Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYPP33T)

DOT Name Proteasome activator complex subunit 2 (PSME2)
Synonyms 11S regulator complex subunit beta; REG-beta; Activator of multicatalytic protease subunit 2; Proteasome activator 28 subunit beta; PA28b; PA28beta
Gene Name PSME2
Related Disease
Advanced cancer ( )
Colonic neoplasm ( )
Esophageal squamous cell carcinoma ( )
Gastric cancer ( )
HIV infectious disease ( )
Plasma cell myeloma ( )
Adenocarcinoma ( )
UniProt ID
PSME2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7DR6; 7DRW; 7NAO; 7NAP; 8CXB
Pfam ID
PF02251 ; PF02252
Sequence
MAKPCGVRLSGEARKQVEVFRQNLFQEAEEFLYRFLPQKIIYLNQLLQEDSLNVADLTSL
RAPLDIPIPDPPPKDDEMETDKQEKKEVHKCGFLPGNEKVLSLLALVKPEVWTLKEKCIL
VITWIQHLIPKIEDGNDFGVAIQEKVLERVNAVKTKVEAFQTTISKYFSERGDAVAKASK
ETHVMDYRALVHERDEAAYGELRAMVLDLRAFYAELYHIISSNLEKIVNPKGEEKPSMY
Function
Implicated in immunoproteasome assembly and required for efficient antigen processing. The PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern of the proteasome.
KEGG Pathway
Proteasome (hsa03050 )
Antigen processing and presentation (hsa04612 )
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 )
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505 )
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

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Colonic neoplasm DISSZ04P Strong Altered Expression [2]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [1]
Gastric cancer DISXGOUK Strong Biomarker [3]
HIV infectious disease DISO97HC Strong Biomarker [4]
Plasma cell myeloma DIS0DFZ0 Strong Altered Expression [5]
Adenocarcinoma DIS3IHTY Limited Biomarker [6]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
15 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Proteasome activator complex subunit 2 (PSME2). [7]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Proteasome activator complex subunit 2 (PSME2). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Proteasome activator complex subunit 2 (PSME2). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Proteasome activator complex subunit 2 (PSME2). [10]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Proteasome activator complex subunit 2 (PSME2). [11]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Proteasome activator complex subunit 2 (PSME2). [12]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Proteasome activator complex subunit 2 (PSME2). [13]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Proteasome activator complex subunit 2 (PSME2). [14]
Tamibarotene DM3G74J Phase 3 Tamibarotene increases the expression of Proteasome activator complex subunit 2 (PSME2). [7]
MG-132 DMKA2YS Preclinical MG-132 decreases the expression of Proteasome activator complex subunit 2 (PSME2). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Proteasome activator complex subunit 2 (PSME2). [16]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Proteasome activator complex subunit 2 (PSME2). [17]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Proteasome activator complex subunit 2 (PSME2). [18]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A decreases the expression of Proteasome activator complex subunit 2 (PSME2). [19]
Phencyclidine DMQBEYX Investigative Phencyclidine decreases the expression of Proteasome activator complex subunit 2 (PSME2). [20]
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⏷ Show the Full List of 15 Drug(s)

References

1 Identification of PA28 as a potential novel biomarker in human esophageal squamous cell carcinoma.Tumour Biol. 2017 Oct;39(10):1010428317719780. doi: 10.1177/1010428317719780.
2 Impaired expression of proteasome subunits and human leukocyte antigens class I in human colon cancer cells.J Gastroenterol Hepatol. 2003 Jan;18(1):32-40. doi: 10.1046/j.1440-1746.2003.02921.x.
3 Characterization of the immune escape phenotype of human gastric cancers with and without high-frequency microsatellite instability.J Pathol. 2007 Apr;211(5):516-523. doi: 10.1002/path.2142.
4 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.
5 Myeloma cell expression of 10 candidate genes for osteolytic bone disease. Only overexpression of DKK1 correlates with clinical bone involvement at diagnosis.Br J Haematol. 2008 Jan;140(1):25-35. doi: 10.1111/j.1365-2141.2007.06871.x. Epub 2007 Nov 12.
6 Potential roles for PA28beta in gastric adenocarcinoma development and diagnosis.J Cancer Res Clin Oncol. 2010 Aug;136(8):1275-82. doi: 10.1007/s00432-010-0778-y. Epub 2010 Feb 6.
7 Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
8 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
9 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.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
11 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
12 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.
13 Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
14 MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
15 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.
16 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.
17 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
18 Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
19 Lipid Rafts Disruption Increases Ochratoxin A Cytotoxicity to Hepatocytes. J Biochem Mol Toxicol. 2016 Feb;30(2):71-9. doi: 10.1002/jbt.21738. Epub 2015 Aug 25.
20 Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.