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Information on EC 2.3.2.32 - cullin-RING-type E3 NEDD8 transferase and Organism(s) Homo sapiens and UniProt Accession P62877

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EC Tree
     2 Transferases
         2.3 Acyltransferases
             2.3.2 Aminoacyltransferases
                2.3.2.32 cullin-RING-type E3 NEDD8 transferase
IUBMB Comments
Some RING-type E3 ubiquitin transferase (EC 2.3.2.27) are not able to bind a substrate protein directly. Instead, they form a complex with a cullin scaffold protein and a substrate recognition module, which is named CRL for Cullin-RING-Ligase. The cullin protein needs to be activated by the ubiquitin-like protein NEDD8 in a process known as neddylation. The transfer of NEDD8 from a NEDD8-specific E2 enzyme onto the cullin protein is a secondary function of the RING-type E3 ubiquitin transferase in the CRL complex. The process requires auxiliary factors that belong to the DCN1 (defective in cullin neddylation 1) family.
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Homo sapiens
UNIPROT: P62877
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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
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[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine
+
[cullin]-L-lysine
=
[E2 NEDD8-conjugating enzyme]-L-cysteine
+
[cullin]-N6-[NEDD8-protein]-yl-L-lysine
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine
+
[cullin]-L-lysine
=
[E2 NEDD8-conjugating enzyme]-L-cysteine
+
[cullin]-N6-[NEDD8-protein]-yl-L-lysine
Synonyms
sccro, dcun1d1, cullin-2, rbx-1, dcn-1, dcun1d5, dcn1p, dcnl5, nedd8 e3 ligase, cullin 2-rbx1 e3 ligase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
cullin 2-RBX1 E3 ligase
-
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Dcn1
-
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DCN1-like protein 5
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DCUN1D1
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RBX-1
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ROC1
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-
SCCRO
-
-
PATHWAY SOURCE
PATHWAYS
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-
SYSTEMATIC NAME
IUBMB Comments
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine:[cullin] [NEDD8-protein] transferase (isopeptide bond-forming; RING-type)
Some RING-type E3 ubiquitin transferase (EC 2.3.2.27) are not able to bind a substrate protein directly. Instead, they form a complex with a cullin scaffold protein and a substrate recognition module, which is named CRL for Cullin-RING-Ligase. The cullin protein needs to be activated by the ubiquitin-like protein NEDD8 in a process known as neddylation. The transfer of NEDD8 from a NEDD8-specific E2 enzyme onto the cullin protein is a secondary function of the RING-type E3 ubiquitin transferase in the CRL complex. The process requires auxiliary factors that belong to the DCN1 (defective in cullin neddylation 1) family.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
[E2 NEDD8-conjugating enzyme Ubc12]-S-[NEDD8-protein]-yl-L-cysteine + [cullin]-L-lysine
[E2 NEDD8-conjugating enzyme Ubc12]-L-cysteine + [cullin]-N6-[NEDD8-protein]-yl-L-lysine
show the reaction diagram
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-
-
?
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin]-L-lysine
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin]-N6-[NEDD8-protein]-yl-L-lysine
show the reaction diagram
-
-
-
?
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin 1]-L-lysine
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin 1]-N6-[NEDD8-protein]-yl-L-lysine
show the reaction diagram
-
-
-
-
?
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin 1]-L-lysine720
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin 1]-N6-[NEDD8-protein]-yl-L-lysine720
show the reaction diagram
-
-
-
-
?
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin 2]-L-lysine
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin 2]-N6-[NEDD8-protein]-yl-L-lysine
show the reaction diagram
-
-
-
-
?
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin 3]-L-lysine
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin 3]-N6-[NEDD8-protein]-yl-L-lysine
show the reaction diagram
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-
-
-
?
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin 4]-L-lysine
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin 4]-N6-[NEDD8-protein]-yl-L-lysine
show the reaction diagram
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-
-
-
?
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin Cdc53]-L-lysine
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin Cdc53]-N6-[NEDD8-protein]-yl-L-lysine
show the reaction diagram
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-
-
-
?
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin-1]-L-lysine
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin-1]-N6-[NEDD8-protein]-yl-L-lysine
show the reaction diagram
-
-
-
-
?
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin]-L-lysine
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin]-N6-[NEDD8-protein]-yl-L-lysine
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin]-L-lysine
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin]-N6-[NEDD8-protein]-yl-L-lysine
show the reaction diagram
-
-
-
?
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin 1]-L-lysine
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin 1]-N6-[NEDD8-protein]-yl-L-lysine
show the reaction diagram
-
-
-
-
?
