Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOU4EY6)

DOT Name Proteasomal ubiquitin receptor ADRM1 (ADRM1)
Synonyms 110 kDa cell membrane glycoprotein; Gp110; Adhesion-regulating molecule 1; ARM-1; Proteasome regulatory particle non-ATPase 13; hRpn13; Rpn13 homolog
Gene Name ADRM1
Related Disease
Advanced cancer ( )
Acute leukaemia ( )
Alzheimer disease ( )
Anemia ( )
Breast cancer ( )
Breast carcinoma ( )
Epithelial ovarian cancer ( )
Epstein barr virus infection ( )
Estrogen-receptor positive breast cancer ( )
Gastric cancer ( )
Herpes simplex infection ( )
HIV infectious disease ( )
Intrahepatic cholangiocarcinoma ( )
leukaemia ( )
Leukemia ( )
Liver cirrhosis ( )
Neoplasm ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Prostate cancer ( )
Prostate carcinoma ( )
Rheumatoid arthritis ( )
T-cell lymphoma ( )
Hepatocellular carcinoma ( )
Fibromyalgia ( )
Migraine disorder ( )
Colorectal carcinoma ( )
Glioblastoma multiforme ( )
Multiple sclerosis ( )
UniProt ID
ADRM1_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2KQZ; 2KR0; 2L5V; 2MKZ; 2NBV; 4UEL; 4UEM; 4WLQ; 4WLR; 5IRS; 5V1Y; 5V1Z; 5YMY; 6CO4; 6OI4; 6UYI; 6UYJ; 7KXI
Pfam ID
PF04683 ; PF16550
Sequence
MTTSGALFPSLVPGSRGASNKYLVEFRAGKMSLKGTTVTPDKRKGLVYIQQTDDSLIHFC
WKDRTSGNVEDDLIIFPDDCEFKRVPQCPSGRVYVLKFKAGSKRLFFWMQEPKTDQDEEH
CRKVNEYLNNPPMPGALGASGSSGHELSALGGEGGLQSLLGNMSHSQLMQLIGPAGLGGL
GGLGALTGPGLASLLGSSGPPGSSSSSSSRSQSAAVTPSSTTSSTRATPAPSAPAAASAT
SPSPAPSSGNGASTAASPTQPIQLSDLQSILATMNVPAGPAGGQQVDLASVLTPEIMAPI
LANADVQERLLPYLPSGESLPQTADEIQNTLTSPQFQQALGMFSAALASGQLGPLMCQFG
LPAEAVEAANKGDVEAFAKAMQNNAKPEQKEGDTKDKKDEEEDMSLD
Function
Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. Within the complex, functions as a proteasomal ubiquitin receptor. Engages and activates 19S-associated deubiquitinases UCHL5 and PSMD14 during protein degradation. UCHL5 reversibly associate with the 19S regulatory particle whereas PSMD14 is an intrinsic subunit of the proteasome lid subcomplex.
