Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

E3 ubiquitin-protein ligase NEDD4

Gene

NEDD4

Organism
Homo sapiens (Human)
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 (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. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. Promotes ubiquitination of RAPGEF2. 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. Involved in the budding of many viruses. 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. 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 (PubMed:25631046).9 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.2 Publications

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.1 Publication
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 sitei1286Glycyl thioester intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

  • beta-2 adrenergic receptor binding Source: UniProtKB
  • phosphoserine binding Source: BHF-UCL
  • phosphothreonine binding Source: BHF-UCL
  • proline-rich region binding Source: UniProtKB
  • protein domain specific binding Source: UniProtKB
  • RNA polymerase binding Source: BHF-UCL
  • sodium channel inhibitor activity Source: BHF-UCL
  • ubiquitin binding Source: BHF-UCL
  • ubiquitin protein ligase activity Source: BHF-UCL

GO - Biological processi

  • adaptive immune response Source: Ensembl
  • blood vessel morphogenesis Source: Ensembl
  • cellular response to UV Source: BHF-UCL
  • development involved in symbiotic interaction Source: UniProtKB
  • endocardial cushion development Source: Ensembl
  • glucocorticoid receptor signaling pathway Source: BHF-UCL
  • lysosomal transport Source: UniProtKB
  • negative regulation of sodium ion transmembrane transporter activity Source: BHF-UCL
  • negative regulation of sodium ion transport Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage Source: BHF-UCL
  • negative regulation of vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
  • neuromuscular junction development Source: Ensembl
  • neuron projection development Source: BHF-UCL
  • outflow tract morphogenesis Source: Ensembl
  • positive regulation of nucleocytoplasmic transport Source: BHF-UCL
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCL
  • positive regulation of protein catabolic process Source: MGI
  • progesterone receptor signaling pathway Source: BHF-UCL
  • protein K63-linked ubiquitination Source: UniProtKB
  • protein monoubiquitination Source: Ensembl
  • protein targeting to lysosome Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: BHF-UCL
  • receptor catabolic process Source: UniProtKB
  • receptor internalization Source: UniProtKB
  • regulation of dendrite morphogenesis Source: UniProtKB
  • regulation of ion transmembrane transport Source: BHF-UCL
  • regulation of macroautophagy Source: ParkinsonsUK-UCL
  • regulation of membrane potential Source: BHF-UCL
  • regulation of potassium ion transmembrane transporter activity Source: BHF-UCL
  • regulation of synapse organization Source: Ensembl
  • response to calcium ion Source: BHF-UCL
  • T cell activation Source: Ensembl
  • transmission of virus Source: BHF-UCL
  • ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Host-virus interaction, Neurogenesis, Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000069869-MONOMER.
BRENDAi2.3.2.B9. 2681.
6.3.2.19. 2681.
ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-1253288. Downregulation of ERBB4 signaling.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiP46934.
UniPathwayiUPA00143.

Protein family/group databases

TCDBi8.A.30.1.2. the nedd4-family interacting protein-2 (nedd4) family.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase NEDD4 (EC:2.3.2.262 Publications)
Alternative name(s):
Cell proliferation-inducing gene 53 protein
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, NEDD4-1
ORF Names:PIG53
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:7727. NEDD4.

Subcellular locationi

  • Cytoplasm By similarity
  • 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 similarity1 Publication

GO - Cellular componenti

  • apicolateral plasma membrane Source: BHF-UCL
  • cell cortex Source: BHF-UCL
  • chromatin Source: BHF-UCL
  • cytoplasm Source: BHF-UCL
  • cytosol Source: BHF-UCL
  • extracellular exosome Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • nucleus Source: GO_Central
  • perinuclear region of cytoplasm Source: BHF-UCL
  • plasma membrane Source: UniProtKB
  • ubiquitin ligase complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi795W → A: Abolishes interaction with ARRDC3; when associated with A-868 and A-920. 1 Publication1
Mutagenesisi868W → A: Abolishes interaction with ARRDC3; when associated with A-795 and A-920. 1 Publication1
Mutagenesisi920W → A: Abolishes interaction with ARRDC3; when associated with A-795 and A-868. 1 Publication1

Organism-specific databases

DisGeNETi4734.
OpenTargetsiENSG00000069869.
PharmGKBiPA31533.

