KDM2A Recombinant Protein

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. [provided by RefSeq, Jan 2012]

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. Ref.12 Ref.14

Catalytic activity: Protein N6,N(6)-dimethyl-L-lysine + 2-oxoglutarate + O2 = protein N(6)-methyl-L-lysine + succinate + formaldehyde + CO2. Ref.12Protein N(6)-methyl-L-lysine + 2-oxoglutarate + O2 = protein L-lysine + succinate + formaldehyde + CO2. Ref.12

Cofactor: Binds 1 Fe2+ ion per subunit. Ref.12

Subunit structure: Part of a SCF (SKP1-cullin-F-box) protein ligase complex

By similarity. Interacts with CBX5/HP1A; the interaction promotes CBX5 localization to chromatin. Ref.14

Subcellular location: Nucleus › nucleoplasm. Note: 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. Ref.14 Ref.19

Tissue specificity: Widely expressed, with highest levels in brain, testis and ovary, followed by lung. Ref.4

Domain: The JmjC domain mediates demethylation activity and is required for satellite silencing. Ref.12 Ref.19The CXXC zinc finger preferentially recognizes nonmethylated CpG DNA, and binding is blocked when the CpG DNA is methylated. Ref.12 Ref.19

Sequence similarities: Belongs to the JHDM1 histone demethylase family.Contains 1 CXXC-type zinc finger.Contains 1 F-box domain.Contains 1 JmjC domain.Contains 6 LRR (leucine-rich) repeats.Contains 1 PHD-type zinc finger.

Sequence caution: The sequence AAD56012.1 differs from that shown. Reason: Erroneous initiation. The sequence BAA76848.2 differs from that shown. Reason: Erroneous initiation. The sequence BAB15795.1 differs from that shown. Reason: Frameshift at position 410. The sequence BAJ05817.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.