Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN3S5YB)

DOT Name Trypsin-3 (PRSS3)
Synonyms EC 3.4.21.4; Brain trypsinogen; Mesotrypsin; Mesotrypsinogen; Serine protease 3; Serine protease 4; Trypsin III; Trypsin IV
Gene Name PRSS3
Related Disease
Neoplasm ( )
Non-small-cell lung cancer ( )
Advanced cancer ( )
Alzheimer disease ( )
Anaplastic large cell lymphoma ( )
Atopic dermatitis ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Chronic pancreatitis ( )
Classic Hodgkin lymphoma ( )
Epithelial ovarian cancer ( )
Esophageal squamous cell carcinoma ( )
Hepatitis C virus infection ( )
Hepatitis D virus infection ( )
Hereditary chronic pancreatitis ( )
Lung adenocarcinoma ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Pancreatitis ( )
Schizophrenia ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Hepatocellular carcinoma ( )
Metastatic prostate carcinoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
Gastric cancer ( )
Metastatic malignant neoplasm ( )
Multiple sclerosis ( )
Stomach cancer ( )
Invasive ductal breast carcinoma ( )
Irritable bowel syndrome ( )
UniProt ID
TRY3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1H4W; 2R9P; 3L33; 3L3T; 3P92; 3P95; 4DG4; 4U30; 4U32; 5C67; 5JBT; 5TP0; 6BX8; 6GFI
EC Number
3.4.21.4
Pfam ID
PF00089
Sequence
MCGPDDRCPARWPGPGRAVKCGKGLAAARPGRVERGGAQRGGAGLELHPLLGGRTWRAAR
DADGCEALGTVAVPFDDDDKIVGGYTCEENSLPYQVSLNSGSHFCGGSLISEQWVVSAAH
CYKTRIQVRLGEHNIKVLEGNEQFINAAKIIRHPKYNRDTLDNDIMLIKLSSPAVINARV
STISLPTTPPAAGTECLISGWGNTLSFGADYPDELKCLDAPVLTQAECKASYPGKITNSM
FCVGFLEGGKDSCQRDSGGPVVCNGQLQGVVSWGHGCAWKNRPGVYTKVYNYVDWIKDTI
AANS
Function Digestive protease that cleaves proteins preferentially after an Arg residue and has proteolytic activity toward Kunitz-type trypsin inhibitors.
Tissue Specificity Detected in pancreas and pancreatic fluid (at protein level) . Expressed in pancreas and brain . Detected in ileum .
KEGG Pathway
Neuroactive ligand-receptor interaction (hsa04080 )
Pancreatic secretion (hsa04972 )
Protein digestion and absorption (hsa04974 )
Influenza A (hsa05164 )
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )
Antimicrobial peptides (R-HSA-6803157 )
Uptake of dietary cobalamins into enterocytes (R-HSA-9758881 )
Alpha-defensins (R-HSA-1462054 )

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Neoplasm DISZKGEW Definitive Altered Expression [1]
Non-small-cell lung cancer DIS5Y6R9 Definitive Biomarker [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Alzheimer disease DISF8S70 Strong Biomarker [4]
Anaplastic large cell lymphoma DISP4D1R Strong Biomarker [5]
Atopic dermatitis DISTCP41 Strong Genetic Variation [6]
Bladder cancer DISUHNM0 Strong Biomarker [7]
Breast cancer DIS7DPX1 Strong Biomarker [8]
Breast carcinoma DIS2UE88 Strong Biomarker [8]
Chronic pancreatitis DISBUOMJ Strong Genetic Variation [9]
Classic Hodgkin lymphoma DISV1LU6 Strong Biomarker [5]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [10]
Esophageal squamous cell carcinoma DIS5N2GV Strong Posttranslational Modification [2]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [11]
Hepatitis D virus infection DISESSLZ Strong Biomarker [12]
Hereditary chronic pancreatitis DISF0J1Q Strong Genetic Variation [13]
Lung adenocarcinoma DISD51WR Strong Biomarker [3]
Ovarian cancer DISZJHAP Strong Altered Expression [14]
Ovarian neoplasm DISEAFTY Strong Altered Expression [14]
Pancreatitis DIS0IJEF Strong Biomarker [15]
Schizophrenia DISSRV2N Strong Biomarker [16]
Urinary bladder cancer DISDV4T7 Strong Biomarker [7]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [7]
Hepatocellular carcinoma DIS0J828 moderate Biomarker [17]
Metastatic prostate carcinoma DISVBEZ9 moderate Biomarker [18]
Prostate cancer DISF190Y moderate Biomarker [18]
Prostate carcinoma DISMJPLE moderate Biomarker [18]
Prostate neoplasm DISHDKGQ moderate Altered Expression [18]
Gastric cancer DISXGOUK Disputed Biomarker [1]
Metastatic malignant neoplasm DIS86UK6 Disputed Altered Expression [1]
Multiple sclerosis DISB2WZI Disputed Biomarker [19]
Stomach cancer DISKIJSX Disputed Biomarker [1]
Invasive ductal breast carcinoma DIS43J58 Limited Biomarker [20]
Irritable bowel syndrome DIS27206 Limited Altered Expression [21]
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⏷ Show the Full List of 34 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Cyclophosphamide DM4O2Z7 Approved Trypsin-3 (PRSS3) affects the response to substance of Cyclophosphamide. [30]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Trypsin-3 (PRSS3). [22]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Trypsin-3 (PRSS3). [24]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Trypsin-3 (PRSS3). [25]
Hydroquinone DM6AVR4 Approved Hydroquinone increases the expression of Trypsin-3 (PRSS3). [26]
Sodium lauryl sulfate DMLJ634 Approved Sodium lauryl sulfate decreases the expression of Trypsin-3 (PRSS3). [27]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Trypsin-3 (PRSS3). [29]
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⏷ Show the Full List of 6 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic increases the methylation of Trypsin-3 (PRSS3). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Trypsin-3 (PRSS3). [28]
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References

