Gene description for NEDD4L
Gene name neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase
Gene symbol NEDD4L
Other names/aliases NEDD4-2
NEDD4.2
RSP5
hNEDD4-2
Species Homo sapiens
 Database cross references - NEDD4L
ExoCarta ExoCarta_23327
Entrez Gene 23327
HGNC 7728
MIM 606384
UniProt Q96PU5  
 NEDD4L identified in exosomes derived from the following tissue/cell type
Colorectal cancer cells 19837982    
Colorectal cancer cells 23161513    
Colorectal cancer cells 23161513    
Colorectal cancer cells 23161513    
Hepatocellular carcinoma cells 26054723    
Melanoma cells 25950383    
Melanoma cells 25950383    
Melanoma cells 25950383    
Melanoma cells 25950383    
Melanoma cells 25950383    
Melanoma cells 25950383    
Ovarian cancer cells 23333927    
Ovarian cancer cells 23333927    
Platelets 25332113    
Platelets 25332113    
Platelets 25332113    
Prostate cancer cells 25844599    
Prostate cancer cells 25844599    
 Gene ontology annotations for NEDD4L
Molecular Function
    ion channel binding GO:0044325 IPI
    ubiquitin-protein transferase activity GO:0004842 TAS
    sodium channel regulator activity GO:0017080 IDA
    potassium channel inhibitor activity GO:0019870 IDA
    sodium channel inhibitor activity GO:0019871 IDA
    ligase activity GO:0016874 IEA
    protein binding GO:0005515 IPI
    potassium channel regulator activity GO:0015459 IDA
Biological Process
    positive regulation of caveolin-mediated endocytosis GO:2001288 ISS
    negative regulation of sodium ion transmembrane transporter activity GO:2000650 IDA
    positive regulation of protein catabolic process GO:0045732 IEA
    ventricular cardiac muscle cell action potential GO:0086005 ISS
    negative regulation of transcription from RNA polymerase II promoter GO:0000122 TAS
    transmembrane transport GO:0055085 TAS
    response to metal ion GO:0010038 IDA
    negative regulation of transforming growth factor beta receptor signaling pathway GO:0030512 TAS
    ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway GO:0043162 IEA
    regulation of membrane repolarization GO:0060306 IDA
    negative regulation of systemic arterial blood pressure GO:0003085 IEA
    gene expression GO:0010467 TAS
    protein K48-linked ubiquitination GO:0070936 IDA
    regulation of potassium ion transmembrane transporter activity GO:1901016 IDA
    viral life cycle GO:0019058 TAS
    positive regulation of endocytosis GO:0045807 NAS
    protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:0042787 IDA
    cellular sodium ion homeostasis GO:0006883 NAS
    positive regulation of dendrite extension GO:1903861 IDA
    negative regulation of potassium ion transmembrane transport GO:1901380 IDA
    protein ubiquitination GO:0016567 NAS
    regulation of protein catabolic process GO:0042176 NAS
    transcription, DNA-templated GO:0006351 TAS
    regulation of membrane depolarization GO:0003254 IDA
    regulation of membrane potential GO:0042391 IDA
    water homeostasis GO:0030104 NAS
    negative regulation of protein localization to cell surface GO:2000009 IDA
    negative regulation of sodium ion transmembrane transport GO:1902306 IDA
    viral process GO:0016032 TAS
    negative regulation of potassium ion transmembrane transporter activity GO:1901017 IDA
    positive regulation of sodium ion transport GO:0010765 IEA
    transforming growth factor beta receptor signaling pathway GO:0007179 TAS
    positive regulation of cation channel activity GO:2001259 IEA
    excretion GO:0007588 NAS
    regulation of ion transmembrane transport GO:0034765 IDA
    response to salt stress GO:0009651 IEA
    sodium ion transport GO:0006814 NAS
    protein monoubiquitination GO:0006513 IEA
    proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043161 IDA
    transcription initiation from RNA polymerase II promoter GO:0006367 TAS
    regulation of bicellular tight junction assembly GO:2000810 IEA
    ion transmembrane transport GO:0034220 TAS
Subcellular Localization
    plasma membrane GO:0005886 IDA
    cytosol GO:0005829 TAS
    intracellular GO:0005622 IC
    cytoplasm GO:0005737 IBA
    extracellular exosome GO:0070062 IDA
    nucleoplasm GO:0005654 TAS
 Experiment description of studies that identified NEDD4L in exosomes
1
Experiment ID 21
ISEV standards
✔
EM|IEM
EV Biophysical techniques
✔
Alix|TSG101|HSP70
EV Cytosolic markers
✔
CD63
EV Membrane markers
✘ EV Negative markers
✘ EV Particle analysis
Identified molecule protein
Identification method
Mass spectrometry   
PubMed ID 19837982    
Organism Homo sapiens
Experiment description Proteomic and bioinformatic analysis of immunoaffinity-purified exosomes derived from the human colon tumor cell line LIM1215.
