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Protein

Methyl-CpG-binding domain protein 3

Gene

MBD3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts as transcriptional repressor and plays a role in gene silencing. Does not bind to DNA by itself (PubMed:12124384). Binds to DNA with a preference for sites containing methylated CpG dinucleotides (in vitro). Binds to a lesser degree DNA containing unmethylated CpG dinucleotides (PubMed:24307175). Recruits histone deacetylases and DNA methyltransferases.6 Publications

GO - Molecular functioni

  • chromatin binding Source: Ensembl
  • DNA binding Source: ProtInc
  • histone deacetylase activity Source: Reactome
  • methyl-CpG binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000071655-MONOMER.
ReactomeiR-HSA-3214815. HDACs deacetylate histones.
R-HSA-427389. ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression.
R-HSA-6804758. Regulation of TP53 Activity through Acetylation.
R-HSA-73762. RNA Polymerase I Transcription Initiation.
SIGNORiO95983.

Names & Taxonomyi

Protein namesi
Recommended name:
Methyl-CpG-binding domain protein 3
Alternative name(s):
Methyl-CpG-binding protein MBD3
Gene namesi
Name:MBD3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:6918. MBD3.

Subcellular locationi

  • Nucleus
  • Chromosome

  • Note: Nuclear, in discrete foci. Detected on chromatin, at promoter regions of active genes.

GO - Cellular componenti

  • cytoplasm Source: Ensembl
  • heterochromatin Source: Ensembl
  • nuclear chromatin Source: UniProtKB
  • nucleoplasm Source: Reactome
  • NuRD complex Source: BHF-UCL
  • protein complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi30H → K: No effect. Confers strong binding to methylated CpG (in vitro); when associated with Y-34. 2 Publications1
Mutagenesisi34F → A: Augments DNA binding activity, irrespective of DNA methylation. 2 Publications1
Mutagenesisi34F → Y: Confers weak binding to methylated CpG (in vitro). Confers strong binding to methylated CpG (in vitro); when associated with K-30. 2 Publications1

Organism-specific databases

DisGeNETi53615.
OpenTargetsiENSG00000071655.
PharmGKBiPA30661.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000962621 – 291Methyl-CpG-binding domain protein 3Add BLAST291

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei56PhosphoserineCombined sources1
Modified residuei85PhosphoserineCombined sources1
Modified residuei144PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO95983.
MaxQBiO95983.
PaxDbiO95983.
PeptideAtlasiO95983.
PRIDEiO95983.

PTM databases

iPTMnetiO95983.
PhosphoSitePlusiO95983.

Expressioni

Gene expression databases

BgeeiENSG00000071655.
CleanExiHS_MBD3.
ExpressionAtlasiO95983. baseline and differential.
GenevisibleiO95983. HS.

Organism-specific databases

HPAiCAB013265.

Interactioni

Subunit structurei

Heterodimer with MBD2. Part of the NuRD and the MeCP1 complex. Interacts with BCL6, HDAC1, MTA2, DNMT1, p66-alpha and p66-beta.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CEP76Q8TAP63EBI-1783068,EBI-742887
DDX5P178444EBI-1783068,EBI-351962
GATAD2BQ8WXI94EBI-1783068,EBI-923440
GOLGA2Q083793EBI-1783068,EBI-618309
ICA1Q050843EBI-1783068,EBI-1046751
KDM1AO603414EBI-1783068,EBI-710124
KRT15P190123EBI-1783068,EBI-739566
RCN3Q96D153EBI-1783068,EBI-746283
SDCBPO005603EBI-1783068,EBI-727004
TRIM54Q9BYV23EBI-1783068,EBI-2130429
ZNF277Q8WWA63EBI-1783068,EBI-10192794

Protein-protein interaction databases

BioGridi119788. 85 interactors.
DIPiDIP-46517N.
IntActiO95983. 63 interactors.
MINTiMINT-4822095.
STRINGi9606.ENSP00000156825.

