COPS5

Summary

COPS5 (COP9 signalosome subunit 5, HGNC:2240) is a protein-coding gene on chromosome 8q13.1, encoding COP9 signalosome complex subunit 5 (Q92905). Probable protease subunit of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. It is a common-essential gene (DepMap: required in 99.5% of cancer cell lines).

The protein encoded by this gene is one of the eight subunits of COP9 signalosome, a highly conserved protein complex that functions as an important regulator in multiple signaling pathways. The structure and function of COP9 signalosome is similar to that of the 19S regulatory particle of 26S proteasome. COP9 signalosome has been shown to interact with SCF-type E3 ubiquitin ligases and act as a positive regulator of E3 ubiquitin ligases. This protein is reported to be involved in the degradation of cyclin-dependent kinase inhibitor CDKN1B/p27Kip1. It is also known to be an coactivator that increases the specificity of JUN/AP1 transcription factors.

Source: NCBI Gene 10987 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 39 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_006837

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2240
Approved symbol	COPS5
Name	COP9 signalosome subunit 5
Location	8q13.1
Locus type	gene with protein product
Status	Approved
Aliases	JAB1, SGN5, MOV-34, CSN5
Ensembl gene	ENSG00000121022
Ensembl biotype	protein_coding
OMIM	604850
Entrez	10987

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 5 protein_coding, 5 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000357849, ENST00000517406, ENST00000517736, ENST00000517793, ENST00000518374, ENST00000518747, ENST00000518768, ENST00000519057, ENST00000519963, ENST00000521386, ENST00000521509, ENST00000523086, ENST00000523890, ENST00000887420, ENST00000960083

RefSeq mRNA: 1 — MANE Select: NM_006837 NM_006837

CCDS: CCDS6198

Canonical transcript exons

ENST00000357849 — 8 exons

Exon	Start	End
ENSE00001426305	67061854	67062133
ENSE00003471094	67045812	67045960
ENSE00003474168	67056519	67056604
ENSE00003549994	67059211	67059445
ENSE00003563767	67043079	67043317
ENSE00003581764	67057380	67057445
ENSE00003650177	67058083	67058211
ENSE00003662333	67051230	67051341

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.5842 / max 434.1932, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93432	50.5675	1823
93433	0.0167	3

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.76	gold quality
heart right ventricle	UBERON:0002080	98.21	gold quality
male germ cell	CL:0000015	98.14	gold quality
left ventricle myocardium	UBERON:0006566	98.03	gold quality
gastrocnemius	UBERON:0001388	98.00	gold quality
biceps brachii	UBERON:0001507	97.84	gold quality
myocardium	UBERON:0002349	97.80	gold quality
vastus lateralis	UBERON:0001379	97.75	gold quality
muscle of leg	UBERON:0001383	97.71	gold quality
muscle organ	UBERON:0001630	97.67	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.66	gold quality
quadriceps femoris	UBERON:0001377	97.64	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.57	gold quality
heart left ventricle	UBERON:0002084	97.54	gold quality
cardiac ventricle	UBERON:0002082	97.53	gold quality
right testis	UBERON:0004534	97.44	gold quality
skeletal muscle tissue	UBERON:0001134	97.41	gold quality
left testis	UBERON:0004533	97.37	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.26	gold quality
muscle tissue	UBERON:0002385	97.23	gold quality
pons	UBERON:0000988	97.22	gold quality
cardiac atrium	UBERON:0002081	97.14	gold quality
right atrium auricular region	UBERON:0006631	97.14	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.11	gold quality
heart	UBERON:0000948	97.09	gold quality
deltoid	UBERON:0001476	97.07	gold quality
diaphragm	UBERON:0001103	96.82	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.64	gold quality
body of tongue	UBERON:0011876	96.56	gold quality
apex of heart	UBERON:0002098	96.55	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-10	no	734.27
E-MTAB-6678	no	3.30
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
CDKN1B	Repression
VEGFA	Activation

Upstream regulators (CollecTRI, top): AP1, CEBPA, CEBPB, CEBPG, CTNNB1, GATA1, HAND2, HNF4A, JUN, PPARG, SP1, STAT1, STAT3, TCF4, TCF7L2

miRNA regulators (miRDB)

15 targeting COPS5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-4700-3P	97.74	68.64	1014
HSA-MIR-582-3P	96.69	67.38	1019

