Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC4G4UF)

• DOT Name: Serine protease 27 (PRSS27)
• Synonyms: EC 3.4.21.-; Marapsin; Pancreasin
• Gene Name: PRSS27
• Related Disease:
  Acute myelogenous leukaemia
  Advanced cancer
  Anemia
  Myelofibrosis
  Primary myelofibrosis
  Thrombocytopenia
  Neoplasm
  Myeloproliferative neoplasm
• UniProt ID: PRS27_HUMAN
• EC Number: 3.4.21.-
• Pfam ID: PF00089
• Sequence:
  MRRPAAVPLLLLLCFGSQRAKAATACGRPRMLNRMVGGQDTQEGEWPWQVSIQRNGSHFC
  GGSLIAEQWVLTAAHCFRNTSETSLYQVLLGARQLVQPGPHAMYARVRQVESNPLYQGTA
  SSADVALVELEAPVPFTNYILPVCLPDPSVIFETGMNCWVTGWGSPSEEDLLPEPRILQK
  LAVPIIDTPKCNLLYSKDTEFGYQPKTIKNDMLCAGFEEGKKDACKGDSGGPLVCLVGQS
  WLQAGVISWGEGCARQNRPGVYIRVTAHHNWIHRIIPKLQFQPARLGGQK
• Tissue Specificity: Expressed predominantly in the pancreas.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Anemia	DISTVL0C	Strong	Genetic Variation	[3]
Myelofibrosis	DISIMP21	Strong	Biomarker	[3]
Primary myelofibrosis	DIS6L0CN	Strong	Biomarker	[3]
Thrombocytopenia	DISU61YW	Strong	Genetic Variation	[3]
Neoplasm	DISZKGEW	moderate	Genetic Variation	[4]
Myeloproliferative neoplasm	DIS5KAPA	Limited	Biomarker	[5]

3 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 Serine protease 27 (PRSS27).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Serine protease 27 (PRSS27).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Serine protease 27 (PRSS27).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Serine protease 27 (PRSS27).	[7]

References

• [1] Genomic profiling and directed ex vivo drug analysis of an unclassifiable myelodysplastic/myeloproliferative neoplasm progressing into acute myeloid leukemia.Genes Chromosomes Cancer. 2016 Nov;55(11):847-54. doi: 10.1002/gcc.22384. Epub 2016 Jul 4.
• [2] pH-sensitive metal-phenolic network capsules for targeted photodynamic therapy against cancer cells.Artif Cells Nanomed Biotechnol. 2018 Dec;46(8):1552-1561. doi: 10.1080/21691401.2017.1377724. Epub 2017 Sep 18.
• [3] Improvement of the hematologic toxicities of ruxolitinib in patients with MPN-associated myelofibrosis using a combination of thalidomide, stanozolol and prednisone.Hematology. 2019 Dec;24(1):516-520. doi: 10.1080/16078454.2019.1631509.
• [4] Effects of polymorphic DNA genes involved in BER and caspase pathways on the clinical outcome of myeloproliferative neoplasms under treatment with hydroxyurea.Mol Med Rep. 2018 Dec;18(6):5243-5255. doi: 10.3892/mmr.2018.9535. Epub 2018 Oct 8.
• [5] Splanchnic Vein Thrombosis in the Myeloproliferative Neoplasms.Curr Hematol Malig Rep. 2018 Jun;13(3):183-190. doi: 10.1007/s11899-018-0446-x.
• [6] 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.
• [7] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [8] 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.
• [9] 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.