ID MBD2_HUMAN Reviewed; 411 AA. AC Q9UBB5; O95242; Q9UIS8; DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 200. DE RecName: Full=Methyl-CpG-binding domain protein 2 {ECO:0000305}; DE AltName: Full=Demethylase; DE Short=DMTase; DE AltName: Full=Methyl-CpG-binding protein MBD2; GN Name=MBD2 {ECO:0000312|HGNC:HGNC:6917}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF RP 157-411 (ISOFORM 3), FUNCTION, AND SUBCELLULAR LOCATION. RC TISSUE=Testis; RX PubMed=9774669; DOI=10.1128/mcb.18.11.6538; RA Hendrich B., Bird A.; RT "Identification and characterization of a family of mammalian methyl-CpG RT binding proteins."; RL Mol. Cell. Biol. 18:6538-6547(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10441743; DOI=10.1007/s003359901112; RA Hendrich B., Abbott C., McQueen H., Chambers D., Cross S.H., Bird A.; RT "Genomic structure and chromosomal mapping of the murine and human mbd1, RT mbd2, mbd3, and mbd4 genes."; RL Mamm. Genome 10:906-912(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP FUNCTION (ISOFORM 1), AND TISSUE SPECIFICITY. RX PubMed=10050851; DOI=10.1038/17533; RA Bhattacharya S.K., Ramchandani S., Cervoni N., Szyf M.; RT "A mammalian protein with specific demethylase activity for mCpG DNA."; RL Nature 397:579-583(1999). RN [5] RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH MECP1 RP AND HDAC1. RX PubMed=10471499; DOI=10.1038/12659; RA Ng H.-H., Zhang Y., Hendrich B., Johnson C.A., Turner B.M., RA Erdjument-Bromage H., Tempst P., Reinberg D., Bird A.; RT "MBD2 is a transcriptional repressor belonging to the MeCP1 histone RT deacetylase complex."; RL Nat. Genet. 23:58-61(1999). RN [6] RP FUNCTION, HETERODIMERIZATION WITH MBD3, AND INTERACTION WITH DNMT1. RX PubMed=10947852; DOI=10.1046/j.1365-2443.2000.00359.x; RA Tatematsu K., Yamazaki T., Ishikawa F.; RT "MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex RT containing DNMT1 at the replication foci in late S phase."; RL Genes Cells 5:677-688(2000). RN [7] RP FUNCTION (ISOFORM 1), AND INTERACTION WITH SIN3A. RX PubMed=10950960; DOI=10.1074/jbc.m005929200; RA Boeke J., Ammerpohl O., Kegel S., Moehren U., Renkawitz R.; RT "The minimal repression domain of MBD2b overlaps with the methyl-CpG- RT binding domain and binds directly to Sin3A."; RL J. Biol. Chem. 275:34963-34967(2000). RN [8] RP INTERACTION WITH HDAC1, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=11102443; DOI=10.1074/jbc.m007372200; RA Humphrey G.W., Wang Y., Russanova V.R., Hirai T., Qin J., Nakatani Y., RA Howard B.H.; RT "Stable histone deacetylase complexes distinguished by the presence of SANT RT domain proteins CoREST/kiaa0071 and Mta-L1."; RL J. Biol. Chem. 276:6817-6824(2001). RN [9] RP INTERACTION WITH MIZF. RX PubMed=11553631; DOI=10.1074/jbc.m107048200; RA Sekimata M., Takahashi A., Murakami-Sekimata A., Homma Y.; RT "Involvement of a novel zinc finger protein, MIZF, in transcriptional