MBD3_HUMAN
ID MBD3_HUMAN Reviewed; 291 AA.
AC O95983; A8K4B7; D6W5Z2; Q6PIL9; Q6PJZ9; Q86XF4;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Methyl-CpG-binding domain protein 3;
DE AltName: Full=Methyl-CpG-binding protein MBD3;
GN Name=MBD3;
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 (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION.
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 [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain, Cervix, Muscle, and Uterus;
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 [6]
RP FUNCTION, HETERODIMERIZATION WITH MBD2, 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 INTERACTION WITH THE HDAC1 COMPLEX, AND IDENTIFICATION BY MASS
RP 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 [8]
RP FUNCTION, INTERACTION WITH HDAC1; MTA2 AND THE NURD COMPLEX, AND
RP MUTAGENESIS OF HIS-30 AND PHE-34.
RX PubMed=12124384; DOI=10.1074/jbc.m203455200;
RA Saito M., Ishikawa F.;
RT "The mCpG-binding domain of human MBD3 does not bind to mCpG but interacts
RT with NuRD/Mi2 components HDAC1 and MTA2.";
RL J. Biol. Chem. 277:35434-35439(2002).
RN [9]
RP INTERACTION WITH P66ALPHA AND P66BETA.
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 [10]
RP INTERACTION WITH P66BETA AND THE MECP1 COMPLEX.
RX PubMed=11756549; DOI=10.1128/mcb.22.2.536-546.2002;
RA Feng Q., Cao R., Xia L., Erdjument-Bromage H., Tempst P., Zhang Y.;
RT "Identification and functional characterization of the p66/p68 components
RT of the MeCP1 complex.";
RL Mol. Cell. Biol. 22:536-546(2002).
RN [11]
RP INTERACTION WITH BCL6, AND IDENTIFICATION IN THE NURD COMPLEX.
RX PubMed=15454082; DOI=10.1016/j.cell.2004.09.014;
RA Fujita N., Jaye D.L., Geigerman C., Akyildiz A., Mooney M.R., Boss J.M.,
RA Wade P.A.;
RT "MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte
RT differentiation.";
RL Cell 119:75-86(2004).
RN [12]
RP IDENTIFICATION BY 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 [13]
RP FUNCTION.
RX PubMed=18644863; DOI=10.1128/mcb.00467-08;
RA Morey L., Brenner C., Fazi F., Villa R., Gutierrez A., Buschbeck M.,
RA Nervi C., Minucci S., Fuks F., Di Croce L.;
RT "MBD3, a component of the NuRD complex, facilitates chromatin alteration
RT and deposition of epigenetic marks.";
RL Mol. Cell. Biol. 28:5912-5923(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56, AND IDENTIFICATION BY
RP 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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56 AND SER-144, AND
RP IDENTIFICATION BY 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 [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56; SER-85 AND SER-144, 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 [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56 AND SER-85, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56 AND SER-85, AND
RP IDENTIFICATION BY 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 [21]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23361464; DOI=10.1093/nar/gkt035;
RA Gunther K., Rust M., Leers J., Boettger T., Scharfe M., Jarek M.,
RA Bartkuhn M., Renkawitz R.;
RT "Differential roles for MBD2 and MBD3 at methylated CpG islands, active
RT promoters and binding to exon sequences.";
RL Nucleic Acids Res. 41:3010-3021(2013).
RN [22]
RP SUBCELLULAR LOCATION.
RX PubMed=24385926; DOI=10.1371/journal.pgen.1004028;
RA Shimbo T., Du Y., Grimm S.A., Dhasarathy A., Mav D., Shah R.R., Shi H.,
RA Wade P.A.;
RT "MBD3 localizes at promoters, gene bodies and enhancers of active genes.";
RL PLoS Genet. 9:E1004028-E1004028(2013).
RN [23]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-73; LYS-90 AND LYS-92, AND
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 [24]
RP STRUCTURE BY NMR OF 1-70, FUNCTION, DNA-BINDING, AND MUTAGENESIS OF HIS-30
RP AND PHE-34.
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).
CC -!- FUNCTION: Acts as transcriptional repressor and plays a role in gene
CC silencing. Does not bind to DNA by itself (PubMed:12124384). Binds to
CC DNA with a preference for sites containing methylated CpG dinucleotides
CC (in vitro). Binds to a lesser degree DNA containing unmethylated CpG
CC dinucleotides (PubMed:24307175). Recruits histone deacetylases and DNA
CC methyltransferases. {ECO:0000269|PubMed:10947852,
CC ECO:0000269|PubMed:12124384, ECO:0000269|PubMed:18644863,
CC ECO:0000269|PubMed:23361464, ECO:0000269|PubMed:24307175,
CC ECO:0000269|PubMed:9774669}.
