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AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
-
-
-
-
r
ATP + ubiquitin + [ubiquitin-activating protein UBA1]-L-cysteine
AMP + diphosphate + [ubiquitin-activating protein UBA1]-S-ubiquitinyl-L-cysteine
-
-
-
?
ATP + ubiquitin + [ubiquitin-activating protein Uba3]-L-cysteine
AMP + diphosphate + [ubiquitin-activating protein Uba3]-S-ubiquitinyl-L-cysteine
-
-
-
?
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [UBC12]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
?
ATP + [NEDD8 protein] + [Ubc12]-L-cysteine
AMP + diphosphate + [Ubc12]-S-[NEDD8 protein]-yl-L-cysteine
ATP + [Ubc12]-L-Cys + [NEDD8 protein]
ADP + diphosphate + [Ubc12]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
-
additional information
?
-
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
-
?
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
-
?
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
-
r
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
?
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
?
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
?
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
-
?
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
?
ATP + [NEDD8 protein] + [Ubc12]-L-cysteine
AMP + diphosphate + [Ubc12]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
-
?
ATP + [NEDD8 protein] + [Ubc12]-L-cysteine
AMP + diphosphate + [Ubc12]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
?
additional information
?
-
-
first, the enzyme associates with the Ublp and catalyses adenylation of the carboxy terminus of the ubiquitin-like protein. Second, the enzyme forms a thioester between its catalytic cysteine and the ubiquitin-like protein. Next, the enzyme is loaded with a second ubiquitin-like protein molecule, adenylating the C terminus of this second ubiquitin-like protein while still carrying the first thioester-bound ubiquitin-like protein. Last, the enzyme binds E2 and promotes ubiquitin-like protein transfer to the catalytic cysteine of E2 enzyme
-
-
-
additional information
?
-
NEDD8 activation requires only one of two E1 subunits, UBA3. The other subunit, APPBP1, only contributes by accelerating the activation reaction rate
-
-
-
additional information
?
-
-
the enzyme catalyzes NEDD8 activation by a multistep mechanism. In step 1, ATP and NEDD8 bind the enzyme to form a NEDD8-acyl adenylate intermediate and release diphosphate. In step 2, NEDD8-AMP reacts with the enzyme active-site thiol to form an enzyme-NEDD8 thioester (with high-energy bond). In step 3, a second ATP and NEDD8 bind the enzyme as in the first step to form a ternary complex containing two NEDD8 molecules bound to the enzyme. This enzyme form is competent for transfer of the thioester-bound NEDD8 to a pathway-specific E2 (primarily UBC12; step 4) and is required for the downstream functions of NEDD8 conjugation
-
-
-
additional information
?
-
-
the enzyme exhibits very low activity with ubiquitin, SUMO1, SUMO2, MAPLC3A, GABRAP, GATE-16, Ufm-1, FAT10 and ISG-15
-
-
-
additional information
?
-
-
proteins But1 and But2 proteins bind to the catalytic subunit Uba3
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
-
-
-
-
r
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [UBC12]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
?
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
-
?
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
-
?
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
-
r
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
?
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
?
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
?
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
-
?
ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine
AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
-
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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0.005 - 0.0511
diphosphate
0.0006 - 0.0012
ubiquitin
0.0045
ATP
chimeric Ub1, pH not specified in the publication, temperature not specified in the publication
0.0054
ATP
mutant DELTA946, pH not specified in the publication, temperature not specified in the publication
0.0055
ATP
wild-type, pH not specified in the publication, temperature not specified in the publication
0.02
ATP
mutant DELTA348, pH not specified in the publication, temperature not specified in the publication
0.02
ATP
mutant enzyme I310N, pH and temperature not specified in the publication
0.027
ATP
mutant enzyme Y352H, pH and temperature not specified in the publication
0.08
ATP
wild type enzyme, pH and temperature not specified in the publication
0.103
ATP
wild-type, pH not specified in the publication, temperature not specified in the publication
0.175
ATP
-
at pH 7.5 and 37°C
0.005
diphosphate
wild type enzyme, pH and temperature not specified in the publication
0.0109
diphosphate
mutant enzyme Y352H, pH and temperature not specified in the publication
0.011
diphosphate
-
at pH 7.5 and 37°C
0.0511
diphosphate
mutant enzyme I310N, pH and temperature not specified in the publication
0.0006
ubiquitin
mutant DELTA946, pH not specified in the publication, temperature not specified in the publication
0.0008
ubiquitin
wild-type, pH not specified in the publication, temperature not specified in the publication
0.0012
ubiquitin
chimeric Ub1, pH not specified in the publication, temperature not specified in the publication
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Tokgoez, Z.; Siepmann, T.J.; Streich, F.; Kumar, B.; Klein, J.M.; Haas, A.L.
E1-E2 interactions in ubiquitin and Nedd8 ligation pathways
J. Biol. Chem.
287
311-321
2012
Homo sapiens (P22314), Homo sapiens (Q8TBC4), Homo sapiens
brenda
Bruzzese, F.J.; Tsu, C.A.; Ma, J.; Loke, H.K.; Wu, D.; Li, Z.; Tayber, O.; Dick, L.R.
