General Information of Drug Off-Target (DOT) (ID: OTY6X27P)

DOT Name 26S proteasome non-ATPase regulatory subunit 8 (PSMD8)
Synonyms 26S proteasome regulatory subunit RPN12; 26S proteasome regulatory subunit S14; p31
Gene Name PSMD8
Related Disease
Neoplasm ( )
Acquired immune deficiency syndrome ( )
Advanced cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Carcinoma ( )
Hepatitis B virus infection ( )
Hepatocellular carcinoma ( )
HIV infectious disease ( )
Liposarcoma ( )
Lung cancer ( )
Lung carcinoma ( )
Mesothelioma ( )
Non-small-cell lung cancer ( )
Nasopharyngeal carcinoma ( )
Thyroid gland papillary carcinoma ( )
Type-1 diabetes ( )
UniProt ID
PSMD8_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
5GJQ ; 5GJR ; 5L4K ; 5LN3 ; 5M32 ; 5T0C ; 5T0G ; 5T0H ; 5T0I ; 5T0J ; 5VFP ; 5VFQ ; 5VFR ; 5VFS ; 5VFT ; 5VFU ; 5VGZ ; 5VHF ; 5VHH ; 5VHI ; 5VHS ; 6MSB ; 6MSD ; 6MSG ; 6MSH ; 6MSJ ; 6MSK ; 6WJD ; 6WJN ; 7QXN ; 7QXP ; 7QXU ; 7QXW ; 7QXX ; 7QY7 ; 7QYA ; 7QYB ; 7W37 ; 7W38 ; 7W39 ; 7W3A ; 7W3B ; 7W3C ; 7W3F ; 7W3G ; 7W3H ; 7W3I ; 7W3J ; 7W3K ; 7W3M ; 8CVT
Pfam ID
PF10075
Sequence
MFIKGRAPRAPPRERRRATRGGLRQVVAPPRALGSTSRPHFRRASVCRRRCRKSGGLLAA
SRKMAAAAVNGAAGFSSSGPAATSGAVLQAATGMYEQLKGEWNRKSPNLSKCGEELGRLK
LVLLELNFLPTTGTKLTKQQLILARDILEIGAQWSILRKDIPSFERYMAQLKCYYFDYKE
QLPESAYMHQLLGLNLLFLLSQNRVAEFHTELERLPAKDIQTNVYIKHPVSLEQYLMEGS
YNKVFLAKGNIPAESYTFFIDILLDTIRDEIAGCIEKAYEKILFTEATRILFFNTPKKMT
DYAKKRGWVLGPNNYYSFASQQQKPEDTTIPSTELAKQVIEYARQLEMIV
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.
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
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha (R-HSA-1234176 )
ER-Phagosome pathway (R-HSA-1236974 )
Cross-presentation of soluble exogenous antigens (endosomes) (R-HSA-1236978 )
Autodegradation of Cdh1 by Cdh1 (R-HSA-174084 )
SCF-beta-TrCP mediated degradation of Emi1 (R-HSA-174113 )
APC/C (R-HSA-174154 )
APC/C (R-HSA-174178 )
Cdc20 (R-HSA-174184 )
Vpu mediated degradation of CD4 (R-HSA-180534 )
Vif-mediated degradation of APOBEC3G (R-HSA-180585 )
SCF(Skp2)-mediated degradation of p27/p21 (R-HSA-187577 )
Degradation of beta-catenin by the destruction complex (R-HSA-195253 )
Downstream TCR signaling (R-HSA-202424 )
Regulation of activated PAK-2p34 by proteasome mediated degradation (R-HSA-211733 )
Separation of Sister Chromatids (R-HSA-2467813 )
FCERI mediated NF-kB activation (R-HSA-2871837 )
Autodegradation of the E3 ubiquitin ligase COP1 (R-HSA-349425 )
Regulation of ornithine decarboxylase (ODC) (R-HSA-350562 )
ABC-family proteins mediated transport (R-HSA-382556 )
AUF1 (hnRNP D0) binds and destabilizes mRNA (R-HSA-450408 )
Asymmetric localization of PCP proteins (R-HSA-4608870 )
Degradation of AXIN (R-HSA-4641257 )
Degradation of DVL (R-HSA-4641258 )
Hedgehog ligand biogenesis (R-HSA-5358346 )
Hh mutants are degraded by ERAD (R-HSA-5362768 )
Dectin-1 mediated noncanonical NF-kB signaling (R-HSA-5607761 )
CLEC7A (Dectin-1) signaling (R-HSA-5607764 )
Degradation of GLI1 by the proteasome (R-HSA-5610780 )
Degradation of GLI2 by the proteasome (R-HSA-5610783 )
GLI3 is processed to GLI3R by the proteasome (R-HSA-5610785 )
Hedgehog 'on' state (R-HSA-5632684 )
Regulation of RAS by GAPs (R-HSA-5658442 )
TNFR2 non-canonical NF-kB pathway (R-HSA-5668541 )
NIK-->noncanonical NF-kB signaling (R-HSA-5676590 )
Defective CFTR causes cystic fibrosis (R-HSA-5678895 )
MAPK6/MAPK4 signaling (R-HSA-5687128 )
UCH proteinases (R-HSA-5689603 )
Ub-specific processing proteases (R-HSA-5689880 )
Assembly of the pre-replicative complex (R-HSA-68867 )
Orc1 removal from chromatin (R-HSA-68949 )
CDK-mediated phosphorylation and removal of Cdc6 (R-HSA-69017 )
G2/M Checkpoints (R-HSA-69481 )
Ubiquitin Mediated Degradation of Phosphorylated Cdc25A (R-HSA-69601 )
