Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDWLPO9)

• DOT Name: Protease-associated domain-containing protein 1 (PRADC1)
• Synonyms: Protease-associated domain-containing protein of 21 kDa; hPAP21
• Gene Name: PRADC1
• Related Disease: Pyelonephritis
• UniProt ID: PADC1_HUMAN
• Pfam ID: PF02225
• Sequence:
  MVPGAAGWCCLVLWLPACVAAHGFRIHDYLYFQVLSPGDIRYIFTATPAKDFGGIFHTRY
  EQIHLVPAEPPEACGELSNGFFIQDQIALVERGGCSFLSKTRVVQEHGGRAVIISDNAVD
  NDSFYVEMIQDSTQRTADIPALFLLGRDGYMIRRSLEQHGLPWAIISIPVNVTSIPTFEL
  LQPPWTFW
• Function: Plays a role in the modulation of physical activity and adiposity.
• Tissue Specificity: Highly expressed in skeletal muscle, heart and liver. Expressed at intermediate level in kidney.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pyelonephritis	DISAOX93	Strong	Altered Expression	[1]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protease-associated domain-containing protein 1 (PRADC1).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protease-associated domain-containing protein 1 (PRADC1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protease-associated domain-containing protein 1 (PRADC1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protease-associated domain-containing protein 1 (PRADC1).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protease-associated domain-containing protein 1 (PRADC1).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Protease-associated domain-containing protein 1 (PRADC1).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Protease-associated domain-containing protein 1 (PRADC1).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protease-associated domain-containing protein 1 (PRADC1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Protease-associated domain-containing protein 1 (PRADC1).	[10]

References

• [1] Phase-variation of pyelonephritis-associated pili in Escherichia coli: evidence for transcriptional regulation.EMBO J. 1989 Feb;8(2):613-20. doi: 10.1002/j.1460-2075.1989.tb03416.x.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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] 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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] 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.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.