Authors Suresh Mathivanan, Justin W.E. Lim, Bow J. Tauro, Hong Ji, Robert L. Moritz and Richard J. Simpson
Journal name MCP
Publication year 2009
Sample Colorectal cancer cells
Sample name LIM1215
Isolation/purification methods Filtration
Ultracentrifugation
Sucrose density gradient
Flotation density 1.10-1.12 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry [Orbitrap]
Western blotting
2
Experiment ID 207
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101|HSP70
EV Cytosolic markers
✔
FLOT1
EV Membrane markers
✔
VDAC
EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 23161513    
Organism Homo sapiens
Experiment description Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS.
Authors Demory Beckler M, Higginbotham JN, Franklin JL, Ham AJ, Halvey PJ, Imasuen IE, Whitwell C, Li M, Liebler DC, Coffey RJ.
Journal name Mol Cell Proteomics
Publication year 2012
Sample Colorectal cancer cells
Sample name DKO-1
Isolation/purification methods Differential centrifugation
Filtration
Flotation density -
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
3
Experiment ID 208
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101|HSP70
EV Cytosolic markers
✔
FLOT1
EV Membrane markers
✔
VDAC
EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 23161513    
Organism Homo sapiens
Experiment description Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS.
Authors Demory Beckler M, Higginbotham JN, Franklin JL, Ham AJ, Halvey PJ, Imasuen IE, Whitwell C, Li M, Liebler DC, Coffey RJ.
Journal name Mol Cell Proteomics
Publication year 2012
Sample Colorectal cancer cells
Sample name Dks-8
Isolation/purification methods Differential centrifugation
Filtration
Flotation density -
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
4
Experiment ID 209
ISEV standards
✘ EV Biophysical techniques
✔
TSG101|HSP70
EV Cytosolic markers
✔
FLOT1
EV Membrane markers
✔
VDAC
EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 23161513    
Organism Homo sapiens
Experiment description Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS.
Authors Demory Beckler M, Higginbotham JN, Franklin JL, Ham AJ, Halvey PJ, Imasuen IE, Whitwell C, Li M, Liebler DC, Coffey RJ.
Journal name Mol Cell Proteomics
Publication year 2012
Sample Colorectal cancer cells
Sample name DLD-1
Isolation/purification methods Differential centrifugation
Filtration
Flotation density -
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
5
Experiment ID 236
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101|Alix|HSC70|GAPDH
EV Cytosolic markers
✘ EV Membrane markers
✔
HSP90B1
EV Negative markers
✔
qNano
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 26054723    
Organism Homo sapiens
Experiment description Hepatocellular carcinoma-derived exosomes promote motility of immortalized hepatocyte through transfer of oncogenic proteins and RNAs
Authors He M, Qin H, Poon TC, Sze SC, Ding X, Co NN, Ngai SM, Chan TF, Wong N
Journal name Carcinogenesis
Publication year 2015
Sample Hepatocellular carcinoma cells
Sample name MHCC97L
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Sucrose density gradient
Flotation density 1.13-1.19 g/mL
Molecules identified in the study Protein
RNA
Methods used in the study Western blotting
Mass spectrometry
RT-PCR
RNA Sequencing
6
Experiment ID 254
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101
EV Cytosolic markers
✔
FLOT1|CD81
EV Membrane markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25950383    
Organism Homo sapiens
Experiment description Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines
Authors Lazar I, Clement E, Ducoux-Petit M, Denat L, Soldan V, Dauvillier S, Balor S4, Burlet-Schiltz O1, Larue L, Muller C Nieto L
Journal name Pigment Cell Melanoma Res
Publication year 2015
Sample Melanoma cells
Sample name MNT-1
Isolation/purification methods Differential centrifugation
Unltracentrifugation
Sucrose density gradient
Flotation density 1.13 - 1.19 g/mL
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
7
Experiment ID 255
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101
EV Cytosolic markers
✔
FLOT1
EV Membrane markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25950383    
Organism Homo sapiens
Experiment description Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines
Authors Lazar I, Clement E, Ducoux-Petit M, Denat L, Soldan V, Dauvillier S, Balor S4, Burlet-Schiltz O1, Larue L, Muller C Nieto L
