Protein detail
NEDD4
E3 ubiquitin-protein ligase NEDD4 (EC 2.3.2.26) (Cell proliferation-inducing gene 53 protein) (HECT-type E3 ubiquitin transferase NEDD4) (Neural precursor cell expressed developmentally down-regulated protein 4) (NEDD-4)
Protein symbol NEDD4 | UniProt ID | EVMP score 0.38 |
Frequency 1 | Transmembrane count | Protein classification EnzymesMetabolic proteinsPredicted intracellular proteinsTransporters |
EVMP score: annotation confidence score.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40
Basic Information
Protein Names
E3 ubiquitin-protein ligase NEDD4 (EC 2.3.2.26) (Cell proliferation-inducing gene 53 protein) (HECT-type E3 ubiquitin transferase NEDD4) (Neural precursor cell expressed developmentally down-regulated protein 4) (NEDD-4)
Protein Class
EnzymesMetabolic proteinsPredicted intracellular proteinsTransporters
Protein Function
- ENZYME proteins:Transferases
- Enzymes
- Predicted intracellular proteins
- Transporters:Accessory Factors Involved in Transport
Ensembl
Entrez Gene Symbol
Gene Synonym
KIAA0093MGC176705NEDD4-1RPF1
Gene Description
NEDD4 E3 ubiquitin protein ligase
Chromosome
15
Position
55826922-55993660
Frequency
1
EVMP Score
0.38
Fluorescence & Localization
Tissue SpecificliverBrain Regional Specificchoroid plexusSingle-Nuclei Brain Specificchoroid plexus epithelial cell
Function & Pathway
Protein Function
- ENZYME proteins:Transferases
- Enzymes
- Predicted intracellular proteins
- Transporters:Accessory Factors Involved in Transport
Cellular Component
- GO:0000151 ubiquitin ligase complex
- GO:0000785 chromatin
- GO:0005634 nucleus
- GO:0005737 cytoplasm
- GO:0005794 Golgi apparatus
- GO:0005829 cytosol
- GO:0005886 plasma membrane
- GO:0005938 cell cortex
- GO:0016327 apicolateral plasma membrane
- GO:0032991 protein-containing complex
- GO:0043197 dendritic spine
- GO:0048471 perinuclear region of cytoplasm
- GO:0070062 extracellular exosome
Molecular Function
- GO:0005515 protein binding
- GO:0019871 sodium channel inhibitor activity
- GO:0019899 enzyme binding
- GO:0019904 protein domain specific binding
- GO:0031698 beta-2 adrenergic receptor binding
- GO:0043130 ubiquitin binding
- GO:0050815 phosphoserine residue binding
- GO:0050816 phosphothreonine residue binding
- GO:0061630 ubiquitin protein ligase activity
- GO:0070063 RNA polymerase binding
- GO:0070064 proline-rich region binding
Biological Process
- GO:1902239 negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator
- GO:1902238 regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator
- GO:1902219 negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress
KEGG
Reactome
- R-hsa-1280218 adaptive immune system
