KDM2A

Domain

The JmjC domain mediates demethylation activity and is required for satellite silencing.

The CXXC zinc finger preferentially recognizes nonmethylated CpG DNA, and binding is blocked when the CpG DNA is methylated (PubMed:20417597). It is essential for its ability to repress the transcriptional activator activity of CLOCK-ARNTL/BMAL1 heterodimer (PubMed:26037310).

The F-box domain mediates interaction with UBB.

Function

Histone demethylase that specifically demethylates 'Lys-36' of histone H3, thereby playing a central role in histone code. Preferentially demethylates dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. May also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. Required to maintain the heterochromatic state. Associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. Required to sustain centromeric integrity and genomic stability, particularly during mitosis. Regulates circadian gene expression by repressing the transcriptional activator activity of CLOCK-ARNTL/BMAL1 heterodimer and RORA in a catalytically-independent manner (PubMed:26037310).

Sequence similarities

Belongs to the JHDM1 histone demethylase family.

Tissue specificity

Widely expressed, with highest levels in brain, testis and ovary, followed by lung.

Cellular localization

• Nucleus
• Nucleoplasm
• Punctate expression throughout the nucleoplasm and enriched in the perinucleolar region. Specifically nucleates at CpG islands where it's presence results in chromatin depleted in H3K36me2.

Alternative names

• Lysine-specific demethylase 2A
• CXXC-type zinc finger protein 8
• F-box and leucine-rich repeat protein 11
• F-box protein FBL7
• F-box protein Lilina
• F-box/LRR-repeat protein 11
• JmjC domain-containing histone demethylation protein 1A
• [Histone-H3]-lysine-36 demethylase 1A
• CXXC8
• FBL7
• FBL11
• KDM2A
• KIAA1004
• JHDM1A
• FBXL11

Database links

• entrezGene:22992
• omim:605657
• swissprot:Q9Y2K7

Target type

Proteins

Molecular weight

132793Da