CC -!- SUBUNIT: Heterodimer with MBD2 (PubMed:10947852). Part of the NuRD and
CC the MeCP1 complex (PubMed:12124384, PubMed:11756549, PubMed:15454082).
CC Interacts with BCL6, HDAC1, MTA2, DNMT1, p66-alpha and p66-beta
CC (PubMed:11102443, PubMed:12124384, PubMed:12183469, PubMed:11756549,
CC PubMed:15454082). Does not interact with PWWP2A and PWWP2B (By
CC similarity). {ECO:0000250|UniProtKB:Q9Z2D8,
CC ECO:0000269|PubMed:10947852, ECO:0000269|PubMed:11102443,
CC ECO:0000269|PubMed:11756549, ECO:0000269|PubMed:12124384,
CC ECO:0000269|PubMed:12183469, ECO:0000269|PubMed:15454082}.
CC -!- INTERACTION:
CC O95983; Q8TAP6: CEP76; NbExp=3; IntAct=EBI-1783068, EBI-742887;
CC O95983; P17844: DDX5; NbExp=4; IntAct=EBI-1783068, EBI-351962;
CC O95983; Q8WXI9: GATAD2B; NbExp=4; IntAct=EBI-1783068, EBI-923440;
CC O95983; Q08379: GOLGA2; NbExp=3; IntAct=EBI-1783068, EBI-618309;
CC O95983; Q13547: HDAC1; NbExp=6; IntAct=EBI-1783068, EBI-301834;
CC O95983; Q05084: ICA1; NbExp=3; IntAct=EBI-1783068, EBI-1046751;
CC O95983; O60341: KDM1A; NbExp=4; IntAct=EBI-1783068, EBI-710124;
CC O95983; O43474: KLF4; NbExp=3; IntAct=EBI-1783068, EBI-7232405;
CC O95983; P19012: KRT15; NbExp=3; IntAct=EBI-1783068, EBI-739566;
CC O95983; P01106: MYC; NbExp=3; IntAct=EBI-1783068, EBI-447544;
CC O95983; Q01860: POU5F1; NbExp=3; IntAct=EBI-1783068, EBI-475687;
CC O95983; Q96D15: RCN3; NbExp=3; IntAct=EBI-1783068, EBI-746283;
CC O95983; O00560: SDCBP; NbExp=3; IntAct=EBI-1783068, EBI-727004;
CC O95983; P48431: SOX2; NbExp=3; IntAct=EBI-1783068, EBI-6124081;
CC O95983; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-1783068, EBI-2130429;
CC O95983; Q8WWA6: ZNF277; NbExp=3; IntAct=EBI-1783068, EBI-10192794;
CC O95983-2; O95994: AGR2; NbExp=3; IntAct=EBI-11978579, EBI-712648;
CC O95983-2; Q7Z3H0-1: ANKRD33; NbExp=3; IntAct=EBI-11978579, EBI-16746154;
CC O95983-2; Q6XD76: ASCL4; NbExp=3; IntAct=EBI-11978579, EBI-10254793;
CC O95983-2; G5E9W6: CCDC183; NbExp=3; IntAct=EBI-11978579, EBI-17212717;
CC O95983-2; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-11978579, EBI-10175300;
CC O95983-2; P24863: CCNC; NbExp=3; IntAct=EBI-11978579, EBI-395261;
CC O95983-2; Q6IPU0: CENPP; NbExp=3; IntAct=EBI-11978579, EBI-10250303;
CC O95983-2; Q8NHQ1: CEP70; NbExp=3; IntAct=EBI-11978579, EBI-739624;
CC O95983-2; Q8TAP6: CEP76; NbExp=3; IntAct=EBI-11978579, EBI-742887;
CC O95983-2; Q8WUE5: CT55; NbExp=3; IntAct=EBI-11978579, EBI-6873363;
CC O95983-2; Q96A65-2: EXOC4; NbExp=3; IntAct=EBI-11978579, EBI-17869840;
CC O95983-2; Q96C01: FAM136A; NbExp=3; IntAct=EBI-11978579, EBI-373319;
CC O95983-2; Q8TAE8: GADD45GIP1; NbExp=3; IntAct=EBI-11978579, EBI-372506;
CC O95983-2; Q86YP4: GATAD2A; NbExp=3; IntAct=EBI-11978579, EBI-726224;
CC O95983-2; Q08379: GOLGA2; NbExp=3; IntAct=EBI-11978579, EBI-618309;
CC O95983-2; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-11978579, EBI-5916454;
CC O95983-2; P24592: IGFBP6; NbExp=3; IntAct=EBI-11978579, EBI-947015;
CC O95983-2; Q13123: IK; NbExp=3; IntAct=EBI-11978579, EBI-713456;
