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Protein

Methyl-CpG-binding domain protein 2

Gene

MBD2

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

Functioni

Binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides. Binds hemimethylated DNA as well. Recruits histone deacetylases and DNA methyltransferases. Acts as transcriptional repressor and plays a role in gene silencing. Functions as a scaffold protein, targeting GATAD2A and GATAD2B to chromatin to promote repression. May enhance the activation of some unmethylated cAMP-responsive promoters.6 Publications

Caution

Functional studies (PubMed:10050851, PubMed:10950960 and PubMed:12665568) have used a C-terminal fragment of isoform 1 which has been described originally as isoform MBD2b but cannot however be proven by supporting cDNA sequences.1 Publication

GO - Molecular functioni

  • C2H2 zinc finger domain binding Source: UniProtKB
  • chromatin binding Source: Ensembl
  • methyl-CpG binding Source: UniProtKB
  • mRNA binding Source: Ensembl
  • protein domain specific binding Source: UniProtKB
  • satellite DNA binding Source: ProtInc
  • siRNA binding Source: Ensembl

GO - Biological processi

Keywordsi

Molecular functionDNA-binding
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-427413 NoRC negatively regulates rRNA expression
R-HSA-73728 RNA Polymerase I Promoter Opening
SIGNORiQ9UBB5

Names & Taxonomyi

Protein namesi
Recommended name:
Methyl-CpG-binding domain protein 2
Alternative name(s):
Demethylase
Short name:
DMTase
Methyl-CpG-binding protein MBD2
Gene namesi
Name:MBD2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

EuPathDBiHostDB:ENSG00000134046.11
HGNCiHGNC:6917 MBD2
MIMi603547 gene
neXtProtiNX_Q9UBB5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi8932
OpenTargetsiENSG00000134046
PharmGKBiPA30660

Chemistry databases

ChEMBLiCHEMBL3707462

Polymorphism and mutation databases

BioMutaiMBD2
DMDMi50401198

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000962601 – 411Methyl-CpG-binding domain protein 2Add BLAST411

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei181PhosphoserineCombined sources1
Modified residuei407PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9UBB5
MaxQBiQ9UBB5
PaxDbiQ9UBB5
PeptideAtlasiQ9UBB5
PRIDEiQ9UBB5
ProteomicsDBi83923
83924 [Q9UBB5-3]

PTM databases

iPTMnetiQ9UBB5
PhosphoSitePlusiQ9UBB5

Expressioni

Tissue specificityi

Highly expressed in brain, heart, kidney, stomach, testis and placenta.1 Publication

Gene expression databases

BgeeiENSG00000134046 Expressed in 235 organ(s), highest expression level in leukocyte
CleanExiHS_MBD2
ExpressionAtlasiQ9UBB5 baseline and differential
GenevisibleiQ9UBB5 HS

Organism-specific databases

HPAiCAB037282
HPA067582
HPA067615

Interactioni

Subunit structurei

Heterodimer with MBD3. Component of the MeCP1 complex that contains HDAC1 and HDAC2. Binds DNMT1, MIZF, GPN1, SIN3A, GATAD2A/p66-alpha and GATAD2B/p66-beta. Interacts with DHX9.10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GATAD2AQ86YP44EBI-923391,EBI-726224

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114445, 51 interactors
ComplexPortaliCPX-880 MBD2/NuRD nucleosome remodeling and deacetylase complex
CORUMiQ9UBB5
IntActiQ9UBB5, 22 interactors
MINTiQ9UBB5
STRINGi9606.ENSP00000256429

Chemistry databases

BindingDBiQ9UBB5

Structurei

Secondary structure

1411
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

DisProtiDP01068
ProteinModelPortaliQ9UBB5
SMRiQ9UBB5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini145 – 213MBDPROSITE-ProRule annotationAdd BLAST69

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 149Necessary for interaction with DHX91 PublicationAdd BLAST149

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi6 – 140Gly-richAdd BLAST135
Compositional biasi50 – 96Arg-richAdd BLAST47

Phylogenomic databases

eggNOGiENOG410INB9 Eukaryota
ENOG410ZPAZ LUCA
GeneTreeiENSGT00410000025376
HOGENOMiHOG000013073
HOVERGENiHBG052417
InParanoidiQ9UBB5
KOiK11590
OMAiPAIWLNT
OrthoDBiEOG091G0I05
PhylomeDBiQ9UBB5
TreeFamiTF325032

