| + |
NEDD4L | up-regulates activity 
ubiquitination
|
NF2 |
0.263 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263662 |
Lys396 |
QITEEEAkLLAQKAA |
Homo sapiens |
|
| pmid |
sentence |
| 33058421 |
Merlin ubiquitination is mediated by the E3 ubiquitin ligase, NEDD4L, which requires a scaffold protein, AMOTL1, to approach Merlin. Several NF2-patient-derived Merlin mutations disrupt its binding to AMOTL1 and its regulation by the AMOTL1-NEDD4L apparatus. Lysine (K) 396 is the major ubiquitin conjugation residue. Disruption of Merlin ubiquitination by the K396R mutation or NEDD4L depletion diminishes its binding to Lats1 and inhibits Lats1 activation. These effects are also accompanied by loss of Merlin's anti-mitogenic and tumor suppressive properties. Thus, we propose that dephosphorylation and ubiquitination compose an intramolecular relay to activate Merlin functions in activating the Hippo pathway during growth control. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hippo Signaling |
| + |
NEDD4L | down-regulates quantity by destabilization 
ubiquitination
|
ULK1 |
0.365 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278523 |
Lys933 |
LCLSSTVkQVVRRLN |
Homo sapiens |
|
| pmid |
sentence |
| 27932573 |
NEDD4L ubiquitylates ULK1 at lysine 925 and lysine 933.|Next, we found that down-regulation of the ULK1 protein by NEDD4L is blocked by proteasome inhibitors (MG132 and lactacystin), but not by lysosomal inhibitors (leupeptin and Clq; XREF_FIG and S2 C), indicating that NEDD4L triggers ULK1 degradation exclusively through the proteasome pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SGK1 | up-regulates
phosphorylation
|
NEDD4L |
0.783 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-113052 |
Ser342 |
SSRLRSCsVTDAVAE |
Homo sapiens |
|
| pmid |
sentence |
| 11742982 |
Here we show by expression studies in xenopus laevis oocytes that the aldosterone-induced sgk1 kinase interacts with the ubiquitin protein ligase nedd4-2 in a py motif-dependent manner and phosphorylates nedd4-2 on ser444 and, to a lesser extent, ser338. Such phosphorylation reduces the interaction between nedd4-2 and enac, leading to elevated enac cell surface expression. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SGK1 | down-regulates
phosphorylation
|
NEDD4L |
0.783 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-133438 |
Ser448 |
IRRPRSLsSPTVTLS |
Homo sapiens |
|
| pmid |
sentence |
| 15677482 |
Nedd4-2 function is negatively regulated by phosphorylation via a serum- and glucocorticoid-inducible protein kinase (sgk1), which serves as a mechanism to inhibit the ubiquitination-dependent degradation of enac. Sgk1 catalyzed phosphorylation of hnedd4-2 at ser-468 maintaining hnedd4-2 in an inactive phosphorylated state. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKACA | down-regulates
phosphorylation
|
NEDD4L |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-128429 |
Ser448 |
IRRPRSLsSPTVTLS |
Homo sapiens |
|
| pmid |
sentence |
| 15328345 |
Nedd4-2 was a substrate for phosphorylation by pka in vitro and in cells;three nedd4-2 residues were phosphorylated by pka and were required for camp to inhibit nedd4-2 (relative functional importance ser-327 > ser-221 > thr-246). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AMPK | up-regulates activity
phosphorylation
|
NEDD4L |
0.257 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276324 |
Ser795 |
VDLKPNGsEIMVTNE |
in vitro |
|
| pmid |
sentence |
| 21501591 |
The AMP-activated protein kinase (AMPK) down-regulates the inward rectifier K+ channel Kir2.1. Expression of wild type Nedd4-2 or of Nedd4-2S795A lacking an AMPK phosphorylation consensus sequence downregulated Kir2.1 currents. The effect of wild type Nedd4-2 but not of Nedd4-2S795A was significantly augmented by additional coexpression of AMPK. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277858 |
Ser795 |
VDLKPNGsEIMVTNE |
in vitro |
|
| pmid |
sentence |
| 21501591 |
Expression of wild type Nedd4-2 or of Nedd4-2S795A lacking an AMPK phosphorylation consensus sequence downregulated Kir2.1 currents. The effect of wild type Nedd4-2 but not of Nedd4-2S795A was significantly augmented by additional coexpression of AMPK. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276326 |
Ser795 |
VDLKPNGsEIMVTNE |
in vitro |
|
| pmid |
sentence |
| 21501591 |
The AMP-activated protein kinase (AMPK) down-regulates the inward rectifier K+ channel Kir2.1. Expression of wild type Nedd4-2 or of Nedd4-2S795A lacking an AMPK phosphorylation consensus sequence downregulated Kir2.1 currents. The effect of wild type Nedd4-2 but not of Nedd4-2S795A was significantly augmented by additional coexpression of AMPK. |
|
| Publications: |
3 |
Organism: |
In Vitro |
| + |
SGK1 | down-regulates activity
phosphorylation
|
NEDD4L |
0.783 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263076 |
Thr383 |
PSVAYVHtTPGLPSG |
in vitro |
|
| pmid |
sentence |
| 12911626 |
