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P46934

- NEDD4_HUMAN

UniProt

P46934 - NEDD4_HUMAN

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Protein

E3 ubiquitin-protein ligase NEDD4

Gene

NEDD4

Organism
Homo sapiens (Human)
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. 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.7 Publications

Enzyme regulationi

Activated by NDFIP1- and NDFIP2-binding.By similarity

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei1286 – 12861Glycyl thioester intermediatePROSITE-ProRule annotation

GO - Molecular functioni

  1. beta-2 adrenergic receptor binding Source: UniProtKB
  2. ligase activity Source: UniProtKB-KW
  3. phosphoserine binding Source: BHF-UCL
  4. phosphothreonine binding Source: BHF-UCL
  5. proline-rich region binding Source: UniProtKB
  6. protein domain specific binding Source: UniProtKB
  7. RNA polymerase binding Source: BHF-UCL
  8. sodium channel inhibitor activity Source: BHF-UCL
  9. ubiquitin binding Source: BHF-UCL
  10. ubiquitin-protein transferase activity Source: BHF-UCL

GO - Biological processi

  1. adaptive immune response Source: Ensembl
  2. blood vessel morphogenesis Source: Ensembl
  3. cellular response to UV Source: BHF-UCL
  4. cytokine-mediated signaling pathway Source: Reactome
  5. development involved in symbiotic interaction Source: UniProtKB
  6. endocardial cushion development Source: Ensembl
  7. glucocorticoid receptor signaling pathway Source: BHF-UCL
  8. lysosomal transport Source: UniProtKB
  9. negative regulation of sodium ion transport Source: UniProtKB
  10. negative regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage Source: BHF-UCL
  11. negative regulation of vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
  12. neuromuscular junction development Source: Ensembl
  13. neuron projection development Source: BHF-UCL
  14. outflow tract morphogenesis Source: Ensembl
  15. positive regulation of nucleocytoplasmic transport Source: BHF-UCL
  16. positive regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCL
  17. positive regulation of protein catabolic process Source: MGI
  18. progesterone receptor signaling pathway Source: BHF-UCL
  19. protein K63-linked ubiquitination Source: UniProtKB
  20. protein monoubiquitination Source: Ensembl
  21. protein targeting to lysosome Source: UniProtKB
  22. protein ubiquitination Source: UniProtKB
  23. protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: BHF-UCL
  24. receptor catabolic process Source: UniProtKB
  25. receptor internalization Source: UniProtKB
  26. regulation of dendrite morphogenesis Source: UniProtKB
  27. regulation of ion transmembrane transport Source: BHF-UCL
  28. regulation of membrane potential Source: BHF-UCL
  29. regulation of potassium ion transmembrane transporter activity Source: BHF-UCL
  30. regulation of synapse organization Source: Ensembl
  31. response to calcium ion Source: BHF-UCL
  32. T cell activation Source: Ensembl
  33. transmission of virus Source: BHF-UCL
  34. ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Host-virus interaction, Neurogenesis, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiREACT_115828. Downregulation of ERBB4 signaling.
REACT_115831. ISG15 antiviral mechanism.
REACT_75842. 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:6.3.2.-)
Alternative name(s):
Cell proliferation-inducing gene 53 protein
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
ProteomesiUP000005640: 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

  1. apicolateral plasma membrane Source: BHF-UCL
  2. cell cortex Source: BHF-UCL
  3. chromatin Source: BHF-UCL
  4. cytoplasm Source: BHF-UCL
  5. cytosol Source: BHF-UCL
  6. extracellular vesicular exosome Source: UniProtKB
  7. Golgi apparatus Source: UniProtKB
  8. nucleus Source: RefGenome
  9. perinuclear region of cytoplasm Source: BHF-UCL
  10. plasma membrane Source: UniProtKB
  11. ubiquitin ligase complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA31533.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 13191319E3 ubiquitin-protein ligase NEDD4PRO_0000120319Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei648 – 6481PhosphothreonineBy similarity
Modified residuei670 – 6701PhosphoserineBy similarity
Modified residuei747 – 7471Phosphoserine2 Publications

Post-translational modificationi

Auto-ubiquitinated.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP46934.
PaxDbiP46934.
PRIDEiP46934.

PTM databases

PhosphoSiteiP46934.

Expressioni

Gene expression databases

BgeeiP46934.
CleanExiHS_NEDD4.
GenevestigatoriP46934.

Organism-specific databases

HPAiCAB001991.
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.By similarity10 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

Protein-protein interaction databases

BioGridi110811. 281 interactions.
DIPiDIP-29815N.
IntActiP46934. 27 interactions.
MINTiMINT-86457.
STRINGi9606.ENSP00000345530.

Structurei

Secondary structure

1
1319
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi520 – 5289Combined sources
Beta strandi546 – 5494Combined sources
Beta strandi561 – 5699Combined sources
Beta strandi846 – 8505Combined sources
Turni852 – 8543Combined sources
Beta strandi856 – 8605Combined sources
Turni861 – 8644Combined sources
Beta strandi865 – 8695Combined sources
Turni871 – 8733Combined sources
Helixi941 – 95111Combined sources
Beta strandi956 – 9583Combined sources
Beta strandi960 – 9667Combined sources
Helixi968 – 9703Combined sources
Helixi971 – 9799Combined sources
Helixi985 – 9895Combined sources
Beta strandi990 – 9967Combined sources
Helixi1004 – 101916Combined sources
Helixi1022 – 10243Combined sources
Beta strandi1025 – 10317Combined sources
Beta strandi1037 – 10393Combined sources
Helixi1043 – 10464Combined sources
Helixi1050 – 106617Combined sources
Beta strandi1071 – 10733Combined sources
Helixi1077 – 10837Combined sources
Helixi1090 – 10945Combined sources
Helixi1098 – 110912Combined sources
Helixi1113 – 11153Combined sources
Beta strandi1118 – 11258Combined sources
Beta strandi1128 – 11358Combined sources
Helixi1138 – 11403Combined sources
Turni1145 – 11473Combined sources
Helixi1148 – 116013Combined sources
Helixi1162 – 11643Combined sources
Helixi1165 – 117511Combined sources
Turni1176 – 11783Combined sources
Helixi1181 – 11844Combined sources
Helixi1189 – 11979Combined sources
Helixi1204 – 12096Combined sources
Beta strandi1211 – 12144Combined sources
Beta strandi1219 – 12213Combined sources
Helixi1222 – 123312Combined sources
Helixi1236 – 124712Combined sources
Beta strandi1248 – 12503Combined sources
Helixi1257 – 12593Combined sources
Beta strandi1263 – 12664Combined sources
Beta strandi1269 – 12735Combined sources
Beta strandi1282 – 12843Combined sources
Helixi1285 – 12873Combined sources
Beta strandi1289 – 12924Combined sources
Helixi1298 – 131013Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP46934.
SMRiP46934. Positions 517-571, 611-642, 768-798, 841-873, 888-932, 938-1312.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP46934.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini610 – 64334WW 1PROSITE-ProRule annotationAdd
BLAST
Domaini767 – 80034WW 2PROSITE-ProRule annotationAdd
BLAST
Domaini840 – 87334WW 3PROSITE-ProRule annotationAdd
BLAST
Domaini892 – 92534WW 4PROSITE-ProRule annotationAdd
BLAST
Domaini984 – 1318335HECTPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni578 – 981404Mediates interaction with TNIKBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi68 – 215148Ser-richAdd
BLAST

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

eggNOGiCOG5021.
GeneTreeiENSGT00760000118966.
HOVERGENiHBG004134.
InParanoidiP46934.
KOiK10591.
OMAiRRICRAF.
OrthoDBiEOG7RFTGT.
PhylomeDBiP46934.
TreeFamiTF323658.

Family and domain databases

Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR000569. HECT.
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.

This entry describes 4 isoformsi produced by alternative splicing. Align

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 BAA07655.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti59 – 591A → T in AL832063. (PubMed:17974005)Curated
Sequence conflicti407 – 4071N → H in AL832063. (PubMed:17974005)Curated
Sequence conflicti620 – 6201Q → R in AAT52215. 1 PublicationCurated
Sequence conflicti620 – 6201Q → R in AAI44285. (PubMed:15489334)Curated
Sequence conflicti863 – 8631T → I in AAI36606. (PubMed:15489334)Curated
Sequence conflicti863 – 8631T → I in AAI44285. (PubMed:15489334)Curated
Sequence conflicti1199 – 11991L → P in BAG65229. (PubMed:14702039)Curated
Sequence conflicti1268 – 12681S → L in AL832063. (PubMed:17974005)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti33 – 331M → V.
Corresponds to variant rs1912403 [ dbSNP | Ensembl ].
VAR_061985
Natural varianti627 – 6271Y → H in a breast cancer sample; somatic mutation. 1 Publication
VAR_036472
Natural varianti679 – 6791R → Q.5 Publications
Corresponds to variant rs2303580 [ dbSNP | Ensembl ].
VAR_047909
Natural varianti698 – 6981N → S.5 Publications
Corresponds to variant rs2303579 [ dbSNP | Ensembl ].
VAR_047910

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 419419Missing in isoform 4. 4 PublicationsVSP_038256Add
BLAST
Alternative sequencei420 – 51697SACLP…SNSCK → MATCAVEVFGLLEDEENSRI VRVRVIAGIGLAKKDILGAS DPYVRVTLYDPMNGVLTSVQ TKTIKKSLNPKWNEEILFRV HPQQHRLLFEVFDENRL in isoform 4. 4 PublicationsVSP_038257Add
BLAST
Alternative sequencei517 – 58872Missing in isoform 3. 1 PublicationVSP_038258Add
BLAST
Alternative sequencei589 – 60416Missing in isoform 2. 1 PublicationVSP_038259Add
BLAST

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_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.3. human. [P46934-3]
uc002adj.3. human. [P46934-1]
uc002adl.3. human. [P46934-4]
uc010ugj.2. human. [P46934-2]

Polymorphism databases

DMDMi313104311.

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 .
CCDSi CCDS10156.1. [P46934-3 ]
CCDS45265.1. [P46934-4 ]
CCDS61643.1. [P46934-2 ]
CCDS61644.1. [P46934-1 ]
RefSeqi NP_001271267.1. NM_001284338.1. [P46934-1 ]
NP_001271268.1. NM_001284339.1. [P46934-2 ]
NP_001271269.1. NM_001284340.1.
NP_006145.2. NM_006154.3. [P46934-4 ]
NP_940682.2. NM_198400.3. [P46934-3 ]
UniGenei Hs.1565.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2KPZ NMR - A 834-878 [» ]
2KQ0 NMR - A 834-878 [» ]
2M3O NMR - W 838-877 [» ]
2XBB X-ray 2.68 A/B 938-1319 [» ]
2XBF X-ray 2.50 A 938-1319 [» ]
3B7Y X-ray 1.80 A/B 517-571 [» ]
4BBN X-ray 2.51 A 938-1319 [» ]
4BE8 X-ray 3.00 A 938-1319 [» ]
4N7F X-ray 1.10 A/B 841-874 [» ]
4N7H X-ray 1.70 A 840-872 [» ]
ProteinModelPortali P46934.
SMRi P46934. Positions 517-571, 611-642, 768-798, 841-873, 888-932, 938-1312.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110811. 281 interactions.
DIPi DIP-29815N.
IntActi P46934. 27 interactions.
MINTi MINT-86457.
STRINGi 9606.ENSP00000345530.

Protein family/group databases

TCDBi 8.A.30.1.2. the nedd4-family interacting protein-2 (nedd4) family.

PTM databases

PhosphoSitei P46934.

Polymorphism databases

DMDMi 313104311.

Proteomic databases

MaxQBi P46934.
PaxDbi P46934.
PRIDEi P46934.

Protocols and materials databases

DNASUi 4734.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000338963 ; ENSP00000345530 ; ENSG00000069869 . [P46934-3 ]
ENST00000435532 ; ENSP00000410613 ; ENSG00000069869 . [P46934-4 ]
ENST00000506154 ; ENSP00000422705 ; ENSG00000069869 . [P46934-2 ]
ENST00000508342 ; ENSP00000424827 ; ENSG00000069869 . [P46934-1 ]
GeneIDi 4734.
KEGGi hsa:4734.
UCSCi uc002adi.3. human. [P46934-3 ]
uc002adj.3. human. [P46934-1 ]
uc002adl.3. human. [P46934-4 ]
uc010ugj.2. human. [P46934-2 ]

Organism-specific databases

CTDi 4734.
GeneCardsi GC15M056119.
HGNCi HGNC:7727. NEDD4.
HPAi CAB001991.
HPA039883.
MIMi 602278. gene.
neXtProti NX_P46934.
PharmGKBi PA31533.
HUGEi Search...
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5021.
GeneTreei ENSGT00760000118966.
HOVERGENi HBG004134.
InParanoidi P46934.
KOi K10591.
OMAi RRICRAF.
OrthoDBi EOG7RFTGT.
PhylomeDBi P46934.
TreeFami TF323658.

Enzyme and pathway databases

UniPathwayi UPA00143 .
Reactomei REACT_115828. Downregulation of ERBB4 signaling.
REACT_115831. ISG15 antiviral mechanism.
REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinki P46934.

Miscellaneous databases

ChiTaRSi NEDD4. human.
EvolutionaryTracei P46934.
GeneWikii NEDD4.
GenomeRNAii 4734.
NextBioi 18250.
PROi P46934.
SOURCEi Search...

Gene expression databases

Bgeei P46934.
CleanExi HS_NEDD4.
Genevestigatori P46934.

Family and domain databases

Gene3Di 2.60.40.150. 1 hit.
InterProi IPR000008. C2_dom.
IPR000569. HECT.
IPR001202. WW_dom.
[Graphical view ]
Pfami PF00632. HECT. 1 hit.
PF00397. WW. 4 hits.
[Graphical view ]
SMARTi SM00119. HECTc. 1 hit.
SM00456. WW. 4 hits.
[Graphical view ]
SUPFAMi SSF51045. SSF51045. 4 hits.
SSF56204. SSF56204. 1 hit.
PROSITEi PS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 4 hits.
PS50020. WW_DOMAIN_2. 4 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, UBIQUITIN LIGASE ACTIVITY, INTERACTION WITH PTEN.
  2. "Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1."
    Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S., Tabata S., Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N.
    DNA Res. 2:37-43(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), VARIANTS GLN-679 AND SER-698.
    Tissue: Bone marrow.
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), VARIANTS GLN-679 AND SER-698.
    Tissue: Trachea.
  4. "Identification of a human cell proliferation inducing gene."
    Kim J.W.
    Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), VARIANTS GLN-679 AND SER-698.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    Tissue: Adipose tissue.
  6. "Analysis of the DNA sequence and duplication history of human chromosome 15."
    Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
    , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
    Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS GLN-679 AND SER-698.
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4), VARIANTS GLN-679 AND SER-698.
    Tissue: Brain and Testis.
  9. "Nedd4 regulates ubiquitination and stability of the guanine-nucleotide exchange factor CNrasGEF."
    Pham N., Rotin D.
    J. Biol. Chem. 276:46995-47003(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH RAPGEF2.
  10. "PPPYVEPTAP motif is the late domain of human T-cell leukemia virus type 1 Gag and mediates its functional interaction with cellular proteins Nedd4 and Tsg101."
    Bouamr F., Melillo J.A., Wang M.Q., Nagashima K., de Los Santos M., Rein A., Goff S.P.
    J. Virol. 77:11882-11895(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HTLV-1 MATRIX PROTEIN P19.
  11. "Nedd4 family-interacting protein 1 (Ndfip1) is required for the exosomal secretion of Nedd4 family proteins."
    Putz U., Howitt J., Lackovic J., Foot N., Kumar S., Silke J., Tan S.S.
    J. Biol. Chem. 283:32621-32627(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  12. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-747, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  13. "ISG15 inhibits Ebola VP40 VLP budding in an L-domain-dependent manner by blocking Nedd4 ligase activity."
    Okumura A., Pitha P.M., Harty R.N.
    Proc. Natl. Acad. Sci. U.S.A. 105:3974-3979(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH ISG15.
  14. "The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization."
    Fouladkou F., Landry T., Kawabe H., Neeb A., Lu C., Brose N., Stambolic V., Rotin D.
    Proc. Natl. Acad. Sci. U.S.A. 105:8585-8590(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH PTEN.
  15. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-747, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  16. "HECT E3 ubiquitin ligase Nedd4-1 ubiquitinates ACK and regulates epidermal growth factor (EGF)-induced degradation of EGF receptor and ACK."
    Lin Q., Wang J., Childress C., Sudol M., Carey D.J., Yang W.
    Mol. Cell. Biol. 30:1541-1554(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TNK2.
  17. Cited for: INTERACTION WITH RAP2A AND TNIK.
  18. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  19. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  20. "Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function."
    Persaud A., Alberts P., Hayes M., Guettler S., Clarke I., Sicheri F., Dirks P., Ciruna B., Rotin D.
    EMBO J. 30:3259-3273(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FGFR1, FUNCTION IN UBIQUITINATION OF FGFR1.
  21. Cited for: INTERACTION WITH OTUD7B.
  22. "Crystal structure of the C2 domain of the E3 ubiquitin-protein ligase Nedd4."
    Structural genomics consortium (SGC)
    Submitted (OCT-2007) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1-152 (ISOFORM 4).
  23. "Human NEDD4 3rd WW domain complex with ebola Zaire virus matrix protein VP40 derived peptide."
    Iglesias-Bexiga M.
    Submitted (OCT-2009) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 834-878.
  24. "Human NEDD4 3rd WW domain complex with human T-cell leukemia virus GAP-Pro polyprotein derived peptide."
    Iglesias-Bexiga M., Luque I., Macias M.
    Submitted (OCT-2009) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 834-878.
  25. "Structure of the HECT:ubiquitin complex and its role in ubiquitin chain elongation."
    Maspero E., Mari S., Valentini E., Musacchio A., Fish A., Pasqualato S., Polo S.
    EMBO Rep. 12:342-349(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 938-1319 IN COMPLEX WITH UBIQUITIN, FUNCTION.
  26. Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-627.

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 26, 2014
This is version 153 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

External Data

Dasty 3