RT repression by interacting with a methyl-CpG-binding protein, MBD2."; RL J. Biol. Chem. 276:42632-42638(2001). RN [10] RP INTERACTION WITH P66ALPHA AND P66BETA, AND SUBCELLULAR LOCATION. RX PubMed=12183469; DOI=10.1074/jbc.m207467200; RA Brackertz M., Boeke J., Zhang R., Renkawitz R.; RT "Two highly related p66 proteins comprise a new family of potent RT transcriptional repressors interacting with MBD2 and MBD3."; RL J. Biol. Chem. 277:40958-40966(2002). RN [11] RP INTERACTION WITH GPN1. RX PubMed=12588985; DOI=10.1128/mcb.23.5.1656-1665.2003; RA Lembo F., Pero R., Angrisano T., Vitiello C., Iuliano R., Bruni C.B., RA Chiariotti L.; RT "MBDin, a novel MBD2-interacting protein, relieves MBD2 repression RT potential and reactivates transcription from methylated promoters."; RL Mol. Cell. Biol. 23:1656-1665(2003). RN [12] RP FUNCTION, AND INTERACTION WITH DHX9. RX PubMed=12665568; DOI=10.1128/mcb.23.8.2645-2657.2003; RA Fujita H., Fujii R., Aratani S., Amano T., Fukamizu A., Nakajima T.; RT "Antithetic effects of MBD2a on gene regulation."; RL Mol. Cell. Biol. 23:2645-2657(2003). RN [13] RP INTERACTION WITH MBD3, AND SUBCELLULAR LOCATION. RX PubMed=15701600; DOI=10.1074/jbc.m413492200; RA Jin S.-G., Jiang C.-L., Rauch T., Li H., Pfeifer G.P.; RT "MBD3L2 interacts with MBD3 and components of the NuRD complex and can RT oppose MBD2-MeCP1-mediated methylation silencing."; RL J. Biol. Chem. 280:12700-12709(2005). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [15] RP FUNCTION, IDENTIFICATION IN THE NURD COMPLEX, INTERACTION WITH PRMT5, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=16428440; DOI=10.1128/mcb.26.3.843-851.2006; RA Le Guezennec X., Vermeulen M., Brinkman A.B., Hoeijmakers W.A., Cohen A., RA Lasonder E., Stunnenberg H.G.; RT "MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical RT and functional properties."; RL Mol. Cell. Biol. 26:843-851(2006). RN [16] RP FUNCTION, AND INTERACTION WITH GATAD2A AND GATAD2B. RX PubMed=16415179; DOI=10.1093/nar/gkj437; RA Brackertz M., Gong Z., Leers J., Renkawitz R.; RT "p66alpha and p66beta of the Mi-2/NuRD complex mediate MBD2 and histone RT interaction."; RL Nucleic Acids Res. 34:397-406(2006). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-407, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [19] RP INTERACTION WITH SPHK2. RX PubMed=19729656; DOI=10.1126/science.1176709; RA Hait N.C., Allegood J., Maceyka M., Strub G.M., Harikumar K.B., Singh S.K., RA Luo C., Marmorstein R., Kordula T., Milstien S., Spiegel S.; RT "Regulation of histone acetylation in the nucleus by sphingosine-1- RT phosphate."; RL Science 325:1254-1257(2009). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [21] RP INTERACTION WITH CDK2AP1, IDENTIFICATION BY MASS SPECTROMETRY, AND RP SUBCELLULAR LOCATION. RX PubMed=20523938; DOI=10.1039/c004108d; RA Spruijt C.G., Bartels S.J., Brinkman A.B., Tjeertes J.V., Poser I., RA Stunnenberg H.G., Vermeulen M.; RT "CDK2AP1/DOC-1 is a bona fide subunit of the Mi-2/NuRD complex."; RL Mol. Biosyst. 