Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT416O2G)

• DOT Name: ATP-dependent RNA helicase SUPV3L1, mitochondrial (SUPV3L1)
• Synonyms: EC 3.6.4.13; Suppressor of var1 3-like protein 1; SUV3-like protein 1
• Gene Name: SUPV3L1
• Related Disease:
  Alopecia
  Androgenetic alopecia
  Baldness, male pattern
  Breast neoplasm
  Mitochondrial disease
  Neoplasm
  Non-syndromic ichthyosis
• UniProt ID: SUV3_HUMAN
• PDB ID: 3RC3; 3RC8; 7W1R
• EC Number: 3.6.4.13
• Pfam ID: PF00271 ; PF12513 ; PF18147 ; PF18114
• Sequence:
  MSFSRALLWARLPAGRQAGHRAAICSALRPHFGPFPGVLGQVSVLATASSSASGGSKIPN
  TSLFVPLTVKPQGPSADGDVGAELTRPLDKNEVKKVLDKFYKRKEIQKLGADYGLDARLF
  HQAFISFRNYIMQSHSLDVDIHIVLNDICFGAAHADDLFPFFLRHAKQIFPVLDCKDDLR
  KISDLRIPPNWYPDARAMQRKIIFHSGPTNSGKTYHAIQKYFSAKSGVYCGPLKLLAHEI
  FEKSNAAGVPCDLVTGEERVTVQPNGKQASHVSCTVEMCSVTTPYEVAVIDEIQMIRDPA
  RGWAWTRALLGLCAEEVHLCGEPAAIDLVMELMYTTGEEVEVRDYKRLTPISVLDHALES
  LDNLRPGDCIVCFSKNDIYSVSRQIEIRGLESAVIYGSLPPGTKLAQAKKFNDPNDPCKI
  LVATDAIGMGLNLSIRRIIFYSLIKPSINEKGERELEPITTSQALQIAGRAGRFSSRFKE
  GEVTTMNHEDLSLLKEILKRPVDPIRAAGLHPTAEQIEMFAYHLPDATLSNLIDIFVDFS
  QVDGQYFVCNMDDFKFSAELIQHIPLSLRVRYVFCTAPINKKQPFVCSSLLQFARQYSRN
  EPLTFAWLRRYIKWPLLPPKNIKDLMDLEAVHDVLDLYLWLSYRFMDMFPDASLIRDLQK
  ELDGIIQDGVHNITKLIKMSETHKLLNLEGFPSGSQSRLSGTLKSQARRTRGTKALGSKA
  TEPPSPDAGELSLASRLVQQGLLTPDMLKQLEKEWMTQQTEHNKEKTESGTHPKGTRRKK
  KEPDSD
• Function: Major helicase player in mitochondrial RNA metabolism. Component of the mitochondrial degradosome (mtEXO) complex, that degrades 3' overhang double-stranded RNA with a 3'-to-5' directionality in an ATP-dependent manner. Involved in the degradation of non-coding mitochondrial transcripts (MT-ncRNA) and tRNA-like molecules. ATPase and ATP-dependent multisubstrate helicase, able to unwind double-stranded (ds) DNA and RNA, and RNA/DNA heteroduplexes in the 5'-to-3' direction. Plays a role in the RNA surveillance system in mitochondria; regulates the stability of mature mRNAs, the removal of aberrantly formed mRNAs and the rapid degradation of non coding processing intermediates. Also implicated in recombination and chromatin maintenance pathways. May protect cells from apoptosis. Associates with mitochondrial DNA.
• Tissue Specificity: Broadly expressed.
• Reactome Pathway: Mitochondrial RNA degradation (R-HSA-9836573)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alopecia	DIS37HU4	Strong	Biomarker	[1]
Androgenetic alopecia	DISSJR1P	Strong	Biomarker	[1]
Baldness, male pattern	DIS9C9RO	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[2]
Mitochondrial disease	DISKAHA3	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[2]
Non-syndromic ichthyosis	DISZ9QBQ	Strong	Biomarker	[1]

11 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 ATP-dependent RNA helicase SUPV3L1, mitochondrial (SUPV3L1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of ATP-dependent RNA helicase SUPV3L1, mitochondrial (SUPV3L1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of ATP-dependent RNA helicase SUPV3L1, mitochondrial (SUPV3L1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ATP-dependent RNA helicase SUPV3L1, mitochondrial (SUPV3L1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ATP-dependent RNA helicase SUPV3L1, mitochondrial (SUPV3L1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of ATP-dependent RNA helicase SUPV3L1, mitochondrial (SUPV3L1).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATP-dependent RNA helicase SUPV3L1, mitochondrial (SUPV3L1).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of ATP-dependent RNA helicase SUPV3L1, mitochondrial (SUPV3L1).	[11]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of ATP-dependent RNA helicase SUPV3L1, mitochondrial (SUPV3L1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ATP-dependent RNA helicase SUPV3L1, mitochondrial (SUPV3L1).	[13]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of ATP-dependent RNA helicase SUPV3L1, mitochondrial (SUPV3L1).	[14]

References

• [1] Disruption of Supv3L1 damages the skin and causes sarcopenia, loss of fat, and death.Mamm Genome. 2009 Feb;20(2):92-108. doi: 10.1007/s00335-008-9168-z. Epub 2009 Jan 15.
• [2] Mitochondrial genome instability resulting from SUV3 haploinsufficiency leads to tumorigenesis and shortened lifespan.Oncogene. 2013 Feb 28;32(9):1193-201. doi: 10.1038/onc.2012.120. Epub 2012 May 7.
• [3] Polyadenylation and degradation of structurally abnormal mitochondrial tRNAs in human cells.Nucleic Acids Res. 2018 Jun 1;46(10):5209-5226. doi: 10.1093/nar/gky159.
• [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] 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.
• [6] 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.
• [7] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [12] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [13] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [14] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.