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Q62940

- NEDD4_RAT

UniProt

Q62940 - NEDD4_RAT

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Protein

E3 ubiquitin-protein ligase NEDD4

Gene

Nedd4

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. Promotes ubiquitination of RAPGEF2. Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Is involved in ubiquitination of ERBB4 intracellular domain E4ICD. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. Ubiquitinates TNK2 and regulates EGF-induced degradation of EGFR and TNF2 (By similarity). Involved in the ubiquitination of ebola virus VP40 protein and this ubiquitination plays a role in facilitating viral budding (By similarity).By similarity

Enzyme regulationi

Activated by NDFIP1- and NDFIP2-binding.By similarity

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei854 – 8541Glycyl thioester intermediatePROSITE-ProRule annotation

GO - Molecular functioni

  1. ligase activity Source: UniProtKB-KW
  2. protein C-terminus binding Source: RGD
  3. ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  1. immune response Source: RGD
  2. negative regulation of vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
  3. protein K63-linked ubiquitination Source: UniProtKB
  4. protein ubiquitination Source: UniProtKB
  5. protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: RefGenome
  6. regulation of dendrite morphogenesis Source: UniProtKB
  7. response to denervation involved in regulation of muscle adaptation Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Neurogenesis, Ubl conjugation pathway

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase NEDD4 (EC:6.3.2.-)
Gene namesi
Name:Nedd4
Synonyms:Nedd4a
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi3157. Nedd4.

Subcellular locationi

Cytoplasm 1 Publication. Cell membrane By similarity; Peripheral membrane protein By similarity
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).By similarity

GO - Cellular componenti

  1. cytoplasm Source: RefGenome
  2. membrane raft Source: RGD
  3. microvillus Source: RGD
  4. nucleus Source: RefGenome
  5. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 887887E3 ubiquitin-protein ligase NEDD4PRO_0000120321Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei284 – 2841PhosphothreonineBy similarity
Modified residuei306 – 3061PhosphoserineBy similarity
Modified residuei382 – 3821PhosphoserineBy similarity

Post-translational modificationi

Auto-ubiquitinated.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ62940.
PRIDEiQ62940.

PTM databases

PhosphoSiteiQ62940.

Expressioni

Tissue specificityi

Ubiquitously expressed. Expression is highest in lung, kidney and brain.1 Publication

Developmental stagei

Down-regulated after synapse formation.1 Publication

Gene expression databases

GenevestigatoriQ62940.

Interactioni

Subunit structurei

Interacts with UBE2D2. Binds, in vitro, through the WW2 and WW3 domains, to neural isoforms of ENAH that contain the PPSY motif. Interacts with BEAN1, LITAF, RNF11, WBP1, WBP2, TMEPAI, NDFIP1, and PRRG2 (By similarity). Interacts (via C2 domain) with GRB10 (via SH2 domain) (By similarity). Binds SCNN1A, SCNN1B and SCNN1G. Interacts with ERBB4. Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase and may induce its recruitment to exosomes (By similarity). Interacts with TNIK; the interaction is direct, allows the TNIK-dependent recruitment of RAP2A and its ubiquitination by NEDD4. 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 (By similarity).By similarity

Protein-protein interaction databases

BioGridi247522. 93 interactions.
IntActiQ62940. 1 interaction.
MINTiMINT-137690.
STRINGi10116.ENSRNOP00000009747.

Structurei

Secondary structure

1
887
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi454 – 4563
Beta strandi465 – 4695
Beta strandi475 – 4795
Turni480 – 4834
Beta strandi484 – 4885
Turni490 – 4923

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1I5HNMR-W452-499[»]
ProteinModelPortaliQ62940.
SMRiQ62940. Positions 70-208, 247-278, 401-435, 451-499, 505-878.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ62940.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini62 – 163102C2PROSITE-ProRule annotationAdd
BLAST
Domaini246 – 27934WW 1PROSITE-ProRule annotationAdd
BLAST
Domaini402 – 43534WW 2PROSITE-ProRule annotationAdd
BLAST
Domaini459 – 49234WW 3PROSITE-ProRule annotationAdd
BLAST
Domaini551 – 887337HECTPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni214 – 548335Mediates interaction with TNIKBy similarityAdd
BLAST

Domaini

The WW domains mediate interaction with LITAF, RNF11, WBP1, WBP2, TMEPAI, NDFIP1 and PRRG2.By similarity

Sequence similaritiesi

Contains 1 C2 domain.PROSITE-ProRule annotation
Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.PROSITE-ProRule annotation
Contains 3 WW domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiCOG5021.
HOGENOMiHOG000208451.
HOVERGENiHBG004134.
InParanoidiQ62940.
KOiK10591.
PhylomeDBiQ62940.