KEGG Pathway
Proteasome (hsa03050 )
Alzheimer disease (hsa05010 )
Parkinson disease (hsa05012 )
Amyotrophic lateral sclerosis (hsa05014 )
Huntington disease (hsa05016 )
Spinocerebellar ataxia (hsa05017 )
Prion disease (hsa05020 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Epstein-Barr virus infection (hsa05169 )
Reactome Pathway
Ub-specific processing proteases (R-HSA-5689880 )
UCH proteinases (R-HSA-5689603 )

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Definitive Biomarker [1]
Acute leukaemia DISDQFDI Strong Biomarker [2]
Alzheimer disease DISF8S70 Strong Biomarker [3]
Anemia DISTVL0C Strong Biomarker [4]
Breast cancer DIS7DPX1 Strong Altered Expression [5]
Breast carcinoma DIS2UE88 Strong Altered Expression [5]
Epithelial ovarian cancer DIS56MH2 Strong Genetic Variation [6]
Epstein barr virus infection DISOO0WT Strong Biomarker [7]
Estrogen-receptor positive breast cancer DIS1H502 Strong Biomarker [5]
Gastric cancer DISXGOUK Strong Biomarker [8]
Herpes simplex infection DISL1SAV Strong Biomarker [9]
HIV infectious disease DISO97HC Strong Biomarker [10]
Intrahepatic cholangiocarcinoma DIS6GOC8 Strong Altered Expression [11]
leukaemia DISS7D1V Strong Altered Expression [2]
Leukemia DISNAKFL Strong Altered Expression [2]
Liver cirrhosis DIS4G1GX Strong Genetic Variation [12]
Neoplasm DISZKGEW Strong Altered Expression [5]
Ovarian cancer DISZJHAP Strong Genetic Variation [6]
Ovarian neoplasm DISEAFTY Strong Genetic Variation [6]
Prostate cancer DISF190Y Strong Genetic Variation [13]
Prostate carcinoma DISMJPLE Strong Genetic Variation [13]
Rheumatoid arthritis DISTSB4J Strong Biomarker [14]
T-cell lymphoma DISSXRTQ Strong Biomarker [15]
Hepatocellular carcinoma DIS0J828 moderate Biomarker [16]
Fibromyalgia DISZJDS2 Disputed Biomarker [17]
Migraine disorder DISFCQTG Disputed Biomarker [17]
Colorectal carcinoma DIS5PYL0 Limited Altered Expression [18]
Glioblastoma multiforme DISK8246 Limited Biomarker [19]
Multiple sclerosis DISB2WZI Limited Biomarker [20]
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⏷ Show the Full List of 29 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 Proteasomal ubiquitin receptor ADRM1 (ADRM1). [21]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Proteasomal ubiquitin receptor ADRM1 (ADRM1). [30]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Proteasomal ubiquitin receptor ADRM1 (ADRM1). [30]
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12 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 Proteasomal ubiquitin receptor ADRM1 (ADRM1). [22]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Proteasomal ubiquitin receptor ADRM1 (ADRM1). [23]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Proteasomal ubiquitin receptor ADRM1 (ADRM1). [24]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Proteasomal ubiquitin receptor ADRM1 (ADRM1). [22]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Proteasomal ubiquitin receptor ADRM1 (ADRM1). [25]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Proteasomal ubiquitin receptor ADRM1 (ADRM1). [26]
Selenium DM25CGV Approved Selenium increases the expression of Proteasomal ubiquitin receptor ADRM1 (ADRM1). [27]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Proteasomal ubiquitin receptor ADRM1 (ADRM1). [27]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Proteasomal ubiquitin receptor ADRM1 (ADRM1). [28]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Proteasomal ubiquitin receptor ADRM1 (ADRM1). [29]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Proteasomal ubiquitin receptor ADRM1 (ADRM1). [31]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Proteasomal ubiquitin receptor ADRM1 (ADRM1). [32]
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⏷ Show the Full List of 12 Drug(s)

References

1 Use of CA125 and HE4 serum markers to predict ovarian cancer in elevated-risk women.Cancer Epidemiol Biomarkers Prev. 2014 Jul;23(7):1383-93. doi: 10.1158/1055-9965.EPI-13-1361. Epub 2014 May 1.
2 Knockdown of Adhesion-Regulating Molecule 1 Inhibits Proliferation in HL60 Cells.Acta Haematol. 2015;134(2):88-100. doi: 10.1159/000369916. Epub 2015 Apr 21.
3 AMYPAD Diagnostic and Patient Management Study: Rationale and design.Alzheimers Dement. 2019 Mar;15(3):388-399. doi: 10.1016/j.jalz.2018.09.003. Epub 2018 Oct 16.
4 Maternal Characteristics Affect Fetal Growth Response in the Women First Preconception Nutrition Trial.Nutrients. 2019 Oct 21;11(10):2534. doi: 10.3390/nu11102534.
5 Prognostic and Therapeutic Significance of Adhesion-regulating Molecule 1 in Estrogen Receptor-positive Breast Cancer.Clin Breast Cancer. 2020 Apr;20(2):131-144.e3. doi: 10.1016/j.clbc.2019.07.009. Epub 2019 Sep 3.