Ubiquitin-dependent degradation of Cyclin D (R-HSA-75815 )
The role of GTSE1 in G2/M progression after G2 checkpoint (R-HSA-8852276 )
FBXL7 down-regulates AURKA during mitotic entry and in early mitosis (R-HSA-8854050 )
RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236 )
Regulation of RUNX2 expression and activity (R-HSA-8939902 )
Regulation of RUNX3 expression and activity (R-HSA-8941858 )
Regulation of PTEN stability and activity (R-HSA-8948751 )
Neddylation (R-HSA-8951664 )
Regulation of expression of SLITs and ROBOs (R-HSA-9010553 )
Interleukin-1 signaling (R-HSA-9020702 )
Negative regulation of NOTCH4 signaling (R-HSA-9604323 )
KEAP1-NFE2L2 pathway (R-HSA-9755511 )
GSK3B and BTRC (R-HSA-9762114 )
Somitogenesis (R-HSA-9824272 )
Antigen processing (R-HSA-983168 )
Activation of NF-kappaB in B cells (R-HSA-1169091 )

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Neoplasm DISZKGEW Definitive Altered Expression [1]
Acquired immune deficiency syndrome DISL5UOX Strong Biomarker [2]
Advanced cancer DISAT1Z9 Strong Altered Expression [3]
Breast cancer DIS7DPX1 Strong Altered Expression [4]
Breast carcinoma DIS2UE88 Strong Altered Expression [4]
Breast neoplasm DISNGJLM Strong Altered Expression [5]
Carcinoma DISH9F1N Strong Altered Expression [3]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [6]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [7]
HIV infectious disease DISO97HC Strong Biomarker [8]
Liposarcoma DIS8IZVM Strong Altered Expression [4]
Lung cancer DISCM4YA Strong Biomarker [9]
Lung carcinoma DISTR26C Strong Biomarker [9]
Mesothelioma DISKWK9M Strong Biomarker [10]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [10]
Nasopharyngeal carcinoma DISAOTQ0 Limited Altered Expression [11]
Thyroid gland papillary carcinoma DIS48YMM Limited Altered Expression [12]
Type-1 diabetes DIS7HLUB Limited Biomarker [13]
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⏷ Show the Full List of 18 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 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 26S proteasome non-ATPase regulatory subunit 8 (PSMD8). [14]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of 26S proteasome non-ATPase regulatory subunit 8 (PSMD8). [15]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of 26S proteasome non-ATPase regulatory subunit 8 (PSMD8). [16]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of 26S proteasome non-ATPase regulatory subunit 8 (PSMD8). [17]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of 26S proteasome non-ATPase regulatory subunit 8 (PSMD8). [19]
Testosterone DM7HUNW Approved Testosterone increases the expression of 26S proteasome non-ATPase regulatory subunit 8 (PSMD8). [20]
Marinol DM70IK5 Approved Marinol decreases the expression of 26S proteasome non-ATPase regulatory subunit 8 (PSMD8). [21]
Selenium DM25CGV Approved Selenium increases the expression of 26S proteasome non-ATPase regulatory subunit 8 (PSMD8). [22]
MG-132 DMKA2YS Preclinical MG-132 increases the expression of 26S proteasome non-ATPase regulatory subunit 8 (PSMD8). [24]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of 26S proteasome non-ATPase regulatory subunit 8 (PSMD8). [25]
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⏷ Show the Full List of 10 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of 26S proteasome non-ATPase regulatory subunit 8 (PSMD8). [18]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of 26S proteasome non-ATPase regulatory subunit 8 (PSMD8). [23]
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References

1 Downregulation of NOB1 suppresses the proliferation and tumor growth of non-small cell lung cancer in vitro and in vivo.Oncol Rep. 2014 Mar;31(3):1271-6. doi: 10.3892/or.2014.2991. Epub 2014 Jan 21.
