KDM2A

KDM2A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2YU1, 2YU2, 4BBQ
Identifiers
Aliases	KDM2A , CXXC8, FBL11, FBL7, FBXL11, JHDM1A, LILINA, lysine demethylase 2A
External IDs	OMIM: 605657 MGI: 1354736 HomoloGene: 56564 GeneCards: KDM2A
Gene location (Human) Chr. Chromosome 11 (human) [1] Band 11q13.2 Start 67,119,263 bp [1] End 67,258,082 bp [1]
Gene location (Mouse) Chr. Chromosome 19 (mouse) [2] Band 19|19 A Start 4,364,447 bp [2] End 4,448,313 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in amniotic fluid germinal epithelium tibia sural nerve nipple visceral pleura parietal pleura bone marrow cells thymus pylorus Top expressed in hand aortic valve ascending aorta lip thymus foot esophagus internal carotid artery cerebellar cortex supraoptic nucleus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding oxidoreductase activity zinc ion binding dioxygenase activity metal ion binding histone demethylase activity protein binding histone H3-methyl-lysine-36 demethylase activity DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleoplasm nucleus Biological process double-strand break repair via nonhomologous end joining regulation of transcription, DNA-templated histone H3-K36 demethylation transcription, DNA-templated chromatin organization regulation of transcription by RNA polymerase II negative regulation of transcription by competitive promoter binding circadian regulation of gene expression regulation of circadian rhythm rhythmic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 22992 225876 Ensembl ENSG00000173120 ENSMUSG00000054611 UniProt Q9Y2K7 P59997 RefSeq (mRNA) NM_001256405 NM_012308 NM_001001984 RefSeq (protein) NP_001243334 NP_036440 NP_001001984 Location (UCSC) Chr 11: 67.12 – 67.26 Mb Chr 19: 4.36 – 4.45 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/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

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

1. GRCh38: Ensembl release 89: ENSG00000173120 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000054611 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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. Bibcode:1999CBio....9.1180W. doi: 10.1016/S0960-9822(00)80021-4 . PMID   10531037. S2CID   14341845.
7. "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. Bibcode:2006Natur.439..811T. doi:10.1038/nature04433. PMID   16362057. S2CID   4415889.
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

• Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (2003). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Res. 9 (3): 99–106. doi: 10.1093/dnares/9.3.99 . PMID   12168954.
• Cenciarelli C, Chiaur DS, Guardavaccaro D, Parks W, Vidal M, Pagano M (1999). "Identification of a family of human F-box proteins". Curr. Biol. 9 (20): 1177–9. Bibcode:1999CBio....9.1177C. doi: 10.1016/S0960-9822(00)80020-2 . PMID   10531035. S2CID   7467493.
• Ilyin GP, Rialland M, Pigeon C, Guguen-Guillouzo C (2001). "cDNA cloning and expression analysis of new members of the mammalian F-box protein family". Genomics. 67 (1): 40–7. doi:10.1006/geno.2000.6211. PMID   10945468.
• Hattori A, Okumura K, Nagase T, Kikuno R, Hirosawa M, Ohara O (2001). "Characterization of long cDNA clones from human adult spleen". DNA Res. 7 (6): 357–66. doi: 10.1093/dnares/7.6.357 . PMID   11214971.
• Watanabe N, Arai H, Nishihara Y, Taniguchi M, Watanabe N, Hunter T, Osada H (2004). "M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP". Proc. Natl. Acad. Sci. U.S.A. 101 (13): 4419–24. Bibcode:2004PNAS..101.4419W. doi: 10.1073/pnas.0307700101 . PMC   384762 . PMID   15070733.
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM (2004). "Functional proteomics mapping of a human signaling pathway". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC   442148 . PMID   15231748.
• Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M (2005). "Nucleolar proteome dynamics". Nature. 433 (7021): 77–83. Bibcode:2005Natur.433...77A. doi:10.1038/nature03207. PMID   15635413. S2CID   4344740.
• Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y (2006). "Histone demethylation by a family of JmjC domain-containing proteins". Nature. 439 (7078): 811–6. Bibcode:2006Natur.439..811T. doi:10.1038/nature04433. PMID   16362057. S2CID   4415889.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi: 10.1016/j.cell.2006.09.026 . PMID   17081983. S2CID   7827573.