9EG8

Cryo-EM structure of COP9 signalosome precatalytic state with neddylated cullin-4A

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0000338	biological_process	protein deneddylation
A	0005095	molecular_function	GTPase inhibitor activity
A	0005515	molecular_function	protein binding
A	0005634	cellular_component	nucleus
A	0005654	cellular_component	nucleoplasm
A	0005737	cellular_component	cytoplasm
A	0005829	cellular_component	cytosol
A	0007254	biological_process	JNK cascade
A	0008180	cellular_component	COP9 signalosome
A	0045116	biological_process	protein neddylation
A	2000434	biological_process	regulation of protein neddylation
B	0000122	biological_process	negative regulation of transcription by RNA polymerase II
B	0000338	biological_process	protein deneddylation
B	0003714	molecular_function	transcription corepressor activity
B	0005515	molecular_function	protein binding
B	0005634	cellular_component	nucleus
B	0005654	cellular_component	nucleoplasm
B	0005737	cellular_component	cytoplasm
B	0005829	cellular_component	cytosol
B	0006366	biological_process	transcription by RNA polymerase II
B	0006468	biological_process	protein phosphorylation
B	0007165	biological_process	signal transduction
B	0008180	cellular_component	COP9 signalosome
B	0030182	biological_process	neuron differentiation
B	0032991	cellular_component	protein-containing complex
B	0045116	biological_process	protein neddylation
B	0045171	cellular_component	intercellular bridge
B	2000434	biological_process	regulation of protein neddylation
C	0000338	biological_process	protein deneddylation
C	0005515	molecular_function	protein binding
C	0005634	cellular_component	nucleus
C	0005654	cellular_component	nucleoplasm
C	0005737	cellular_component	cytoplasm
C	0005829	cellular_component	cytosol
C	0006511	biological_process	ubiquitin-dependent protein catabolic process
C	0007165	biological_process	signal transduction
C	0008180	cellular_component	COP9 signalosome
C	0009416	biological_process	response to light stimulus
C	0043516	biological_process	regulation of DNA damage response, signal transduction by p53 class mediator
C	0045116	biological_process	protein neddylation
C	0048471	cellular_component	perinuclear region of cytoplasm
C	2000434	biological_process	regulation of protein neddylation
D	0000338	biological_process	protein deneddylation
D	0005515	molecular_function	protein binding
D	0005634	cellular_component	nucleus
D	0005654	cellular_component	nucleoplasm
D	0005737	cellular_component	cytoplasm
D	0005829	cellular_component	cytosol
D	0008021	cellular_component	synaptic vesicle
D	0008180	cellular_component	COP9 signalosome
D	0016607	cellular_component	nuclear speck
D	0019784	molecular_function	deNEDDylase activity
D	0031410	cellular_component	cytoplasmic vesicle
D	0032991	cellular_component	protein-containing complex
D	0045116	biological_process	protein neddylation
D	2000434	biological_process	regulation of protein neddylation
E	0000338	biological_process	protein deneddylation
E	0000785	cellular_component	chromatin
E	0003713	molecular_function	transcription coactivator activity
E	0003743	molecular_function	translation initiation factor activity
E	0005515	molecular_function	protein binding
E	0005634	cellular_component	nucleus
E	0005654	cellular_component	nucleoplasm
E	0005737	cellular_component	cytoplasm
E	0005829	cellular_component	cytosol
E	0005852	cellular_component	eukaryotic translation initiation factor 3 complex
E	0006412	biological_process	translation
E	0006413	biological_process	translational initiation
E	0006508	biological_process	proteolysis
E	0008021	cellular_component	synaptic vesicle
E	0008180	cellular_component	COP9 signalosome
E	0008233	molecular_function	peptidase activity
E	0008237	molecular_function	metallopeptidase activity
E	0016787	molecular_function	hydrolase activity
E	0019784	molecular_function	deNEDDylase activity
E	0019899	molecular_function	enzyme binding
E	0031410	cellular_component	cytoplasmic vesicle
E	0035718	molecular_function	macrophage migration inhibitory factor binding
E	0043066	biological_process	negative regulation of apoptotic process
E	0043687	biological_process	post-translational protein modification
E	0045116	biological_process	protein neddylation
