Reviewed, UniProtKB/Swiss-Prot P46934 (NEDD4_HUMAN)

Names and origin

Protein names

Recommended name:
    E3 ubiquitin-protein ligase NEDD4
    EC=6.3.2.-
Alternative name(s):
    Neural precursor cell expressed developmentally down-regulated protein 4
      Short name=NEDD-4
    Cell proliferation-inducing gene 53 protein

Gene names

Name:	NEDD4
Synonyms:	KIAA0093, NEDD4-1
ORF Names:	PIG53

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1319 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Polyubiquitinates the tumor suppressor PTEN and thus targets PTEN for proteasomal degradation. Regulates tumorigenesis in a PTEN-dependent manner. Involved in the budding of many viruses. Ref.1
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 LITAF, RNF11, WBP1, WBP2, TMEPAI, NDFIP1 and PRRG2 By similarity. Interacts with PTEN. 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. Ref.1 Ref.9
Subcellular location	Cytoplasm By similarity.
Domain	The WW domains mediate interaction with LITAF, RNF11, WBP1, WBP2, TMEPAI, NDFIP1 and PRRG2 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.

Ontologies

Keywords
Biological process	Host-virus interaction Ubl conjugation pathway
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Molecular function	Ligase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	development during symbiotic interaction Inferred from mutant phenotype. Source: UniProtKB glucocorticoid receptor signaling pathway Inferred from direct assay. Source: UniProtKB negative regulation of sodium ion transport Inferred from direct assay. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage Inferred from mutant phenotype. Source: UniProtKB neuron projection development Inferred from expression pattern. Source: UniProtKB positive regulation of nucleocytoplasmic transport Inferred from direct assay. Source: UniProtKB positive regulation of phosphoinositide 3-kinase cascade Ref.1 Inferred from mutant phenotype. Source: UniProtKB positive regulation of protein catabolic process Inferred from direct assay. Source: MGI progesterone receptor signaling pathway Inferred from direct assay. Source: UniProtKB protein targeting to lysosome Inferred from direct assay. Source: UniProtKB protein ubiquitination during ubiquitin-dependent protein catabolic process Ref.1 Inferred from mutant phenotype. Source: UniProtKB receptor catabolic process Inferred from direct assay. Source: UniProtKB receptor internalization Inferred from direct assay. Source: UniProtKB response to calcium ion Traceable author statement. Source: UniProtKB transmission of virus Inferred from mutant phenotype. Source: UniProtKB
Cellular component	apicolateral plasma membrane Traceable author statement. Source: UniProtKB cell cortex Inferred from direct assay. Source: UniProtKB chromatin Inferred from direct assay. Source: UniProtKB cytosol Inferred from sequence or structural similarity. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay. Source: UniProtKB ubiquitin ligase complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	RNA polymerase binding Inferred from physical interaction. Source: UniProtKB beta-2 adrenergic receptor binding Inferred from direct assay. Source: UniProtKB phosphoserine binding Inferred from sequence or structural similarity. Source: UniProtKB phosphothreonine binding Inferred from sequence or structural similarity. Source: UniProtKB proline-rich region binding Inferred from physical interaction. Source: UniProtKB protein domain specific binding Inferred from physical interaction. Source: UniProtKB sodium channel inhibitor activity Inferred from direct assay. Source: UniProtKB ubiquitin binding Inferred from direct assay. Source: UniProtKB ubiquitin-protein ligase activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RPS27A	P62988	1	EBI-726944,EBI-413034

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1319

1319

E3 ubiquitin-protein ligase NEDD4

PRO_0000120319

Regions

Domain

610 – 643

34

WW 1

Domain

767 – 800

34

WW 2

Domain

840 – 873

34

WW 3

Domain

892 – 925

34

WW 4

Domain

984 – 1318

335

HECT

Compositional bias

68 – 215

148

Ser-rich

Sites

Active site

1286

1

Glycyl thioester intermediate By similarity

Amino acid modifications

Modified residue

648

1

Phosphothreonine By similarity

Modified residue

670

1

Phosphoserine By similarity

Modified residue

747

1

Phosphoserine Ref.10 Ref.12

Natural variations

Alternative sequence

1 – 419

419

Missing in isoform 4.

