lysine demethylase 1A

Target id: 2669

Nomenclature: lysine demethylase 1A

Family: 1.14.11.- Histone demethylases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for lysine demethylase 1A in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 876 1p36.12 KDM1A lysine demethylase 1A
Mouse - 853 4 D3 Kdm1a lysine (K)-specific demethylase 1A
Rat - 872 5q36 Kdm1a lysine demethylase 1A
Previous and Unofficial Names
AOF2 | KDM1 | LSD1 | lysine (K)-specific demethylase 1A
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
ORY-1001 Hs Inhibition >7.7 pIC50 5
pIC50 >7.7 (IC50 <2x10-8 M) [5]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
GSK-LSD1 Hs Inhibition 7.8 pIC50 9
pIC50 7.8 (IC50 1.6x10-8 M) [9]
OG-L002 Hs Inhibition 7.7 pIC50 4
pIC50 7.7 (IC50 2x10-8 M) [4]
Description: In vitro KDM1A demethylation assay using purified human KDM1A protein and dimethylated H3K4 peptide as substrate.
RN-1 Hs Inhibition 6.2 – 7.0 pIC50 7
pIC50 6.2 – 7.0 (IC50 7x10-7 – 1x10-7 M) [7]
Description: values.
GSK2879552 Hs Inhibition 6.4 pIC50 2
pIC50 6.4 [2]
NCL-1 Hs Inhibition 5.8 pIC50 8
pIC50 5.8 (IC50 1.6x10-6 M) [8]
tranylcypromine Hs Inhibition 4.4 pIC50 4
pIC50 4.4 (IC50 3.966x10-5 M) [4]
Description: In vitro KDM1A demethylation assay using purified human KDM1A protein and dimethylated H3K4 peptide as substrate.
Inhibitor Comments
Note that NCL-1 used to generate the IC50 in the table above is the 1S, 2R optical isomer [8].
Physiological Functions
Acts as a transcriptional coactivator or corepressor by demethylating lysine 4 and/or lysine 9 of histone H3 ( (H3K4me and H3K9me respectively). Acts only as part of a transcriptional complex eg with RCOR1/CoREST.
Species:  Human
Tissue: 
References:  1,3,6,10

References

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1. Hakimi MA, Bochar DA, Chenoweth J, Lane WS, Mandel G, Shiekhattar R. (2002) A core-BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes. Proc. Natl. Acad. Sci. U.S.A.99 (11): 7420-5. [PMID:12032298]

2. Johnson NW, Kasparec J, Miller WH, Rouse MB, Suarez D, Tian X. (2012) Cyclopropylamines as lsd1 inhibitors. Patent number: WO2012135113 A2. Assignee: Glaxosmithkline Llc. Priority date: 25/03/2011. Publication date: 04/10/2012.

3. Lee MG, Wynder C, Cooch N, Shiekhattar R. (2005) An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation. Nature437 (7057): 432-5. [PMID:16079794]

4. Liang Y, Quenelle D, Vogel JL, Mascaro C, Ortega A, Kristie TM. (2013) A novel selective LSD1/KDM1A inhibitor epigenetically blocks herpes simplex virus lytic replication and reactivation from latency. MBio4 (1): e00558-12. [PMID:23386436]

5. Maes T, Mascaró C, Ortega A, Lunardi S, Ciceri F, Somervaille TC, Buesa C. (2015) KDM1 histone lysine demethylases as targets for treatments of oncological and neurodegenerative disease. Epigenomics7 (4): 609-26. [PMID:26111032]

6. Metzger E, Wissmann M, Yin N, Müller JM, Schneider R, Peters AH, Günther T, Buettner R, Schüle R. (2005) LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature437 (7057): 436-9. [PMID:16079795]

7. Neelamegam R, Ricq EL, Malvaez M, Patnaik D, Norton S, Carlin SM, Hill IT, Wood MA, Haggarty SJ, Hooker JM. (2012) Brain-penetrant LSD1 inhibitors can block memory consolidation. ACS Chem Neurosci3 (2): 120-128. [PMID:22754608]

8. Ogasawara D, Suzuki T, Mino K, Ueda R, Khan MN, Matsubara T, Koseki K, Hasegawa M, Sasaki R, Nakagawa H et al.. (2011) Synthesis and biological activity of optically active NCL-1, a lysine-specific demethylase 1 selective inhibitor. Bioorg. Med. Chem.19 (12): 3702-8. [PMID:21227703]

9. SGC. GSK-LSD1 - a chemical probe for LSD1. Accessed on 03/03/2015. Modified on 03/03/2015. thegsk.org, http://www.thesgc.org/chemical-probes/LSD1

10. Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y. (2004) Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell119 (7): 941-53. [PMID:15620353]

How to cite this page

1.14.11.- Histone demethylases: lysine demethylase 1A. Last modified on 04/04/2017. Accessed on 22/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2669.