- R-hsa-983168 antigen processing ubiquitination proteasome degradation
- R-hsa-1169410 antimicrobial mechanism of ifn stimulated genes
- R-hsa-983169 class i mhc mediated antigen processing presentation
- R-hsa-1280215 cytokine signaling in immune system
- R-hsa-1253288 downregulation of erbb4 signaling
- R-hsa-913531 interferon signaling
- R-hsa-9006925 intracellular signaling by second messengers
- R-hsa-1169408 isg15 antiviral mechanism
- R-hsa-6807070 pten regulation
- R-hsa-8948747 regulation of pten localization
- R-hsa-8948751 regulation of pten stability and activity
- R-hsa-1236394 signaling by erbb4
- R-hsa-9006934 signaling by receptor tyrosine kinases
Canonical Pathways
- M236 Pid delta np63 pathway
- M145 Pid p53 downstream pathway
Mediation Categories
Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
13 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| NEDD4 | CASP3 | P42574 | D | 526 | cleavage | HPRD | HPRD:9593687 |
| NEDD4 | CASP3 | P42574 | D | 179 | cleavage | HPRD | HPRD:9593687 |
| NEDD4 | CASP6 | P55212 | D | 526 | cleavage | HPRD | HPRD:9593687 |
| NEDD4 | CASP6 | P55212 | D | 179 | cleavage | HPRD | HPRD:9593687 |
| NEDD4 | CASP7 | P55210 | D | 526 | cleavage | HPRD | HPRD:9593687 |
| NEDD4 | CASP7 | P55210 | D | 179 | cleavage | HPRD | HPRD:9593687 |
| NEDD4 | CASP1 | P29466 | D | 526 | cleavage | HPRD | HPRD:9593687 |
| NEDD4 | CASP1 | P29466 | D | 179 | cleavage | HPRD | HPRD:9593687 |
| NEDD4 | SRC | P12931 | Y | 332 | phosphorylation | PhosphoSite | |
| NEDD4 | SRC | P12931 | Y | 43 | phosphorylation | PhosphoSite |
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Ligand-Receptor Signaling
7 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| intracellular | intracellular | LOCATE | No | No | No | No | No |
| intracellular | intracellular | ComPPI | No | No | No | No | No |
| intracellular | intracellular | GO_Intercell | No | No | No | No | No |
| intracellular | intracellular | UniProt_location | No | No | No | No | No |
| intracellular | intracellular | OmniPath | No | No | No | No | No |
| plasma_membrane | plasma_membrane | UniProt_location | No | No | No | No | No |
| plasma_membrane | plasma_membrane | OmniPath | No | No | No | No | No |
Regulatory Interaction Network
169 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| COMPLEX:P62979_Q9Y385 | NEDD4 | P46934 | Yes | Yes | No | SIGNOR | SIGNOR:34199813 | |
| COMPLEX:P0CG48_P51965 | NEDD4 | P46934 | Yes | Yes | No | SIGNOR | SIGNOR:34199813 | |
| COMPLEX:P62987_Q96LR5 | NEDD4 | P46934 | Yes | Yes | No | SIGNOR | SIGNOR:34199813 | |
| COMPLEX:P0CG48_Q8WVN8 | NEDD4 | P46934 | Yes | Yes | No | SIGNOR | SIGNOR:34199813 | |
