Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSBTLO0)

DOT Name TNF receptor-associated factor 5 (TRAF5)
Synonyms RING finger protein 84
Gene Name TRAF5
Related Disease
Autoimmune disease ( )
Behcet disease ( )
Central nervous system neoplasm ( )
Colitis ( )
Colorectal carcinoma ( )
Crohn disease ( )
Dermatitis ( )
Diabetic kidney disease ( )
Gastric cancer ( )
Glioma ( )
Hepatocellular carcinoma ( )
Inflammatory bowel disease ( )
Pneumonia ( )
Pneumonitis ( )
Psoriatic arthritis ( )
Stomach cancer ( )
T-cell acute lymphoblastic leukaemia ( )
Ulcerative colitis ( )
Ankylosing spondylitis ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Rheumatoid arthritis ( )
Uveitis ( )
UniProt ID
TRAF5_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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PDB ID
7L3L
Pfam ID
PF21355 ; PF21363 ; PF02176
Sequence
MAYSEEHKGMPCGFIRQNSGNSISLDFEPSIEYQFVERLEERYKCAFCHSVLHNPHQTGC
GHRFCQHCILSLRELNTVPICPVDKEVIKSQEVFKDNCCKREVLNLYVYCSNAPGCNAKV
ILGRYQDHLQQCLFQPVQCSNEKCREPVLRKDLKEHLSASCQFRKEKCLYCKKDVVVINL
QNHEENLCPEYPVFCPNNCAKIILKTEVDEHLAVCPEAEQDCPFKHYGCAVTDKRRNLQQ
HEHSALREHMRLVLEKNVQLEEQISDLHKSLEQKESKIQQLAETIKKLEKEFKQFAQLFG
KNGSFLPNIQVFASHIDKSAWLEAQVHQLLQMVNQQQNKFDLRPLMEAVDTVKQKITLLE
NNDQRLAVLEEETNKHDTHINIHKAQLSKNEERFKLLEGTCYNGKLIWKVTDYKMKKREA
VDGHTVSIFSQSFYTSRCGYRLCARAYLNGDGSGRGSHLSLYFVVMRGEFDSLLQWPFRQ
RVTLMLLDQSGKKNIMETFKPDPNSSSFKRPDGEMNIASGCPRFVAHSVLENAKNAYIKD
DTLFLKVAVDLTDLEDL
Function
Adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to different signaling pathways by association with the receptor cytoplasmic domain and kinases. Mediates activation of NF-kappa-B and probably JNK. Seems to be involved in apoptosis. Plays a role in mediating activation of NF-kappa-B by EIF2AK2/PKR.
Tissue Specificity Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon, and peripheral blood.
KEGG Pathway
NF-kappa B sig.ling pathway (hsa04064 )
Necroptosis (hsa04217 )
NOD-like receptor sig.ling pathway (hsa04621 )
IL-17 sig.ling pathway (hsa04657 )
TNF sig.ling pathway (hsa04668 )
Shigellosis (hsa05131 )
Human cytomegalovirus infection (hsa05163 )
Herpes simplex virus 1 infection (hsa05168 )
Epstein-Barr virus infection (hsa05169 )
Human immunodeficiency virus 1 infection (hsa05170 )
Pathways in cancer (hsa05200 )
Viral carcinogenesis (hsa05203 )
Small cell lung cancer (hsa05222 )

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autoimmune disease DISORMTM Strong Biomarker [1]
Behcet disease DISSYMBS Strong Genetic Variation [1]
Central nervous system neoplasm DISFC18W Strong Genetic Variation [2]
Colitis DISAF7DD Strong Altered Expression [3]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [4]
Crohn disease DIS2C5Q8 Strong Altered Expression [3]
Dermatitis DISY5SZC Strong Biomarker [5]
Diabetic kidney disease DISJMWEY Strong Altered Expression [6]
Gastric cancer DISXGOUK Strong Altered Expression [7]
Glioma DIS5RPEH Strong Genetic Variation [2]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [8]
Inflammatory bowel disease DISGN23E Strong Biomarker [3]
Pneumonia DIS8EF3M Strong Biomarker [9]
Pneumonitis DIS88E0K Strong Biomarker [9]
Psoriatic arthritis DISLWTG2 Strong Biomarker [10]
Stomach cancer DISKIJSX Strong Altered Expression [7]
T-cell acute lymphoblastic leukaemia DIS17AI2 Strong Biomarker [11]
Ulcerative colitis DIS8K27O Strong Altered Expression [3]
Ankylosing spondylitis DISRC6IR Limited Genetic Variation [12]
Coronary atherosclerosis DISKNDYU Limited Altered Expression [13]
Coronary heart disease DIS5OIP1 Limited Altered Expression [13]
Rheumatoid arthritis DISTSB4J Limited Biomarker [14]
Uveitis DISV0RYS Limited Genetic Variation [12]
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⏷ Show the Full List of 23 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of TNF receptor-associated factor 5 (TRAF5). [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of TNF receptor-associated factor 5 (TRAF5). [24]
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11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of TNF receptor-associated factor 5 (TRAF5). [16]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of TNF receptor-associated factor 5 (TRAF5). [17]
Estradiol DMUNTE3 Approved Estradiol affects the expression of TNF receptor-associated factor 5 (TRAF5). [18]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of TNF receptor-associated factor 5 (TRAF5). [19]
Ethanol DMDRQZU Approved Ethanol increases the expression of TNF receptor-associated factor 5 (TRAF5). [20]
Paclitaxel DMLB81S Approved Paclitaxel decreases the expression of TNF receptor-associated factor 5 (TRAF5). [21]
Menthol DMG2KW7 Approved Menthol decreases the expression of TNF receptor-associated factor 5 (TRAF5). [22]
Tamibarotene DM3G74J Phase 3 Tamibarotene decreases the expression of TNF receptor-associated factor 5 (TRAF5). [23]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of TNF receptor-associated factor 5 (TRAF5). [25]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of TNF receptor-associated factor 5 (TRAF5). [18]
GALLICACID DM6Y3A0 Investigative GALLICACID decreases the expression of TNF receptor-associated factor 5 (TRAF5). [26]
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⏷ Show the Full List of 11 Drug(s)