VSP_038256

Alternative sequence

420 – 516

97

SACLP…SNSCK → MATCAVEVFGLLEDEENSRI VRVRVIAGIGLAKKDILGAS DPYVRVTLYDPMNGVLTSVQ TKTIKKSLNPKWNEEILFRV HPQQHRLLFEVFDENRL in isoform 4.

VSP_038257

Alternative sequence

517 – 588

72

Missing in isoform 3.

VSP_038258

Alternative sequence

589 – 604

16

Missing in isoform 2.

VSP_038259

Natural variant

33

1

M → V: dbSNP rs1912403.

VAR_061985

Natural variant

627

1

Y → H in a breast cancer sample; somatic mutation. Ref.14

VAR_036472

Natural variant

679

1

Q → R: dbSNP rs2303580. Ref.5 Ref.6 Ref.8

VAR_047909

Natural variant

698

1

S → N: dbSNP rs2303579. Ref.5 Ref.6 Ref.8

VAR_047910

Experimental info

Sequence conflict

59

1

A → T in AL832063. Ref.5

Sequence conflict

407

1

N → H in AL832063. Ref.5

Sequence conflict

620

1

Q → R in AAT52215. Ref.4

Sequence conflict

620

1

Q → R in AAI44285. Ref.8

Sequence conflict

863

1

T → I in AAI36606. Ref.8

Sequence conflict

863

1

T → I in AAI44285. Ref.8

Sequence conflict

1199

1

L → P in BAG65229. Ref.3

Sequence conflict

1268

1

S → L in AL832063. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

1319

Helix Strand Turn

Details...

