Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1OYTXA)

• DOT Name: Testis-specific serine/threonine-protein kinase 6 (TSSK6)
• Synonyms: TSK-6; TSSK-6; Testis-specific kinase 6; EC 2.7.11.1; Cancer/testis antigen 72; CT72; Serine/threonine-protein kinase SSTK; Small serine/threonine kinase
• Gene Name: TSSK6
• Related Disease: Neoplasm
• UniProt ID: TSSK6_HUMAN
• EC Number: 2.7.11.1
• Pfam ID: PF00069
• Sequence:
  MSGDKLLSELGYKLGRTIGEGSYSKVKVATSKKYKGTVAIKVVDRRRAPPDFVNKFLPRE
  LSILRGVRHPHIVHVFEFIEVCNGKLYIVMEAAATDLLQAVQRNGRIPGVQARDLFAQIA
  GAVRYLHDHHLVHRDLKCENVLLSPDERRVKLTDFGFGRQAHGYPDLSTTYCGSAAYASP
  EVLLGIPYDPKKYDVWSMGVVLYVMVTGCMPFDDSDIAGLPRRQKRGVLYPEGLELSERC
  KALIAELLQFSPSARPSAGQVARNCWLRAGDSG
• Function: Required for sperm production and function. Plays a role in DNA condensation during postmeiotic chromatin remodeling.
• Tissue Specificity: Highly expressed in testis. Expressed at lower levels in colon, small intestine, ovary, prostate, thymus, spleen and peripheral blood leukocytes.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Genetic Variation	[1]

2 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 Testis-specific serine/threonine-protein kinase 6 (TSSK6).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Testis-specific serine/threonine-protein kinase 6 (TSSK6).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Testis-specific serine/threonine-protein kinase 6 (TSSK6).	[3]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Testis-specific serine/threonine-protein kinase 6 (TSSK6).	[4]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of Testis-specific serine/threonine-protein kinase 6 (TSSK6).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Testis-specific serine/threonine-protein kinase 6 (TSSK6).	[7]

References

• [1] Landscape of tumor-infiltrating T cell repertoire of human cancers.Nat Genet. 2016 Jul;48(7):725-32. doi: 10.1038/ng.3581. Epub 2016 May 30.
• [2] 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.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [7] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.