Journal name Pigment Cell Melanoma Res
Publication year 2015
Sample Melanoma cells
Sample name G1
Isolation/purification methods Differential centrifugation
Unltracentrifugation
Sucrose density gradient
Flotation density 1.13 - 1.19 g/mL
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
8
Experiment ID 256
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101
EV Cytosolic markers
✔
FLOT1
EV Membrane markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25950383    
Organism Homo sapiens
Experiment description Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines
Authors Lazar I, Clement E, Ducoux-Petit M, Denat L, Soldan V, Dauvillier S, Balor S4, Burlet-Schiltz O1, Larue L, Muller C Nieto L
Journal name Pigment Cell Melanoma Res
Publication year 2015
Sample Melanoma cells
Sample name 501mel
Isolation/purification methods Differential centrifugation
Unltracentrifugation
Sucrose density gradient
Flotation density 1.13 - 1.19 g/mL
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
9
Experiment ID 257
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101
EV Cytosolic markers
✔
FLOT1
EV Membrane markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25950383    
Organism Homo sapiens
Experiment description Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines
Authors Lazar I, Clement E, Ducoux-Petit M, Denat L, Soldan V, Dauvillier S, Balor S4, Burlet-Schiltz O1, Larue L, Muller C Nieto L
Journal name Pigment Cell Melanoma Res
Publication year 2015
Sample Melanoma cells
Sample name Daju
Isolation/purification methods Differential centrifugation
Unltracentrifugation
Sucrose density gradient
Flotation density 1.13 - 1.19 g/mL
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
10
Experiment ID 258
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101
EV Cytosolic markers
✔
FLOT1|CD81
EV Membrane markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25950383    
Organism Homo sapiens
Experiment description Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines
Authors Lazar I, Clement E, Ducoux-Petit M, Denat L, Soldan V, Dauvillier S, Balor S4, Burlet-Schiltz O1, Larue L, Muller C Nieto L
Journal name Pigment Cell Melanoma Res
Publication year 2015
Sample Melanoma cells
Sample name SKMEL28
Isolation/purification methods Differential centrifugation
Unltracentrifugation
Sucrose density gradient
Flotation density 1.13 - 1.19 g/mL
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
11
Experiment ID 259
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101
EV Cytosolic markers
✔
FLOT1
EV Membrane markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25950383    
Organism Homo sapiens
Experiment description Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines
Authors Lazar I, Clement E, Ducoux-Petit M, Denat L, Soldan V, Dauvillier S, Balor S4, Burlet-Schiltz O1, Larue L, Muller C Nieto L
Journal name Pigment Cell Melanoma Res
Publication year 2015
Sample Melanoma cells
Sample name A375M
Isolation/purification methods Differential centrifugation
Unltracentrifugation
Sucrose density gradient
Flotation density 1.13 - 1.19 g/mL
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
12
Experiment ID 211
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101|Alix
EV Cytosolic markers
✔
EpCAM|TFRC
EV Membrane markers
✔
cytochrome c|GOLGA2
EV Negative markers
✘ EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 23333927    
Organism Homo sapiens
Experiment description Characterization and proteomic analysis of ovarian cancer-derived exosomes.
Authors Liang B, Peng P, Chen S, Li L, Zhang M, Cao D, Yang J, Li H, Gui T, Li X, Shen K.
Journal name J Proteomics
Publication year 2013
Sample Ovarian cancer cells
Sample name IGROV1
Isolation/purification methods Differential centrifugation
Ultracentrifugation
Sucrose density gradient
Flotation density 1.09-1.15 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
13
Experiment ID 212
ISEV standards
✔
CEM
EV Biophysical techniques
✔
TSG101|Alix
EV Cytosolic markers
✔
EpCAM|TFRC
EV Membrane markers
✔
Cytochrome C|GOLGA2
EV Negative markers
✘ EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 23333927    
Organism Homo sapiens
Experiment description Characterization and proteomic analysis of ovarian cancer-derived exosomes.
Authors Liang B, Peng P, Chen S, Li L, Zhang M, Cao D, Yang J, Li H, Gui T, Li X, Shen K.