CC O95983-2; P08779: KRT16; NbExp=3; IntAct=EBI-11978579, EBI-356410;
CC O95983-2; O95751: LDOC1; NbExp=3; IntAct=EBI-11978579, EBI-740738;
CC O95983-2; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-11978579, EBI-11742507;
CC O95983-2; P43356: MAGEA2B; NbExp=3; IntAct=EBI-11978579, EBI-5650739;
CC O95983-2; Q99687-3: MEIS3; NbExp=3; IntAct=EBI-11978579, EBI-18582591;
CC O95983-2; P50221: MEOX1; NbExp=3; IntAct=EBI-11978579, EBI-2864512;
CC O95983-2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-11978579, EBI-16439278;
CC O95983-2; Q8TD10: MIPOL1; NbExp=3; IntAct=EBI-11978579, EBI-2548751;
CC O95983-2; Q13064: MKRN3; NbExp=3; IntAct=EBI-11978579, EBI-2340269;
CC O95983-2; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-11978579, EBI-11522433;
CC O95983-2; P15173: MYOG; NbExp=3; IntAct=EBI-11978579, EBI-3906629;
CC O95983-2; Q9BYU1: PBX4; NbExp=3; IntAct=EBI-11978579, EBI-10302990;
CC O95983-2; P04085-2: PDGFA; NbExp=3; IntAct=EBI-11978579, EBI-11995148;
CC O95983-2; O15212: PFDN6; NbExp=3; IntAct=EBI-11978579, EBI-356973;
CC O95983-2; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-11978579, EBI-79165;
CC O95983-2; Q96KN3: PKNOX2; NbExp=5; IntAct=EBI-11978579, EBI-2692890;
CC O95983-2; P31321: PRKAR1B; NbExp=3; IntAct=EBI-11978579, EBI-2805516;
CC O95983-2; Q96QF0-7: RAB3IP; NbExp=3; IntAct=EBI-11978579, EBI-11984839;
CC O95983-2; Q96D15: RCN3; NbExp=3; IntAct=EBI-11978579, EBI-746283;
CC O95983-2; Q04864-2: REL; NbExp=3; IntAct=EBI-11978579, EBI-10829018;
CC O95983-2; Q6NUQ1: RINT1; NbExp=3; IntAct=EBI-11978579, EBI-726876;
CC O95983-2; Q9UJW9: SERTAD3; NbExp=3; IntAct=EBI-11978579, EBI-748621;
CC O95983-2; Q93045: STMN2; NbExp=3; IntAct=EBI-11978579, EBI-714194;
CC O95983-2; Q8N0S2: SYCE1; NbExp=3; IntAct=EBI-11978579, EBI-6872807;
CC O95983-2; Q8N5T2: TBC1D19; NbExp=3; IntAct=EBI-11978579, EBI-1221022;
CC O95983-2; Q9Y5J6: TIMM10B; NbExp=3; IntAct=EBI-11978579, EBI-1200382;
CC O95983-2; P19237: TNNI1; NbExp=3; IntAct=EBI-11978579, EBI-746692;
CC O95983-2; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-11978579, EBI-2130429;
CC O95983-2; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-11978579, EBI-9090990;
CC O95983-2; Q8N720: ZNF655; NbExp=3; IntAct=EBI-11978579, EBI-625509;
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome. Note=Nuclear, in discrete
CC foci. Detected on chromatin, at promoter regions of active genes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O95983-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95983-2; Sequence=VSP_011081;
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH32443.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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; AF072247; AAC68876.1; -; mRNA.
DR EMBL; AK290882; BAF83571.1; -; mRNA.
DR EMBL; AC005943; AAC72104.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69477.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69478.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69481.1; -; Genomic_DNA.
DR EMBL; BC009372; AAH09372.1; -; mRNA.