6 Early and consistent overexpression of ADRM1 in ovarian high-grade serous carcinoma.J Ovarian Res. 2017 Aug 7;10(1):53. doi: 10.1186/s13048-017-0347-y.
7 Epstein-Barr virus and rheumatoid arthritis.Autoimmun Rev. 2004 Jul;3(5):362-7. doi: 10.1016/j.autrev.2004.02.002.
8 ADRM1 gene amplification is a candidate driver for metastatic gastric cancers.Clin Exp Metastasis. 2014 Aug;31(6):727-33. doi: 10.1007/s10585-014-9663-4. Epub 2014 Jun 27.
9 Glycoprotein 110, the Epstein-Barr virus homolog of herpes simplex virus glycoprotein B, is essential for Epstein-Barr virus replication in vivo.J Virol. 1996 Mar;70(3):2049-54. doi: 10.1128/JVI.70.3.2049-2054.1996.
10 Lack of permissivity of human monoclonal CD4+ lymphocytes to HIV.Cancer Detect Prev. 1990;14(4):445-56.
11 RA190, a Proteasome Subunit ADRM1 Inhibitor, Suppresses Intrahepatic Cholangiocarcinoma by Inducing NF-KB-Mediated Cell Apoptosis.Cell Physiol Biochem. 2018;47(3):1152-1166. doi: 10.1159/000490210. Epub 2018 Jun 15.
12 Efficacy and safety of simeprevir and sofosbuvir with and without ribavirin in subjects with recurrent genotype 1 hepatitis C postorthotopic liver transplant: the randomized GALAXY study.Transpl Int. 2017 Feb;30(2):196-208. doi: 10.1111/tri.12896. Epub 2017 Jan 20.
13 The role of hypofractionated radiotherapy for the definitive treatment of localized prostate cancer: early results of a randomized trial.J Cancer. 2019 Oct 16;10(25):6217-6224. doi: 10.7150/jca.35510. eCollection 2019.
14 Pathophysiological links between rheumatoid arthritis and the Epstein-Barr virus: an update.Joint Bone Spine. 2007 Oct;74(5):418-26. doi: 10.1016/j.jbspin.2007.05.001. Epub 2007 Jun 8.
15 Glycoprotein gp110 of Epstein-Barr virus determines viral tropism and efficiency of infection.Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):15036-41. doi: 10.1073/pnas.232381299. Epub 2002 Oct 30.
16 Long-Read RNA Sequencing Identifies Alternative Splice Variants in Hepatocellular Carcinoma and Tumor-Specific Isoforms.Hepatology. 2019 Sep;70(3):1011-1025. doi: 10.1002/hep.30500. Epub 2019 Mar 22.
17 Bidirectional association between migraine and fibromyalgia: retrospective cohort analyses of two populations.BMJ Open. 2019 Apr 8;9(4):e026581. doi: 10.1136/bmjopen-2018-026581.
18 Knockdown of the novel proteasome subunit Adrm1 located on the 20q13 amplicon inhibits colorectal cancer cell migration, survival and tumorigenicity.Oncol Rep. 2009 Feb;21(2):531-7.
19 Phase II study of Dovitinib in recurrent glioblastoma.J Neurooncol. 2019 Sep;144(2):359-368. doi: 10.1007/s11060-019-03236-6. Epub 2019 Jul 11.
20 Human Herpesvirus-6 (HHV-6) infection in multiple sclerosis: a preliminary report.Mult Scler. 1998 Dec;4(6):490-6. doi: 10.1177/135245859800400606.
21 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.
22 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.
23 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
24 Phosphorylated TP63 induces transcription of RPN13, leading to NOS2 protein degradation. J Biol Chem. 2010 Dec 31;285(53):41422-31. doi: 10.1074/jbc.M110.158642. Epub 2010 Oct 19.
25 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.
26 Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
27 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
28 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.
29 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.
30 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
31 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.
32 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.