background:
F-box proteins are critical components of the SCF (Skp1-CUL-1-F-box protein) type E3 ubiquitin ligase complex and are involved in substrate recognition and protein recruitment. F-box proteins are members of a large family that regulate the cell cycle, immune response, signaling cascades and developmental programs by targeting proteins, such as cyclins, for degradation by the proteasome after ubiquitination. FBL11, also known as FBXL11 (F-box and leucine-rich repeat protein 11), CXXC8, KDM2A, JHDM1A (JmjC domain-containing histone demethylation protein 1A) or LILINA, is a 1,162 amino acid member of the F-box protein family that contains one F-box domain and localizes to the nucleus. Expressed ubiquitously with highest expression in testis, ovary and brain, FBL11 functions to demethylate the Lys-36 residue of histone H3, thereby modulating the histone code. Additionally, FBL11 is thought to promote the ubiquitination and subsequent degradation of various phosphorylated proteins. Three isoforms of FBL11 exist due to alternative splicing events.
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.
Subunit:
Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with CBX5/HP1A; the interaction promotes CBX5 localization to chromatin.
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.
Tissue Specificity:
Widely expressed, with highest levels in brain, testis and ovary, followed by lung.
Post-translational modifications:
Phosphorylated upon DNA damage, probably by ATM or ATR.
Similarity:
Belongs to the JHDM1 histone demethylase family.
Contains 1 CXXSLCtype zinc finger.
Contains 1 F-box domain.
Contains 1 JmjC domain.
Contains 6 LRR (leucine-rich) repeats.
Contains 1 PHD-type zinc finger.
Database links:
Entrez Gene: 22992 Human
Entrez Gene: 225876 Mouse
Omim: 605657 Human
SwissProt: Q9Y2K7 Human
SwissProt: P59997 Mouse
Unigene: 124147 Human
Unigene: 31941 Mouse
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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