Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2TQXS7)

• DOT Name: Kallikrein-5 (KLK5)
• Synonyms: EC 3.4.21.-; Kallikrein-like protein 2; KLK-L2; Stratum corneum tryptic enzyme
• Gene Name: KLK5
• UniProt ID: KLK5_HUMAN
• PDB ID: 2PSX; 2PSY; 6QFE; 7U5B
• EC Number: 3.4.21.-
• Pfam ID: PF00089
• Sequence:
  MATARPPWMWVLCALITALLLGVTEHVLANNDVSCDHPSNTVPSGSNQDLGAGAGEDARS
  DDSSSRIINGSDCDMHTQPWQAALLLRPNQLYCGAVLVHPQWLLTAAHCRKKVFRVRLGH
  YSLSPVYESGQQMFQGVKSIPHPGYSHPGHSNDLMLIKLNRRIRPTKDVRPINVSSHCPS
  AGTKCLVSGWGTTKSPQVHFPKVLQCLNISVLSQKRCEDAYPRQIDDTMFCAGDKAGRDS
  CQGDSGGPVVCNGSLQGLVSWGDYPCARPNRPGVYTNLCKFTKWIQETIQANS
• Function: May be involved in desquamation.
• Tissue Specificity: Expressed in skin, breast, brain and testis. Expressed at the stratum granulosum of palmar skin.
• Reactome Pathway: Formation of the cornified envelope (R-HSA-6809371)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Kallikrein-5 (KLK5) affects the response to substance of Cisplatin.	[9]

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 Kallikrein-5 (KLK5).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Kallikrein-5 (KLK5).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Kallikrein-5 (KLK5).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Kallikrein-5 (KLK5).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Kallikrein-5 (KLK5).	[4]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Kallikrein-5 (KLK5).	[5]
Citrate	DM37NYK	Preclinical	Citrate increases the activity of Kallikrein-5 (KLK5).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Kallikrein-5 (KLK5).	[8]

References

• [1] 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.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [6] 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.
• [7] Human tissue kallikrein 5 is a member of a proteolytic cascade pathway involved in seminal clot liquefaction and potentially in prostate cancer progression. J Biol Chem. 2006 May 5;281(18):12743-50. doi: 10.1074/jbc.M600326200. Epub 2006 Mar 3.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [9] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.