| + |
NEDD4 | up-regulates quantity 
monoubiquitination
|
DCUN1D1 |
0.375 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272717 |
Lys 143 |
KLKAQIPkMEQELKE |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 21813641 |
Here we revealed a previously unknown mechanism that regulates hDCNL1. In cultured mammalian cells ectopically expressed hDCNL1 was mono-ubiquitinated predominantly at K143, K149, and K171. Using a classical chromatographic purification strategy, we identified Nedd4-1 as an E3 ligase that can catalyze mono-ubiquitination of hDCNL1 in a reconstituted ubiquitination system.Taken together, these results suggest a mono-ubiquitination-mediated mechanism that governs nuclear-cytoplasmic trafficking of hDCNL1, |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272718 |
Lys149 |
PKMEQELkEPGRFKD |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 21813641 |
Here we revealed a previously unknown mechanism that regulates hDCNL1. In cultured mammalian cells ectopically expressed hDCNL1 was mono-ubiquitinated predominantly at K143, K149, and K171. Using a classical chromatographic purification strategy, we identified Nedd4-1 as an E3 ligase that can catalyze mono-ubiquitination of hDCNL1 in a reconstituted ubiquitination system.Taken together, these results suggest a mono-ubiquitination-mediated mechanism that governs nuclear-cytoplasmic trafficking of hDCNL1, |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272719 |
Lys171 |
FAKNPGQkGLDLEMA |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 21813641 |
Here we revealed a previously unknown mechanism that regulates hDCNL1. In cultured mammalian cells ectopically expressed hDCNL1 was mono-ubiquitinated predominantly at K143, K149, and K171. Using a classical chromatographic purification strategy, we identified Nedd4-1 as an E3 ligase that can catalyze mono-ubiquitination of hDCNL1 in a reconstituted ubiquitination system.Taken together, these results suggest a mono-ubiquitination-mediated mechanism that governs nuclear-cytoplasmic trafficking of hDCNL1, |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
SRC | up-regulates activity
phosphorylation
|
NEDD4 (isoform 4) |
0.427 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276859 |
Tyr43 |
ILGASDPyVRVTLYD |
Homo sapiens |
|
| pmid |
sentence |
| 25292214 |
Activation of c-Src by epidermal growth factor (EGF) also promoted tyrosine phosphorylation and enhanced the activity of NEDD4. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276860 |
Tyr585 |
DGEKGLDyGGVAREW |
Homo sapiens |
|
| pmid |
sentence |
| 25292214 |
Activation of c-Src by epidermal growth factor (EGF) also promoted tyrosine phosphorylation and enhanced the activity of NEDD4. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
AP1G2 | up-regulates activity
binding
|
NEDD4 |
0.41 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272636 |
|
|
Homo sapiens |
HuH-7 Cell |
| pmid |
sentence |
| 18772139 |
Gamma2-Adaptin is a putative member of the clathrin adaptor protein family with unknown physiological function. We previously reported that gamma2-adaptin acts as a ubiquitin receptor by virtue of its ubiquitin-interacting motif. Here we demonstrate that this motif mediates a specific physical interaction with the ubiquitin ligase Nedd4 and promotes ubiquitination of gamma2-adaptin. These antibodies clearly recognized the 96 kDa form, thus demonstrating that a fraction of γ2-adaptin is modified by monoubiquitination (Fig. 1C). Thus, binding of γ2-adaptin to Nedd4 is not necessary for its membrane association.Accordingly, one possible function of γ2-adaptin may be to act as an adaptor for Nedd4, recruiting it to membrane compartments for subsequent ubiquitination. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4 | up-regulates activity
monoubiquitination, polyubiquitination
|
AP1G2 |
0.41 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272634 |
|
|
Homo sapiens |
HuH-7 Cell |
| pmid |
sentence |
| 18772139 |
Gamma2-Adaptin is a putative member of the clathrin adaptor protein family with unknown physiological function. We previously reported that gamma2-adaptin acts as a ubiquitin receptor by virtue of its ubiquitin-interacting motif. Here we demonstrate that this motif mediates a specific physical interaction with the ubiquitin ligase Nedd4 and promotes ubiquitination of gamma2-adaptin. These antibodies clearly recognized the 96 kDa form, thus demonstrating that a fraction of γ2-adaptin is modified by monoubiquitination (Fig. 1C). Thus, binding of γ2-adaptin to Nedd4 is not necessary for its membrane association.Accordingly, one possible function of γ2-adaptin may be to act as an adaptor for Nedd4, recruiting it to membrane compartments for subsequent ubiquitination. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272635 |
|
|
Homo sapiens |
HuH-7 Cell |
| pmid |
sentence |
| 18772139 |