1 High-level expression of PRSS3 correlates with metastasis and poor prognosis in patients with gastric cancer.J Surg Oncol. 2019 Jun;119(8):1108-1121. doi: 10.1002/jso.25448. Epub 2019 Mar 25.
2 Epigenetic silencing of the PRSS3 putative tumor suppressor gene in non-small cell lung cancer.Mol Carcinog. 2005 Oct;44(2):146-50. doi: 10.1002/mc.20125.
3 PRSS3/Mesotrypsin and kallikrein-related peptidase 5 are associated with poor prognosis and contribute to tumor cell invasion and growth in lung adenocarcinoma.Sci Rep. 2019 Feb 12;9(1):1844. doi: 10.1038/s41598-018-38362-0.
4 A comprehensive analysis on preservation patterns of gene co-expression networks during Alzheimer's disease progression.BMC Bioinformatics. 2017 Dec 20;18(1):579. doi: 10.1186/s12859-017-1946-8.
5 Sub-megabase resolution tiling (SMRT) array-based comparative genomic hybridization profiling reveals novel gains and losses of chromosomal regions in Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma cell lines.Mol Cancer. 2008 Jan 7;7:2. doi: 10.1186/1476-4598-7-2.
6 Exonic mutations associated with atopic dermatitis disrupt lympho-epithelial Kazal-type related inhibitor action and enhance its degradation.Allergy. 2020 Feb;75(2):403-411. doi: 10.1111/all.14018. Epub 2019 Sep 9.
7 Carcinogen exposure and gene promoter hypermethylation in bladder cancer. Carcinogenesis. 2006 Jan;27(1):112-6. doi: 10.1093/carcin/bgi172. Epub 2005 Jun 29.
8 The P(2)' residue is a key determinant of mesotrypsin specificity: engineering a high-affinity inhibitor with anticancer activity.Biochem J. 2011 Nov 15;440(1):95-105. doi: 10.1042/BJ20110788.
9 Mesotrypsin Signature Mutation in a Chymotrypsin C (CTRC) Variant Associated with Chronic Pancreatitis.J Biol Chem. 2015 Jul 10;290(28):17282-92. doi: 10.1074/jbc.M114.618439. Epub 2015 May 26.
10 Clinical significance and expression of the PRSS3 and Wiskott-Aldrich syndrome protein family verprolin-homologous protein 1 for the early detection of epithelial ovarian cancer.Tumour Biol. 2016 May;37(5):6769-73. doi: 10.1007/s13277-015-4586-5. Epub 2015 Dec 10.
11 A rare and severe cutaneous adverse effect of telaprevir: drug rash with eosinophilia and systemic symptoms.G Ital Dermatol Venereol. 2019 Aug;154(4):488-491. doi: 10.23736/S0392-0488.17.05151-3.
12 Long-term interferon-alpha treatment of children with chronic hepatitis delta: a multicentre study.J Viral Hepat. 1996 May;3(3):123-8. doi: 10.1111/j.1365-2893.1996.tb00002.x.
13 Mutations in the cationic trypsinogen gene and evidence for genetic heterogeneity in hereditary pancreatitis.J Med Genet. 1999 Mar;36(3):228-32.
14 PRSS3 expression is associated with tumor progression and poor prognosis in epithelial ovarian cancer.Gynecol Oncol. 2015 Jun;137(3):546-52. doi: 10.1016/j.ygyno.2015.02.022. Epub 2015 Feb 28.
15 Human mesotrypsin defies natural trypsin inhibitors: from passive resistance to active destruction.Protein Pept Lett. 2005 Jul;12(5):457-64. doi: 10.2174/0929866054395356.
16 Oxytocin Enhances an Amygdala Circuit Associated With Negative Symptoms in Schizophrenia: A Single-Dose, Placebo-Controlled, Crossover, Randomized Control Trial.Schizophr Bull. 2020 Apr 10;46(3):661-669. doi: 10.1093/schbul/sbz091.
17 Epigenetic silencing of PRSS3 provides growth and metastasis advantage for human hepatocellular carcinoma.J Mol Med (Berl). 2017 Nov;95(11):1237-1249. doi: 10.1007/s00109-017-1578-5. Epub 2017 Aug 26.
18 PRSS3/mesotrypsin is a therapeutic target for metastatic prostate cancer.Mol Cancer Res. 2012 Dec;10(12):1555-66. doi: 10.1158/1541-7786.MCR-12-0314.
19 Myelin basic protein, an autoantigen in multiple sclerosis, is selectively processed by human trypsin 4.FEBS Lett. 2006 Jan 23;580(2):545-52. doi: 10.1016/j.febslet.2005.12.067. Epub 2005 Dec 29.
20 PRSS3 is a prognostic marker in invasive ductal carcinoma of the breast.Oncotarget. 2017 Mar 28;8(13):21444-21453. doi: 10.18632/oncotarget.15590.
21 Epithelial expression and function of trypsin-3 in irritable bowel syndrome.Gut. 2017 Oct;66(10):1767-1778. doi: 10.1136/gutjnl-2016-312094. Epub 2017 Jan 17.
22 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
23 Carcinogen exposure and gene promoter hypermethylation in bladder cancer. Carcinogenesis. 2006 Jan;27(1):112-6. doi: 10.1093/carcin/bgi172. Epub 2005 Jun 29.
24 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.
25 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
26 Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
27 CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
28 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.
29 Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
30 Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.