Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFV57T8)

DOT Name Proteasome subunit beta type-9 (PSMB9)
Synonyms EC 3.4.25.1; Low molecular mass protein 2; Macropain chain 7; Multicatalytic endopeptidase complex chain 7; Proteasome chain 7; Proteasome subunit beta-1i; Really interesting new gene 12 protein
Gene Name PSMB9
Related Disease
Proteasome-associated autoinflammatory syndrome 3 ( )
UniProt ID
PSB9_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6AVO; 6E5B; 7AWE; 7B12
EC Number
3.4.25.1
Pfam ID
PF00227
Sequence
MLRAGAPTGDLPRAGEVHTGTTIMAVEFDGGVVMGSDSRVSAGEAVVNRVFDKLSPLHER
IYCALSGSAADAQAVADMAAYQLELHGIELEEPPLVLAAANVVRNISYKYREDLSAHLMV
AGWDQREGGQVYGTLGGMLTRQPFAIGGSGSTFIYGYVDAAYKPGMSPEECRRFTTDAIA
LAMSRDGSSGGVIYLVTITAAGVDHRVILGNELPKFYDE
Function
The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB6 by PSMB9 increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues.
KEGG Pathway
Proteasome (hsa03050 )
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

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Proteasome-associated autoinflammatory syndrome 3 DIST9D7E Limited Unknown [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
22 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 subunit beta type-9 (PSMB9). [2]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Proteasome subunit beta type-9 (PSMB9). [3]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Proteasome subunit beta type-9 (PSMB9). [4]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Proteasome subunit beta type-9 (PSMB9). [5]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Proteasome subunit beta type-9 (PSMB9). [6]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Proteasome subunit beta type-9 (PSMB9). [7]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Proteasome subunit beta type-9 (PSMB9). [8]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Proteasome subunit beta type-9 (PSMB9). [9]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of Proteasome subunit beta type-9 (PSMB9). [10]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of Proteasome subunit beta type-9 (PSMB9). [11]
Sodium lauryl sulfate DMLJ634 Approved Sodium lauryl sulfate decreases the expression of Proteasome subunit beta type-9 (PSMB9). [12]
Salicyclic acid DM2F8XZ Approved Salicyclic acid increases the expression of Proteasome subunit beta type-9 (PSMB9). [6]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Proteasome subunit beta type-9 (PSMB9). [13]
Tamibarotene DM3G74J Phase 3 Tamibarotene increases the expression of Proteasome subunit beta type-9 (PSMB9). [4]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Proteasome subunit beta type-9 (PSMB9). [14]
GEA-6414 DM8J0MK Phase 1/2 GEA-6414 increases the expression of Proteasome subunit beta type-9 (PSMB9). [6]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Proteasome subunit beta type-9 (PSMB9). [15]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Proteasome subunit beta type-9 (PSMB9). [16]
MG-132 DMKA2YS Preclinical MG-132 increases the expression of Proteasome subunit beta type-9 (PSMB9). [17]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Proteasome subunit beta type-9 (PSMB9). [18]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Proteasome subunit beta type-9 (PSMB9). [19]
QUERCITRIN DM1DH96 Investigative QUERCITRIN decreases the expression of Proteasome subunit beta type-9 (PSMB9). [20]
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⏷ Show the Full List of 22 Drug(s)

References

1 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
2 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.
3 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.
4 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.
5 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
6 Pathophysiological roles of aldo-keto reductases (AKR1C1 and AKR1C3) in development of cisplatin resistance in human colon cancers. Chem Biol Interact. 2013 Feb 25;202(1-3):234-42.
7 Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
8 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.
9 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
10 Inhibition of PARP1 Increases IRF-dependent Gene Transcription in Jurkat Cells. Curr Med Sci. 2019 Jun;39(3):356-362. doi: 10.1007/s11596-019-2043-1. Epub 2019 Jun 17.
11 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
12 CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
13 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
14 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.
15 Label-free quantitative proteomic analysis identifies the oncogenic role of FOXA1 in BaP-transformed 16HBE cells. Toxicol Appl Pharmacol. 2020 Sep 15;403:115160. doi: 10.1016/j.taap.2020.115160. Epub 2020 Jul 25.
16 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
17 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.
18 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.
19 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
20 Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.