UniProtKB - P46935 (NEDD4_MOUSE)
E3 ubiquitin-protein ligase NEDD4
Nedd4
Functioni
Miscellaneous
Catalytic activityi
- S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.By similarity EC:2.3.2.26
Activity regulationi
: protein ubiquitination Pathwayi
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 854 | Glycyl thioester intermediate | 1 |
GO - Molecular functioni
- ionotropic glutamate receptor binding Source: ParkinsonsUK-UCL
- phosphoserine residue binding Source: BHF-UCL
- phosphothreonine residue binding Source: BHF-UCL
- proline-rich region binding Source: MGI
- protein C-terminus binding Source: MGI
- sodium channel inhibitor activity Source: MGI
- ubiquitin protein ligase activity Source: MGI
- ubiquitin-protein transferase activity Source: MGI
GO - Biological processi
- adaptive immune response Source: MGI
- blood vessel morphogenesis Source: MGI
- endocardial cushion development Source: MGI
- negative regulation of sodium ion transmembrane transporter activity Source: GO_Central
- negative regulation of sodium ion transport Source: MGI
- negative regulation of transcription by RNA polymerase II Source: MGI
- negative regulation of vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
- neuromuscular junction development Source: MGI
- neuron projection development Source: GO_Central
- outflow tract morphogenesis Source: MGI
- positive regulation of protein catabolic process Source: MGI
- proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
- protein K63-linked ubiquitination Source: UniProtKB
- protein monoubiquitination Source: MGI
- protein polyubiquitination Source: GO_Central
- protein targeting to lysosome Source: GO_Central
- protein ubiquitination Source: MGI
- receptor catabolic process Source: GO_Central
- receptor internalization Source: GO_Central
- regulation of dendrite morphogenesis Source: UniProtKB
- regulation of postsynaptic neurotransmitter receptor internalization Source: MGI
- regulation of protein catabolic process at postsynapse, modulating synaptic transmission Source: MGI
- regulation of synapse organization Source: MGI
- T cell activation Source: MGI
- ubiquitin-dependent protein catabolic process Source: MGI
Keywordsi
Molecular function | Transferase |
Biological process | Neurogenesis, Ubl conjugation pathway |
Enzyme and pathway databases
Reactomei | R-MMU-1169408, ISG15 antiviral mechanism R-MMU-1253288, Downregulation of ERBB4 signaling R-MMU-8948747, Regulation of PTEN localization R-MMU-8948751, Regulation of PTEN stability and activity R-MMU-983168, Antigen processing: Ubiquitination & Proteasome degradation |
UniPathwayi | UPA00143 |
Names & Taxonomyi
Protein namesi | Recommended name: E3 ubiquitin-protein ligase NEDD4 (EC:2.3.2.26By similarity)Alternative name(s): HECT-type E3 ubiquitin transferase NEDD4 Neural precursor cell expressed developmentally down-regulated protein 4 Short name: NEDD-4 |
Gene namesi | Name:Nedd4 Synonyms:Kiaa0093, Nedd-4, Nedd4-1, Nedd4a |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:97297, Nedd4 |
Subcellular locationi
Plasma membrane
Other locations
Note: 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.By similarity
Cytosol
- cytosol Source: MGI
- postsynaptic cytosol Source: SynGO
Plasma Membrane
- plasma membrane Source: UniProtKB-SubCell
Other locations
- cytoplasm Source: MGI
- dendritic spine Source: SynGO
- glutamatergic synapse Source: SynGO
- membrane Source: MGI
- membrane raft Source: MGI
- microvillus Source: MGI
- ubiquitin ligase complex Source: MGI
Keywords - Cellular componenti
Cell membrane, Cytoplasm, MembranePathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 854 | C → S: Loss of ubiquitin-ligase activity. No effect on VEGFR-2/KDFR degradation. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000120320 | 1 – 887 | E3 ubiquitin-protein ligase NEDD4Add BLAST | 887 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 215 | PhosphoserineBy similarity | 1 | |
Modified residuei | 287 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 309 | PhosphoserineCombined sources | 1 | |
Modified residuei | 380 | PhosphoserineBy similarity | 1 | |
Modified residuei | 385 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
EPDi | P46935 |
jPOSTi | P46935 |
MaxQBi | P46935 |
PaxDbi | P46935 |
PRIDEi | P46935 |
PTM databases
iPTMneti | P46935 |
PhosphoSitePlusi | P46935 |
SwissPalmi | P46935 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSMUSG00000032216, Expressed in metanephric loop of Henle and 328 other tissues |
ExpressionAtlasi | P46935, baseline and differential |
Genevisiblei | P46935, MM |
Interactioni
Subunit structurei
Binds SCNN1A, SCNN1B and SCNN1G.
Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase and may induce its recruitment to exosomes.
Interacts with UBE2D2 (PubMed:9182527). Binds, in vitro, through the WW2 and WW3 domains, to neural isoforms of ENAH that contain the PPSY motif (PubMed:9407065).
Interacts with BEAN1, LITAF, RNF11, WBP1, WBP2, PMEPAI and PRRG2 (PubMed:11042109).
Interacts with murine leukemia virus Gag polyprotein (via PPXY motif) (PubMed:15908698).
Interacts (via C2 domain) with GRB10 (via SH2 domain) (PubMed:12697834, PubMed:15060076, PubMed:18286479, PubMed:20980250).
Interacts with ERBB4 (PubMed:19193720, PubMed:19047365).
Interacts with TNIK; the interaction is direct, allows the TNIK-dependent recruitment of RAP2A and its ubiquitination by NEDD4 (PubMed:20159449).
Interacts (via WW3 domain) with TNK2; EGF promotes this interaction.
Interacts (via WW3 domain) with FGFR1 (via C-terminus).
Interacts with OTUD7B (By similarity).
Interacts with ISG15 (By similarity).
Interacts (via WW domain) with RAPGEF2; this interaction leads to ubiquitination and degradation via the proteasome pathway.
Interacts (via WW domains) with ARRDC3 (via PPXY motifs) (By similarity).
Interacts with LAPTM4B; may play a role in the lysosomal sorting of LAPTM4B (By similarity).
Interacts with ZBTB7B (PubMed:28784777).
By similarity12 PublicationsBinary interactionsi
Hide detailsP46935
GO - Molecular functioni
- ionotropic glutamate receptor binding Source: ParkinsonsUK-UCL
- phosphoserine residue binding Source: BHF-UCL
- phosphothreonine residue binding Source: BHF-UCL
- proline-rich region binding Source: MGI
- protein C-terminus binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 201723, 80 interactors |
DIPi | DIP-32323N |
ELMi | P46935 |
IntActi | P46935, 23 interactors |
MINTi | P46935 |
STRINGi | 10090.ENSMUSP00000034740 |
Miscellaneous databases
RNActi | P46935, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P46935 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 58 – 183 | C2PROSITE-ProRule annotationAdd BLAST | 126 | |
Domaini | 249 – 282 | WW 1PROSITE-ProRule annotationAdd BLAST | 34 | |
Domaini | 405 – 438 | WW 2PROSITE-ProRule annotationAdd BLAST | 34 | |
Domaini | 460 – 493 | WW 3PROSITE-ProRule annotationAdd BLAST | 34 | |
Domaini | 552 – 887 | HECTPROSITE-ProRule annotationAdd BLAST | 336 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 217 – 549 | Mediates interaction with TNIK1 PublicationAdd BLAST | 333 |
Domaini
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG0940, Eukaryota |
GeneTreei | ENSGT00940000158905 |
HOGENOMi | CLU_002173_0_3_1 |
InParanoidi | P46935 |
OMAi | FRVNPQK |
OrthoDBi | 271539at2759 |
PhylomeDBi | P46935 |
TreeFami | TF323658 |
Family and domain databases
CDDi | cd00078, HECTc, 1 hit cd00201, WW, 3 hits |
Gene3Di | 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR000008, C2_dom IPR035892, C2_domain_sf IPR024928, E3_ub_ligase_SMURF1 IPR000569, HECT_dom IPR035983, Hect_E3_ubiquitin_ligase IPR001202, WW_dom IPR036020, WW_dom_sf |
Pfami | View protein in Pfam PF00168, C2, 1 hit PF00632, HECT, 1 hit PF00397, WW, 3 hits |
