCAAGAGCGATGTCTACTACTTC
AGTCCAAGTGGTAAGAAGTTCAGAAGCAAGCCTCAGTTGGCAAGGTACCTGGGAAATACT
GTTGATCTCAGCAGTTTTGACTTCAGAACTGGAAAGATGATGCCTAGTAAATTACAGAAG
AACAAACAGAGACTGCGAAACGATCCTCTCAATCAAAATAAGGGTAAACCAGACTTGAAT
ACAACATTGCCAATTAGACAAACAGCATCAATTTTCAAACAACCGGTAACCAAAGTCACA
AATCATCCTAGTAATAAAGTGAAATCAGACCCACAACGAATGAATGAACAGCCACGTCAG
CTTTTCTGGGAGAAGAGGCTACAAGGACTTAGTGCATCAGATGTAACAGAACAAATTATA
AAAACCATGGAACTACCCAAAGGTCTTCAAGGAGTTGGTCCAGGTAGCAATGATGAGACC
CTTTTATCTGCTGTTGCCAGTGCTTTGCACACAAGCTCTGCGCCAATCACAGGGCAAGTC
TCCGCTGCTGTGGAAAAGAACCCTGCTGTTTGGCTTAACACATCTCAACCCCTCTGCAAA
GCTTTTATTGTCACAGATGAAGACATCAGGAAACAGGAAGAGCGAGTACAGCAAGTACGC
AAGAAATTGGAAGAAGCACTGATGGCAGACATCTTGTCGCGAGCTGCTGATACAGAAGAG
ATGGATATTGAAATGGACAGTGGAGATGAAGCCTAA
GenBank Gene IDAF072242
GeneCard IDNot Available
GenAtlas IDMBD2
HGNC IDHGNC:6917
Chromosome Location18
Locus18q21
References
  1. Hendrich B, Bird A: Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol. 1998 Nov;18(11):6538-47. 9774669
  2. Hendrich B, Abbott C, McQueen H, Chambers D, Cross S, Bird A: Genomic structure and chromosomal mapping of the murine and human Mbd1, Mbd2, Mbd3, and Mbd4 genes. Mamm Genome. 1999 Sep;10(9):906-12. 10441743
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  4. Bhattacharya SK, Ramchandani S, Cervoni N, Szyf M: A mammalian protein with specific demethylase activity for mCpG DNA. Nature. 1999 Feb 18;397(6720):579-83. 10050851
  5. Ng HH, Zhang Y, Hendrich B, Johnson CA, Turner BM, Erdjument-Bromage H, Tempst P, Reinberg D, Bird A: MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nat Genet. 1999 Sep;23(1):58-61. 10471499
  6. Tatematsu KI, Yamazaki T, Ishikawa F: MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase. Genes Cells. 2000 Aug;5(8):677-88. 10947852
  7. Boeke J, Ammerpohl O, Kegel S, Moehren U, Renkawitz R: The minimal repression domain of MBD2b overlaps with the methyl-CpG-binding domain and binds directly to Sin3A. J Biol Chem. 2000 Nov 10;275(45):34963-7. 10950960
  8. Humphrey GW, Wang Y, Russanova VR, Hirai T, Qin J, Nakatani Y, Howard BH: Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1. J Biol Chem. 2001 Mar 2;276(9):6817-24. Epub 2000 Dec 1. 11102443
  9. Sekimata M, Takahashi A, Murakami-Sekimata A, Homma Y: Involvement of a novel zinc finger protein, MIZF, in transcriptional repression by interacting with a methyl-CpG-binding protein, MBD2. J Biol Chem. 2001 Nov 16;276(46):42632-8. Epub 2001 Sep 11. 11553631
  10. Brackertz M, Boeke J, Zhang R, Renkawitz R: Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3. J Biol Chem. 2002 Oct 25;277(43):40958-66. Epub 2002 Aug 14. 12183469
  11. Lembo F, Pero R, Angrisano T, Vitiello C, Iuliano R, Bruni CB, Chiariotti L: MBDin, a novel MBD2-interacting protein, relieves MBD2 repression potential and reactivates transcription from methylated promoters. Mol Cell Biol. 2003 Mar;23(5):1656-65. 12588985
  12. Fujita H, Fujii R, Aratani S, Amano T, Fukamizu A, Nakajima T: Antithetic effects of MBD2a on gene regulation. Mol Cell Biol. 2003 Apr;23(8):2645-57. 12665568
  13. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. 17081983
  14. Brackertz M, Gong Z, Leers J, Renkawitz R: p66alpha and p66beta of the Mi-2/NuRD complex mediate MBD2 and histone interaction. Nucleic Acids Res. 2006 Jan 13;34(2):397-406. Print 2006. 16415179
  15. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  16. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. 19413330
  17. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  18. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. 20068231
  19. Cramer JM, Scarsdale JN, Walavalkar NM, Buchwald WA, Ginder GD, Williams DC Jr: Probing the dynamic distribution of bound states for methylcytosine-binding domains on DNA. J Biol Chem. 2014 Jan 17;289(3):1294-302. doi: 10.1074/jbc.M113.512236. Epub 2013 Dec 4. 24307175
  20. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  21. Gnanapragasam MN, Scarsdale JN, Amaya ML, Webb HD, Desai MA, Walavalkar NM, Wang SZ, Zu Zhu S, Ginder GD, Williams DC Jr: p66Alpha-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7487-92. doi: 10.1073/pnas.1015341108. Epub 2011 Apr 13. 21490301