Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZEPV2T)

• DOT Name: COP9 signalosome complex subunit 7b (COPS7B)
• Synonyms: SGN7b; Signalosome subunit 7b; JAB1-containing signalosome subunit 7b
• Gene Name: COPS7B
• Related Disease:
  Clear cell renal carcinoma
  Renal cell carcinoma
• UniProt ID: CSN7B_HUMAN
• PDB ID: 6R6H; 6R7F; 6R7H; 6R7I; 6R7N; 8H38; 8H3A; 8H3F
• Pfam ID: PF18392 ; PF01399
• Sequence:
  MAGEQKPSSNLLEQFILLAKGTSGSALTALISQVLEAPGVYVFGELLELANVQELAEGAN
  AAYLQLLNLFAYGTYPDYIANKESLPELSTAQQNKLKHLTIVSLASRMKCIPYSVLLKDL
  EMRNLRELEDLIIEAVYTDIIQGKLDQRNQLLEVDFCIGRDIRKKDINNIVKTLHEWCDG
  CEAVLLGIEQQVLRANQYKENHNRTQQQVEAEVTNIKKTLKATASSSAQEMEQQLAEREC
  PPHAEQRQPTKKMSKVKGLVSSRH
• Function: Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, JUN, I-kappa-B-alpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively.
• Reactome Pathway:
  Formation of TC-NER Pre-Incision Complex (R-HSA-6781823)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Neddylation (R-HSA-8951664)
  DNA Damage Recognition in GG-NER (R-HSA-5696394)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[1]
Renal cell carcinoma	DISQZ2X8	moderate	Biomarker	[1]

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of COP9 signalosome complex subunit 7b (COPS7B).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of COP9 signalosome complex subunit 7b (COPS7B).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of COP9 signalosome complex subunit 7b (COPS7B).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of COP9 signalosome complex subunit 7b (COPS7B).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of COP9 signalosome complex subunit 7b (COPS7B).	[8]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of COP9 signalosome complex subunit 7b (COPS7B).	[9]

2 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 COP9 signalosome complex subunit 7b (COPS7B).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of COP9 signalosome complex subunit 7b (COPS7B).	[7]

References

• [1] Novel insights into biomarkers associated with renal cell carcinoma.Oncol Lett. 2018 Jul;16(1):83-90. doi: 10.3892/ol.2018.8665. Epub 2018 May 8.
• [2] 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.
• [3] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [7] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [8] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [9] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.