Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT52SSS5)

DOT Name Probable oxidoreductase PXDNL (PXDNL)
Synonyms EC 1.-.-.-; Cardiac peroxidase; Inactive peroxidasin-like protein; Polysomal ribonuclease 1; PRM1; Vascular peroxidase 2
Gene Name PXDNL
Related Disease
Breast cancer ( )
Breast carcinoma ( )
Hailey-Hailey disease ( )
Parkinson disease ( )
UniProt ID
PXDNL_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
1.-.-.-
Pfam ID
PF03098 ; PF07679 ; PF13927 ; PF13855 ; PF00093
Sequence
MEPRLFCWTTLFLLAGWCLPGLPCPSRCLCFKSTVRCMHLMLDHIPQVPQQTTVLDLRFN
RIREIPGSAFKKLKNLNTLLLNNNHIRKISRNAFEGLENLLYLYLYKNEIHALDKQTFKG
LISLEHLYIHFNQLEMLQPETFGDLLRLERLFLHNNKLSKIPAGSFSNLDSLKRLRLDSN
ALVCDCDLMWLGELLQGFAQHGHTQAAATCEYPRRLHGRAVASVTVEEFNCQSPRITFEP
QDVEVPSGNTVYFTCRAEGNPKPEIIWIHNNHSLDLEDDTRLNVFDDGTLMIRNTRESDQ
GVYQCMARNSAGEAKTQSAMLRYSSLPAKPSFVIQPQDTEVLIGTSTTLECMATGHPHPL
ITWTRDNGLELDGSRHVATSSGLYLQNITQRDHGRFTCHANNSHGTVQAAANIIVQAPPQ
FTVTPKDQVVLEEHAVEWLCEADGNPPPVIVWTKTGGQLPVEGQHTVLSSGTLRIDRAAQ
HDQGQYECQAVSSLGVKKVSVQLTVKPKALAVFTQLPQDTSVEVGKNINISCHAQGEPQP
IITWNKEGVQITESGKFHVDDEGTLTIYDAGFPDQGRYECVARNSFGLAVTNMFLTVTAI
QGRQAGDDFVESSILDAVQRVDSAINSTRRHLFSQKPHTSSDLLAQFHYPRDPLIVEMAR
AGEIFEHTLQLIRERVKQGLTVDLEGKEFRYNDLVSPRSLSLIANLSGCTARRPLPNCSN
RCFHAKYRAHDGTCNNLQQPTWGAALTAFARLLQPAYRDGIRAPRGLGLPVGSRQPLPPP
RLVATVWARAAAVTPDHSYTRMLMHWGWFLEHDLDHTVPALSTARFSDGRPCSSVCTNDP
PCFPMNTRHADPRGTHAPCMLFARSSPACASGRPSATVDSVYAREQINQQTAYIDGSNVY
GSSERESQALRDPSVPRGLLKTGFPWPPSGKPLLPFSTGPPTECARQEQESPCFLAGDHR
ANEHLALAAMHTLWFREHNRMATELSALNPHWEGNTVYQEARKIVGAELQHITYSHWLPK
VLGDPGTRMLRGYRGYNPNVNAGIINSFATAAFRFGHTLINPILYRLNATLGEISEGHLP
FHKALFSPSRIIKEGGIDPVLRGLFGVAAKWRAPSYLLSPELTQRLFSAAYSAAVDSAAT
IIQRGRDHGIPPYVDFRVFCNLTSVKNFEDLQNEIKDSEIRQKLRKLYGSPGDIDLWPAL
MVEDLIPGTRVGPTLMCLFVTQFQRLRDGDRFWYENPGVFTPAQLTQLKQASLSRVLCDN
GDSIQQVQADVFVKAEYPQDYLNCSEIPKVDLRVWQDCCADCRSRGQFRAVTQESQKKRS
AQYSYPVDKDMELSHLRSRQQDKIYVGEDARNVTVLAKTKFSQDFSTFAAEIQETITALR
EQINKLEARLRQAGCTDVRGVPRKAEERWMKEDCTHCICESGQVTCVVEICPPAPCPSPE
LVKGTCCPVCRDRGMPSDSPEKR
Function
Probable oxidoreductase (Probable). Lacks peroxidase activity. Inhibits the peroxidase activity of PXDN through its interaction ; [Isoform PMR1]: Endonuclease selectively degrading some target mRNAs while they are engaged by translating ribosomes, among which albumin and beta-globin mRNAs.
Tissue Specificity the 57 kDa isoform PMR1 is the only form detected at protein levels in human cell lines . Expressed in heart .

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Strong Biomarker [1]
Breast carcinoma DIS2UE88 Strong Biomarker [1]
Hailey-Hailey disease DISCM9SG Strong Genetic Variation [2]
Parkinson disease DISQVHKL Limited Altered Expression [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Probable oxidoreductase PXDNL (PXDNL). [4]
Quercetin DM3NC4M Approved Quercetin increases the expression of Probable oxidoreductase PXDNL (PXDNL). [5]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Probable oxidoreductase PXDNL (PXDNL). [6]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Probable oxidoreductase PXDNL (PXDNL). [7]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Probable oxidoreductase PXDNL (PXDNL). [8]
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References

1 High peroxidasin-like expression is a potential and independent prognostic biomarker in breast cancer.Medicine (Baltimore). 2019 Nov;98(44):e17703. doi: 10.1097/MD.0000000000017703.
2 Pmr-1 gene affects susceptibility of Caenorhabditis elegans to Staphylococcus aureus infection through glycosylation and stress response pathways' alterations.Virulence. 2019 Dec;10(1):1013-1025. doi: 10.1080/21505594.2019.1697118.
3 The Ca2+/Mn2+ ion-pump PMR1 links elevation of cytosolic Ca(2+) levels to -synuclein toxicity in Parkinson's disease models.Cell Death Differ. 2013 Mar;20(3):465-77. doi: 10.1038/cdd.2012.142. Epub 2012 Nov 16.
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 Quercetin reduces oxidative damage induced by paraquat via modulating expression of antioxidant genes in A549 cells. J Appl Toxicol. 2013 Dec;33(12):1460-7. doi: 10.1002/jat.2812. Epub 2012 Sep 20.
6 Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
7 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
8 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.