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[E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine + [E2 NEDD8-conjugating enzyme]-L-cysteine
[E1 NEDD8-activating enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine
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[E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine + [E2 NEDD8-conjugating enzyme]-L-cysteine
[E1 NEDD8-activating enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine
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[E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine + [E2 NEDD8-conjugating enzyme]-L-cysteine
[E1 NEDD8-activating enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine
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[E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine + [E2 NEDD8-conjugating enzyme]-L-cysteine
[E1 NEDD8-activating enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine
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[E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine + [E2 NEDD8-conjugating enzyme]-L-cysteine
[E1 NEDD8-activating enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine
Substrates: conjugation of NEDD8 to UBC12 requires the involvement of APP-BP1 and UBA3
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[E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine + [E2 NEDD8-conjugating enzyme]-L-cysteine
[E1 NEDD8-activating enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine
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Substrates: RBX2 is specific for UBE2F, which mediates neddylation of the RBX2 partner, cullin 5
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Substrates: RBX2 is specific for UBE2F, which mediates neddylation of the RBX2 partner, cullin 5
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Substrates: RBX2 is specific for UBE2F, which mediates neddylation of the RBX2 partner, cullin 5
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additional information
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Substrates: the enzyme participates in neddylation of DNA-dependent protein kinase catalytic subunit
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Substrates: UBC12 is specific for RBX1 and mediates neddylation of RBX1-associated cullins 1, 2, 3 and 4
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Substrates: UBC12 is specific for RBX1 and mediates neddylation of RBX1-associated cullins 1, 2, 3 and 4
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Substrates: UBC12 is specific for RBX1 and mediates neddylation of RBX1-associated cullins 1, 2, 3 and 4
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[E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine + [E2 NEDD8-conjugating enzyme]-L-cysteine
[E1 NEDD8-activating enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine
[E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine + [E2 NEDD8-conjugating enzyme]-L-cysteine
[E1 NEDD8-activating enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine
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[E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine + [E2 NEDD8-conjugating enzyme]-L-cysteine
[E1 NEDD8-activating enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine
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Products: -
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[E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine + [E2 NEDD8-conjugating enzyme]-L-cysteine
[E1 NEDD8-activating enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine
Substrates: -
Products: -
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[E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine + [E2 NEDD8-conjugating enzyme]-L-cysteine
[E1 NEDD8-activating enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine
Substrates: conjugation of NEDD8 to UBC12 requires the involvement of APP-BP1 and UBA3
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[E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine + [E2 NEDD8-conjugating enzyme]-L-cysteine
[E1 NEDD8-activating enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine
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Atherosclerosis
Identification of candidate targets for the diagnosis and treatment of atherosclerosis by bioinformatics analysis.
Breast Neoplasms
UBC12-mediated SREBP-1 neddylation worsens metastatic tumor prognosis.
Carcinoma
Control of cell proliferation via elevated NEDD8 conjugation in oral squamous cell carcinoma.
Carcinoma
Improvement of Oral Bioavailability of Pyrazolo-Pyridone Inhibitors of the Interaction of DCN1/2 and UBE2M.
Carcinoma
NEDD8-conjugating enzyme UBC12 as a novel therapeutic target in esophageal squamous cell carcinoma.
Carcinoma
UBE2M-mediated p27(Kip1) degradation in gemcitabine cytotoxicity.
Carcinoma, Hepatocellular
UBC12-mediated SREBP-1 neddylation worsens metastatic tumor prognosis.
Carcinoma, Hepatocellular
UBE2M promotes cell proliferation via the ?-catenin/cyclin D1 signaling in hepatocellular carcinoma.
Carcinoma, Squamous Cell
Improvement of Oral Bioavailability of Pyrazolo-Pyridone Inhibitors of the Interaction of DCN1/2 and UBE2M.
