Details of Drug Off-Target (DOT)

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

• DOT Name: Archaemetzincin-2 (AMZ2)
• Synonyms: EC 3.4.-.-; Archeobacterial metalloproteinase-like protein 2
• Gene Name: AMZ2
• UniProt ID: AMZ2_HUMAN
• EC Number: 3.4.-.-
• Pfam ID: PF07998
• Sequence:
  MQIIRHSEQTLKTALISKNPVLVSQYEKLNAGEQRLMNEAFQPASDLFGPITLHSPSDWI
  TSHPEAPQDFEQFFSDPYRKTPSPNKRSIYIQSIGSLGNTRIISEEYIKWLTGYCKAYFY
  GLRVKLLEPVPVSVTRCSFRVNENTHNLQIHAGDILKFLKKKKPEDAFCVVGITMIDLYP
  RDSWNFVFGQASLTDGVGIFSFARYGSDFYSMHYKGKVKKLKKTSSSDYSIFDNYYIPEI
  TSVLLLRSCKTLTHEIGHIFGLRHCQWLACLMQGSNHLEEADRRPLNLCPICLHKLQCAV
  GFSIVERYKALVRWIDDESSDTPGATPEHSHEDNGNLPKPVEAFKEWKEWIIKCLAVLQK
• Function: Probable zinc metalloprotease.
• Tissue Specificity: Down-regulated in testis from patients with maturation arrest (MA) or Sertoli cell-only syndrome (SCOS).

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Archaemetzincin-2 (AMZ2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Archaemetzincin-2 (AMZ2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Archaemetzincin-2 (AMZ2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Archaemetzincin-2 (AMZ2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Archaemetzincin-2 (AMZ2).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Archaemetzincin-2 (AMZ2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Archaemetzincin-2 (AMZ2).	[6]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [7] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.