Family and domain databases

Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR024928. E3_ub_ligase_SMURF1.
IPR000569. HECT.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF00397. WW. 3 hits.
[Graphical view]
PIRSFiPIRSF001569. E3_ub_ligase_SMURF1. 1 hit.
SMARTiSM00239. C2. 1 hit.
SM00119. HECTc. 1 hit.
SM00456. WW. 3 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF51045. SSF51045. 3 hits.
SSF56204. SSF56204. 1 hit.
PROSITEiPS50004. C2. 1 hit.
PS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 3 hits.
PS50020. WW_DOMAIN_2. 3 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q62940-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAADDTEAPV LSEDEVWEFC LDKNEEGGGS PGSDVTDTCE PPCGCWELNP
60 70 80 90 100
SSLEEEHVLF TAESIISSFN NDDTRVVRVK VIAGIGLAKK DILGASDPYV
110 120 130 140 150
RVTLYDPMSG VLTSVQTKTI KKSLNPKWNE EILFRVLPQQ HRILFEVFDE
160 170 180 190 200
NRLTRDDFLG QVDVPLYPLP TENPRMERPY TFKDFVLHPR SHKSRVKGYL
210 220 230 240 250
RLKMTYLPKN GSDDENADQA EELEPGWVVL DQPDAATHLQ HPPEPSPLPP
260 270 280 290 300
GWEERQDVLG RTYYVNHESR TTQWKRPSPE DDLTDDENGD IQLQAHGAFT
310 320 330 340 350
TRRQISEDVD GPDNHESPEN WEIVREDENT IYSGQAVQSP PSGHPDVQVR
360 370 380 390 400
LAEELDTRLT MYGNPATSQP VTSSNHSSRG GSSQTCIFEE QPTLPVLLPT
410 420 430 440 450
SSGLPPGWEE KQDDRGRSYY VDHNSKTTTW SKPTMQDDPR SKIPAHLRGK
460 470 480 490 500
TPVDSNDLGP LPPGWEERTH TDGRVFFINH NIKKTQWEDP RMQNVAITGP
510 520 530 540 550
AEPYSRDYKR KYEFFRRKLK KQTDIPNKFE MKLRRANILE DSYRRIMGVK
560 570 580 590 600
RADFLKARLW IEFDGEKGLD YGGVAREWFF LISKEMFNPY YGLFEYSATE
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
ELKTGGSEVV VTNKNKKEYI YLVIQWRFVN RIQKQMAAFK EGFFELIPQD
760 770 780 790 800
LIKIFDENEL ELLMCGLGDV DVNDWREHTK YKNGYSLNHQ VIHWFWKAVL
810 820 830 840 850
MMDSEKRIRL LQFVTGTSRV PMNGFAELYG SNGPQSFTVE QWGTPDKLPR
860 870 880
AHTCFNRLDL PPYESFDELW DKLQMAIENT QGFDGVD
Length:887
Mass (Da):102,395
Last modified:November 1, 1996 - v1
Checksum:iD74B1097688CD9A1
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U50842 mRNA. Translation: AAB48949.1.
PIRiS70642.
RefSeqiNP_037118.1. NM_012986.1.
UniGeneiRn.99540.

Genome annotation databases

GeneIDi25489.
KEGGirno:25489.
UCSCiRGD:3157. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U50842 mRNA. Translation: AAB48949.1 .
PIRi S70642.
RefSeqi NP_037118.1. NM_012986.1.
UniGenei Rn.99540.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1I5H NMR - W 452-499 [» ]
ProteinModelPortali Q62940.
SMRi Q62940. Positions 70-208, 247-278, 401-435, 451-499, 505-878.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 247522. 93 interactions.
IntActi Q62940. 1 interaction.
MINTi MINT-137690.
STRINGi 10116.ENSRNOP00000009747.

PTM databases

PhosphoSitei Q62940.

Proteomic databases

PaxDbi Q62940.
PRIDEi Q62940.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 25489.
KEGGi rno:25489.
UCSCi RGD:3157. rat.

Organism-specific databases

CTDi 4734.
RGDi 3157. Nedd4.

Phylogenomic databases

eggNOGi COG5021.
HOGENOMi HOG000208451.
HOVERGENi HBG004134.
InParanoidi Q62940.
KOi K10591.
PhylomeDBi Q62940.

Enzyme and pathway databases

UniPathwayi UPA00143 .

Miscellaneous databases

EvolutionaryTracei Q62940.
NextBioi 606851.
PROi Q62940.

Gene expression databases

Genevestigatori Q62940.

Family and domain databases

Gene3Di 2.60.40.150. 1 hit.
InterProi IPR000008. C2_dom.
IPR024928. E3_ub_ligase_SMURF1.
IPR000569. HECT.
IPR001202. WW_dom.
[Graphical view ]
Pfami PF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF00397. WW. 3 hits.
[Graphical view ]
PIRSFi PIRSF001569. E3_ub_ligase_SMURF1. 1 hit.
SMARTi SM00239. C2. 1 hit.
SM00119. HECTc. 1 hit.
SM00456. WW. 3 hits.
[Graphical view ]
SUPFAMi SSF49562. SSF49562. 1 hit.
SSF51045. SSF51045. 3 hits.
SSF56204. SSF56204. 1 hit.
PROSITEi PS50004. C2. 1 hit.
PS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 3 hits.
PS50020. WW_DOMAIN_2. 3 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle's syndrome."
    Staub O., Dho S., Henry P., Correa J., Ishikawa T., McGlade J., Rotin D.
    EMBO J. 15:2371-2380(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH SCNN1A; SCNN1B AND SCNN1G.
    Tissue: Lung.
  2. Cited for: FUNCTION, INTERACTION WITH RAP2A AND TNIK, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
  3. "Solution structure of a Nedd4 WW domain-ENaC peptide complex."
    Kanelis V., Rotin D., Forman-Kay J.D.
    Nat. Struct. Biol. 8:407-412(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 452-499 IN COMPLEX WITH SCNN1B, INTERACTION WITH SCNN1A; SCNN1B AND SCNN1G.

Entry informationi

Entry nameiNEDD4_RAT
AccessioniPrimary (citable) accession number: Q62940
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 3, 2003
Last sequence update: November 1, 1996
Last modified: October 29, 2014
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

A cysteine residue is required for ubiquitin-thioester formation.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3