Biology:KDM2A

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Lysine-specific demethylase 2A (KDM2A) also known as F-box and leucine-rich repeat protein 11 (FBXL11) is an enzyme that in humans is encoded by the KDM2A gene. KDM2A is a member of the superfamily of alpha-ketoglutarate-dependent hydroxylases, which are non-haem iron-containing proteins.

Function

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 6 highly degenerated leucine-rich repeats.

FBXL11/KDM2A is a histone H3 lysine 36 demethylase enzyme. The enzymatic activity of FBXL11/KDM2A relies on a conserved JmjC domain in the N-terminus of the protein that co-ordinates iron and alphaketoglutarate to catalyze demethylation via a hydroxylation based mechanism. It has recently been demonstrated that a ZF-CxxC DNA binding domain within FBXL11/KDM2A has the capacity to interact with non-methylated DNA and this domain targets FBXL11/KDM2A to CpG island regions of the genome where it specifically removes histone H3 lysine 36 methylation. This mechanism acts to create a chromatin environment at CpG islands that highlights these regulatory elements and differentiates them from non-regulatory regions in large complex mammalian genomes. In a study in mouse hepatocytes, this gene was shown to regulate hepatic gluconeogenesis.

Further reading

• "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.". DNA Res. 9 (3): 99–106. 2003. doi:10.1093/dnares/9.3.99. PMID 12168954. 
• "Identification of a family of human F-box proteins.". Curr. Biol. 9 (20): 1177–9. 1999. doi:10.1016/S0960-9822(00)80020-2. PMID 10531035. 
• "cDNA cloning and expression analysis of new members of the mammalian F-box protein family.". Genomics 67 (1): 40–7. 2001. doi:10.1006/geno.2000.6211. PMID 10945468. 
• "Characterization of long cDNA clones from human adult spleen.". DNA Res. 7 (6): 357–66. 2001. doi:10.1093/dnares/7.6.357. PMID 11214971. 
• "M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP.". Proc. Natl. Acad. Sci. U.S.A. 101 (13): 4419–24. 2004. doi:10.1073/pnas.0307700101. PMID 15070733. Bibcode: 2004PNAS..101.4419W. 
• "Functional proteomics mapping of a human signaling pathway.". Genome Res. 14 (7): 1324–32. 2004. doi:10.1101/gr.2334104. PMID 15231748. 
• "Nucleolar proteome dynamics.". Nature 433 (7021): 77–83. 2005. doi:10.1038/nature03207. PMID 15635413. Bibcode: 2005Natur.433...77A. 
• "Histone demethylation by a family of JmjC domain-containing proteins.". Nature 439 (7078): 811–6. 2006. doi:10.1038/nature04433. PMID 16362057. Bibcode: 2006Natur.439..811T. 
• "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.". Cell 127 (3): 635–48. 2006. doi:10.1016/j.cell.2006.09.026. PMID 17081983.