Family and domain databases

InterProiView protein in InterPro
IPR016177 DNA-bd_dom_sf
IPR032343 MBD2/MBD3_p55-bd
IPR025884 MeCpG-bd_2/3_C_dom
IPR001739 Methyl_CpG_DNA-bd
PfamiView protein in Pfam
PF01429 MBD, 1 hit
PF14048 MBD_C, 1 hit
PF16564 MBDa, 1 hit
SMARTiView protein in SMART
SM00391 MBD, 1 hit
SUPFAMiSSF54171 SSF54171, 1 hit
PROSITEiView protein in PROSITE
PS50982 MBD, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9UBB5-1) [UniParc]FASTAAdd to basket
Also known as: MBD2a, MBD2b

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
MRAHPGGGRC CPEQEEGESA AGGSGAGGDS AIEQGGQGSA LAPSPVSGVR
60 70 80 90 100
REGARGGGRG RGRWKQAGRG GGVCGRGRGR GRGRGRGRGR GRGRGRPPSG
110 120 130 140 150
GSGLGGDGGG CGGGGSGGGG APRREPVPFP SGSAGPGPRG PRATESGKRM
160 170 180 190 200
DCPALPPGWK KEEVIRKSGL SAGKSDVYYF SPSGKKFRSK PQLARYLGNT
210 220 230 240 250
VDLSSFDFRT GKMMPSKLQK NKQRLRNDPL NQNKGKPDLN TTLPIRQTAS
260 270 280 290 300
IFKQPVTKVT NHPSNKVKSD PQRMNEQPRQ LFWEKRLQGL SASDVTEQII
310 320 330 340 350
KTMELPKGLQ GVGPGSNDET LLSAVASALH TSSAPITGQV SAAVEKNPAV
360 370 380 390 400
WLNTSQPLCK AFIVTDEDIR KQEERVQQVR KKLEEALMAD ILSRAADTEE
410
MDIEMDSGDE A
Length:411
Mass (Da):43,255
Last modified:May 1, 2000 - v1
Checksum:iFC4E5E0CF9BA0FFA
GO
Isoform 3 (identifier: Q9UBB5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     235-302: GKPDLNTTLP...SDVTEQIIKT → LRWNTHRPAP...YSRQNQSFPP
     303-411: Missing.

Note: Incomplete sequence.
Show »
Length:302
Mass (Da):31,745
Checksum:iCCEC65D926222717
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
X6RBL6X6RBL6_HUMAN
Methyl-CpG-binding domain protein 2
MBD2
241Annotation score:
J3KSA7J3KSA7_HUMAN
Methyl-CpG-binding domain protein 2
MBD2
72Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011077235 – 302GKPDL…QIIKT → LRWNTHRPAPWHALSRLCLL IRCLLCLECAYPLPLHLVNS YSSKTQLHCLHLWEACPAYS RQNQSFPP in isoform 3. 1 PublicationAdd BLAST68
Alternative sequenceiVSP_011078303 – 411Missing in isoform 3. 1 PublicationAdd BLAST109

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF072242 mRNA Translation: AAC68871.1
AF072246 mRNA Translation: AAC68875.1
AF120989, AF120988 Genomic DNA Translation: AAD56596.1
AF120993
, AF120988, AF120989, AF120990, AF120991, AF120992 Genomic DNA Translation: AAD56597.1
BC032638 mRNA Translation: AAH32638.1
CCDSiCCDS11953.1 [Q9UBB5-1]
CCDS45871.1 [Q9UBB5-3]
RefSeqiNP_003918.1, NM_003927.4 [Q9UBB5-1]
NP_056647.1, NM_015832.4 [Q9UBB5-3]
UniGeneiHs.25674

Genome annotation databases

EnsembliENST00000256429; ENSP00000256429; ENSG00000134046 [Q9UBB5-1]
ENST00000583046; ENSP00000464554; ENSG00000134046 [Q9UBB5-3]
GeneIDi8932
KEGGihsa:8932
UCSCiuc002lfg.2 human [Q9UBB5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF072242 mRNA Translation: AAC68871.1
AF072246 mRNA Translation: AAC68875.1
AF120989, AF120988 Genomic DNA Translation: AAD56596.1
AF120993
, AF120988, AF120989, AF120990, AF120991, AF120992 Genomic DNA Translation: AAD56597.1
BC032638 mRNA Translation: AAH32638.1
CCDSiCCDS11953.1 [Q9UBB5-1]
CCDS45871.1 [Q9UBB5-3]
RefSeqiNP_003918.1, NM_003927.4 [Q9UBB5-1]
NP_056647.1, NM_015832.4 [Q9UBB5-3]
UniGeneiHs.25674

