Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR6GDQM)

• DOT Name: Serine protease 57 (PRSS57)
• Synonyms: EC 3.4.21.-; Neutrophil serine protease 4; NSP4; Serine protease 1-like protein 1
• Gene Name: PRSS57
• Related Disease:
  Chikungunya virus infection
  Dengue
  Diarrhea
  Gastroenteritis
  Influenza
  Rhabdomyosarcoma
• UniProt ID: PRS57_HUMAN
• PDB ID: 4Q7X; 4Q7Y; 4Q7Z; 4Q80
• EC Number: 3.4.21.-
• Pfam ID: PF00089
• Sequence:
  MGLGLRGWGRPLLTVATALMLPVKPPAGSWGAQIIGGHEVTPHSRPYMASVRFGGQHHCG
  GFLLRARWVVSAAHCFSHRDLRTGLVVLGAHVLSTAEPTQQVFGIDALTTHPDYHPMTHA
  NDICLLRLNGSAVLGPAVGLLRPPGRRARPPTAGTRCRVAGWGFVSDFEELPPGLMEAKV
  RVLDPDVCNSSWKGHLTLTMLCTRSGDSHRRGFCSADSGGPLVCRNRAHGLVSFSGLWCG
  DPKTPDVYTQVSAFVAWIWDVVRRSSPQPGPLPGTTRPPGEAA
• Function: Serine protease that cleaves preferentially after Arg residues. Can also cleave after citrulline (deimidated arginine) and methylarginine residues.
• Tissue Specificity: Detected in peripheral blood neutrophil granulocytes, but not in other types of leukocytes. Detected in neutrophils and neutrophil precursors in bone marrow (at protein level) . Detected in myeloblasts and promyelocytes in bone marrow .

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chikungunya virus infection	DISDXEHY	Strong	Biomarker	[1]
Dengue	DISKH221	Strong	Biomarker	[2]
Diarrhea	DISWTJQL	Strong	Genetic Variation	[3]
Gastroenteritis	DISXQCG5	Strong	Biomarker	[4]
Influenza	DIS3PNU3	Strong	Biomarker	[5]
Rhabdomyosarcoma	DISNR7MS	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine protease 57 (PRSS57).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Serine protease 57 (PRSS57).	[7]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Serine protease 57 (PRSS57).	[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 Serine protease 57 (PRSS57).	[8]

References

• [1] An amino acid change in nsP4 of chikungunya virus confers fitness advantage in human cell lines rather than in Aedes albopictus.J Gen Virol. 2019 Nov;100(11):1541-1553. doi: 10.1099/jgv.0.001338.
• [2] Simultaneous detection of Zika, Chikungunya and Dengue viruses by a multiplex real-time RT-PCR assay.J Clin Virol. 2016 Oct;83:66-71. doi: 10.1016/j.jcv.2016.09.001. Epub 2016 Sep 1.
• [3] G3P2 rotaviruses causing diarrhoeal disease in neonates differ in VP4, VP7 and NSP4 sequence from G3P2 strains causing asymptomatic neonatal infection.Arch Virol. 1996;141(9):1661-76. doi: 10.1007/BF01718290.
• [4] Mutation distribution in the NSP4 protein in rotaviruses isolated from Mexican children with moderate to severe gastroenteritis.Viruses. 2013 Mar 11;5(3):792-805. doi: 10.3390/v5030792.
• [5] Increased immunogenicity and protective efficacy of influenza M2e fused to a tetramerizing protein.PLoS One. 2012;7(10):e46395. doi: 10.1371/journal.pone.0046395. Epub 2012 Oct 1.
• [6] 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.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [9] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.