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• JAB1 colocalizes with PGP9.5 in both the cytoplasm and nucleus (PMID:12082530)
• Kip1 inhibits Jab1 mediated c-Jun dependent transcription (PMID:12119282)
• jab1 plays a role in the progression of thyroid carcinomas, especially those of aggressive phenotypes, and it may be responsible for p27 degradation in anaplastic and papillary carcinomas. (PMID:12860294)
• JAB1 contributes to the progression of malignant lymphoma of the thyroid especially with aggressive phenotypes, possibly by degrading p27. (PMID:14666612)
• Overexpression of Skp2 and Jab1 is associated with the reduction of p27(KIP1) expression, and may have a role in the progression of Oral Squamous Cell Carcinoma. (PMID:14707456)
• Jab1 might play an important role in carcinogenesis of pancreatic cancer. Cell cycle control targeting p27Kip1 might be a promising future therapeutic modality against pancreatic cancer. (PMID:14719054)
• Jab1/CSN5 as an adapter that targets Smad7 for degradation, thus releasing Smad7-mediated suppression of TGF-beta1 signaling. (PMID:14993265)
• identified an interactive domain for Jab1/CSN5, which promoted the degradation of topo IIalpha (PMID:15126503)
• High expression of Jab1 in metastatic melanoma suggests that Jab1 may be involved in survival and proliferation of metastatic melanoma cells. (PMID:15154004)
• JAB1 may act as a key molecule in selecting the unfolded protein response or cell death by association and dissociation with IRE1alpha (PMID:15234121)
• regulation of p27 via modulation of the Jab1 subcomplex is a novel mechanism whereby Bcr-Abl oncogenic signals accelerate abnormal cell proliferation. (PMID:15353483)
• Trx may regulate cell cycle and growth through a novel modulation of AP-1 activity and p27Kip1 degradation with Jab1 (PMID:15480426)
• Jab1 protein may contribute to the tumor progression in laryngeal squamous cell carcinomas (PMID:15671554)
• CSN5/Jab1 causes an increase in ligand-induced ERalpha degradation. (PMID:15899841)
• The S100A7-Jab1 pathway acts to enhance survival under conditions of cellular stress, such as anoikis, which may promote progression of breast cancer. (PMID:15994944)
• High expression of Jab1 is associated with hepatocellular carcinoma (PMID:16000397)
• Data show that macrophage migration inhibitory factor (MIF) activates the ERK pathway, involves the upstream activation of a Src-type kinase and is co-regulated by the cellular MIF binding protein JAB1/CSN5. (PMID:16122907)
• Jab1 is required for the hyperphosphorylation of 53BP1 upon mitotic stress conditions and is involved in proper activation of mitotic checkpoint mechanism. (PMID:16187115)
• Jab1 promotes cell growth by decreasing p27 level. (PMID:16300740)
• Jab1 is an important effector that mediates a novel signal transduction pathway for PAR-2-dependent gene expression (PMID:16410250)
• CSN5 is a protein that plays a newly defined functional role in association with the cardiac L-type Ca(2+) channel. (PMID:16483597)
• Jab1 is required to remove post-translationally modified p53 in coordination with mdm2 (PMID:16624822)
• Has a potential protective effect against pathogenic West Nile virus capsid. (PMID:16882664)
• JAB1 regulates ubiquitination of TRAF2 (PMID:16936264)
• Jab1 overexpression contributes to pancreatic cancer cell proliferation and survival. (PMID:17027978)
• NRBP may be an important negative regulator of Jab1-mediated functions such as gene transcription and tumor progression. (PMID:17052710)
• Jab1 is a newly identified intracellular (negative) modulator of BMP signaling in chondrocytes that appears to crosslink the BMP and interleukin-1 pathways. (PMID:17133595)
• results suggest that Jab1 is an important regulator for the stability of protein 9-1-1 control in cells (PMID:17583730)
• CSN5 is a pivotal regulator for both p53 and MDM2 (PMID:17879958)
• HER-2/neu transcriptionally activates Jab1 expression to promote proliferation of breast cancer cells. (PMID:17914096)
• JAB1 is involved in the regulation of mitochondrial apoptotic pathway through specific interaction with BclGs. (PMID:18006276)
• CSN5 isopeptidase activity links COP9 signalosome to breast cancer progression. (PMID:18199546)
• Jab1 is a downstream target for HER-2/neu and its overexpression is linked with HER-2/neu expression in breast cancer. (PMID:18246048)
• During the proliferation process of lymphoma U937 cells, Jab1 and CRM1 may influence the location and expression of p27kip1. (PMID:18246793)
• Jab1 protein may contribute to the tumor progression through Jab1-mediated p27kip1 degradation and that control of Jab1 expression is a novel therapeutic target in non-Hoddgkin’s lymphoma. (PMID:18285702)
• expression of Jab1 in human hepatocellular carcinoma (PMID:18346358)
• Expression of p27(kip1) is regulated by Jab1 in lymphoma cell lines. (PMID:18476592)
• Jab1 is a target of EGFR signaling in ERalpha- cell lines and breast tumors (PMID:18534028)
• Jab1 is overexpressed in HCC and PPARgamma ligands may suppress Jab1 to inhibit the proliferation of HCC cells (PMID:18593980)
• the expression and function of JAB1 are critical for the proliferation and maintenance of hematopoietic progenitors (PMID:18667426)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cops5	ENSDARG00000057624
mus_musculus	Cops5	ENSMUSG00000025917
rattus_norvegicus	Cops5	ENSRNOG00000006499
drosophila_melanogaster	CSN5	FBGN0027053
caenorhabditis_elegans		WBGENE00000817

Paralogs (3): PSMD14 (ENSG00000115233), EIF3H (ENSG00000147677), BRCC3 (ENSG00000185515)

Protein

Protein identifiers

COP9 signalosome complex subunit 5 — Q92905 (reviewed: Q92905)

Alternative names: Jun activation domain-binding protein 1

All UniProt accessions (7): A0A024R7W9, E5RFS1, E5RG35, E5RHF2, E5RHH5, E5RK55, Q92905

UniProt curated annotations — full annotation on UniProt →

Function. Probable protease subunit 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 the 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, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, 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. In the complex, it probably acts as the catalytic center that mediates the cleavage of Nedd8 from cullins. It however has no metalloprotease activity by itself and requires the other subunits of the CSN complex. Interacts directly with a large number of proteins that are regulated by the CSN complex, confirming a key role in the complex. Promotes the proteasomal degradation of BRSK2.

Subunit / interactions. Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COPS6, COPS7 (COPS7A or COPS7B), COPS8 and COPS9 isoform 1. In the complex, it probably interacts directly with COPS1, COPS2, COPS4, COPS6 and COPS7 (COPS7A or COPS7B) and COPS9 isoform 1. Interacts with COPS9 isoform 2. The CSN complex interacts with the BRISC complex. Also exists as monomeric form. Interacts with TP53, MIF, JUN, UCHL1, NCOA1, HIF1A, CDKN1B, BCL3, GFER, PGR, LHCGR, SMAD4, SMAD7, ID1, ID3, ITGB2 and TOP2A. Part of a complex consisting of RANBP9, Ran, DYRK1B and COPS5. Interacts with IFIT3. Interacts with BRSK2. Interacts with ZDHHC16. Interacts with MINDY3. Interacts with FANK1; regulates the phosphorylation of JUN and the transcriptional activity of AP-1. Interacts with NUPR1; this interaction allows COPS5-dependent CDKN1B nuclear to cytoplasm translocation.

Subcellular location. Cytoplasm. Cytosol. Nucleus. Perinuclear region. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle.

Domain organisation. The JAMM motif is essential for the protease activity of the CSN complex resulting in deneddylation of cullins. It constitutes the catalytic center of the complex.

Miscellaneous. The CSN complex is associated with some ‘Lys-63’-specific deubiquitination. Such activity is however not mediated by the core CSN complex but by the BRCC3/BRCC36 component of the BRISC complex.

Similarity. Belongs to the peptidase M67A family. CSN5 subfamily.

RefSeq proteins (1): NP_006828* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000555	JAMM/MPN+_dom	Domain
IPR037518	MPN	Domain
IPR040961	CSN5_C	Domain
IPR050242	JAMM_MPN+_peptidase_M67A	Family

Pfam: PF01398, PF18323

UniProt features (30 total): helix 8, strand 8, turn 3, binding site 3, sequence conflict 2, initiator methionine 1, chain 1, domain 1, short sequence motif 1, modified residue 1, mutagenesis site 1

Structure

Experimental structures (PDB)

31 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5JOH	X-RAY DIFFRACTION	1.99
5M5Q	X-RAY DIFFRACTION	2.2
5JOG	X-RAY DIFFRACTION	2.46
4F7O	X-RAY DIFFRACTION	2.6
9QO4	ELECTRON MICROSCOPY	2.95
9EFQ	ELECTRON MICROSCOPY	2.96
9PH4	ELECTRON MICROSCOPY	3
9QO6	ELECTRON MICROSCOPY	3
9EFV	ELECTRON MICROSCOPY	3.03
9EFM	ELECTRON MICROSCOPY	3.16
9QO1	ELECTRON MICROSCOPY	3.23
9QO0	ELECTRON MICROSCOPY	3.26
9E77	ELECTRON MICROSCOPY	3.3
9E81	ELECTRON MICROSCOPY	3.3
9EG8	ELECTRON MICROSCOPY	3.39
9E5Z	ELECTRON MICROSCOPY	3.4
9EG1	ELECTRON MICROSCOPY	3.52
4D10	X-RAY DIFFRACTION	3.8
9QO2	ELECTRON MICROSCOPY	3.8
9EGL	ELECTRON MICROSCOPY	3.93
9QO5	ELECTRON MICROSCOPY	4
4D18	X-RAY DIFFRACTION	4.08
8H38	ELECTRON MICROSCOPY	4.25
9QO3	ELECTRON MICROSCOPY	4.6
4WSN	X-RAY DIFFRACTION	5.5
6R7I	ELECTRON MICROSCOPY	5.9
8H3F	ELECTRON MICROSCOPY	6.73
8H3A	ELECTRON MICROSCOPY	7.51
6R7F	ELECTRON MICROSCOPY	8.2
6R6H	ELECTRON MICROSCOPY	8.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92905-F1	86.68	0.58

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 138; 140; 151

Post-translational modifications (1): 2

Mutagenesis-validated functional residues (1):

Position	Phenotype
138	abolishes ability to deneddylate cullins, without affecting the ’lys-63’-specific deubiquitination associated with the c

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-5696394	DNA Damage Recognition in GG-NER
R-HSA-6781823	Formation of TC-NER Pre-Incision Complex
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8951664	Neddylation
R-HSA-9929356	GSK3B-mediated proteasomal degradation of PD-L1(CD274)

MSigDB gene sets: 318 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, MORF_MTA1, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, MORF_MBD4, GOBP_IRE1_MEDIATED_UNFOLDED_PROTEIN_RESPONSE, TSENG_IRS1_TARGETS_UP, MORF_SMC1L1, TGCGCANK_UNKNOWN, GOBP_VESICLE_LOCALIZATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOMF_METALLOPEPTIDASE_ACTIVITY, HOFMANN_CELL_LYMPHOMA_UP, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, MORF_HDAC1

GO Biological Process (14): protein deneddylation (GO:0000338), translation (GO:0006412), proteolysis (GO:0006508), negative regulation of apoptotic process (GO:0043066), post-translational protein modification (GO:0043687), protein neddylation (GO:0045116), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of JNK cascade (GO:0046328), obsolete positive regulation of DNA-binding transcription factor activity (GO:0051091), regulation of cell cycle (GO:0051726), regulation of IRE1-mediated unfolded protein response (GO:1903894), exosomal secretion (GO:1990182), regulation of protein neddylation (GO:2000434), translational initiation (GO:0006413)

