Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX2GXXX)

• DOT Name: Endonuclease V (ENDOV)
• Synonyms: hEndoV; EC 3.1.26.-; Inosine-specific endoribonuclease
• Gene Name: ENDOV
• Related Disease:
  Actinic keratosis
  Bipolar disorder
  Cockayne syndrome
  Colonic neoplasm
  Precancerous condition
  Schizophrenia
  Skin cancer
  Xeroderma pigmentosum
  Diabetes insipidus
• UniProt ID: ENDOV_HUMAN
• PDB ID: 4NSP; 6OZE
• EC Number: 3.1.26.-
• Pfam ID: PF04493
• Sequence:
  MALEAAGGPPEETLSLWKREQARLKAHVVDRDTEAWQRDPAFSGLQRVGGVDVSFVKGDS
  VRACASLVVLSFPELEVVYEESRMVSLTAPYVSGFLAFREVPFLLELVQQLREKEPGLMP
  QVLLVDGNGVLHHRGFGVACHLGVLTDLPCVGVAKKLLQVDGLENNALHKEKIRLLQTRG
  DSFPLLGDSGTVLGMALRSHDRSTRPLYISVGHRMSLEAAVRLTCCCCRFRIPEPVRQAD
  ICSREHIRKSLGLPGPPTPRSPKAQRPVACPKGDSGESSALC
• Function: [Isoform 1]: Endoribonuclease that specifically cleaves inosine-containing RNAs: cleaves RNA at the second phosphodiester bond 3' to inosine. Active against both single-stranded and double-stranded RNAs. Has strong preference for single-stranded RNAs (ssRNAs) toward double-stranded RNAs (dsRNAs). Cleaves mRNAs and tRNAs containing inosine. Also able to cleave structure-specific dsRNA substrates containing the specific sites 5'-IIUI-3' and 5'-UIUU-3'. Inosine is present in a number of RNAs following editing; the function of inosine-specific endoribonuclease is still unclear: it could either play a regulatory role in edited RNAs, or be involved in antiviral response by removing the hyperedited long viral dsRNA genome that has undergone A-to-I editing (Probable). Binds branched DNA structures ; [Isoform 6]: Endoribonuclease that specifically cleaves inosine-containing RNAs: cleaves RNA at the second phosphodiester bond 3' to inosine. Active against both single-stranded and double-stranded RNAs. Cleaves tRNAs containing inosine ; [Isoform 7]: Endoribonuclease that specifically cleaves inosine-containing RNAs: cleaves RNA at the second phosphodiester bond 3' to inosine. Active against both single-stranded and double-stranded RNAs. Cleaves tRNAs containing inosine.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Actinic keratosis	DISR1RC5	Strong	Biomarker	[1]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[2]
Cockayne syndrome	DISW6GL2	Strong	Biomarker	[3]
Colonic neoplasm	DISSZ04P	Strong	Genetic Variation	[4]
Precancerous condition	DISV06FL	Strong	Biomarker	[5]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[2]
Skin cancer	DISTM18U	Strong	Biomarker	[1]
Xeroderma pigmentosum	DISQ9H19	Strong	Biomarker	[6]
Diabetes insipidus	DIS0U6CJ	Limited	Biomarker	[7]

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 Endonuclease V (ENDOV).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Endonuclease V (ENDOV).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Endonuclease V (ENDOV).	[9]

References

• [1] DNA repair, immunosuppression, and skin cancer.Cutis. 2004 Nov;74(5 Suppl):10-3.
• [2] Analysis of t(9;17)(q33.2;q25.3) chromosomal breakpoint regions and genetic association reveals novel candidate genes for bipolar disorder.Bipolar Disord. 2015 Mar;17(2):205-11. doi: 10.1111/bdi.12239. Epub 2014 Jul 23.
• [3] Incomplete complementation of the DNA repair defect in cockayne syndrome cells by the denV gene from bacteriophage T4 suggests a deficiency in base excision repair.Mutat Res. 1997 Oct;385(1):59-74. doi: 10.1016/s0921-8777(97)00039-6.
• [4] An endonuclease/ligase based mutation scanning method especially suited for analysis of neoplastic tissue.Oncogene. 2002 Mar 14;21(12):1909-21. doi: 10.1038/sj.onc.1205109.
• [5] Effect of xenogenic repair enzymes on photoimmunology and photocarcinogenesis.J Photochem Photobiol B. 2001 Dec 31;65(2-3):105-8. doi: 10.1016/s1011-1344(01)00246-9.
• [6] Cell-free repair of UV-damaged simian virus 40 chromosomes in human cell extracts. II. Defective DNA repair synthesis by xeroderma pigmentosum cell extracts.J Biol Chem. 1993 Apr 25;268(12):9105-9.
• [7] Application of single nucleotide extension and MALDI-TOF mass spectrometry in proofreading and DNA repair assay.DNA Repair (Amst). 2018 Jan;61:63-75. doi: 10.1016/j.dnarep.2017.11.011. Epub 2017 Dec 2.
• [8] 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.
• [9] 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.
• [10] 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.