Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ6NVMW)

DOT Name	RNA transcription, translation and transport factor protein (RTRAF)
Synonyms	CLE7 homolog; CLE; hCLE
Gene Name	RTRAF
Related Disease	Advanced cancer ( ) Autoimmune disease ( ) Bladder cancer ( ) Brain neoplasm ( ) Breast cancer ( ) Breast carcinoma ( ) Crohn disease ( ) Cutaneous lupus erythematosus ( ) Dermatitis ( ) Dermatomyositis ( ) Esophageal squamous cell carcinoma ( ) Fatty liver disease ( ) Hepatocellular carcinoma ( ) Leukoencephalopathy with vanishing white matter ( ) Lung cancer ( ) Lung carcinoma ( ) Lung neoplasm ( ) Neoplasm ( ) Non-small-cell lung cancer ( ) Pancreatic tumour ( ) Skin disease ( ) Systemic lupus erythematosus ( ) Systemic sclerosis ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( ) Niemann-Pick disease type C ( ) Barrett esophagus ( ) Cervical cancer ( ) Cervical carcinoma ( ) Nasopharyngeal carcinoma ( )
UniProt ID	RTRAF_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	7P3A
Pfam ID	PF10036
Sequence	MFRRKLTALDYHNPAGFNCKDETEFRNFIVWLEDQKIRHYKIEDRGNLRNIHSSDWPKFF EKYLRDVNCPFKIQDRQEAIDWLLGLAVRLEYGDNAEKYKDLVPDNSKTADNATKNAEPL INLDVNNPDFKAGVMALANLLQIQRHDDYLVMLKAIRILVQERLTQDAVAKANQTKEGLP VALDKHILGFDTGDAVLNEAAQILRLLHIEELRELQTKINEAIVAVQAIIADPKTDHRLG KVGR
Function	RNA-binding protein involved in modulation of mRNA transcription by Polymerase II. Component of the tRNA-splicing ligase complex and is required for tRNA ligation. May be required for RNA transport ; (Microbial infection) In case of infection by influenza virus A (IVA), is involved in viral replication.
Tissue Specificity	Widely expressed. Expressed at high level in heart and skeletal muscle. Expressed at intermediate level in liver, pancreas, fetal brain and fetal lung. Weakly expressed in adult brain, adult lung, placenta, fetal liver and fetal kidney. Overexpressed in many brain tumors.
Reactome Pathway	tRNA processing in the nucleus (R-HSA-6784531 )
BioCyc Pathway	MetaCyc:ENSG00000087302-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Autoimmune disease	DISORMTM	Strong	Biomarker	[2]
Bladder cancer	DISUHNM0	Strong	Biomarker	[3]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[6]
Cutaneous lupus erythematosus	DISOIX6L	Strong	Biomarker	[2]
Dermatitis	DISY5SZC	Strong	Biomarker	[2]
Dermatomyositis	DIS50C5O	Strong	Genetic Variation	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[8]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[10]
Leukoencephalopathy with vanishing white matter	DIS3J8NN	Strong	Biomarker	[11]
Lung cancer	DISCM4YA	Strong	Biomarker	[12]
Lung carcinoma	DISTR26C	Strong	Biomarker	[12]
Lung neoplasm	DISVARNB	Strong	Biomarker	[12]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[13]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[14]
Skin disease	DISDW8R6	Strong	Biomarker	[15]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[2]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[7]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[3]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[3]
Niemann-Pick disease type C	DIS492ZO	moderate	Altered Expression	[16]
Barrett esophagus	DIS416Y7	Limited	Biomarker	[11]
Cervical cancer	DISFSHPF	Limited	Altered Expression	[1]
Cervical carcinoma	DIST4S00	Limited	Altered Expression	[1]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[17]
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⏷ Show the Full List of 30 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
Josamycin	DMKJ8LB	Approved	RNA transcription, translation and transport factor protein (RTRAF) affects the response to substance of Josamycin.	[28]
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9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of RNA transcription, translation and transport factor protein (RTRAF).	[18]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of RNA transcription, translation and transport factor protein (RTRAF).	[19]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RNA transcription, translation and transport factor protein (RTRAF).	[20]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of RNA transcription, translation and transport factor protein (RTRAF).	[21]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of RNA transcription, translation and transport factor protein (RTRAF).	[22]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RNA transcription, translation and transport factor protein (RTRAF).	[23]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide decreases the expression of RNA transcription, translation and transport factor protein (RTRAF).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of RNA transcription, translation and transport factor protein (RTRAF).	[26]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of RNA transcription, translation and transport factor protein (RTRAF).	[27]
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⏷ Show the Full List of 9 Drug(s)