GO Molecular Function (11): transcription coactivator activity (GO:0003713), translation initiation factor activity (GO:0003743), metallopeptidase activity (GO:0008237), deNEDDylase activity (GO:0019784), enzyme binding (GO:0019899), macrophage migration inhibitory factor binding (GO:0035718), metal ion binding (GO:0046872), metal-dependent deubiquitinase activity (GO:0140492), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (11): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), eukaryotic translation initiation factor 3 complex (GO:0005852), synaptic vesicle (GO:0008021), COP9 signalosome (GO:0008180), perinuclear region of cytoplasm (GO:0048471), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Global Genome Nucleotide Excision Repair (GG-NER)	1
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	1
Clathrin-mediated endocytosis	1
Post-translational protein modification	1
Regulation of PD-L1(CD274) Post-translational modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	4
translational initiation	2
protein metabolic process	2
positive regulation of DNA-templated transcription	2
protein modification by small protein removal	1
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein biosynthetic process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
protein modification process	1
protein modification by small protein conjugation	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
JNK cascade	1
regulation of MAPK cascade	1
cell cycle	1
regulation of cellular process	1
IRE1-mediated unfolded protein response	1
regulation of endoplasmic reticulum unfolded protein response	1
exocytosis	1
establishment of vesicle localization	1
extracellular exosome biogenesis	1
protein neddylation	1
regulation of protein modification by small protein conjugation or removal	1
formation of translation initiation ternary complex	1
translation	1
metabolic process	1
transcription coregulator activity	1
translation factor activity	1
peptidase activity	1
ubiquitin-like protein peptidase activity	1
protein binding	1
cytokine binding	1
cation binding	1
metallopeptidase activity	1

Protein interactions and networks

STRING

4758 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COPS5	JUN	P05412	995
COPS5	COPS6	Q7L5N1	986
COPS5	COPS4	Q9BT78	979
COPS5	NEDD8	Q15843	943
COPS5	MIF	P14174	940
COPS5	CDKN1B	P46527	937
COPS5	COPS8	Q99627	931
COPS5	COPS7A	Q9UBW8	927
COPS5	COPS2	P61201	926
COPS5	CUL1	Q13616	923
COPS5	PSMD7	P51665	911
COPS5	COPS3	Q9UNS2	899
COPS5	GPS1	Q13098	895
COPS5	TP53	P04637	878
COPS5	STAMBPL1	Q96FJ0	847

IntAct

329 interactions, top by confidence:

A	B	Type	Score
CUL1	CAND1	psi-mi:“MI:0914”(association)	0.960
CUL1	SKP1	psi-mi:“MI:0914”(association)	0.960
CUL2	VHL	psi-mi:“MI:0914”(association)	0.940
NEDD8	UBE2M	psi-mi:“MI:0914”(association)	0.940
COPS3	COPS5	psi-mi:“MI:0915”(physical association)	0.930
COPS5	COPS6	psi-mi:“MI:0915”(physical association)	0.930
COPS5	COPS2	psi-mi:“MI:0914”(association)	0.910
FBXO7	SKP1	psi-mi:“MI:0914”(association)	0.900
COPS6	COPS2	psi-mi:“MI:0914”(association)	0.880
COPS3	COPS2	psi-mi:“MI:0914”(association)	0.870
GPS1	COPS2	psi-mi:“MI:0915”(physical association)	0.860

BioGRID (1714): PTGS2 (Reconstituted Complex), COPS6 (Reconstituted Complex), NEDD8 (Reconstituted Complex), CUL1 (Biochemical Activity), COPS6 (Co-crystal Structure), COPS5 (Affinity Capture-Western), COPS5 (Affinity Capture-Western), COPS5 (Affinity Capture-Western), COPS5 (Affinity Capture-Western), COPS5 (Affinity Capture-Western), COPS5 (Two-hybrid), OPRM1 (Reconstituted Complex), COPS5 (Reconstituted Complex), COPS5 (Affinity Capture-Western), cul1 (Biochemical Activity)

ESM2 similar proteins: A8QCY3, A8WVY9, B0WDA9, B3MP94, B4JAS7, B4KGS4, B4LTW0, B4N116, B5DJJ2, B5FY35, E2AXC7, O00487, O01974, O15372, O35593, O35864, O76577, O94454, P0CQ24, P0CQ25, P41878, P41883, P43588, P91001, Q170C2, Q4IJM4, Q4WZP2, Q54PF3, Q56JZ5, Q5BBF1, Q5ZLE6, Q6C703, Q6FKS1, Q6GLM9, Q6P635, Q6P9U8, Q6PC30, Q750E9, Q7RXX8, Q86IJ1

Diamond homologs: A0A009IHW8, A0A0H2V8B5, A0A0P0FGV9, A0A151EH88, A0A1I4KS07, A1AY86, C0RGW8, O35864, P0CQ24, P0CQ25, P0DTS9, P91001, Q2YPC4, Q4IJM4, Q4WZP2, Q54PF3, Q59PG6, Q5BBF1, Q6BMQ3, Q6CRJ8, Q6GLM9, Q6P635, Q6PC30, Q75E19, Q7RXX8, Q8YF53, Q92905, Q9XZ58, A0A8M3B525, A5PJP6, B0KWU8, B2RYM5, B5X8M4, E2AXC7, P46736, P46737, Q3TV65, Q4VA72, Q5R9L6, Q66GV6

