Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA5UXAX)

• DOT Name: L-seryl-tRNA(Sec) kinase (PSTK)
• Synonyms: EC 2.7.1.164; O-phosphoseryl-tRNA(Sec) kinase
• Gene Name: PSTK
• Related Disease: High blood pressure
• UniProt ID: PSTK_HUMAN
• EC Number: 2.7.1.164
• Pfam ID: PF08433
• Sequence:
  MKTAENIRGTGSDGPRKRGLCVLCGLPAAGKSTFARALAHRLQQEQGWAIGVVAYDDVMP
  DAFLAGARARPAPSQWKLLRQELLKYLEYFLMAVINGCQMSVPPNRTEAMWEDFITCLKD
  QDLIFSAAFEAQSCYLLTKTAVSRPLFLVLDDNFYYQSMRYEVYQLARKYSLGFCQLFLD
  CPLETCLQRNGQRPQALPPETIHLMGRKLEKPNPEKNAWEHNSLTIPSPACASEASLEVT
  DLLLTALENPVKYAEDNMEQKDTDRIICSTNILHKTDQTLRRIVSQTMKEAKGNQEAFSE
  MTFKQRWVRANHAAIWRIILGNEHIKCRSAKVGWLQCCRIEKRPLSTG
• Function: Specifically phosphorylates seryl-tRNA(Sec) to O-phosphoseryl-tRNA(Sec), an activated intermediate for selenocysteine biosynthesis.
• KEGG Pathway:
  Selenocompound metabolism (hsa00450)
  Aminoacyl-tR. biosynthesis (hsa00970)
• Reactome Pathway: Selenocysteine synthesis (R-HSA-2408557)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
High blood pressure	DISY2OHH	Strong	Genetic Variation	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	L-seryl-tRNA(Sec) kinase (PSTK) decreases the response to substance of Arsenic trioxide.	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of L-seryl-tRNA(Sec) kinase (PSTK).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of L-seryl-tRNA(Sec) kinase (PSTK).	[3]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of L-seryl-tRNA(Sec) kinase (PSTK).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of L-seryl-tRNA(Sec) kinase (PSTK).	[5]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of L-seryl-tRNA(Sec) kinase (PSTK).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of L-seryl-tRNA(Sec) kinase (PSTK).	[7]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of L-seryl-tRNA(Sec) kinase (PSTK).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of L-seryl-tRNA(Sec) kinase (PSTK).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of L-seryl-tRNA(Sec) kinase (PSTK).	[6]

References

• [1] Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension.PLoS Genet. 2010 Oct 28;6(10):e1001177. doi: 10.1371/journal.pgen.1001177.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [5] 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.
• [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] 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.
• [8] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [9] 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.
• [10] Functional Profiling Identifies Determinants of Arsenic Trioxide Cellular Toxicity. Toxicol Sci. 2019 May 1;169(1):108-121. doi: 10.1093/toxsci/kfz024.