Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDH9XM0)

• DOT Name: Archaemetzincin-1 (AMZ1)
• Synonyms: EC 3.4.-.-; Archeobacterial metalloproteinase-like protein 1
• Gene Name: AMZ1
• Related Disease:
  Cardiac failure
  Chagas disease
  Chronic obstructive pulmonary disease
  Congestive heart failure
  Inflammatory bowel disease
  Ulcerative colitis
• UniProt ID: AMZ1_HUMAN
• EC Number: 3.4.-.-
• Sequence:
  MLQCRPAQEFSFGPRALKDALVSTDAALQQLYVSAFSPAERLFLAEAYNPQRTLFCTLLI
  RTGFDWLLSRPEAPEDFQTFHASLQHRKPRLARKHIYLQPIDLSEEPVGSSLLHQLCSCT
  EAFFLGLRVKCLPSVAAASIRCSSRPSRDSDRLQLHTDGILSFLKNNKPGDALCVLGLTL
  SDLYPHEAWSFTFSKFLPGHEVGVCSFARFSGEFPKSGPSAPDLALVEAAADGPEAPLQD
  RGWALCFSALGMVQCCKVTCHELCHLLGLGNCRWLRCLMQGALSLDEALRRPLDLCPICL
  RKLQHVLGFRLIERYQRLYTWTQAVVGTWPSQEAGEPSVWEDTPPASADSGMCCESDSEP
  GTSVSEPLTPDAGSHTFASGPEEGLSYLAASEAPLPPGGPAEAIKEHERWLAMCIQALQR
  EVAEEDLVQVDRAVDALDRWEMFTGQLPATRQDPPSSRDSVGLRKVLGDKFSSLRRKLSA
  RKLARAESAPRPWDGEES
• Function: Probable zinc metalloprotease.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac failure	DISDC067	Strong	Biomarker	[1]
Chagas disease	DIS8KNVF	Strong	Biomarker	[1]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[2]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[1]
Inflammatory bowel disease	DISGN23E	Limited	Genetic Variation	[3]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[3]

2 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 Archaemetzincin-1 (AMZ1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Archaemetzincin-1 (AMZ1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Archaemetzincin-1 (AMZ1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Archaemetzincin-1 (AMZ1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Archaemetzincin-1 (AMZ1).	[8]

References

• [1] Archaea Symbiont of T. cruzi Infection May Explain Heart Failure in Chagas Disease.Front Cell Infect Microbiol. 2018 Nov 21;8:412. doi: 10.3389/fcimb.2018.00412. eCollection 2018.
• [2] Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations.Nat Genet. 2019 Mar;51(3):494-505. doi: 10.1038/s41588-018-0342-2. Epub 2019 Feb 25.
• [3] Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.Nat Genet. 2017 Feb;49(2):256-261. doi: 10.1038/ng.3760. Epub 2017 Jan 9.
• [4] 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.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] 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.
• [7] 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.
• [8] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.