6:1700-1706(2010). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-407, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [24] RP FUNCTION, AND DNA-BINDING. RX PubMed=24307175; DOI=10.1074/jbc.m113.512236; RA Cramer J.M., Scarsdale J.N., Walavalkar N.M., Buchwald W.A., Ginder G.D., RA Williams D.C. Jr.; RT "Probing the dynamic distribution of bound states for methylcytosine- RT binding domains on DNA."; RL J. Biol. Chem. 289:1294-1302(2014). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [26] RP INTERACTION WITH GATAD2A AND GATAD2B, IDENTIFICATION IN THE NURD COMPLEX, RP AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=27732854; DOI=10.1016/j.celrep.2016.09.037; RA Spruijt C.G., Luijsterburg M.S., Menafra R., Lindeboom R.G., Jansen P.W., RA Edupuganti R.R., Baltissen M.P., Wiegant W.W., Voelker-Albert M.C., RA Matarese F., Mensinga A., Poser I., Vos H.R., Stunnenberg H.G., RA van Attikum H., Vermeulen M.; RT "ZMYND8 Co-localizes with NuRD on Target Genes and Regulates Poly(ADP- RT Ribose)-Dependent Recruitment of GATAD2A/NuRD to Sites of DNA Damage."; RL Cell Rep. 17:783-798(2016). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [28] RP FUNCTION, IDENTIFICATION IN THE NURD COMPLEX, IDENTIFICATION BY MASS RP SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=28977666; DOI=10.1093/nar/gkx711; RA Hoffmeister H., Fuchs A., Erdel F., Pinz S., Groebner-Ferreira R., RA Bruckmann A., Deutzmann R., Schwartz U., Maldonado R., Huber C., RA Dendorfer A.S., Rippe K., Laengst G.; RT "CHD3 and CHD4 form distinct NuRD complexes with different yet overlapping RT functionality."; RL Nucleic Acids Res. 45:10534-10554(2017). RN [29] RP IDENTIFICATION IN THE NURD COMPLEX, INTERACTION WITH GATAD2A, RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=33283408; DOI=10.1111/febs.15650; RA Spruijt C.G., Graewe C., Kleinendorst S.C., Baltissen M.P.A., Vermeulen M.; RT "Cross-linking mass spectrometry reveals the structural topology of RT peripheral NuRD subunits relative to the core complex."; RL FEBS J. 288:3231-3245(2021). RN [30] RP STRUCTURE BY NMR OF 360-393 IN COMPLEX WITH GATAD2A, SUBUNIT, AND RP INTERACTION WITH GATAD2A. RX PubMed=21490301; DOI=10.1073/pnas.1015341108; RA Gnanapragasam M.N., Scarsdale J.N., Amaya M.L., Webb H.D., Desai M.A., RA Walavalkar N.M., Wang S.Z., Zu Zhu S., Ginder G.D., Williams D.C. Jr.; RT "p66Alpha-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical RT for globin gene silencing by the MBD2-NuRD complex."; RL Proc. Natl. Acad. Sci. U.S.A. 108:7487-7492(2011). CC -!