MBD3_MOUSE
ID MBD3_MOUSE Reviewed; 285 AA.
AC Q9Z2D8; Q792D3; Q8CFJ1;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Methyl-CpG-binding domain protein 3;
DE AltName: Full=Methyl-CpG-binding protein MBD3;
GN Name=Mbd3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP 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.
RC STRAIN=129;
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 2).
RC STRAIN=C57BL/6J; TISSUE=Mammary tumor;
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 SUBCELLULAR LOCATION.
RX PubMed=14610093; DOI=10.1074/jbc.m309393200;
RA Ghoshal K., Majumder S., Datta J., Motiwala T., Bai S., Sharma S.M.,
RA Frankel W., Jacob S.T.;
RT "Role of human ribosomal RNA (rRNA) promoter methylation and of methyl-CpG-
RT binding protein MBD2 in the suppression of rRNA gene expression.";
RL J. Biol. Chem. 279:6783-6793(2004).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP ABSENCE OF INTERACTION WITH PWWP2A AND PWWP2B.
RX PubMed=30228260; DOI=10.1038/s41467-018-06235-9;
RA Zhang T., Wei G., Millard C.J., Fischer R., Konietzny R., Kessler B.M.,
RA Schwabe J.W.R., Brockdorff N.;
RT "A variant NuRD complex containing PWWP2A/B excludes MBD2/3 to regulate
RT transcription at active genes.";
RL Nat. Commun. 9:3798-3798(2018).
RN [7]
RP ABSENCE OF INTERACTION WITH PWWP2A.
RX PubMed=30327463; DOI=10.1038/s41467-018-06665-5;
RA Link S., Spitzer R.M.M., Sana M., Torrado M., Voelker-Albert M.C.,
RA Keilhauer E.C., Burgold T., Puenzeler S., Low J.K.K., Lindstroem I.,
RA Nist A., Regnard C., Stiewe T., Hendrich B., Imhof A., Mann M.,
RA Mackay J.P., Bartkuhn M., Hake S.B.;
RT "PWWP2A binds distinct chromatin moieties and interacts with an MTA1-
RT specific core NuRD complex.";
RL Nat. Commun. 9:4300-4300(2018).
CC -!- FUNCTION: Acts as transcriptional repressor and plays a role in gene
CC silencing. Does not bind DNA by itself. Binds to DNA with a preference
CC for sites containing methylated CpG dinucleotides (in vitro). Binds to
CC a lesser degree DNA containing unmethylated CpG dinucleotides (By
CC similarity). Recruits histone deacetylases and DNA methyltransferases.
CC {ECO:0000250, ECO:0000269|PubMed:9774669}.
CC -!- SUBUNIT: Heterodimer with MBD2. Part of the NuRD and the MeCP1 complex.
CC Interacts with BCL6, HDAC1, MTA2, DNMT1, p66-alpha and p66-beta (By
CC similarity). Does not interact with PWWP2A and PWWP2B (PubMed:30228260,
CC PubMed:30327463). {ECO:0000250|UniProtKB:O95983,
CC ECO:0000269|PubMed:30228260, ECO:0000269|PubMed:30327463}.
CC -!- INTERACTION:
CC Q9Z2D8; P14404: Mecom; NbExp=4; IntAct=EBI-1994548, EBI-1994523;
CC Q9Z2D8-1; P14404: Mecom; NbExp=5; IntAct=EBI-1994598, EBI-1994523;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14610093,
CC ECO:0000269|PubMed:9774669}. Chromosome {ECO:0000250}. Note=Detected on
CC chromatin, at promoter regions of active genes (By similarity).
CC Nuclear, in discrete foci. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Z2D8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Z2D8-2; Sequence=VSP_011082;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, heart, kidney, liver,
CC lung, skeletal muscle, spleen and testis. Detected at lower levels in
CC embryonic stem cells. {ECO:0000269|PubMed:9774669}.
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DR EMBL; AF072248; AAC68877.1; -; mRNA.
DR EMBL; AF120995; AAD48909.1; -; Genomic_DNA.
DR EMBL; BC038264; AAH38264.1; -; mRNA.
DR CCDS; CCDS24020.1; -. [Q9Z2D8-1]
DR CCDS; CCDS78860.1; -. [Q9Z2D8-2]
DR RefSeq; NP_001293072.1; NM_001306143.1. [Q9Z2D8-2]
DR RefSeq; NP_038623.1; NM_013595.3. [Q9Z2D8-1]
DR AlphaFoldDB; Q9Z2D8; -.
DR BMRB; Q9Z2D8; -.
DR SMR; Q9Z2D8; -.
DR BioGRID; 201332; 22.