E	0045944	biological_process	positive regulation of transcription by RNA polymerase II
E	0046328	biological_process	regulation of JNK cascade
E	0046872	molecular_function	metal ion binding
E	0048471	cellular_component	perinuclear region of cytoplasm
E	0051091	biological_process	positive regulation of DNA-binding transcription factor activity
E	0051726	biological_process	regulation of cell cycle
E	0101005	molecular_function	deubiquitinase activity
E	0140492	molecular_function	metal-dependent deubiquitinase activity
E	1903894	biological_process	regulation of IRE1-mediated unfolded protein response
E	1990182	biological_process	exosomal secretion
E	2000434	biological_process	regulation of protein neddylation
F	0000338	biological_process	protein deneddylation
F	0005515	molecular_function	protein binding
F	0005634	cellular_component	nucleus
F	0005654	cellular_component	nucleoplasm
F	0005737	cellular_component	cytoplasm
F	0005829	cellular_component	cytosol
F	0008180	cellular_component	COP9 signalosome
F	0008233	molecular_function	peptidase activity
F	0045116	biological_process	protein neddylation
F	0048471	cellular_component	perinuclear region of cytoplasm
F	0140492	molecular_function	metal-dependent deubiquitinase activity
F	2000434	biological_process	regulation of protein neddylation
G	0000338	biological_process	protein deneddylation
G	0005515	molecular_function	protein binding
G	0005634	cellular_component	nucleus
G	0005654	cellular_component	nucleoplasm
G	0005737	cellular_component	cytoplasm
G	0005829	cellular_component	cytosol
G	0008180	cellular_component	COP9 signalosome
G	0032991	cellular_component	protein-containing complex
G	2000434	biological_process	regulation of protein neddylation
H	0000338	biological_process	protein deneddylation
H	0005515	molecular_function	protein binding
H	0005634	cellular_component	nucleus
H	0005654	cellular_component	nucleoplasm
H	0005737	cellular_component	cytoplasm
H	0005829	cellular_component	cytosol
H	0006468	biological_process	protein phosphorylation
H	0007250	biological_process	activation of NF-kappaB-inducing kinase activity
H	0008180	cellular_component	COP9 signalosome
H	0008285	biological_process	negative regulation of cell population proliferation
H	0045116	biological_process	protein neddylation
H	0048471	cellular_component	perinuclear region of cytoplasm
H	0070062	cellular_component	extracellular exosome
H	2000434	biological_process	regulation of protein neddylation
I	0005515	molecular_function	protein binding
I	0005634	cellular_component	nucleus
I	0005654	cellular_component	nucleoplasm
I	0005737	cellular_component	cytoplasm
I	0005829	cellular_component	cytosol
I	0006508	biological_process	proteolysis
I	0006511	biological_process	ubiquitin-dependent protein catabolic process
I	0009653	biological_process	anatomical structure morphogenesis
I	0016567	biological_process	protein ubiquitination
I	0019941	biological_process	modification-dependent protein catabolic process
I	0030162	biological_process	regulation of proteolysis
I	0031386	molecular_function	protein tag activity
I	0031625	molecular_function	ubiquitin protein ligase binding
I	0036211	biological_process	protein modification process
I	0045116	biological_process	protein neddylation
I	0070062	cellular_component	extracellular exosome
I	0072757	biological_process	cellular response to camptothecin
I	0098794	cellular_component	postsynapse
I	0098978	cellular_component	glutamatergic synapse
I	0150052	biological_process	regulation of postsynapse assembly
J	0000082	biological_process	G1/S transition of mitotic cell cycle
J	0001701	biological_process	in utero embryonic development
J	0005515	molecular_function	protein binding
J	0005634	cellular_component	nucleus
J	0005654	cellular_component	nucleoplasm
J	0005737	cellular_component	cytoplasm
J	0006281	biological_process	DNA repair
J	0006289	biological_process	nucleotide-excision repair
J	0006974	biological_process	DNA damage response
J	0007283	biological_process	spermatogenesis
J	0008283	biological_process	cell population proliferation
J	0010506	biological_process	regulation of autophagy
J	0016567	biological_process	protein ubiquitination
J	0030174	biological_process	regulation of DNA-templated DNA replication initiation
