3DPL

Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation.

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B [auth R]	d3dplr_	Small proteins	RING/U-box	RING/U-box	RING finger domain, C3HC4	RIGG-box protein 1 (RBX1) of SCF ubiquitin ligase complex	(Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
B [auth R]	SCOP2 Family	RING finger domain C3HC4	8028487	4000374	SCOP2 (2022-06-29)
B [auth R]	SCOP2 Superfamily	RING/U-box like	8040866	3000160	SCOP2 (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A [auth C]	PF00888	e3dplC4	A: alpha arrays	X: HTH	H: HTH	T: winged	F: PF00888	ECOD (1.6)
A [auth C]	PF10557	e3dplC3	A: alpha arrays	X: HTH	H: HTH	T: winged	F: PF10557	ECOD (1.6)
A [auth C]	PF00888	e3dplC2	A: alpha superhelices	X: Repetitive alpha hairpins	H: ARM repeat (From Topology)	T: ARM repeat	F: PF00888	ECOD (1.6)
A [auth C]	PF00888	e3dplC1	A: a+b duplicates or obligate multimers	X: a+b domain in cullin-like proteins (From Topology)	H: a+b domain in cullin-like proteins (From Topology)	T: a+b domain in cullin-like proteins	F: PF00888	ECOD (1.6)
B [auth R]	PF12678	e3dplR1	A: few secondary structure elements	X: RING/U-box-like	H: RING/U-box-like	T: RING/U-box	F: PF12678	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A [auth C]	1.20.1310.10	Mainly Alpha	Up-down Bundle	5 helical Cullin repeat like	Cullin Repeats	CATH (4.3.0)
A [auth C]	3.30.230.130	Alpha Beta	2-Layer Sandwich	Ribosomal Protein S5	domain 2	CATH (4.3.0)
A [auth C]	1.10.10.10	Mainly Alpha	Orthogonal Bundle	Arc Repressor Mutant, subunit A	Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain	CATH (4.3.0)
B [auth R]	3.30.40.10	Alpha Beta	2-Layer Sandwich	Herpes Virus-1	Zinc/RING finger domain, C3HC4 (zinc finger)	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A [auth C]	PF00888	Cullin family (Cullin)	Cullin family	-	Repeat
A [auth C]	PF10557	Cullin protein neddylation domain (Cullin_Nedd8)	Cullin protein neddylation domain	This is the neddylation site of cullin proteins which are a family of structurally related proteins containing an evolutionarily conserved cullin domain. With the exception of APC2, each member of the cullin family is modified by Nedd8 and several cu ...	This is the neddylation site of cullin proteins which are a family of structurally related proteins containing an evolutionarily conserved cullin domain. With the exception of APC2, each member of the cullin family is modified by Nedd8 and several cullins function in Ubiquitin-dependent proteolysis, a process in which the 26S proteasome recognises and subsequently degrades a target protein tagged with K48-linked poly-ubiquitin chains. Cullins are molecular scaffolds responsible for assembling the ROC1/Rbx1 RING-based E3 ubiquitin ligases, of which several play a direct role in tumorigenesis. Nedd8/Rub1 is a small ubiquitin-like protein, which was originally found to be conjugated to Cdc53, a cullin component of the SCF (Skp1-Cdc53/CUL1-F-box protein) E3 Ub ligase complex in Saccharomyces cerevisiae, and Nedd8 modification has now emerged as a regulatory pathway of fundamental importance for cell cycle control and for embryogenesis in metazoans. The only identified Nedd8 substrates are cullins. Neddylation results in covalent conjugation of a Nedd8 moiety onto a conserved cullin lysine residue [1].	Domain
B [auth R]	PF12678	RING-H2 zinc finger domain (zf-rbx1)	RING-H2 zinc finger domain	There are 8 cysteine/ histidine residues which are proposed to be the conserved residues involved in zinc binding. The protein, of which this domain is the conserved region, participates in diverse functions relevant to chromosome metabolism and cell ...	There are 8 cysteine/ histidine residues which are proposed to be the conserved residues involved in zinc binding. The protein, of which this domain is the conserved region, participates in diverse functions relevant to chromosome metabolism and cell cycle control [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A [auth C]	Cullin-5	molecular transducer activity signaling receptor activity ubiquitin protein ligase binding protein binding binding ubiquitin-like protein ligase binding enzyme binding aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity transferase activity catalytic activity ubiquitin-protein transferase activity molecular transducer activity signaling receptor activity ubiquitin protein ligase binding protein binding binding ubiquitin-like protein ligase binding enzyme binding aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity transferase activity catalytic activity