Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT14Z6RJ)

• DOT Name: Probable methyltransferase TARBP1 (TARBP1)
• Synonyms: EC 2.1.1.-; TAR RNA-binding protein 1; TAR RNA-binding protein of 185 kDa; TRP-185
• Gene Name: TARBP1
• Related Disease:
  Advanced cancer
  Carcinoma of liver and intrahepatic biliary tract
  Hepatocellular carcinoma
  Liver cancer
  Neoplasm
  Non-small-cell lung cancer
  Sjogren syndrome
• UniProt ID: TARB1_HUMAN
• PDB ID: 2HA8
• EC Number: 2.1.1.-
• Pfam ID: PF00588
• Sequence:
  MEWVLAEALLSQSRDPRALLGALCQGEASAERVETLRFLLQRLEDEEARGSGGAGALPEA
  AREVAAGYLVPLLRSLRGRPAGGPDPSLQPRHRRRVLRAAGAALRSCVRLAGRPQLAAAL
  AEEALRDLLAGWRAPGAEAAVEVLAAVGPCLRPREDGPLLERVAGTAVALALGGGGDGDE
  AGPAEDAAALVAGRLLPVLVQCGGAALRAVWGGLAAPGASLGSGRVEEKLLVLSALAEKL
  LPEPGGDRARGAREAGPDARRCWRFWRTVQAGLGQADALTRKRARYLLQRAVEVSAELGA
  DCTCGPQEGNGPSLFWWSERKKDELLKFWENYILIMETLEGNQIHVIKPVLPKLNNLFEY
  AVSEENGCWLFHPSWHMCIYKRMFESENKILSKEGVIHFLELYETKILPFSPEFSEFIIG
  PLMDALSESSLYSRSPGQPIGSCSPLGLKLQKFLVTYISLLPEEIKSSFLLKFIRKMTSR
  HWCAVPILFLSKALANVPRHKALGIDGLLALRDVIHCTMITHQILLRGAAQCYLLQTAMN
  LLDVEKVSLSDVSTFLMSLRQEESLGRGTSLWTELCDWLRVNESYFKPSPTCSSIGLHKT
  SLNAYVKSIVQEYVKSSAWETGENCFMPDWFEAKLVSLMVLLAVDVEGMKTQYSGKQRTE
  NVLRIFLDPLLDVLMKFSTNAYMPLLKTDRCLQLLLKLLNTCRLKGSSAQDDEVSTVLQN
  FFMSTTESISEFILRRLTMNELNSVSDLDRCHLYLMVLTELINLHLKVGWKRGNPIWRVI
  SLLKNASIQHLQEMDSGQEPTVGSQIQRVVSMAALAMVCEAIDQKPELQLDSLHAGPLES
  FLSSLQLNQTLQKPHAEEQSSYAHPLECSSVLEESSSSQGWGKIVAQYIHDQWVCLSFLL
  KKYHTLIPTTGSEILEPFLPAVQMPIRTLQSALEALTVLSSDQVLPVFHCLKVLVPKLLT
  SSESLCIESFDMAWKIISSLSNTQLIFWANLKAFVQFVFDNKVLTIAAKIKGQAYFKIKE
  IMYKIIEMSAIKTGVFNTLISYCCQSWIVSASNVSQGSLSSAKNYSELILEACIFGTVFR
  RDQRLVQDVQTFIENLGHDCAANIVMENTKREDHYVRICAVKFLCLLDGSNMSHKLFIED
  LAIKLLDKDELVSKSKKRYYVNSLQHRVKNRVWQTLLVLFPRLDQNFLNGIIDRIFQAGF
  TNNQASIKYFIEWIIILILHKFPQFLPKFWDCFSYGEENLKTSICTFLAVLSHLDIITQN
  IPEKKLILKQALIVVLQWCFNHNFSVRLYALVALKKLWTVCKVLSVEEFDALTPVIESSL
  HQVESMHGAGNAKKNWQRIQEHFFFATFHPLKDYCLETIFYILPRLSGLIEDEWITIDKF
  TRFTDVPLAAGFQWYLSQTQLSKLKPGDWSQQDIGTNLVEADNQAEWTDVQKKIIPWNSR
  VSDLDLELLFQDRAARLGKSISRLIVVASLIDKPTNLGGLCRTCEVFGASVLVVGSLQCI
  SDKQFQHLSVSAEQWLPLVEVKPPQLIDYLQQKKTEGYTIIGVEQTAKSLDLTQYCFPEK
  SLLLLGNEREGIPANLIQQLDVCVEIPQQGIIRSLNVHVSGALLIWEYTRQQLLSHGDTK
  P
• Function: Probable S-adenosyl-L-methionine-dependent methyltransferase which methylates RNA molecules such as tRNAs; (Microbial infection) In case of infection by HIV-1, it binds to the loop region of TAR RNA, a region also bound by RNA polymerase II. Binding of TARBP1 and RNA polymerase II to HIV-1 TAR RNA is mutually exclusive, suggesting that TARBP1 may function alone or in conjunction with HIV-1 Tat to disengage RNA polymerase II from HIV-1 TAR RNA.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Liver cancer	DISDE4BI	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[1]
Sjogren syndrome	DISUBX7H	Strong	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Probable methyltransferase TARBP1 (TARBP1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Probable methyltransferase TARBP1 (TARBP1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Probable methyltransferase TARBP1 (TARBP1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Probable methyltransferase TARBP1 (TARBP1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Probable methyltransferase TARBP1 (TARBP1).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Probable methyltransferase TARBP1 (TARBP1).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Probable methyltransferase TARBP1 (TARBP1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Probable methyltransferase TARBP1 (TARBP1).	[8]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Probable methyltransferase TARBP1 (TARBP1).	[11]

References

• [1] Expression of TARBP1 protein in human non-small-cell lung cancer and its prognostic significance.Oncol Lett. 2018 May;15(5):7182-7190. doi: 10.3892/ol.2018.8202. Epub 2018 Mar 7.
• [2] Expression of protein TARBP1 in human hepatocellular carcinoma and its prognostic significance.Int J Clin Exp Pathol. 2015 Aug 1;8(8):9089-96. eCollection 2015.
• [3] Variants at potential loci associated with Sjogren's syndrome in Koreans: A genetic association study.Clin Immunol. 2019 Oct;207:79-86. doi: 10.1016/j.clim.2019.07.010. Epub 2019 Jul 23.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.