- FUNCTION: Binds CpG islands in promoters where the DNA is methylated at CC position 5 of cytosine within CpG dinucleotides (PubMed:9774669). Binds CC hemimethylated DNA as well (PubMed:10947852, PubMed:24307175). Recruits CC histone deacetylases and DNA methyltransferases to chromatin CC (PubMed:10471499, PubMed:10947852). Acts as a component of the histone CC deacetylase NuRD complex which participates in the remodeling of CC chromatin (PubMed:16428440, PubMed:28977666). Acts as a transcriptional CC repressor and plays a role in gene silencing (PubMed:10471499, CC PubMed:10947852, PubMed:16415179). Functions as a scaffold protein, CC targeting GATAD2A and GATAD2B to chromatin to promote repression CC (PubMed:16415179). May enhance the activation of some unmethylated CC cAMP-responsive promoters (PubMed:12665568). CC {ECO:0000269|PubMed:10471499, ECO:0000269|PubMed:10947852, CC ECO:0000269|PubMed:12665568, ECO:0000269|PubMed:16415179, CC ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:24307175, CC ECO:0000269|PubMed:28977666, ECO:0000269|PubMed:9774669}. CC -!- SUBUNIT: Heterodimer with MBD3 (via N-terminus) (PubMed:10947852, CC PubMed:15701600). Component of the MeCP1 complex that contains HDAC1 CC and HDAC2 (PubMed:10471499, PubMed:11102443). Component of the CC nucleosome remodeling and deacetylase (NuRD) repressor complex, CC composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, CC MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, CC GATAD2A, GATAD2B, CHD3, CHD4 and CHD5 (PubMed:33283408, CC PubMed:28977666, PubMed:16428440, PubMed:27732854). The exact CC stoichiometry of the NuRD complex is unknown, and some subunits such as CC MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define CC mutually exclusive NuRD complexes (PubMed:33283408, PubMed:28977666, CC PubMed:16428440). Interacts with CDK2AP1 (PubMed:20523938). Interacts CC with DHX9 (PubMed:12665568). Interacts with DNMT1 (PubMed:10947852). CC Interacts with GATAD2A/p66-alpha (PubMed:12183469, PubMed:16415179, CC PubMed:21490301, PubMed:33283408, PubMed:27732854). Interacts with CC GATAD2B/p66-beta (PubMed:12183469, PubMed:16415179, PubMed:27732854). CC Interacts with GPN1 (PubMed:12588985). Interacts with MIZF CC (PubMed:11553631). Interacts with PRMT5 (PubMed:16428440). Interacts CC with SIN3A (PubMed:10950960). Interacts with SPHK2 (PubMed:19729656). CC {ECO:0000269|PubMed:10471499, ECO:0000269|PubMed:10947852, CC ECO:0000269|PubMed:10950960, ECO:0000269|PubMed:11102443, CC ECO:0000269|PubMed:11553631, ECO:0000269|PubMed:12183469, CC ECO:0000269|PubMed:12588985, ECO:0000269|PubMed:12665568, CC ECO:0000269|PubMed:15701600, ECO:0000269|PubMed:16415179, CC ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:19729656, CC ECO:0000269|PubMed:20523938, ECO:0000269|PubMed:21490301, CC ECO:0000269|PubMed:27732854, ECO:0000269|PubMed:33283408}. CC -!