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
COPS5	down-regulates	SMAD4	ubiquitination
COPS5	“form complex”	“COP9 signalosome variant 2”	binding
COPS5	“form complex”	“COP9 signalosome variant 1”	binding
COPS5	“up-regulates quantity by stabilization”	CD274	deubiquitination
CHUK	“down-regulates activity”	COPS5	phosphorylation
IKBKB	“down-regulates activity”	COPS5	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 127 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
DNA Damage Recognition in GG-NER	11	34.5×	2e-12
RHOBTB1 GTPase cycle	5	26.1×	1e-04
Formation of TC-NER Pre-Incision Complex	10	23.2×	2e-09
Iron uptake and transport	5	19.0×	3e-04
FOXO-mediated transcription	5	18.5×	3e-04
MAP kinase activation	5	17.0×	3e-04
Toll Like Receptor 10 (TLR10) Cascade	6	14.2×	2e-04
Toll Like Receptor 5 (TLR5) Cascade	6	14.2×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of protein neddylation	9	73.3×	6e-13
protein neddylation	10	61.1×	3e-13
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	7	22.8×	4e-06
intrinsic apoptotic signaling pathway	6	18.7×	1e-04
G1/S transition of mitotic cell cycle	7	12.2×	2e-04
JNK cascade	5	11.8×	4e-03
MAPK cascade	7	9.3×	8e-04
protein K48-linked ubiquitination	6	8.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

39 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2568 predictions. Top by Δscore:

Variant	Effect	Δscore
8:67045806:TCTTA:T	donor_loss	1.0000
8:67045807:CTTAC:C	donor_loss	1.0000
8:67045808:TTAC:T	donor_loss	1.0000
8:67045809:TAC:T	donor_loss	1.0000
8:67045810:A:T	donor_loss	1.0000
8:67045811:C:CG	donor_loss	1.0000
8:67045811:CCTGT:C	donor_gain	1.0000
8:67051225:CTTA:C	donor_loss	1.0000
8:67051226:TTA:T	donor_loss	1.0000
8:67051227:TA:T	donor_loss	1.0000
8:67051228:A:AC	donor_gain	1.0000
8:67051228:A:C	donor_loss	1.0000
8:67051229:C:CC	donor_gain	1.0000
8:67051229:CA:C	donor_gain	1.0000
8:67051229:CAGTA:C	donor_gain	1.0000
8:67051342:C:CC	acceptor_gain	1.0000
8:67051344:A:C	acceptor_gain	1.0000
8:67056515:TTA:T	donor_loss	1.0000
8:67056516:TACTG:T	donor_loss	1.0000
8:67056517:A:AC	donor_gain	1.0000
8:67056518:C:CT	donor_gain	1.0000
8:67056518:CT:C	donor_gain	1.0000
8:67056518:CTG:C	donor_gain	1.0000
8:67056603:CC:C	acceptor_gain	1.0000
8:67056604:CC:C	acceptor_gain	1.0000
8:67057441:TCAAT:T	acceptor_gain	1.0000
8:67057442:CAAT:C	acceptor_gain	1.0000
8:67057442:CAATC:C	acceptor_gain	1.0000
8:67057445:TC:T	acceptor_loss	1.0000
8:67057446:C:CA	acceptor_loss	1.0000

AlphaMissense

2213 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:67045816:C:G	D306H	1.000
8:67051263:C:A	W246C	1.000
8:67051263:C:G	W246C	1.000
8:67051265:A:G	W246R	1.000
8:67051265:A:T	W246R	1.000
8:67051340:A:C	Y221D	1.000
8:67051340:A:G	Y221H	1.000
8:67056527:G:C	H217Q	1.000
8:67056527:G:T	H217Q	1.000
8:67056529:G:C	H217D	1.000
8:67056534:C:A	G215V	1.000
8:67056534:C:T	G215D	1.000
8:67056535:C:A	G215C	1.000
8:67056535:C:G	G215R	1.000
8:67056536:A:C	F214L	1.000
8:67056536:A:T	F214L	1.000
8:67056537:A:C	F214C	1.000
8:67056537:A:G	F214S	1.000
8:67056538:A:C	F214V	1.000
8:67056538:A:G	F214L	1.000
8:67056538:A:T	F214I	1.000
8:67056540:T:A	D213V	1.000
8:67056540:T:C	D213G	1.000
8:67056541:C:G	D213H	1.000
8:67056548:T:A	K210N	1.000
8:67056548:T:G	K210N	1.000
8:67056549:T:A	K210I	1.000
8:67056550:T:C	K210E	1.000
8:67056558:G:T	P207Q	1.000
8:67056561:A:C	I206S	1.000

dbSNP variants (sampled 300 via entrez): RS1000234446 (8:67044191 C>T), RS1000248986 (8:67045344 C>A), RS1000577943 (8:67047281 G>A), RS1000636883 (8:67046921 TAAAC>T), RS1000916301 (8:67050191 C>T), RS1000961241 (8:67054262 G>A), RS1001126563 (8:67050062 G>A), RS1001235902 (8:67046094 T>C), RS1001516496 (8:67059672 A>G), RS1001582493 (8:67052901 G>A), RS1001615771 (8:67052067 T>C), RS1001636784 (8:67060127 T>C), RS1001799367 (8:67052600 T>C), RS1001853949 (8:67059312 T>G), RS1001950986 (8:67053682 CAG>C)