ubiquitin-protein transferase activity calcium channel activity monoatomic cation transmembrane transporter activity monoatomic ion channel activity monoatomic cation channel activity passive transmembrane transporter activity calcium ion transmembrane transporter activity inorganic molecular entity transmembrane transporter activity channel activity inorganic cation transmembrane transporter activity monoatomic ion transmembrane transporter activity transporter activity metal ion transmembrane transporter activity transmembrane transporter activity protein-macromolecule adaptor activity molecular adaptor activity	cellular response to stimulus ERBB2 signaling pathway regulation of biological process regulation of cellular process cell surface receptor signaling pathway response to stimulus signaling biological regulation cell surface receptor protein tyrosine kinase signaling pathway cell communication ERBB signaling pathway cellular process signal transduction enzyme-linked receptor protein signaling pathway cellular response to stimulus ERBB2 signaling pathway regulation of biological process regulation of cellular process cell surface receptor signaling pathway response to stimulus signaling biological regulation cell surface receptor protein tyrosine kinase signaling pathway cell communication ERBB signaling pathway cellular process signal transduction enzyme-linked receptor protein signaling pathway cell death intracellular signal transduction apoptotic signaling pathway apoptotic process intrinsic apoptotic signaling pathway programmed cell death mitotic cell cycle process cell cycle phase transition cell cycle G1/S transition of mitotic cell cycle cell cycle G1/S phase transition mitotic cell cycle mitotic cell cycle phase transition cell cycle process organonitrogen compound metabolic process primary metabolic process organic substance metabolic process protein ubiquitination macromolecule modification metabolic process protein metabolic process macromolecule metabolic process post-translational protein modification protein modification process protein modification by small protein conjugation protein modification by small protein conjugation or removal organonitrogen compound catabolic process catabolic process proteolysis involved in protein catabolic process proteasomal protein catabolic process protein catabolic process proteasome-mediated ubiquitin-dependent protein catabolic process macromolecule catabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis SCF-dependent proteasomal ubiquitin-dependent protein catabolic process ubiquitin-dependent protein catabolic process organic substance catabolic process	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol cullin-RING ubiquitin ligase complex protein-containing complex ubiquitin ligase complex catalytic complex transferase complex intracellular protein-containing complex Cul5-RING ubiquitin ligase complex SCF ubiquitin ligase complex membrane-bounded organelle intracellular organelle intracellular anatomical structure cytoplasm cellular anatomical entity cytosol cullin-RING ubiquitin ligase complex protein-containing complex ubiquitin ligase complex catalytic complex transferase complex intracellular protein-containing complex Cul5-RING ubiquitin ligase complex SCF ubiquitin ligase complex membrane-bounded organelle intracellular organelle organelle nucleus intracellular membrane-bounded organelle intracellular non-membrane-bounded organelle site of DNA damage chromosome non-membrane-bounded organelle
B [auth R]	RING-box protein 1	aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity ubiquitin-ubiquitin ligase activity ubiquitin-like protein ligase activity ubiquitin protein ligase activity transferase activity catalytic activity ubiquitin-protein transferase activity molecular adaptor activity ubiquitin protein ligase binding protein binding binding aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity ubiquitin-ubiquitin ligase activity ubiquitin-like protein ligase activity ubiquitin protein ligase activity transferase activity catalytic activity ubiquitin-protein transferase activity molecular adaptor activity ubiquitin protein ligase binding protein binding binding ubiquitin-like protein ligase binding enzyme binding cullin family protein binding transcription factor binding RNA polymerase II-specific DNA-binding transcription factor binding DNA-binding transcription factor binding NEDD8 transferase activity NEDD8 ligase activity cation binding transition metal ion binding zinc ion binding ion binding