KDM2A

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Lysine (K)-specific demethylase 2A
Protein FBXL11 PDB 2yu1.png
PDB rendering based on 2yu1.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols KDM2A ; CXXC8; FBL11; FBL7; FBXL11; JHDM1A; LILINA
External IDs OMIM605657 MGI1354736 HomoloGene56564 GeneCards: KDM2A Gene
EC number 1.14.11.27
RNA expression pattern
PBB GE FBXL11 208987 s at tn.png
PBB GE FBXL11 208988 at tn.png
PBB GE FBXL11 208989 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 22992 225876
Ensembl ENSG00000173120 ENSMUSG00000054611
UniProt Q9Y2K7 P59997
RefSeq (mRNA) NM_001256405 NM_001001984
RefSeq (protein) NP_001243334 NP_001001984
Location (UCSC) Chr 11:
66.89 – 67.03 Mb
Chr 19:
4.32 – 4.4 Mb
PubMed search [1] [2]

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.[1][2][3]

Function[edit]

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.[3]

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.[4] 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.[5] 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.[6]

References[edit]

  1. ^ Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Jul 1999). "Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res 6 (1): 63–70. doi:10.1093/dnares/6.1.63. PMID 10231032. 
  2. ^ Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW (Dec 1999). "A family of mammalian F-box proteins". Curr Biol 9 (20): 1180–2. doi:10.1016/S0960-9822(00)80021-4. PMID 10531037. 
  3. ^ a b "Entrez Gene: FBXL11 F-box and leucine-rich repeat protein 11". 
  4. ^ Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y (February 2006). "Histone demethylation by a family of JmjC domain-containing proteins". Nature 439 (7078): 811–6. doi:10.1038/nature04433. PMID 16362057. 
  5. ^ Blackledge NP, Zhou JC, Tolstorukov MY, Farcas AM, Park PJ, Klose RJ (Apr 2010). "CpG islands recruit a histone H3 lysine 36 demethylase". Molecular Cell 38 (2): 179–90. doi:10.1016/j.molcel.2010.04.009. PMID 20417597. 
  6. ^ Pan, Dongning; Mao, Chunxiao; Zou, Tie; Yao, Annie Y.; Cooper, Marcus P.; Boyartchuk, Victor; Wang, Yong-Xu; Zierath, Juleen R. "The Histone Demethylase Jhdm1a Regulates Hepatic Gluconeogenesis". PLoS Genetics 8 (6): e1002761. doi:10.1371/journal.pgen.1002761. 

Further reading[edit]