KDM2B

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KDM2B
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesKDM2B, CXXC2, FBXL10, Fbl10, JHDM1B, PCCX2, lysine demethylase 2B
External IDsMGI: 1354737 HomoloGene: 13069 GeneCards: KDM2B
Gene location (Human)
Chromosome 12 (human)
Chr.Chromosome 12 (human)[1]
Chromosome 12 (human)
Genomic location for KDM2B
Genomic location for KDM2B
Band12q24.31Start121,429,097 bp[1]
End121,581,015 bp[1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001005366
NM_032590

NM_001003953
NM_001005866
NM_013910

RefSeq (protein)

NP_001005366
NP_115979

NP_001003953
NP_038938

Location (UCSC)Chr 12: 121.43 – 121.58 MbChr 5: 122.87 – 122.99 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The human KDM2B gene encodes the protein Lysine (K)-specific demethylase 2B.[5]

Tissue and subcellular distribution[edit]

KDM2B is broadly and highly expressed in embryonic tissues (especially in the developing central nervous system of vertebrates). Expression of KDM2B is also retained in most organs in adults.[6] The protein is present in the nucleoplasm and is enriched in the nucleolus where it binds the transcribed region of ribosomal RNA to represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation.[7]

Structure[edit]

KDM2B protein has several domains including a JmjC domain that has a histone demethylase activity demethylating trimethylated Lys-4 and dimethylated Lys-36 of histone H3.[8][7] It is also the core scaffold of the non-canonical polycomb repressive complex 1.1 (ncPRC1.1) containing BCOR, PCGF1, RING1/2 and RYBP that mono-ubiquitylates histone H2A on K119.[9][10][11][12]

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. Multiple alternatively spliced transcript variants have been found for this gene, but the full-length nature of some variants has not been determined.[5]

As part of the ncPRC1.1 complex, KDM2B was found to rapidly and transiently recruite to sites of DNA damage in a PARP1- and TIMELESS-dependent manner to promote mono-ubiquitylation of histone H2A on K119 with concomitant local decrease of H2A levels and an increase of H2A.Z. These events promote transcriptional repression at DNA lesions, double strand break signaling, and homologous recombination repair. The activity of the ncPRC1.1 complex at DNA lesions was necessary for the proper recruitment of the two canonical PRC1 complexes (cPRC1.2 and cPRC1.4), defined by their PCGF subunits, MEL18 and BMI1 respectively. Therefore, recruitment of the ncPRC1.1 complex represents an early and critical regulatory step in homologous recombination repair.[13]

Clinical significance[edit]

Loss of KDM2B leads to severe developmental defects (growth defects in the brain, including failure of neural tube closure and craniofacial malformations, hematopoietic development) leading to embryonic lethality[14]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000089094 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029475 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ a b "Entrez Gene: Lysine (K)-specific demethylase 2B".
  6. ^ Saritas-Yildirim B, Pliner HA, Ochoa A, Silva EM (2015). "Genome-Wide Identification and Expression of Xenopus F-Box Family of Proteins". PLOS One. 10 (9): e0136929. doi:10.1371/journal.pone.0136929. PMC 4556705. PMID 26327321.
  7. ^ a b Frescas D, Guardavaccaro D, Bassermann F, Koyama-Nasu R, Pagano M (November 2007). "JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes". Nature. 450 (7167): 309–13. doi:10.1038/nature06255. PMID 17994099.
  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. ^ Gao Z, Zhang J, Bonasio R, Strino F, Sawai A, Parisi F, Kluger Y, Reinberg D (February 2012). "PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes". Molecular Cell. 45 (3): 344–56. doi:10.1016/j.molcel.2012.01.002. PMC 3293217. PMID 22325352.
  10. ^ Sánchez C, Sánchez I, Demmers JA, Rodriguez P, Strouboulis J, Vidal M (May 2007). "Proteomics analysis of Ring1B/Rnf2 interactors identifies a novel complex with the Fbxl10/Jhdm1B histone demethylase and the Bcl6 interacting corepressor". Molecular & Cellular Proteomics. 6 (5): 820–34. doi:10.1074/mcp.M600275-MCP200. PMID 17296600.
  11. ^ Gearhart MD, Corcoran CM, Wamstad JA, Bardwell VJ (September 2006). "Polycomb group and SCF ubiquitin ligases are found in a novel BCOR complex that is recruited to BCL6 targets". Molecular and Cellular Biology. 26 (18): 6880–9. doi:10.1128/MCB.00630-06. PMC 1592854. PMID 16943429.
  12. ^ Andricovich J, Kai Y, Peng W, Foudi A, Tzatsos A (March 2016). "Histone demethylase KDM2B regulates lineage commitment in normal and malignant hematopoiesis". The Journal of Clinical Investigation. 126 (3): 905–20. doi:10.1172/JCI84014. PMC 4767361. PMID 26808549.
  13. ^ Rona G, Roberti D, Yin Y, Pagan JK, Homer H, Sassani E, Zeke A, Busino L, Rothenberg E, Pagano M (July 2018). "PARP1-dependent recruitment of the FBXL10-RNF68-RNF2 ubiquitin ligase to sites of DNA damage controls H2A.Z loading". eLife. 7. doi:10.7554/eLife.38771. PMC 6037479. PMID 29985131.
  14. ^ Wang H, Wang L, Erdjument-Bromage H, Vidal M, Tempst P, Jones RS, Zhang Y (October 2004). "Role of histone H2A ubiquitination in Polycomb silencing". Nature. 431 (7010): 873–8. doi:10.1038/nature02985. PMID 15386022.

Further reading[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.