Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFD29NF)

• DOT Name: Tetranectin (CLEC3B)
• Synonyms: TN; C-type lectin domain family 3 member B; Plasminogen kringle 4-binding protein
• Gene Name: CLEC3B
• Related Disease:
  Acute myocardial infarction
  Adenocarcinoma
  Advanced cancer
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Hepatocellular carcinoma
  Macular dystrophy, retinal, 4
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Clear cell renal carcinoma
  Gastric cancer
  Stomach cancer
• UniProt ID: TETN_HUMAN
• PDB ID: 1HTN; 1RJH; 1TN3; 3L9J
• Pfam ID: PF00059
• Sequence:
  MELWGAYLLLCLFSLLTQVTTEPPTQKPKKIVNAKKDVVNTKMFEELKSRLDTLAQEVAL
  LKEQQALQTVCLKGTKVHMKCFLAFTQTKTFHEASEDCISRGGTLGTPQTGSENDALYEY
  LRQSVGNEAEIWLGLNDMAAEGTWVDMTGARIAYKNWETEITAQPDGGKTENCAVLSGAA
  NGKWFDKRCRDQLPYICQFGIV
• Function: Tetranectin binds to plasminogen and to isolated kringle 4. May be involved in the packaging of molecules destined for exocytosis. Plays a role in retinal function.
• Tissue Specificity: Found in plasma.
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Colon cancer	DISVC52G	Strong	Altered Expression	[4]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[6]
Macular dystrophy, retinal, 4	DISABS8P	Strong	Autosomal dominant	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Prostate cancer	DISF190Y	Strong	Biomarker	[8]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[8]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[9]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[10]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tetranectin (CLEC3B).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tetranectin (CLEC3B).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Tetranectin (CLEC3B).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Tetranectin (CLEC3B).	[14]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Tetranectin (CLEC3B).	[15]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Tetranectin (CLEC3B).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Tetranectin (CLEC3B).	[18]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of Tetranectin (CLEC3B).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tetranectin (CLEC3B).	[17]

References

• [1] Inverse changes in plasma tetranectin and titin levels in patients with type 2 diabetes mellitus: a potential predictor of acute myocardial infarction?.Acta Pharmacol Sin. 2018 Jul;39(7):1197-1207. doi: 10.1038/aps.2017.141. Epub 2018 Feb 8.
• [2] Tetranectin expression in gastric adenocarcinomas.Histol Histopathol. 2002 Apr;17(2):471-5. doi: 10.14670/HH-17.471.
• [3] Exome-wide Association Study Identifies CLEC3B Missense Variant p.S106G as Being Associated With Extreme Longevity in East Asian Populations.J Gerontol A Biol Sci Med Sci. 2017 Mar 1;72(3):309-318. doi: 10.1093/gerona/glw074.
• [4] Tetranectin, a plasminogen kringle 4-binding protein. Cloning and gene expression pattern in human colon cancer.Lab Invest. 1992 Aug;67(2):253-62.
• [5] Cancer-associated fibroblasts promote colorectal cancer progression by secreting CLEC3B.Cancer Biol Ther. 2019;20(7):967-978. doi: 10.1080/15384047.2019.1591122. Epub 2019 Mar 20.
• [6] External Radiation versus Internal Radiation for Patients with Advanced Unresectable HCC -A SEER Based Study.J Cancer. 2019 Jan 29;10(5):1171-1180. doi: 10.7150/jca.28983. eCollection 2019.
• [7] CLEC3B is a novel causative gene for macular-retinal dystrophy. Genet Med. 2022 Jun;24(6):1249-1260. doi: 10.1016/j.gim.2022.02.012. Epub 2022 Mar 22.
• [8] iTRAQ-based Comparative Serum Proteomic Analysis of Prostate Cancer Patients with or without Bone Metastasis.J Cancer. 2019 Jul 10;10(18):4165-4177. doi: 10.7150/jca.33497. eCollection 2019.
• [9] CLEC3B is downregulated and inhibits proliferation in clear cell renal cell carcinoma.Oncol Rep. 2018 Oct;40(4):2023-2035. doi: 10.3892/or.2018.6590. Epub 2018 Jul 23.
• [10] High Intratumoral Expression of Tetranectin Associates with Poor Prognosis of Patients with Gastric Cancer after Gastrectomy.J Cancer. 2017 Oct 9;8(17):3623-3630. doi: 10.7150/jca.19438. eCollection 2017.
• [11] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [12] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [13] Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. Arch Toxicol. 2017 May;91(5):2067-2078. doi: 10.1007/s00204-016-1879-4. Epub 2016 Nov 12.
• [14] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [15] The impact of luteal phase support on gene expression of extracellular matrix protein and adhesion molecules in the human endometrium during the window of implantation following controlled ovarian stimulation with a GnRH antagonist protocol. Fertil Steril. 2010 Nov;94(6):2264-71. doi: 10.1016/j.fertnstert.2010.01.068. Epub 2010 Mar 12.
• [16] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [17] 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.
• [18] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.