Gamma2-Adaptin is a putative member of the clathrin adaptor protein family with unknown physiological function. We previously reported that gamma2-adaptin acts as a ubiquitin receptor by virtue of its ubiquitin-interacting motif. Here we demonstrate that this motif mediates a specific physical interaction with the ubiquitin ligase Nedd4 and promotes ubiquitination of gamma2-adaptin. These antibodies clearly recognized the 96 kDa form, thus demonstrating that a fraction of γ2-adaptin is modified by monoubiquitination (Fig. 1C). Thus, binding of γ2-adaptin to Nedd4 is not necessary for its membrane association.Accordingly, one possible function of γ2-adaptin may be to act as an adaptor for Nedd4, recruiting it to membrane compartments for subsequent ubiquitination. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
NDFIP2 | down-regulates activity 
relocalization
|
NEDD4 |
0.586 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260995 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 26363003 |
Ndfip1 is primarily localized in the Golgi apparatus where it recruits Nedd4-2 to mediate the degradation of mature hERG proteins during channel trafficking to the plasma membrane. Although Ndfip2 directs Nedd4-2 to the Golgi apparatus, it also recruits Nedd4-2 to the multivesicular bodies (MVBs), which may impair MVB function and impede the degradation of mature hERG proteins mediated by Nedd4-2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NDFIP2 | up-regulates activity
relocalization
|
NEDD4 |
0.586 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260996 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 26363003 |
Ndfip1 is primarily localized in the Golgi apparatus where it recruits Nedd4-2 to mediate the degradation of mature hERG proteins during channel trafficking to the plasma membrane. Although Ndfip2 directs Nedd4-2 to the Golgi apparatus, it also recruits Nedd4-2 to the multivesicular bodies (MVBs), which may impair MVB function and impede the degradation of mature hERG proteins mediated by Nedd4-2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4 | down-regulates quantity by destabilization
polyubiquitination
|
GUCD1 |
0.43 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272846 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 24743017 |
The E3 ligase NEDD4 regulates GUCD1 degradation. many polyubiquitinylated species of GUCD1 appeared as high molecular weight forms, suggesting that GUCD1 is degraded by the proteasome, after polyubiquitin chain formation, in the presence of NEDD4-1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4 | down-regulates quantity by destabilization
polyubiquitination
|
LYN |
0.439 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272558 |
|
|
Homo sapiens |
BJAB Cell |
| pmid |
sentence |
| 10683340 |
These findings suggest that LMP2A recruits Nedd4-like ubiquitin-protein ligases and B-cell signal transduction molecules, resulting in the degradation of LMP2A and Lyn by a ubiquitin-dependent mechanism. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4 | down-regulates quantity by destabilization
polyubiquitination
|
SYK |
0.296 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272581 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11046148 |
The latent membrane protein (LMP) 2A of Epstein-Barr virus (EBV) is implicated in the maintenance of viral latency and appears to function in part by inhibiting B-cell receptor (BCR) signaling. LMP2A enhances Lyn and Syk ubiquitination in vivo in a fashion that depends on the activity of Nedd4 family members and correlates with destabilization of the Lyn tyrosine kinase. These results suggest that LMP2A serves as a molecular scaffold to recruit both B-cell tyrosine kinases and C2/WW/Hect domain E3 protein-ubiquitin ligases. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ANXA13 | up-regulates quantity
relocalization
|
NEDD4 |
0.35 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272571 |
|
|
in vitro |
|
| pmid |
sentence |
| 10871286 |
Annexin XIII has two known isoforms, a and b, that are apically localized, although XIIIa is also found in the basolateral compartment. In vitro binding and coprecipitation experiments showed that the Nedd4-C2 domain interacts with both annexin XIIIa and b in the presence of Ca2+, and the interaction is direct and optimal at 1 μM Ca2+.These results suggest that the apical membrane localization of Nedd4 is mediated by an association of its C2 domain with the apically targeted annexin XIIIb. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
SIRT2 | down-regulates quantity by repression 
transcriptional regulation
|
NEDD4 |
0.265 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255144 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23175188 |
SIRT2 repressed NEDD4 gene expression by directly binding to the NEDD4 gene core promoter and deacetylating histone H4 lysine 16. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
UBE2L3 | up-regulates activity
ubiquitination
|
NEDD4 |
0.56 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272735 |
|
|
in vitro |
|
| pmid |
sentence |
| 19240029 |