| COMPLEX:P51668_P62979 | NEDD4 | P46934 | Yes | Yes | No | SIGNOR | SIGNOR:34199813 | |
| COMPLEX:P60604_P62987 | NEDD4 | P46934 | Yes | Yes | No | SIGNOR | SIGNOR:34199813 | |
| COMPLEX:P0CG48_P61086 | NEDD4 | P46934 | Yes | Yes | No | SIGNOR | SIGNOR:34199813 | |
| COMPLEX:P62987_Q5JXB2 | NEDD4 | P46934 | Yes | Yes | No | SIGNOR | SIGNOR:34199813 | |
| COMPLEX:P51965_P62979 | NEDD4 | P46934 | Yes | Yes | No | SIGNOR | SIGNOR:34199813 | |
| COMPLEX:P0CG47_Q9Y385 | NEDD4 | P46934 | Yes | Yes | No | SIGNOR | SIGNOR:34199813 |
Protein Complex Composition
39 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| NDFIP1-NEDD4L-SLC11A2 complex | NDFIP1NEDD4LSLC11A2 | P49281Q96PU5Q9BT67 | 0:0:0 | CORUM | CORUM:7358 | 19706893 |
| Ub:HECT_E3 | NEDD4UBB | P0CG47P46934 | 0:0 | SIGNOR | SIGNOR:SIGNOR-C518 | |
| Ub:HECT_E3 | NEDD4LUBB | P0CG47Q96PU5 | 0:0 | SIGNOR | SIGNOR:SIGNOR-C518 | |
| Ub:HECT_E3 | NEDD4UBC | P0CG48P46934 | 2:2 | SIGNORPDB | SIGNOR:SIGNOR-C518PDB:5c7j | |
| Ub:HECT_E3 | NEDD4LUBC | P0CG48Q96PU5 | 0:0 | SIGNOR | SIGNOR:SIGNOR-C518 | |
| Ub:HECT_E3 | NEDD4RPS27A | P46934P62979 | 0:0 | SIGNOR | SIGNOR:SIGNOR-C518 | |
| Ub:HECT_E3 | NEDD4UBA52 | P46934P62987 | 0:0 | SIGNOR | SIGNOR:SIGNOR-C518 | |
| Ub:HECT_E3 | NEDD4LRPS27A | P62979Q96PU5 | 0:0 | SIGNOR | SIGNOR:SIGNOR-C518 | |
| Ub:HECT_E3 | NEDD4LUBA52 | P62987Q96PU5 | 1:1 | SIGNORPDB | SIGNOR:SIGNOR-C518PDB:5hpk | |
| ARRDC1HGSITCHNDFIP1NDFIP2NEDD4NEDD4LSLC11A2TSG101UBBUBCWWP2 | O00308O14964P0CG47P0CG48P46934P49281Q8N5I2Q96J02Q96PU5Q99816Q9BT67Q9NV92 | 1:1:1:1:1:1:1:1:1:1:1:1 | NetworkBlastCompleat | Compleat:HC6473 |
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Sequence, Structure & Domains
Sequences
Length
1,319
Mass
149,114
Sequence
MAQSLRLHFAARRSNTYPLSETSGDDLDSHVHMCFKRPTRISTSNVVQMKLTPRQTALAPLIKENVQSQERSSVPSSENVNKKSSCLQISLQPTRYSGYLQSSNVLADSDDASFTCILKDGIYSSAVVDNELNAVNDGHLVSSPAICSGSLSNFSTSDNGSYSSNGSDFGSCASITSGGSYTNSVISDSSSYTFPPSDDTFLGGNLPSDSTSNRSVPNRNTTPCEIFSRSTSTDPFVQDDLEHGLEIMKLPVSRNTKIPLKRYSSLVIFPRSPSTTRPTSPTSLCTLLSKGSYQTSHQFIISPSEIAHNEDGTSAKGFLSTAVNGLRLSKTICTPGEVRDIRPLHRKGSLQKKIVLSNNTPRQTVCEKSSEGYSCVSVHFTQRKAATLDCETTNGDCKPEMSEIKLNSDSEYIKLMHRTSACLPSSQNVDCQININGELERPHSQMNKNHGILRRSISLGGAYPNISCLSSLKHNCSKGGPSQLLIKFASGNEGKVDNLSRDSNRDCTNELSNSCKTRDDFLGQVDVPLYPLPTENPRLERPYTFKDFVLHPRSHKSRVKGYLRLKMTYLPKTSGSEDDNAEQAEELEPGWVVLDQPDAACHLQQQQEPSPLPPGWEERQDILGRTYYVNHESRRTQWKRPTPQDNLTDAENGNIQLQAQRAFTTRRQISEETESVDNRESSENWEIIREDEATMYSNQAFPSPPPSSNLDVPTHLAEELNARLTIFGNSAVSQPASSSNHSSRRGSLQAYTFEEQPTLPVLLPTSSGLPPGWEEKQDERGRSYYVDHNSRTTTWTKPTVQATVETSQLTSSQSSAGPQSQASTSDSGQQVTQPSEIEQGFLPKGWEVRHAPNGRPFFIDHNTKTTTWEDPRLKIPAHLRGKTSLDTSNDLGPLPPGWEERTHTDGRIFYINHNIKRTQWEDPRLENVAITGPAVPYSRDYKRKYEFFRRKLKKQNDIPNKFEMKLRRATVLEDSYRRIMGVKRADFLKARLWIEFDGEKGLDYGGVAREWFFLISKEMFNPYYGLFEYSATDNYTLQINPNSGLCNEDHLSYFKFIGRVAGMAVYHGKLLDGFFIRPFYKMMLHKPITLHDMESVDSEYYNSLRWILENDPTELDLRFIIDEELFGQTHQHELKNGGSEIVVTNKNKKEYIYLVIQWRFVNRIQKQMAAFKEGFFELIPQDLIKIFDENELELLMCGLGDVDVNDWREHTKYKNGYSANHQVIQWFWKAVLMMDSEKRIRLLQFVTGTSRVPMNGFAELYGSNGPQSFTVEQWGTPEKLPRAHTCFNRLDLPPYESFEELWDKLQMAIENTQGFDGVD