Chemistry databases

ChEMBLiCHEMBL3621023.

Polymorphism and mutation databases

BioMutaiNEDD4.
DMDMi313104311.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001203191 – 1319E3 ubiquitin-protein ligase NEDD4Add BLAST1319
Isoform 4 (identifier: P46934-4)
Initiator methionineiRemovedCombined sources

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei576PhosphoserineBy similarity1
Modified residuei648PhosphothreonineBy similarity1
Modified residuei670PhosphoserineBy similarity1
Modified residuei742PhosphoserineCombined sources1
Modified residuei747PhosphoserineCombined sources1
Isoform 4 (identifier: P46934-4)
Modified residuei2N-acetylalanineCombined sources1

Post-translational modificationi

Auto-ubiquitinated.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP46934.
MaxQBiP46934.
PaxDbiP46934.
PeptideAtlasiP46934.
PRIDEiP46934.

PTM databases

iPTMnetiP46934.
PhosphoSitePlusiP46934.

Expressioni

Gene expression databases

BgeeiENSG00000069869.
CleanExiHS_NEDD4.
ExpressionAtlasiP46934. baseline and differential.
GenevisibleiP46934. HS.

Organism-specific databases

HPAiCAB001991.
CAB072833.
HPA039883.

Interactioni

Subunit structurei

Interacts with UBE2D2. Binds SCNN1A, SCNN1B and SCNN1G. 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 and PRRG2 (By similarity). Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase and may induce its recruitment to exosomes (By similarity). Interaction with PTEN is questionable according to PubMed:18562292. Interacts with viral proteins that contain a late- budding motif P-P-P-Y. This interaction is essential for viral particle budding of a lot of retroviruses, like HTLV-1 Gag and MLV Gag. Interacts (via C2 domain) with GRB10 (via SH2 domain). Interacts with ERBB4 (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. Interacts with ISG15. 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) (PubMed:20559325, PubMed:24379409).By similarity13 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
FGFR1P1136226EBI-726944,EBI-1028277
GABARAPO951666EBI-726944,EBI-712001
GABARAPL1Q9H0R86EBI-726944,EBI-746969
GABARAPL2P605206EBI-726944,EBI-720116
LITAFQ997324EBI-726944,EBI-725647
PTENP604844EBI-726944,EBI-696162
RNF11Q9Y3C52EBI-726944,EBI-396669
SCNN1BP511684EBI-726944,EBI-2547187

GO - Molecular functioni

  • beta-2 adrenergic receptor binding Source: UniProtKB
  • phosphoserine binding Source: BHF-UCL
  • phosphothreonine binding Source: BHF-UCL
  • proline-rich region binding Source: UniProtKB
  • protein domain specific binding Source: UniProtKB
  • RNA polymerase binding Source: BHF-UCL
  • ubiquitin binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi110811. 306 interactors.
DIPiDIP-29815N.
IntActiP46934. 33 interactors.
MINTiMINT-86457.
STRINGi9606.ENSP00000345530.

