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Protein

E3 ubiquitin-protein ligase NEDD4

Gene

Nedd4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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. Specifically ubiquitinates 'Lys-63' in target proteins (By similarity). 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. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (By similarity).By similarity1 Publication

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

Enzyme regulationi

Activated by NDFIP1- and NDFIP2-binding.By similarity

Pathwayi: protein ubiquitination

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 keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei854Glycyl thioester intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

  • protein C-terminus binding Source: RGD
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Neurogenesis, Ubl conjugation pathway

Enzyme and pathway databases

UniPathwayiUPA00143.

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
Gene namesi
Name:Nedd4
Synonyms:Nedd4a
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3157. Nedd4.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: GO_Central
  • membrane raft Source: RGD
  • microvillus Source: RGD
  • nucleus Source: GO_Central
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001203211 – 887E3 ubiquitin-protein ligase NEDD4Add BLAST887

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei212PhosphoserineCombined sources1
Modified residuei284PhosphothreonineBy similarity1
Modified residuei306PhosphoserineCombined sources1
Modified residuei377PhosphoserineBy similarity1
Modified residuei382PhosphoserineBy similarity1

Post-translational modificationi

Auto-ubiquitinated.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ62940.
PeptideAtlasiQ62940.
PRIDEiQ62940.

PTM databases

iPTMnetiQ62940.
PhosphoSitePlusiQ62940.

Expressioni

Tissue specificityi

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

Developmental stagei

Down-regulated after synapse formation.1 Publication

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 (PubMed:8665844, PubMed:11323714). 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 (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).By similarity3 Publications

GO - Molecular functioni

  • protein C-terminus binding Source: RGD

Protein-protein interaction databases

BioGridi247522. 95 interactors.
IntActiQ62940. 2 interactors.
MINTiMINT-137690.
STRINGi10116.ENSRNOP00000063797.

Structurei

Secondary structure

1887
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi252 – 256Combined sources5
Beta strandi262 – 266Combined sources5
Turni267 – 269Combined sources3
Beta strandi272 – 275Combined sources4
Beta strandi401 – 404Combined sources4
Beta strandi408 – 412Combined sources5
Beta strandi414 – 416Combined sources3
Beta strandi418 – 422Combined sources5
Turni423 – 426Combined sources4
Beta strandi427 – 429Combined sources3
Beta strandi454 – 456Combined sources3
Beta strandi465 – 469Combined sources5
Beta strandi475 – 479Combined sources5
Turni480 – 483Combined sources4
Beta strandi484 – 488Combined sources5
Turni490 – 492Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1I5HNMR-W452-499[»]
2N8SNMR-A245-281[»]
2N8TNMR-A401-437[»]
2N8UNMR-A401-437[»]
ProteinModelPortaliQ62940.
SMRiQ62940.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ62940.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini62 – 163C2PROSITE-ProRule annotationAdd BLAST102
Domaini246 – 279WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini402 – 435WW 2PROSITE-ProRule annotationAdd BLAST34
Domaini459 – 492WW 3PROSITE-ProRule annotationAdd BLAST34
Domaini551 – 887HECTPROSITE-ProRule annotationAdd BLAST337

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni214 – 548Mediates interaction with TNIKBy similarityAdd BLAST335

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

eggNOGiKOG0940. Eukaryota.
COG5021. LUCA.
HOGENOMiHOG000208451.
HOVERGENiHBG004134.
InParanoidiQ62940.
KOiK10591.
PhylomeDBiQ62940.

Family and domain databases

CDDicd00078. HECTc. 1 hit.
Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR000569. HECT_dom.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF00397. WW. 3 hits.
[Graphical view]
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
Links Updated
U50842 mRNA. Translation: AAB48949.1.
PIRiS70642.
RefSeqiNP_037118.1. NM_012986.1.
UniGeneiRn.99540.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1I5HNMR-W452-499[»]
2N8SNMR-A245-281[»]
2N8TNMR-A401-437[»]
2N8UNMR-A401-437[»]
ProteinModelPortaliQ62940.
SMRiQ62940.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247522. 95 interactors.
IntActiQ62940. 2 interactors.
MINTiMINT-137690.
STRINGi10116.ENSRNOP00000063797.

PTM databases

iPTMnetiQ62940.
PhosphoSitePlusiQ62940.

Proteomic databases

PaxDbiQ62940.
PeptideAtlasiQ62940.
PRIDEiQ62940.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4734.
RGDi3157. Nedd4.

Phylogenomic databases

eggNOGiKOG0940. Eukaryota.
COG5021. LUCA.
HOGENOMiHOG000208451.
HOVERGENiHBG004134.
InParanoidiQ62940.
KOiK10591.
PhylomeDBiQ62940.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

EvolutionaryTraceiQ62940.
PROiQ62940.

Family and domain databases

CDDicd00078. HECTc. 1 hit.
Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR000569. HECT_dom.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF00397. WW. 3 hits.
[Graphical view]
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]
ProtoNetiSearch...

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: November 30, 2016
This is version 138 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.