KDM2A

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
KDM2A
Protein FBXL11 PDB 2yu1.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesKDM2A, CXXC8, FBL11, FBL7, FBXL11, JHDM1A, LILINA, lysine demethylase 2A
External IDsMGI: 1354736 HomoloGene: 56564 GeneCards: KDM2A
Gene location (Human)
Chromosome 11 (human)
Chr.Chromosome 11 (human)[1]
Chromosome 11 (human)
Genomic location for KDM2A
Genomic location for KDM2A
Band11q13.2Start67,119,263 bp[1]
End67,258,082 bp[1]
RNA expression pattern
PBB GE FBXL11 208989 s at fs.png

PBB GE FBXL11 208987 s at fs.png

PBB GE FBXL11 208988 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001256405
NM_012308

NM_001001984

RefSeq (protein)

NP_001243334
NP_036440

NP_001001984

Location (UCSC)Chr 11: 67.12 – 67.26 MbChr 19: 4.31 – 4.4 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5][6][7] KDM2A is a member of the superfamily of alpha-ketoglutarate-dependent hydroxylases, which are non-haem iron-containing proteins.

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.[7]

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.[8] 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.[9] 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.[10]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000173120 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000054611 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ 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.
  6. ^ 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.
  7. ^ a b "Entrez Gene: FBXL11 F-box and leucine-rich repeat protein 11".
  8. ^ 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.
  9. ^ 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. PMC 3098377. PMID 20417597.
  10. ^ Pan D, Mao C, Zou T, Yao AY, Cooper MP, Boyartchuk V, Wang YX (2012). "The Histone Demethylase Jhdm1a Regulates Hepatic Gluconeogenesis". PLoS Genetics. 8 (6): e1002761. doi:10.1371/journal.pgen.1002761. PMC 3375226. PMID 22719268.

Further reading[edit]