J	0031297	biological_process	replication fork processing
J	0031464	cellular_component	Cul4A-RING E3 ubiquitin ligase complex
J	0031625	molecular_function	ubiquitin protein ligase binding
J	0032502	biological_process	developmental process
J	0032814	biological_process	regulation of natural killer cell activation
J	0034644	biological_process	cellular response to UV
J	0040029	biological_process	epigenetic regulation of gene expression
J	0042110	biological_process	T cell activation
J	0042127	biological_process	regulation of cell population proliferation
J	0042254	biological_process	ribosome biogenesis
J	0042981	biological_process	regulation of apoptotic process
J	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
J	0045732	biological_process	positive regulation of protein catabolic process
J	0045995	biological_process	regulation of embryonic development
J	0048511	biological_process	rhythmic process
J	0051246	biological_process	regulation of protein metabolic process
J	0060964	biological_process	regulation of miRNA-mediated gene silencing
J	0061630	molecular_function	ubiquitin protein ligase activity
J	0080008	cellular_component	Cul4-RING E3 ubiquitin ligase complex
J	0080135	biological_process	regulation of cellular response to stress
J	0097193	biological_process	intrinsic apoptotic signaling pathway
J	0140627	biological_process	ubiquitin-dependent protein catabolic process via the C-end degron rule pathway
J	0160072	molecular_function	ubiquitin ligase complex scaffold activity
J	1901987	biological_process	regulation of cell cycle phase transition
J	1902412	biological_process	regulation of mitotic cytokinesis
J	1904178	biological_process	negative regulation of adipose tissue development
J	2000036	biological_process	regulation of stem cell population maintenance
K	0000082	biological_process	G1/S transition of mitotic cell cycle
K	0000122	biological_process	negative regulation of transcription by RNA polymerase II
K	0000165	biological_process	MAPK cascade
K	0000209	biological_process	protein polyubiquitination
K	0004842	molecular_function	ubiquitin-protein transferase activity
K	0005515	molecular_function	protein binding
K	0005634	cellular_component	nucleus
K	0005654	cellular_component	nucleoplasm
K	0005737	cellular_component	cytoplasm
K	0005794	cellular_component	Golgi apparatus
K	0005813	cellular_component	centrosome
K	0005829	cellular_component	cytosol
K	0006281	biological_process	DNA repair
K	0006283	biological_process	transcription-coupled nucleotide-excision repair
K	0006289	biological_process	nucleotide-excision repair
K	0006355	biological_process	regulation of DNA-templated transcription
K	0006511	biological_process	ubiquitin-dependent protein catabolic process
K	0006513	biological_process	protein monoubiquitination
K	0006879	biological_process	intracellular iron ion homeostasis
K	0006974	biological_process	DNA damage response
K	0007283	biological_process	spermatogenesis
K	0007346	biological_process	regulation of mitotic cell cycle
K	0008270	molecular_function	zinc ion binding
K	0008283	biological_process	cell population proliferation
K	0010506	biological_process	regulation of autophagy
K	0010564	biological_process	regulation of cell cycle process
K	0010824	biological_process	regulation of centrosome duplication
K	0014033	biological_process	neural crest cell differentiation
K	0016567	biological_process	protein ubiquitination
K	0016740	molecular_function	transferase activity
K	0019005	cellular_component	SCF ubiquitin ligase complex
K	0019788	molecular_function	NEDD8 transferase activity
K	0030174	biological_process	regulation of DNA-templated DNA replication initiation
K	0030510	biological_process	regulation of BMP signaling pathway
K	0030891	cellular_component	VCB complex
K	0031146	biological_process	SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
K	0031297	biological_process	replication fork processing
K	0031461	cellular_component	cullin-RING ubiquitin ligase complex
K	0031462	cellular_component	Cul2-RING ubiquitin ligase complex
K	0031463	cellular_component	Cul3-RING ubiquitin ligase complex
K	0031464	cellular_component	Cul4A-RING E3 ubiquitin ligase complex
K	0031465	cellular_component	Cul4B-RING E3 ubiquitin ligase complex