PIRSFi | PIRSF001569, E3_ub_ligase_SMURF1, 1 hit |
SMARTi | View protein in SMART SM00239, C2, 1 hit SM00119, HECTc, 1 hit SM00456, WW, 3 hits |
SUPFAMi | SSF51045, SSF51045, 3 hits SSF56204, SSF56204, 1 hit |
PROSITEi | View protein in PROSITE PS50004, C2, 1 hit PS50237, HECT, 1 hit PS01159, WW_DOMAIN_1, 3 hits PS50020, WW_DOMAIN_2, 3 hits |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 6 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MSSDMAADES EAPVLSEDEV WEFCLDKTED GGGSPGSDVT DTCEPPCGCW
60 70 80 90 100
ELNPNSLEEE HVLFTADPYL ELHNDDTRVV RVKVIAGIGL AKKDILGASD
110 120 130 140 150
PYVRVTLYDP MSGILTSVQT KTIKKSLNPK WNEEILFRVL PQRHRILFEV
160 170 180 190 200
FDENRLTRDD FLGQVDVPLY PLPTENPRME RPYTFKDFVL HPRSHKSRVK
210 220 230 240 250
GYLRLKMTYL PKNGSEDENA DQAEELEPGW VVLDQPDAAT HLPHPPEPSP
260 270 280 290 300
LPPGWEERQD VLGRTYYVNH ESRRTQWKRP SPDDDLTDED NDDMQLQAQR
310 320 330 340 350
AFTTRRQISE DVDGPDNRES PENWEIVRED ENTEYSGQAV QSPPSGHIDV
360 370 380 390 400
QTHLAEEFNT RLAVCGNPAT SQPVTSSNHS SRGGSLQTCI FEEQPTLPVL
410 420 430 440 450
LPTSSGLPPG WEEKQDDRGR SYYVDHNSKT TTWSKPTMQD DPRSKIPAHL
460 470 480 490 500
RGKTDSNDLG PLPPGWEERT HTDGRVFFIN HNIKKTQWED PRLQNVAITG
510 520 530 540 550
PAVPYSRDYK RKYEFFRRKL KKQTDIPNKF EMKLRRANIL EDSYRRIMGV
560 570 580 590 600
KRADLLKARL WIEFDGEKGL DYGGVAREWF FLISKEMFNP YYGLFEYSAT
610 620 630 640 650
DNYTLQINPN SGLCNEDHLS YFKFIGRVAG MAVYHGKLLD GFFIRPFYKM
660 670 680 690 700
MLQKLITLHD MESVDSEYYS SLRWILENDP TELDLRFIID EELFGQTHQH
710 720 730 740 750
ELKTGGSEIV VTNKNKKEYI YLVIQWRFVN RIQKQMAAFK EGFFELIPQD
760 770 780 790 800
LIKIFDENEL ELLMCGLGDV DVNDWREHTK YKNGYSMNHQ VIHWFWKAVW
810 820 830 840 850
MMDSEKRIRL LQFVTGTSRV PMNGFAELYG SNGPQSFTVE QWGTPDKLPR
860 870 880
AHTCFNRLDL PPYESFDELW DKLQMAIENT QGFDGVD
Computationally mapped potential isoform sequencesi
There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A571BDN7 | A0A571BDN7_MOUSE | HECT-type E3 ubiquitin transferase | Nedd4 | 1,136 | Annotation score: | ||
A0A571BEP7 | A0A571BEP7_MOUSE | E3 ubiquitin-protein ligase NEDD4 | Nedd4 | 496 | Annotation score: | ||
V9GXK3 | V9GXK3_MOUSE | E3 ubiquitin-protein ligase NEDD4 | Nedd4 | 195 | Annotation score: | ||
Q3V335 | Q3V335_MOUSE | E3 ubiquitin-protein ligase NEDD4 | Nedd4 | 305 | Annotation score: | ||
V9GWV8 | V9GWV8_MOUSE | E3 ubiquitin-protein ligase NEDD4 | Nedd4 | 196 | Annotation score: | ||
V9GXS6 | V9GXS6_MOUSE | E3 ubiquitin-protein ligase NEDD4 | Nedd4 | 30 | Annotation score: |
Sequence cautioni
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D85414 mRNA Translation: BAA12803.1 U96635 mRNA Translation: AAB63360.1 Frameshift. AK088620 mRNA Translation: BAC40458.1 AK088767 mRNA Translation: BAC40558.1 AK122203 mRNA Translation: BAC65485.1 AK133838 mRNA Translation: BAE21875.1 |
CCDSi | CCDS72275.1 |
RefSeqi | NP_035020.2, NM_010890.3 |
Genome annotation databases
Ensembli | ENSMUST00000034740; ENSMUSP00000034740; ENSMUSG00000032216 |
GeneIDi | 17999 |
KEGGi | mmu:17999 |