Cholangiocarcinoma
Knockdown of Nedd8?conjugating enzyme UBE2M suppresses the proliferation and induces the apoptosis of intrahepatic cholangiocarcinoma cells.
Colorectal Neoplasms
The covalent modifier Nedd8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis.
Endometrial Neoplasms
MLN4924 inhibits cell proliferation by targeting the activated neddylation pathway in endometrial carcinoma.
Esophageal Squamous Cell Carcinoma
NEDD8-conjugating enzyme UBC12 as a novel therapeutic target in esophageal squamous cell carcinoma.
Hypersensitivity
Neddylation promotes ubiquitylation and release of Ku from DNA-damage sites.
Infections
RNF111-facilitated neddylation potentiates cGAS-mediated antiviral innate immune response.
Infections
Treatment of Yersinia similis with the cationic lipid DOTAP enhances adhesion to and invasion into intestinal epithelial cells - A proof-of-principle study.
Kidney Neoplasms
A first-in-class inhibitor, MLN4924 (pevonedistat), induces cell-cycle arrest, senescence, and apoptosis in human renal cell carcinoma by suppressing UBE2M-dependent neddylation modification.
Lung Neoplasms
Induction of NEDD8-conjugating enzyme E2 UBE2F by platinum protects lung cancer cells from apoptosis and confers to platinum-insensitivity.
Lung Neoplasms
Neddylation E2 UBE2F promotes the survival of lung cancer cells by activating CRL5 to degrade NOXA via the K11 linkage.
Lung Neoplasms
UBE2M Is a Stress-Inducible Dual E2 for Neddylation and Ubiquitylation that Promotes Targeted Degradation of UBE2F.
Lung Neoplasms
Validation of NEDD8-conjugating enzyme UBC12 as a new therapeutic target in lung cancer.
Lymphatic Metastasis
UBC12-mediated SREBP-1 neddylation worsens metastatic tumor prognosis.
Neoplasm Metastasis
UBC12-mediated SREBP-1 neddylation worsens metastatic tumor prognosis.
Neoplasms
Correlation of histopathologic characteristics to protein expression and function in malignant melanoma.
Neoplasms
Knockdown of Nedd8?conjugating enzyme UBE2M suppresses the proliferation and induces the apoptosis of intrahepatic cholangiocarcinoma cells.
Neoplasms
MLN4924 (Pevonedistat), a protein neddylation inhibitor, suppresses proliferation and migration of human clear cell renal cell carcinoma.
Neoplasms
Neddylation E2 UBE2F promotes the survival of lung cancer cells by activating CRL5 to degrade NOXA via the K11 linkage.
Neoplasms
Negative Regulation of NEDD8 Conjugation Pathway by Novel Molecules and Agents for Anticancer Therapy.
Neoplasms
NPRL2 reduces the niraparib sensitivity of castration-resistant prostate cancer via interacting with UBE2M and enhancing neddylation.
Neoplasms
Suppression of glioblastoma by targeting the overactivated protein neddylation pathway.
Neoplasms
Targeting neddylation E2s: a novel therapeutic strategy in cancer.
Neoplasms
The covalent modifier Nedd8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis.
Neoplasms
UBC12-mediated SREBP-1 neddylation worsens metastatic tumor prognosis.
Neoplasms
UBE2M promotes cell proliferation via the ?-catenin/cyclin D1 signaling in hepatocellular carcinoma.
Neoplasms
UBE2M-mediated p27(Kip1) degradation in gemcitabine cytotoxicity.
Pancreatitis
Neddylation pathway alleviates chronic pancreatitis by reducing HIF1?-CCL5-dependent macrophage infiltration.
Prostatic Neoplasms
Flavokawain B targets protein neddylation for enhancing the anti-prostate cancer effect of Bortezomib via Skp2 degradation.
Prostatic Neoplasms
Gartanin is a novel NEDDylation inhibitor for induction of Skp2 degradation, FBXW2 expression, and autophagy.
