Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT72MHP7)

• DOT Name: Myeloblastin (PRTN3)
• Synonyms: EC 3.4.21.76; AGP7; C-ANCA antigen; Leukocyte proteinase 3; PR-3; PR3; Neutrophil proteinase 4; NP-4; P29; Wegener autoantigen
• Gene Name: PRTN3
• UniProt ID: PRTN3_HUMAN
• PDB ID: 1FUJ
• EC Number: 3.4.21.76
• Pfam ID: PF00089
• Sequence:
  MAHRPPSPALASVLLALLLSGAARAAEIVGGHEAQPHSRPYMASLQMRGNPGSHFCGGTL
  IHPSFVLTAAHCLRDIPQRLVNVVLGAHNVRTQEPTQQHFSVAQVFLNNYDAENKLNDVL
  LIQLSSPANLSASVATVQLPQQDQPVPHGTQCLAMGWGRVGAHDPPAQVLQELNVTVVTF
  FCRPHNICTFVPRRKAGICFGDSGGPLICDGIIQGIDSFVIWGCATRLFPDFFTRVALYV
  DWIRSTLRRVEAKGRP
• Function: Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro). By cleaving and activating receptor F2RL1/PAR-2, enhances endothelial cell barrier function and thus vascular integrity during neutrophil transendothelial migration. May play a role in neutrophil transendothelial migration, probably when associated with CD177.
• Tissue Specificity: Expressed in polymorphonuclear leukocytes (at protein level) . Expressed in neutrophils (at protein level) . Expressed in differentiating neutrophils .
• Reactome Pathway:
  Other interleukin signaling (R-HSA-449836)
  Neutrophil degranulation (R-HSA-6798695)
  Antimicrobial peptides (R-HSA-6803157)
  Common Pathway of Fibrin Clot Formation (R-HSA-140875)

Molecular Interaction Atlas (MIA) of This DOT

1 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 Myeloblastin (PRTN3).	[1]

9 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 Myeloblastin (PRTN3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Myeloblastin (PRTN3).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Myeloblastin (PRTN3).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Myeloblastin (PRTN3).	[5]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Myeloblastin (PRTN3).	[6]
Pazopanib	DMF57DM	Approved	Pazopanib increases the expression of Myeloblastin (PRTN3).	[7]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Myeloblastin (PRTN3).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Myeloblastin (PRTN3).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Myeloblastin (PRTN3).	[10]

References

• [1] 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.
• [2] Arsenic trioxide augments all-trans retinoic acid-induced differentiation of HL-60 cells. Life Sci. 2016 Mar 15;149:42-50. doi: 10.1016/j.lfs.2016.02.054. Epub 2016 Feb 16.
• [3] 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.
• [4] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [5] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [6] Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
• [7] Activation of inflammasomes by tyrosine kinase inhibitors of vascular endothelial growth factor receptor: Implications for VEGFR TKIs-induced immune related adverse events. Toxicol In Vitro. 2021 Mar;71:105063. doi: 10.1016/j.tiv.2020.105063. Epub 2020 Dec 1.
• [8] Induction of class II major histocompatibility complex expression in human multiple myeloma cells by retinoid. Haematologica. 2007 Jan;92(1):115-20.
• [9] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [10] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.