Structurei

Secondary structure

11319
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi520 – 528Combined sources9
Beta strandi546 – 549Combined sources4
Beta strandi561 – 569Combined sources9
Beta strandi841 – 843Combined sources3
Beta strandi846 – 850Combined sources5
Turni852 – 854Combined sources3
Beta strandi856 – 860Combined sources5
Turni861 – 864Combined sources4
Beta strandi865 – 869Combined sources5
Turni871 – 873Combined sources3
Helixi941 – 951Combined sources11
Beta strandi956 – 958Combined sources3
Beta strandi960 – 966Combined sources7
Helixi968 – 970Combined sources3
Helixi971 – 979Combined sources9
Helixi985 – 989Combined sources5
Beta strandi990 – 996Combined sources7
Helixi1004 – 1019Combined sources16
Helixi1022 – 1024Combined sources3
Beta strandi1025 – 1031Combined sources7
Beta strandi1037 – 1039Combined sources3
Helixi1043 – 1046Combined sources4
Helixi1050 – 1067Combined sources18
Beta strandi1071 – 1073Combined sources3
Helixi1077 – 1083Combined sources7
Helixi1091 – 1096Combined sources6
Helixi1098 – 1109Combined sources12
Helixi1113 – 1115Combined sources3
Beta strandi1118 – 1125Combined sources8
Beta strandi1128 – 1135Combined sources8
Helixi1138 – 1140Combined sources3
Turni1145 – 1147Combined sources3
Helixi1148 – 1160Combined sources13
Helixi1162 – 1164Combined sources3
Helixi1165 – 1178Combined sources14
Helixi1181 – 1184Combined sources4
Helixi1189 – 1196Combined sources8
Helixi1204 – 1209Combined sources6
Beta strandi1212 – 1214Combined sources3
Beta strandi1219 – 1221Combined sources3
Helixi1222 – 1233Combined sources12
Helixi1236 – 1247Combined sources12
Beta strandi1248 – 1250Combined sources3
Helixi1257 – 1259Combined sources3
Beta strandi1263 – 1266Combined sources4
Beta strandi1270 – 1272Combined sources3
Beta strandi1282 – 1284Combined sources3
Helixi1285 – 1287Combined sources3
Beta strandi1289 – 1291Combined sources3
Helixi1298 – 1309Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KPZNMR-A834-878[»]
2KQ0NMR-A834-878[»]
2M3ONMR-W838-877[»]
2XBBX-ray2.68A/B938-1319[»]
2XBFX-ray2.50A938-1319[»]
3B7YX-ray1.80A/B517-571[»]
4BBNX-ray2.51A938-1319[»]
4BE8X-ray3.00A938-1319[»]
4N7FX-ray1.10A/B841-874[»]
4N7HX-ray1.70A840-872[»]
5AHTNMR-A838-877[»]
5C7JX-ray3.00A/B939-1319[»]
5C91X-ray2.44A938-1312[»]
ProteinModelPortaliP46934.
SMRiP46934.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP46934.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini610 – 643WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini767 – 800WW 2PROSITE-ProRule annotationAdd BLAST34
Domaini840 – 873WW 3PROSITE-ProRule annotationAdd BLAST34
Domaini892 – 925WW 4PROSITE-ProRule annotationAdd BLAST34
Domaini984 – 1318HECTPROSITE-ProRule annotationAdd BLAST335

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni578 – 981Mediates interaction with TNIKBy similarityAdd BLAST404

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi68 – 215Ser-richAdd BLAST148

Domaini

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

Sequence similaritiesi

Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.PROSITE-ProRule annotation
Contains 4 WW domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0940. Eukaryota.
COG5021. LUCA.
GeneTreeiENSGT00760000118966.
HOVERGENiHBG004134.
InParanoidiP46934.
KOiK10591.
OMAiYRRILSV.
OrthoDBiEOG091G0SS8.
PhylomeDBiP46934.
TreeFamiTF323658.

