Contents:
Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | - | 1643 | 17p13.1 | KDM6B | lysine demethylase 6B | |
| Mouse | - | 1641 | 11 B3 | Kdm6b | KDM1 lysine (K)-specific demethylase 6B | |
| Rat | - | 1361 | 10q24 | Kdm6b | lysine demethylase 6B | |
| Previous and Unofficial Names |
| JMJD3 | KDM1 lysine (K)-specific demethylase 6B | lysine (K)-specific demethylase 6B |
| Database Links |
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| Alphafold | O15054 (Hs), Q5NCY0 (Mm) |
| CATH/Gene3D | 1.25.40.10 |
| ChEMBL Target | CHEMBL1938211 (Hs) |
| Ensembl Gene | ENSG00000132510 (Hs), ENSMUSG00000018476 (Mm), ENSRNOG00000037613 (Rn) |
| Entrez Gene | 23135 (Hs), 216850 (Mm), 363630 (Rn) |
| Human Protein Atlas | ENSG00000132510 (Hs) |
| KEGG Gene | hsa:23135 (Hs), mmu:216850 (Mm), rno:363630 (Rn) |
| OMIM | 611577 (Hs) |
| Pharos | O15054 (Hs) |
| RefSeq Nucleotide | NM_001080424 (Hs), NM_001017426 (Mm), NM_001108829 (Rn) |
| RefSeq Protein | NP_001073893 (Hs), NP_001017426 (Mm), NP_001102299 (Rn) |
| SynPHARM | 81842 (in complex with IOX1) |
| UniProtKB | O15054 (Hs), Q5NCY0 (Mm) |
| Wikipedia | KDM6B (Hs) |
Download all structure-activity data for this target as a CSV file 
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Immunopharmacology Comments |
| In relation to the immune system, overexpression of KDM6B (JMJD3) is associated with inflammation [4-5] and with immune cell cancers such as T‐cell acute lymphoblastic leukemia and Hodgkin's lymphoma [1,9]. Selective KDM6B inhibitors which restore H3K27 tri-methylation marks on KDM6B transcriptional target genes are being developed e.g. Compound 3 [PMID: 29633584], with clinical efficacy applicable to the treatment of cancer, inflammation and neurological disorders being the ultimate goal. KDM6A and KDM6B have been reported as key regulators of metabolic switches that are involved in metabolic reprogramming of human T helper cell subsets [3]. In vitro, inhibition by GSK-J4 (the ester prodrug of GSK-J1, a KDM6A/B inhibitor) increases repressive H3K27me3 histone marks which causes down-regulation of the key transcription factor RORγt during Th17 differentiation, and in mature Th17 cells leads to metabolic reprogramming, suppression of IL-17 cytokine levels and reduced proliferation. This work suggests that inhibiting KDM6 demethylases may be an effective intervention in autoimmune inflammation. |
| Immuno Process Associations | ||
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References
1. Anderton JA, Bose S, Vockerodt M, Vrzalikova K, Wei W, Kuo M, Helin K, Christensen J, Rowe M, Murray PG et al.. (2011) The H3K27me3 demethylase, KDM6B, is induced by Epstein-Barr virus and over-expressed in Hodgkin's Lymphoma. Oncogene, 30 (17): 2037-43. [PMID:21242977]
2. Boloor A, Chen YK, Wallace MB. (2015) Histone demethylase inhibitors. Patent number: WO2015200709A1. Assignee: Quanticel Pharmaceuticals, Inc.. Priority date: 25/06/2015. Publication date: 30/12/2015.
3. Cribbs AP, Terlecki-Zaniewicz S, Philpott M, Baardman J, Ahern D, Lindow M, Obad S, Oerum H, Sampey B, Mander PK et al.. (2020) Histone H3K27me3 demethylases regulate human Th17 cell development and effector functions by impacting on metabolism. Proc Natl Acad Sci USA, 117 (11): 6056-6066. [PMID:32123118]
4. De Santa F, Narang V, Yap ZH, Tusi BK, Burgold T, Austenaa L, Bucci G, Caganova M, Notarbartolo S, Casola S et al.. (2009) Jmjd3 contributes to the control of gene expression in LPS-activated macrophages. EMBO J, 28 (21): 3341-52. [PMID:19779457]
5. De Santa F, Totaro MG, Prosperini E, Notarbartolo S, Testa G, Natoli G. (2007) The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing. Cell, 130 (6): 1083-94. [PMID:17825402]
6. Giordano A, Del Gaudio F, Johansson C, Riccio R, Oppermann U, Di Micco S. (2018) Virtual Fragment Screening Identification of a Quinoline-5,8-dicarboxylic Acid Derivative as a Selective JMJD3 Inhibitor. ChemMedChem, 13 (12): 1160-1164. [PMID:29633584]
7. Heinemann B, Nielsen JM, Hudlebusch HR, Lees MJ, Larsen DV, Boesen T, Labelle M, Gerlach LO, Birk P, Helin K. (2014) Inhibition of demethylases by GSK-J1/J4. Nature, 514 (7520): E1-2. [PMID:25279926]
8. Kruidenier L, Chung CW, Cheng Z, Liddle J, Che K, Joberty G, Bantscheff M, Bountra C, Bridges A, Diallo H et al.. (2012) A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature, 488 (7411): 404-8. [PMID:22842901]
9. Ntziachristos P, Tsirigos A, Welstead GG, Trimarchi T, Bakogianni S, Xu L, Loizou E, Holmfeldt L, Strikoudis A, King B et al.. (2014) Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia. Nature, 514 (7523): 513-7. [PMID:25132549]
10. Schiller R, Scozzafava G, Tumber A, Wickens JR, Bush JT, Rai G, Lejeune C, Choi H, Yeh TL, Chan MC et al.. (2014) A cell-permeable ester derivative of the JmjC histone demethylase inhibitor IOX1. ChemMedChem, 9 (3): 566-71. [PMID:24504543]
How to cite this page
1.14.11.- Histone demethylases: lysine demethylase 6B. Last modified on 20/07/2023. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2685.
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