DR ComplexPortal; CPX-954; MBD3/NuRD nucleosome remodeling and deacetylase complex.
DR CORUM; Q9Z2D8; -.
DR DIP; DIP-46518N; -.
DR IntAct; Q9Z2D8; 12.
DR MINT; Q9Z2D8; -.
DR STRING; 10090.ENSMUSP00000089948; -.
DR iPTMnet; Q9Z2D8; -.
DR PhosphoSitePlus; Q9Z2D8; -.
DR EPD; Q9Z2D8; -.
DR jPOST; Q9Z2D8; -.
DR MaxQB; Q9Z2D8; -.
DR PaxDb; Q9Z2D8; -.
DR PeptideAtlas; Q9Z2D8; -.
DR PRIDE; Q9Z2D8; -.
DR ProteomicsDB; 295800; -. [Q9Z2D8-1]
DR ProteomicsDB; 295801; -. [Q9Z2D8-2]
DR Antibodypedia; 22760; 447 antibodies from 41 providers.
DR DNASU; 17192; -.
DR Ensembl; ENSMUST00000092295; ENSMUSP00000089948; ENSMUSG00000035478. [Q9Z2D8-1]
DR Ensembl; ENSMUST00000105349; ENSMUSP00000100986; ENSMUSG00000035478. [Q9Z2D8-2]
DR GeneID; 17192; -.
DR KEGG; mmu:17192; -.
DR UCSC; uc007gda.1; mouse. [Q9Z2D8-2]
DR UCSC; uc007gdb.1; mouse. [Q9Z2D8-1]
DR CTD; 53615; -.
DR MGI; MGI:1333812; Mbd3.
DR VEuPathDB; HostDB:ENSMUSG00000035478; -.
DR eggNOG; KOG4161; Eukaryota.
DR GeneTree; ENSGT00950000183005; -.
DR HOGENOM; CLU_069710_0_0_1; -.
DR InParanoid; Q9Z2D8; -.
DR OMA; WECLALP; -.
DR OrthoDB; 1431783at2759; -.
DR PhylomeDB; Q9Z2D8; -.
DR TreeFam; TF325032; -.
DR Reactome; R-MMU-3214815; HDACs deacetylate histones.
DR Reactome; R-MMU-6804758; Regulation of TP53 Activity through Acetylation.
DR Reactome; R-MMU-73762; RNA Polymerase I Transcription Initiation.
DR Reactome; R-MMU-8943724; Regulation of PTEN gene transcription.
DR BioGRID-ORCS; 17192; 8 hits in 76 CRISPR screens.
DR ChiTaRS; Mbd3; mouse.
DR PRO; PR:Q9Z2D8; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9Z2D8; protein.
DR Bgee; ENSMUSG00000035478; Expressed in ventricular zone and 261 other tissues.
DR ExpressionAtlas; Q9Z2D8; baseline and differential.
DR Genevisible; Q9Z2D8; MM.
DR GO; GO:0000785; C:chromatin; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0000792; C:heterochromatin; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0016581; C:NuRD complex; IPI:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0008327; F:methyl-CpG binding; ISS: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; ISO:MGI.
DR GO; GO:0006346; P:DNA methylation-dependent heterochromatin assembly; IDA:MGI.
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; IMP:MGI.
DR GO; GO:0016575; P:histone deacetylation; ISO:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
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; IMP:MGI.
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 Alternative splicing; Chromosome; Coiled coil; DNA-binding;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..285
FT /note="Methyl-CpG-binding domain protein 3"
FT /id="PRO_0000096263"
FT DOMAIN 1..69
FT /note="MBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00338"
FT REGION 255..285
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 221..279
FT /evidence="ECO:0000255"
FT COMPBIAS 264..285
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 56
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95983"
FT MOD_RES 144
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95983"
FT CROSSLNK 73
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O95983"
FT CROSSLNK 90
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O95983"
FT CROSSLNK 92
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O95983"
FT VAR_SEQ 5..36
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011082"
SQ SEQUENCE 285 AA; 32168 MW; E4E57BD48463643F CRC64;
MERKRWECPA LPQGWEREEV PRRSGLSAGH RDVFYYSPSG KKFRSKPQLA RYLGGSMDLS
TFDFRTGKML MNKMNKSRQR VRYDSSNQVK GKPDLNTALP VRQTASIFKQ PVTKITNHPS
NKVKSDPQKA VDQPRQLFWE KKLSGLSAFD IAEELVRTMD LPKGLQGVGP GCTDETLLSA
IASALHTSTL PITGQLSAAV EKNPGVWLNT AQPLCKAFMV TDDDIRKQEE LVQQVRKRLE
EALMADMLAH VEELARDGEA PLDKACAEEE EEEEEEEEEP EPERV
