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Protein

E3 ubiquitin-protein ligase Nedd-4

Gene

Nedd4

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Essential 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. Down-regulates Notch/N signaling pathway by promoting Notch ubiquitination, endocytosis and degradation.3 Publications

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

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 sitei974Glycyl thioester intermediate1

GO - Molecular functioni

  • myosin binding Source: FlyBase
  • Notch binding Source: UniProtKB
  • protein domain specific binding Source: FlyBase
  • ubiquitin protein ligase activity Source: FlyBase
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  • axon guidance Source: FlyBase
  • axon midline choice point recognition Source: UniProtKB
  • negative regulation of Notch signaling pathway Source: UniProtKB
  • neuromuscular junction development Source: FlyBase
  • Notch signaling pathway Source: UniProtKB-KW
  • positive regulation of endocytosis Source: FlyBase
  • positive regulation of receptor internalization Source: FlyBase
  • positive regulation of synapse assembly Source: FlyBase
  • protein ubiquitination Source: UniProtKB
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: GO_Central
  • receptor internalization Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Transferase

Keywords - Biological processi

Notch signaling pathway, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-DME-1169408. ISG15 antiviral mechanism.
R-DME-1253288. Downregulation of ERBB4 signaling.
R-DME-2173795. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
R-DME-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiQ9VVI3.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase Nedd-4 (EC:2.3.2.26By similarity)
Short name:
DNedd4
Alternative name(s):
HECT-type E3 ubiquitin transferase NEDD4
Gene namesi
Name:Nedd4
ORF Names:CG7555
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 3L

Organism-specific databases

FlyBaseiFBgn0259174. Nedd4.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleus Source: GO_Central
  • plasma membrane Source: FlyBase
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi974C → A: Abolishes activity; no effect on interaction with comm. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001203221 – 1007E3 ubiquitin-protein ligase Nedd-4Add BLAST1007

Proteomic databases

PaxDbiQ9VVI3.
PRIDEiQ9VVI3.

Expressioni

Tissue specificityi

Ubiquitously expressed.2 Publications

Gene expression databases

BgeeiFBgn0259174.
ExpressionAtlasiQ9VVI3. baseline.
GenevisibleiQ9VVI3. DM.

Interactioni

Subunit structurei

Interacts with comm and N.2 Publications

GO - Molecular functioni

  • myosin binding Source: FlyBase
  • Notch binding Source: UniProtKB
  • protein domain specific binding Source: FlyBase

Protein-protein interaction databases

BioGridi65246. 9 interactors.
DIPiDIP-29040N.
IntActiQ9VVI3. 6 interactors.
STRINGi7227.FBpp0289746.

Structurei

Secondary structure

11007
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi535 – 539Combined sources5
Beta strandi543 – 549Combined sources7
Turni550 – 553Combined sources4
Beta strandi554 – 558Combined sources5
Turni560 – 562Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EZ5NMR-W526-566[»]
ProteinModelPortaliQ9VVI3.
SMRiQ9VVI3.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9VVI3.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini57 – 159C2PROSITE-ProRule annotationAdd BLAST103
Domaini246 – 279WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini529 – 562WW 2PROSITE-ProRule annotationAdd BLAST34
Domaini580 – 613WW 3PROSITE-ProRule annotationAdd BLAST34
Domaini672 – 1006HECTPROSITE-ProRule annotationAdd BLAST335

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi434 – 482Gln-richAdd BLAST49

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.
GeneTreeiENSGT00760000118966.
InParanoidiQ9VVI3.
KOiK10591.
OrthoDBiEOG091G0SS8.
PhylomeDBiQ9VVI3.

