COPS5

Entrez Summary: N/A
UniProt Summary: 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. {ECO:0000269|PubMed:11285227, ECO:0000269|PubMed:11337588, ECO:0000269|PubMed:12628923, ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:19214193, ECO:0000269|PubMed:20978819, ECO:0000269|PubMed:22609399, ECO:0000269|PubMed:9535219}.

Pfam Domains GO Terms

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
4-Nitroquinoline-1-oxide 0.5μM R08 exp446	-1.99
Ethanol 0.01 R05 exp234	-1.86
Palbociclib 1μM R07 exp382	-1.77
iCRT14 30μM R08 exp492	-1.73
5-Fluorouracil 2μM R00 exp1	-1.71
Aphidicolin 0.4μM R08 exp440	-1.71
Cytochalasin-B 5μM R07 exp349	1.7
Tozasertib 0.1μM R07 exp414	1.74
IL-3 9ng/ml R08 exp493	1.88
PFI-3 10μM R03 exp144	1.88
Taxol 0.004μM R03 exp103	1.95
MLN-4924 0.2μM R00 exp21	3.13

Global Fraction of Cell Lines Where Essential: 704/726

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	1/1
909776.0	1/1
bile duct	28/28
blood	27/28
bone	25/25
breast	31/33
central nervous system	54/56
cervix	4/4
colorectal	17/17
esophagus	13/13
fibroblast	1/1
gastric	14/15
kidney	21/21
liver	20/20
lung	74/75
lymphocyte	14/14
ovary	25/26
pancreas	23/24
peripheral nervous system	14/16
plasma cell	15/15
prostate	1/1
skin	24/24
soft tissue	7/7
thyroid	2/2
upper aerodigestive	18/22
urinary tract	28/29
uterus	5/5

Expression Distribution

macrophage migration inhibitory factor binding
exosomal secretion
extracellular exosome biogenesis
NEDD8-specific protease activity
extracellular vesicle biogenesis
protein deneddylation
regulation of IRE1-mediated unfolded protein response
eukaryotic translation initiation factor 3 complex
nucleotide-excision repair, DNA damage recognition
regulation of endoplasmic reticulum unfolded protein response
COP9 signalosome
translation initiation factor activity
metallopeptidase activity
transcription-coupled nucleotide-excision repair
regulation of response to endoplasmic reticulum stress
metalloendopeptidase activity
thiol-dependent ubiquitin-specific protease activity
nucleotide-excision repair
chromatin
synaptic vesicle
translational initiation
regulation of JNK cascade
regulation of stress-activated MAPK cascade
regulation of stress-activated protein kinase signaling cascade
positive regulation of DNA-binding transcription factor activity
protein deubiquitination
transcription coactivator activity
protein modification by small protein removal
enzyme binding
post-translational protein modification
translation
peptide biosynthetic process
regulation of DNA-binding transcription factor activity
transcription by RNA polymerase II
DNA repair
amide biosynthetic process
peptide metabolic process
cell junction
transcription, DNA-templated
nucleic acid-templated transcription