Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKAN9G7)

DOT Name	Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B)
Synonyms	Decoy receptor 3; DcR3; Decoy receptor for Fas ligand; M68
Gene Name	TNFRSF6B
Related Disease	Advanced cancer ( ) Alzheimer disease ( ) Autoimmune disease ( ) Breast cancer ( ) Breast carcinoma ( ) Carcinoma ( ) Clear cell renal carcinoma ( ) Colon cancer ( ) Colon carcinoma ( ) Colorectal carcinoma ( ) Coronary heart disease ( ) Crohn disease ( ) Gastric neoplasm ( ) Hepatitis B virus infection ( ) Hepatocellular carcinoma ( ) Inflammatory bowel disease ( ) Invasive ductal breast carcinoma ( ) Liver cancer ( ) Lung adenocarcinoma ( ) Metastatic malignant neoplasm ( ) Osteoarthritis ( ) Psoriasis ( ) Renal cell carcinoma ( ) Rheumatoid arthritis ( ) Systemic lupus erythematosus ( ) Type-1/2 diabetes ( ) Ulcerative colitis ( ) Adult lymphoma ( ) B-cell neoplasm ( ) Gastric cancer ( ) Lymphoma ( ) Osteosarcoma ( ) Pancreatic cancer ( ) Pediatric lymphoma ( ) Stomach cancer ( ) Coronary atherosclerosis ( ) Adenocarcinoma ( ) Adult glioblastoma ( ) Ankylosing spondylitis ( ) Astrocytoma ( ) Atopic dermatitis ( ) Epithelial ovarian cancer ( ) Glioblastoma multiforme ( ) Glioma ( ) Glomerulonephritis ( ) IgA nephropathy ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Sclerosing cholangitis ( )
UniProt ID	TNF6B_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	3K51; 3MHD; 3MI8; 4J6G; 4KGG; 4KGQ; 4MSV; 5L36
Pfam ID	PF00020
Sequence	MRALEGPGLSLLCLVLALPALLPVPAVRGVAETPTYPWRDAETGERLVCAQCPPGTFVQR PCRRDSPTTCGPCPPRHYTQFWNYLERCRYCNVLCGEREEEARACHATHNRACRCRTGFF AHAGFCLEHASCPPGAGVIAPGTPSQNTQCQPCPPGTFSASSSSSEQCQPHRNCTALGLA LNVPGSSSHDTLCTSCTGFPLSTRVPGAEECERAVIDFVAFQDISIKRLQRLLQALEAPE GWGPTPRAGRAALQLKLRRRLTELLGAQDGALLVRLLQALRVARMPGLERSVRERFLPVH
Function	Decoy receptor that can neutralize the cytotoxic ligands TNFS14/LIGHT, TNFSF15 and TNFSF6/FASL. Protects against apoptosis.
Tissue Specificity	Detected in fetal lung, brain and liver. Detected in adult stomach, spinal cord, lymph node, trachea, spleen, colon and lung. Highly expressed in several primary tumors from colon, stomach, rectum, esophagus and in SW480 colon carcinoma cells.