2 An HTLV-III peptide produced by recombinant DNA is immunoreactive with sera from patients with AIDS.Nature. 1985 May 9-15;315(6015):151-4. doi: 10.1038/315151a0.
3 Epstein-Barr virus gene expression in human breast cancer: protagonist or passenger?.Br J Cancer. 2003 Jul 7;89(1):113-9. doi: 10.1038/sj.bjc.6601027.
4 Conjugated linoleic acid (CLA) inhibits expression of the Spot 14 (THRSP) and fatty acid synthase genes and impairs the growth of human breast cancer and liposarcoma cells.Nutr Cancer. 2009;61(1):114-22. doi: 10.1080/01635580802348666.
5 S14 protein in breast cancer cells: direct evidence of regulation by SREBP-1c, superinduction with progestin, and effects on cell growth.Exp Cell Res. 2006 Feb 1;312(3):278-88. doi: 10.1016/j.yexcr.2005.10.022. Epub 2005 Nov 21.
6 Polypeptides coded for by the region pre-S and gene S of hepatitis B virus DNA with the receptor for polymerized human serum albumin: expression on hepatitis B particles produced in the HBeAg or anti-HBe phase of hepatitis B virus infection.J Immunol. 1986 May 1;136(9):3467-72.
7 Downregulation of NIN/RPN12 binding protein inhibit the growth of human hepatocellular carcinoma cells.Mol Biol Rep. 2012 Jan;39(1):501-7. doi: 10.1007/s11033-011-0764-8. Epub 2011 May 15.
8 Host cell gene expression during human immunodeficiency virus type 1 latency and reactivation and effects of targeting genes that are differentially expressed in viral latency.J Virol. 2004 Sep;78(17):9458-73. doi: 10.1128/JVI.78.17.9458-9473.2004.
9 Synergistic anticancer activity of arsenic trioxide with erlotinib is based on inhibition of EGFR-mediated DNA double-strand break repair.Mol Cancer Ther. 2013 Jun;12(6):1073-84. doi: 10.1158/1535-7163.MCT-13-0065. Epub 2013 Apr 2.
10 Bioenergetics of acquired cisplatin resistant H1299 non-small cell lung cancer and P31 mesothelioma cells.Oncotarget. 2017 Oct 16;8(55):94711-94725. doi: 10.18632/oncotarget.21885. eCollection 2017 Nov 7.
11 Expression of BARF1 gene encoded by Epstein-Barr virus in nasopharyngeal carcinoma biopsies.Cancer Res. 2000 Oct 1;60(19):5584-8.
12 Expression of the NOB1 gene and its clinical significance in papillary thyroid carcinoma.J Int Med Res. 2013 Jun;41(3):568-72. doi: 10.1177/0300060513479862. Epub 2013 May 17.
13 Prevention of Type 1 Diabetes with Acetalated Dextran Microparticles Containing Rapamycin and Pancreatic Peptide P31.Adv Healthc Mater. 2018 Sep;7(18):e1800341. doi: 10.1002/adhm.201800341. Epub 2018 Jul 26.
14 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.
15 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.
16 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
17 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.
18 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
19 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
20 Evaluation of early biomarkers of muscle anabolic response to testosterone. J Cachexia Sarcopenia Muscle. 2011 Mar;2(1):45-56. doi: 10.1007/s13539-011-0021-y. Epub 2011 Feb 26.
21 JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
22 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.
23 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.
24 Proteasome inhibition creates a chromatin landscape favorable to RNA Pol II processivity. J Biol Chem. 2020 Jan 31;295(5):1271-1287. doi: 10.1074/jbc.RA119.011174. Epub 2019 Dec 5.
25 Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.