MBD3

Last updated
MBD3
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases MBD3 , methyl-CpG binding domain protein 3
External IDs OMIM: 603573 MGI: 1333812 HomoloGene: 2917 GeneCards: MBD3
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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: 80.39 – 80.4 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]

Contents

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:

Related Research Articles

MBD1

Methyl-CpG-binding domain protein 1 is a protein that in humans is encoded by the MBD1 gene. The protein encoded by MBD1 binds to methylated sequences in DNA, and thereby influences transcription. It binds to a variety of methylated sequences, and appears to mediate repression of gene expression. It has been shown to play a role in chromatin modification through interaction with the histone H3K9 methyltransferase SETDB1. H3K9me3 is a repressive modification.

HDAC1

Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the HDAC1 gene.

Histone deacetylase 2

Histone deacetylase 2 (HDAC2) is an enzyme that in humans is encoded by the HDAC2 gene. It belongs to the histone deacetylase class of enzymes responsible for the removal of acetyl groups from lysine residues at the N-terminal region of the core histones. As such, it plays an important role in gene expression by facilitating the formation of transcription repressor complexes and for this reason is often considered an important target for cancer therapy.

HDAC3

Histone deacetylase 3 is an enzyme encoded by the HDAC3 gene in both humans and mice.

SIN3A

Paired amphipathic helix protein Sin3a is a protein that in humans is encoded by the SIN3A gene.

RBBP4

Histone-binding protein RBBP4 is a protein that in humans is encoded by the RBBP4 gene.

HDAC4

Histone deacetylase 4, also known as HDAC4, is a protein that in humans is encoded by the HDAC4 gene.

SUV39H1

Histone-lysine N-methyltransferase SUV39H1 is an enzyme that in humans is encoded by the SUV39H1 gene.

Methyl-CpG-binding domain protein 2

Methyl-CpG-binding domain protein 2 is a protein that in humans is encoded by the MBD2 gene.

MTA1

Metastasis-associated protein MTA1 is a protein that in humans is encoded by the MTA1 gene. MTA1 is the founding member of the MTA family of genes. MTA1 is primarily localized in the nucleus but also found to be distributed in the extra-nuclear compartments. MTA1 is a component of several chromatin remodeling complexes including the nucleosome remodeling and deacetylation complex (NuRD). MTA1 regulates gene expression by functioning as a coregulator to integrate DNA-interacting factors to gene activity. MTA1 participates in physiological functions in the normal and cancer cells. MTA1 is one of the most upregulated proteins in human cancer and associates with cancer progression, aggressive phenotypes, and poor prognosis of cancer patients.

RBBP7

Histone-binding protein RBBP7 is a protein that in humans is encoded by the RBBP7 gene.

Histone deacetylase 5

Histone deacetylase 5 is an enzyme that in humans is encoded by the HDAC5 gene.

HDAC9

Histone deacetylase 9 is an enzyme that in humans is encoded by the HDAC9 gene.

EIF3A

Eukaryotic translation initiation factor 3 subunit A (eIF3a) is a protein that in humans is encoded by the EIF3A gene. It is one of the subunits of Eukaryotic initiation factor 3 (eIF3) a multiprotein complex playing major roles in translation initiation in eukaryotes.

SAP30

Sin3A-associated protein, 30kDa, also known as SAP30, is a protein which in humans is encoded by the SAP30 gene.

CHD4

Chromodomain-helicase-DNA-binding protein 4 is an enzyme that in humans is encoded by the CHD4 gene.

MTA2

Metastasis-associated protein MTA2 is a protein that in humans is encoded by the MTA2 gene.

MIZF

Histone H4 transcription factor is a protein that in humans is encoded by the HINFP gene.

CBX5 (gene)

Chromobox protein homolog 5 is a protein that in humans is encoded by the CBX5 gene. It is a highly conserved, non-histone protein part of the heterochromatin family. The protein itself is more commonly called HP1α. Heterochromatin protein-1 (HP1) has an N-terminal domain that acts on methylated lysines residues leading to epigenetic repression. The C-terminal of this protein has a chromo shadow-domain (CSD) that is responsible for homodimerizing, as well as interacting with a variety of chromatin-associated, non-histone proteins.

In the field of molecular biology, the Mi-2/NuRDcomplex, is a group of associated proteins with both ATP-dependent chromatin remodeling and histone deacetylase activities. As of 2007, Mi-2/NuRD was the only known protein complex that couples chromatin remodeling ATPase and chromatin deacetylation enzymatic functions.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000071655 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 "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. 1 2 3 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. 1 2 3 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. 1 2 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