ZMYND11

Domain

The PWWP domain specifically recognizes and binds histone H3.3 trimethylated at 'Lys-36' (H3.3K36me3) and adopts a five-bladed beta-barrel fold with an extended C-terminal alpha-helix, with a conserved H3.3K36me3-binding aromatic cage formed by Phe-291 and Trp-294 of the beta1-beta2 loop and Phe-310 of the beta3-beta4 loop. Specific recognition of H3.3 histone is mediated by the encapsulation of the H3.3-specific 'Ser 31' residue in a composite pocket formed by the tandem bromo-PWWP domains.

Function

Chromatin reader that specifically recognizes and binds histone H3.3 trimethylated at 'Lys-36' (H3.3K36me3) and regulates RNA polymerase II elongation. Does not bind other histone H3 subtypes (H3.1 or H3.2) (By similarity). Colocalizes with highly expressed genes and functions as a transcription corepressor by modulating RNA polymerase II at the elongation stage. Binds non-specifically to dsDNA (PubMed:24675531). Acts as a tumor-suppressor by repressing a transcriptional program essential for tumor cell growth.

(Microbial infection) Inhibits Epstein-Barr virus EBNA2-mediated transcriptional activation and host cell proliferation, through direct interaction.

Involvement in disease

A chromosomal aberration involving ZMYND11 is a cause of acute poorly differentiated myeloid leukemia. Translocation (10;17)(p15;q21) with MBTD1.

Intellectual developmental disorder, autosomal dominant 30, with speech delay and behavioral abnormalities

MRD30

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD30 patients manifest intellectual disability, speech delay, and subtle facial dysmorphisms, including hypertelorism, ptosis, and a wide mouth. Behavioral abnormalities, including attention deficit-hyperactivity disorder, autistic features, and aggression are commonly observed.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Sumoylated following its interaction with PIAS1 and UBE2I.

Ubiquitinated, leading to proteasomal degradation.

Tissue Specificity

Ubiquitous.

Cellular localization

• Nucleus
• Chromosome
• Associates with chromatin and mitotic chromosomes.

Alternative names

BRAM1, BS69, ZMYND11, Zinc finger MYND domain-containing protein 11, Adenovirus 5 E1A-binding protein, Bone morphogenetic protein receptor-associated molecule 1, Protein BS69

Database links

swissprot:Q15326 genbank:NP_006615 entrezGene:10771 omim:608668 genbank:NP_997644