K	0031466	cellular_component	Cul5-RING ubiquitin ligase complex
K	0031467	cellular_component	Cul7-RING ubiquitin ligase complex
K	0031625	molecular_function	ubiquitin protein ligase binding
K	0032006	biological_process	regulation of TOR signaling
K	0032436	biological_process	positive regulation of proteasomal ubiquitin-dependent protein catabolic process
K	0032480	biological_process	negative regulation of type I interferon production
K	0032814	biological_process	regulation of natural killer cell activation
K	0034450	molecular_function	ubiquitin-ubiquitin ligase activity
K	0034599	biological_process	cellular response to oxidative stress
K	0034644	biological_process	cellular response to UV
K	0040029	biological_process	epigenetic regulation of gene expression
K	0042110	biological_process	T cell activation
K	0042127	biological_process	regulation of cell population proliferation
K	0042752	biological_process	regulation of circadian rhythm
K	0042770	biological_process	signal transduction in response to DNA damage
K	0042981	biological_process	regulation of apoptotic process
K	0043123	biological_process	positive regulation of canonical NF-kappaB signal transduction
K	0043124	biological_process	negative regulation of canonical NF-kappaB signal transduction
K	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
K	0043687	biological_process	post-translational protein modification
K	0044314	biological_process	protein K27-linked ubiquitination
K	0044877	molecular_function	protein-containing complex binding
K	0045116	biological_process	protein neddylation
K	0045732	biological_process	positive regulation of protein catabolic process
K	0045995	biological_process	regulation of embryonic development
K	0046627	biological_process	negative regulation of insulin receptor signaling pathway
K	0046872	molecular_function	metal ion binding
K	0050727	biological_process	regulation of inflammatory response
K	0051298	biological_process	centrosome duplication
K	0051726	biological_process	regulation of cell cycle
K	0060090	molecular_function	molecular adaptor activity
K	0060173	biological_process	limb development
K	0060271	biological_process	cilium assembly
K	0060964	biological_process	regulation of miRNA-mediated gene silencing
K	0061629	molecular_function	RNA polymerase II-specific DNA-binding transcription factor binding
K	0061630	molecular_function	ubiquitin protein ligase activity
K	0061663	molecular_function	NEDD8 ligase activity
K	0062197	biological_process	cellular response to chemical stress
K	0070936	biological_process	protein K48-linked ubiquitination
K	0071230	biological_process	cellular response to amino acid stimulus
K	0080008	cellular_component	Cul4-RING E3 ubiquitin ligase complex
K	0080135	biological_process	regulation of cellular response to stress
K	0090090	biological_process	negative regulation of canonical Wnt signaling pathway
K	0090734	cellular_component	site of DNA damage
K	0097602	molecular_function	cullin family protein binding
K	0140627	biological_process	ubiquitin-dependent protein catabolic process via the C-end degron rule pathway
K	0160240	biological_process	RNA polymerase II transcription initiation surveillance
K	0160276	biological_process	negative regulation of beige fat cell differentiation
K	1900076	biological_process	regulation of cellular response to insulin stimulus
K	1901524	biological_process	regulation of mitophagy
K	1901525	biological_process	negative regulation of mitophagy
K	1901987	biological_process	regulation of cell cycle phase transition
K	1902412	biological_process	regulation of mitotic cytokinesis
K	1902499	biological_process	positive regulation of protein autoubiquitination
K	1902883	biological_process	negative regulation of response to oxidative stress
K	1904178	biological_process	negative regulation of adipose tissue development
K	1904263	biological_process	positive regulation of TORC1 signaling
K	1904415	biological_process	regulation of xenophagy
K	1990116	biological_process	ribosome-associated ubiquitin-dependent protein catabolic process
K	2000001	biological_process	regulation of DNA damage checkpoint
K	2000036	biological_process	regulation of stem cell population maintenance
K	2000104	biological_process	negative regulation of DNA-templated DNA replication