metal ion binding small molecule binding	cellular response to stimulus cellular response to stress response to stimulus DNA damage response response to stress cellular process multicellular organismal process regulation of cellular process cellular biosynthetic process negative regulation of biological process negative regulation of cellular metabolic process negative regulation of type I interferon production organic substance metabolic process cytokine production cellular response to stimulus cellular response to stress response to stimulus DNA damage response response to stress cellular process multicellular organismal process regulation of cellular process cellular biosynthetic process negative regulation of biological process negative regulation of cellular metabolic process negative regulation of type I interferon production organic substance metabolic process cytokine production organic substance biosynthetic process negative regulation of cellular process regulation of cytokine production regulation of multicellular organismal process negative regulation of macromolecule metabolic process regulation of biosynthetic process regulation of biological process type I interferon production cellular metabolic process negative regulation of metabolic process biological regulation negative regulation of cytokine production regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process negative regulation of cellular biosynthetic process regulation of cellular biosynthetic process regulation of gene expression negative regulation of gene expression biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process metabolic process regulation of macromolecule biosynthetic process macromolecule metabolic process negative regulation of multicellular organismal process regulation of metabolic process regulation of type I interferon production developmental process spermatogenesis sexual reproduction reproductive process multicellular organismal reproductive process developmental process involved in reproduction male gamete generation gamete generation signaling negative regulation of signaling regulation of canonical Wnt signaling pathway canonical Wnt signaling pathway regulation of signal transduction negative regulation of cell communication cell communication negative regulation of Wnt signaling pathway signal transduction Wnt signaling pathway regulation of signaling cell surface receptor signaling pathway regulation of Wnt signaling pathway negative regulation of response to stimulus negative regulation of signal transduction negative regulation of canonical Wnt signaling pathway regulation of response to stimulus regulation of cell communication positive regulation of proteasomal protein catabolic process catabolic process positive regulation of protein metabolic process proteolysis involved in protein catabolic process positive regulation of biological process proteasome-mediated ubiquitin-dependent protein catabolic process macromolecule catabolic process regulation of ubiquitin-dependent protein catabolic process regulation of primary metabolic process positive regulation of metabolic process positive regulation of ubiquitin-dependent protein catabolic process regulation of proteolysis regulation of proteolysis involved in protein catabolic process modification-dependent macromolecule catabolic process proteolysis positive regulation of macromolecule metabolic process protein metabolic process organonitrogen compound catabolic process organonitrogen compound metabolic process regulation of protein metabolic process primary metabolic process proteasomal protein catabolic process protein catabolic process regulation of catabolic process positive regulation of protein catabolic process positive regulation of proteolysis involved in protein catabolic process positive regulation of catabolic process regulation of proteasomal ubiquitin-dependent protein catabolic process modification-dependent protein catabolic process positive regulation of proteolysis regulation of proteasomal protein catabolic process positive regulation of proteasomal ubiquitin-dependent protein catabolic process ubiquitin-dependent protein catabolic process organic substance catabolic process regulation of protein catabolic process protein ubiquitination macromolecule modification post-translational protein modification protein modification process protein modification by small protein conjugation protein modification by small protein conjugation or removal intracellular signal transduction intracellular signaling