Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO5U2TK)

• DOT Name: Transmembrane protease serine 11E (TMPRSS11E)
• Synonyms: EC 3.4.21.-; Serine protease DESC1; Transmembrane protease serine 11E2
• Gene Name: TMPRSS11E
• Related Disease:
  Esophageal squamous cell carcinoma
  Head-neck squamous cell carcinoma
  Neoplasm
  Squamous cell carcinoma
• UniProt ID: TM11E_HUMAN
• PDB ID: 2OQ5
• EC Number: 3.4.21.-
• Pfam ID: PF01390 ; PF00089
• Sequence:
  MMYRPDVVRARKRVCWEPWVIGLVIFISLIVLAVCIGLTVHYVRYNQKKTYNYYSTLSFT
  TDKLYAEFGREASNNFTEMSQRLESMVKNAFYKSPLREEFVKSQVIKFSQQKHGVLAHML
  LICRFHSTEDPETVDKIVQLVLHEKLQDAVGPPKVDPHSVKIKKINKTETDSYLNHCCGT
  RRSKTLGQSLRIVGGTEVEEGEWPWQASLQWDGSHRCGATLINATWLVSAAHCFTTYKNP
  ARWTASFGVTIKPSKMKRGLRRIIVHEKYKHPSHDYDISLAELSSPVPYTNAVHRVCLPD
  ASYEFQPGDVMFVTGFGALKNDGYSQNHLRQAQVTLIDATTCNEPQAYNDAITPRMLCAG
  SLEGKTDACQGDSGGPLVSSDARDIWYLAGIVSWGDECAKPNKPGVYTRVTALRDWITSK
  TGI
• Function: Serine protease which possesses both gelatinolytic and caseinolytic activities. Shows a preference for Arg in the P1 position.
• Tissue Specificity: Expression can only be detected in tissues derived from the head and neck, and in skin, prostate and testis.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[1]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Transmembrane protease serine 11E (TMPRSS11E).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Transmembrane protease serine 11E (TMPRSS11E).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transmembrane protease serine 11E (TMPRSS11E).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transmembrane protease serine 11E (TMPRSS11E).	[6]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Transmembrane protease serine 11E (TMPRSS11E).	[7]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Transmembrane protease serine 11E (TMPRSS11E).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Transmembrane protease serine 11E (TMPRSS11E).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transmembrane protease serine 11E (TMPRSS11E).	[11]

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 Transmembrane protease serine 11E (TMPRSS11E).	[10]

References

• [1] LncRNA-TUSC7/miR-224 affected chemotherapy resistance of esophageal squamous cell carcinoma by competitively regulating DESC1.J Exp Clin Cancer Res. 2018 Mar 12;37(1):56. doi: 10.1186/s13046-018-0724-4.
• [2] Human DESC1 serine protease confers tumorigenic properties to MDCK cells and it is upregulated in tumours of different origin.Br J Cancer. 2007 Jul 16;97(2):201-9. doi: 10.1038/sj.bjc.6603856. Epub 2007 Jun 19.
• [3] Expression of the serine protease DESC1 correlates directly with normal keratinocyte differentiation and inversely with head and neck squamous cell carcinoma progression.Head Neck. 2006 May;28(5):432-40. doi: 10.1002/hed.20346.
• [4] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [5] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [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] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [8] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [9] 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.
• [10] 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.
• [11] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.