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]
PfamiPF00632. HECT. 1 hit.
PF00397. WW. 4 hits.
[Graphical view]
SMARTiSM00119. HECTc. 1 hit.
SM00456. WW. 4 hits.
[Graphical view]
SUPFAMiSSF51045. SSF51045. 4 hits.
SSF56204. SSF56204. 1 hit.
PROSITEiPS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 4 hits.
PS50020. WW_DOMAIN_2. 4 hits.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: P46934-1) [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
MAQSLRLHFA ARRSNTYPLS ETSGDDLDSH VHMCFKRPTR ISTSNVVQMK
60 70 80 90 100
LTPRQTALAP LIKENVQSQE RSSVPSSENV NKKSSCLQIS LQPTRYSGYL
110 120 130 140 150
QSSNVLADSD DASFTCILKD GIYSSAVVDN ELNAVNDGHL VSSPAICSGS
160 170 180 190 200
LSNFSTSDNG SYSSNGSDFG SCASITSGGS YTNSVISDSS SYTFPPSDDT
210 220 230 240 250
FLGGNLPSDS TSNRSVPNRN TTPCEIFSRS TSTDPFVQDD LEHGLEIMKL
260 270 280 290 300
PVSRNTKIPL KRYSSLVIFP RSPSTTRPTS PTSLCTLLSK GSYQTSHQFI
310 320 330 340 350
ISPSEIAHNE DGTSAKGFLS TAVNGLRLSK TICTPGEVRD IRPLHRKGSL
360 370 380 390 400
QKKIVLSNNT PRQTVCEKSS EGYSCVSVHF TQRKAATLDC ETTNGDCKPE
410 420 430 440 450
MSEIKLNSDS EYIKLMHRTS ACLPSSQNVD CQININGELE RPHSQMNKNH
460 470 480 490 500
GILRRSISLG GAYPNISCLS SLKHNCSKGG PSQLLIKFAS GNEGKVDNLS
510 520 530 540 550
RDSNRDCTNE LSNSCKTRDD FLGQVDVPLY PLPTENPRLE RPYTFKDFVL
560 570 580 590 600
HPRSHKSRVK GYLRLKMTYL PKTSGSEDDN AEQAEELEPG WVVLDQPDAA
610 620 630 640 650
CHLQQQQEPS PLPPGWEERQ DILGRTYYVN HESRRTQWKR PTPQDNLTDA
660 670 680 690 700
ENGNIQLQAQ RAFTTRRQIS EETESVDNRE SSENWEIIRE DEATMYSNQA
710 720 730 740 750
FPSPPPSSNL DVPTHLAEEL NARLTIFGNS AVSQPASSSN HSSRRGSLQA
760 770 780 790 800
YTFEEQPTLP VLLPTSSGLP PGWEEKQDER GRSYYVDHNS RTTTWTKPTV
810 820 830 840 850
QATVETSQLT SSQSSAGPQS QASTSDSGQQ VTQPSEIEQG FLPKGWEVRH
860 870 880 890 900
APNGRPFFID HNTKTTTWED PRLKIPAHLR GKTSLDTSND LGPLPPGWEE
910 920 930 940 950
RTHTDGRIFY INHNIKRTQW EDPRLENVAI TGPAVPYSRD YKRKYEFFRR
960 970 980 990 1000
KLKKQNDIPN KFEMKLRRAT VLEDSYRRIM GVKRADFLKA RLWIEFDGEK
1010 1020 1030 1040 1050
GLDYGGVARE WFFLISKEMF NPYYGLFEYS ATDNYTLQIN PNSGLCNEDH
1060 1070 1080 1090 1100
LSYFKFIGRV AGMAVYHGKL LDGFFIRPFY KMMLHKPITL HDMESVDSEY
1110 1120 1130 1140 1150
YNSLRWILEN DPTELDLRFI IDEELFGQTH QHELKNGGSE IVVTNKNKKE
1160 1170 1180 1190 1200
YIYLVIQWRF VNRIQKQMAA FKEGFFELIP QDLIKIFDEN ELELLMCGLG
1210 1220 1230 1240 1250
DVDVNDWREH TKYKNGYSAN HQVIQWFWKA VLMMDSEKRI RLLQFVTGTS
1260 1270 1280 1290 1300
RVPMNGFAEL YGSNGPQSFT VEQWGTPEKL PRAHTCFNRL DLPPYESFEE
1310
LWDKLQMAIE NTQGFDGVD
Note: No experimental confirmation available.
Length:1,319
Mass (Da):149,114
Last modified:November 30, 2010 - v4
Checksum:iD56EBBC50A34F13B
GO
Isoform 2 (identifier: P46934-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     589-604: Missing.

Note: No experimental confirmation available.
Show »
Length:1,303
Mass (Da):147,384
Checksum:iC40112E4C9BC8416
GO
Isoform 3 (identifier: P46934-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     517-588: Missing.

Note: No experimental confirmation available.
Show »
Length:1,247
Mass (Da):140,696
Checksum:i827AC55FB4AFB6A3
GO
Isoform 4 (identifier: P46934-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-419: Missing.
     420-516: SACLPSSQNV...CTNELSNSCK → MATCAVEVFG...LFEVFDENRL