Disease associations

OMIM: gene MIM:604850 | disease phenotypes: MIM:615636

GenCC curated gene-disease

Mondo (1): Joubert syndrome 21 (MONDO:0014288)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105809 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 26,682 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL295124	BERBERINE	4	26,682

PharmGKB: 1 entry (VIP=true, CPIC=false)

Binding affinities (BindingDB)

30 measured of 32 human assays (32 total across all organisms); most potent 30 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-(pyridin-4-ylmethyl)-8-sulfanylquinoline-3-carboxamide	IC50	200 nM	US-10005735: Inhibitors of RPN11
N-[3-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]propyl]-8-sulfanylquinoline-3-carboxamide	IC50	200 nM	US-10005735: Inhibitors of RPN11
8-sulfanyl-N-(2-thiophen-2-ylethyl)quinoline-3-carboxamide	IC50	300 nM	US-10005735: Inhibitors of RPN11
Capzimin	IC50	340 nM	US-10005735: Inhibitors of RPN11
N-[2-[2-[2-[2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]ethoxy]ethoxy]ethoxy]ethyl]-8-sulfanylquinoline-3-carboxamide	IC50	400 nM	US-10005735: Inhibitors of RPN11
8-sulfanyl-N-(1,3-thiazol-2-yl)quinoline-3-carboxamide	IC50	450 nM	US-10005735: Inhibitors of RPN11
8-sulfanyl-N-(1,3-thiazol-2-ylmethyl)quinoline-3-carboxamide	IC50	500 nM	US-10005735: Inhibitors of RPN11
N-[2-(4,5-dimethyl-1,3-thiazol-2-yl)ethyl]-8-sulfanylquinoline-3-carboxamide	IC50	500 nM	US-10005735: Inhibitors of RPN11
8-sulfanyl-N-[[4-(trifluoromethyl)phenyl]methyl]quinoline-3-carboxamide	IC50	700 nM	US-10005735: Inhibitors of RPN11
8-sulfanyl-N-(2-thiophen-2-ylethyl)quinoline-4-carboxamide	IC50	700 nM	US-10005735: Inhibitors of RPN11
ethyl 2-[2-[(8-sulfanylquinoline-3-carbonyl)amino]ethyl]-1,3-thiazole-4-carboxylate	IC50	700 nM	US-10005735: Inhibitors of RPN11
8-sulfanyl-N-(thiophen-2-ylmethyl)quinoline-3-carboxamide	IC50	800 nM	US-10005735: Inhibitors of RPN11
N-[(4-morpholin-4-ylphenyl)methyl]-8-sulfanylquinoline-3-carboxamide	IC50	800 nM	US-10005735: Inhibitors of RPN11
N-(furan-2-ylmethyl)-8-sulfanylquinoline-3-carboxamide	IC50	900 nM	US-10005735: Inhibitors of RPN11
N-(1,3-benzodioxol-5-ylmethyl)-8-sulfanylquinoline-3-carboxamide	IC50	900 nM	US-10005735: Inhibitors of RPN11
8-sulfanylquinoline-3-carboxamide	IC50	1000 nM	US-10005735: Inhibitors of RPN11
N-[2-(furan-2-yl)ethyl]-8-sulfanylquinoline-4-carboxamide	IC50	1000 nM	US-10005735: Inhibitors of RPN11
N-benzyl-8-sulfanylquinoline-3-carboxamide	IC50	1100 nM	US-10005735: Inhibitors of RPN11
4-methyl-2-[2-[(8-sulfanylquinoline-3-carbonyl)amino]ethyl]-1,3-thiazole-5-carboxylic acid	IC50	1100 nM	US-10005735: Inhibitors of RPN11
N-[2-(furan-2-yl)ethyl]-8-sulfanylquinoline-3-carboxamide	IC50	1200 nM	US-10005735: Inhibitors of RPN11
8-sulfanyl-N-(thiophen-2-ylmethyl)quinoline-4-carboxamide	IC50	1200 nM	US-10005735: Inhibitors of RPN11
N-methyl-8-sulfanylquinoline-3-carboxamide	IC50	1600 nM	US-10005735: Inhibitors of RPN11
N-(furan-2-ylmethyl)-8-sulfanylquinoline-4-carboxamide	IC50	2200 nM	US-10005735: Inhibitors of RPN11
N-(1,3-oxazol-2-yl)-8-sulfanylquinoline-3-carboxamide	IC50	2600 nM	US-10005735: Inhibitors of RPN11
methyl 2-[(8-sulfanylquinoline-3-carbonyl)amino]acetate	IC50	2800 nM	US-10005735: Inhibitors of RPN11
N-(pyridin-3-ylmethyl)-8-sulfanylquinoline-3-carboxamide	IC50	3100 nM	US-10005735: Inhibitors of RPN11
N-(pyridin-2-ylmethyl)-8-sulfanylquinoline-3-carboxamide	IC50	3900 nM	US-10005735: Inhibitors of RPN11
N-(oxolan-2-ylmethyl)-8-sulfanylquinoline-3-carboxamide	IC50	4600 nM	US-10005735: Inhibitors of RPN11
N-(2-morpholin-4-ylethyl)-8-sulfanylquinoline-3-carboxamide	IC50	6400 nM	US-10005735: Inhibitors of RPN11
N-[2-(4-phenyl-1,3-thiazol-2-yl)ethyl]-8-sulfanylquinoline-3-carboxamide	IC50	11100 nM	US-10005735: Inhibitors of RPN11

