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IUBMB CommentsIn the first step the enzyme transfers ubiquitin from the E2 ubiquitin-conjugating enzyme (EC 2.3.2.23) to a cysteine residue in its HECT domain (which is located in the C-terminal region), forming a thioester bond. In a subsequent step the enzyme transfers the ubiquitin to an acceptor protein, resulting in the formation of an isopeptide bond between the C-terminal glycine residue of ubiquitin and the epsilon-amino group of an L-lysine residue of the acceptor protein. cf. EC 2.3.2.27, RING-type E3 ubiquitin transferase and EC 2.3.2.31, RBR-type E3 ubiquitin transferase.
Synonyms
nedd4, smurf1, smurf2, huwe1, nedd4l, nedd4-1, e6-ap, ube3c, trp120, trip12,
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[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:[acceptor protein] ubiquitin transferase (isopeptide bond-forming)
In the first step the enzyme transfers ubiquitin from the E2 ubiquitin-conjugating enzyme (EC 2.3.2.23) to a cysteine residue in its HECT domain (which is located in the C-terminal region), forming a thioester bond. In a subsequent step the enzyme transfers the ubiquitin to an acceptor protein, resulting in the formation of an isopeptide bond between the C-terminal glycine residue of ubiquitin and the epsilon-amino group of an L-lysine residue of the acceptor protein. cf. EC 2.3.2.27, RING-type E3 ubiquitin transferase and EC 2.3.2.31, RBR-type E3 ubiquitin transferase.
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S-(ubiquitin)n-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [Glis3]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-(ubiquitin)n-[Glis3]-L-lysine
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Glis i.e. transcription factor Gli-similar 3
isoform Itch significantly contributes to Glis3 polyubiquitination and reduces Glis3 stability by enhancing its proteasomal degradation. Itch-mediated degradation of Glis3 requires the PPxY motif-dependent interaction between Glis3 and the WW-domains of Itch as well as the presence of the Glis3 zinc finger domains. Itch dramatically inhibits Glis3-mediated transactivation and endogenous Ins2 expression by increasing Glis3 protein turnover
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HERC4_RAT
1057
0
118540
Swiss-Prot
other Location (Reliability: 2)
HUWE1_RAT
322
0
37361
Swiss-Prot
other Location (Reliability: 2)
NEDD4_RAT
887
0
102395
Swiss-Prot
other Location (Reliability: 1)
UBR5_RAT
2788
0
308027
Swiss-Prot
other Location (Reliability: 4)
UBE3D_RAT
370
0
41056
Swiss-Prot
other Location (Reliability: 2)
HACE1_RAT
909
0
102159
Swiss-Prot
Mitochondrion (Reliability: 5)
TRIPC_RAT
2025
0
223928
Swiss-Prot
other Location (Reliability: 5)
D4ADD3_RAT
1578
0
176517
TrEMBL
Mitochondrion (Reliability: 2)
A0A8I5ZKY8_RAT
873
0
100196
TrEMBL
Mitochondrion (Reliability: 5)
Q3KR60_RAT
500
0
57413
TrEMBL
other Location (Reliability: 2)
F1M3F2_RAT
748
0
86094
TrEMBL
Mitochondrion (Reliability: 4)
A0A0G2JUY1_RAT
921
0
105569
TrEMBL
Secretory Pathway (Reliability: 4)
A0A8I6A1F1_RAT
735
0
84488
TrEMBL
Mitochondrion (Reliability: 5)
A0A8I5ZK23_RAT
706
0
80384
TrEMBL
other Location (Reliability: 1)
A0A8I6ANY7_RAT
888
0
102488
TrEMBL
other Location (Reliability: 1)
Q4V8H7_RAT
918
0
104600
TrEMBL
other Location (Reliability: 4)
A0A8I5ZM14_RAT
867
0
100092
TrEMBL
Mitochondrion (Reliability: 5)
A0A8I5ZZU1_RAT
882
0
100831
TrEMBL
Secretory Pathway (Reliability: 4)
M0R8Z5_RAT
1059
0
121395
TrEMBL
Mitochondrion (Reliability: 5)
D4ACN3_RAT
4530
0
493616
TrEMBL
Secretory Pathway (Reliability: 2)
A0A0G2JZS6_RAT
404
1
44888
TrEMBL
other Location (Reliability: 2)
A0A8I6GLU0_RAT
956
0
110141
TrEMBL
other Location (Reliability: 1)
A0A8I6AJU5_RAT
1138
0
128343
TrEMBL
Mitochondrion (Reliability: 5)
A0A8I6AG92_RAT
1603
0
179655
TrEMBL
other Location (Reliability: 5)
A0A0G2K9T1_RAT
864
0
98793
TrEMBL
other Location (Reliability: 1)
A0A8I5ZLT5_RAT
869
0
100363
TrEMBL
other Location (Reliability: 1)
A0A0G2K105_RAT
709
0
80907
TrEMBL
Mitochondrion (Reliability: 4)
A0A0G2K612_RAT
757
0
86104
TrEMBL
Mitochondrion (Reliability: 4)
A0A8I6GFW6_RAT
1223
0
137936
TrEMBL
Mitochondrion (Reliability: 5)
A0A0G2K8P3_RAT
889
0
102754
TrEMBL
other Location (Reliability: 1)
A0A8I6A6J7_RAT
921
0
105487
TrEMBL
other Location (Reliability: 1)
A0A8I6ADN0_RAT
824
0
94175
TrEMBL
Mitochondrion (Reliability: 2)
D3ZLS5_RAT
2610
0
289034
TrEMBL
other Location (Reliability: 4)
A0A8I5ZVG1_RAT
4800
0
523409
TrEMBL
other Location (Reliability: 2)
D3ZHB7_RAT
1083
0
123969
TrEMBL
other Location (Reliability: 4)
F1LRN8_RAT
856
0
98106
TrEMBL
other Location (Reliability: 5)
F7FIK1_RAT
968
0
110488
TrEMBL
other Location (Reliability: 2)
B4F767_RAT
870
0
98778
TrEMBL
Mitochondrion (Reliability: 2)
D7NIW0_RAT
968
0
111495
TrEMBL
other Location (Reliability: 3)
A0A1B0GWW0_RAT
1065
0
121691
TrEMBL
other Location (Reliability: 2)
A0A0G2JVW5_RAT
3941
0
434080
TrEMBL
other Location (Reliability: 4)
A0A8I6GKS9_RAT
942
0
107879
TrEMBL
other Location (Reliability: 3)
A0A0A0MXY4_RAT
1950
0
215446
TrEMBL
other Location (Reliability: 5)
A0A8I6AEH7_RAT
1071
0
121654
TrEMBL
other Location (Reliability: 5)
A0A0G2JUC9_RAT
4836
0
527477
TrEMBL
other Location (Reliability: 2)
A0A8I6AVL7_RAT
855
0
98045
TrEMBL
other Location (Reliability: 5)
A0A8I5ZNU0_RAT
2549
0
281986
TrEMBL
other Location (Reliability: 4)
F1M7B8_RAT
868
0
99753
TrEMBL
other Location (Reliability: 3)
Q5YB86_RAT
854
0
97746
TrEMBL
other Location (Reliability: 3)
A0A8I6A634_RAT
4378
0
482724
TrEMBL
other Location (Reliability: 3)
Q5U1Z5_RAT
440
0
51737
TrEMBL
other Location (Reliability: 2)
A0A8I5ZXL3_RAT
999
0
114593
TrEMBL
Mitochondrion (Reliability: 5)
A0A8I5ZUV2_RAT
695
0
80022
TrEMBL
Mitochondrion (Reliability: 4)
A0A8I6AIV5_RAT
872
0
100886
TrEMBL
other Location (Reliability: 1)
A0A8I6GL04_RAT
912
0
105041
TrEMBL
other Location (Reliability: 1)
A0A1W2Q676_RAT
1966
0
217154
TrEMBL
other Location (Reliability: 5)
A0A8I6A475_RAT
1588
0
177938
TrEMBL
Mitochondrion (Reliability: 2)
F1M4Q8_RAT
1594
0
178726
TrEMBL
Mitochondrion (Reliability: 2)
A0A0G2K6U6_RAT
1321
0
146772
TrEMBL
Mitochondrion (Reliability: 2)
D3ZCF5_RAT
718
0
81768
TrEMBL
other Location (Reliability: 5)
A0A8I6AHN4_RAT
2067
0
228617
TrEMBL
other Location (Reliability: 4)
A0A0G2JU73_RAT
2038
0
225676
TrEMBL
other Location (Reliability: 4)
A0A8I5ZQP0_RAT
1602
0
179621
TrEMBL
Mitochondrion (Reliability: 4)
A0A8I6A4L5_RAT
976
0
112200
TrEMBL
other Location (Reliability: 1)
A0A0G2K0B4_RAT
867
0
100398
TrEMBL
other Location (Reliability: 1)
A0A8I6APS3_RAT
4454
0
489705
TrEMBL
other Location (Reliability: 3)
A0A0G2K0E7_RAT
1070
0
122617
TrEMBL
Mitochondrion (Reliability: 5)
A0A8I5Y0P5_RAT
756
1
87314
TrEMBL
Secretory Pathway (Reliability: 1)
E9PSZ5_RAT
4320
0
474331
TrEMBL
other Location (Reliability: 3)
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Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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ZeRuth, G.T.; Williams, J.G.; Cole, Y.C.; Jetten, A.M.
HECT E3 ubiquitin ligase Itch functions as a novel negative regulator of Gli-Similar 3 (Glis3) transcriptional activity
PLoS ONE
10
e0131303
2015
Rattus norvegicus
brenda
Otaki, Y.; Takahashi, H.; Watanabe, T.; Funayama, A.; Netsu, S.; Honda, Y.; Narumi, T.; Kadowaki, S.; Hasegawa, H.; Honda, S.; Arimoto, T.; Shishido, T.; Miyamoto, T.; Kamata, H.; Nakajima, O.; Kubota, I.
HECT-type ubiquitin E3 ligase ITCH interacts with thioredoxin-interacting protein and ameliorates reactive oxygen species-induced cardiotoxicity
J. Am. Heart Assoc.
5
e002485
2016
Mus musculus, Rattus norvegicus
brenda