- INTERACTION: CC Q9UBB5; Q86YP4: GATAD2A; NbExp=8; IntAct=EBI-923391, EBI-726224; CC Q9UBB5; Q96QR8: PURB; NbExp=3; IntAct=EBI-923391, EBI-2880222; CC Q9UBB5; Q16637: SMN2; NbExp=2; IntAct=EBI-923391, EBI-395421; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12183469, CC ECO:0000269|PubMed:15701600, ECO:0000269|PubMed:20523938, CC ECO:0000269|PubMed:27732854, ECO:0000269|PubMed:28977666, CC ECO:0000269|PubMed:33283408, ECO:0000269|PubMed:9774669}. Chromosome CC {ECO:0000269|PubMed:20523938, ECO:0000269|PubMed:27732854}. CC Note=Nuclear, in discrete foci (PubMed:12183469). Detected at CC replication foci in late S phase. Localizes to methylated chromatin CC (PubMed:16428440). Localizes to sites of DNA damage in a manner CC partially dependent on ZMYND8 (PubMed:27732854). CC {ECO:0000269|PubMed:12183469, ECO:0000269|PubMed:16428440, CC ECO:0000269|PubMed:27732854}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=MBD2a, MBD2b; CC IsoId=Q9UBB5-1; Sequence=Displayed; CC Name=3; CC IsoId=Q9UBB5-3; Sequence=VSP_011077, VSP_011078; CC -!- TISSUE SPECIFICITY: Highly expressed in brain, heart, kidney, stomach, CC testis and placenta. {ECO:0000269|PubMed:10050851}. CC -!- MISCELLANEOUS: [Isoform 3]: Incomplete sequence. {ECO:0000305}. CC -!- CAUTION: Functional studies (PubMed:10050851, PubMed:10950960, CC PubMed:12665568) have used a C-terminal fragment of isoform 1 which has CC been described originally as isoform MBD2b but cannot however be proven CC by supporting cDNA sequences. {ECO:0000305|PubMed:9774669}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41309/mbd2"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF072242; AAC68871.1; -; mRNA. DR EMBL; AF072246; AAC68875.1; -; mRNA. DR EMBL; AF120989; AAD56596.1; -; Genomic_DNA. DR EMBL; AF120988; AAD56596.1; JOINED; Genomic_DNA. DR EMBL; AF120993; AAD56597.1; -; Genomic_DNA. DR EMBL; AF120988; AAD56597.1; JOINED; Genomic_DNA. DR EMBL; AF120989; AAD56597.1; JOINED; Genomic_DNA. DR EMBL; AF120990; AAD56597.1; JOINED; Genomic_DNA. DR EMBL; AF120991; AAD56597.1; JOINED; Genomic_DNA. DR EMBL; AF120992; AAD56597.1; JOINED; Genomic_DNA. DR EMBL; BC032638; AAH32638.1; -; mRNA. DR CCDS; CCDS11953.1; -. [Q9UBB5-1] DR CCDS; CCDS45871.1; -. [Q9UBB5-3] DR RefSeq; NP_003918.1; NM_003927.4. [Q9UBB5-1] DR RefSeq; NP_056647.1; NM_015832.4. [Q9UBB5-3] DR PDB; 2L2L; NMR; -; B=360-393. DR PDB; 6C1A; X-ray; 2.05 A; A/B/E/F=143-220. DR PDB; 6C1T; X-ray; 1.84 A; A/D=143-220. DR PDB; 6C1U; X-ray; 2.30 A; A/B/E/F=143-220. DR PDB; 6C1V; X-ray; 2.30 A; A/B/E/F=143-220. DR PDB; 6C2F; X-ray; 2.65 A; A/D/G/J/M/P=143-220. DR PDB; 6CNP; X-ray; 2.10 A; A/B=143-220. DR PDB; 6CNQ; X-ray; 2.15 A; A/B=143-220. DR PDB; 7AO8; EM; 4.50 A; C=1-411. DR PDB; 7AO9; EM; 6.10 A; C=1-411. DR PDB; 7AOA; EM; 19.40 A; C=1-411. DR PDB; 7MWK; X-ray; 2.45 A; A/B=143-220. DR PDB; 7MWM; X-ray; 1.60 A; A/B=143-220. DR PDB; 7RAY; X-ray; 1.78 A; A=143-220. DR PDBsum; 2L2L; -. DR PDBsum; 6C1A; -. DR PDBsum; 6C1T; -. DR PDBsum; 6C1U; -. DR PDBsum; 6C1V; -. DR PDBsum; 6C2F; -. DR PDBsum; 6CNP; -. DR PDBsum; 6CNQ; -. DR PDBsum; 7AO8; -. DR PDBsum; 7AO9; -. DR PDBsum; 7AOA; -. DR PDBsum; 