ChEMBL bioactivities

73 potent at pChembl≥5 of 115 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.24	IC50	5.8	nM	CHEMBL4528101
8.22	IC50	6	nM	CHEMBL4528101
7.22	IC50	60	nM	CHEMBL4447716
7.05	IC50	90	nM	CHEMBL4447716
6.77	IC50	170	nM	NAPHTHAZALIN
6.72	IC50	190	nM	SHIKONIN
6.60	IC50	250	nM	CHEMBL6149563
6.57	IC50	270	nM	ALKANNIN
6.54	IC50	290	nM	CHEMBL6145253
6.52	IC50	300	nM	CHEMBL4088568
6.51	IC50	310	nM	CHEMBL6162853
6.51	IC50	310	nM	CHEMBL6163084
6.44	IC50	360	nM	CHEMBL6163378
6.39	IC50	410	nM	SHIKONIN
6.37	IC50	430	nM	ACETYLSHIKONIN
6.30	IC50	500	nM	CHEMBL4096289
6.30	IC50	500	nM	CHEMBL6120733
6.29	IC50	510	nM	CHEMBL6160777
6.22	IC50	600	nM	ISOBUTYLSHIKONIN
6.22	IC50	600	nM	CHEMBL6168758
6.18	IC50	660	nM	CHEMBL6142730
6.17	IC50	680	nM	CHEMBL6142969
6.10	IC50	800	nM	ALKANNIN
6.10	IC50	790	nM	CHEMBL6133980
6.08	IC50	840	nM	CHEMBL4447716
6.07	IC50	860	nM	CHEMBL6143669
6.06	IC50	870	nM	CHEMBL6164460
6.04	IC50	910	nM	NAPHTHAZALIN
6.03	IC50	940	nM	CHEMBL6160437
6.03	IC50	940	nM	CHEMBL6171611
6.01	IC50	980	nM	CHEMBL6152696
5.97	IC50	1070	nM	ACETYLSHIKONIN
5.95	IC50	1120	nM	CHEMBL6167716
5.93	IC50	1170	nM	ISOBUTYLSHIKONIN
5.91	IC50	1230	nM	CHEMBL6167782
5.91	IC50	1220	nM	CHEMBL6149919
5.90	IC50	1250	nM	CHEMBL6142964
5.90	IC50	1250	nM	CHEMBL6171018
5.86	IC50	1370	nM	CHEMBL6142433
5.85	IC50	1420	nM	CHEMBL6162339
5.84	IC50	1440	nM	CHEMBL6142513
5.83	IC50	1480	nM	CHEMBL6147975
5.82	IC50	1500	nM	CHEMBL6145339
5.80	IC50	1600	nM	CHEMBL4101230
5.80	IC50	1570	nM	CHEMBL6166228
5.79	IC50	1620	nM	CHEMBL6169234
5.78	IC50	1650	nM	CHEMBL6160166
5.73	IC50	1850	nM	CHEMBL6170193
5.70	IC50	2000	nM	CHEMBL6147398
5.68	IC50	2090	nM	CHEMBL6165971

