Details of Drug Off-Target (DOT)

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

• DOT Name: Brain-specific serine protease 4 (PRSS22)
• Synonyms: BSSP-4; EC 3.4.21.-; Serine protease 22; Serine protease 26; Tryptase epsilon
• Gene Name: PRSS22
• Related Disease:
  Advanced cancer
  Colon cancer
  Colon carcinoma
  Hepatocellular carcinoma
  Glioma
  Nematode infection
  Ovarian cancer
• UniProt ID: BSSP4_HUMAN
• EC Number: 3.4.21.-
• Pfam ID: PF00089
• Sequence:
  MVVSGAPPALGGGCLGTFTSLLLLASTAILNAARIPVPPACGKPQQLNRVVGGEDSTDSE
  WPWIVSIQKNGTHHCAGSLLTSRWVITAAHCFKDNLNKPYLFSVLLGAWQLGNPGSRSQK
  VGVAWVEPHPVYSWKEGACADIALVRLERSIQFSERVLPICLPDASIHLPPNTHCWISGW
  GSIQDGVPLPHPQTLQKLKVPIIDSEVCSHLYWRGAGQGPITEDMLCAGYLEGERDACLG
  DSGGPLMCQVDGAWLLAGIISWGEGCAERNRPGVYISLSAHRSWVEKIVQGVQLRGRAQG
  GGALRAPSQGSGAAARS
• Function: Preferentially cleaves the synthetic substrate H-D-Leu-Thr-Arg-pNA compared to tosyl-Gly-Pro-Arg-pNA.
• Tissue Specificity: Expressed abundantly in the epithelial cells of the airways, including trachea, esophagus and fetal lung. Scarce in adult lung. Expressed at low levels in placenta, pancreas, prostate and thyroid gland.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Limited	Altered Expression	[3]
Nematode infection	DISVFLRK	Limited	Altered Expression	[4]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[3]

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 Brain-specific serine protease 4 (PRSS22).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Brain-specific serine protease 4 (PRSS22).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Brain-specific serine protease 4 (PRSS22).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Brain-specific serine protease 4 (PRSS22).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Brain-specific serine protease 4 (PRSS22).	[7]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Brain-specific serine protease 4 (PRSS22).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Brain-specific serine protease 4 (PRSS22).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Brain-specific serine protease 4 (PRSS22).	[10]

References

• [1] Thyroid hormone enhanced human hepatoma cell motility involves brain-specific serine protease 4 activation via ERK signaling.Mol Cancer. 2014 Jul 1;13:162. doi: 10.1186/1476-4598-13-162.
• [2] Microarray-based identification and RT-PCR test screening for epithelial-specific mRNAs in peripheral blood of patients with colon cancer.BMC Cancer. 2006 Oct 20;6:250. doi: 10.1186/1471-2407-6-250.
• [3] A novel serine protease highly expressed in the pancreas is expressed in various kinds of cancer cells.FEBS J. 2005 Oct;272(19):4911-23. doi: 10.1111/j.1742-4658.2005.04901.x.
• [4] Differential expression of genes in fetal brain as a consequence of maternal protein deficiency and nematode infection.Int J Parasitol. 2018 Jan;48(1):51-58. doi: 10.1016/j.ijpara.2017.07.005. Epub 2017 Sep 10.
• [5] 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.
• [6] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [7] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [9] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [10] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [11] Maternal environmental exposure to bisphenols and epigenome-wide DNA methylation in infant cord blood. Environ Epigenet. 2020 Dec 23;6(1):dvaa021. doi: 10.1093/eep/dvaa021. eCollection 2020.