DR EMBL; BC009438; AAH09438.1; -; mRNA.
DR EMBL; BC032443; AAH32443.1; ALT_INIT; mRNA.
DR EMBL; BC043619; AAH43619.1; -; mRNA.
DR CCDS; CCDS12072.1; -. [O95983-1]
DR CCDS; CCDS62481.1; -. [O95983-2]
DR RefSeq; NP_001268382.1; NM_001281453.1. [O95983-1]
DR RefSeq; NP_001268383.1; NM_001281454.1. [O95983-2]
DR PDB; 2MB7; NMR; -; A=1-70.
DR PDB; 6CC8; X-ray; 1.95 A; A/B=1-71.
DR PDB; 6CCG; X-ray; 1.90 A; A/B=1-71.
DR PDB; 6CEU; X-ray; 2.00 A; A/B=1-71.
DR PDB; 6CEV; X-ray; 2.00 A; A/B=1-71.
DR PDBsum; 2MB7; -.
DR PDBsum; 6CC8; -.
DR PDBsum; 6CCG; -.
DR PDBsum; 6CEU; -.
DR PDBsum; 6CEV; -.
DR AlphaFoldDB; O95983; -.
DR BMRB; O95983; -.
DR SMR; O95983; -.
DR BioGRID; 119788; 225.
DR ComplexPortal; CPX-922; MBD3/NuRD nucleosome remodeling and deacetylase complex.
DR CORUM; O95983; -.
DR DIP; DIP-46517N; -.
DR IntAct; O95983; 111.
DR MINT; O95983; -.
DR STRING; 9606.ENSP00000412302; -.
DR GlyGen; O95983; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O95983; -.
DR MetOSite; O95983; -.
DR PhosphoSitePlus; O95983; -.
DR BioMuta; MBD3; -.
DR EPD; O95983; -.
DR jPOST; O95983; -.
DR MassIVE; O95983; -.
DR MaxQB; O95983; -.
DR PaxDb; O95983; -.
DR PeptideAtlas; O95983; -.
DR PRIDE; O95983; -.
DR ProteomicsDB; 51159; -. [O95983-1]
DR ProteomicsDB; 51160; -. [O95983-2]
DR Antibodypedia; 22760; 447 antibodies from 41 providers.
DR DNASU; 53615; -.
DR Ensembl; ENST00000156825.5; ENSP00000156825.2; ENSG00000071655.18. [O95983-2]
DR Ensembl; ENST00000434436.8; ENSP00000412302.2; ENSG00000071655.18. [O95983-1]
DR GeneID; 53615; -.
DR KEGG; hsa:53615; -.
DR MANE-Select; ENST00000434436.8; ENSP00000412302.2; NM_001281453.2; NP_001268382.1.
DR UCSC; uc002ltj.5; human. [O95983-1]
DR CTD; 53615; -.
DR DisGeNET; 53615; -.
DR GeneCards; MBD3; -.
DR HGNC; HGNC:6918; MBD3.
DR HPA; ENSG00000071655; Low tissue specificity.
DR MIM; 603573; gene.
DR neXtProt; NX_O95983; -.
DR OpenTargets; ENSG00000071655; -.
DR PharmGKB; PA30661; -.
DR VEuPathDB; HostDB:ENSG00000071655; -.
DR eggNOG; KOG4161; Eukaryota.
DR GeneTree; ENSGT00950000183005; -.
DR HOGENOM; CLU_069710_0_0_1; -.
DR InParanoid; O95983; -.
DR OMA; WECLALP; -.
DR OrthoDB; 1431783at2759; -.
DR PhylomeDB; O95983; -.
DR TreeFam; TF325032; -.
DR PathwayCommons; O95983; -.
DR Reactome; R-HSA-3214815; HDACs deacetylate histones.
DR Reactome; R-HSA-427389; ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression.
DR Reactome; R-HSA-6804758; Regulation of TP53 Activity through Acetylation.
DR Reactome; R-HSA-73762; RNA Polymerase I Transcription Initiation.
DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR SignaLink; O95983; -.
DR SIGNOR; O95983; -.
DR BioGRID-ORCS; 53615; 45 hits in 1098 CRISPR screens.
DR ChiTaRS; MBD3; human.
DR GeneWiki; MBD3; -.
DR GenomeRNAi; 53615; -.
DR Pharos; O95983; Tbio.
DR PRO; PR:O95983; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O95983; protein.
