Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDAZSY5)

• DOT Name: Popeye domain-containing protein 2 (POPDC2)
• Synonyms: Popeye protein 2
• Gene Name: POPDC2
• Related Disease:
  Prostate cancer
  Prostate carcinoma
  Bacterial infection
  Arrhythmia
• UniProt ID: POPD2_HUMAN
• Pfam ID: PF04831
• Sequence:
  MSANSSRVGQLLLQGSACIRWKQDVEGAVYHLANCLLLLGFMGGSGVYGCFYLFGFLSAG
  YLCCVLWGWFSACGLDIVLWSFLLAVVCLLQLAHLVYRLREDTLPEEFDLLYKTLCLPLQ
  VPLQTYKEIVHCCEEQVLTLATEQTYAVEGETPINRLSLLLSGRVRVSQDGQFLHYIFPY
  QFMDSPEWESLQPSEEGVFQVTLTAETSCSYISWPRKSLHLLLTKERYISCLFSALLGYD
  ISEKLYTLNDKLFAKFGLRFDIRLPSLYHVLGPTAADAGPESEKGDEEVCEPAVSPPQAT
  PTSLQQTPPCSTPPATTNFPAPPTRARLSRPDSGILASRIPLQSYSQVISRGQAPLAPTH
  TPEL
• Function: Important for the maintenance of cardiac function. Plays a regulatory function in heart rate dynamics mediated, at least in part, through cAMP-binding and, probably, by increasing cell surface expression of the potassium channel KCNK2 and enhancing current density.
• Tissue Specificity: Expressed predominantly in the heart and in the skeletal muscle.
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Adrenergic sig.ling in cardiomyocytes (hsa04261)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[1]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[2]
Arrhythmia	DISFF2NI	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Popeye domain-containing protein 2 (POPDC2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Popeye domain-containing protein 2 (POPDC2).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Popeye domain-containing protein 2 (POPDC2).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Popeye domain-containing protein 2 (POPDC2).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Popeye domain-containing protein 2 (POPDC2).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Popeye domain-containing protein 2 (POPDC2).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat affects the expression of Popeye domain-containing protein 2 (POPDC2).	[10]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Popeye domain-containing protein 2 (POPDC2).	[11]
Gallium nitrate	DMF9O6B	Approved	Gallium nitrate decreases the expression of Popeye domain-containing protein 2 (POPDC2).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Popeye domain-containing protein 2 (POPDC2).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 affects the expression of Popeye domain-containing protein 2 (POPDC2).	[10]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Popeye domain-containing protein 2 (POPDC2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Popeye domain-containing protein 2 (POPDC2).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Popeye domain-containing protein 2 (POPDC2).	[16]

References

• [1] Novel biomarkers for prostate cancer including noncoding transcripts.Am J Pathol. 2009 Dec;175(6):2264-76. doi: 10.2353/ajpath.2009.080868. Epub 2009 Nov 5.
• [2] Pyrin-only protein 2 limits inflammation but improves protection against bacteria.Nat Commun. 2017 Jun 5;8:15564. doi: 10.1038/ncomms15564.
• [3] The Popeye domain containing gene family encoding a family of cAMP-effector proteins with important functions in striated muscle and beyond.J Muscle Res Cell Motil. 2019 Jun;40(2):169-183. doi: 10.1007/s10974-019-09523-z. Epub 2019 Jun 13.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] The Bromodomain Inhibitor JQ1 and the Histone Deacetylase Inhibitor Panobinostat Synergistically Reduce N-Myc Expression and Induce Anticancer Effects. Clin Cancer Res. 2016 May 15;22(10):2534-44. doi: 10.1158/1078-0432.CCR-15-1666. Epub 2016 Jan 5.
• [11] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [12] Role of oxidative stress in the induction of metallothionein-2A and heme oxygenase-1 gene expression by the antineoplastic agent gallium nitrate in human lymphoma cells. Free Radic Biol Med. 2008 Sep 15;45(6):763-72.
• [13] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [14] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [15] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.