Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT09H6WH)

• DOT Name: Inactive serine protease 35 (PRSS35)
• Gene Name: PRSS35
• Related Disease:
  Cleft lip/palate
  Acute myelogenous leukaemia
  Bipolar disorder
  Asthma
• UniProt ID: PRS35_HUMAN
• Pfam ID: PF00089
• Sequence:
  MENMLLWLIFFTPGWTLIDGSEMEWDFMWHLRKVPRIVSERTFHLTSPAFEADAKMMVNT
  VCGIECQKELPTPSLSELEDYLSYETVFENGTRTLTRVKVQDLVLEPTQNITTKGVSVRR
  KRQVYGTDSRFSILDKRFLTNFPFSTAVKLSTGCSGILISPQHVLTAAHCVHDGKDYVKG
  SKKLRVGLLKMRNKSGGKKRRGSKRSRREASGGDQREGTREHLRERAKGGRRRKKSGRGQ
  RIAEGRPSFQWTRVKNTHIPKGWARGGMGDATLDYDYALLELKRAHKKKYMELGISPTIK
  KMPGGMIHFSGFDNDRADQLVYRFCSVSDESNDLLYQYCDAESGSTGSGVYLRLKDPDKK
  NWKRKIIAVYSGHQWVDVHGVQKDYNVAVRITPLKYAQICLWIHGNDANCAYG

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cleft lip/palate	DIS14IG3	Strong	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[2]
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[3]
Asthma	DISW9QNS	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Inactive serine protease 35 (PRSS35).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Inactive serine protease 35 (PRSS35).	[6]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Inactive serine protease 35 (PRSS35).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Inactive serine protease 35 (PRSS35).	[8]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Inactive serine protease 35 (PRSS35).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Inactive serine protease 35 (PRSS35).	[10]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Inactive serine protease 35 (PRSS35).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Inactive serine protease 35 (PRSS35).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Inactive serine protease 35 (PRSS35).	[14]

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 increases the methylation of Inactive serine protease 35 (PRSS35).	[12]

References

• [1] Novel cleft susceptibility genes in chromosome 6q.J Dent Res. 2010 Sep;89(9):927-32. doi: 10.1177/0022034510370004. Epub 2010 May 28.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] Genome-wide association of mood-incongruent psychotic bipolar disorder.Transl Psychiatry. 2012 Oct 23;2(10):e180. doi: 10.1038/tp.2012.106.
• [4] Genome-wide association study of leukotriene modifier response in asthma.Pharmacogenomics J. 2016 Apr;16(2):151-7. doi: 10.1038/tpj.2015.34. Epub 2015 Jun 2.
• [5] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [6] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [7] 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.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [11] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [12] 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.
• [13] 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.
• [14] 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.