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2L2LNMR-B360-393[»]
6C1AX-ray2.05A/B/E/F143-220[»]
6C1TX-ray1.84A/D143-220[»]
6C1UX-ray2.30A/B/E/F143-220[»]
6C1VX-ray2.30A/B/E/F143-220[»]
6C2FX-ray2.65A/D/G/J/M/P143-220[»]
6CNPX-ray2.10A/B143-220[»]
6CNQX-ray2.15A/B143-220[»]
DisProtiDP01068
ProteinModelPortaliQ9UBB5
SMRiQ9UBB5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114445, 51 interactors
ComplexPortaliCPX-880 MBD2/NuRD nucleosome remodeling and deacetylase complex
CORUMiQ9UBB5
IntActiQ9UBB5, 22 interactors
MINTiQ9UBB5
STRINGi9606.ENSP00000256429

Chemistry databases

BindingDBiQ9UBB5
ChEMBLiCHEMBL3707462

PTM databases

iPTMnetiQ9UBB5
PhosphoSitePlusiQ9UBB5

Polymorphism and mutation databases

BioMutaiMBD2
DMDMi50401198

Proteomic databases

EPDiQ9UBB5
MaxQBiQ9UBB5
PaxDbiQ9UBB5
PeptideAtlasiQ9UBB5
PRIDEiQ9UBB5
ProteomicsDBi83923
83924 [Q9UBB5-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000256429; ENSP00000256429; ENSG00000134046 [Q9UBB5-1]
ENST00000583046; ENSP00000464554; ENSG00000134046 [Q9UBB5-3]
GeneIDi8932
KEGGihsa:8932
UCSCiuc002lfg.2 human [Q9UBB5-1]

Organism-specific databases

CTDi8932
DisGeNETi8932
EuPathDBiHostDB:ENSG00000134046.11
GeneCardsiMBD2
HGNCiHGNC:6917 MBD2
HPAiCAB037282
HPA067582
HPA067615
MIMi603547 gene
neXtProtiNX_Q9UBB5
OpenTargetsiENSG00000134046
PharmGKBiPA30660
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410INB9 Eukaryota
ENOG410ZPAZ LUCA
GeneTreeiENSGT00410000025376
HOGENOMiHOG000013073
HOVERGENiHBG052417
InParanoidiQ9UBB5
KOiK11590
OMAiPAIWLNT
OrthoDBiEOG091G0I05
PhylomeDBiQ9UBB5
TreeFamiTF325032

Enzyme and pathway databases

ReactomeiR-HSA-427413 NoRC negatively regulates rRNA expression
R-HSA-73728 RNA Polymerase I Promoter Opening
SIGNORiQ9UBB5

Miscellaneous databases

ChiTaRSiMBD2 human
GeneWikiiMethyl-CpG-binding_domain_protein_2
GenomeRNAii8932
PROiPR:Q9UBB5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134046 Expressed in 235 organ(s), highest expression level in leukocyte
CleanExiHS_MBD2
ExpressionAtlasiQ9UBB5 baseline and differential
GenevisibleiQ9UBB5 HS

Family and domain databases

InterProiView protein in InterPro
IPR016177 DNA-bd_dom_sf
IPR032343 MBD2/MBD3_p55-bd
IPR025884 MeCpG-bd_2/3_C_dom
IPR001739 Methyl_CpG_DNA-bd
PfamiView protein in Pfam
PF01429 MBD, 1 hit
PF14048 MBD_C, 1 hit
PF16564 MBDa, 1 hit
SMARTiView protein in SMART
SM00391 MBD, 1 hit
SUPFAMiSSF54171 SSF54171, 1 hit
PROSITEiView protein in PROSITE
PS50982 MBD, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMBD2_HUMAN
AccessioniPrimary (citable) accession number: Q9UBB5
Secondary accession number(s): O95242, Q9UIS8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: May 1, 2000
Last modified: November 7, 2018
This is version 166 of the entry and version 1 of the sequence. See 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  2. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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