Beta strand

520 – 528

9

Beta strand

546 – 549

4

Beta strand

561 – 569

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 13, 2009. Version 3. Checksum: 4014BA98ACF2D82D	FASTA	1,319	149,059
	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 EETESVDNQE SSENWEIIRE DEATMYSSQA 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
	Isoform 2. Checksum: 517B13B96F7AAD00	FASTA	1,303	147,328
	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 AEQAEELEQQ QEPSPLPPGW 610 620 630 640 650 660 EERQDILGRT YYVNHESRRT QWKRPTPQDN LTDAENGNIQ LQAQRAFTTR RQISEETESV 670 680 690 700 710 720 DNQESSENWE IIREDEATMY SSQAFPSPPP SSNLDVPTHL AEELNARLTI FGNSAVSQPA 730 740 750 760 770 780 SSSNHSSRRG SLQAYTFEEQ PTLPVLLPTS SGLPPGWEEK QDERGRSYYV DHNSRTTTWT 790 800 810 820 830 840 KPTVQATVET SQLTSSQSSA GPQSQASTSD SGQQVTQPSE IEQGFLPKGW EVRHAPNGRP 850 860 870 880 890 900 FFIDHNTKTT TWEDPRLKIP AHLRGKTSLD TSNDLGPLPP GWEERTHTDG RIFYINHNIK 910 920 930 940 950 960 RTQWEDPRLE NVAITGPAVP YSRDYKRKYE FFRRKLKKQN DIPNKFEMKL RRATVLEDSY 970 980 990 1000 1010 1020 RRIMGVKRAD FLKARLWIEF DGEKGLDYGG VAREWFFLIS KEMFNPYYGL FEYSATDNYT 1030 1040 1050 1060 1070 1080 LQINPNSGLC NEDHLSYFKF IGRVAGMAVY HGKLLDGFFI RPFYKMMLHK PITLHDMESV 1090 1100 1110 1120 1130 1140 DSEYYNSLRW ILENDPTELD LRFIIDEELF GQTHQHELKN GGSEIVVTNK NKKEYIYLVI 1150 1160 1170 1180 1190 1200 QWRFVNRIQK QMAAFKEGFF ELIPQDLIKI FDENELELLM CGLGDVDVND WREHTKYKNG 1210 1220 1230 1240 1250 1260 YSANHQVIQW FWKAVLMMDS EKRIRLLQFV TGTSRVPMNG FAELYGSNGP QSFTVEQWGT 1270 1280 1290 1300 PEKLPRAHTC FNRLDLPPYE SFEELWDKLQ MAIENTQGFD GVD
	Isoform 3. Checksum: 1700C40212699FB5	FASTA	1,247	140,641
	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 LSNSCKPGWV VLDQPDAACH LQQQQEPSPL 550 560 570 580 590 600 PPGWEERQDI LGRTYYVNHE SRRTQWKRPT PQDNLTDAEN GNIQLQAQRA FTTRRQISEE 610 620 630 640 650 660 TESVDNQESS ENWEIIREDE ATMYSSQAFP SPPPSSNLDV PTHLAEELNA RLTIFGNSAV 670 680 690 700 710 720 SQPASSSNHS SRRGSLQAYT FEEQPTLPVL LPTSSGLPPG WEEKQDERGR SYYVDHNSRT 730 740 750 760 770 780 TTWTKPTVQA TVETSQLTSS QSSAGPQSQA STSDSGQQVT QPSEIEQGFL PKGWEVRHAP 790 800 810 820 830 840 NGRPFFIDHN TKTTTWEDPR LKIPAHLRGK TSLDTSNDLG PLPPGWEERT HTDGRIFYIN 850 860 870 880 890 900 HNIKRTQWED PRLENVAITG PAVPYSRDYK RKYEFFRRKL KKQNDIPNKF EMKLRRATVL 910 920 930 940 950 960 EDSYRRIMGV KRADFLKARL WIEFDGEKGL DYGGVAREWF FLISKEMFNP YYGLFEYSAT 970 980 990 1000 1010 1020 DNYTLQINPN SGLCNEDHLS YFKFIGRVAG MAVYHGKLLD GFFIRPFYKM MLHKPITLHD 1030 1040 1050 1060 1070 1080 MESVDSEYYN SLRWILENDP TELDLRFIID EELFGQTHQH ELKNGGSEIV VTNKNKKEYI 1090 1100 1110 1120 1130 1140 YLVIQWRFVN RIQKQMAAFK EGFFELIPQD LIKIFDENEL ELLMCGLGDV DVNDWREHTK 1150 1160 1170 1180 1190 1200 YKNGYSANHQ VIQWFWKAVL MMDSEKRIRL LQFVTGTSRV PMNGFAELYG SNGPQSFTVE 1210 1220 1230 1240 QWGTPEKLPR AHTCFNRLDL PPYESFEELW DKLQMAIENT QGFDGVD
	Isoform 4. Checksum: D679292097F598D1	FASTA	900	104,162
	10 20 30 40 50 60 MATCAVEVFG LLEDEENSRI VRVRVIAGIG LAKKDILGAS DPYVRVTLYD PMNGVLTSVQ 70 80 90 100 110 120 TKTIKKSLNP KWNEEILFRV HPQQHRLLFE VFDENRLTRD DFLGQVDVPL YPLPTENPRL 130 140 150 160 170 180 ERPYTFKDFV LHPRSHKSRV KGYLRLKMTY LPKTSGSEDD NAEQAEELEP GWVVLDQPDA 190 200 210 220 230 240 ACHLQQQQEP SPLPPGWEER QDILGRTYYV NHESRRTQWK RPTPQDNLTD AENGNIQLQA 250 260 270 280 290 300 QRAFTTRRQI SEETESVDNQ ESSENWEIIR EDEATMYSSQ AFPSPPPSSN LDVPTHLAEE 310 320 330 340 350 360 LNARLTIFGN SAVSQPASSS NHSSRRGSLQ AYTFEEQPTL PVLLPTSSGL PPGWEEKQDE 370 380 390 400 410 420 RGRSYYVDHN SRTTTWTKPT VQATVETSQL TSSQSSAGPQ SQASTSDSGQ QVTQPSEIEQ 430 440 450 460 470 480 GFLPKGWEVR HAPNGRPFFI DHNTKTTTWE DPRLKIPAHL RGKTSLDTSN DLGPLPPGWE 490 500 510 520 530 540 ERTHTDGRIF YINHNIKRTQ WEDPRLENVA ITGPAVPYSR DYKRKYEFFR RKLKKQNDIP 550 560 570 580 590 600 NKFEMKLRRA TVLEDSYRRI MGVKRADFLK ARLWIEFDGE KGLDYGGVAR EWFFLISKEM 610 620 630 640 650 660 FNPYYGLFEY SATDNYTLQI NPNSGLCNED HLSYFKFIGR VAGMAVYHGK LLDGFFIRPF 670 680 690 700 710 720 YKMMLHKPIT LHDMESVDSE YYNSLRWILE NDPTELDLRF IIDEELFGQT HQHELKNGGS 730 740 750 760 770 780 EIVVTNKNKK EYIYLVIQWR FVNRIQKQMA AFKEGFFELI PQDLIKIFDE NELELLMCGL 790 800 810 820 830 840 GDVDVNDWRE HTKYKNGYSA NHQVIQWFWK AVLMMDSEKR IRLLQFVTGT SRVPMNGFAE 850 860 870 880 890 900 LYGSNGPQSF TVEQWGTPEK LPRAHTCFNR LDLPPYESFE ELWDKLQMAI ENTQGFDGVD

