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Reviewed, UniProtKB/Swiss-Prot O95983 (MBD3_HUMAN)

Last modified June 16, 2009. Version 64. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Methyl-CpG-binding domain protein 3
Alternative name(s):
    Methyl-CpG-binding protein MBD3
Gene names
Name: MBD3
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length291 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Does not bind DNA by itself. Recruits histone deacetylases and DNA methyltransferases. Acts as transcriptional repressor and plays a role in gene silencing. Ref.1 Ref.4 Ref.6

Subunit structure

Heterodimer with MBD2. Part of the NuRD and the MeCP1 complex. Binds HDAC1, MTA2, DNMT1, p66-alpha and p66-beta. Ref.4

Subcellular location

Nucleus. Note: Nuclear, in discrete foci. Ref.1

Sequence similarities

Contains 1 MBD (methyl-CpG-binding) domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DomainCoiled coil
   PTMPhosphoprotein
Gene Ontology (GO)
   Biological processtranscription

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular functionDNA binding Ref.1

Traceable author statement. Source: ProtInc

protein binding Ref.7

Inferred from physical interaction. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Evi1P144041EBI-1783068,EBI-1994523From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O95983-1)

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.
Isoform 2 (identifier: O95983-2)

The sequence of this isoform differs from the canonical sequence as follows:
     5-36: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 291291Methyl-CpG-binding domain protein 3
PRO_0000096262

Regions

Domain1 – 7272MBD
Coiled coil216 – 24530 Potential
Compositional bias272 – 28110Poly-Glu

Amino acid modifications

Modified residue561Phosphoserine Ref.9

Natural variations

Alternative sequence5 – 3632Missing in isoform 2.
VSP_011081

Experimental info

Mutagenesis301H → K: No effect. Confers strong binding to methylated CpG (in vitro); when associated with Y-30. Ref.6
Mutagenesis341F → A: Augments DNA binding activity, irrespective of DNA methylation. Ref.6
Mutagenesis341F → Y: Confers weak binding to methylated CpG (in vitro). Confers strong binding to methylated CpG (in vitro); when associated with K-30. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: B62134DD1BEB636B

FASTA29132,844
        10         20         30         40         50         60 
MERKRWECPA LPQGWEREEV PRRSGLSAGH RDVFYYSPSG KKFRSKPQLA RYLGGSMDLS 

        70         80         90        100        110        120 
TFDFRTGKML MSKMNKSRQR VRYDSSNQVK GKPDLNTALP VRQTASIFKQ PVTKITNHPS 

       130        140        150        160        170        180 
NKVKSDPQKA VDQPRQLFWE KKLSGLNAFD IAEELVKTMD LPKGLQGVGP GCTDETLLSA 

       190        200        210        220        230        240 
IASALHTSTM PITGQLSAAV EKNPGVWLNT TQPLCKAFMV TDEDIRKQEE LVQQVRKRLE 

       250        260        270        280        290 
EALMADMLAH VEELARDGEA PLDKACAEDD DEEDEEEEEE EPDPDPEMEH V 

« Hide

Isoform 2.

Checksum: 2578753C1E5D6A0B
Show »

FASTA25929,014

References

« Hide 'large scale' references
[1]"Identification and characterization of a family of mammalian methyl-CpG binding proteins."
Hendrich B., Bird A.
Mol. Cell. Biol. 18:6538-6547(1998) [PubMed: 9774669] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION.
[2]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed: 15057824] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain, Cervix, Muscle and Uterus.
[4]"MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase."
Tatematsu K., Yamazaki T., Ishikawa F.
Genes Cells 5:677-688(2000) [PubMed: 10947852] [Abstract]
Cited for: FUNCTION, HETERODIMERIZATION WITH MBD2, INTERACTION WITH DNMT1.
[5]"Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1."
Humphrey G.W., Wang Y., Russanova V.R., Hirai T., Qin J., Nakatani Y., Howard B.H.
J. Biol. Chem. 276:6817-6824(2001) [PubMed: 11102443] [Abstract]
Cited for: INTERACTION WITH THE HDAC1 COMPLEX, MASS SPECTROMETRY.
[6]"The mCpG-binding domain of human MBD3 does not bind to mCpG but interacts with NuRD/Mi2 components HDAC1 and MTA2."
Saito M., Ishikawa F.
J. Biol. Chem. 277:35434-35439(2002) [PubMed: 12124384] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HDAC1; MTA2 AND THE NURD COMPLEX, MUTAGENESIS OF HIS-30 AND PHE-34.
[7]"Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3."
Brackertz M., Boeke J., Zhang R., Renkawitz R.
J. Biol. Chem. 277:40958-40966(2002) [PubMed: 12183469] [Abstract]
Cited for: INTERACTION WITH P66ALPHA AND P66BETA.
[8]"Identification and functional characterization of the p66/p68 components of the MeCP1 complex."
Feng Q., Cao R., Xia L., Erdjument-Bromage H., Tempst P., Zhang Y.
Mol. Cell. Biol. 22:536-546(2002) [PubMed: 11756549] [Abstract]
Cited for: INTERACTION WITH P66BETA AND THE MECP1 COMPLEX.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56, MASS SPECTROMETRY.
[10]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+Additional computationally mapped references.

Cross-references

Sequence databases

AF072247 mRNA. Translation: AAC68876.1.
AC005943 Genomic DNA. Translation: AAC72104.1.
BC009372 mRNA. Translation: AAH09372.1.
BC009438 mRNA. Translation: AAH09438.1.
BC032443 mRNA. Translation: AAH32443.1. Different initiation.
BC043619 mRNA. Translation: AAH43619.1.
IPIIPI00439194.
IPI00439195.
RefSeqNP_003917.1.
UniGeneHs.178728

3D structure databases

HSSPHSSP built from PDB template 1IG4 based on UniProtKB Q9UIS9.
ModBaseSearch...

Protein-protein interaction databases

IntActO95983. 2 interactions.

PTM databases

PhosphoSiteO95983.

Proteomic databases

PRIDEO95983.

Genome annotation databases

EnsemblENSG00000071655. Homo sapiens. [Contig view]
GeneID53615.
KEGGhsa:53615.

Organism-specific databases

GeneCardsGC19M001527.
H-InvDBHIX0014590.
HGNCHGNC:6918. MBD3.
HPACAB013265.
MIM603573. gene.
PharmGKBPA30661.
GenAtlasSearch...

Phylogenomic databases

HOGENOMO95983.
HOVERGENO95983.
OMAO95983. RQRMRYD.

Enzyme and pathway databases

Pathway_Interaction_DBhdac_classi_pathway. Signaling events mediated by HDAC Class I.

Gene expression databases

ArrayExpressO95983.
BgeeO95983.
CleanExHS_MBD3.
GermOnlineENSG00000071655. Homo sapiens.

Family and domain databases

InterProIPR001739. Methyl_CpG_DNA-bd.
[Graphical view]
Gene3DG3DSA:3.30.890.10. Methyl_CpG_DNA-bd. 1 hit.
PfamPF01429. MBD. 1 hit.
[Graphical view]
SMARTSM00391. MBD. 1 hit.
[Graphical view]
PROSITEPS50982. MBD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio56092.
SOURCESearch...

Entry information

Entry nameMBD3_HUMAN
AccessionPrimary (citable) accession number: O95983
Secondary accession number(s): Q6PIL9, Q6PJZ9, Q86XF4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: May 1, 1999
Last modified: June 16, 2009
This is version 64 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents