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P46934 (NEDD4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:NEDD4
Synonyms:KIAA0093, NEDD4-1
ORF Names:PIG53
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1319 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 Ref.14 the direct link between NEDD4 and PTEN regulation through polyubiquitination described in Ref.1 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. Ref.1 Ref.9 Ref.13 Ref.14 Ref.16 Ref.20 Ref.25

Enzyme regulation

Activated by NDFIP1- and NDFIP2-binding By similarity.

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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 Ref.14. 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. Ref.1 Ref.9 Ref.10 Ref.13 Ref.14 Ref.16 Ref.17 Ref.20 Ref.21

Subcellular location

Cytoplasm By similarity. Cell membrane; 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. Ref.11

Domain

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

Post-translational modification

Auto-ubiquitinated By similarity.

Miscellaneous

A cysteine residue is required for ubiquitin-thioester formation.

Sequence similarities

Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.

Contains 4 WW domains.

Sequence caution

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

Ontologies

Keywords
   Biological processHost-virus interaction
Neurogenesis
Ubl conjugation pathway
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   Molecular functionLigase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell activation

Inferred from electronic annotation. Source: Ensembl

adaptive immune response

Inferred from electronic annotation. Source: Ensembl

blood vessel morphogenesis

Inferred from electronic annotation. Source: Ensembl

cellular response to UV

Inferred from mutant phenotype PubMed 17996703. Source: BHF-UCL

cytokine-mediated signaling pathway

Traceable author statement. Source: Reactome

development involved in symbiotic interaction

Inferred from mutant phenotype PubMed 15126635. Source: UniProtKB

endocardial cushion development

Inferred from electronic annotation. Source: Ensembl

glucocorticoid receptor signaling pathway

Inferred from direct assay PubMed 8649367. Source: BHF-UCL

lysosomal transport

Inferred from direct assay PubMed 18544533. Source: UniProtKB

negative regulation of sodium ion transport

Inferred from direct assay PubMed 10642508. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage

Inferred from mutant phenotype PubMed 17996703. Source: BHF-UCL

negative regulation of vascular endothelial growth factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

neuromuscular junction development

Inferred from electronic annotation. Source: Ensembl

neuron projection development

Inferred from expression pattern PubMed 9990509. Source: BHF-UCL

outflow tract morphogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of nucleocytoplasmic transport

Inferred from direct assay PubMed 17218261. Source: BHF-UCL

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

positive regulation of protein catabolic process

Inferred from direct assay PubMed 14973438. Source: MGI

progesterone receptor signaling pathway

Inferred from direct assay PubMed 8649367. Source: BHF-UCL

protein K63-linked ubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

protein monoubiquitination

Inferred from electronic annotation. Source: Ensembl

protein targeting to lysosome

Inferred from direct assay PubMed 17116753. Source: UniProtKB

protein ubiquitination

Inferred from direct assay Ref.13. Source: UniProtKB

protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Inferred from direct assay Ref.16. Source: BHF-UCL

receptor catabolic process

Inferred from direct assay PubMed 18544533. Source: UniProtKB

receptor internalization

Inferred from direct assay PubMed 18544533. Source: UniProtKB

regulation of dendrite morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of ion transmembrane transport

Inferred from direct assay PubMed 17289006. Source: BHF-UCL

regulation of membrane potential

Inferred from direct assay PubMed 17289006. Source: BHF-UCL

regulation of potassium ion transmembrane transporter activity

Inferred from direct assay PubMed 17289006. Source: BHF-UCL

regulation of synapse organization

Inferred from electronic annotation. Source: Ensembl

response to calcium ion

Traceable author statement PubMed 9405440. Source: BHF-UCL

transmission of virus

Inferred from mutant phenotype PubMed 15126635. Source: BHF-UCL

ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway

Inferred from mutant phenotype Ref.16. Source: BHF-UCL

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 16118794. Source: UniProtKB

apicolateral plasma membrane

Traceable author statement PubMed 9405440. Source: BHF-UCL

cell cortex

Inferred from direct assay PubMed 9990509. Source: BHF-UCL

chromatin

Inferred from direct assay PubMed 17996703. Source: BHF-UCL

cytoplasm

Inferred from direct assay PubMed 12796489. Source: BHF-UCL

cytosol

Inferred from sequence or structural similarity. Source: BHF-UCL

nucleus

Inferred from Biological aspect of Ancestor. Source: RefGenome

perinuclear region of cytoplasm

Inferred from direct assay PubMed 9990509. Source: BHF-UCL

plasma membrane

Inferred from direct assay PubMed 16118794. Source: UniProtKB

ubiquitin ligase complex

Inferred from sequence or structural similarity. Source: BHF-UCL

   Molecular_functionRNA polymerase binding

Inferred from physical interaction PubMed 17996703. Source: BHF-UCL

beta-2 adrenergic receptor binding

Inferred from direct assay PubMed 18544533. Source: UniProtKB

phosphoserine binding

Inferred from sequence or structural similarity. Source: BHF-UCL

phosphothreonine binding

Inferred from sequence or structural similarity. Source: BHF-UCL

proline-rich region binding

Inferred from physical interaction PubMed 11342538. Source: UniProtKB

protein domain specific binding

Inferred from physical interaction PubMed 12907594. Source: UniProtKB

sodium channel inhibitor activity

Inferred from direct assay PubMed 10642508. Source: BHF-UCL

ubiquitin binding

Inferred from direct assay PubMed 9990509. Source: BHF-UCL

ubiquitin-protein ligase activity

Inferred from direct assay PubMed 17996703Ref.16. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P46934-1)

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.
Note: No experimental confirmation available.
Isoform 2 (identifier: P46934-2)

The sequence of this isoform differs from the canonical sequence as follows:
     589-604: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: P46934-3)

The sequence of this isoform differs from the canonical sequence as follows:
     517-588: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: P46934-4)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 13191319E3 ubiquitin-protein ligase NEDD4
PRO_0000120319

Regions

Domain610 – 64334WW 1
Domain767 – 80034WW 2
Domain840 – 87334WW 3
Domain892 – 92534WW 4
Domain984 – 1318335HECT
Region578 – 981404Mediates interaction with TNIK By similarity
Compositional bias68 – 215148Ser-rich

Sites

Active site12861Glycyl thioester intermediate By similarity

Amino acid modifications

Modified residue6481Phosphothreonine By similarity
Modified residue6701Phosphoserine By similarity
Modified residue7471Phosphoserine Ref.12 Ref.15

Natural variations

Alternative sequence1 – 419419Missing in isoform 4.
VSP_038256
Alternative sequence420 – 51697SACLP…SNSCK → MATCAVEVFGLLEDEENSRI VRVRVIAGIGLAKKDILGAS DPYVRVTLYDPMNGVLTSVQ TKTIKKSLNPKWNEEILFRV HPQQHRLLFEVFDENRL in isoform 4.
VSP_038257
Alternative sequence517 – 58872Missing in isoform 3.
VSP_038258
Alternative sequence589 – 60416Missing in isoform 2.
VSP_038259
Natural variant331M → V.
Corresponds to variant rs1912403 [ dbSNP | Ensembl ].
VAR_061985
Natural variant6271Y → H in a breast cancer sample; somatic mutation. Ref.26
VAR_036472
Natural variant6791R → Q. Ref.2 Ref.3 Ref.4 Ref.6 Ref.8
Corresponds to variant rs2303580 [ dbSNP | Ensembl ].
VAR_047909
Natural variant6981N → S. Ref.2 Ref.3 Ref.4 Ref.6 Ref.8
Corresponds to variant rs2303579 [ dbSNP | Ensembl ].
VAR_047910

Experimental info

Sequence conflict591A → T in AL832063. Ref.5
Sequence conflict4071N → H in AL832063. Ref.5
Sequence conflict6201Q → R in AAT52215. Ref.4
Sequence conflict6201Q → R in AAI44285. Ref.8
Sequence conflict8631T → I in AAI36606. Ref.8
Sequence conflict8631T → I in AAI44285. Ref.8
Sequence conflict11991L → P in BAG65229. Ref.3
Sequence conflict12681S → L in AL832063. Ref.5

Secondary structure

.......................................................................................... 1319
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 30, 2010. Version 4.
Checksum: D56EBBC50A34F13B

FASTA1,319149,114
        10         20         30         40         50         60 
MAQSLRLHFA ARRSNTYPLS ETSGDDLDSH VHMCFKRPTR ISTSNVVQMK LTPRQTALAP 

        70         80         90        100        110        120 
LIKENVQSQE RSSVPSSENV NKKSSCLQIS LQPTRYSGYL QSSNVLADSD DASFTCILKD 

       130        140        150        160        170        180 
GIYSSAVVDN ELNAVNDGHL VSSPAICSGS LSNFSTSDNG SYSSNGSDFG SCASITSGGS 

       190        200        210        220        230        240 
YTNSVISDSS SYTFPPSDDT FLGGNLPSDS TSNRSVPNRN TTPCEIFSRS TSTDPFVQDD 

       250        260        270        280        290        300 
LEHGLEIMKL PVSRNTKIPL KRYSSLVIFP RSPSTTRPTS PTSLCTLLSK GSYQTSHQFI 

       310        320        330        340        350        360 
ISPSEIAHNE DGTSAKGFLS TAVNGLRLSK TICTPGEVRD IRPLHRKGSL QKKIVLSNNT 

       370        380        390        400        410        420 
PRQTVCEKSS EGYSCVSVHF TQRKAATLDC ETTNGDCKPE MSEIKLNSDS EYIKLMHRTS 

       430        440        450        460        470        480 
ACLPSSQNVD CQININGELE RPHSQMNKNH GILRRSISLG GAYPNISCLS SLKHNCSKGG 

       490        500        510        520        530        540 
PSQLLIKFAS GNEGKVDNLS RDSNRDCTNE LSNSCKTRDD FLGQVDVPLY PLPTENPRLE 

       550        560        570        580        590        600 
RPYTFKDFVL HPRSHKSRVK GYLRLKMTYL PKTSGSEDDN AEQAEELEPG WVVLDQPDAA 

       610        620        630        640        650        660 
CHLQQQQEPS PLPPGWEERQ DILGRTYYVN HESRRTQWKR PTPQDNLTDA ENGNIQLQAQ 

       670        680        690        700        710        720 
RAFTTRRQIS EETESVDNRE SSENWEIIRE DEATMYSNQA FPSPPPSSNL DVPTHLAEEL 

       730        740        750        760        770        780 
NARLTIFGNS AVSQPASSSN HSSRRGSLQA YTFEEQPTLP VLLPTSSGLP PGWEEKQDER 

       790        800        810        820        830        840 
GRSYYVDHNS RTTTWTKPTV QATVETSQLT SSQSSAGPQS QASTSDSGQQ VTQPSEIEQG 

       850        860        870        880        890        900 
FLPKGWEVRH APNGRPFFID HNTKTTTWED PRLKIPAHLR GKTSLDTSND LGPLPPGWEE 

       910        920        930        940        950        960 
RTHTDGRIFY INHNIKRTQW EDPRLENVAI TGPAVPYSRD YKRKYEFFRR KLKKQNDIPN 

       970        980        990       1000       1010       1020 
KFEMKLRRAT VLEDSYRRIM GVKRADFLKA RLWIEFDGEK GLDYGGVARE WFFLISKEMF 

      1030       1040       1050       1060       1070       1080 
NPYYGLFEYS ATDNYTLQIN PNSGLCNEDH LSYFKFIGRV AGMAVYHGKL LDGFFIRPFY 

      1090       1100       1110       1120       1130       1140 
KMMLHKPITL HDMESVDSEY YNSLRWILEN DPTELDLRFI IDEELFGQTH QHELKNGGSE 

      1150       1160       1170       1180       1190       1200 
IVVTNKNKKE YIYLVIQWRF VNRIQKQMAA FKEGFFELIP QDLIKIFDEN ELELLMCGLG 

      1210       1220       1230       1240       1250       1260 
DVDVNDWREH TKYKNGYSAN HQVIQWFWKA VLMMDSEKRI RLLQFVTGTS RVPMNGFAEL 

      1270       1280       1290       1300       1310 
YGSNGPQSFT VEQWGTPEKL PRAHTCFNRL DLPPYESFEE LWDKLQMAIE NTQGFDGVD 

« Hide

Isoform 2 [UniParc].

Checksum: C40112E4C9BC8416
Show »

FASTA1,303147,384
Isoform 3 [UniParc].

Checksum: 827AC55FB4AFB6A3
Show »

FASTA1,247140,696
Isoform 4 [UniParc].

Checksum: 4303287D3133B1C7
Show »

FASTA900104,217

References

« Hide 'large scale' references
[1]"NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN."
Wang X., Trotman L.C., Koppie T., Alimonti A., Chen Z., Gao Z., Wang J., Erdjument-Bromage H., Tempst P., Cordon-Cardo C., Pandolfi P.P., Jiang X.
Cell 128:129-139(2007) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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]"Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development."
Kawabe H., Neeb A., Dimova K., Young S.M. Jr., Takeda M., Katsurabayashi S., Mitkovski M., Malakhova O.A., Zhang D.E., Umikawa M., Kariya K., Goebbels S., Nave K.A., Rosenmund C., Jahn O., Rhee J., Brose N.
Neuron 65:358-372(2010) [PubMed] [Europe PMC] [Abstract]
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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]"Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression."
Pareja F., Ferraro D.A., Rubin C., Cohen-Dvashi H., Zhang F., Aulmann S., Ben-Chetrit N., Pines G., Navon R., Crosetto N., Kostler W., Carvalho S., Lavi S., Schmitt F., Dikic I., Yakhini Z., Sinn P., Mills G.B., Yarden Y.
Oncogene 31:4599-4608(2012) [PubMed] [Europe PMC] [Abstract]
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]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-627.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001271267.1. NM_001284338.1.
NP_001271268.1. NM_001284339.1.
NP_001271269.1. NM_001284340.1.
NP_006145.2. NM_006154.3.
NP_940682.2. NM_198400.3.
UniGeneHs.1565.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP46934.
SMRP46934. Positions 517-571, 611-642, 768-798, 841-875, 888-932, 938-1312.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110811. 259 interactions.
DIPDIP-29815N.
IntActP46934. 27 interactions.
MINTMINT-86457.
STRING9606.ENSP00000345530.

Protein family/group databases

TCDB8.A.30.1.2. the nedd4-family interacting protein-2 (nedd4) family.

PTM databases

PhosphoSiteP46934.

Polymorphism databases

DMDM313104311.

Proteomic databases

PaxDbP46934.
PRIDEP46934.

Protocols and materials databases

DNASU4734.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000338963; ENSP00000345530; ENSG00000069869. [P46934-3]
ENST00000435532; ENSP00000410613; ENSG00000069869. [P46934-4]
ENST00000506154; ENSP00000422705; ENSG00000069869. [P46934-2]
ENST00000508342; ENSP00000424827; ENSG00000069869. [P46934-1]
GeneID4734.
KEGGhsa:4734.
UCSCuc002adi.3. human. [P46934-3]
uc002adj.3. human. [P46934-1]
uc002adl.3. human. [P46934-4]
uc010ugj.2. human. [P46934-2]

Organism-specific databases

CTD4734.
GeneCardsGC15M056119.
HGNCHGNC:7727. NEDD4.
HPACAB001991.
HPA039883.
MIM602278. gene.
neXtProtNX_P46934.
PharmGKBPA31533.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5021.
HOVERGENHBG004134.
KOK10591.
OMAYRRILSV.
OrthoDBEOG7RFTGT.
PhylomeDBP46934.
TreeFamTF323658.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_6900. Immune System.
SignaLinkP46934.
UniPathwayUPA00143.

Gene expression databases

BgeeP46934.
CleanExHS_NEDD4.
GenevestigatorP46934.

Family and domain databases

Gene3D2.60.40.150. 1 hit.
InterProIPR000008. C2_dom.
IPR000569. HECT.
IPR001202. WW_dom.
[Graphical view]
PfamPF00632. HECT. 1 hit.
PF00397. WW. 4 hits.
[Graphical view]
SMARTSM00119. HECTc. 1 hit.
SM00456. WW. 4 hits.
[Graphical view]
SUPFAMSSF51045. SSF51045. 4 hits.
SSF56204. SSF56204. 1 hit.
PROSITEPS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 4 hits.
PS50020. WW_DOMAIN_2. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNEDD4. human.
EvolutionaryTraceP46934.
GeneWikiNEDD4.
GenomeRNAi4734.
NextBio18250.
PROP46934.
SOURCESearch...

Entry information

Entry nameNEDD4_HUMAN
AccessionPrimary (citable) accession number: P46934
Secondary accession number(s): A1KY35 expand/collapse secondary AC list , A6ND72, A7MD29, B4E2R7, B7ZM59, B7ZM60, B9EGN5, D6RF89
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 30, 2010
Last modified: April 16, 2014
This is version 146 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM