Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8FBKY0)

• DOT Name: Prenylcysteine oxidase 1 (PCYOX1)
• Synonyms: EC 1.8.3.5; Prenylcysteine lyase
• Gene Name: PCYOX1
• Related Disease: Cardiovascular disease
• UniProt ID: PCYOX_HUMAN
• EC Number: 1.8.3.5
• Pfam ID: PF13450 ; PF07156
• Sequence:
  MGRVVAELVSSLLGLWLLLCSCGCPEGAELRAPPDKIAIIGAGIGGTSAAYYLRQKFGKD
  VKIDLFEREEVGGRLATMMVQGQEYEAGGSVIHPLNLHMKRFVKDLGLSAVQASGGLLGI
  YNGETLVFEESNWFIINVIKLVWRYGFQSLRMHMWVEDVLDKFMRIYRYQSHDYAFSSVE
  KLLHALGGDDFLGMLNRTLLETLQKAGFSEKFLNEMIAPVMRVNYGQSTDINAFVGAVSL
  SCSDSGLWAVEGGNKLVCSGLLQASKSNLISGSVMYIEEKTKTKYTGNPTKMYEVVYQIG
  TETRSDFYDIVLVATPLNRKMSNITFLNFDPPIEEFHQYYQHIVTTLVKGELNTSIFSSR
  PIDKFGLNTVLTTDNSDLFINSIGIVPSVREKEDPEPSTDGTYVWKIFSQETLTKAQILK
  LFLSYDYAVKKPWLAYPHYKPPEKCPSIILHDRLYYLNGIECAASAMEMSAIAAHNAALL
  AYHRWNGHTDMIDQDGLYEKLKTEL
• Function: Prenylcysteine oxidase that cleaves the thioether bond of prenyl-L-cysteines, such as farnesylcysteine and geranylgeranylcysteine. Only active against free prenylcysteines and not prenylcysteine residues within prenylated proteins or peptides. Involved in the final step in the degradation of prenylated proteins, by degrading prenylcysteines after the protein has been degraded.
• Tissue Specificity: Widely expressed.
• KEGG Pathway: Terpenoid backbone biosynthesis (hsa00900)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Prenylcysteine oxidase 1 (PCYOX1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Prenylcysteine oxidase 1 (PCYOX1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Prenylcysteine oxidase 1 (PCYOX1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Prenylcysteine oxidase 1 (PCYOX1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Prenylcysteine oxidase 1 (PCYOX1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Prenylcysteine oxidase 1 (PCYOX1).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Prenylcysteine oxidase 1 (PCYOX1).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Prenylcysteine oxidase 1 (PCYOX1).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Prenylcysteine oxidase 1 (PCYOX1).	[10]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Prenylcysteine oxidase 1 (PCYOX1).	[11]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Prenylcysteine oxidase 1 (PCYOX1).	[12]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Prenylcysteine oxidase 1 (PCYOX1).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Prenylcysteine oxidase 1 (PCYOX1).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Prenylcysteine oxidase 1 (PCYOX1).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Prenylcysteine oxidase 1 (PCYOX1).	[17]

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 increases the methylation of Prenylcysteine oxidase 1 (PCYOX1).	[14]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Prenylcysteine oxidase 1 (PCYOX1).	[18]

References

• [1] Prenylcysteine oxidase 1, a pro-oxidant enzyme of low density lipoproteins.Front Biosci (Landmark Ed). 2018 Jan 1;23(6):1020-1037. doi: 10.2741/4631.
• [2] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] 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.
• [9] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [10] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [11] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [12] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [13] Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res. 2006 Jul 15;66(14):7334-40.
• [14] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [15] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [16] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [17] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [18] 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.