Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTURUR9B)

DOT Name Proteasome subunit beta type-10 (PSMB10)
Synonyms EC 3.4.25.1; Low molecular mass protein 10; Macropain subunit MECl-1; Multicatalytic endopeptidase complex subunit MECl-1; Proteasome MECl-1; Proteasome subunit beta-2i
Gene Name PSMB10
Related Disease
Proteasome-associated autoinflammatory syndrome 5 ( )
UniProt ID
PSB10_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; 6HV3; 6HV4; 6HV5; 6HV7; 6HVA; 6HVR; 6HVS; 6HVT; 6HVU; 6HVV; 6HVW; 7AWE; 7B12
EC Number
3.4.25.1
Pfam ID
PF12465 ; PF00227
Sequence
MLKPALEPRGGFSFENCQRNASLERVLPGLKVPHARKTGTTIAGLVFQDGVILGADTRAT
NDSVVADKSCEKIHFIAPKIYCCGAGVAADAEMTTRMVASKMELHALSTGREPRVATVTR
ILRQTLFRYQGHVGASLIVGGVDLTGPQLYGVHPHGSYSRLPFTALGSGQDAALAVLEDR
FQPNMTLEAAQGLLVEAVTAGILGDLGSGGNVDACVITKTGAKLLRTLSSPTEPVKRSGR
YHFVPGTTAVLTQTVKPLTLELVEETVQAMEVE
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.
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 5 DIS3I982 Limited Unknown [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
23 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Proteasome subunit beta type-10 (PSMB10). [2]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Proteasome subunit beta type-10 (PSMB10). [3]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Proteasome subunit beta type-10 (PSMB10). [4]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Proteasome subunit beta type-10 (PSMB10). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Proteasome subunit beta type-10 (PSMB10). [6]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Proteasome subunit beta type-10 (PSMB10). [7]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Proteasome subunit beta type-10 (PSMB10). [8]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Proteasome subunit beta type-10 (PSMB10). [9]
Testosterone DM7HUNW Approved Testosterone increases the expression of Proteasome subunit beta type-10 (PSMB10). [9]
Selenium DM25CGV Approved Selenium increases the expression of Proteasome subunit beta type-10 (PSMB10). [10]
Fluorouracil DMUM7HZ Approved Fluorouracil decreases the expression of Proteasome subunit beta type-10 (PSMB10). [11]
Sodium lauryl sulfate DMLJ634 Approved Sodium lauryl sulfate decreases the expression of Proteasome subunit beta type-10 (PSMB10). [12]
Diphenylpyraline DMW4X37 Approved Diphenylpyraline increases the expression of Proteasome subunit beta type-10 (PSMB10). [13]
Salicyclic acid DM2F8XZ Approved Salicyclic acid increases the expression of Proteasome subunit beta type-10 (PSMB10). [7]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Proteasome subunit beta type-10 (PSMB10). [14]
OTX-015 DMI8RG1 Phase 1/2 OTX-015 decreases the expression of Proteasome subunit beta type-10 (PSMB10). [15]
GEA-6414 DM8J0MK Phase 1/2 GEA-6414 increases the expression of Proteasome subunit beta type-10 (PSMB10). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Proteasome subunit beta type-10 (PSMB10). [16]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Proteasome subunit beta type-10 (PSMB10). [17]
Mivebresib DMCPF90 Phase 1 Mivebresib decreases the expression of Proteasome subunit beta type-10 (PSMB10). [15]
MG-132 DMKA2YS Preclinical MG-132 decreases the expression of Proteasome subunit beta type-10 (PSMB10). [18]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Proteasome subunit beta type-10 (PSMB10). [19]
Milchsaure DM462BT Investigative Milchsaure affects the expression of Proteasome subunit beta type-10 (PSMB10). [20]
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⏷ Show the Full List of 23 Drug(s)

References

1 A novel LMNA nonsense mutation causes two distinct phenotypes of cardiomyopathy with high risk of sudden cardiac death in a large five-generation family. Europace. 2018 Dec 1;20(12):2003-2013. doi: 10.1093/europace/euy127.
2 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
3 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
4 Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
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 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
7 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.
8 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
9 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
10 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.
11 Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
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 Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers. J Allergy Clin Immunol. 2016 Dec;138(6):1690-1700. doi: 10.1016/j.jaci.2016.02.038. Epub 2016 Apr 24.
14 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
15 Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
16 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.
17 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.
18 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.
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 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.