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]
PRINTSiPR00360. C2DOMAIN.
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]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9VVI3-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSARSSGLVA AAALPVPSSS SSVAGGDVPR PPPRRRAASV AGQQQTRQEF
60 70 80 90 100
GNGYTPRRSL AAVNDSGDSC HLRIVVLTGQ SLAKKDIFGA SDPYVRIDLN
110 120 130 140 150
TINGDINIDS VLTKTKKKTL NPTWNEEFIF RVKPSEHKLV FQVFDENRLT
160 170 180 190 200
RDDFLGMVEL TLVNLPTEQE GRTIGEQSYT LRPRRSVGAK SRIKGTLRIY
210 220 230 240 250
HAFIRETREQ SEPSSGNSDG EWEHVEATNA GETSAQPHPF PTGGHDALPA
260 270 280 290 300
GWEERQDANG RTYYVNHTAR TTQWDRPTVL NSHSSQSTDD QLASDFQRRF
310 320 330 340 350
HISVDDTESG RSADSISHNS IEDNNNAAGL AYTPKTAATS SAPPNTPTNN
360 370 380 390 400
NGILAQIAMQ YRAEEDQDPT VDHTSFVYNS LRHPVAHRQP EISATSLQND
410 420 430 440 450
LRPVREAPGV PDIAITNPFT RRAAGNMAGG AGWQQERRRQ QMQLHIQQHQ
460 470 480 490 500
QRQQQQQQNR ILLDVDHRQQ EPQHRGQRHQ QQHRPSNEDT DHTDSHNPSD
510 520 530 540 550
ISAPSTRRNS EEDNAAVPPM EQNTGGEEEP LPPRWSMQVA PNGRTFFIDH
560 570 580 590 600
ASRRTTWIDP RNGRASPMPN QTRRVEDDLG PLPEGWEERV HTDGRVFYID
610 620 630 640 650
HNTRTTQWED PRLSNPNIAG QAVPYSRDYK QKYEYFKSHI RKPTNVPNKF
660 670 680 690 700
EIRIRRTSIL EDSYRIISSV TKTDLLKTKL WVEFEGETGL DYGGLAREWF
710 720 730 740 750
YLLSKEMFNP YYGLFEYSAM DNYTLQINNG SGLCNEEHLS YFKFIGRIAG
760 770 780 790 800
MAVYHGKLLD AFFIRPFYKM MLQKPIDLKD MESVDTEYYN SLMWIKENDP
810 820 830 840 850
RILELTFCLD EDVFGQKSQH ELKPGGANID VTNENKDEYI KLVIEWRFVA
860 870 880 890 900
RVKEQMSSFL DGFGSIIPLN LIKIFDEHEL ELLMCGIQNI DVKDWRENTL
910 920 930 940 950
YKGDYHMNHI IIQWFWRAVL SFSNEMRSRL LQFVTGTSRV PMNGFKELYG
960 970 980 990 1000
SNGPQMFTIE KWGTPNNFPR AHTCFNRLDL PPYEGYLQLK DKLIKAIEGS

QGFAGVD
Length:1,007
Mass (Da):114,875
Last modified:October 1, 2002 - v2
Checksum:iDC5994BD19543760
GO
Isoform 2 (identifier: Q9VVI3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: Missing.
     39-63: SVAGQQQTRQEFGNGYTPRRSLAAV → MAESTTTSPSVTSEDGQIHGCNNSD
     375-387: Missing.

Note: No experimental confirmation available.
Show »
Length:956
Mass (Da):109,544
Checksum:iD42D3130C86B5F5A
GO
Isoform 3 (identifier: Q9VVI3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     314-486: Missing.

Note: No experimental confirmation available.
Show »
Length:834
Mass (Da):95,303
Checksum:iCD0B385C93C95B00
GO
Isoform 4 (identifier: Q9VVI3-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: Missing.
     39-63: SVAGQQQTRQEFGNGYTPRRSLAAV → MAESTTTSPSVTSEDGQIHGCNNSD
     314-486: Missing.