Structurei

Secondary structure

1291
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi16 – 24Combined sources9
Beta strandi27 – 36Combined sources10
Helixi46 – 53Combined sources8
Turni54 – 56Combined sources3
Turni64 – 67Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MB7NMR-A1-70[»]
ProteinModelPortaliO95983.
SMRiO95983.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 72MBDPROSITE-ProRule annotationAdd BLAST72

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili216 – 245Sequence analysisAdd BLAST30

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi272 – 281Poly-Glu10

Sequence similaritiesi

Contains 1 MBD (methyl-CpG-binding) domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410INB5. Eukaryota.
ENOG410XSPC. LUCA.
GeneTreeiENSGT00410000025376.
HOGENOMiHOG000013073.
HOVERGENiHBG052417.
InParanoidiO95983.
KOiK11591.
OMAiQDQEMEH.
OrthoDBiEOG091G0I05.
PhylomeDBiO95983.
TreeFamiTF325032.

Family and domain databases

Gene3Di3.30.890.10. 2 hits.
InterProiIPR016177. DNA-bd_dom.
IPR032343. MBD2/MBD3_p55-bd.
IPR025884. MeCpG-bd_2/3_C_dom.
IPR001739. Methyl_CpG_DNA-bd.
[Graphical view]
PfamiPF01429. MBD. 1 hit.
PF14048. MBD_C. 1 hit.
PF16564. MBDa. 1 hit.
[Graphical view]
SMARTiSM00391. MBD. 1 hit.
[Graphical view]
SUPFAMiSSF54171. SSF54171. 1 hit.
PROSITEiPS50982. MBD. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95983-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MERKRWECPA LPQGWEREEV PRRSGLSAGH RDVFYYSPSG KKFRSKPQLA
60 70 80 90 100
RYLGGSMDLS TFDFRTGKML MSKMNKSRQR VRYDSSNQVK GKPDLNTALP
110 120 130 140 150
VRQTASIFKQ PVTKITNHPS NKVKSDPQKA VDQPRQLFWE KKLSGLNAFD
160 170 180 190 200
IAEELVKTMD LPKGLQGVGP GCTDETLLSA IASALHTSTM PITGQLSAAV
210 220 230 240 250
EKNPGVWLNT TQPLCKAFMV TDEDIRKQEE LVQQVRKRLE EALMADMLAH
260 270 280 290
VEELARDGEA PLDKACAEDD DEEDEEEEEE EPDPDPEMEH V
Length:291
Mass (Da):32,844
Last modified:May 1, 1999 - v1
Checksum:iB62134DD1BEB636B
GO
Isoform 2 (identifier: O95983-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     5-36: Missing.

Note: No experimental confirmation available.
Show »
Length:259
Mass (Da):29,014
Checksum:i2578753C1E5D6A0B
GO

Sequence cautioni

The sequence AAH32443 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0110815 – 36Missing in isoform 2. 1 PublicationAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF072247 mRNA. Translation: AAC68876.1.
AK290882 mRNA. Translation: BAF83571.1.
AC005943 Genomic DNA. Translation: AAC72104.1.
CH471139 Genomic DNA. Translation: EAW69477.1.
CH471139 Genomic DNA. Translation: EAW69478.1.
CH471139 Genomic DNA. Translation: EAW69481.1.
BC009372 mRNA. Translation: AAH09372.1.
BC009438 mRNA. Translation: AAH09438.1.
BC032443 mRNA. Translation: AAH32443.1. Different initiation.
BC043619 mRNA. Translation: AAH43619.1.
CCDSiCCDS12072.1. [O95983-1]
CCDS62481.1. [O95983-2]
RefSeqiNP_001268382.1. NM_001281453.1. [O95983-1]
NP_001268383.1. NM_001281454.1. [O95983-2]
UniGeneiHs.178728.
Hs.595754.

Genome annotation databases

EnsembliENST00000156825; ENSP00000156825; ENSG00000071655. [O95983-2]
ENST00000434436; ENSP00000412302; ENSG00000071655. [O95983-1]
GeneIDi53615.
KEGGihsa:53615.
UCSCiuc002ltj.5. human. [O95983-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF072247 mRNA. Translation: AAC68876.1.
AK290882 mRNA. Translation: BAF83571.1.
AC005943 Genomic DNA. Translation: AAC72104.1.
CH471139 Genomic DNA. Translation: EAW69477.1.
CH471139 Genomic DNA. Translation: EAW69478.1.
CH471139 Genomic DNA. Translation: EAW69481.1.
BC009372 mRNA. Translation: AAH09372.1.
BC009438 mRNA. Translation: AAH09438.1.
BC032443 mRNA. Translation: AAH32443.1. Different initiation.
BC043619 mRNA. Translation: AAH43619.1.
CCDSiCCDS12072.1. [O95983-1]
CCDS62481.1. [O95983-2]
RefSeqiNP_001268382.1. NM_001281453.1. [O95983-1]
NP_001268383.1. NM_001281454.1. [O95983-2]
UniGeneiHs.178728.
Hs.595754.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MB7NMR-A1-70[»]
ProteinModelPortaliO95983.
SMRiO95983.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119788. 85 interactors.
DIPiDIP-46517N.
IntActiO95983. 63 interactors.
MINTiMINT-4822095.
STRINGi9606.ENSP00000156825.

PTM databases

iPTMnetiO95983.
PhosphoSitePlusiO95983.

Proteomic databases

EPDiO95983.
MaxQBiO95983.
PaxDbiO95983.
PeptideAtlasiO95983.
PRIDEiO95983.

Protocols and materials databases

DNASUi53615.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000156825; ENSP00000156825; ENSG00000071655. [O95983-2]
ENST00000434436; ENSP00000412302; ENSG00000071655. [O95983-1]
GeneIDi53615.
KEGGihsa:53615.
UCSCiuc002ltj.5. human. [O95983-1]

Organism-specific databases

CTDi53615.
DisGeNETi53615.
GeneCardsiMBD3.
H-InvDBHIX0014590.
HGNCiHGNC:6918. MBD3.
HPAiCAB013265.
MIMi603573. gene.
neXtProtiNX_O95983.
OpenTargetsiENSG00000071655.
PharmGKBiPA30661.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410INB5. Eukaryota.
ENOG410XSPC. LUCA.
GeneTreeiENSGT00410000025376.
HOGENOMiHOG000013073.
HOVERGENiHBG052417.
InParanoidiO95983.
KOiK11591.
OMAiQDQEMEH.
OrthoDBiEOG091G0I05.
PhylomeDBiO95983.
TreeFamiTF325032.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000071655-MONOMER.
ReactomeiR-HSA-3214815. HDACs deacetylate histones.
R-HSA-427389. ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression.
R-HSA-6804758. Regulation of TP53 Activity through Acetylation.
R-HSA-73762. RNA Polymerase I Transcription Initiation.
SIGNORiO95983.

Miscellaneous databases

ChiTaRSiMBD3. human.
GeneWikiiMBD3.
GenomeRNAii53615.
PROiO95983.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000071655.
CleanExiHS_MBD3.
ExpressionAtlasiO95983. baseline and differential.
GenevisibleiO95983. HS.

Family and domain databases

Gene3Di3.30.890.10. 2 hits.
InterProiIPR016177. DNA-bd_dom.
IPR032343. MBD2/MBD3_p55-bd.
IPR025884. MeCpG-bd_2/3_C_dom.
IPR001739. Methyl_CpG_DNA-bd.
[Graphical view]
PfamiPF01429. MBD. 1 hit.
PF14048. MBD_C. 1 hit.
PF16564. MBDa. 1 hit.
[Graphical view]
SMARTiSM00391. MBD. 1 hit.
[Graphical view]
SUPFAMiSSF54171. SSF54171. 1 hit.
PROSITEiPS50982. MBD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMBD3_HUMAN
AccessioniPrimary (citable) accession number: O95983
Secondary accession number(s): A8K4B7
, D6W5Z2, Q6PIL9, Q6PJZ9, Q86XF4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: May 1, 1999
Last modified: November 30, 2016
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.