Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8LOD2U)

• DOT Name: Kallikrein-13 (KLK13)
• Synonyms: EC 3.4.21.-; Kallikrein-like protein 4; KLK-L4
• Gene Name: KLK13
• Related Disease:
  Advanced cancer
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Colon cancer
  Colon carcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Gastric neoplasm
  Lung cancer
  Lung carcinoma
  Neoplasm of testis
  Non-small-cell lung cancer
  Oral cancer
  Ovarian cancer
  Ovarian neoplasm
  Stomach cancer
  Testicular cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Adenocarcinoma
  Colon adenocarcinoma
  Lung neoplasm
  Prostate cancer
  Prostate carcinoma
• UniProt ID: KLK13_HUMAN
• EC Number: 3.4.21.-
• Pfam ID: PF00089
• Sequence:
  MWPLALVIASLTLALSGGVSQESSKVLNTNGTSGFLPGGYTCFPHSQPWQAALLVQGRLL
  CGGVLVHPKWVLTAAHCLKEGLKVYLGKHALGRVEAGEQVREVVHSIPHPEYRRSPTHLN
  HDHDIMLLELQSPVQLTGYIQTLPLSHNNRLTPGTTCRVSGWGTTTSPQVNYPKTLQCAN
  IQLRSDEECRQVYPGKITDNMLCAGTKEGGKDSCEGDSGGPLVCNRTLYGIVSWGDFPCG
  QPDRPGVYTRVSRYVLWIRETIRKYETQQQKWLKGPQ
• Tissue Specificity: Expressed in prostate, breast, testis and salivary gland.
• Reactome Pathway:
  Formation of the cornified envelope (R-HSA-6809371)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Bladder cancer	DISUHNM0	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[4]
Carcinoma	DISH9F1N	Strong	Biomarker	[5]
Colon cancer	DISVC52G	Strong	Biomarker	[6]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[6]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[8]
Gastric cancer	DISXGOUK	Strong	Biomarker	[5]
Gastric neoplasm	DISOKN4Y	Strong	Altered Expression	[5]
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung carcinoma	DISTR26C	Strong	Biomarker	[1]
Neoplasm of testis	DISK4XHT	Strong	Altered Expression	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[10]
Oral cancer	DISLD42D	Strong	Altered Expression	[11]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[7]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[7]
Stomach cancer	DISKIJSX	Strong	Biomarker	[5]
Testicular cancer	DIS6HNYO	Strong	Genetic Variation	[9]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[2]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[2]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[12]
Colon adenocarcinoma	DISDRE0J	Limited	Biomarker	[13]
Lung neoplasm	DISVARNB	Limited	Altered Expression	[12]
Prostate cancer	DISF190Y	Limited	Genetic Variation	[14]
Prostate carcinoma	DISMJPLE	Limited	Genetic Variation	[14]

5 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-13 (KLK13).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Kallikrein-13 (KLK13).	[16]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate increases the expression of Kallikrein-13 (KLK13).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Kallikrein-13 (KLK13).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Kallikrein-13 (KLK13).	[20]

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 affects the methylation of Kallikrein-13 (KLK13).	[18]

References

• [1] Epigenetic activation of human kallikrein 13 enhances malignancy of lung adenocarcinoma by promoting N-cadherin expression and laminin degradation.Biochem Biophys Res Commun. 2011 Jun 10;409(3):442-7. doi: 10.1016/j.bbrc.2011.05.022. Epub 2011 May 8.
• [2] Downregulated KLK13 expression in bladder cancer highlights tumor aggressiveness and unfavorable patients' prognosis.J Cancer Res Clin Oncol. 2017 Mar;143(3):521-532. doi: 10.1007/s00432-016-2301-6. Epub 2016 Nov 17.
• [3] Human kallikrein gene 13 (KLK13) expression by quantitative RT-PCR: an independent indicator of favourable prognosis in breast cancer.Br J Cancer. 2002 May 6;86(9):1457-64. doi: 10.1038/sj.bjc.6600283.
• [4] Development of Chemical Tools to Monitor Human Kallikrein 13 (KLK13) Activity.Int J Mol Sci. 2019 Mar 28;20(7):1557. doi: 10.3390/ijms20071557.
• [5] Kallikrein-related peptidase 13 (KLK13) gene expressional status contributes significantly in the prognosis of primary gastric carcinomas.Clin Biochem. 2010 Oct;43(15):1205-11. doi: 10.1016/j.clinbiochem.2010.07.016. Epub 2010 Jul 30.
• [6] Mucin 16 and kallikrein 13 as potential prognostic factors in colon cancer: Results of an oncological 92-multiplex immunoassay.Tumour Biol. 2019 Jul;41(7):1010428319860728. doi: 10.1177/1010428319860728.
• [7] Advanced high-grade serous ovarian cancer: inverse association of KLK13 and KLK14 mRNA levels in tumor tissue and patients' prognosis.J Cancer Res Clin Oncol. 2018 Jun;144(6):1109-1118. doi: 10.1007/s00432-018-2623-7. Epub 2018 Mar 15.
• [8] Correction to: Expression of kallikrein-related peptidase 13 is associated with poor prognosis in esophageal squamous cell carcinoma.Gen Thorac Cardiovasc Surg. 2018 Jun;66(6):376-377. doi: 10.1007/s11748-018-0923-0.
• [9] Identification and molecular characterization of five novel kallikrein gene 13 (KLK13; KLK-L4) splice variants: differential expression in the human testis and testicular cancer.Anticancer Res. 2001 Sep-Oct;21(5):3147-52.
• [10] Kallikrein-related peptidase 13: an independent indicator of favorable prognosis for patients with nonsmall cell lung cancer.Tumour Biol. 2015 Jul;36(7):4979-86. doi: 10.1007/s13277-015-3148-1. Epub 2015 Feb 13.
• [11] Decreased expression of kallikrein-related peptidase 13: possible contribution to metastasis of human oral cancer.Mol Carcinog. 2014 Jul;53(7):557-65. doi: 10.1002/mc.22007. Epub 2013 Jan 31.
• [12] Quantitative RT-PCR analysis and immunohistochemical localization of the kallikrein-related peptidases 13 and 14 in lung.Biol Chem. 2008 Jun;389(6):781-6. doi: 10.1515/BC.2008.089.
• [13] Diagnostic and prognostic biomarker potential of kallikrein family genes in different cancer types.Oncotarget. 2018 Apr 3;9(25):17876-17888. doi: 10.18632/oncotarget.24947. eCollection 2018 Apr 3.
• [14] Common variation in Kallikrein genes KLK5, KLK6, KLK12, and KLK13 and risk of prostate cancer and tumor aggressiveness.Urol Oncol. 2013 Jul;31(5):635-43. doi: 10.1016/j.urolonc.2011.05.011. Epub 2011 Jul 8.
• [15] 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.
• [16] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [17] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [18] 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.
• [19] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.