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 RNA transcription, translation and transport factor protein (RTRAF).	[25]
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References

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2	Hypersensitive IFN Responses in Lupus Keratinocytes Reveal Key Mechanistic Determinants in Cutaneous Lupus.J Immunol. 2019 Apr 1;202(7):2121-2130. doi: 10.4049/jimmunol.1800650. Epub 2019 Feb 11.
3	C14orf166 is a high-risk biomarker for bladder cancer and promotes bladder cancer cell proliferation.J Transl Med. 2016 Feb 23;14:55. doi: 10.1186/s12967-016-0801-4.
4	A novel ninein-interaction protein, CGI-99, blocks ninein phosphorylation by GSK3beta and is highly expressed in brain tumors.FEBS Lett. 2004 May 21;566(1-3):162-8. doi: 10.1016/j.febslet.2004.04.024.
5	CLE-10 from Carpesium abrotanoides L. Suppresses the Growth of Human Breast Cancer Cells (MDA-MB-231) In Vitro by Inducing Apoptosis and Pro-Death Autophagy Via the PI3K/Akt/mTOR Signaling Pathway.Molecules. 2019 Mar 20;24(6):1091. doi: 10.3390/molecules24061091.
6	Usefulness of confocal laser endomicroscopy for predicting postoperative recurrence in patients with Crohn's disease: apilot study.Gastrointest Endosc. 2019 Jul;90(1):151-157. doi: 10.1016/j.gie.2019.02.030. Epub 2019 Mar 5.
7	Prevalence of Pruritus in Cutaneous Lupus Erythematosus: Brief Report of a Multicenter, Multinational Cross-Sectional Study.Biomed Res Int. 2018 Jul 25;2018:3491798. doi: 10.1155/2018/3491798. eCollection 2018.
8	Expression and clinical significance of C14orf166 in esophageal squamous cell carcinoma.Mol Med Rep. 2017 Feb;15(2):605-612. doi: 10.3892/mmr.2016.6056. Epub 2016 Dec 16.
9	Arctic berry extracts target the gut-liver axis to alleviate metabolic endotoxaemia, insulin resistance and hepatic steatosis in diet-induced obese mice.Diabetologia. 2018 Apr;61(4):919-931. doi: 10.1007/s00125-017-4520-z. Epub 2017 Dec 21.
10	C14orf166 Is a Biomarker for Predicting Hepatocellular Carcinoma Recurrence.J Invest Surg. 2020 Dec;33(10):914-923. doi: 10.1080/08941939.2019.1586015. Epub 2019 Mar 24.
11	Analysis of a new begomovirus unveils a composite element conserved in the CP gene promoters of several Geminiviridae genera: Clues to comprehend the complex regulation of late genes.PLoS One. 2019 Jan 23;14(1):e0210485. doi: 10.1371/journal.pone.0210485. eCollection 2019.
12	Needle-based confocal laser endomicroscopy for real-time diagnosingand staging of lung cancer.Eur Respir J. 2019 Jun 20;53(6):1801520. doi: 10.1183/13993003.01520-2018. Print 2019 Jun.
13	Overexpressed C14orf166 associates with disease progression and poor prognosis in non-small-cell lung cancer.Biosci Rep. 2018 Sep 13;38(5):BSR20180479. doi: 10.1042/BSR20180479. Print 2018 Oct 31.
14	Proteomic profiling in pancreatic cancer with and without lymph node metastasis.Int J Cancer. 2009 Apr 1;124(7):1614-21. doi: 10.1002/ijc.24163.
15	JAK inhibitor ruxolitinib inhibits the expression of cytokines characteristic of cutaneous lupus erythematosus.Exp Dermatol. 2017 Aug;26(8):728-730. doi: 10.1111/exd.13253. Epub 2017 May 3.
16	Overexpression of chromosome 14 open reading frame 166 correlates with disease progression and poorer prognosis in human NPC.Tumour Biol. 2015 Sep;36(10):7977-86. doi: 10.1007/s13277-015-3518-8. Epub 2015 May 12.
17	Probe-based confocal laser endomicroscopy for diagnosis of nasopharyngeal carcinoma in vivo.Laryngoscope. 2019 Apr;129(4):897-902. doi: 10.1002/lary.27450. Epub 2018 Aug 27.
18	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.
19	Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
20	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.
21	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
22	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
23	Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
24	Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: role of myeloperoxidase and arylamine free radicals. Chem Biol Interact. 2015 Sep 5;239:129-38.
25	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.
26	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.
27	Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
28	A genome-wide analysis of targets of macrolide antibiotics in mammalian cells. J Biol Chem. 2020 Feb 14;295(7):2057-2067. doi: 10.1074/jbc.RA119.010770. Epub 2020 Jan 8.