Details of Drug Off-Target (DOT)

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

• DOT Name: Suppressor of tumorigenicity 14 protein (ST14)
• Synonyms: EC 3.4.21.109; Matriptase; Membrane-type serine protease 1; MT-SP1; Prostamin; Serine protease 14; Serine protease TADG-15; Tumor-associated differentially-expressed gene 15 protein
• Gene Name: ST14
• Related Disease: Autosomal recessive congenital ichthyosis 11
• UniProt ID: ST14_HUMAN
• PDB ID: 1EAW; 1EAX; 2GV6; 2GV7; 3BN9; 3NCL; 3NPS; 3P8F; 3P8G; 3SO3; 4IS5; 4ISL; 4ISN; 4ISO; 4JYT; 4JZ1; 4JZI; 4O97; 4O9V; 4R0I; 5LYO; 6N4T; 6T9T
• EC Number: 3.4.21.109
• Pfam ID: PF00431 ; PF00057 ; PF01390 ; PF00089
• Sequence:
  MGSDRARKGGGGPKDFGAGLKYNSRHEKVNGLEEGVEFLPVNNVKKVEKHGPGRWVVLAA
  VLIGLLLVLLGIGFLVWHLQYRDVRVQKVFNGYMRITNENFVDAYENSNSTEFVSLASKV
  KDALKLLYSGVPFLGPYHKESAVTAFSEGSVIAYYWSEFSIPQHLVEEAERVMAEERVVM
  LPPRARSLKSFVVTSVVAFPTDSKTVQRTQDNSCSFGLHARGVELMRFTTPGFPDSPYPA
  HARCQWALRGDADSVLSLTFRSFDLASCDERGSDLVTVYNTLSPMEPHALVQLCGTYPPS
  YNLTFHSSQNVLLITLITNTERRHPGFEATFFQLPRMSSCGGRLRKAQGTFNSPYYPGHY
  PPNIDCTWNIEVPNNQHVKVRFKFFYLLEPGVPAGTCPKDYVEINGEKYCGERSQFVVTS
  NSNKITVRFHSDQSYTDTGFLAEYLSYDSSDPCPGQFTCRTGRCIRKELRCDGWADCTDH
  SDELNCSCDAGHQFTCKNKFCKPLFWVCDSVNDCGDNSDEQGCSCPAQTFRCSNGKCLSK
  SQQCNGKDDCGDGSDEASCPKVNVVTCTKHTYRCLNGLCLSKGNPECDGKEDCSDGSDEK
  DCDCGLRSFTRQARVVGGTDADEGEWPWQVSLHALGQGHICGASLISPNWLVSAAHCYID
  DRGFRYSDPTQWTAFLGLHDQSQRSAPGVQERRLKRIISHPFFNDFTFDYDIALLELEKP
  AEYSSMVRPICLPDASHVFPAGKAIWVTGWGHTQYGGTGALILQKGEIRVINQTTCENLL
  PQQITPRMMCVGFLSGGVDSCQGDSGGPLSSVEADGRIFQAGVVSWGDGCAQRNKPGVYT
  RLPLFRDWIKENTGV
• Function: Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site. Involved in the terminal differentiation of keratinocytes through prostasin (PRSS8) activation and filaggrin (FLG) processing. Proteolytically cleaves and therefore activates TMPRSS13.
• KEGG Pathway: MicroR.s in cancer (hsa05206)
• Reactome Pathway: Formation of the cornified envelope (R-HSA-6809371)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive congenital ichthyosis 11	DISOZX40	Strong	Autosomal recessive	[1]

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 Suppressor of tumorigenicity 14 protein (ST14).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Suppressor of tumorigenicity 14 protein (ST14).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Suppressor of tumorigenicity 14 protein (ST14).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Suppressor of tumorigenicity 14 protein (ST14).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Suppressor of tumorigenicity 14 protein (ST14).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of Suppressor of tumorigenicity 14 protein (ST14).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Suppressor of tumorigenicity 14 protein (ST14).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Suppressor of tumorigenicity 14 protein (ST14).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Suppressor of tumorigenicity 14 protein (ST14).	[10]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] 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.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [5] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [6] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] 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.