CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007852
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 E3 ubiquitin-protein ligase NEDD4 
Protein Synonyms/Alias
 Cell proliferation-inducing gene 53 protein; Neural precursor cell expressed developmentally down-regulated protein 4; NEDD-4 
Gene Name
 NEDD4 
Gene Synonyms/Alias
 KIAA0093; NEDD4-1; PIG53 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
639ESRRTQWKRPTPQDNubiquitination[1, 2]
864FFIDHNTKTTTWEDPubiquitination[1]
874TWEDPRLKIPAHLRGubiquitination[2]
882IPAHLRGKTSLDTSNubiquitination[1, 2, 3]
916FYINHNIKRTQWEDPubiquitination[1, 2, 4]
Reference
 [1] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473] 
Functional Description
 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. 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. 
Sequence Annotation
 DOMAIN 610 643 WW 1.
 DOMAIN 767 800 WW 2.
 DOMAIN 840 873 WW 3.
 DOMAIN 892 925 WW 4.
 DOMAIN 984 1318 HECT.
 REGION 578 981 Mediates interaction with TNIK (By
 ACT_SITE 1286 1286 Glycyl thioester intermediate (By
 MOD_RES 648 648 Phosphothreonine (By similarity).
 MOD_RES 670 670 Phosphoserine (By similarity).
 MOD_RES 747 747 Phosphoserine.  
Keyword
 3D-structure; Alternative splicing; Cell membrane; Complete proteome; Cytoplasm; Host-virus interaction; Ligase; Membrane; Neurogenesis; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1319 AA 
Protein Sequence
MAQSLRLHFA ARRSNTYPLS ETSGDDLDSH VHMCFKRPTR ISTSNVVQMK LTPRQTALAP 60
LIKENVQSQE RSSVPSSENV NKKSSCLQIS LQPTRYSGYL QSSNVLADSD DASFTCILKD 120
GIYSSAVVDN ELNAVNDGHL VSSPAICSGS LSNFSTSDNG SYSSNGSDFG SCASITSGGS 180
YTNSVISDSS SYTFPPSDDT FLGGNLPSDS TSNRSVPNRN TTPCEIFSRS TSTDPFVQDD 240
LEHGLEIMKL PVSRNTKIPL KRYSSLVIFP RSPSTTRPTS PTSLCTLLSK GSYQTSHQFI 300
ISPSEIAHNE DGTSAKGFLS TAVNGLRLSK TICTPGEVRD IRPLHRKGSL QKKIVLSNNT 360
PRQTVCEKSS EGYSCVSVHF TQRKAATLDC ETTNGDCKPE MSEIKLNSDS EYIKLMHRTS 420
ACLPSSQNVD CQININGELE RPHSQMNKNH GILRRSISLG GAYPNISCLS SLKHNCSKGG 480
PSQLLIKFAS GNEGKVDNLS RDSNRDCTNE LSNSCKTRDD FLGQVDVPLY PLPTENPRLE 540
RPYTFKDFVL HPRSHKSRVK GYLRLKMTYL PKTSGSEDDN AEQAEELEPG WVVLDQPDAA 600
CHLQQQQEPS PLPPGWEERQ DILGRTYYVN HESRRTQWKR PTPQDNLTDA ENGNIQLQAQ 660
RAFTTRRQIS EETESVDNRE SSENWEIIRE DEATMYSNQA FPSPPPSSNL DVPTHLAEEL 720
NARLTIFGNS AVSQPASSSN HSSRRGSLQA YTFEEQPTLP VLLPTSSGLP PGWEEKQDER 780
GRSYYVDHNS RTTTWTKPTV QATVETSQLT SSQSSAGPQS QASTSDSGQQ VTQPSEIEQG 840
FLPKGWEVRH APNGRPFFID HNTKTTTWED PRLKIPAHLR GKTSLDTSND LGPLPPGWEE 900
RTHTDGRIFY INHNIKRTQW EDPRLENVAI TGPAVPYSRD YKRKYEFFRR KLKKQNDIPN 960
KFEMKLRRAT VLEDSYRRIM GVKRADFLKA RLWIEFDGEK GLDYGGVARE WFFLISKEMF 1020
NPYYGLFEYS ATDNYTLQIN PNSGLCNEDH LSYFKFIGRV AGMAVYHGKL LDGFFIRPFY 1080
KMMLHKPITL HDMESVDSEY YNSLRWILEN DPTELDLRFI IDEELFGQTH QHELKNGGSE 1140
IVVTNKNKKE YIYLVIQWRF VNRIQKQMAA FKEGFFELIP QDLIKIFDEN ELELLMCGLG 1200
DVDVNDWREH TKYKNGYSAN HQVIQWFWKA VLMMDSEKRI RLLQFVTGTS RVPMNGFAEL 1260
YGSNGPQSFT VEQWGTPEKL PRAHTCFNRL DLPPYESFEE LWDKLQMAIE NTQGFDGVD 1319 
Gene Ontology
 GO:0016327; C:apicolateral plasma membrane; TAS:BHF-UCL.