Show »
Length:900
Mass (Da):104,217
Checksum:i4303287D3133B1C7
GO

Sequence cautioni

The sequence BAA07655 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti59A → T in AL832063 (PubMed:17974005).Curated1
Sequence conflicti407N → H in AL832063 (PubMed:17974005).Curated1
Sequence conflicti620Q → R in AAT52215 (Ref. 4) Curated1
Sequence conflicti620Q → R in AAI44285 (PubMed:15489334).Curated1
Sequence conflicti863T → I in AAI36606 (PubMed:15489334).Curated1
Sequence conflicti863T → I in AAI44285 (PubMed:15489334).Curated1
Sequence conflicti1199L → P in BAG65229 (PubMed:14702039).Curated1
Sequence conflicti1268S → L in AL832063 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06198533M → V.Corresponds to variant rs1912403dbSNPEnsembl.1
Natural variantiVAR_036472627Y → H in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_047909679R → Q.5 PublicationsCorresponds to variant rs2303580dbSNPEnsembl.1
Natural variantiVAR_047910698N → S.5 PublicationsCorresponds to variant rs2303579dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0382561 – 419Missing in isoform 4. 4 PublicationsAdd BLAST419
Alternative sequenceiVSP_038257420 – 516SACLP…SNSCK → MATCAVEVFGLLEDEENSRI VRVRVIAGIGLAKKDILGAS DPYVRVTLYDPMNGVLTSVQ TKTIKKSLNPKWNEEILFRV HPQQHRLLFEVFDENRL in isoform 4. 4 PublicationsAdd BLAST97
Alternative sequenceiVSP_038258517 – 588Missing in isoform 3. 1 PublicationAdd BLAST72
Alternative sequenceiVSP_038259589 – 604Missing in isoform 2. 1 PublicationAdd BLAST16

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D42055 mRNA. Translation: BAA07655.1. Different initiation.
AK304394 mRNA. Translation: BAG65229.1.
AY550969 mRNA. Translation: AAT52215.1.
AL832063 Genomic DNA. No translation available.
AC009997 Genomic DNA. No translation available.
AC039057 Genomic DNA. No translation available.
CH471082 Genomic DNA. Translation: EAW77495.1.
BC136605 mRNA. Translation: AAI36606.1.
BC144284 mRNA. Translation: AAI44285.1.
BC144285 mRNA. Translation: AAI44286.1.
BC152452 mRNA. Translation: AAI52453.1.
BC152562 mRNA. Translation: AAI52563.1.
CCDSiCCDS10156.1. [P46934-3]
CCDS45265.1. [P46934-4]
CCDS61643.1. [P46934-2]
CCDS61644.1. [P46934-1]
RefSeqiNP_001271267.1. NM_001284338.1. [P46934-1]
NP_001271268.1. NM_001284339.1. [P46934-2]
NP_001271269.1. NM_001284340.1.
NP_001316141.1. NM_001329212.1.
NP_006145.2. NM_006154.3. [P46934-4]
NP_940682.2. NM_198400.3. [P46934-3]
UniGeneiHs.1565.

Genome annotation databases

EnsembliENST00000338963; ENSP00000345530; ENSG00000069869. [P46934-3]
ENST00000435532; ENSP00000410613; ENSG00000069869. [P46934-4]
ENST00000506154; ENSP00000422705; ENSG00000069869. [P46934-2]
ENST00000508342; ENSP00000424827; ENSG00000069869. [P46934-1]
GeneIDi4734.
KEGGihsa:4734.
UCSCiuc002adi.5. human. [P46934-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D42055 mRNA. Translation: BAA07655.1. Different initiation.
AK304394 mRNA. Translation: BAG65229.1.
AY550969 mRNA. Translation: AAT52215.1.
AL832063 Genomic DNA. No translation available.
AC009997 Genomic DNA. No translation available.
AC039057 Genomic DNA. No translation available.
CH471082 Genomic DNA. Translation: EAW77495.1.
BC136605 mRNA. Translation: AAI36606.1.
BC144284 mRNA. Translation: AAI44285.1.
BC144285 mRNA. Translation: AAI44286.1.
BC152452 mRNA. Translation: AAI52453.1.
BC152562 mRNA. Translation: AAI52563.1.
CCDSiCCDS10156.1. [P46934-3]
CCDS45265.1. [P46934-4]
CCDS61643.1. [P46934-2]
CCDS61644.1. [P46934-1]
RefSeqiNP_001271267.1. NM_001284338.1. [P46934-1]
NP_001271268.1. NM_001284339.1. [P46934-2]
NP_001271269.1. NM_001284340.1.
NP_001316141.1. NM_001329212.1.
NP_006145.2. NM_006154.3. [P46934-4]
NP_940682.2. NM_198400.3. [P46934-3]
UniGeneiHs.1565.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KPZNMR-A834-878[»]
2KQ0NMR-A834-878[»]
2M3ONMR-W838-877[»]
2XBBX-ray2.68A/B938-1319[»]
2XBFX-ray2.50A938-1319[»]
3B7YX-ray1.80A/B517-571[»]
4BBNX-ray2.51A938-1319[»]
4BE8X-ray3.00A938-1319[»]
4N7FX-ray1.10A/B841-874[»]
4N7HX-ray1.70A840-872[»]
5AHTNMR-A838-877[»]
5C7JX-ray3.00A/B939-1319[»]
5C91X-ray2.44A938-1312[»]
ProteinModelPortaliP46934.
SMRiP46934.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110811. 306 interactors.
DIPiDIP-29815N.
IntActiP46934. 33 interactors.
MINTiMINT-86457.
STRINGi9606.ENSP00000345530.

Chemistry databases

ChEMBLiCHEMBL3621023.

Protein family/group databases

TCDBi8.A.30.1.2. the nedd4-family interacting protein-2 (nedd4) family.

PTM databases

iPTMnetiP46934.
PhosphoSitePlusiP46934.

Polymorphism and mutation databases

BioMutaiNEDD4.
DMDMi313104311.

Proteomic databases

EPDiP46934.
MaxQBiP46934.
PaxDbiP46934.
PeptideAtlasiP46934.
PRIDEiP46934.

Protocols and materials databases

DNASUi4734.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000338963; ENSP00000345530; ENSG00000069869. [P46934-3]
ENST00000435532; ENSP00000410613; ENSG00000069869. [P46934-4]
ENST00000506154; ENSP00000422705; ENSG00000069869. [P46934-2]
ENST00000508342; ENSP00000424827; ENSG00000069869. [P46934-1]
GeneIDi4734.
KEGGihsa:4734.
UCSCiuc002adi.5. human. [P46934-1]

Organism-specific databases

CTDi4734.
DisGeNETi4734.
GeneCardsiNEDD4.
HGNCiHGNC:7727. NEDD4.
HPAiCAB001991.
CAB072833.
HPA039883.
MIMi602278. gene.
neXtProtiNX_P46934.
OpenTargetsiENSG00000069869.
PharmGKBiPA31533.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0940. Eukaryota.
COG5021. LUCA.
GeneTreeiENSGT00760000118966.
HOVERGENiHBG004134.
InParanoidiP46934.
KOiK10591.
OMAiYRRILSV.
OrthoDBiEOG091G0SS8.
PhylomeDBiP46934.
TreeFamiTF323658.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000069869-MONOMER.
BRENDAi2.3.2.B9. 2681.
6.3.2.19. 2681.
ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-1253288. Downregulation of ERBB4 signaling.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiP46934.

Miscellaneous databases

ChiTaRSiNEDD4. human.
EvolutionaryTraceiP46934.
GeneWikiiNEDD4.
GenomeRNAii4734.
PROiP46934.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000069869.
CleanExiHS_NEDD4.
ExpressionAtlasiP46934. baseline and differential.
GenevisibleiP46934. HS.

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]
PfamiPF00632. HECT. 1 hit.
PF00397. WW. 4 hits.
[Graphical view]
SMARTiSM00119. HECTc. 1 hit.
SM00456. WW. 4 hits.
[Graphical view]
SUPFAMiSSF51045. SSF51045. 4 hits.
SSF56204. SSF56204. 1 hit.
PROSITEiPS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 4 hits.
PS50020. WW_DOMAIN_2. 4 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNEDD4_HUMAN
AccessioniPrimary (citable) accession number: P46934
Secondary accession number(s): A1KY35
, A6ND72, A7MD29, B4E2R7, B7ZM59, B7ZM60, B9EGN5, D6RF89
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 30, 2010
Last modified: November 30, 2016
This is version 176 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

A cysteine residue is required for ubiquitin-thioester formation.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.