Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVCZ5V1)

• DOT Name: Thymus-specific serine protease (PRSS16)
• Synonyms: EC 3.4.-.-; Serine protease 16
• Gene Name: PRSS16
• Related Disease:
  Autoimmune disease
  Colitis
  Multiple sclerosis
  Neoplasm
  Nervous system inflammation
  Type-1 diabetes
  Myasthenia gravis
• UniProt ID: TSSP_HUMAN
• EC Number: 3.4.-.-
• Pfam ID: PF05577
• Sequence:
  MAVWLAQWLGPLLLVSLWGLLAPASLLRRLGEHIQQFQESSAQGLGLSLGPGAAALPKVG
  WLEQLLDPFNVSDRRSFLQRYWVNDQHWVGQDGPIFLHLGGEGSLGPGSVMRGHPAALAP
  AWGALVISLEHRFYGLSIPAGGLEMAQLRFLSSRLALADVVSARLALSRLFNISSSSPWI
  CFGGSYAGSLAAWARLKFPHLIFASVASSAPVRAVLDFSEYNDVVSRSLMSTAIGGSLEC
  RAAVSVAFAEVERRLRSGGAAQAALRTELSACGPLGRAENQAELLGALQALVGGVVQYDG
  QTGAPLSVRQLCGLLLGGGGNRSHSTPYCGLRRAVQIVLHSLGQKCLSFSRAETVAQLRS
  TEPQLSGVGDRQWLYQTCTEFGFYVTCENPRCPFSQLPALPSQLDLCEQVFGLSALSVAQ
  AVAQTNSYYGGQTPGANKVLFVNGDTDPWHVLSVTQALGSSESTLLIRTGSHCLDMAPER
  PSDSPSLRLGRQNIFQQLQTWLKLAKESQIKGEV
• Function: Protease that may play a role in T-cell development.
• Tissue Specificity: Expressed predominantly in cortical thymic epithelial cells.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Biomarker	[1]
Colitis	DISAF7DD	Strong	Biomarker	[2]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[3]
Type-1 diabetes	DIS7HLUB	Strong	Biomarker	[4]
Myasthenia gravis	DISELRCI	Limited	Biomarker	[5]

4 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 Thymus-specific serine protease (PRSS16).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Thymus-specific serine protease (PRSS16).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Thymus-specific serine protease (PRSS16).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Thymus-specific serine protease (PRSS16).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Thymus-specific serine protease (PRSS16).	[10]

References

• [1] Polymorphisms in the gene encoding thymus-specific serine protease in the extended HLA complex: a potential candidate gene for autoimmune and HLA-associated diseases.Genes Immun. 2002 Aug;3(5):306-12. doi: 10.1038/sj.gene.6363858.
• [2] The thymus-specific serine protease TSSP/PRSS16 is crucial for the antitumoral role of CD4(+) T cells.Cell Rep. 2015 Jan 6;10(1):39-46. doi: 10.1016/j.celrep.2014.12.009. Epub 2014 Dec 24.
• [3] Thymic-Specific Serine Protease Limits Central Tolerance and Exacerbates Experimental Autoimmune Encephalomyelitis.J Immunol. 2017 Dec 1;199(11):3748-3756. doi: 10.4049/jimmunol.1700667. Epub 2017 Oct 23.
• [4] Reproducible association with type 1 diabetes in the extended class I region of the major histocompatibility complex.Genes Immun. 2009 Jun;10(4):323-33. doi: 10.1038/gene.2009.13. Epub 2009 Mar 19.
• [5] Alternatively spliced transcripts of the thymus-specific protease PRSS16 are differentially expressed in human thymus.Genes Immun. 2005 Feb;6(1):1-7. doi: 10.1038/sj.gene.6364142.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] 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.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.