Only UbcH5 and Related Class I E2s Support Ubiquitination of S5a—UbcH5 belongs to the Class I family of E2s which contains a catalytic core (UBC domain) without a distinct Ub binding domain (38). To test whether other Class I E2s can also support ubiquitination of S5a, we assayed the ubiquitination of S5a with UbcH7 and the E3s, Nedd4, or Parkin. With either of these E3s, UbcH7 supported ubiquitination of S5a (Fig. 8, A and B). In addition, another Class I E2, Ubc4, a close homolog of UbcH5, supported ubiquitination of S5a by the APC, a multimeric Ring finger E3 responsible for cell cycle progression through mitosis (39) (Fig. 8C). Thus, multiple Class I E2s can support ubiquitination of S5a by various types of E3s (Table 1). |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
NEDD4 | down-regulates quantity by destabilization
polyubiquitination
|
SAG |
0.383 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272843 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 25216516 |
Here we report that NEDD4-1, a HECT domain-containing E3 ubiquitin ligase, binds via its HECT domain directly with SAG's C-terminal RING domain and ubiquitylates SAG for proteasome-mediated. We also found that SAG bridges NEDD4-1 via its C-terminus and CUL-5 via its N-terminus to form a NEDD4-1/SAG/CUL-5 tri-complex. Biologically, NEDD4-1 overexpression sensitizes cancer cells to etoposide-induced apoptosis by reducing SAG levels through targeted degradation. Thus, SAG is added to a growing list of NEDD4-1 substrates and mediates its biological function. degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4 | down-regulates quantity by destabilization
ubiquitination
|
KCNH2 |
0.271 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260998 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 26363003 |
We have previously shown that the E3 ubiquitin (Ub) ligase Nedd4-2 (neural precursor cell expressed developmentally down-regulated protein 4-2) targets the PY motif of hERG channels to initiate channel degradation. Although both immature and mature hERG channels contain the PY motif, Nedd4-2 selectively mediates the degradation of mature hERG channels. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Ub:E2 | up-regulates activity
ubiquitination
|
NEDD4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271300 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 34199813 |
The ubiquitination process is mediated sequentially by three classes of enzymes consisting of a Ub-activating enzyme E1, a Ub-conjugating enzyme E2, and a Ub ligase E3. Ub is first activated by E1 in an adenosine 5′-triphosphate (ATP)-dependent manner t |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4 | down-regulates quantity by destabilization
polyubiquitination
|
PSMD4 |
0.463 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272753 |
|
|
in vitro |
|
| pmid |
sentence |
| 19240029 |
S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
NEDD4 | up-regulates activity
monoubiquitination
|
N4BP1 |
0.46 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272626 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17114934 |
This observation, together with the monoubiquitination of Nedd4-BP1 by the ubiquitin ligase Nedd4 suggests that the NYN domain proteins of eukaryotes are regulated by monoubiquitination. Given the localization of Nedd4-BP1 to punctuate nuclear bodies, it is likely that they are parts of nuclear RNA-processing complexes that are dependent on monoubiquitination for their assembly. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4 | down-regulates quantity by destabilization
polyubiquitination
|
SPRY2 |
0.398 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271425 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19864419 |
Endogenous and overexpressed Nedd4 polyubiquitinate Spry2 via Lys(48) on ubiquitin and decrease its stability. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4 | down-regulates quantity by destabilization
polyubiquitination
|
KIF26B |
0.321 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272906 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22768111 |
We find that Kif26b interacts with an E3 ubiquitin ligase, neural precursor cell expressed developmentally down-regulated protein 4 (Nedd4) in developing kidney. Phosphorylation of Kif26b at Thr-1859 and Ser-1962 by the cyclin-dependent kinases (CDKs) enhances the interaction of Kif26b with Nedd4. Nedd4 polyubiquitinates Kif26b and thereby promotes degradation of Kif26b via the ubiquitin-proteasome pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NDFIP1 | up-regulates activity
relocalization
|
NEDD4 |
0.608 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260997 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 26363003 |
Ndfip1 is primarily localized in the Golgi apparatus where it recruits Nedd4-2 to mediate the degradation of mature hERG proteins during channel trafficking to the plasma membrane. Although Ndfip2 directs Nedd4-2 to the Golgi apparatus, it also recruits Nedd4-2 to the multivesicular bodies (MVBs), which may impair MVB function and impede the degradation of mature hERG proteins mediated by Nedd4-2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
NEDD4
- 
- 