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lysine demethylase 5B

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Target not currently curated in GtoImmuPdb

Target id: 2681

Nomenclature: lysine demethylase 5B

Family: 1.14.11.- Histone demethylases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1544 1q32.1 KDM5B lysine demethylase 5B
Mouse - 1544 1 58.24 cM Kdm5b lysine demethylase 5B
Rat - 1544 13q13 Kdm5b lysine demethylase 5B
Previous and Unofficial Names Click here for help
JARID1B | jumonji/ARID domain-containing protein 1B | Jumonji AT-rich interactive domain 1B | lysine (K)-specific demethylase 5B | PLU1
Database Links Click here for help
Alphafold Q9UGL1 (Hs), Q80Y84 (Mm)
CATH/Gene3D 3.30.40.10
ChEMBL Target CHEMBL3774295 (Hs)
Ensembl Gene ENSG00000117139 (Hs), ENSMUSG00000042207 (Mm), ENSRNOG00000060544 (Rn)
Entrez Gene 10765 (Hs), 75605 (Mm), 304809 (Rn)
Human Protein Atlas ENSG00000117139 (Hs)
KEGG Gene hsa:10765 (Hs), mmu:75605 (Mm), rno:304809 (Rn)
OMIM 605393 (Hs)
Pharos Q9UGL1 (Hs)
RefSeq Nucleotide NM_006618 (Hs), NM_152895 (Mm), NM_001107177 (Rn)
RefSeq Protein NP_006609 (Hs), NP_690855 (Mm), NP_001100647 (Rn)
SynPHARM 83291 (in complex with GSK-J1)
UniProtKB Q9UGL1 (Hs), Q80Y84 (Mm)
Wikipedia KDM5B (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human PLU-1 (JARID1B) in complex with KDOAM25a (note that JARID1B=KDM5B).
PDB Id:  5A3N
Ligand:  KDOAM25
Resolution:  2.0Å
Species:  Human
References: 

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
KDOAM25 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.7 pIC50 5
⤷ pIC50 7.7 (IC50 1.9x10-8 M) [5]
GSK-J1 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.8 pIC50 2
⤷ pIC50 6.8 (IC50 1.7x10-7 M) [2]
KDM5 inhibitor N71 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Irreversible inhibition 6.7 pIC50 3
⤷ pIC50 6.7 (IC50 2.2x10-7 M) [3]
Description: AlphaLISA derived IC50 values of the inhibition of KDM5B-mediated histone demethylation.
Compound 9 [doi:10.26434/chemrxiv.7072592.v1] Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 6.5 pIC50 6
⤷ pIC50 6.5 (IC50 3x10-7 M) [6]
PBIT Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.5 pIC50 4
⤷ pIC50 5.5 (IC50 3x10-6 M) [4]
GSK-J4 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.0 pIC50 2
⤷ pIC50 5.0 (IC50 9.7x10-6 M) [2]
Inhibitor Comments
PBIT also inhibits KDM5A and KDM5C, with IC50 values of 6000 and 4900 nm respectively [4].
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
Gene Expression and Pathophysiology Click here for help
Overexpression
Tissue or cell type: 
Pathophysiology:  Various cancers
Species:  Human
Technique: 
References:  1
General Comments
KDM5B is an H3K4 histone demethylase [7], belonging to a subfamily of demethylases responsible for the demethylation of H3K4me3 [4].

References

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1. Blair LP, Cao J, Zou MR, Sayegh J, Yan Q. (2011) Epigenetic Regulation by Lysine Demethylase 5 (KDM5) Enzymes in Cancer. Cancers (Basel), 3 (1): 1383-404. [PMID:21544224]

2. 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]

3. Horton JR, Woodcock CB, Chen Q, Liu X, Zhang X, Shanks J, Rai G, Mott BT, Jansen DJ, Kales SC et al.. (2018) Structure-Based Engineering of Irreversible Inhibitors against Histone Lysine Demethylase KDM5A. J Med Chem, 61 (23): 10588-10601. [PMID:30392349]

4. Sayegh J, Cao J, Zou MR, Morales A, Blair LP, Norcia M, Hoyer D, Tackett AJ, Merkel JS, Yan Q. (2013) Identification of small molecule inhibitors of Jumonji AT-rich interactive domain 1B (JARID1B) histone demethylase by a sensitive high throughput screen. J Biol Chem, 288 (13): 9408-17. [PMID:23408432]

5. Tumber A, Nuzzi A, Hookway ES, Hatch SB, Velupillai S, Johansson C, Kawamura A, Savitsky P, Yapp C, Szykowska A et al.. (2017) Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma Cells. Cell Chem Biol, 24 (3): 371-380. [PMID:28262558]

6. Vazquez-Rodriguez S, Wright M, Rogers CM, Cribbs AP, Velupillai S, Philpott M, Lee H, Dunford JE, Huber KVM, Robers MB et al.. (2019) Design, Synthesis and Characterization of Covalent KDM5 Inhibitors. Angew Chem Int Ed Engl, 58 (2): 515-519. DOI: 10.26434/chemrxiv.7072592.v1 [PMID:30431220]

7. Yamane K, Tateishi K, Klose RJ, Fang J, Fabrizio LA, Erdjument-Bromage H, Taylor-Papadimitriou J, Tempst P, Zhang Y. (2007) PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation. Mol Cell, 25 (6): 801-12. [PMID:17363312]

How to cite this page

1.14.11.- Histone demethylases: lysine demethylase 5B. Last modified on 04/08/2023. Accessed on 11/09/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2681.