Details of Drug Off-Target (DOT)

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

• DOT Name: Protein LTV1 homolog (LTV1)
• Gene Name: LTV1
• Related Disease: Inflammatory poikiloderma with hair abnormalities and acral keratoses
• UniProt ID: LTV1_HUMAN
• PDB ID: 6G18; 6G4S; 6G4W; 6G51; 6G53; 7WTT; 7WTU; 7WTW; 7WTX; 7WTZ; 7WU0
• Pfam ID: PF04180
• Sequence:
  MPHRKKKPFIEKKKAVSFHLVHRSQRDPLAADESAPQRVLLPTQKIDNEERRAEQRKYGV
  FFDDDYDYLQHLKEPSGPSELIPSSTFSAHNRREEKEETLVIPSTGIKLPSSVFASEFEE
  DVGLLNKAAPVSGPRLDFDPDIVAALDDDFDFDDPDNLLEDDFILQANKATGEEEGMDIQ
  KSENEDDSEWEDVDDEKGDSNDDYDSAGLLSDEDCMSVPGKTHRAIADHLFWSEETKSRF
  TEYSMTSSVMRRNEQLTLHDERFEKFYEQYDDDEIGALDNAELEGSIQVDSNRLQEVLND
  YYKEKAENCVKLNTLEPLEDQDLPMNELDESEEEEMITVVLEEAKEKWDCESICSTYSNL
  YNHPQLIKYQPKPKQIRISSKTGIPLNVLPKKGLTAKQTERIQMINGSDLPKVSTQPRSK
  NESKEDKRARKQAIKEERKERRVEKKANKLAFKLEKRRQEKELLNLKKNVEGLKL
• Function: Essential for ribosome biogenesis.
• Tissue Specificity: Expressed in the epidermis.
• Reactome Pathway: Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Inflammatory poikiloderma with hair abnormalities and acral keratoses	DIS5XTFN	Limited	Unknown	[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 Protein LTV1 homolog (LTV1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein LTV1 homolog (LTV1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein LTV1 homolog (LTV1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein LTV1 homolog (LTV1).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein LTV1 homolog (LTV1).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Protein LTV1 homolog (LTV1).	[6]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Protein LTV1 homolog (LTV1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein LTV1 homolog (LTV1).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein LTV1 homolog (LTV1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Protein LTV1 homolog (LTV1).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein LTV1 homolog (LTV1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein LTV1 homolog (LTV1).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Protein LTV1 homolog (LTV1).	[10]

References

• [1] Mutations in the ribosome biogenesis factor gene LTV1 are linked to LIPHAK syndrome, a novel poikiloderma-like disorder. Hum Mol Genet. 2022 Jun 22;31(12):1970-1978. doi: 10.1093/hmg/ddab368.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [12] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.