References

	« Hide 'large scale' referencesShow '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: 17218260] [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: 7788527] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). 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).
[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: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANTS ARG-679 AND ASN-698. 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: 16572171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS ARG-679 AND ASN-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. , 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4), VARIANTS ARG-679 AND ASN-698. Tissue: Brain and Testis.
[9]	"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: 14581525] [Abstract] Cited for: INTERACTION WITH HTLV-1 MATRIX PROTEIN P19.
[10]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-747, MASS SPECTROMETRY.
[11]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[12]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-747, MASS SPECTROMETRY. Tissue: T-cell.
[13]	"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 (1.0 ANGSTROMS) OF 1-152 (ISOFORM 4).
[14]	"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. , 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: 16959974] [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.

IPI

IPI00384495.
IPI00940829.
IPI00944928.
IPI00945379.

RefSeq

NP_006145.2.

UniGene

Hs.1565

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3B7Y	X-ray	1.80	A/B	517-571	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29815N.

IntAct

P46934. 2 interactions.

STRING

P46934.

PTM databases

PhosphoSite

P46934.

Proteomic databases

PRIDE

P46934.

Genome annotation databases

Ensembl

ENST00000164316; ENSP00000164316; ENSG00000069869; Homo sapiens. [Genome view]
ENST00000338963; ENSP00000345530; ENSG00000069869; Homo sapiens. [Genome view]
ENST00000435532; ENSP00000410613; ENSG00000069869; Homo sapiens. [Genome view]

GeneID

4734.

KEGG

hsa:4734.

Organism-specific databases

CTD

4734.

GeneCards

GC15M053906.

HGNC

HGNC:7727. NEDD4.

HPA

CAB001991.

MIM

602278. gene.

PharmGKB

PA31533.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P46934.

PhylomeDB

P46934.

Enzyme and pathway databases

Pathway_Interaction_DB

ps1pathway. Presenilin action in Notch and Wnt signaling.
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.

Gene expression databases

ArrayExpress

P46934.

Bgee

P46934.

CleanEx

HS_NEDD4.

Genevestigator

P46934.

GermOnline

ENSG00000069869. Homo sapiens.

Family and domain databases

InterPro

IPR000569. HECT.
IPR001202. WW_Rsp5_WWP.
[Graphical view]

Pfam

PF00632. HECT. 1 hit.
PF00397. WW. 4 hits.
[Graphical view]

SMART

SM00119. HECTc. 1 hit.
SM00456. WW. 4 hits.
[Graphical view]

PROSITE

PS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 4 hits.
PS50020. WW_DOMAIN_2. 4 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

18250.

SOURCE

Search...

Entry information

Entry name

NEDD4_HUMAN

Accession

Primary (citable) accession number: P46934
Secondary accession number(s): A1KY35 , A6ND72, A7MD29, B4E2R7, B7ZM59, B7ZM60, B9EGN5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	October 13, 2009
Last modified:	January 19, 2010
This is version 98 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.