Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZN0DCX)

• DOT Name: UPF0489 protein C5orf22 (C5ORF22)
• Gene Name: C5ORF22
• UniProt ID: CE022_HUMAN
• Pfam ID: PF12640
• Sequence:
  MSDSAGGRAGLRRYPKLPVWVVEDHQEVLPFIYRAIGSKHLPASNVSFLHFDSHPDLLIP
  VNMPADTVFDKETLFGELSIENWIMPAVYAGHFSHVIWFHPTWAQQIREGRHHFLVGKDT
  STTTIRVTSTDHYFLSDGLYVPEDQLENQKPLQLDVIMVKPYKLCNNQEENDAVSSAKKP
  KLALEDSENTASTNCDSSSEGLEKDTATQRSDQTCLEPSCSCSSENQECQTAASTGEILE
  ILKKGKAFVLDIDLDFFSVKNPFKEMFTQEEYKILQELYQFKKPGTNLTEEDLVDIVDTR
  IHQLEDLEATFADLCDGDDEETVQRWASNPGMESLVPLVQSLKKRMEVPDYEMVHQAGLT
  CDYSELPHHISTEQEIECLIQSVHYLLKNLPNPTLVTIARSSLDDYCPSDQVDTIQEKVL
  NMLRALYGNLDLQVYAAESPPS

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	UPF0489 protein C5orf22 (C5ORF22) affects the response to substance of Etoposide.	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of UPF0489 protein C5orf22 (C5ORF22).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of UPF0489 protein C5orf22 (C5ORF22).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of UPF0489 protein C5orf22 (C5ORF22).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of UPF0489 protein C5orf22 (C5ORF22).	[4]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of UPF0489 protein C5orf22 (C5ORF22).	[5]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of UPF0489 protein C5orf22 (C5ORF22).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of UPF0489 protein C5orf22 (C5ORF22).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of UPF0489 protein C5orf22 (C5ORF22).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of UPF0489 protein C5orf22 (C5ORF22).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [6] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [7] 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.
• [8] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [9] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [10] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.