Site‐directed mutagenesis of the SGK1 phosphorylation sites in the Nedd4‐2 protein (S382A,S468ANedd4‐2) and in the EAAT1 protein (T482AEAAT1, T482DEAAT1) significantly blunts the effect of S422DSGK1. Introduction of a negative charge at the SGK phosphorylation site in the EAAT1 protein leads to a strong stimulation of the carrier, whereas replacement with alanine markedly decreases the EAAT1‐mediated current. These observations suggest that SGK1 exerts its effect not only by phosphorylation of Nedd4‐2 but also by phosphorylation of EAAT1. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251949 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15586017 |
The serum and glucocorticoid inducible kinase 1 (SGK1) is induced in the aldosterone sensitive distal nephron (ASDN) where it may stimulate Na reabsorption, partly by inhibiting ubiquitin ligase Nedd4-2-mediated retrieval of epithelial Na+ channel ENaC from the luminal membrane. |
|
| Publications: |
2 |
Organism: |
In Vitro, Homo Sapiens |
| + |
NEDD4L | down-regulates
ubiquitination
|
SMAD2 |
0.775 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161710 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19917253 |
Through its ww domain, nedd4l specifically recognizes a tgf-beta-induced phosphothr-protyr motif in the linker region, resulting in smad2/3 polyubiquitination and degradation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4L | down-regulates quantity by destabilization
ubiquitination
|
SCN10A |
0.324 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253463 |
|
|
Mus musculus |
Neuron |
| pmid |
sentence |
| 23778145 |
The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
NEDD4L | down-regulates quantity by destabilization
ubiquitination
|
SCN8A |
0.328 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253461 |
|
|
Mus musculus |
Neuron |
| pmid |
sentence |
| 23778145 |
The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
NEDD4L | down-regulates quantity by destabilization
polyubiquitination
|
TTYH2 |
0.289 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272632 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 18577513 |
Our data indicate that Nedd4-2 binds to two family members, TTYH2 and TTYH3, which contain consensus PY ((L/P)PXY) binding sites for HECT type E3 ubiquitin ligases, but not to TTYH1, which lacks this motif. Consistently, Nedd4-2 ubiquitinates both TTYH2 and TTYH3. Importantly, we have shown that endogenous TTYH2 and Nedd4-2 are binding partners and demonstrated that the TTYH2 PY motif is essential for these interactions. We have also shown that Nedd4-2-mediated ubiquitination of TTYH2 is a critical regulator of cell surface and total cellular levels of this protein. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4L | down-regulates quantity by destabilization
ubiquitination
|
SCN9A |
0.338 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253458 |
|
|
Mus musculus |
Neuron |
| pmid |
sentence |
| 23778145 |
The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
NEDD4L | down-regulates activity
ubiquitination
|
SMAD3 |
0.799 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-232104 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19917253 |
Through its ww domain, nedd4l specifically recognizes a tgf-beta-induced phosphothr-protyr motif in the linker region, resulting in smad2/3 polyubiquitination and degradation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4L | down-regulates activity
ubiquitination
|
SMAD2 |
0.775 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217622 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19917253 |
Through its ww domain, nedd4l specifically recognizes a tgf-beta-induced phosphothr-protyr motif in the linker region, resulting in smad2/3 polyubiquitination and degradation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4L | down-regulates
ubiquitination
|
SMAD3 |
0.799 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161713 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19917253 |
Through its ww domain, nedd4l specifically recognizes a tgf-beta-induced phosphothr-protyr motif in the linker region, resulting in smad2/3 polyubiquitination and degradation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4L | down-regulates quantity by destabilization
ubiquitination
|
SCN5A |
0.471 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253456 |
|
|
Mus musculus |
Neuron |
| pmid |
sentence |
| 23778145 |
The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
NEDD4L | down-regulates quantity by destabilization
ubiquitination
|
SCN3A |
0.285 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253464 |
|
|
Mus musculus |
Neuron |
| pmid |
sentence |
| 23778145 |
The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
NEDD4L | down-regulates quantity by destabilization
ubiquitination
|
SCNN1A |
0.77 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251948 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15586017 |
The serum and glucocorticoid inducible kinase 1 (SGK1) is induced in the aldosterone sensitive distal nephron (ASDN) where it may stimulate Na reabsorption, partly by inhibiting ubiquitin ligase Nedd4-2-mediated retrieval of epithelial Na+ channel ENaC from the luminal membrane. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4L | down-regulates quantity by destabilization
ubiquitination
|
SCN1A |
0.294 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253457 |
|