References

1 TRAF5 and TRAF3IP2 gene polymorphisms are associated with Behet's disease and Vogt-Koyanagi-Harada syndrome: a case-control study.PLoS One. 2014 Jan 8;9(1):e84214. doi: 10.1371/journal.pone.0084214. eCollection 2014.
2 Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility.Nat Genet. 2009 Aug;41(8):905-8. doi: 10.1038/ng.408. Epub 2009 Jul 5.
3 Up-regulation and pre-activation of TRAF3 and TRAF5 in inflammatory bowel disease.Int J Med Sci. 2013;10(2):156-63. doi: 10.7150/ijms.5457. Epub 2013 Jan 3.
4 MiR-141-3p inhibits cell proliferation, migration and invasion by targeting TRAF5 in colorectal cancer.Biochem Biophys Res Commun. 2019 Jun 30;514(3):699-705. doi: 10.1016/j.bbrc.2019.05.002. Epub 2019 May 9.
5 TNF Receptor-Associated Factor 5 Limits Function of Plasmacytoid Dendritic Cells by Controlling IFN Regulatory Factor 5 Expression.J Immunol. 2019 Sep 15;203(6):1447-1456. doi: 10.4049/jimmunol.1900188. Epub 2019 Aug 16.
6 Astragaloside IV/lncRNA-TUG1/TRAF5 signaling pathway participates in podocyte apoptosis of diabetic nephropathy rats.Drug Des Devel Ther. 2018 Sep 6;12:2785-2793. doi: 10.2147/DDDT.S166525. eCollection 2018.
7 miR-135a suppresses migration of gastric cancer cells by targeting TRAF5-mediated NF-B activation.Onco Targets Ther. 2019 Feb 1;12:975-984. doi: 10.2147/OTT.S189976. eCollection 2019.
8 LINC00467 promotes cell proliferation and metastasis by binding with IGF2BP3 to enhance the mRNA stability of TRAF5 in hepatocellular carcinoma.J Gene Med. 2020 Mar;22(3):e3134. doi: 10.1002/jgm.3134. Epub 2020 Jan 20.
9 TNF receptor associated factor 5 controls oncostatin M-mediated lung inflammation.Biochem Biophys Res Commun. 2018 May 15;499(3):544-550. doi: 10.1016/j.bbrc.2018.03.186. Epub 2018 Apr 2.
10 New insight into the functions of the interleukin-17 receptor adaptor protein Act1 in psoriatic arthritis.Arthritis Res Ther. 2012 Oct 31;14(5):226. doi: 10.1186/ar4071.
11 miR-141-3p and TRAF5 Network Contributes to the Progression of T-Cell Acute Lymphoblastic Leukemia.Cell Transplant. 2019 Dec;28(1_suppl):59S-65S. doi: 10.1177/0963689719887370. Epub 2019 Nov 14.
12 TNF receptor-associated factor 5 gene confers genetic predisposition to acute anterior uveitis and pediatric uveitis.Arthritis Res Ther. 2013;15(5):R113. doi: 10.1186/ar4293.
13 TRAF5 deficiency accelerates atherogenesis in mice by increasing inflammatory cell recruitment and foam cell formation.Circ Res. 2010 Sep 17;107(6):757-66. doi: 10.1161/CIRCRESAHA.110.219295. Epub 2010 Jul 22.
14 Investigation of association between the TRAF family genes and RA susceptibility.Ann Rheum Dis. 2007 Oct;66(10):1322-6. doi: 10.1136/ard.2006.065706. Epub 2007 Feb 2.
15 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.
16 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
17 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
18 Gene alterations of ovarian cancer cells expressing estrogen receptors by estrogen and bisphenol a using microarray analysis. Lab Anim Res. 2011 Jun;27(2):99-107. doi: 10.5625/lar.2011.27.2.99. Epub 2011 Jun 22.
19 Arsenic trioxide induces different gene expression profiles of genes related to growth and apoptosis in glioma cells dependent on the p53 status. Mol Biol Rep. 2008 Sep;35(3):421-9.
20 Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
21 Effects of paclitaxel on proliferation and apoptosis in human acute myeloid leukemia HL-60 cells. Acta Pharmacol Sin. 2004 Mar;25(3):378-84.
22 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.
23 Induction of class II major histocompatibility complex expression in human multiple myeloma cells by retinoid. Haematologica. 2007 Jan;92(1):115-20.
24 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.
25 Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
26 Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.