MBD3

MBD3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2MB7
Identifiers
Aliases	MBD3 , methyl-CpG binding domain protein 3
External IDs	OMIM: 603573; MGI: 1333812; HomoloGene: 2917; GeneCards: MBD3; OMA:MBD3 - orthologs
Gene location (Human) Chr. Chromosome 19 (human) [1] Band 19p13.3 Start 1,573,596 bp [1] End 1,592,865 bp [1]
Gene location (Mouse) Chr. Chromosome 10 (mouse) [2] Band 10 C1|10 39.72 cM Start 80,228,373 bp [2] End 80,235,384 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in apex of heart right frontal lobe cingulate gyrus anterior cingulate cortex amygdala mucosa of transverse colon anterior pituitary left uterine tube right hemisphere of cerebellum Brodmann area 10 Top expressed in ventricular zone dentate gyrus of hippocampal formation granule cell lip yolk sac muscle of thigh superior frontal gyrus choroid plexus of fourth ventricle right kidney epiblast primary visual cortex More reference expression data BioGPS More reference expression data
Gene ontology Molecular function methyl-CpG binding DNA binding nucleosomal DNA binding RNA polymerase II cis-regulatory region sequence-specific DNA binding protein binding chromatin binding histone deacetylase activity Cellular component nucleus nucleoplasm heterochromatin chromosome NuRD complex cytoplasm chromatin protein-containing complex Biological process response to estradiol tissue development embryonic organ development regulation of DNA methylation in utero embryonic development response to organic cyclic compound regulation of transcription, DNA-templated heart development DNA methylation-dependent heterochromatin assembly histone acetylation negative regulation of transcription by RNA polymerase II ageing brain development response to nutrient levels transcription, DNA-templated regulation of signal transduction by p53 class mediator histone deacetylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 10: 80.23 – 80.24 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

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. ^[9]

Interactions

MBD3 has been shown to interact with:

• AURKA, ^[10]
• GATAD2B, ^{[11] [12]}
• HDAC1, ^{[10] [13] [14]}
• MTA2, ^{[10] [13] [14]} and
• MBD2. ^{[13] [15]}

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

• Shen L, Zhang Y (June 2013). "5-Hydroxymethylcytosine: generation, fate, and genomic distribution". Current Opinion in Cell Biology. 25 (3): 289–96. doi:10.1016/j.ceb.2013.02.017. PMC   4060438 . PMID   23498661.
• Abbott WM, Mellor A, Edwards Y, Feizi T (April 1989). "Soluble bovine galactose-binding lectin. cDNA cloning reveals the complete amino acid sequence and an antigenic relationship with the major encephalitogenic domain of myelin basic protein". The Biochemical Journal. 259 (1): 283–90. doi:10.1042/bj2590283. PMC   1138502 . PMID   2470348.
• Zhang Y, LeRoy G, Seelig HP, Lane WS, Reinberg D (October 1998). "The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities". Cell. 95 (2): 279–89. doi: 10.1016/S0092-8674(00)81758-4 . PMID   9790534. S2CID   18786866.
• Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL (October 1998). "Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex". Nature. 395 (6705): 917–21. Bibcode:1998Natur.395..917T. doi:10.1038/27699. PMID   9804427. S2CID   4355885.
• 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.
• Wade PA, Gegonne A, Jones PL, Ballestar E, Aubry F, Wolffe AP (September 1999). "Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation". Nature Genetics. 23 (1): 62–6. doi:10.1038/12664. PMID   10471500. S2CID   52868103.
• Tatematsu KI, Yamazaki T, Ishikawa F (August 2000). "MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase". Genes to Cells. 5 (8): 677–88. doi: 10.1046/j.1365-2443.2000.00359.x . PMID   10947852. S2CID   25185979.
• Humphrey GW, Wang Y, Russanova VR, Hirai T, Qin J, Nakatani Y, Howard BH (March 2001). "Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1". The Journal of Biological Chemistry. 276 (9): 6817–24. doi: 10.1074/jbc.M007372200 . PMID   11102443.
• Shi Y, Downes M, Xie W, Kao HY, Ordentlich P, Tsai CC, Hon M, Evans RM (May 2001). "Sharp, an inducible cofactor that integrates nuclear receptor repression and activation". Genes & Development. 15 (9): 1140–51. doi:10.1101/gad.871201. PMC   312688 . PMID   11331609.
• 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.
• Schlegel J, Güneysu S, Mennel HD (2002). "Expression of the genes of methyl-binding domain proteins in human gliomas". Oncology Reports. 9 (2): 393–5. doi:10.3892/or.9.2.393. PMID   11836615.
• 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.
• 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.
• 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.
• Fujita N, Jaye DL, Kajita M, Geigerman C, Moreno CS, Wade PA (April 2003). "MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer". Cell. 113 (2): 207–19. doi: 10.1016/S0092-8674(03)00234-4 . PMID   12705869. S2CID   5773916.
• Fujita N, Jaye DL, Geigerman C, Akyildiz A, Mooney MR, Boss JM, Wade PA (October 2004). "MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation". Cell. 119 (1): 75–86. doi: 10.1016/j.cell.2004.09.014 . PMID   15454082. S2CID   17391732.