|
Mus musculus |
Neuron |
| pmid |
sentence |
| 23778145 |
The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
NEDD4L | down-regulates quantity by destabilization
ubiquitination
|
CLCN5 |
0.295 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272665 |
|
|
Didelphis virginiana |
OK Cell |
| pmid |
sentence |
| 15489223 |
The presence of albumin triggers the formation of an endocytic complex that includes ClC-5. (iii) Nedd4-2 is recruited to this complex and ubiquitinates ClC-5. This ubiquitination by Nedd4-2 shunts ClC-5 into the albumin uptake/degradative pathway. |
|
| Publications: |
1 |
Organism: |
Didelphis Virginiana |
| + |
NEDD4L | down-regulates quantity by destabilization
ubiquitination
|
SCN2A |
0.321 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253459 |
|
|
Mus musculus |
Neuron |
| pmid |
sentence |
| 23778145 |
The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
Ub:E2 | up-regulates activity
ubiquitination
|
NEDD4L |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271287 |
|
|
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 |
| + |
NEDD4L | down-regulates quantity by destabilization
ubiquitination
|
SCN11A |
0.291 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253462 |
|
|
Mus musculus |
Neuron |
| pmid |
sentence |
| 23778145 |
The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
NEDD4L | down-regulates quantity by destabilization
ubiquitination
|
SCN4A |
0.282 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253460 |
|
|
Mus musculus |
Neuron |
| pmid |
sentence |
| 23778145 |
The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
NEDD4L | up-regulates activity
ubiquitination
|
TRAF3 |
0.271 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278587 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 33608556 |
Nedd4l promotes TRAF3 to interact with cIAP1/2 and HECTD3.|Ubiquitination of TRAF3 by Nedd4l promotes interaction of TRAF3 with proteins such as cIAP1/2, HECTD3, and TBK1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4L | down-regulates quantity by destabilization
ubiquitination
|
OGG1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278639 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 33282879 |
We demonstrate that recombinant NEDD4L stimulates ubiquitylation of OGG1 in vitro, particularly on lysine 341, and that NEDD4L and OGG1 interact in U2OS cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4L | down-regulates quantity by destabilization
ubiquitination
|
SPHK2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278660 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 34305532 |
In this study, we found that NEDD4L interacted with SphK2 to ubiquitinate SphK2 protein.|NEDD4L Mediates the Degradation of SphK2 Protein Through the Ubiquitin-Proteasomal Pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4L | down-regulates quantity
ubiquitination
|
SLC1A2 |
0.308 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278706 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28151476 |
Our results confirm that Nedd4-2 knockdown in MPTP treated mice increased GLT-1 expression at the membrane protein level (XREF_FIG; P < 0.01).|These results suggest that Nedd4-2 mediates the ubiquitination of both GLT-1 and GLAST in the midbrain in MPTP treated mice, and Nedd4-2 maybe a potential target in regulating glutamate transporters in PD. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4L | down-regulates quantity by destabilization
ubiquitination
|
KCNH2 |
0.404 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278771 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21463633 |
As quantified in Fig. 5 B, only Nedd4-2 significantly increased the basal ubiquitylation of hERG1, while Nedd4-2-C801S and the other ubiquitin ligases had no effect.|The major findings of this study are as follows : 1) hERG1 interacts via its PY motif with the ubiquitin ligase Nedd4-2, 2) this interaction promotes the down-regulation of the functional form of the channel at the plasma membrane through Nedd4-2 ubiquitylation of the channel, and 3) I hERG1 is strongly decreased by Nedd4-2 catalytic dependent activity.The hERG1 PY motif is a highly conserved sequence across animal species lines, highlighting its crucial role in the regulation of the hERG1 channel at the cell surface. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEDD4L | down-regulates quantity by destabilization
polyubiquitination
|
TTYH3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272633 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 18577513 |
Our data indicate that Nedd4-2 binds to two family members, TTYH2 and TTYH3, which contain consensus PY ((L/P)PXY) binding sites for HECT type E3 ubiquitin ligases, but not to TTYH1, which lacks this motif. Consistently, Nedd4-2 ubiquitinates both TTYH2 and TTYH3. Importantly, we have shown that endogenous TTYH2 and Nedd4-2 are binding partners and demonstrated that the TTYH2 PY motif is essential for these interactions. We have also shown that Nedd4-2-mediated ubiquitination of TTYH2 is a critical regulator of cell surface and total cellular levels of this protein. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
NEDD4L
- 
- 