Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW8C1V0)

• DOT Name: ER lumen protein-retaining receptor 3 (KDELR3)
• Synonyms: KDEL endoplasmic reticulum protein retention receptor 3; KDEL receptor 3
• Gene Name: KDELR3
• UniProt ID: ERD23_HUMAN
• Pfam ID: PF00810
• Sequence:
  MNVFRILGDLSHLLAMILLLGKIWRSKCCKGISGKSQILFALVFTTRYLDLFTNFISIYN
  TVMKVVFLLCAYVTVYMIYGKFRKTFDSENDTFRLEFLLVPVIGLSFLENYSFTLLEILW
  TFSIYLESVAILPQLFMISKTGEAETITTHYLFFLGLYRALYLANWIRRYQTENFYDQIA
  VVSGVVQTIFYCDFFYLYVTKVLKGKKLSLPMPI
• Function: Receptor for the C-terminal sequence motif K-D-E-L that is present on endoplasmic reticulum resident proteins and that mediates their recycling from the Golgi back to the endoplasmic reticulum.
• KEGG Pathway: Vibrio cholerae infection (hsa05110)
• Reactome Pathway:
  COPI-mediated anterograde transport (R-HSA-6807878)
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  XBP1(S) activates chaperone genes (R-HSA-381038)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of ER lumen protein-retaining receptor 3 (KDELR3).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of ER lumen protein-retaining receptor 3 (KDELR3).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[7]
Marinol	DM70IK5	Approved	Marinol decreases the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[10]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[11]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[12]
Orlistat	DMRJSP8	Approved	Orlistat increases the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[14]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of ER lumen protein-retaining receptor 3 (KDELR3).	[19]

References

• [1] 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.
• [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] 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.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [8] Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [11] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [12] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [13] Inhibition of fatty-acid synthase induces caspase-8-mediated tumor cell apoptosis by up-regulating DDIT4. J Biol Chem. 2008 Nov 14;283(46):31378-84. doi: 10.1074/jbc.M803384200. Epub 2008 Sep 16.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [16] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [17] 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.
• [18] 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.
• [19] 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.