Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB35677)

• DOT Name: Transmembrane protease serine 11A (TMPRSS11A)
• Synonyms: EC 3.4.21.-; Airway trypsin-like protease 1; Epidermal type-II transmembrane serine protease; Esophageal cancer-susceptibility gene 1 protein
• Gene Name: TMPRSS11A
• Related Disease:
  Esophageal squamous cell carcinoma
  Neoplasm
  Neuroendocrine cancer
  Squamous cell carcinoma
  Middle East Respiratory Syndrome (MERS)
• UniProt ID: TM11A_HUMAN
• EC Number: 3.4.21.-
• Pfam ID: PF01390 ; PF00089
• Sequence:
  MMYRTVGFGTRSRNLKPWMIAVLIVLSLTVVAVTIGLLVHFLVFDQKKEYYHGSFKILDP
  QINNNFGQSNTYQLKDLRETTENLVDEIFIDSAWKKNYIKNQVVRLTPEEDGVKVDVIMV
  FQFPSTEQRAVREKKIQSILNQKIRNLRALPINASSVQVNAMSSSTGELTVQASCGKRVV
  PLNVNRIASGVIAPKAAWPWQASLQYDNIHQCGATLISNTWLVTAAHCFQKYKNPHQWTV
  SFGTKINPPLMKRNVRRFIIHEKYRSAAREYDIAVVQVSSRVTFSDDIRQICLPEASASF
  QPNLTVHITGFGALYYGGESQNDLREARVKIISDDVCKQPQVYGNDIKPGMFCAGYMEGI
  YDACRGDSGGPLVTRDLKDTWYLIGIVSWGDNCGQKDKPGVYTQVTYYRNWIASKTGI
• Function: Probable serine protease which may play a role in cellular senescence. Overexpression inhibits cell growth and induce G1 cell cycle arrest.
• Tissue Specificity: Expressed in esophagus, liver, colon and lung. Down-regulated in esophagus cancers.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Neuroendocrine cancer	DISVGJET	moderate	Biomarker	[2]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[3]
Middle East Respiratory Syndrome (MERS)	DIS5VPYU	Limited	Biomarker	[4]

2 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 increases the methylation of Transmembrane protease serine 11A (TMPRSS11A).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Transmembrane protease serine 11A (TMPRSS11A).	[6]

References

• [1] Modification of risk, but not survival of esophageal cancer patients by esophageal cancer-related gene 1 Arg290Gln polymorphism: a case-control study and meta-analysis.J Gastroenterol Hepatol. 2013 Nov;28(11):1717-24. doi: 10.1111/jgh.12335.
• [2] ECRG1, a novel esophageal gene, cloned and identified from human esophagus and its inhibition effect on tumors.Carcinogenesis. 2008 Jan;29(1):157-60. doi: 10.1093/carcin/bgm203. Epub 2007 Oct 29.
• [3] Single nucleotide polymorphism in esophageal cancer related gene 1: an analysis in resected oral squamous cell carcinoma patients.Int J Oral Maxillofac Surg. 2009 Jul;38(7):779-84. doi: 10.1016/j.ijom.2009.02.021. Epub 2009 Apr 25.
• [4] TMPRSS11A activates the influenza A virus hemagglutinin and the MERS coronavirus spike protein and is insensitive against blockade by HAI-1.J Biol Chem. 2018 Sep 7;293(36):13863-13873. doi: 10.1074/jbc.RA118.001273. Epub 2018 Jul 5.
• [5] 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.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.