Alternative Products
Event=Alternative splicing; Named isoforms=4; Name=1; IsoId=P46934-1; Sequence=Displayed; Name=2; IsoId=P46934-2; Sequence=VSP_038259; Name=3; IsoId=P46934-3; Sequence=VSP_038258; Name=4; IsoId=P46934-4; Sequence=VSP_038256, VSP_038257
Alternative Sequence
1..419; Missing (in isoform 4); 420..516; SACLPSSQNVDCQININGELERPHSQMNKNHGILRRSISLGGAYPNISCLSSLKHNCSKGGPSQLLIKFASGNEGKVDNLSRDSNRDCTNELSNSCK -> MATCAVEVFGLLEDEENSRIVRVRVIAGIGLAKKDILGASDPYVRVTLYDPMNGVLTSVQTKTIKKSLNPKWNEEILFRVHPQQHRLLFEVFDENRL (in isoform 4); 517..588; Missing (in isoform 3); 589..604; Missing (in isoform 2)
3D Structural Models
Turn
852..854; 861..864; 871..873; 1145..1147
Helix
941..951; 968..970; 971..979; 985..989; 1004..1019; 1022..1024; 1043..1046; 1050..1067; 1077..1083; 1091..1096; 1098..1109; 1113..1115; 1138..1140; 1148..1160; 1162..1164; 1165..1178; 1181..1184; 1189..1196; 1204..1209; 1222..1233; 1236..1247; 1257..1259; 1285..1287; 1298..1309
Beta Strand
520..528; 546..549; 561..569; 841..843; 846..850; 856..860; 865..869; 956..958; 960..966; 990..996; 1025..1031; 1037..1039; 1071..1073; 1118..1125; 1128..1135; 1212..1214; 1219..1221; 1248..1250; 1263..1266; 1270..1272; 1282..1284; 1289..1291
3D Structure
NMR spectroscopy (4); X-ray crystallography (11)
Domain & Motif Annotations
Compositional Bias
207..229; Polar residues; 796..809; Polar residues; 810..825; Low complexity
Motif
716..726; Nuclear export signal
Domain (CC)
WW domains are involved in recognizing PPxY motifs in substrate proteins (PubMed:21191027, PubMed:23665454, PubMed:24379409). The WW domains mediate interaction with LITAF, RNF11, WBP1, WBP2, PMEPAI, NDFIP1 and PRRG2 (By similarity).
Domain (FT)
610..643; WW 1; 767..800; WW 2; 840..873; WW 3; 892..925; WW 4; 984..1318; HECT
Region
204..229; Disordered; 578..981; Mediates interaction with TNIK; 755..780; Disordered; 796..834; Disordered
Clinical Relevance
Drugs
Interaction Protein
ENSG00000034713ENSG00000077782ENSG00000078900ENSG00000108953ENSG00000111319ENSG00000113369ENSG00000120215ENSG00000123091ENSG00000124496ENSG00000131188ENSG00000135063ENSG00000135378ENSG00000139112ENSG00000140941ENSG00000146648ENSG00000155099ENSG00000162511ENSG00000168447ENSG00000168675ENSG00000170296ENSG00000171729ENSG00000171862ENSG00000172689ENSG00000189067ENSG00000198382
Interaction Count
25
Interaction Dataset
intact_biogrid