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
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
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
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]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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]
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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]
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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.