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin 1]-L-lysine720
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin 1]-N6-[NEDD8-protein]-yl-L-lysine720
show the reaction diagram
-
-
-
-
?
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin 2]-L-lysine
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin 2]-N6-[NEDD8-protein]-yl-L-lysine
show the reaction diagram
-
-
-
-
?
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin 3]-L-lysine
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin 3]-N6-[NEDD8-protein]-yl-L-lysine
show the reaction diagram
-
-
-
-
?
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin 4]-L-lysine
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin 4]-N6-[NEDD8-protein]-yl-L-lysine
show the reaction diagram
-
-
-
-
?
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin Cdc53]-L-lysine
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin Cdc53]-N6-[NEDD8-protein]-yl-L-lysine
show the reaction diagram
-
-
-
-
?
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin-1]-L-lysine
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin-1]-N6-[NEDD8-protein]-yl-L-lysine
show the reaction diagram
-
-
-
-
?
[E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine + [cullin]-L-lysine
[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin]-N6-[NEDD8-protein]-yl-L-lysine
show the reaction diagram
-
-
-
-
?
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
down-regulation of RBX1 significantly induces RhoB accumulation and blocks tumor suppressor RhoB degradation in the presence of cycloheximide
metabolism
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
RBX1_HUMAN
108
0
12274
Swiss-Prot
other Location (Reliability: 3)
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
DCNL5 is a direct substrate of the kinase IKKalpha during immune signalling. Upon activation of Toll-like receptors, DCNL5 gets rapidly and transiently phosphorylated on N-terminal serine residue S41
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, using 2% (w/v) PEG3350, 0.1M HEPES, 0.2 M L-Pro, pH 8.0
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hanging drop vapor diffusion method, using about 20% (w/v) PEG3350, 0.2 M ammonium citrate, pH 7.0
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structures of the neddylated and deneddylated COP9 signalosome-cullin-2 complexes. The structures suggest a conserved mechanism of COP9 signalosome activation, consisting of conformational clamping of the cullin-2 substrate by COP9 signalosome subunits CSN2/CSN4, release of the catalytic CSN5/CSN6 heterodimer and finally activation of the CSN5 deneddylation machinery. Cullin-2 activates CSN5/CSN6 in a neddylation-independent manner
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
I44A
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the mutation reduces cullin NEDD8ylation activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
glutathione affinity column chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in 293T cells
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expressed in Escherichia coli or insect cells
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expressed in MEF cells
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
development of peptides to probe the protein-protein interaction between the cullin-2 scaffold protein and the adaptor subunit elongin BC within the context of the von Hippel-Lindau complex. Peptides MSLKPRVV and MS-cyclohexylglycine-KPRVV can disrupt the native interaction between the von Hippel-Landau complex and Cul2
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Onel, M.; Sumbul, F.; Liu, J.; Nussinov, R.; Haliloglu, T.
Cullin neddylation may allosterically tune polyubiquitin chain length and topology
Biochem. J.
474
781-795
2017
Homo sapiens (P62877)
Manually annotated by BRENDA team
Duda, D.; Borg, L.; Scott, D.; Hunt, H.; Hammel, M.; Schulman, B.
Structural insights into NEDD8 activation of Cullin-RING ligases conformational control of conjugation
Cell
134
995-1006
2008
Homo sapiens
Manually annotated by BRENDA team
Scott, D.; Sviderskiy, V.; Monda, J.; Lydeard, J.; Cho, S.; Harper, J.; Schulman, B.
Structure of a RING E3 trapped in action reveals ligation mechanism for the ubiquitin-like protein NEDD8
Cell
157
1671-1684
2014
Homo sapiens
Manually annotated by BRENDA team
Megumi, Y.; Miyauchi, Y.; Sakurai, H.; Nobeyama, H.; Lorick, K.; Nakamura, E.; Chiba, T.; Tanaka, K.; Weissman, A.; Kirisako, T.; Ogawa, O.; Iwai, K.
Multiple roles of Rbx1 in the VBC-Cul2 ubiquitin ligase complex
Genes Cells
10
679-691
2005
Homo sapiens
Manually annotated by BRENDA team
Kamura, T.; Conrad, M.; Yan, Q.; Conaway, R.; Conaway, J.
The Rbx1 subunit of SCF and VHL E3 ubiquitin ligase activates Rub1 modification of cullins Cdc53 and Cul2
Genes Dev.
