Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8YBS5G)

• DOT Name: ER lumen protein-retaining receptor 1 (KDELR1)
• Synonyms: KDEL endoplasmic reticulum protein retention receptor 1; KDEL receptor 1; Putative MAPK-activating protein PM23
• Gene Name: KDELR1
• Related Disease:
  Complete hydatidiform mole
  Dermatomyositis
  Hepatocellular carcinoma
  Inclusion body myositis
  Prostate cancer
  Prostate neoplasm
• UniProt ID: ERD21_HUMAN
• Pfam ID: PF00810
• Sequence:
  MNLFRFLGDLSHLLAIILLLLKIWKSRSCAGISGKSQVLFAVVFTARYLDLFTNYISLYN
  TCMKVVYIACSFTTVWLIYSKFKATYDGNHDTFRVEFLVVPTAILAFLVNHDFTPLEILW
  TFSIYLESVAILPQLFMVSKTGEAETITSHYLFALGVYRTLYLFNWIWRYHFEGFFDLIA
  IVAGLVQTVLYCDFFYLYITKVLKGKKLSLPA
• 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-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  COPI-mediated anterograde transport (R-HSA-6807878)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Complete hydatidiform mole	DIS5QPI0	Strong	Biomarker	[1]
Dermatomyositis	DIS50C5O	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Inclusion body myositis	DISZXXG5	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[4]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	ER lumen protein-retaining receptor 1 (KDELR1) affects the response to substance of Methotrexate.	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ER lumen protein-retaining receptor 1 (KDELR1).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of ER lumen protein-retaining receptor 1 (KDELR1).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of ER lumen protein-retaining receptor 1 (KDELR1).	[8]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of ER lumen protein-retaining receptor 1 (KDELR1).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of ER lumen protein-retaining receptor 1 (KDELR1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of ER lumen protein-retaining receptor 1 (KDELR1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of ER lumen protein-retaining receptor 1 (KDELR1).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of ER lumen protein-retaining receptor 1 (KDELR1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of ER lumen protein-retaining receptor 1 (KDELR1).	[12]

References

• [1] Incidence of hydatidiform mole in a Tokyo hospital: a 5-year (1989 to 1993) prospective, morphological, and flow cytometric study.Hum Pathol. 1995 Jul;26(7):758-64. doi: 10.1016/0046-8177(95)90224-4.
• [2] A three-way interplay of DR4, autoantibodies and synovitis in biopsy-proven idiopathic inflammatory myositis.Rheumatol Int. 2012 Mar;32(3):611-9. doi: 10.1007/s00296-010-1637-5. Epub 2010 Dec 2.
• [3] Plasma membrane gp96 enhances invasion and metastatic potential of liver cancer via regulation of uPAR.Mol Oncol. 2015 Aug;9(7):1312-23. doi: 10.1016/j.molonc.2015.03.004. Epub 2015 Mar 24.
• [4] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Ornithine decarboxylase antizyme upregulates DNA-dependent protein kinase and enhances the nonhomologous end-joining repair of DNA double-strand breaks in human oral cancer cells. Biochemistry. 2007 Aug 7;46(31):8920-32. doi: 10.1021/bi7000328. Epub 2007 Jul 14.
• [10] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [11] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [12] 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.
• [13] 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.
• [14] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.