Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ1SKOA)

• DOT Name: Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 2 (RPN2)
• Synonyms: Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 63 kDa subunit; RIBIIR; Ribophorin II; RPN-II; Ribophorin-2
• Gene Name: RPN2
• Related Disease:
  Non-small-cell lung cancer
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma of esophagus
  Colon carcinoma
  Colorectal carcinoma
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Neoplasm of esophagus
  Prostate cancer
  Prostate neoplasm
  Stomach cancer
  Bipolar disorder
  Schizoaffective disorder
  Schizophrenia
  OPTN-related open angle glaucoma
  Myeloid neoplasm
  Nasopharyngeal carcinoma
  Non-insulin dependent diabetes
• UniProt ID: RPN2_HUMAN
• PDB ID: 6S7O; 6S7T; 8B6L
• Pfam ID: PF05817
• Sequence:
  MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSS
  LGAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDS
  SVTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI
  VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNAI
  FSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQPL
  TQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDNRYIA
  NTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFALFFQL
  VDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDSASGTYT
  LYLIIGDATLKNPILWNVADVVIKFPEEEAPSTVLSQNLFTPKQEIQHLFREPEKRPPTV
  VSNTFTALILSPLLLLFALWIRIGANVSNFTFAPSTIIFHLGHAAMLGLMYVYWTQLNMF
  QTLKYLAILGSVTFLAGNRMLAQQAVKRTAH
• Function: Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity.
• Tissue Specificity: Expressed in all tissues tested.
• KEGG Pathway:
  N-Glycan biosynthesis (hsa00510)
  Various types of N-glycan biosynthesis (hsa00513)
  Metabolic pathways (hsa01100)
  Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway:
  Asparagine N-linked glycosylation (R-HSA-446203)
  Maturation of spike protein (R-HSA-9694548)
  SRP-dependent cotranslational protein targeting to membrane (R-HSA-1799339)

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[3]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[4]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[6]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[4]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[7]
Gastric cancer	DISXGOUK	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[8]
Lung cancer	DISCM4YA	Strong	Biomarker	[9]
Lung carcinoma	DISTR26C	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[10]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[10]
Stomach cancer	DISKIJSX	Strong	Biomarker	[2]
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[11]
Schizoaffective disorder	DISLBW6B	moderate	Genetic Variation	[11]
Schizophrenia	DISSRV2N	moderate	Genetic Variation	[11]
OPTN-related open angle glaucoma	DISDR98A	Disputed	Genetic Variation	[12]
Myeloid neoplasm	DIS2YOWO	Limited	Biomarker	[13]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[14]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[15]

2 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 Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 2 (RPN2).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 2 (RPN2).	[24]

9 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 Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 2 (RPN2).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 2 (RPN2).	[18]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 2 (RPN2).	[19]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 2 (RPN2).	[20]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 2 (RPN2).	[21]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 2 (RPN2).	[22]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 2 (RPN2).	[23]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 2 (RPN2).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 2 (RPN2).	[26]

References

• [1] Prognostic and therapeutic impact of RPN2-mediated tumor malignancy in non-small-cell lung cancer.Oncotarget. 2015 Feb 20;6(5):3335-45. doi: 10.18632/oncotarget.2793.
• [2] Ribophorin II potentiates P-glycoprotein- and ABCG2-mediated multidrug resistance via activating ERK pathway in gastric cancer.Int J Biol Macromol. 2019 May 1;128:574-582. doi: 10.1016/j.ijbiomac.2019.01.195. Epub 2019 Jan 30.
• [3] RPN2 gene confers docetaxel resistance in breast cancer.Nat Med. 2008 Sep;14(9):939-48. doi: 10.1038/nm.1858.
• [4] Ribophorin II promotes cell proliferation, migration, and invasion in esophageal cancer cells in vitro and in vivo.Biosci Rep. 2019 May 7;39(5):BSR20182448. doi: 10.1042/BSR20182448. Print 2019 May 31.
• [5] Downregulation of RPN2 induces apoptosis and inhibits migration and invasion in colon carcinoma.Oncol Rep. 2018 Jul;40(1):283-293. doi: 10.3892/or.2018.6434. Epub 2018 May 10.
• [6] MicroRNA-128 targeting RPN2 inhibits cell proliferation and migration through the Akt-p53-cyclin pathway in colorectal cancer cells.Oncol Lett. 2018 Dec;16(6):6940-6949. doi: 10.3892/ol.2018.9506. Epub 2018 Sep 26.
• [7] RPN2 expression predicts response to docetaxel in oesophageal squamous cell carcinoma.Br J Cancer. 2012 Oct 9;107(8):1233-8. doi: 10.1038/bjc.2012.396. Epub 2012 Sep 6.
• [8] RPN2 promotes metastasis of hepatocellular carcinoma cell and inhibits autophagy via STAT3 and NF-B pathways.Aging (Albany NY). 2019 Sep 3;11(17):6674-6690. doi: 10.18632/aging.102167. Epub 2019 Sep 3.
• [9] A novel platform to enable inhaled naked RNAi medicine for lung cancer.Sci Rep. 2013 Nov 25;3:3325. doi: 10.1038/srep03325.
• [10] 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.
• [11] Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study.Transl Psychiatry. 2017 Oct 24;7(10):e1249. doi: 10.1038/tp.2017.210.
• [12] A genome-wide association study for primary open angle glaucoma and macular degeneration reveals novel Loci.PLoS One. 2013;8(3):e58657. doi: 10.1371/journal.pone.0058657. Epub 2013 Mar 11.
• [13] A yeast artificial chromosome-based map of the region of chromosome 20 containing the diabetes-susceptibility gene, MODY1, and a myeloid leukemia related gene.Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):3937-41. doi: 10.1073/pnas.93.9.3937.
• [14] Downregulation of ribophorin II suppresses tumor growth, migration, and invasion of nasopharyngeal carcinoma.Onco Targets Ther. 2018 Jun 15;11:3485-3494. doi: 10.2147/OTT.S158355. eCollection 2018.
• [15] A susceptibility locus for early-onset non-insulin dependent (type 2) diabetes mellitus maps to chromosome 20q, proximal to the phosphoenolpyruvate carboxykinase gene.Hum Mol Genet. 1997 Sep;6(9):1401-8. doi: 10.1093/hmg/6.9.1401.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [21] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [22] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [23] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [24] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [25] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [26] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.