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sirtuin 2

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Target id: 2708

Nomenclature: sirtuin 2

Family: 3.5.1.- Histone deacetylases (HDACs)

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 389 19q13.2 SIRT2 sirtuin 2
Mouse - 389 7 B1 Sirt2 sirtuin 2
Rat - 350 1q21 Sirt2 sirtuin 2
Database Links Click here for help
Alphafold Q8IXJ6 (Hs), Q8VDQ8 (Mm), Q5RJQ4 (Rn)
BRENDA 3.5.1.-
CATH/Gene3D 3.40.50.1220
ChEMBL Target CHEMBL4462 (Hs), CHEMBL3232691 (Mm), CHEMBL3232690 (Rn)
Ensembl Gene ENSG00000068903 (Hs), ENSMUSG00000015149 (Mm), ENSRNOG00000020102 (Rn)
Entrez Gene 22933 (Hs), 64383 (Mm), 361532 (Rn)
Human Protein Atlas ENSG00000068903 (Hs)
KEGG Enzyme 3.5.1.-
KEGG Gene hsa:22933 (Hs), mmu:64383 (Mm), rno:361532 (Rn)
OMIM 604480 (Hs)
Pharos Q8IXJ6 (Hs)
RefSeq Nucleotide NM_012237 (Hs), NM_022432 (Mm), NM_001008368 (Rn)
RefSeq Protein NP_036369 (Hs), NP_071877 (Mm), NP_001008369 (Rn)
UniProtKB Q8IXJ6 (Hs), Q8VDQ8 (Mm), Q5RJQ4 (Rn)
Wikipedia SIRT2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Human SIRT2 histone deacetylase
PDB Id:  1J8F
Resolution:  1.7Å
Species:  Human
References:  4
Enzyme Reaction Click here for help
EC Number: 3.5.1.-

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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
compound 86 [PMID: 26982234] Small molecule or natural product Primary target of this compound Hs Inhibition 7.1 pKi 1
⤷ pKi 7.1 (Ki 7.3x10-8 M) [1]
compound 17 [PMID: 23570514] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pIC50 3
⤷ pIC50 8.7 (IC50 1.8x10-9 M) [3]
AGK2 Small molecule or natural product Hs Inhibition 4.5 – 5.8 pIC50 2,6
⤷ pIC50 4.5 – 5.8 (IC50 3.5x10-5 – 1.56x10-6 M) [2,6]
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Antigen presentation
General Comments
SIRT2 is NAD+-dependent protein deacetylase, which deacetylates internal lysines on histone, α-tubulin and some transcription factors. SIRT2 is the most abundant sirtuin in the brain [7]. Selective pharmacological blockade of SIRT2 is being investigated for potential clinical benefit in neurodegenerative diseases (and cancers [5]), with initial research focussing on the synucleinopathy, Parkinson's disease [6].

References

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1. Ai T, Wilson DJ, More SS, Xie J, Chen L. (2016) 5-((3-Amidobenzyl)oxy)nicotinamides as Sirtuin 2 Inhibitors. J Med Chem, 59 (7): 2928-41. [PMID:26982234]

2. Cui H, Kamal Z, Ai T, Xu Y, More SS, Wilson DJ, Chen L. (2014) Discovery of potent and selective sirtuin 2 (SIRT2) inhibitors using a fragment-based approach. J Med Chem, 57 (20): 8340-57. [PMID:25275824]

3. Disch JS, Evindar G, Chiu CH, Blum CA, Dai H, Jin L, Schuman E, Lind KE, Belyanskaya SL, Deng J et al.. (2013) Discovery of thieno[3,2-d]pyrimidine-6-carboxamides as potent inhibitors of SIRT1, SIRT2, and SIRT3. J Med Chem, 56 (9): 3666-79. [PMID:23570514]

4. Finnin MS, Donigian JR, Pavletich NP. (2001) Structure of the histone deacetylase SIRT2. Nat Struct Biol, 8 (7): 621-5. [PMID:11427894]

5. Hu J, Jing H, Lin H. (2014) Sirtuin inhibitors as anticancer agents. Future Med Chem, 6 (8): 945-66. [PMID:24962284]

6. Outeiro TF, Kontopoulos E, Altmann SM, Kufareva I, Strathearn KE, Amore AM, Volk CB, Maxwell MM, Rochet JC, McLean PJ et al.. (2007) Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science, 317 (5837): 516-9. [PMID:17588900]

7. Pandithage R, Lilischkis R, Harting K, Wolf A, Jedamzik B, Lüscher-Firzlaff J, Vervoorts J, Lasonder E, Kremmer E, Knöll B et al.. (2008) The regulation of SIRT2 function by cyclin-dependent kinases affects cell motility. J Cell Biol, 180 (5): 915-29. [PMID:18332217]

How to cite this page

3.5.1.- Histone deacetylases (HDACs): sirtuin 2. Last modified on 14/07/2016. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2708.