Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN4FJ5J)

• DOT Name: Popeye domain-containing protein 3 (POPDC3)
• Synonyms: Popeye protein 3
• Gene Name: POPDC3
• Related Disease:
  Adult respiratory distress syndrome
  Gastric cancer
  Limb-girdle muscular dystrophy
  Muscular dystrophy, limb-girdle, autosomal recessive 26
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
  Visceral leishmaniasis
  Head-neck squamous cell carcinoma
• UniProt ID: POPD3_HUMAN
• Pfam ID: PF04831
• Sequence:
  MERNSSLWKNLIDEHPVCTTWKQEAEGAIYHLASILFVVGFMGGSGFFGLLYVFSLLGLG
  FLCSAVWAWVDVCAADIFSWNFVLFVICFMQFVHIAYQVRSITFAREFQVLYSSLFQPLG
  ISLPVFRTIALSSEVVTLEKEHCYAMQGKTSIDKLSLLVSGRIRVTVDGEFLHYIFPLQF
  LDSPEWDSLRPTEEGIFQVTLTAETDCRYVSWRRKKLYLLFAQHRYISRLFSVLIGSDIA
  DKLYALNDRVYIGKRYHYDIRLPNFYQMSTPEIRRSPLTQHFQNSRRYCDK
• Function: May play a role in the maintenance of heart function mediated, at least in part, through cAMP-binding. May play a role in the regulation of KCNK2/TREK-1-mediated current amplitude.
• Tissue Specificity: Expressed predominantly in skeletal muscle (at protein level) . Also detected in heart .
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Adrenergic sig.ling in cardiomyocytes (hsa04261)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult respiratory distress syndrome	DISIJV47	Strong	Genetic Variation	[1]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[2]
Limb-girdle muscular dystrophy	DISI9Y1Z	Strong	Genetic Variation	[3]
Muscular dystrophy, limb-girdle, autosomal recessive 26	DISBPXU2	Strong	Autosomal recessive	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[4]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[4]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[2]
Visceral leishmaniasis	DISTKEYK	Strong	Biomarker	[5]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	Popeye domain-containing protein 3 (POPDC3) affects the response to substance of DTI-015.	[21]

14 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 Popeye domain-containing protein 3 (POPDC3).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Popeye domain-containing protein 3 (POPDC3).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Popeye domain-containing protein 3 (POPDC3).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Popeye domain-containing protein 3 (POPDC3).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Popeye domain-containing protein 3 (POPDC3).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Popeye domain-containing protein 3 (POPDC3).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Popeye domain-containing protein 3 (POPDC3).	[12]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Popeye domain-containing protein 3 (POPDC3).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Popeye domain-containing protein 3 (POPDC3).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Popeye domain-containing protein 3 (POPDC3).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Popeye domain-containing protein 3 (POPDC3).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Popeye domain-containing protein 3 (POPDC3).	[18]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Popeye domain-containing protein 3 (POPDC3).	[19]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Popeye domain-containing protein 3 (POPDC3).	[20]

1 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 Popeye domain-containing protein 3 (POPDC3).	[15]

References

• [1] Distinct and replicable genetic risk factors for acute respiratory distress syndrome of pulmonary or extrapulmonary origin.J Med Genet. 2012 Nov;49(11):671-80. doi: 10.1136/jmedgenet-2012-100972. Epub 2012 Oct 9.
• [2] Reduced Popdc3 expression correlates with high risk and poor survival in patients with gastric cancer.World J Gastroenterol. 2012 May 21;18(19):2423-9. doi: 10.3748/wjg.v18.i19.2423.
• [3] POPDC3 Gene Variants Associate with a New Form of Limb Girdle Muscular Dystrophy. Ann Neurol. 2019 Dec;86(6):832-843. doi: 10.1002/ana.25620. Epub 2019 Oct 28.
• [4] 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.
• [5] The genetic structure of Leishmania infantum populations in Brazil and its possible association with the transmission cycle of visceral leishmaniasis.PLoS One. 2012;7(5):e36242. doi: 10.1371/journal.pone.0036242. Epub 2012 May 11.
• [6] POPDC3 is a potential biomarker for prognosis and radioresistance in patients with head and neck squamous cell carcinoma.Oncol Lett. 2019 Nov;18(5):5468-5480. doi: 10.3892/ol.2019.10888. Epub 2019 Sep 19.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [15] 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.
• [16] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [17] 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.
• [18] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [19] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [20] Early gene response in lithium chloride induced apoptosis. Apoptosis. 2005 Jan;10(1):75-90. doi: 10.1007/s10495-005-6063-x.
• [21] Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.