Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5G6U7Q)

• DOT Name: Sentrin-specific protease 8 (SENP8)
• Synonyms: EC 3.4.22.-; Deneddylase-1; NEDD8-specific protease 1; Protease, cysteine 2; Sentrin/SUMO-specific protease SENP8
• Gene Name: SENP8
• UniProt ID: SENP8_HUMAN
• PDB ID: 1XT9; 2BKQ; 2BKR
• EC Number: 3.4.22.-
• Pfam ID: PF02902
• Sequence:
  MDPVVLSYMDSLLRQSDVSLLDPPSWLNDHIIGFAFEYFANSQFHDCSDHVSFISPEVTQ
  FIKCTSNPAEIAMFLEPLDLPNKRVVFLAINDNSNQAAGGTHWSLLVYLQDKNSFFHYDS
  HSRSNSVHAKQVAEKLEAFLGRKGDKLAFVEEKAPAQQNSYDCGMYVICNTEALCQNFFR
  QQTESLLQLLTPAYITKKRGEWKDLITTLAKK
• Function: Protease that catalyzes two essential functions in the NEDD8 pathway: processing of full-length NEDD8 to its mature form and deconjugation of NEDD8 from targeted proteins such as cullins or p53.
• Tissue Specificity: Broadly expressed, with highest levels in kidney and pancreas.
• Reactome Pathway:
  Neddylation (R-HSA-8951664)
  UCH proteinases (R-HSA-5689603)

Molecular Interaction Atlas (MIA) of This DOT

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Sentrin-specific protease 8 (SENP8).	[1]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sentrin-specific protease 8 (SENP8).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sentrin-specific protease 8 (SENP8).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sentrin-specific protease 8 (SENP8).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Sentrin-specific protease 8 (SENP8).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Sentrin-specific protease 8 (SENP8).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Sentrin-specific protease 8 (SENP8).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Sentrin-specific protease 8 (SENP8).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Sentrin-specific protease 8 (SENP8).	[9]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.