cassette MAPK cascade protein polyubiquitination ubiquitin-dependent protein catabolic process via the C-end degron rule pathway cellular response to acid chemical cellular response to amino acid stimulus response to acid chemical response to organic substance cellular response to chemical stimulus response to chemical response to amino acid DNA metabolic process nucleic acid metabolic process nucleobase-containing compound metabolic process organic cyclic compound metabolic process DNA repair protein K48-linked ubiquitination protein monoubiquitination positive regulation of cell communication positive regulation of signal transduction positive regulation of canonical NF-kappaB signal transduction positive regulation of response to stimulus regulation of intracellular signal transduction positive regulation of cellular process positive regulation of intracellular signal transduction canonical NF-kappaB signal transduction regulation of canonical NF-kappaB signal transduction positive regulation of signaling protein neddylation SCF-dependent proteasomal ubiquitin-dependent protein catabolic process regulation of protein modification process regulation of protein autoubiquitination regulation of protein ubiquitination positive regulation of post-translational protein modification positive regulation of protein modification process regulation of protein modification by small protein conjugation or removal positive regulation of protein modification by small protein conjugation or removal positive regulation of protein ubiquitination regulation of post-translational protein modification protein autoubiquitination positive regulation of protein autoubiquitination positive regulation of TORC1 signaling positive regulation of TOR signaling regulation of TORC1 signaling TOR signaling regulation of TOR signaling TORC1 signaling T cell activation immune system process cell activation lymphocyte activation leukocyte activation response to light stimulus cellular response to radiation response to UV cellular response to environmental stimulus cellular response to light stimulus response to radiation response to abiotic stimulus cellular response to abiotic stimulus cellular response to UV cellular response to chemical stress	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol cullin-RING ubiquitin ligase complex protein-containing complex ubiquitin ligase complex catalytic complex transferase complex intracellular protein-containing complex Cul5-RING ubiquitin ligase complex Cul4-RING E3 ubiquitin ligase complex Cul4A-RING E3 ubiquitin ligase complex membrane-bounded organelle intracellular anatomical structure cytoplasm cellular anatomical entity cytosol cullin-RING ubiquitin ligase complex protein-containing complex ubiquitin ligase complex catalytic complex transferase complex intracellular protein-containing complex Cul5-RING ubiquitin ligase complex Cul4-RING E3 ubiquitin ligase complex Cul4A-RING E3 ubiquitin ligase complex membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen SCF ubiquitin ligase complex Cul7-RING ubiquitin ligase complex Cul3-RING ubiquitin ligase complex Cul4B-RING E3 ubiquitin ligase complex Cul2-RING ubiquitin ligase complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A [auth C]	IPR045093	Cullin	Family
A [auth C]	IPR019559	Cullin protein, neddylation domain	Domain
A [auth C]	IPR016158	Cullin homology domain	Domain
A [auth C]	IPR036388	Winged helix-like DNA-binding domain superfamily	Homologous Superfamily
A [auth C]	IPR016157	Cullin, conserved site	Conserved Site
A [auth C]	IPR036390	Winged helix DNA-binding domain superfamily	Homologous Superfamily
A [auth C]	IPR036317	Cullin homology domain superfamily	Homologous Superfamily
A [auth C]	IPR001373	Cullin, N-terminal	Domain
A [auth C]	IPR016159	Cullin repeat-like-containing domain superfamily	Homologous Superfamily
B [auth R]	IPR024766	Zinc finger, RING-H2-type	Domain
B [auth R]	IPR013083	Zinc finger, RING/FYVE/PHD-type	Homologous Superfamily
B [auth R]	IPR001841	Zinc finger, RING-type	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A [auth C]	Pharos: Q93034	breast carcinoma breast cancer malignant mesothelioma Mammary Neoplasms, Human plasma cell myeloma osteosarcoma psoriasis lymphoplasmacytic lymphoma ovarian cancer rheumatoid arthritis
B [auth R]	Pharos: P62877	Stevens-Johnson syndrome acute myeloid leukemia Drug-Induced Stevens Johnson Syndrome ovarian cancer toxic epidermal necrolysis astrocytic tumor endogenous depression Crohn disease

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.