KDM2B

KDM2B
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4O64
Identifiers
Aliases	KDM2B, CXXC2, FBXL10, Fbl10, JHDM1B, PCCX2, lysine demethylase 2B
External IDs	OMIM: 609078; MGI: 1354737; HomoloGene: 13069; GeneCards: KDM2B; OMA:KDM2B - orthologs
Gene location (Human) Chr. Chromosome 12 (human) Band 12q24.31 Start 121,429,096 bp End 121,581,023 bp
Gene location (Mouse) Chr. Chromosome 5 (mouse) Band 5|5 F Start 123,008,728 bp End 123,127,886 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of arm mucosa of ileum buccal mucosa cell ganglionic eminence ventricular zone cerebellar vermis thymus epithelium of nasopharynx monocyte tibialis anterior muscle Top expressed in zygote ganglionic eminence primary oocyte secondary oocyte spermatocyte morula spermatid mesencephalon epiblast neural tube More reference expression data BioGPS n/a
Gene ontology Molecular function DNA binding rRNA binding zinc ion binding dioxygenase activity metal ion binding histone demethylase activity protein binding histone H3-methyl-lysine-36 demethylase activity RNA binding oxidoreductase activity RNA polymerase II cis-regulatory region sequence-specific DNA binding Cellular component nucleoplasm nucleolus PcG protein complex nucleus chromosome Biological process negative regulation of neuron apoptotic process midbrain-hindbrain boundary morphogenesis regulation of transcription, DNA-templated lateral ventricle development histone H2A monoubiquitination negative regulation of neural precursor cell proliferation hindbrain development negative regulation of transcription by RNA polymerase II transcription, DNA-templated third ventricle development positive regulation of cell growth embryonic camera-type eye morphogenesis histone H3-K36 demethylation spermatogenesis forebrain development positive regulation of stem cell population maintenance initiation of neural tube closure midbrain development fourth ventricle development chromatin organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 84678 30841 Ensembl ENSG00000089094 ENSMUSG00000029475 UniProt Q8NHM5 Q6P1G2 RefSeq (mRNA) NM_001005366 NM_032590 NM_001003953 NM_001005866 NM_013910 NM_001378863 NM_001378864 NM_001378865 RefSeq (protein) NP_001005366 NP_115979 NP_001003953 NP_038938 NP_001365792 NP_001365793 NP_001365794 Location (UCSC) Chr 12: 121.43 – 121.58 Mb Chr 5: 123.01 – 123.13 Mb PubMed search
Wikidata
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The human KDM2B gene encodes the protein lysine (K)-specific demethylase 2B.

Tissue and subcellular distribution

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. 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.

Structure

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. KDM2B specifically recognizes and bind non-methylated DNA in CpG islands through its ZF-CxxC DNA binding domain. KDM2B consequently recruits the non-canonical polycomb repressive complex 1.1 (ncPRC1) to unmethylated CpG islands via a direct interaction with BCOR and PCGF1 leading to the mono-ubiquitylation of histone H2A on K119 and gene repression.

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

As part of the ncPRC1.1 complex, KDM2B was found to be rapidly and transiently recruited 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.

Clinical significance

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

Further reading

• Fujino T, Hasegawa M, Shibata S, Kishimoto T, Imai S, Takano T (May 2000). "PCCX1, a novel DNA-binding protein with PHD finger and CXXC domain, is regulated by proteolysis". Biochemical and Biophysical Research Communications. 271 (2): 305–10. doi:10.1006/bbrc.2000.2614. PMID 10799292.
• Tzatsos A, Paskaleva P, Ferrari F, Deshpande V, Stoykova S, Contino G, Wong KK, Lan F, Trojer P, Park PJ, Bardeesy N (February 2013). "KDM2B promotes pancreatic cancer via Polycomb-dependent and -independent transcriptional programs". The Journal of Clinical Investigation. 123 (2): 727–39. doi:10.1172/JCI64535. PMC 3561797. PMID 23321669.
• Tzatsos A, Pfau R, Kampranis SC, Tsichlis PN (February 2009). "Ndy1/KDM2B immortalizes mouse embryonic fibroblasts by repressing the Ink4a/Arf locus". Proceedings of the National Academy of Sciences of the United States of America. 106 (8): 2641–6. Bibcode:2009PNAS..106.2641T. doi:10.1073/pnas.0813139106. PMC 2650317. PMID 19202064.
• Janzer A, Stamm K, Becker A, Zimmer A, Buettner R, Kirfel J (September 2012). "The H3K4me3 histone demethylase Fbxl10 is a regulator of chemokine expression, cellular morphology, and the metabolome of fibroblasts". The Journal of Biological Chemistry. 287 (37): 30984–92. doi:10.1074/jbc.M112.341040. PMC 3438931. PMID 22825849.
• 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. Bibcode:2007Natur.450..309F. doi:10.1038/nature06255. PMID 17994099. S2CID 4325942.
• Koyama-Nasu R, David G, Tanese N (September 2007). "The F-box protein Fbl10 is a novel transcriptional repressor of c-Jun". Nature Cell Biology. 9 (9): 1074–80. doi:10.1038/ncb1628. PMID 17704768. S2CID 30551299.
• Szafranski K, Schindler S, Taudien S, Hiller M, Huse K, Jahn N, Schreiber S, Backofen R, Platzer M (2007). "Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns". Genome Biology. 8 (8): R154. doi:10.1186/gb-2007-8-8-r154. PMC 2374985. PMID 17672918.
• 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.
• Ge R, Wang Z, Zeng Q, Xu X, Olumi AF (July 2011). "F-box protein 10, an NF-κB-dependent anti-apoptotic protein, regulates TRAIL-induced apoptosis through modulating c-Fos/c-FLIP pathway". Cell Death and Differentiation. 18 (7): 1184–95. doi:10.1038/cdd.2010.185. PMC 3131965. PMID 21252908.

External links

• Overview of all the structural information available in the PDB for UniProt: Q8NHM5 (Lysine-specific demethylase 2B) at the PDBe-KB.

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