UCSCi | uc009qqe.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D85414 mRNA Translation: BAA12803.1 U96635 mRNA Translation: AAB63360.1 Frameshift. AK088620 mRNA Translation: BAC40458.1 AK088767 mRNA Translation: BAC40558.1 AK122203 mRNA Translation: BAC65485.1 AK133838 mRNA Translation: BAE21875.1 |
CCDSi | CCDS72275.1 |
RefSeqi | NP_035020.2, NM_010890.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3M7F | X-ray | 2.00 | B | 71-246 | [»] | |
SMRi | P46935 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 201723, 80 interactors |
DIPi | DIP-32323N |
ELMi | P46935 |
IntActi | P46935, 23 interactors |
MINTi | P46935 |
STRINGi | 10090.ENSMUSP00000034740 |
PTM databases
iPTMneti | P46935 |
PhosphoSitePlusi | P46935 |
SwissPalmi | P46935 |
Proteomic databases
EPDi | P46935 |
jPOSTi | P46935 |
MaxQBi | P46935 |
PaxDbi | P46935 |
PRIDEi | P46935 |
Protocols and materials databases
Antibodypediai | 25114, 274 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000034740; ENSMUSP00000034740; ENSMUSG00000032216 |
GeneIDi | 17999 |
KEGGi | mmu:17999 |
UCSCi | uc009qqe.1, mouse |
Organism-specific databases
CTDi | 4734 |
MGIi | MGI:97297, Nedd4 |
Rougei | Search... |
Phylogenomic databases
eggNOGi | KOG0940, Eukaryota |
GeneTreei | ENSGT00940000158905 |
HOGENOMi | CLU_002173_0_3_1 |
InParanoidi | P46935 |
OMAi | FRVNPQK |
OrthoDBi | 271539at2759 |
PhylomeDBi | P46935 |
TreeFami | TF323658 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
Reactomei | R-MMU-1169408, ISG15 antiviral mechanism R-MMU-1253288, Downregulation of ERBB4 signaling R-MMU-8948747, Regulation of PTEN localization R-MMU-8948751, Regulation of PTEN stability and activity R-MMU-983168, Antigen processing: Ubiquitination & Proteasome degradation |
Miscellaneous databases
BioGRID-ORCSi | 17999, 0 hits in 13 CRISPR screens |
ChiTaRSi | Nedd4, mouse |
PROi | PR:P46935 |
RNActi | P46935, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000032216, Expressed in metanephric loop of Henle and 328 other tissues |
ExpressionAtlasi | P46935, baseline and differential |
Genevisiblei | P46935, MM |
Family and domain databases
CDDi | cd00078, HECTc, 1 hit cd00201, WW, 3 hits |
Gene3Di | 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR000008, C2_dom IPR035892, C2_domain_sf IPR024928, E3_ub_ligase_SMURF1 IPR000569, HECT_dom IPR035983, Hect_E3_ubiquitin_ligase IPR001202, WW_dom IPR036020, WW_dom_sf |
Pfami | View protein in Pfam PF00168, C2, 1 hit PF00632, HECT, 1 hit PF00397, WW, 3 hits |
PIRSFi | PIRSF001569, E3_ub_ligase_SMURF1, 1 hit |
SMARTi | View protein in SMART SM00239, C2, 1 hit SM00119, HECTc, 1 hit SM00456, WW, 3 hits |
SUPFAMi | SSF51045, SSF51045, 3 hits SSF56204, SSF56204, 1 hit |
PROSITEi | View protein in PROSITE PS50004, C2, 1 hit PS50237, HECT, 1 hit PS01159, WW_DOMAIN_1, 3 hits PS50020, WW_DOMAIN_2, 3 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NEDD4_MOUSE | |
Accessioni | P46935Primary (citable) accession number: P46935 Secondary accession number(s): O08758, Q3UZI2, Q8BGB3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1995 |
Last sequence update: | June 20, 2003 | |
Last modified: | December 2, 2020 | |
This is version 201 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references