Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIWGMO2)

DOT Name	Kallikrein-7 (KLK7)
Synonyms	hK7; EC 3.4.21.117; Serine protease 6; Stratum corneum chymotryptic enzyme; hSCCE
Gene Name	KLK7
UniProt ID	KLK7_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2QXG; 2QXH; 2QXI; 2QXJ; 3BSQ; 5FAH; 5Y9L; 5YJK; 6SHH; 6SHI; 6SJU; 6Y4S
EC Number	3.4.21.117
Pfam ID	PF00089
Sequence	MARSLLLPLQILLLSLALETAGEEAQGDKIIDGAPCARGSHPWQVALLSGNQLHCGGVLV NERWVLTAAHCKMNEYTVHLGSDTLGDRRAQRIKASKSFRHPGYSTQTHVNDLMLVKLNS QARLSSMVKKVRLPSRCEPPGTTCTVSGWGTTTSPDVTFPSDLMCVDVKLISPQDCTKVY KDLLENSMLCAGIPDSKKNACNGDSGGPLVCRGTLQGLVSWGTFPCGQPNDPGVYTQVCK FTKWINDTMKKHR
Function	May catalyze the degradation of intercellular cohesive structures in the cornified layer of the skin in the continuous shedding of cells from the skin surface. Specific for amino acid residues with aromatic side chains in the P1 position. Cleaves insulin A chain at '14-Tyr-\|-Gln-15' and insulin B chain at '6-Leu-\|-Cys-7', '16-Tyr-\|-Leu-17', '25-Phe-\|-Tyr-26' and '26-Tyr-\|-Thr-27'. Could play a role in the activation of precursors to inflammatory cytokines.
Tissue Specificity	Abundantly expressed in the skin and is expressed by keratinocytes in the epidermis. Also expressed in the brain, mammary gland, cerebellum, spinal cord and kidney. Lower levels in salivary glands, uterus, thymus, thyroid, placenta, trachea and testis. Up-regulated in ovarian carcinoma, especially late-stage serous carcinoma, compared with normal ovaries and benign adenomas (at protein level).
Reactome Pathway	Degradation of the extracellular matrix (R-HSA-1474228 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas 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-7 (KLK7) affects the response to substance of Cisplatin.	[9]
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8 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 Kallikrein-7 (KLK7).	[1]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Kallikrein-7 (KLK7).	[2]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Kallikrein-7 (KLK7).	[3]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Kallikrein-7 (KLK7).	[4]
Exemestane	DM9HPW3	Approved	Exemestane increases the expression of Kallikrein-7 (KLK7).	[5]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Kallikrein-7 (KLK7).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Kallikrein-7 (KLK7).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Kallikrein-7 (KLK7).	[8]
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⏷ Show the Full List of 8 Drug(s)

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 increases the methylation of Kallikrein-7 (KLK7).	[6]
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References

1	Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
2	Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
3	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
4	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.
5	Effects of aromatase inhibitors on human osteoblast and osteoblast-like cells: a possible androgenic bone protective effects induced by exemestane. Bone. 2007 Apr;40(4):876-87. doi: 10.1016/j.bone.2006.11.029. Epub 2006 Dec 28.
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	CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
8	Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
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.