Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT585WY8)

DOT Name 26S proteasome non-ATPase regulatory subunit 3 (PSMD3)
Synonyms 26S proteasome regulatory subunit RPN3; 26S proteasome regulatory subunit S3; Proteasome subunit p58
Gene Name PSMD3
Related Disease
Alzheimer disease ( )
Asthma ( )
Breast cancer ( )
Breast carcinoma ( )
Hepatitis C virus infection ( )
HIV infectious disease ( )
Leukopenia ( )
Melanoma ( )
Primary biliary cholangitis ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
UniProt ID
PSMD3_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 ; 6MSE ; 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
PF01399 ; PF08375
Sequence
MKQEGSARRRGADKAKPPPGGGEQEPPPPPAPQDVEMKEEAATGGGSTGEADGKTAAAAA
EHSQRELDTVTLEDIKEHVKQLEKAVSGKEPRFVLRALRMLPSTSRRLNHYVLYKAVQGF
FTSNNATRDFLLPFLEEPMDTEADLQFRPRTGKAASTPLLPEVEAYLQLLVVIFMMNSKR
YKEAQKISDDLMQKISTQNRRALDLVAAKCYYYHARVYEFLDKLDVVRSFLHARLRTATL
RHDADGQATLLNLLLRNYLHYSLYDQAEKLVSKSVFPEQANNNEWARYLYYTGRIKAIQL
EYSEARRTMTNALRKAPQHTAVGFKQTVHKLLIVVELLLGEIPDRLQFRQPSLKRSLMPY
FLLTQAVRTGNLAKFNQVLDQFGEKFQADGTYTLIIRLRHNVIKTGVRMISLSYSRISLA
DIAQKLQLDSPEDAEFIVAKAIRDGVIEASINHEKGYVQSKEMIDIYSTREPQLAFHQRI
SFCLDIHNMSVKAMRFPPKSYNKDLESAEERREREQQDLEFAKEMAEDDDDSFP
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 )
Neutrophil degranulation (R-HSA-6798695 )
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

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alzheimer disease DISF8S70 Strong Biomarker [1]
Asthma DISW9QNS Strong Genetic Variation [2]
Breast cancer DIS7DPX1 Strong Biomarker [3]
Breast carcinoma DIS2UE88 Strong Biomarker [3]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [4]
HIV infectious disease DISO97HC Strong Biomarker [5]
Leukopenia DISJMBMM Strong Genetic Variation [6]
Melanoma DIS1RRCY Strong Biomarker [7]
Primary biliary cholangitis DIS43E0O Strong Genetic Variation [8]
Neoplasm DISZKGEW Limited Altered Expression [3]
Non-insulin dependent diabetes DISK1O5Z Limited Genetic Variation [9]
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⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 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 26S proteasome non-ATPase regulatory subunit 3 (PSMD3). [10]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of 26S proteasome non-ATPase regulatory subunit 3 (PSMD3). [11]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of 26S proteasome non-ATPase regulatory subunit 3 (PSMD3). [12]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of 26S proteasome non-ATPase regulatory subunit 3 (PSMD3). [13]
MG-132 DMKA2YS Preclinical MG-132 increases the expression of 26S proteasome non-ATPase regulatory subunit 3 (PSMD3). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of 26S proteasome non-ATPase regulatory subunit 3 (PSMD3). [16]
Milchsaure DM462BT Investigative Milchsaure affects the expression of 26S proteasome non-ATPase regulatory subunit 3 (PSMD3). [17]
KOJIC ACID DMP84CS Investigative KOJIC ACID decreases the expression of 26S proteasome non-ATPase regulatory subunit 3 (PSMD3). [18]
AHPN DM8G6O4 Investigative AHPN decreases the expression of 26S proteasome non-ATPase regulatory subunit 3 (PSMD3). [19]
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⏷ Show the Full List of 9 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of 26S proteasome non-ATPase regulatory subunit 3 (PSMD3). [14]
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References

1 Upregulation of Proteolytic Pathways and Altered Protein Biosynthesis Underlie Retinal Pathology in a Mouse Model of Alzheimer's Disease.Mol Neurobiol. 2019 Sep;56(9):6017-6034. doi: 10.1007/s12035-019-1479-4. Epub 2019 Feb 1.
2 Shared genetics of asthma and mental health disorders: a large-scale genome-wide cross-trait analysis.Eur Respir J. 2019 Dec 19;54(6):1901507. doi: 10.1183/13993003.01507-2019. Print 2019 Dec.
3 Proteasome 26S Subunit, non-ATPase 3 (PSMD3) Regulates Breast Cancer by Stabilizing HER2 from Degradation.Cancers (Basel). 2019 Apr 12;11(4):527. doi: 10.3390/cancers11040527.
4 Characterization of a Threonine-Rich Cluster in Hepatitis C Virus Nonstructural Protein 5A and Its Contribution to Hyperphosphorylation.J Virol. 2018 Nov 27;92(24):e00737-18. doi: 10.1128/JVI.00737-18. Print 2018 Dec 15.
5 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.
6 Genome-wide association study identifies a PSMD3 variant associated with neutropenia in interferon-based therapy for chronic hepatitis C.Hum Genet. 2015 Mar;134(3):279-89. doi: 10.1007/s00439-014-1520-7. Epub 2014 Dec 17.
7 Identification of key candidate genes involved in melanoma metastasis.Mol Med Rep. 2019 Aug;20(2):903-914. doi: 10.3892/mmr.2019.10314. Epub 2019 May 30.
8 Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants.Hum Mol Genet. 2012 Dec 1;21(23):5209-21. doi: 10.1093/hmg/dds359. Epub 2012 Aug 29.
9 Interaction between Erythrocyte Phospholipid Fatty Acids Composition and Variants of Inflammation-Related Genes on Type 2 Diabetes.J Nutrigenet Nutrigenomics. 2014;7(4-6):252-63. doi: 10.1159/000381347. Epub 2015 May 7.
10 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
11 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.
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 A comprehensive analysis of Wnt/beta-catenin signaling pathway-related genes and crosstalk pathways in the treatment of As2O3 in renal cancer. Ren Fail. 2018 Nov;40(1):331-339.
14 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.
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 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
17 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
18 Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
19 ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.