Details of Drug Off-Target (DOT)

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

• DOT Name: Pseudouridine-5'-phosphatase (PUDP)
• Synonyms: EC 3.1.3.96; Haloacid dehalogenase-like hydrolase domain-containing protein 1; Haloacid dehalogenase-like hydrolase domain-containing protein 1A; Protein GS1; Pseudouridine-5'-monophosphatase; 5'-PsiMPase
• Gene Name: PUDP
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Melanoma
  Non-syndromic ichthyosis
  Squamous cell carcinoma
  Recessive X-linked ichthyosis
• UniProt ID: HDHD1_HUMAN
• PDB ID: 3L5K
• EC Number: 3.1.3.96
• Pfam ID: PF13419
• Sequence:
  MAAPPQPVTHLIFDMDGLLLDTERLYSVVFQEICNRYDKKYSWDVKSLVMGKKALEAAQI
  IIDVLQLPMSKEELVEESQTKLKEVFPTAALMPGAEKLIIHLRKHGIPFALATSSGSASF
  DMKTSRHKEFFSLFSHIVLGDDPEVQHGKPDPDIFLACAKRFSPPPAMEKCLVFEDAPNG
  VEAALAAGMQVVMVPDGNLSRDLTTKATLVLNSLQDFQPELFGLPSYE
• Function: Dephosphorylates pseudouridine 5'-phosphate, a potential intermediate in rRNA degradation. Pseudouridine is then excreted intact in urine.
• Reactome Pathway: Pyrimidine salvage (R-HSA-73614)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[1]
Non-syndromic ichthyosis	DISZ9QBQ	Strong	Genetic Variation	[3]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[1]
Recessive X-linked ichthyosis	DISZY56W	moderate	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Pseudouridine-5'-phosphatase (PUDP) affects the response to substance of Methotrexate.	[12]

7 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 Pseudouridine-5'-phosphatase (PUDP).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Pseudouridine-5'-phosphatase (PUDP).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Pseudouridine-5'-phosphatase (PUDP).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Pseudouridine-5'-phosphatase (PUDP).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Pseudouridine-5'-phosphatase (PUDP).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Pseudouridine-5'-phosphatase (PUDP).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Pseudouridine-5'-phosphatase (PUDP).	[11]

References

• [1] Qualitative and quantitative changes in nuclear DNA and phenotypic gene expression in human malignant skin tumors during their progression.Eur J Histochem. 1992;36(3):289-302.
• [2] Antisense RNA transcripts in the blood may be novel diagnostic markers for colorectal cancer.Oncol Lett. 2017 Sep;14(3):3487-3493. doi: 10.3892/ol.2017.6572. Epub 2017 Jul 15.
• [3] Expanding the genetic spectrum of ANOS1 mutations in patients with congenital hypogonadotropic hypogonadism.Hum Reprod. 2017 Mar 1;32(3):704-711. doi: 10.1093/humrep/dew354.
• [4] HDHD1, which is often deleted in X-linked ichthyosis, encodes a pseudouridine-5'-phosphatase.Biochem J. 2010 Oct 15;431(2):237-44. doi: 10.1042/BJ20100174.
• [5] 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.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.