Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7ETD15)

• DOT Name: Transmembrane protease serine 9 (TMPRSS9)
• Synonyms: EC 3.4.21.-; Polyserase-I; Polyserine protease 1; Polyserase-1
• Gene Name: TMPRSS9
• Related Disease:
  Pancreatic cancer
  Parkinson disease
• UniProt ID: TMPS9_HUMAN
• EC Number: 3.4.21.-
• Pfam ID: PF00057 ; PF00089
• Sequence:
  MEPTVADVHLVPRTTKEVPALDAACCRAASIGVVATSLVVLTLGVLLAFLSTQGFHVDHT
  AELRGIRWTSSLRRETSDYHRTLTPTLEALLHFLLRPLQTLSLGLEEELLQRGIRARLRE
  HGISLAAYGTIVSAELTGRHKGPLAERDFKSGRCPGNSFSCGNSQCVTKVNPECDDQEDC
  SDGSDEAHCECGLQPAWRMAGRIVGGMEASPGEFPWQASLRENKEHFCGAAIINARWLVS
  AAHCFNEFQDPTKWVAYVGATYLSGSEASTVRAQVVQIVKHPLYNADTADFDVAVLELTS
  PLPFGRHIQPVCLPAATHIFPPSKKCLISGWGYLKEDFLVKPEVLQKATVELLDQALCAS
  LYGHSLTDRMVCAGYLDGKVDSCQGDSGGPLVCEEPSGRFFLAGIVSWGIGCAEARRPGV
  YARVTRLRDWILEATTKASMPLAPTMAPAPAAPSTAWPTSPESPVVSTPTKSMQALSTVP
  LDWVTVPKLQECGARPAMEKPTRVVGGFGAASGEVPWQVSLKEGSRHFCGATVVGDRWLL
  SAAHCFNHTKVEQVRAHLGTASLLGLGGSPVKIGLRRVVLHPLYNPGILDFDLAVLELAS
  PLAFNKYIQPVCLPLAIQKFPVGRKCMISGWGNTQEGNATKPELLQKASVGIIDQKTCSV
  LYNFSLTDRMICAGFLEGKVDSCQGDSGGPLACEEAPGVFYLAGIVSWGIGCAQVKKPGV
  YTRITRLKGWILEIMSSQPLPMSPPSTTRMLATTSPRTTAGLTVPGATPSRPTPGAASRV
  TGQPANSTLSAVSTTARGQTPFPDAPEATTHTQLPDCGLAPAALTRIVGGSAAGRGEWPW
  QVSLWLRRREHRCGAVLVAERWLLSAAHCFDVYGDPKQWAAFLGTPFLSGAEGQLERVAR
  IYKHPFYNLYTLDYDVALLELAGPVRRSRLVRPICLPEPAPRPPDGTRCVITGWGSVREG
  GSMARQLQKAAVRLLSEQTCRRFYPVQISSRMLCAGFPQGGVDSCSGDAGGPLACREPSG
  RWVLTGVTSWGYGCGRPHFPGVYTRVAAVRGWIGQHIQE
• Function: Serase-1 and serase-2 are serine proteases that hydrolyze the peptides N-t-Boc-Gln-Ala-Arg-AMC and N-t-Boc-Gln-Gly-Arg-AMC. In contrast, N-t-Boc-Ala-Phe-Lys-AMC and N-t-Boc-Ala-Pro-Ala-AMC are not significantly hydrolyzed.
• Tissue Specificity: Expressed in fetal human tissues, such as kidney, liver, lung and brain, and in a variety of tumor cell lines. Weakly expressed in adult tissues including skeletal muscle, liver, placenta and heart.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pancreatic cancer	DISJC981	Strong	Biomarker	[1]
Parkinson disease	DISQVHKL	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 Transmembrane protease serine 9 (TMPRSS9).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Transmembrane protease serine 9 (TMPRSS9).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transmembrane protease serine 9 (TMPRSS9).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Transmembrane protease serine 9 (TMPRSS9).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Transmembrane protease serine 9 (TMPRSS9).	[7]

References

• [1] Polyserase-1/TMPRSS9 induces pro-tumor effects in pancreatic cancer cells by activation of pro-uPA.Oncol Rep. 2014 Jun;31(6):2792-6. doi: 10.3892/or.2014.3146. Epub 2014 Apr 23.
• [2] A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci.Nat Genet. 2017 Oct;49(10):1511-1516. doi: 10.1038/ng.3955. Epub 2017 Sep 11.
• [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] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [5] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [6] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [7] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.