Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP978LK)

• DOT Name: RNA helicase Mov10l1 (MOV10L1)
• Synonyms: EC 3.6.4.13; Moloney leukemia virus 10-like protein 1; MOV10-like protein 1
• Gene Name: MOV10L1
• Related Disease:
  Cardiac failure
  Congestive heart failure
  Male infertility
  Non-small-cell lung cancer
  Type-1/2 diabetes
  Sarcoma
  Soft tissue sarcoma
  Fibromatosis
  Leiomyosarcoma
  Multi-drug resistant tuberculosis
  Neoplasm
  Tuberculosis
• UniProt ID: M10L1_HUMAN
• EC Number: 3.6.4.13
• Pfam ID: PF13086 ; PF13087 ; PF21634
• Sequence:
  MLSLAAKLVAFFWRTADTPREEAGQLEPELAEGDTKLKTVRGVVTRYCSDYGMIDDMIYF
  SSDAVTSRVLLNVGQEVIAVVEENKVSNGLKAIRVEAVSDKWEDDSRNHGSPSDCGPRVL
  IGCVTSLVEGAGCISQTTYFSLESVCEGFEPCKGDWVEAEYRIRPGTWSSEATSVKPLRY
  KRVDKVCISSLCGRNGVLEESIFFTLDSLKLPDGYTPRRGDVVNAVVVESSQSCYVWRAL
  CMTLVKRRDAAPVHEATHFYGTILLKNKGDIEVTQVTHFGTLKEGRSKTMVIWIENKGDI
  PQNLVSCKLAGWDKSKQFRFQMLDKDQMCPVVSFVSVPEKENSSDENINSLNSHTKNKTS
  QMSESSLVNNRGISPGDCTCKGENGEKDNILSRKQMTEPEPGGLVPPGGKTFIVVICDGK
  NPGRCKELLLLCFSDFLIGRYLEVNVISGEESLIAAREPFSWKKLKSSQALTSAKTTVVV
  TAQKRNSRRQLPSFLPQYPIPDRLRKCVEQKIDILTFQPLLAELLNMSNYKEKFSTLLWL
  EEIYAEMELKEYNMSGIILRRNGDLLVLEVPGLAEGRPSLYAGDKLILKTQEYNGHAIEY
  ISYVTEIHEEDVTLKINPEFEQAYNFEPMDVEFTYNRTTSRRCHFALEHVIHLGVKVLFP
  EEIILQSPQVTGNWNHAQDTKSSGQSTSKKNRKTMTDQAEHGTEERRVGDKDLPVLAPFT
  AEMSDWVDEIQTPKARKMEFFNPVLNENQKLAVKRILSGDCRPLPYILFGPPGTGKTVTI
  IEAVLQVHFALPDSRILVCAPSNSAADLVCLRLHESKVLQPATMVRVNATCRFEEIVIDA
  VKPYCRDGEDIWKASRFRIIITTCSSSGLFYQIGVRVGHFTHVFVDEAGQASEPECLIPL
  GLMSDISGQIVLAGDPMQLGPVIKSRLAMAYGLNVSFLERLMSRPAYQRDENAFGACGAH
  NPLLVTKLVKNYRSHEALLMLPSRLFYHRELEVCADPTVVTSLLGWEKLPKKGFPLIFHG
  VRGSEAREGKSPSWFNPAEAVQVLRYCCLLAHSISSQVSASDIGVITPYRKQVEKIRILL
  RNVDLMDIKVGSVEEFQGQEYLVIIISTVRSNEDRFEDDRYFLGFLSNSKRFNVAITRPK
  ALLIVLGNPHVLVRDPCFGALLEYSITNGVYMGCDLPPALQSLQNCGEGVADPSYPVVPE
  STGPEKHQEPS
• Function: ATP-dependent RNA helicase required during spermatogenesis to repress transposable elements and prevent their mobilization, which is essential for germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Involved in the primary piRNA metabolic process. Specifically binds to piRNA precursors and promotes the generation of intermediate piRNA processing fragments that are subsequently loaded to Piwi proteins. Acts via its ATP-dependent RNA helicase activity: displays 5'-3' RNA unwinding activity and probably mediates unwinding and funneling of single-stranded piRNA precursor transcripts to the endonuclease that catalyzes the first cleavage step of piRNA processing to generate piRNA intermediate fragments that are subsequently loaded to Piwi proteins.
• Tissue Specificity: .Specifically expressed in testis.
• Reactome Pathway: PIWI-interacting RNA (piRNA) biogenesis (R-HSA-5601884)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac failure	DISDC067	Strong	Biomarker	[1]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[1]
Male infertility	DISY3YZZ	Strong	Genetic Variation	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[3]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[4]
Sarcoma	DISZDG3U	moderate	Genetic Variation	[5]
Soft tissue sarcoma	DISSN8XB	moderate	Genetic Variation	[5]
Fibromatosis	DIS7535C	Limited	Genetic Variation	[6]
Leiomyosarcoma	DIS6COXM	Limited	Biomarker	[7]
Multi-drug resistant tuberculosis	DIS1A2CS	Limited	Biomarker	[8]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[9]
Tuberculosis	DIS2YIMD	Limited	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of RNA helicase Mov10l1 (MOV10L1).	[10]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of RNA helicase Mov10l1 (MOV10L1).	[11]

