NEDD4
entrez
4734
canonical
uniprot
P46934
canonical
ensembl
ENSG00000069869
resolver
ensp
ENSP00000345530
resolver
ensp
ENSP00000410613
resolver
ensp
ENSP00000422455
resolver
ensp
ENSP00000422705
resolver
ensp
ENSP00000424827
resolver
genesymbol
NEDD4
resolver
genesymbol_syn
KIAA0093
resolver
genesymbol_syn
NEDD4-1
resolver
genesymbol_syn
RPF1
resolver
hgnc
HGNC:7727
resolver
uniprot
A1KY35
resolver
uniprot
A6ND72
resolver
uniprot
A7MD29
resolver
uniprot
B4E2R7
resolver
uniprot
B7ZM59
resolver
uniprot
B7ZM60
resolver
uniprot
B9EGN5
resolver
uniprot
D6RF89
resolver
uniprot_entry
NEDD4_HUMAN
resolver
uniprot_sec
A1KY35
resolver
uniprot_sec
A6ND72
resolver
uniprot_sec
A7MD29
resolver
uniprot_sec
B4E2R7
resolver
uniprot_sec
B7ZM59
resolver
uniprot_sec
B7ZM60
resolver
uniprot_sec
B9EGN5
resolver
uniprot_sec
D6RF89
resolver
activity_regulation
ACTIVITY REGULATION: Activated by NDFIP1- and NDFIP2-binding. {ECO:0000250}.
uniprot
proteins
amino_acid_sequence
MAQSLRLHFAARRSNTYPLSETSGDDLDSHVHMCFKRPTRISTSNVVQMKLTPRQTALAPLIKENVQSQERSSVPSSENVNKKSSCLQISLQPTRYSGYLQSSNVLADSDDASFTCILKDGIYSSAVVDNELNAVNDGHLVSSPAICSGSLSNFSTSDNGSYSSNGSDFGSCASITSGGSYTNSVISDSSSYTFPPSDDTFLGGNLPSDSTSNRSVPNRNTTPCEIFSRSTSTDPFVQDDLEHGLEIMKLPVSRNTKIPLKRYSSLVIFPRSPSTTRPTSPTSLCTLLSKGSYQTSHQFIISPSEIAHNEDGTSAKGFLSTAVNGLRLSKTICTPGEVRDIRPLHRKGSLQKKIVLSNNTPRQTVCEKSSEGYSCVSVHFTQRKAATLDCETTNGDCKPEMSEIKLNSDSEYIKLMHRTSACLPSSQNVDCQININGELERPHSQMNKNHGILRRSISLGGAYPNISCLSSLKHNCSKGGPSQLLIKFASGNEGKVDNLSRDSNRDCTNELSNSCKTRDDFLGQVDVPLYPLPTENPRLERPYTFKDFVLHPRSHKSRVKGYLRLKMTYLPKTSGSEDDNAEQAEELEPGWVVLDQPDAACHLQQQQEPSPLPPGWEERQDILGRTYYVNHESRRTQWKRPTPQDNLTDAENGNIQLQAQRAFTTRRQISEETESVDNRESSENWEIIREDEATMYSNQAFPSPPPSSNLDVPTHLAEELNARLTIFGNSAVSQPASSSNHSSRRGSLQAYTFEEQPTLPVLLPTSSGLPPGWEEKQDERGRSYYVDHNSRTTTWTKPTVQATVETSQLTSSQSSAGPQSQASTSDSGQQVTQPSEIEQGFLPKGWEVRHAPNGRPFFIDHNTKTTTWEDPRLKIPAHLRGKTSLDTSNDLGPLPPGWEERTHTDGRIFYINHNIKRTQWEDPRLENVAITGPAVPYSRDYKRKYEFFRRKLKKQNDIPNKFEMKLRRATVLEDSYRRIMGVKRADFLKARLWIEFDGEKGLDYGGVAREWFFLISKEMFNPYYGLFEYSATDNYTLQINPNSGLCNEDHLSYFKFIGRVAGMAVYHGKLLDGFFIRPFYKMMLHKPITLHDMESVDSEYYNSLRWILENDPTELDLRFIIDEELFGQTHQHELKNGGSEIVVTNKNKKEYIYLVIQWRFVNRIQKQMAAFKEGFFELIPQDLIKIFDENELELLMCGLGDVDVNDWREHTKYKNGYSANHQVIQWFWKAVLMMDSEKRIRLLQFVTGTSRVPMNGFAELYGSNGPQSFTVEQWGTPEKLPRAHTCFNRLDLPPYESFEELWDKLQMAIENTQGFDGVD
uniprot
proteins
ec_number
2.3.2.26
uniprot
proteins
function
FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Specifically ubiquitinates 'Lys-63' in target proteins (PubMed:19920177, PubMed:21399620, PubMed:23644597). Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes (By similarity). Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes (PubMed:21765395). Promotes ubiquitination of RAPGEF2 (PubMed:11598133). According to PubMed:18562292 the direct link between NEDD4 and PTEN regulation through polyubiquitination described in PubMed:17218260 is questionable. Involved in ubiquitination of ERBB4 intracellular domain E4ICD (By similarity). Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development (By similarity). Ubiquitinates TNK2 and regulates EGF-induced degradation of EGFR and TNF2 (PubMed:20086093). Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Ubiquitinates DAZAP2, leading to its proteasomal degradation (PubMed:11342538). Ubiquitinates POLR2A (PubMed:19920177). Functions as a platform to recruit USP13 to form an NEDD4-USP13 deubiquitination complex that plays a critical role in cleaving the 'Lys-48'-linked ubiquitin chains of VPS34 and then stabilizing VPS34, thus promoting the formation of autophagosomes (PubMed:32101753). {ECO:0000250|UniProtKB:P46935, ECO:0000269|PubMed:11342538, ECO:0000269|PubMed:11598133, ECO:0000269|PubMed:17218260, ECO:0000269|PubMed:18562292, ECO:0000269|PubMed:21399620, ECO:0000269|PubMed:21765395, ECO:0000269|PubMed:23644597, ECO:0000269|PubMed:25631046, ECO:0000269|PubMed:32101753}.; FUNCTION: (Microbial infection) Involved in the ubiquitination of Ebola virus protein VP40 which plays a role in viral budding. {ECO:0000269|PubMed:12559917, ECO:0000269|PubMed:18305167}.
uniprot
proteins
mass_dalton
149114
uniprot
proteins
mutagenesis
MUTAGEN 724..726; /note="LTI->ATA: Increased nuclear localization."; /evidence="ECO:0000269|PubMed:11342538"; MUTAGEN 795; /note="W->A: Abolishes interaction with ARRDC3; when associated with A-868 and A-920."; /evidence="ECO:0000269|PubMed:24379409"; MUTAGEN 868; /note="W->A: Abolishes interaction with ARRDC3; when associated with A-795 and A-920."; /evidence="ECO:0000269|PubMed:24379409"; MUTAGEN 920; /note="W->A: Abolishes interaction with ARRDC3; when associated with A-795 and A-868."; /evidence="ECO:0000269|PubMed:24379409"; MUTAGEN 1286; /note="C->A: Abolishes ubiquitination of DAZAP2."; /evidence="ECO:0000269|PubMed:11342538
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:23644597}.
uniprot
proteins
post_translational_modification
PTM: Undergoes 'Lys-29'-linked auto-ubiquitination at Lys-1279 and serves as a scaffold for recruiting USP13 to form an NEDD4-USP13 deubiquitination complex. {ECO:0000269|PubMed:32101753}.
uniprot
proteins
pubmed
11342538
uniprot
proteins
pubmed
11598133
uniprot
proteins
pubmed
12559917
uniprot
proteins
pubmed
14581525
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16572171
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17218260
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18305167
uniprot
proteins
pubmed
18353951
uniprot
proteins
pubmed
18562292
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18819914
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19920177
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20086093
uniprot
proteins
pubmed
20159449
uniprot
proteins
pubmed
20559325
uniprot
proteins
pubmed
21191027
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21399620
uniprot
proteins
pubmed
21765395
uniprot
proteins
pubmed
22096579
uniprot
proteins
pubmed
22179831
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
23166351
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23644597
uniprot
proteins
pubmed
23665454
uniprot
proteins
pubmed
23873930
uniprot
proteins
pubmed
24379409
uniprot
proteins
pubmed
25631046
uniprot
proteins
pubmed
26854353
uniprot
proteins
pubmed
32101753
uniprot
proteins
pubmed
7788527
uniprot
proteins
sequence_length
1319
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11342538}. Nucleus {ECO:0000269|PubMed:11342538}. Cell membrane {ECO:0000250|UniProtKB:P46935}; Peripheral membrane protein {ECO:0000250|UniProtKB:P46935}. Note=Predominantly cytoplasmic but also located in the nucleus (PubMed:11342538). Recruited to the plasma membrane by GRB10. Once complexed with GRB10 and IGF1R, follows IGF1R internalization, remaining associated with early endosomes. Uncouples from IGF1R-containing endosomes before the sorting of the receptor to the lysosomal compartment (By similarity). May be recruited to exosomes by NDFIP1 (PubMed:18819914). {ECO:0000250|UniProtKB:P46935, ECO:0000269|PubMed:11342538, ECO:0000269|PubMed:18819914}.
uniprot
proteins