KDM2A

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class and, in addition to an F-box, contains at least six highly degenerated leucine-rich repeats. This family member plays a role in epigenetic silencing. It nucleates at CpG islands and specifically demethylates both mono- and di-methylated lysine-36 of histone H3. Alternative splicing results in multiple transcript variants.

Full Name

KDM2A

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).

Biological Process

Chromatin organizationIEA:UniProtKB-KW
Circadian regulation of gene expressionManual Assertion Based On ExperimentIMP:UniProtKB
Double-strand break repair via nonhomologous end joiningManual Assertion Based On ExperimentIMP:UniProtKB
Histone H3-K36 demethylationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of transcription by competitive promoter bindingManual Assertion Based On ExperimentIMP:UniProtKB
Protein demethylationManual Assertion Based On ExperimentIBA:GO_Central
Regulation of circadian rhythmManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central

Cellular Location

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.