Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVMGE2H)

• DOT Name: Endoplasmic reticulum resident protein 27 (ERP27)
• Synonyms: ER protein 27; ERp27; Inactive protein disulfide-isomerase 27
• Gene Name: ERP27
• UniProt ID: ERP27_HUMAN
• PDB ID: 2L4C; 4F9Z
• Pfam ID: PF13848
• Sequence:
  MEAAPSRFMFLLFLLTCELAAEVAAEVEKSSDGPGAAQEPTWLTDVPAAMEFIAATEVAV
  IGFFQDLEIPAVPILHSMVQKFPGVSFGISTDSEVLTHYNITGNTICLFRLVDNEQLNLE
  DEDIESIDATKLSRFIEINSLHMVTEYNPVTVIGLFNSVIQIHLLLIMNKASPEYEENMH
  RYQKAAKLFQGKILFILVDSGMKENGKVISFFKLKESQLPALAIYQTLDDEWDTLPTAEV
  SVEHVQNFCDGFLSGKLLKENRESEGKTPKVEL
• Function: Specifically binds unfolded proteins and may recruit protein disulfide isomerase PDIA3 to unfolded substrates. Binds protein substrates via a hydrophobic pocket in the C-terminal domain. May play a role in the unfolded stress response.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[2]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[7]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[11]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[12]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[11]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[13]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[16]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Endoplasmic reticulum resident protein 27 (ERP27).	[17]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] 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.
• [3] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] 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.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] 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.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [11] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [12] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [13] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [14] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [15] The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
• [16] 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.
• [17] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.