PubChem BioAssay actives

24 with measured affinity, of 105 total; 18 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-(difluoromethyl)-N-[4-[(5S,6S)-6-hydroxy-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepin-5-yl]-3-phenylphenyl]-1-propan-2-ylpyrazole-5-carboxamide	1558727: Inhibition of CSN5 (unknown origin) using fluorescence-labeled CRL substrate by TR-FRET assay	ic50	0.0058	uM
1-[(3R)-3-(1H-benzimidazol-2-yl)morpholin-4-yl]-3-[2-(4-methyl-2-phenylphenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]propan-1-one	1558727: Inhibition of CSN5 (unknown origin) using fluorescence-labeled CRL substrate by TR-FRET assay	ic50	0.0600	uM
5,8-dihydroxynaphthalene-1,4-dione	2111462: Inhibition of N-terminal His6-tagged CSN5 (2 to 257 residues) (unknown origin) transfected in Transetta cells preincubated for 20 mins followed by N-(2-(3-(3’,6’-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9’-xanthen]-5-yl)thioureido)ethyl)-3-(2-(5-methyl-[1,1’-biphenyl]-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)propanamide probe addition and measured after 1 hr by fluorescence polarization assay	ic50	0.1700	uM
5,8-dihydroxy-2-[(1R)-1-hydroxy-4-methylpent-3-enyl]naphthalene-1,4-dione	2111462: Inhibition of N-terminal His6-tagged CSN5 (2 to 257 residues) (unknown origin) transfected in Transetta cells preincubated for 20 mins followed by N-(2-(3-(3’,6’-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9’-xanthen]-5-yl)thioureido)ethyl)-3-(2-(5-methyl-[1,1’-biphenyl]-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)propanamide probe addition and measured after 1 hr by fluorescence polarization assay	ic50	0.1900	uM
5,8-dihydroxy-2-[(1S)-1-hydroxy-4-methylpent-3-enyl]naphthalene-1,4-dione	2111462: Inhibition of N-terminal His6-tagged CSN5 (2 to 257 residues) (unknown origin) transfected in Transetta cells preincubated for 20 mins followed by N-(2-(3-(3’,6’-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9’-xanthen]-5-yl)thioureido)ethyl)-3-(2-(5-methyl-[1,1’-biphenyl]-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)propanamide probe addition and measured after 1 hr by fluorescence polarization assay	ic50	0.2700	uM
8-[[3-[(4-morpholin-4-ylphenyl)methylcarbamoyl]quinolin-8-yl]disulfanyl]-N-[(4-piperidin-1-ylphenyl)methyl]quinoline-3-carboxamide	1480591: Inhibition of CSN5 (unknown origin) using SCFskp2-Nedd8OG as substrate after 1 hr by fluorescence polarization assay	ic50	0.3000	uM
[(1R)-1-(1,4-dihydroxy-5,8-dioxonaphthalen-2-yl)-4-methylpent-3-enyl] acetate	2111462: Inhibition of N-terminal His6-tagged CSN5 (2 to 257 residues) (unknown origin) transfected in Transetta cells preincubated for 20 mins followed by N-(2-(3-(3’,6’-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9’-xanthen]-5-yl)thioureido)ethyl)-3-(2-(5-methyl-[1,1’-biphenyl]-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)propanamide probe addition and measured after 1 hr by fluorescence polarization assay	ic50	0.4300	uM
N-(furan-2-ylmethyl)-8-[[3-(furan-2-ylmethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480591: Inhibition of CSN5 (unknown origin) using SCFskp2-Nedd8OG as substrate after 1 hr by fluorescence polarization assay	ic50	0.5000	uM
N-[(4-methoxyphenyl)methyl]-8-[[3-[(4-methoxyphenyl)methylcarbamoyl]quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480591: Inhibition of CSN5 (unknown origin) using SCFskp2-Nedd8OG as substrate after 1 hr by fluorescence polarization assay	ic50	0.5000	uM
[(1R)-1-(1,4-dihydroxy-5,8-dioxonaphthalen-2-yl)-4-methylpent-3-enyl] 2-methylpropanoate	2111462: Inhibition of N-terminal His6-tagged CSN5 (2 to 257 residues) (unknown origin) transfected in Transetta cells preincubated for 20 mins followed by N-(2-(3-(3’,6’-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9’-xanthen]-5-yl)thioureido)ethyl)-3-(2-(5-methyl-[1,1’-biphenyl]-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)propanamide probe addition and measured after 1 hr by fluorescence polarization assay	ic50	0.6000	uM
6-methylquinoline-8-thiol	1480591: Inhibition of CSN5 (unknown origin) using SCFskp2-Nedd8OG as substrate after 1 hr by fluorescence polarization assay	ic50	1.6000	uM
5,8-dihydroxy-6-(4-methylpent-3-enyl)naphthalene-1,4-dione	2111462: Inhibition of N-terminal His6-tagged CSN5 (2 to 257 residues) (unknown origin) transfected in Transetta cells preincubated for 20 mins followed by N-(2-(3-(3’,6’-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9’-xanthen]-5-yl)thioureido)ethyl)-3-(2-(5-methyl-[1,1’-biphenyl]-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)propanamide probe addition and measured after 1 hr by fluorescence polarization assay	ic50	2.5100	uM
5-methylquinoline-8-thiol	1480591: Inhibition of CSN5 (unknown origin) using SCFskp2-Nedd8OG as substrate after 1 hr by fluorescence polarization assay	ic50	2.9000	uM
N-(2-thiophen-2-ylethyl)-8-[[3-(2-thiophen-2-ylethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480591: Inhibition of CSN5 (unknown origin) using SCFskp2-Nedd8OG as substrate after 1 hr by fluorescence polarization assay	ic50	4.0000	uM
N-[2-(furan-2-yl)ethyl]-8-[[3-[2-(furan-2-yl)ethylcarbamoyl]quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480591: Inhibition of CSN5 (unknown origin) using SCFskp2-Nedd8OG as substrate after 1 hr by fluorescence polarization assay	ic50	6.9000	uM
N-(1,3-benzodioxol-5-ylmethyl)-8-[[3-(1,3-benzodioxol-5-ylmethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480591: Inhibition of CSN5 (unknown origin) using SCFskp2-Nedd8OG as substrate after 1 hr by fluorescence polarization assay	ic50	7.0000	uM
N-(pyridin-4-ylmethyl)-8-[[3-(pyridin-4-ylmethylcarbamoyl)quinolin-8-yl]disulfanyl]quinoline-3-carboxamide	1480591: Inhibition of CSN5 (unknown origin) using SCFskp2-Nedd8OG as substrate after 1 hr by fluorescence polarization assay	ic50	7.0000	uM
3-methylquinoline-8-thiol	1480591: Inhibition of CSN5 (unknown origin) using SCFskp2-Nedd8OG as substrate after 1 hr by fluorescence polarization assay	ic50	7.1000	uM

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol AF	increases expression	2
Arsenic Trioxide	affects cotreatment, decreases expression, increases localization	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
3,3’-dimethylbisphenol A	increases expression	1
dicrotophos	decreases expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
beta-methylcholine	affects expression	1
cylindrospermopsin	increases expression	1
deguelin	decreases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Antimycin A	decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Cisplatin	increases response to substance	1
Diethylhexyl Phthalate	increases expression	1
Docosahexaenoic Acids	affects cotreatment, decreases expression	1
Emodin	affects cotreatment, decreases expression	1
Environmental Pollutants	affects expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1

ChEMBL screening assays

48 unique, capped per target: 48 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4049706	Binding	Inhibition of CSN5 (unknown origin) using SCFskp2-Nedd8OG as substrate after 1 hr by fluorescence polarization assay	Discovery of an Inhibitor of the Proteasome Subunit Rpn11. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.