MBD3

Protein-coding gene in the species Homo sapiens
MBD3
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

2MB7

Identifiers
AliasesMBD3, methyl-CpG binding domain protein 3
External IDsOMIM: 603573; MGI: 1333812; HomoloGene: 2917; GeneCards: MBD3; OMA:MBD3 - orthologs
Gene location (Human)
Chromosome 19 (human)
Chr.Chromosome 19 (human)[1]
Chromosome 19 (human)
Genomic location for MBD3
Genomic location for MBD3
Band19p13.3Start1,573,596 bp[1]
End1,592,865 bp[1]
Gene location (Mouse)
Chromosome 10 (mouse)
Chr.Chromosome 10 (mouse)[2]
Chromosome 10 (mouse)
Genomic location for MBD3
Genomic location for MBD3
Band10 C1|10 39.72 cMStart80,228,373 bp[2]
End80,235,384 bp[2]
RNA expression pattern
Bgee
HumanMouse (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
  • human ageing
  • brain development
  • response to nutrient levels
  • transcription, DNA-templated
  • regulation of signal transduction by p53 class mediator
  • histone deacetylation
Sources:Amigo / QuickGO
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

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:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000071655 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b "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. ^ a b c 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. ^ a b c 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. ^ a b 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.