Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRATM7R)

• DOT Name: Testis-specific serine/threonine-protein kinase 1 (TSSK1B)
• Synonyms: TSK-1; TSK1; TSSK-1; Testis-specific kinase 1; EC 2.7.11.1; Serine/threonine-protein kinase 22A
• Gene Name: TSSK1B
• Related Disease:
  Systemic sclerosis
  Anxiety
  Anxiety disorder
  Autoimmune disease
  Depression
  Graft-versus-host disease
  Male infertility
  Scleroderma
  Cardiomyopathy
  Chronic graft versus host disease
• UniProt ID: TSSK1_HUMAN
• EC Number: 2.7.11.1
• Pfam ID: PF00069
• Sequence:
  MDDAAVLKRRGYLLGINLGEGSYAKVKSAYSERLKFNVAIKIIDRKKAPADFLEKFLPRE
  IEILAMLNHCSIIKTYEIFETSHGKVYIVMELAVQGDLLELIKTRGALHEDEARKKFHQL
  SLAIKYCHDLDVVHRDLKCDNLLLDKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPA
  YAAPEVLQGIPYQPKVYDIWSLGVILYIMVCGSMPYDDSNIKKMLRIQKEHRVNFPRSKH
  LTGECKDLIYHMLQPDVNRRLHIDEILSHCWMQPKARGSPSVAINKEGESSRGTEPLWTP
  EPGSDKKSATKLEPEGEAQPQAQPETKPEGTAMQMSRQSEILGFPSKPSTMETEEGPPQQ
  PPETRAQ
• Function: Testis-specific serine/threonine-protein kinase required during spermatid development. Phosphorylates 'Ser-288' of TSKS. Involved in the late stages of spermatogenesis, during the reconstruction of the cytoplasm. During spermatogenesis, required for the transformation of a ring-shaped structure around the base of the flagellum originating from the chromatoid body.
• Tissue Specificity: Testis-specific. Present in sperm (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Systemic sclerosis	DISF44L6	Definitive	Biomarker	[1]
Anxiety	DISIJDBA	Strong	Biomarker	[2]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[2]
Autoimmune disease	DISORMTM	Strong	Biomarker	[3]
Depression	DIS3XJ69	Strong	Biomarker	[2]
Graft-versus-host disease	DIS0QADF	Strong	Biomarker	[4]
Male infertility	DISY3YZZ	Strong	Genetic Variation	[5]
Scleroderma	DISVQ342	Strong	Biomarker	[6]
Cardiomyopathy	DISUPZRG	moderate	Biomarker	[1]
Chronic graft versus host disease	DIS1MM9J	moderate	Biomarker	[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 1 (TSSK1B).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Testis-specific serine/threonine-protein kinase 1 (TSSK1B).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Testis-specific serine/threonine-protein kinase 1 (TSSK1B).	[9]

References

• [1] Cardiomyopathy in murine models of systemic sclerosis.Arthritis Rheumatol. 2015 Feb;67(2):508-16. doi: 10.1002/art.38942.
• [2] Kinesiophobia and depression affect total knee arthroplasty outcome in a multivariate analysis of psychological and physical factors on 200 patients.Knee Surg Sports Traumatol Arthrosc. 2017 Nov;25(11):3417-3423. doi: 10.1007/s00167-016-4201-3. Epub 2016 Jun 21.
• [3] Mercuric chloride induces a strong immune activation, but does not accelerate the development of dermal fibrosis in tight skin 1 mice.Scand J Immunol. 2004 May;59(5):469-77. doi: 10.1111/j.0300-9475.2004.01415.x.
• [4] Identification of Optimal Mouse Models of Systemic Sclerosis by Interspecies Comparative Genomics.Arthritis Rheumatol. 2016 Aug;68(8):2003-15. doi: 10.1002/art.39658.
• [5] Targeted deletion of Tssk1 and 2 causes male infertility due to haploinsufficiency.Dev Biol. 2008 Jul 15;319(2):211-22. doi: 10.1016/j.ydbio.2008.03.047. Epub 2008 Apr 23.
• [6] Transgenic analysis of scleroderma: understanding key pathogenic events in vivo.Autoimmun Rev. 2004 Jun;3(4):285-93. doi: 10.1016/j.autrev.2003.10.003.
• [7] 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.
• [8] 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.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.