Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ5UILU)

• DOT Name: Tesmin (TESMIN)
• Synonyms: Metallothionein-like 5, testis-specific; Testis-specific metallothionein-like protein
• Gene Name: TESMIN
• Related Disease:
  Advanced cancer
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Osteoporosis
• UniProt ID: MTL5_HUMAN
• Pfam ID: PF03638
• Sequence:
  MEEGPLPGGLPSPEDAMVTELLSPEGPFASENIGLKAPVKYEEDEFHVFKEAYLGPADPK
  EPVLHAFNPALGADCKGQVKAKLAGGDSDGGELLGEYPGIPELSALEDVALLQAPQPPAC
  NVHFLSSLLPAHRSPAVLPLGAWVLEGASHPGVRMIPVEIKEAGGTTTSNNPEEATLQNL
  LAQESCCKFPSSQELEDASCCSLKKDSNPMVICQLKGGTQMLCIDNSRTRELKALHLVPQ
  YQDQNNYLQSDVPKPMTALVGRFLPASTKLNLITQQLEGALPSVVNGSAFPSGSTLPGPP
  KITLAGYCDCFASGDFCNNCNCNNCCNNLHHDIERFKAIKACLGRNPEAFQPKIGKGQLG
  NVKPQHNKGCNCRRSGCLKNYCECYEAQIMCSSICKCIGCKNYEESPERKTLMSMPNYMQ
  TGGLEGSHYLPPTKFSGLPRFSHDRRPSSCISWEVVEATCACLLAQGEEAEKEHCSKCLA
  EQMILEEFGRCLSQILHTEFKSKGLKME
• Function: Essential for normal spermatogenesis and male fertility. Required for the completion of meiosis in male germ cells.
• Tissue Specificity: Expressed specifically in testis.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung carcinoma	DISTR26C	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[1]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[2]

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 Tesmin (TESMIN).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Tesmin (TESMIN).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Tesmin (TESMIN).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Tesmin (TESMIN).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Tesmin (TESMIN).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Tesmin (TESMIN).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tesmin (TESMIN).	[9]

References

• [1] Expression of tesmin (MTL5) in nonsmall cell lung cancer: A preliminary study.Oncol Rep. 2019 Jul;42(1):253-262. doi: 10.3892/or.2019.7145. Epub 2019 May 2.
• [2] Functional relevance for associations between osteoporosis and genetic variants.PLoS One. 2017 Apr 3;12(4):e0174808. doi: 10.1371/journal.pone.0174808. eCollection 2017.
• [3] 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.
• [4] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [5] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [9] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.