Journal name J Proteomics
Publication year 2013
Sample Ovarian cancer cells
Sample name OVCAR-3
Isolation/purification methods Differential centrifugation
Ultracentrifugation
Sucrose density gradient
Flotation density 1.09-1.15 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
14
Experiment ID 231
ISEV standards
✘ EV Biophysical techniques
✔
Alix
EV Cytosolic markers
✔
CD63|CD9
EV Membrane markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25332113    
Organism Homo sapiens
Experiment description Lipidomic and proteomic characterization of platelet extracellular vesicle subfractions from senescent platelets
Authors Pienimaeki-Roemer A, Kuhlmann K, Bottcher A, Konovalova T, Black A, Orso E, Liebisch G, Ahrens M, Eisenacher M, Meyer HE, Schmitz G.
Journal name Transfusion
Publication year 2015
Sample Platelets
Sample name PL-Exs - Rep 1
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Optiprep density gradient
Flotation density 1.12-1.15 g/mL
Molecules identified in the study Protein
Lipids
Methods used in the study Western blotting
Mass spectrometry
15
Experiment ID 232
ISEV standards
✘ EV Biophysical techniques
✘ EV Cytosolic markers
✘ EV Membrane markers
✘ EV Negative markers
✘ EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25332113    
Organism Homo sapiens
Experiment description Lipidomic and proteomic characterization of platelet extracellular vesicle subfractions from senescent platelets
Authors Pienimaeki-Roemer A, Kuhlmann K, Bottcher A, Konovalova T, Black A, Orso E, Liebisch G, Ahrens M, Eisenacher M, Meyer HE, Schmitz G.
Journal name Transfusion
Publication year 2015
Sample Platelets
Sample name PL-Exs - Rep 2
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Optiprep density gradient
Flotation density 1.12-1.15 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
16
Experiment ID 233
ISEV standards
✘ EV Biophysical techniques
✘ EV Cytosolic markers
✘ EV Membrane markers
✘ EV Negative markers
✘ EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25332113    
Organism Homo sapiens
Experiment description Lipidomic and proteomic characterization of platelet extracellular vesicle subfractions from senescent platelets
Authors Pienimaeki-Roemer A, Kuhlmann K, Bottcher A, Konovalova T, Black A, Orso E, Liebisch G, Ahrens M, Eisenacher M, Meyer HE, Schmitz G.
Journal name Transfusion
Publication year 2015
Sample Platelets
Sample name PL-Exs - Rep 3
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Optiprep density gradient
Flotation density 1.12-1.15 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
17
Experiment ID 275
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101|Alix|RAB5A
EV Cytosolic markers
✔
CD9|CD82|CD63|CD81
EV Membrane markers
✔
AIF
EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25844599    
Organism Homo sapiens
Experiment description Molecular profiling of prostate cancer derived exosomes may reveal a predictive signature for response to docetaxel.
Authors Kharaziha P, Chioureas D, Rutishauser D, Baltatzis G, Lennartsson L, Fonseca P, Azimi A, Hultenby K, Zubarev R, Ullen A, Yachnin J, Nilsson S, Panaretakis T.
Journal name Oncotarget
Publication year 2015
Sample Prostate cancer cells
Sample name DU145 - Docetaxel sensitive
Isolation/purification methods Filtration
Ultracentrifugation
Sucrose density gradient
Flotation density 1.12-1.19 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry/Flow cytometry/Western blotting
18
Experiment ID 274
ISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101|Alix|RAB5A
EV Cytosolic markers
✔
CD9|CD82|CD63|CD81
EV Membrane markers
✔
AIF
EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25844599    
Organism Homo sapiens
Experiment description Molecular profiling of prostate cancer derived exosomes may reveal a predictive signature for response to docetaxel.
Authors Kharaziha P, Chioureas D, Rutishauser D, Baltatzis G, Lennartsson L, Fonseca P, Azimi A, Hultenby K, Zubarev R, Ullen A, Yachnin J, Nilsson S, Panaretakis T.
Journal name Oncotarget
Publication year 2015
Sample Prostate cancer cells
Sample name DU145 - Docetaxel resistant
Isolation/purification methods Filtration
Ultracentrifugation
Sucrose density gradient
Flotation density 1.13-1.18 g/mL
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
Flow cytometry
Western blotting
 Protein-protein interactions for NEDD4L
  Protein Interactor ExoCarta ID Identification method PubMed Species
1 SCNN1B  
Invitro Homo sapiens
2 SFN 2810
Affinity Capture-MS Homo sapiens
3 ARHGDIA 396
Two-hybrid Homo sapiens
4 SCNN1G  
Invitro Homo sapiens
5 NR3C1 2908
Reconstituted Complex Homo sapiens
6 SGK1  
Affinity Capture-MS Homo sapiens
7 SCNN1A  
Invitro Homo sapiens
8 RNF11 26994
Affinity Capture-MS Homo sapiens
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