Functional Information from PROSITE/UniProt

site_id	PS00299
Number of Residues	26
Details	UBIQUITIN_1 Ubiquitin domain signature. KerVeEkegIPpqqQrLIYsGkqmnD

Chain	Residue	Details
I	LYS27-ASP52

---

site_id	PS01256
Number of Residues	28
Details	CULLIN_1 Cullin family signature. LKkrIesLIDRdYMeRdkdnpnqYhYvA

Chain	Residue	Details
J	LEU732-ALA759

---

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	270
Details	Domain: {"description":"MPN","evidences":[{"source":"PROSITE-ProRule","id":"PRU01182","evidenceCode":"ECO:0000255"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI2
Number of Residues	13
Details	Motif: {"description":"JAMM motif","evidences":[{"source":"PROSITE-ProRule","id":"PRU01182","evidenceCode":"ECO:0000255"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI3
Number of Residues	3
Details	Binding site: {"evidences":[{"source":"PROSITE-ProRule","id":"PRU01182","evidenceCode":"ECO:0000255"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI4
Number of Residues	2
Details	Region: {"description":"Interaction with UBE1C","evidences":[{"source":"PubMed","id":"14690597","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI5
Number of Residues	2
Details	Site: {"description":"Interaction with UBE1C","evidences":[{"source":"PubMed","id":"14690597","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI6
Number of Residues	1
Details	Modified residue: {"description":"(Microbial infection) Deamidated glutamine","evidences":[{"source":"PubMed","id":"20688984","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"21903097","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"23175788","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"23589306","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"26632597","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI7
Number of Residues	1
Details	Modified residue: {"description":"N6-acetyllysine","evidences":[{"source":"UniProtKB","id":"P29595","evidenceCode":"ECO:0000250"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI8
Number of Residues	2
Details	Cross-link: {"description":"Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins)","evidences":[{"source":"PubMed","id":"38316879","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI9
Number of Residues	2
Details	Cross-link: {"description":"Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8)","evidences":[{"source":"PubMed","id":"38316879","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI10
Number of Residues	661
Details	Domain: {"description":"PCI","evidences":[{"source":"PROSITE-ProRule","id":"PRU01185","evidenceCode":"ECO:0000255"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI11
Number of Residues	1
Details	Modified residue: {"description":"Phosphoserine","evidences":[{"source":"UniProtKB","id":"O88543","evidenceCode":"ECO:0000250"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI12
Number of Residues	1
Details	Modified residue: {"description":"N-acetylalanine","evidences":[{"source":"PubMed","id":"18850735","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"19413330","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI13
Number of Residues	1
Details	Modified residue: {"description":"N6-acetyllysine","evidences":[{"source":"PubMed","id":"19608861","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI14
Number of Residues	7
Details	Binding site: {"evidences":[{"source":"PubMed","id":"11961546","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"38605244","evidenceCode":"ECO:0000269"},{"source":"PDB","id":"1LDJ","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"1LDK","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"1U6G","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"2HYE","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3DPL","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3DQV","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3RTR","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4F52","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4P5O","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"8Q7H","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"8RHZ","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI15
Number of Residues	4
Details	Binding site: {"evidences":[{"source":"PubMed","id":"11961546","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"38605244","evidenceCode":"ECO:0000269"},{"source":"PDB","id":"1LDJ","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"1LDK","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"1U6G","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"2HYE","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3DPL","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3DQV","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3RTR","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4F52","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4P5O","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"7Z8B","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"8Q7H","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"8RHZ","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI16
Number of Residues	1
Details	Binding site: {"evidences":[{"source":"PubMed","id":"11961546","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"38605244","evidenceCode":"ECO:0000269"},{"source":"PDB","id":"1LDJ","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"1LDK","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"1U6G","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"2HYE","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3DQV","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3RTR","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4F52","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4P5O","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"8Q7H","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"8RHZ","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---