MBD3

Methyl-CpG-binding domain protein 3 is a protein that in humans is encoded by the MBD3 gene.[5][6][7]

MBD3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMBD3, methyl-CpG binding domain protein 3
External IDsOMIM: 603573 MGI: 1333812 HomoloGene: 2917 GeneCards: MBD3
Orthologs
SpeciesHumanMouse
Entrez

53615

17192

Ensembl

ENSG00000071655

ENSMUSG00000035478

UniProt

O95983

Q9Z2D8

RefSeq (mRNA)

NM_003926
NM_001281453
NM_001281454

NM_013595
NM_001306143

RefSeq (protein)

NP_001268382
NP_001268383

NP_001293072
NP_038623

Location (UCSC)Chr 19: 1.57 – 1.59 MbChr 10: 80.23 – 80.24 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). However, unlike the other family members, MBD3 is not capable of binding to methylated DNA but instead binds to hydroxymethylated DNA.[8] The predicted MBD3 protein shares 71% and 94% identity with MBD2 (isoform 1) and mouse Mbd3. MBD3 is a subunit of the NuRD, a multisubunit complex containing nucleosome remodeling and histone deacetylase activities. MBD3 mediates the association of metastasis-associated protein 2 (MTA2) with the core histone deacetylase complex.[7]

MBD3 also contains the coiled‐coil domain common to all three MBD3 isoforms. The coiled‐coil domain, but not the MBD domain, helps to maintain pluripotency of embryonic stem cells via the recruitment of polycomb repressive complex 2 to a subset of genes linked to development and organogenesis, thus establishing stable transcriptional repression.[9]

Interactions

MBD3 has been shown to interact with:

References

  1. GRCh38: Ensembl release 89: ENSG00000071655 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000035478 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Hendrich B, Bird A (November 1998). "Identification and characterization of a family of mammalian methyl-CpG binding proteins". Molecular and Cellular Biology. 18 (11): 6538–47. doi:10.1128/mcb.18.11.6538. PMC 109239. PMID 9774669.
  6. Hendrich B, Abbott C, McQueen H, Chambers D, Cross S, Bird A (September 1999). "Genomic structure and chromosomal mapping of the murine and human Mbd1, Mbd2, Mbd3, and Mbd4 genes". Mammalian Genome. 10 (9): 906–12. doi:10.1007/s003359901112. PMID 10441743. S2CID 819148.
  7. "Entrez Gene: MBD3 methyl-CpG binding domain protein 3".
  8. Yildirim O, Li R, Hung JH, Chen PB, Dong X, Ee LS, Weng Z, Rando OJ, Fazzio TG (December 2011). "Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells". Cell. 147 (7): 1498–510. doi:10.1016/j.cell.2011.11.054. PMC 3252821. PMID 22196727.
  9. Hirasaki M, Ueda A, Asaka MN, Uranishi K, Suzuki A, Kohda M, Mizuno Y, Okazaki Y, Nishimoto M, Sharif J, Koseki H, Okuda A (May 2018). "Identification of the Coiled-Coil Domain as an Essential Mbd3 Element for Preserving Lineage Commitment Potential of Embryonic Stem Cells". Stem Cells. 36 (9): 1355–1367. doi:10.1002/stem.2849. PMID 29761578.
  10. Sakai H, Urano T, Ookata K, Kim MH, Hirai Y, Saito M, Nojima Y, Ishikawa F (December 2002). "MBD3 and HDAC1, two components of the NuRD complex, are localized at Aurora-A-positive centrosomes in M phase". The Journal of Biological Chemistry. 277 (50): 48714–23. doi:10.1074/jbc.M208461200. PMID 12354758.
  11. Brackertz M, Boeke J, Zhang R, Renkawitz R (October 2002). "Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3". The Journal of Biological Chemistry. 277 (43): 40958–66. doi:10.1074/jbc.M207467200. PMID 12183469.
  12. Feng Q, Cao R, Xia L, Erdjument-Bromage H, Tempst P, Zhang Y (January 2002). "Identification and functional characterization of the p66/p68 components of the MeCP1 complex". Molecular and Cellular Biology. 22 (2): 536–46. doi:10.1128/MCB.22.2.536-546.2002. PMC 139742. PMID 11756549.
  13. Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D (August 1999). "Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation". Genes & Development. 13 (15): 1924–35. doi:10.1101/gad.13.15.1924. PMC 316920. PMID 10444591.
  14. Saito M, Ishikawa F (September 2002). "The mCpG-binding domain of human MBD3 does not bind to mCpG but interacts with NuRD/Mi2 components HDAC1 and MTA2". The Journal of Biological Chemistry. 277 (38): 35434–9. doi:10.1074/jbc.M203455200. PMID 12124384.
  15. Jiang CL, Jin SG, Pfeifer GP (December 2004). "MBD3L1 is a transcriptional repressor that interacts with methyl-CpG-binding protein 2 (MBD2) and components of the NuRD complex". The Journal of Biological Chemistry. 279 (50): 52456–64. doi:10.1074/jbc.M409149200. PMID 15456747.

Further reading

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