KEGG Pathway	Cytokine-cytokine receptor interaction (hsa04060 )
Reactome Pathway	TNFs bind their physiological receptors (R-HSA-5669034 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Carcinoma	DISH9F1N	Strong	Altered Expression	[5]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[6]
Colon cancer	DISVC52G	Strong	Altered Expression	[7]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[9]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[10]
Gastric neoplasm	DISOKN4Y	Strong	Altered Expression	[11]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[10]
Invasive ductal breast carcinoma	DIS43J58	Strong	Altered Expression	[13]
Liver cancer	DISDE4BI	Strong	Altered Expression	[14]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[15]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[16]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[17]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[18]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[6]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[17]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[19]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[20]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[10]
Adult lymphoma	DISK8IZR	moderate	Altered Expression	[21]
B-cell neoplasm	DISVY326	moderate	Altered Expression	[21]
Gastric cancer	DISXGOUK	moderate	Biomarker	[22]
Lymphoma	DISN6V4S	moderate	Altered Expression	[21]
Osteosarcoma	DISLQ7E2	moderate	Altered Expression	[23]
Pancreatic cancer	DISJC981	moderate	Biomarker	[24]
Pediatric lymphoma	DIS51BK2	moderate	Altered Expression	[21]
Stomach cancer	DISKIJSX	moderate	Biomarker	[22]
Coronary atherosclerosis	DISKNDYU	Disputed	Biomarker	[9]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[25]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[26]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[18]
Astrocytoma	DISL3V18	Limited	Biomarker	[26]
Atopic dermatitis	DISTCP41	Limited	Genetic Variation	[27]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[28]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[26]
Glioma	DIS5RPEH	Limited	Biomarker	[29]
Glomerulonephritis	DISPZIQ3	Limited	Biomarker	[30]
IgA nephropathy	DISZ8MTK	Limited	Biomarker	[30]
Ovarian cancer	DISZJHAP	Limited	Altered Expression	[28]
Ovarian neoplasm	DISEAFTY	Limited	Altered Expression	[28]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[18]
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⏷ Show the Full List of 49 Disease(s)

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
Topotecan	DMP6G8T	Approved	Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B) affects the response to substance of Topotecan.	[37]
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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 Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B).	[35]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B).	[32]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B).	[33]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B).	[36]
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References

1	Role of TGF3-Smads-Sp1 axis in DcR3-mediated immune escape of hepatocellular carcinoma.Oncogenesis. 2019 Aug 13;8(8):43. doi: 10.1038/s41389-019-0152-0.
2	Amelioration of amyloid--induced deficits by DcR3 in an Alzheimer's disease model.Mol Neurodegener. 2017 Apr 24;12(1):30. doi: 10.1186/s13024-017-0173-0.
3	Overexpression of human decoy receptor 3 in mice results in a systemic lupus erythematosus-like syndrome.Arthritis Rheum. 2007 Nov;56(11):3748-58. doi: 10.1002/art.22978.
4	Subgrouping breast cancer patients based on immune evasion mechanisms unravels a high involvement of transforming growth factor-beta and decoy receptor 3.PLoS One. 2018 Dec 4;13(12):e0207799. doi: 10.1371/journal.pone.0207799. eCollection 2018.
5	Clinical significance of expression and amplification of the DcR3 gene in pancreatic carcinomas.Asian Pac J Cancer Prev. 2012;13(2):719-24. doi: 10.7314/apjcp.2012.13.2.719.
6	The soluble Decoy Receptor 3 is regulated by a PI3K-dependent mechanism and promotes migration and invasion in renal cell carcinoma.Mol Cancer. 2013 Oct 10;12(1):120. doi: 10.1186/1476-4598-12-120.
7	DcR3 regulates the growth and metastatic potential of SW480 colon cancer cells.Oncol Rep. 2013 Dec;30(6):2741-8. doi: 10.3892/or.2013.2769. Epub 2013 Oct 1.
8	DcR3 induces epithelial-mesenchymal transition through activation of the TGF-3/SMAD signaling pathway in CRC.Oncotarget. 2016 Nov 22;7(47):77306-77318. doi: 10.18632/oncotarget.12639.
9	Decoy receptor-3 regulates inflammation and apoptosis via PI3K/AKT signaling pathway in coronary heart disease.Exp Ther Med. 2019 Apr;17(4):2614-2622. doi: 10.3892/etm.2019.7222. Epub 2019 Jan 30.
10	Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease.Gastroenterology. 2017 Jan;152(1):206-217.e2. doi: 10.1053/j.gastro.2016.09.032. Epub 2016 Sep 28.
11	High DcR3 expression predicts stage pN2-3 in gastric cancer.Am J Clin Oncol. 2008 Feb;31(1):79-83. doi: 10.1097/COC.0b013e3180ca77ad.
12	Hepatitis B X protein upregulates decoy receptor 3 expression via the PI3K/NF-B pathway.Cell Signal. 2019 Oct;62:109346. doi: 10.1016/j.cellsig.2019.109346. Epub 2019 Jun 21.