13
2928-2933
1999
Homo sapiens
Manually annotated by BRENDA team
Huang, G.; Kaufman, A.; Ramanathan, Y.; Singh, B.
SCCRO (DCUN1D1) promotes nuclear translocation and assembly of the neddylation E3 complex
J. Biol. Chem.
286
10297-10304
2011
Homo sapiens
Manually annotated by BRENDA team
Huang, D.; Ayrault, O.; Hunt, H.; Taherbhoy, A.; Duda, D.; Scott, D.; Borg, L.; Neale, G.; Murray, P.; Roussel, M.; Schulman, B.
E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification
Mol. Cell.
33
483-495
2009
Homo sapiens
Manually annotated by BRENDA team
Xu, J.; Li, L.; Yu, G.; Ying, W.; Gao, Q.; Zhang, W.; Li, X.; Ding, C.; Jiang, Y.; Wei, D.; Duan, S.; Lei, Q.; Li, P.; Shi, T.; Qian, X.; Qin, J.; Jia, L.
The neddylation-cullin 2-RBX1 E3 ligase axis targets tumor suppressor RhoB for degradation in liver cancer
Mol. Cell. Proteomics
14
499-509
2015
Homo sapiens
Manually annotated by BRENDA team
Sakata, E.; Yamaguchi, Y.; Miyauchi, Y.; Iwai, K.; Chiba, T.; Saeki, Y.; Matsuda, N.; Tanaka, K.; Kato, K.
Direct interactions between NEDD8 and ubiquitin E2 conjugating enzymes upregulate cullin-based E3 ligase activity
Nat. Struct. Mol. Biol.
14
167-168
2007
Homo sapiens
Manually annotated by BRENDA team
Rahighi, S.; Dikic, I.
Conformational flexibility and rotation of the RING domain in activation of cullin-RING ligases
Nat. Struct. Mol. Biol.
18
863-865
2011
Homo sapiens
-
Manually annotated by BRENDA team
Calabrese, M.; Scott, D.; Duda, D.; Grace, C.; Kurinov, I.; Kriwacki, R.; Schulman, B.
A RING E3-substrate complex poised for ubiquitin-like protein transfer Structural insights into cullin-RING ligases
Nat. Struct. Mol. Biol.
18
947-949
2011
Homo sapiens
Manually annotated by BRENDA team
Monda, J.; Scott, D.; Miller, D.; Lydeard, J.; King, D.; Harper, J.; Bennett, E.; Schulman, B.
Structural conservation of distinctive N-terminal acetylation-dependent interactions across a family of mammalian NEDD8 ligation enzymes
Structure
21
42-53
2013
Homo sapiens
Manually annotated by BRENDA team
Cardote, T.A.F.; Ciulli, A.
Structure-guided design of peptides as tools to probe the protein-protein interaction between cullin-2 and elongin BC substrate adaptor in cullin RING E3 ubiquitin ligases
ChemMedChem
12
1491-1496
2017
Homo sapiens (Q13617)
Manually annotated by BRENDA team
Coleman, K.E.; Bekes, M.; Chapman, J.R.; Crist, S.B.; Jones, M.J.; Ueberheide, B.M.; Huang, T.T.
SENP8 limits aberrant neddylation of NEDD8 pathway components to promote cullin-RING ubiquitin ligase function
eLife
6
e24325
2017
Homo sapiens (P62877)
Manually annotated by BRENDA team
Faull, S.V.; Lau, A.M.C.; Martens, C.; Ahdash, Z.; Hansen, K.; Yebenes, H.; Schmidt, C.; Beuron, F.; Cronin, N.B.; Morris, E.P.; Politis, A.
Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome
Nat. Commun.
10
3814
2019
Homo sapiens (Q13617)
Manually annotated by BRENDA team
Baek, K.; Krist, D.T.; Prabu, J.R.; Hill, S.; Kluegel, M.; Neumaier, L.M.; von Gronau, S.; Kleiger, G.; Schulman, B.A.
NEDD8 nucleates a multivalent cullin-RING-UBE2D ubiquitin ligation assembly
Nature
578
461-466
2020
Homo sapiens (P62877)
Manually annotated by BRENDA team
Thomas, Y.; Scott, D.C.; Kristariyanto, Y.A.; Rinehart, J.; Clark, K.; Cohen, P.; Kurz, T.
The NEDD8 E3 ligase DCNL5 is phosphorylated by IKK alpha during Toll-like receptor activation
PLoS ONE
13
e0199197
2018
Homo sapiens (Q9BTE7)
Manually annotated by BRENDA team