2 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 helicase Mov10l1 (MOV10L1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of RNA helicase Mov10l1 (MOV10L1).	[13]

References

• [1] Comparison of Hydralazine/Nitrate and Angiotensin Receptor Neprilysin Inhibitor Use Among Black Versus Nonblack Americans With Heart Failure and Reduced Ejection Fraction (from CHAMP-HF).Am J Cardiol. 2019 Dec 15;124(12):1900-1906. doi: 10.1016/j.amjcard.2019.09.020. Epub 2019 Sep 26.
• [2] Association of MOV10L1 gene polymorphisms and male infertility in azoospermic men with complete maturation arrest.J Assist Reprod Genet. 2014 Jul;31(7):865-71. doi: 10.1007/s10815-014-0240-1. Epub 2014 May 10.
• [3] CHAMP: A Phase II Study of Panitumumab With Pemetrexed and Cisplatin Versus Pemetrexed and Cisplatin in the Treatment of Patients With Advanced-Stage Primary Nonsquamous Non-Small-Cell Lung Cancer With Particular Regard to the KRAS Status.Clin Lung Cancer. 2015 Nov;16(6):447-56. doi: 10.1016/j.cllc.2015.05.009. Epub 2015 Jun 2.
• [4] Statin Therapy and Risk of Incident Diabetes Mellitus in Adults With Cardiovascular Risk Factors.Am J Cardiol. 2020 Feb 15;125(4):534-541. doi: 10.1016/j.amjcard.2019.11.011. Epub 2019 Nov 19.
• [5] Cytogenetic analysis of 46 pleomorphic soft tissue sarcomas and correlation with morphologic and clinical features: a report of the CHAMP Study Group. Chromosomes and MorPhology.Genes Chromosomes Cancer. 1998 May;22(1):16-25. doi: 10.1002/(sici)1098-2264(199805)22:1<16::aid-gcc3>3.0.co;2-a.
• [6] Cytogenetic, clinical, and morphologic correlations in 78 cases of fibromatosis: a report from the CHAMP Study Group. CHromosomes And Morphology.Mod Pathol. 2000 Oct;13(10):1080-5. doi: 10.1038/modpathol.3880200.
• [7] Comparative cytogenetic study of spindle cell and pleomorphic leiomyosarcomas of soft tissues: a report from the CHAMP Study Group.Cancer Genet Cytogenet. 2000 Jan 1;116(1):66-73. doi: 10.1016/s0165-4608(99)00114-4.
• [8] Levofloxacin versus placebo for the prevention of tuberculosis disease in child contacts of multidrug-resistant tuberculosis: study protocol for a phase III cluster randomised controlled trial (TB-CHAMP).Trials. 2018 Dec 20;19(1):693. doi: 10.1186/s13063-018-3070-0.
• [9] Combined morphologic and karyotypic study of 59 atypical lipomatous tumors. Evaluation of their relationship and differential diagnosis with other adipose tissue tumors (a report of the CHAMP Study Group).Am J Surg Pathol. 1996 Oct;20(10):1182-9. doi: 10.1097/00000478-199610000-00002.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [12] 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.
• [13] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.