Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7BVG17)

• DOT Name: Kallikrein-15 (KLK15)
• Synonyms: EC 3.4.21.-; ACO protease
• Gene Name: KLK15
• Related Disease:
  Advanced cancer
  Benign prostatic hyperplasia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Chronic kidney disease
  Colorectal carcinoma
  Epithelial ovarian cancer
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Benign neoplasm
  Chronic obstructive pulmonary disease
  Prostate neoplasm
  Adenocarcinoma
  Asthma
  Prostate adenocarcinoma
  Prostate cancer
  Prostate carcinoma
• UniProt ID: KLK15_HUMAN
• EC Number: 3.4.21.-
• Pfam ID: PF00089
• Sequence:
  MWLLLTLSFLLASTAAQDGDKLLEGDECAPHSQPWQVALYERGRFNCGASLISPHWVLSA
  AHCQSRFMRVRLGEHNLRKRDGPEQLRTTSRVIPHPRYEARSHRNDIMLLRLVQPARLNP
  QVRPAVLPTRCPHPGEACVVSGWGLVSHNEPGTAGSPRSQVSLPDTLHCANISIISDTSC
  DKSYPGRLTNTMVCAGAEGRGAESCEGDSGGPLVCGGILQGIVSWGDVPCDNTTKPGVYT
  KVCHYLEWIRETMKRN
• Function: Protease whose physiological substrate is not yet known.
• Tissue Specificity: Highest expression in the thyroid gland. Also expressed in the prostate, salivary, and adrenal glands and in the colon testis and kidney.

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[4]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[7]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[7]
Benign neoplasm	DISDUXAD	moderate	Altered Expression	[8]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[9]
Prostate neoplasm	DISHDKGQ	moderate	Altered Expression	[8]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[10]
Asthma	DISW9QNS	Limited	Biomarker	[11]
Prostate adenocarcinoma	DISBZYU8	Limited	Altered Expression	[10]
Prostate cancer	DISF190Y	Limited	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Kallikrein-15 (KLK15) affects the response to substance of Cisplatin.	[17]

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-15 (KLK15).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Kallikrein-15 (KLK15).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Kallikrein-15 (KLK15).	[13]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Kallikrein-15 (KLK15).	[14]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Kallikrein-15 (KLK15).	[15]

References

• [1] Biochemical characterization of human tissue kallikrein 15 and examination of its potential role in cancer.Clin Biochem. 2018 Aug;58:108-115. doi: 10.1016/j.clinbiochem.2018.06.007. Epub 2018 Jun 18.
• [2] Expression analysis and study of the KLK15 mRNA splice variants in prostate cancer and benign prostatic hyperplasia.Cancer Sci. 2010 Mar;101(3):693-9. doi: 10.1111/j.1349-7006.2009.01450.x. Epub 2009 Nov 27.
• [3] Prognostic value of quantitatively assessed KLK7 expression in ovarian cancer.Clin Biochem. 2003 Mar;36(2):135-43. doi: 10.1016/s0009-9120(02)00446-0.
• [4] The androgen-regulated gene human kallikrein 15 (KLK15) is an independent and favourable prognostic marker for breast cancer.Br J Cancer. 2002 Nov 18;87(11):1294-300. doi: 10.1038/sj.bjc.6600590.
• [5] Intelligent Diagnostic Prediction and Classification System for Chronic Kidney Disease.Sci Rep. 2019 Jul 3;9(1):9583. doi: 10.1038/s41598-019-46074-2.
• [6] Does a transition to accountable care in Medicaid shift the modality of colorectal cancer testing?.BMC Health Serv Res. 2019 Jan 21;19(1):54. doi: 10.1186/s12913-018-3864-5.
• [7] A Kallikrein 15 (KLK15) single nucleotide polymorphism located close to a novel exon shows evidence of association with poor ovarian cancer survival.BMC Cancer. 2011 Apr 1;11:119. doi: 10.1186/1471-2407-11-119.
• [8] Quantified KLK15 gene expression levels discriminate prostate cancer from benign tumors and constitute a novel independent predictor of disease progression.Prostate. 2013 Aug;73(11):1191-201. doi: 10.1002/pros.22667. Epub 2013 Apr 26.
• [9] Burden of asthma and COPD overlap (ACO) in Taiwan: a nationwide population-based study.BMC Pulm Med. 2018 Jan 25;18(1):16. doi: 10.1186/s12890-017-0571-7.
• [10] KLK15 is a prognostic marker for progression-free survival in patients with radical prostatectomy.Int J Cancer. 2010 Nov 15;127(10):2386-94. doi: 10.1002/ijc.25435.
• [11] Reliability, validity and responsiveness of E-RS:COPD in patients with spirometric asthma-COPD overlap.Respir Res. 2019 May 31;20(1):107. doi: 10.1186/s12931-019-1070-6.
• [12] 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.
• [13] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [14] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [15] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [16] 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.
• [17] 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.