Note: No experimental confirmation available.
Show »
Length:796
Mass (Da):91,480
Checksum:iB94B1A42F4213939
GO

Sequence cautioni

The sequence AAL13848 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti185 – 188RSVG → S in AAS64973 (PubMed:10731132).Curated4

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0154401 – 38Missing in isoform 2 and isoform 4. 1 PublicationAdd BLAST38
Alternative sequenceiVSP_01544139 – 63SVAGQ…SLAAV → MAESTTTSPSVTSEDGQIHG CNNSD in isoform 2 and isoform 4. 1 PublicationAdd BLAST25
Alternative sequenceiVSP_015442314 – 486Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST173
Alternative sequenceiVSP_015443375 – 387Missing in isoform 2. 1 PublicationAdd BLAST13

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ278468 mRNA. Translation: CAC42101.1.
AE014296 Genomic DNA. Translation: AAF49328.2.
AE014296 Genomic DNA. Translation: AAS64973.1.
AE014296 Genomic DNA. Translation: AAN11694.1.
AE014296 Genomic DNA. Translation: AAN11695.1.
AY061595 mRNA. Translation: AAL29143.1.
AY058619 mRNA. Translation: AAL13848.1. Different initiation.
RefSeqiNP_648993.1. NM_140736.3. [Q9VVI3-1]
NP_730282.1. NM_168736.4. [Q9VVI3-3]
NP_730283.1. NM_168737.2. [Q9VVI3-2]
NP_996116.1. NM_206394.2.
UniGeneiDm.988.

Genome annotation databases

EnsemblMetazoaiFBtr0300519; FBpp0289746; FBgn0259174. [Q9VVI3-1]
GeneIDi39958.
KEGGidme:Dmel_CG42279.
UCSCiCG42279-RC. d. melanogaster. [Q9VVI3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ278468 mRNA. Translation: CAC42101.1.
AE014296 Genomic DNA. Translation: AAF49328.2.
AE014296 Genomic DNA. Translation: AAS64973.1.
AE014296 Genomic DNA. Translation: AAN11694.1.
AE014296 Genomic DNA. Translation: AAN11695.1.
AY061595 mRNA. Translation: AAL29143.1.
AY058619 mRNA. Translation: AAL13848.1. Different initiation.
RefSeqiNP_648993.1. NM_140736.3. [Q9VVI3-1]
NP_730282.1. NM_168736.4. [Q9VVI3-3]
NP_730283.1. NM_168737.2. [Q9VVI3-2]
NP_996116.1. NM_206394.2.
UniGeneiDm.988.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EZ5NMR-W526-566[»]
ProteinModelPortaliQ9VVI3.
SMRiQ9VVI3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi65246. 9 interactors.
DIPiDIP-29040N.
IntActiQ9VVI3. 6 interactors.
STRINGi7227.FBpp0289746.

Proteomic databases

PaxDbiQ9VVI3.
PRIDEiQ9VVI3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiFBtr0300519; FBpp0289746; FBgn0259174. [Q9VVI3-1]
GeneIDi39958.
KEGGidme:Dmel_CG42279.
UCSCiCG42279-RC. d. melanogaster. [Q9VVI3-1]

Organism-specific databases

CTDi4734.
FlyBaseiFBgn0259174. Nedd4.

Phylogenomic databases

eggNOGiKOG0940. Eukaryota.
COG5021. LUCA.
GeneTreeiENSGT00760000118966.
InParanoidiQ9VVI3.
KOiK10591.
OrthoDBiEOG091G0SS8.
PhylomeDBiQ9VVI3.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-DME-1169408. ISG15 antiviral mechanism.
R-DME-1253288. Downregulation of ERBB4 signaling.
R-DME-2173795. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
R-DME-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiQ9VVI3.

Miscellaneous databases

ChiTaRSiNedd4. fly.
EvolutionaryTraceiQ9VVI3.
GenomeRNAii39958.
PROiQ9VVI3.

Gene expression databases

BgeeiFBgn0259174.
ExpressionAtlasiQ9VVI3. baseline.
GenevisibleiQ9VVI3. DM.

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]
PRINTSiPR00360. C2DOMAIN.
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_DROME
AccessioniPrimary (citable) accession number: Q9VVI3
Secondary accession number(s): Q7KUR2
, Q8IQR6, Q95R64, Q95TQ0, Q95ZF9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: October 1, 2002
Last modified: November 30, 2016
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Caution

According to some authors (PubMed:12165468) it is involved in axon guidance by promoting ubiquitination of comm and subsequent endocytosis of the comm/robo complex. However, according to others (PubMed:15657595), it is not the case.2 Publications

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.