Aliases for SETD2 Gene
Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein belonging to a class of huntingtin interacting proteins characterized by WW motifs. This protein is a histone methyltransferase that is specific for lysine-36 of histone H3, and methylation of this residue is associated with active chromatin. This protein also contains a novel transcriptional activation domain and has been found associated with hyperphosphorylated RNA polymerase II. [provided by RefSeq, Aug 2008]
GeneCards Summary for SETD2 Gene
SETD2 (SET Domain Containing 2) is a Protein Coding gene. Diseases associated with SETD2 include Sotos Syndrome 1 and Retinal Ischemia. Among its related pathways are Chromatin organization and Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3. GO annotations related to this gene include histone-lysine N-methyltransferase activity. An important paralog of this gene is EHMT1.
UniProtKB/Swiss-Prot for SETD2 Gene
Histone methyltransferase that specifically trimethylates Lys-36 of histone H3 (H3K36me3) using dimethylated Lys-36 (H3K36me2) as substrate. Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation. Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A. Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction. H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A. H3K36me3 is also enhanced in intron-containing genes, suggesting that SETD2 recruitment is enhanced by splicing and that splicing is coupled to recruitment of elongating RNA polymerase. Required during angiogenesis. Recruited to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression.