Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1Z52Q7)

• DOT Name: UPF0688 protein C1orf174 (C1ORF174)
• Gene Name: C1ORF174
• UniProt ID: CA174_HUMAN
• Pfam ID: PF15772
• Sequence:
  MRSRKLTGAVRSSARLKARSCSAARLASAQEVAGSTSAKTACLTSSSHKATDTRTSKKFK
  CDKGHLVKSELQKLVPKNDSASLPKVTPETPCENEFAEGSALLPGSEAGVSVQQGAASLP
  LGGCRVVSDSRLAKTRDGLSVPKHSAGSGAEESNSSSTVQKQNEPGLQTEDVQKPPLQMD
  NSVFLDDDSNQPMPVSRFFGNVELMQDLPPASSSCPSMSRREFRKMHFRAKDDDDDDDDD
  AEM

Molecular Interaction Atlas (MIA) of This DOT

4 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 UPF0688 protein C1orf174 (C1ORF174).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of UPF0688 protein C1orf174 (C1ORF174).	[2]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of UPF0688 protein C1orf174 (C1ORF174).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of UPF0688 protein C1orf174 (C1ORF174).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of UPF0688 protein C1orf174 (C1ORF174).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of UPF0688 protein C1orf174 (C1ORF174).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of UPF0688 protein C1orf174 (C1ORF174).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of UPF0688 protein C1orf174 (C1ORF174).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of UPF0688 protein C1orf174 (C1ORF174).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of UPF0688 protein C1orf174 (C1ORF174).	[9]

References

• [1] 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.
• [2] 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.
• [3] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [5] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [6] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [8] 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.
• [9] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.