7MWK; -. DR PDBsum; 7MWM; -. DR PDBsum; 7RAY; -. DR AlphaFoldDB; Q9UBB5; -. DR BMRB; Q9UBB5; -. DR EMDB; EMD-11837; -. DR EMDB; EMD-11838; -. DR EMDB; EMD-11839; -. DR SMR; Q9UBB5; -. DR BioGRID; 114445; 170. DR ComplexPortal; CPX-880; MBD2/NuRD nucleosome remodeling and deacetylase complex. DR CORUM; Q9UBB5; -. DR IntAct; Q9UBB5; 40. DR MINT; Q9UBB5; -. DR STRING; 9606.ENSP00000256429; -. DR BindingDB; Q9UBB5; -. DR ChEMBL; CHEMBL3707462; -. DR iPTMnet; Q9UBB5; -. DR PhosphoSitePlus; Q9UBB5; -. DR BioMuta; MBD2; -. DR DMDM; 50401198; -. DR EPD; Q9UBB5; -. DR jPOST; Q9UBB5; -. DR MassIVE; Q9UBB5; -. DR MaxQB; Q9UBB5; -. DR PaxDb; 9606-ENSP00000256429; -. DR PeptideAtlas; Q9UBB5; -. DR ProteomicsDB; 83923; -. [Q9UBB5-1] DR ProteomicsDB; 83924; -. [Q9UBB5-3] DR Pumba; Q9UBB5; -. DR Antibodypedia; 9530; 455 antibodies from 38 providers. DR DNASU; 8932; -. DR Ensembl; ENST00000256429.8; ENSP00000256429.3; ENSG00000134046.12. [Q9UBB5-1] DR Ensembl; ENST00000583046.1; ENSP00000464554.1; ENSG00000134046.12. [Q9UBB5-3] DR GeneID; 8932; -. DR KEGG; hsa:8932; -. DR MANE-Select; ENST00000256429.8; ENSP00000256429.3; NM_003927.5; NP_003918.1. DR UCSC; uc002lfg.2; human. [Q9UBB5-1] DR AGR; HGNC:6917; -. DR CTD; 8932; -. DR DisGeNET; 8932; -. DR GeneCards; MBD2; -. DR HGNC; HGNC:6917; MBD2. DR HPA; ENSG00000134046; Low tissue specificity. DR MIM; 603547; gene. DR neXtProt; NX_Q9UBB5; -. DR OpenTargets; ENSG00000134046; -. DR PharmGKB; PA30660; -. DR VEuPathDB; HostDB:ENSG00000134046; -. DR eggNOG; KOG4161; Eukaryota. DR GeneTree; ENSGT00950000183005; -. DR HOGENOM; CLU_055454_0_0_1; -. DR InParanoid; Q9UBB5; -. DR OMA; CKAFTIT; -. DR OrthoDB; 5262043at2759; -. DR PhylomeDB; Q9UBB5; -. DR TreeFam; TF325032; -. DR PathwayCommons; Q9UBB5; -. DR Reactome; R-HSA-427413; NoRC negatively regulates rRNA expression. DR Reactome; R-HSA-73728; RNA Polymerase I Promoter Opening. DR SignaLink; Q9UBB5; -. DR SIGNOR; Q9UBB5; -. DR BioGRID-ORCS; 8932; 42 hits in 1184 CRISPR screens. DR ChiTaRS; MBD2; human. DR GeneWiki; Methyl-CpG-binding_domain_protein_2; -. DR GenomeRNAi; 8932; -. DR Pharos; Q9UBB5; Tchem. DR PRO; PR:Q9UBB5; -. DR Proteomes; UP000005640; Chromosome 18. DR RNAct; Q9UBB5; Protein. DR Bgee; ENSG00000134046; Expressed in gingival epithelium and 212 other cell types or tissues. DR ExpressionAtlas; Q9UBB5; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0016581; C:NuRD complex; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; HDA:UniProtKB. DR GO; GO:0070742; F:C2H2 zinc finger domain binding; IPI:UniProtKB. DR GO; GO:0008327; F:methyl-CpG binding; IDA:UniProtKB. DR GO; GO:0060090; F:molecular adaptor activity; EXP:DisProt. DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB. DR GO; GO:0003696; F:satellite DNA binding; TAS:ProtInc. DR GO; GO:0006338; P:chromatin remodeling; IDA:UniProtKB. DR GO; GO:0006346; P:DNA methylation-dependent heterochromatin formation; IGI:BHF-UCL. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; NAS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; NAS:ComplexPortal. DR CDD; cd01396; MeCP2_MBD; 1. DR DisProt; DP01068; -. DR IDEAL; IID00739; -. DR InterPro; IPR016177; DNA-bd_dom_sf. DR InterPro; IPR032343; MBD2/MBD3_p55-bd. DR InterPro; IPR025884; MeCpG-bd_2/3_C_dom. DR InterPro; IPR001739; Methyl_CpG_DNA-bd. DR PANTHER; PTHR12396; METHYL-CPG BINDING PROTEIN, MBD; 1. DR PANTHER; PTHR12396:SF5; METHYL-CPG-BINDING DOMAIN PROTEIN 2; 1. DR Pfam; PF01429; MBD; 1. DR Pfam; PF14048; MBD_C; 1. DR Pfam; PF16564; MBDa; 1. DR SMART; SM00391; MBD; 1. DR SUPFAM; SSF54171; DNA-binding domain; 1. DR PROSITE; PS50982; MBD; 1. DR Genevisible; Q9UBB5; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chromosome; DNA-binding; Nucleus; KW Phosphoprotein; Reference proteome; Transcription; KW Transcription regulation. FT CHAIN 1..411 FT /note="Methyl-CpG-binding domain protein 2" FT /id="PRO_0000096260" FT DOMAIN 145..213 FT /note="MBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00338" FT REGION 1..158 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1..149 FT /note="Required for interaction with DHX9 and PRMT5" FT /evidence="ECO:0000269|PubMed:12665568, FT ECO:0000269|PubMed:16428440" FT REGION 214..241 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 79..93 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 181 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 407 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:24275569" FT VAR_SEQ 235..302 FT /note="GKPDLNTTLPIRQTASIFKQPVTKVTNHPSNKVKSDPQRMNEQPRQLFWEKR FT LQGLSASDVTEQIIKT -> LRWNTHRPAPWHALSRLCLLIRCLLCLECAYPLPLHLVN FT SYSSKTQLHCLHLWEACPAYSRQNQSFPP (in isoform 3)" FT /evidence="ECO:0000303|PubMed:9774669" FT /id="VSP_011077" FT VAR_SEQ 303..411 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:9774669" FT /id="VSP_011078" FT STRAND 160..165 FT /evidence="ECO:0007829|PDB:7MWM" FT TURN 170..173 FT /evidence="ECO:0007829|PDB:7MWM" FT STRAND 175..180 FT /evidence="ECO:0007829|PDB:7MWM" FT HELIX 190..197 FT /evidence="ECO:0007829|PDB:7MWM" FT HELIX 198..200 FT /evidence="ECO:0007829|PDB:7MWM" FT STRAND 204..207 FT /evidence="ECO:0007829|PDB:6C2F" FT TURN 208..211 FT /evidence="ECO:0007829|PDB:7MWM" FT HELIX 366..388 FT /evidence="ECO:0007829|PDB:2L2L" FT TURN 389..392 FT /evidence="ECO:0007829|PDB:2L2L" SQ SEQUENCE 411 AA; 43255 MW; FC4E5E0CF9BA0FFA CRC64; MRAHPGGGRC CPEQEEGESA AGGSGAGGDS AIEQGGQGSA LAPSPVSGVR REGARGGGRG RGRWKQAGRG GGVCGRGRGR GRGRGRGRGR GRGRGRPPSG GSGLGGDGGG CGGGGSGGGG APRREPVPFP SGSAGPGPRG PRATESGKRM DCPALPPGWK KEEVIRKSGL SAGKSDVYYF SPSGKKFRSK PQLARYLGNT VDLSSFDFRT GKMMPSKLQK NKQRLRNDPL NQNKGKPDLN TTLPIRQTAS IFKQPVTKVT NHPSNKVKSD PQRMNEQPRQ LFWEKRLQGL SASDVTEQII KTMELPKGLQ GVGPGSNDET LLSAVASALH TSSAPITGQV SAAVEKNPAV WLNTSQPLCK AFIVTDEDIR KQEERVQQVR KKLEEALMAD ILSRAADTEE MDIEMDSGDE A //