13	DcR3 gene polymorphisms are associated with sporadic breast infiltrating ductal carcinoma in Northeast Chinese women.Oncotarget. 2016 Sep 6;7(36):57970-57977. doi: 10.18632/oncotarget.11153.
14	The siRNA silencing of DcR3 expression induces Fas ligand-mediated apoptosis in HepG2 cells.Exp Ther Med. 2018 May;15(5):4370-4378. doi: 10.3892/etm.2018.5964. Epub 2018 Mar 19.
15	Decoy Receptor 3 Expression Is Associated With Wild-Type EGFR Status, Poor Differentiation of Tumor, and Unfavorable Patient Outcome.Am J Clin Pathol. 2019 Jul 5;152(2):207-216. doi: 10.1093/ajcp/aqz035.
16	Expression of decoy receptor 3 in liver tissue microarrays.Natl Med J India. 2008 Nov-Dec;21(6):275-8.
17	Decoy receptor 3 down-regulates centrosomal protein 70kDa specifically in rheumatoid synovial fibroblasts.Mod Rheumatol. 2018 Mar;28(2):287-292. doi: 10.1080/14397595.2017.1341593. Epub 2017 Jul 11.
18	Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
19	DcR3 mutations in patients with juvenile-onset systemic lupus erythematosus lead to enhanced lymphocyte proliferation.J Rheumatol. 2013 Aug;40(8):1316-26. doi: 10.3899/jrheum.121285. Epub 2013 Jun 1.
20	DcR3 protects islet beta cells from apoptosis through modulating Adcyap1 and Bank1 expression.J Immunol. 2009 Dec 15;183(12):8157-66. doi: 10.4049/jimmunol.0901165.
21	Expression of a soluble decoy receptor 3 in patients with diffuse large B-cell lymphoma predicts clinical outcome.Int J Oncol. 2008 Sep;33(3):549-54.
22	DcR3 induces proliferation, migration, invasion, and EMT in gastric cancer cells via the PI3K/AKT/GSK-3/-catenin signaling pathway.Onco Targets Ther. 2018 Jul 19;11:4177-4187. doi: 10.2147/OTT.S172713. eCollection 2018.
23	Sodium valproate, a histone deacetylase inhibitor, modulates the vascular endothelial growth inhibitor-mediated cell death in human osteosarcoma and vascular endothelial cells.Int J Oncol. 2015 May;46(5):1994-2002. doi: 10.3892/ijo.2015.2924. Epub 2015 Mar 12.
24	A Panel of Three Biomarkers Identified by iTRAQ for the Early Diagnosis of Pancreatic Cancer.Proteomics Clin Appl. 2019 Sep;13(5):e1800195. doi: 10.1002/prca.201800195. Epub 2019 May 7.
25	Overexpression of decoy receptor 3 in precancerous lesions and adenocarcinoma of the esophagus.Am J Clin Pathol. 2005 Aug;124(2):282-7. doi: 10.1309/XK59-4E4B-5WU8-2QR6.
26	Frequent gene amplification and overexpression of decoy receptor 3 in glioblastoma.Acta Neuropathol. 2005 Mar;109(3):294-8. doi: 10.1007/s00401-004-0956-6. Epub 2004 Dec 31.
27	Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms.Am J Hum Genet. 2015 Jan 8;96(1):104-20. doi: 10.1016/j.ajhg.2014.12.004.
28	DcR3 binds to ovarian cancer via heparan sulfate proteoglycans and modulates tumor cells response to platinum with corresponding alteration in the expression of BRCA1.BMC Cancer. 2012 May 14;12:176. doi: 10.1186/1471-2407-12-176.
29	Soluble decoy receptor 3 is expressed by malignant gliomas and suppresses CD95 ligand-induced apoptosis and chemotaxis.Cancer Res. 2001 Mar 15;61(6):2759-65.
30	Decoy receptor 3 inhibits renal mononuclear leukocyte infiltration and apoptosis and prevents progression of IgA nephropathy in mice.Am J Physiol Renal Physiol. 2011 Dec;301(6):F1218-30. doi: 10.1152/ajprenal.00050.2011. Epub 2011 Sep 7.
31	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.
32	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
33	Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
34	Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
35	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.
36	Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
37	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.