MBD5
Domain
Isoform 1
Possesses a methyl-binding domain (MBD) and a Pro-Trp-Trp-Pro (PWWP) domain (PubMed:20700456). Both MBD and PWWP domains are necessary for chromocentric localization (PubMed:20700456).
Isoform 2
Possesses a methyl-binding domain (MBD) but lacks the Pro-Trp-Trp-Pro (PWWP) domain.
The MBD may lack methyl-binding activity.
Function
Non-catalytic component of the polycomb repressive deubiquitinase (PR-DUB) complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-120' (H2AK119ub1) (PubMed:24634419). Important for stability of PR-DUB components and stimulating its ubiquitinase activity (PubMed:36180891). As part of the PR-DUB complex, associates with chromatin enriched in histone marks H3K4me1, H3K4me3, and H3K27Ac, but not in H3K27me3 (PubMed:36180891). The PR-DUB complex is an epigenetic regulator of gene expression, including genes involved in cell growth and survivability (PubMed:36180891). MBD5 and MBD6 containing complexes associate with distinct chromatin regions enriched in genes involved in different pathways (PubMed:36180891). Heterochromatin recruitment is not mediated by DNA methylation (PubMed:20700456). The PR-DUB complex is an epigenetic regulator of gene expression, including genes involved in development, cell communication, signaling, cell proliferation and cell viability (PubMed:36180891).
Involvement in disease
Intellectual developmental disorder, autosomal dominant 1
MRD1
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
None
The disease is caused by variants affecting the gene represented in this entry.
Tissue Specificity
Detected in heart, placenta, liver, skeletal muscle, kidney and pancreas.
Cellular localization
- Isoform 1
- Nucleus
- Chromosome
- Associates with heterochromatin containing chromocentres in a DNA methylation-independent manner (PubMed:20700456). Does not localize to sites of DNA damage (PubMed:24634419).
- Isoform 2
- Nucleus
- Does not associate with heterochromatin containing chromocentres (PubMed:20700456). Does not localize to sites of DNA damage (PubMed:24634419).
Alternative names
KIAA1461, MBD5, Methyl-CpG-binding domain protein 5, Methyl-CpG-binding protein MBD5