Development of a charcoal paper adenosine triphosphate pyrophosphate exchange assay kinetic characterization of NEDD8 activating enzyme
Anal. Biochem.
394
24-29
2009
Homo sapiens
brenda
Yashiroda, H.; Tanaka, K.
But1 and But2 proteins bind to Uba3, a catalytic subunit of E1 for neddylation, in fission yeast
Biochem. Biophys. Res. Commun.
311
691-695
2003
Schizosaccharomyces pombe
brenda
Ohki, Y.; Funatsu, N.; Konishi, N.; Chiba, T.
The mechanism of poly-NEDD8 chain formation in vitro
Biochem. Biophys. Res. Commun.
381
443-447
2009
Mus musculus
brenda
Souphron, J.; Waddell, M.; Paydar, A.; Tokgoez-Gromley, Z.; Martine F Roussel, O.; Schulman, B.
Structural dissection of a gating mechanism preventing misactivation of ubiquitin by NEDD8s E1
Biochemistry
47
8961-8969
2008
Homo sapiens (Q13564 and Q8TBC4)
brenda
Muraoka, H.; Yoshimura, C.; Kawabata, R.; Tsuji, S.; Hashimoto, A.; Ochiiwa, H.; Nakagawa, F.; Fujioka, Y.; Matsuo, K.; Ohkubo, S.
Activity of TAS4464, a novel NEDD8 activating enzyme E1 inhibitor, against multiple myeloma via inactivation of nuclear factor ?B pathways
Cancer Sci.
110
3802-3810
2019
Homo sapiens
brenda
Yang, X.; Brownell, J.E.; Xu, Q.; Zhu, F.; Ma, J.; Loke, H.K.; Rollins, N.; Soucy, T.A.; Minissale, J.J.; Thomas, M.P.; Mallender, W.D.; Dick, L.R.; Li, P.; Liao, H.
Absolute quantification of E1, ubiquitin-like proteins and Nedd8-MLN4924 adduct by mass spectrometry
Cell Biochem. Biophys.
67
139-147
2013
Homo sapiens
brenda
Yu, G.; Liu, X.; Tang, J.; Xu, C.; Ouyang, G.; Xiao, W.
Neddylation facilitates the antiviral response in zebrafish
Front. Immunol.
10
1432
2019
Danio rerio
brenda
Osaka, F.; Kawasaki, H.; Aida, N.; Saeki, M.; Chiba, T.; Kawashima, S.; Tanaka, K.; Kato, S.
A new NEDD8-ligating system for cullin-4A
Genes Dev.
12
2263-2268
1998
Homo sapiens
brenda
Gong, L.; Yeh, E.
Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway
J. Biol. Chem.
274
12036-12042
1999
Saccharomyces cerevisiae (Q99344), Saccharomyces cerevisiae
brenda
Huang, D.; Schulman, B.
Expression, purification, and characterization of the E1 for human NEDD8, the heterodimeric APPBP1-UBA3 complex
Methods Enzymol.
398
9-20
2005
Homo sapiens
brenda
Bruzzese, F.J.; Milhollen, M.A.; Gavin, J.M.; Josephine, H.R.; Brownell, J.E.
Identification and application of NEDD8 E1 inhibitors
Methods Mol. Biol.
832
577-588
2012
Homo sapiens
brenda
Walden, H.; Podgorski, M.; Huang, D.; Miller, D.; Howard, R.; Minor Jr., D.; Holton, J.; Schulman, B.
The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1
Mol. Cell.
12
1427-1437
2003
Homo sapiens
brenda
Walden, H.; Podgorski, M.; Schulman, B.
Insights into the ubiquitin transfer cascade from the structure of the activating enzyme for NEDD8
Nature
422
330-334
2003
Homo sapiens
brenda
Xu, G.W.; Toth, J.I.; da Silva, S.R.; Paiva, S.L.; Lukkarila, J.L.; Hurren, R.; Maclean, N.; Sukhai, M.A.; Bhattacharjee, R.N.; Goard, C.A.; Medeiros, B.; Gunning, P.T.; Dhe-Paganon, S.; Petroski, M.D.; Schimmer, A.D.
Mutations in UBA3 confer resistance to the NEDD8-activating enzyme inhibitor MLN4924 in human leukemic cells
PLoS ONE
9
e93530
2014
Homo sapiens (Q8TBC4), Homo sapiens
brenda
Malik-Chaudhry, H.; Gaieb, Z.; Saavedra, A.; Reyes, M.; Kung, R.; Le, F.; Morikis, D.; Liao, J.
Dissecting distinct roles of NEDDylation E1 ligase heterodimer APPBP1 and UBA3 reveals potential evolution process for activation of ubiquitin-related pathways
Sci. Rep.
8
10108
2018
Homo sapiens (Q8TBC4 and Q13564)
brenda