DR Bgee; ENSG00000071655; Expressed in apex of heart and 195 other tissues.
DR ExpressionAtlas; O95983; baseline and differential.
DR Genevisible; O95983; HS.
DR GO; GO:0000785; C:chromatin; HDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0000792; C:heterochromatin; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0016581; C:NuRD complex; NAS:BHF-UCL.
DR GO; GO:0032991; C:protein-containing complex; HDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0008327; F:methyl-CpG binding; IDA:UniProtKB.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0006338; P:chromatin remodeling; IDA:ComplexPortal.
DR GO; GO:0006346; P:DNA methylation-dependent heterochromatin assembly; IEA:Ensembl.
DR GO; GO:0048568; P:embryonic organ development; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0016573; P:histone acetylation; IEA:Ensembl.
DR GO; GO:0016575; P:histone deacetylation; IDA:ComplexPortal.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IC:ComplexPortal.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IC:ComplexPortal.
DR GO; GO:0042659; P:regulation of cell fate specification; IC:ComplexPortal.
DR GO; GO:0044030; P:regulation of DNA methylation; IEA:Ensembl.
DR GO; GO:2000736; P:regulation of stem cell differentiation; IC:ComplexPortal.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
DR GO; GO:0009888; P:tissue development; IEA:Ensembl.
DR InterPro; IPR016177; DNA-bd_dom_sf.
DR InterPro; IPR032343; MBD2/MBD3_p55-bd.
DR InterPro; IPR037965; MBD3.
DR InterPro; IPR025884; MeCpG-bd_2/3_C_dom.
DR InterPro; IPR001739; Methyl_CpG_DNA-bd.
DR PANTHER; PTHR12396:SF12; PTHR12396:SF12; 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; SSF54171; 1.
DR PROSITE; PS50982; MBD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromosome; Coiled coil; DNA-binding;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..291
FT /note="Methyl-CpG-binding domain protein 3"
FT /id="PRO_0000096262"
FT DOMAIN 1..72
FT /note="MBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00338"
FT REGION 254..291
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 216..245
FT /evidence="ECO:0000255"
FT COMPBIAS 264..291
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 56
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 144
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231"
FT CROSSLNK 73
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 90
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 92
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 5..36
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011081"
FT MUTAGEN 30
FT /note="H->K: No effect. Confers strong binding to
FT methylated CpG (in vitro); when associated with Y-34."
FT /evidence="ECO:0000269|PubMed:12124384,
FT ECO:0000269|PubMed:24307175"
FT MUTAGEN 34
FT /note="F->A: Augments DNA binding activity, irrespective of
FT DNA methylation."
FT /evidence="ECO:0000269|PubMed:12124384,
FT ECO:0000269|PubMed:24307175"
FT MUTAGEN 34
FT /note="F->Y: Confers weak binding to methylated CpG (in
FT vitro). Confers strong binding to methylated CpG (in
FT vitro); when associated with K-30."
FT /evidence="ECO:0000269|PubMed:12124384,
FT ECO:0000269|PubMed:24307175"
FT STRAND 4..7
FT /evidence="ECO:0007829|PDB:6CCG"
FT STRAND 16..21
FT /evidence="ECO:0007829|PDB:6CCG"
FT TURN 26..29
FT /evidence="ECO:0007829|PDB:6CCG"
FT STRAND 31..36
FT /evidence="ECO:0007829|PDB:6CCG"
FT HELIX 46..53
FT /evidence="ECO:0007829|PDB:6CCG"
FT TURN 54..56
FT /evidence="ECO:0007829|PDB:6CCG"
FT TURN 64..67
FT /evidence="ECO:0007829|PDB:6CCG"
SQ SEQUENCE 291 AA; 32844 MW; B62134DD1BEB636B CRC64;
MERKRWECPA LPQGWEREEV PRRSGLSAGH RDVFYYSPSG KKFRSKPQLA RYLGGSMDLS
TFDFRTGKML MSKMNKSRQR VRYDSSNQVK GKPDLNTALP VRQTASIFKQ PVTKITNHPS
NKVKSDPQKA VDQPRQLFWE KKLSGLNAFD IAEELVKTMD LPKGLQGVGP GCTDETLLSA
IASALHTSTM PITGQLSAAV EKNPGVWLNT TQPLCKAFMV TDEDIRKQEE LVQQVRKRLE
EALMADMLAH VEELARDGEA PLDKACAEDD DEEDEEEEEE EPDPDPEMEH V