Prostatic Neoplasms
NPRL2 reduces the niraparib sensitivity of castration-resistant prostate cancer via interacting with UBE2M and enhancing neddylation.
ring-type e3 ubiquitin transferase deficiency
RNF111-facilitated neddylation potentiates cGAS-mediated antiviral innate immune response.
Squamous Cell Carcinoma of Head and Neck
The Nedd8-activating enzyme inhibitor MLN4924 (TAK-924/Pevonedistat) induces apoptosis via c-Myc-Noxa axis in head and neck squamous cell carcinoma.
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physiological function
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UBE2M is a dual E2 for targeted ubiquitylation and degradation of UBE2F, acting as a neddylation E2 to activate cullin 3-Keap1 E3 under physiological condition, but as an ubiquitylation E2 for Parkin-DJ-1 E3 under stressed conditions. UBE2M-induced UBE2F degradation leads to CRL5 inactivation and subsequent NOXA accumulation to suppress the growth of lung cancer cells
malfunction
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enzyme depletion results in decreased DNA-dependent protein kinase catalytic subunit neddylation
malfunction
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knocking down Ube2m leads to decreased Nedd8-ylation of endogenous cullins 1-4, and a marginal increase in Nedd8-modified cullin 5 By contrast, knocking down Ube2f virtually eliminates the presence of Nedd8-ylated cullin 5, and has no effect on the levels of Nedd8-modified cullins 1-4
metabolism
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the enzyme incorporates with E3 neddylation ligase to induce cullin-RING ligase-5 neddylation, leading to activation of cullin-RING ligase-5 E3 to promote NOXA polyubiquitylation via K11 linkage for proteasomal degradation
metabolism
the N-terminal extension of Ubc12 is a selective peptide motif that optimally recruits NEDD8 E1 for the NEDD8 transfer cascade and plays an important role in mitogenesis
metabolism
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UBC12 pairs with RBX1/ROC1 to regulate the neddylation of cullin 1, 2, 3, 4a, 4b and 7, while UBE2F pairs with RBX2/ROC2 to regulate the neddylation of cullin 5
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UB2FA_MOUSE
185
0
21110
Swiss-Prot
other Location (Reliability: 5)
UB2FB_MOUSE
185
0
21352
Swiss-Prot
other Location (Reliability: 2)
UBC12_KLULA
Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
184
0
21166
Swiss-Prot
other Location (Reliability: 2)
UBC12_MOUSE
183
0
20900
Swiss-Prot
other Location (Reliability: 2)
UBC12_SCHPO
Schizosaccharomyces pombe (strain 972 / ATCC 24843)
177
0
20062
Swiss-Prot
other Location (Reliability: 2)
UBC12_XENLA
183
0
20953
Swiss-Prot
other Location (Reliability: 2)
UBC12_XENLA
183
0
20953
Swiss-Prot
other Location (Reliability: 2)
UBC12_XENTR
183
0
20966
Swiss-Prot
other Location (Reliability: 2)
UBC12_YARLI
Yarrowia lipolytica (strain CLIB 122 / E 150)
179
0
20271
Swiss-Prot
other Location (Reliability: 2)
UBC12_YEAST
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
188
0
21203
Swiss-Prot
other Location (Reliability: 5)
UBC2M_DROME
181
0
20738
Swiss-Prot
other Location (Reliability: 2)
UBC12_ASHGO
Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056)
184
0
20776
Swiss-Prot
Mitochondrion (Reliability: 3)
UBC12_BOVIN
183
0
20900
Swiss-Prot
other Location (Reliability: 2)
UBC12_CAEEL
180
0
21101
Swiss-Prot
other Location (Reliability: 3)
UBC12_CANGA
Candida glabrata (strain ATCC 2001 / CBS 138 / JCM 3761 / NBRC 0622 / NRRL Y-65)
187
0
21004
Swiss-Prot
Mitochondrion (Reliability: 4)
UBC12_DICDI
230
0
26066
Swiss-Prot
other Location (Reliability: 4)
UBC12_HUMAN
183
0
20900
Swiss-Prot
other Location (Reliability: 2)
UBE2F_HUMAN
185
0
21077
Swiss-Prot
-
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F5A
the mutant shows a strongly decreased Km value for E1 NEDD8-activating enzyme compared to the wild type
F5A/L7A
the mutant shows a strongly decreased Km value for E1 NEDD8-activating enzyme compared to the wild type
K11A
the mutant shows a wild type Km value for E1 NEDD8-activating enzyme
K12A
the mutant shows a decreased Km value for E1 NEDD8-activating enzyme compared to the wild type
L4A
the mutant shows a decreased Km value for E1 NEDD8-activating enzyme compared to the wild type
L4A/F5A/L7A
the mutant shows a strongly decreased Km value for E1 NEDD8-activating enzyme compared to the wild type
L7A
the mutant shows a strongly decreased Km value for E1 NEDD8-activating enzyme compared to the wild type
M1A
the mutant shows an increased Km value for E1 NEDD8-activating enzyme compared to the wild type
Q10A
the mutant shows a wild type Km value for E1 NEDD8-activating enzyme
Q9A
the mutant shows a decreased Km value for E1 NEDD8-activating enzyme compared to the wild type
S6A
the mutant shows a decreased Km value for E1 NEDD8-activating enzyme compared to the wild type
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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 (P61081), Homo sapiens (Q969M7), Homo sapiens
brenda
Zhang, S.; Sun, Y.
Cullin RING Ligase 5 (CRL-5) neddylation activation and biological functions
Adv. Exp. Med. Biol.
1217
261-283
2020
Homo sapiens
brenda
Guo, Z.; Wang, S.; Xie, Y.; Han, Y.; Hu, S.; Guan, H.; Xie, D.; Bai, C.; Liu, X.; Gu, Y.; Zhou, P.K.; Ma, T.
HUWE1-dependent DNA-PKcs neddylation modulates its autophosphorylation in DNA damage response
Cell Death Dis.
11
400
2020
Homo sapiens
brenda
Yin, L.; Xue, Y.; Shang, Q.; Zhu, H.; Liu, M.; Liu, Y.; Hu, Q.
Pharmaceutical inhibition of neddylation as promising treatments for various cancers
Curr. Top. Med. Chem.
19
1059-1069
2019
Homo sapiens (P61081)
brenda
Li, L.; Kang, J.; Zhang, W.; Cai, L.; Wang, S.; Liang, Y.; Jiang, Y.; Liu, X.; Zhang, Y.; Ruan, H.; Chen, G.; Wang, M.; Jia, L.
Validation of NEDD8-conjugating enzyme UBC12 as a new therapeutic target in lung cancer
EBioMedicine
45
81-91
2019
Homo sapiens
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 (P61081)
brenda
Gong, L.; Yeh, E.
Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway
J. Biol. Chem.
274
12036-12042
1999
Homo sapiens (P61081), Homo sapiens
brenda
Huang, D.T.; Ayrault, O.; Hunt, H.W.; Taherbhoy, A.M.; Duda, D.M.; Scott, D.C.; Borg, L.A.; Neale, G.; Murray, P.J.; Roussel, M.F.; Schulman, B.A.
E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification
Mol. Cell
33
483-495
2009
Mus musculus
brenda
Zhou, W.; Xu, J.; Tan, M.; Li, H.; Li, H.; Wei, W.; Sun, Y.
UBE2M is a stress-inducible dual E2 for neddylation and ubiquitylation that promotes targeted degradation of UBE2F
Mol. Cell
70
1008-1024
2018
Homo sapiens
brenda
Huang, D.; Miller, D.; Mathew, R.; Cassell, R.; Holton, J.; Roussel, M.; Schulman, B.
A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8
Nat. Struct. Mol. Biol.
11
927-935
2004
Homo sapiens (P61081)
brenda