Details of Drug Off-Target (DOT)

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

DOT Name Proteasome activator complex subunit 1 (PSME1)
Synonyms
11S regulator complex subunit alpha; REG-alpha; Activator of multicatalytic protease subunit 1; Interferon gamma up-regulated I-5111 protein; IGUP I-5111; Proteasome activator 28 subunit alpha; PA28a; PA28alpha
Gene Name PSME1
Related Disease
Carcinoma ( )
Esophageal squamous cell carcinoma ( )
Autoimmune disease ( )
Childhood acute lymphoblastic leukemia ( )
Colonic neoplasm ( )
HIV infectious disease ( )
Inclusion body myositis ( )
Myofibrillar myopathy ( )
Ovarian neoplasm ( )
Undifferentiated carcinoma ( )
Lateral meningocele syndrome ( )
Limb-mammary syndrome ( )
Tuberculosis ( )
UniProt ID
PSME1_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1AVO; 7DR6; 7DRW; 7NAO; 7NAP; 8CXB
Pfam ID
PF02251 ; PF02252
Sequence
MAMLRVQPEAQAKVDVFREDLCTKTENLLGSYFPKKISELDAFLKEPALNEANLSNLKAP
LDIPVPDPVKEKEKEERKKQQEKEDKDEKKKGEDEDKGPPCGPVNCNEKIVVLLQRLKPE
IKDVIEQLNLVTTWLQLQIPRIEDGNNFGVAVQEKVFELMTSLHTKLEGFHTQISKYFSE
RGDAVTKAAKQPHVGDYRQLVHELDEAEYRDIRLMVMEIRNAYAVLYDIILKNFEKLKKP
RGETKGMIY
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 )
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

13 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Carcinoma DISH9F1N Definitive Biomarker [1]
Esophageal squamous cell carcinoma DIS5N2GV Definitive Biomarker [2]
Autoimmune disease DISORMTM Strong Altered Expression [3]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Altered Expression [4]
Colonic neoplasm DISSZ04P Strong Altered Expression [5]
HIV infectious disease DISO97HC Strong Biomarker [6]
Inclusion body myositis DISZXXG5 Strong Biomarker [7]
Myofibrillar myopathy DISF24LW Strong Biomarker [7]
Ovarian neoplasm DISEAFTY Strong Biomarker [8]
Undifferentiated carcinoma DISIAZST Disputed Biomarker [1]
Lateral meningocele syndrome DISG74RP Limited Genetic Variation [9]
Limb-mammary syndrome DIS7H4FP Limited Genetic Variation [9]
Tuberculosis DIS2YIMD Limited Biomarker [10]
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⏷ Show the Full List of 13 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
Valproate DMCFE9I Approved Valproate increases the expression of Proteasome activator complex subunit 1 (PSME1). [11]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Proteasome activator complex subunit 1 (PSME1). [12]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Proteasome activator complex subunit 1 (PSME1). [13]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Proteasome activator complex subunit 1 (PSME1). [14]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Proteasome activator complex subunit 1 (PSME1). [15]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Proteasome activator complex subunit 1 (PSME1). [16]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Proteasome activator complex subunit 1 (PSME1). [17]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Proteasome activator complex subunit 1 (PSME1). [18]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Proteasome activator complex subunit 1 (PSME1). [16]
Selenium DM25CGV Approved Selenium increases the expression of Proteasome activator complex subunit 1 (PSME1). [19]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Proteasome activator complex subunit 1 (PSME1). [20]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Proteasome activator complex subunit 1 (PSME1). [21]
MG-132 DMKA2YS Preclinical MG-132 decreases the expression of Proteasome activator complex subunit 1 (PSME1). [22]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Proteasome activator complex subunit 1 (PSME1). [23]
Lithium chloride DMHYLQ2 Investigative Lithium chloride increases the expression of Proteasome activator complex subunit 1 (PSME1). [24]
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⏷ Show the Full List of 15 Drug(s)

References

1 Global gene expression profiling of chemically induced rat mammary gland carcinomas and adenomas.Toxicol Pathol. 2005;33(7):768-75. doi: 10.1080/01926230500437027.
2 Using proteomic approach to identify tumor-associated proteins as biomarkers in human esophageal squamous cell carcinoma.J Proteome Res. 2011 Jun 3;10(6):2863-72. doi: 10.1021/pr200141c. Epub 2011 May 3.
3 Immunoproteasome subunit LMP2 expression is deregulated in Sjogren's syndrome but not in other autoimmune disorders.Ann Rheum Dis. 2006 Aug;65(8):1021-7. doi: 10.1136/ard.2005.045930. Epub 2006 Jan 13.
4 Differential expression pattern of protein markers for predicting chemosensitivity of dexamethasone-based chemotherapy of B cell acute lymphoblastic leukemia.Cancer Chemother Pharmacol. 2017 Jul;80(1):177-185. doi: 10.1007/s00280-017-3347-0. Epub 2017 Jun 5.
5 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.
6 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.
7 Proteasomal expression, induction of immunoproteasome subunits, and local MHC class I presentation in myofibrillar myopathy and inclusion body myositis.J Neuropathol Exp Neurol. 2004 May;63(5):484-98. doi: 10.1093/jnen/63.5.484.
8 Specific MALDI imaging and profiling for biomarker hunting and validation: fragment of the 11S proteasome activator complex, Reg alpha fragment, is a new potential ovary cancer biomarker.J Proteome Res. 2007 Nov;6(11):4127-34. doi: 10.1021/pr0702722. Epub 2007 Oct 16.
9 High-grade sarcoma diagnosis and prognosis: Biomarker discovery by mass spectrometry imaging.Proteomics. 2016 Jun;16(11-12):1802-13. doi: 10.1002/pmic.201500514.
10 PCR assay based on DNA coding for 16S rRNA for detection and identification of mycobacteria in clinical samples.J Clin Microbiol. 1995 Dec;33(12):3225-33. doi: 10.1128/jcm.33.12.3225-3233.1995.
11 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
12 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
13 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.
14 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.
15 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
16 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
17 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
18 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.
19 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.
20 Benzo[a]pyrene increases the Nrf2 content by downregulating the Keap1 message. Toxicol Sci. 2010 Aug;116(2):549-61.
21 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
22 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.
23 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.
24 Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.