 GO:0005938; C:cell cortex; IDA:BHF-UCL.
 GO:0000785; C:chromatin; IDA:BHF-UCL.
 GO:0005829; C:cytosol; ISS:BHF-UCL.
 GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
 GO:0005634; C:nucleus; IBA:RefGenome.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
 GO:0000151; C:ubiquitin ligase complex; ISS:BHF-UCL.
 GO:0031698; F:beta-2 adrenergic receptor binding; IDA:UniProtKB.
 GO:0050815; F:phosphoserine binding; ISS:BHF-UCL.
 GO:0050816; F:phosphothreonine binding; ISS:BHF-UCL.
 GO:0070064; F:proline-rich region binding; IMP:BHF-UCL.
 GO:0019871; F:sodium channel inhibitor activity; IDA:BHF-UCL.
 GO:0043130; F:ubiquitin binding; IDA:BHF-UCL.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:BHF-UCL.
 GO:0002250; P:adaptive immune response; IEA:Compara.
 GO:0048514; P:blood vessel morphogenesis; IEA:Compara.
 GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
 GO:0044111; P:development involved in symbiotic interaction; IMP:UniProtKB.
 GO:0003197; P:endocardial cushion development; IEA:Compara.
 GO:0042921; P:glucocorticoid receptor signaling pathway; IDA:BHF-UCL.
 GO:0010766; P:negative regulation of sodium ion transport; IDA:UniProtKB.
 GO:0010768; P:negative regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage; IMP:BHF-UCL.
 GO:0030948; P:negative regulation of vascular endothelial growth factor receptor signaling pathway; ISS:UniProtKB.
 GO:0007528; P:neuromuscular junction development; IEA:Compara.
 GO:0031175; P:neuron projection development; IEP:BHF-UCL.
 GO:0003151; P:outflow tract morphogenesis; IEA:Compara.
 GO:0046824; P:positive regulation of nucleocytoplasmic transport; IDA:BHF-UCL.
 GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase cascade; IMP:BHF-UCL.
 GO:0045732; P:positive regulation of protein catabolic process; IDA:MGI.
 GO:0050847; P:progesterone receptor signaling pathway; IDA:BHF-UCL.
 GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
 GO:0006513; P:protein monoubiquitination; IEA:Compara.
 GO:0006622; P:protein targeting to lysosome; IDA:UniProtKB.
 GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
 GO:0032801; P:receptor catabolic process; IDA:UniProtKB.
 GO:0031623; P:receptor internalization; IDA:UniProtKB.
 GO:0048814; P:regulation of dendrite morphogenesis; ISS:UniProtKB.
 GO:0042391; P:regulation of membrane potential; IDA:BHF-UCL.
 GO:1901016; P:regulation of potassium ion transmembrane transporter activity; IDA:BHF-UCL.
 GO:0050807; P:regulation of synapse organization; IEA:Compara.
 GO:0051592; P:response to calcium ion; TAS:BHF-UCL.
 GO:0042110; P:T cell activation; IEA:Compara.
 GO:0019089; P:transmission of virus; IMP:BHF-UCL.
 GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IMP:BHF-UCL.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
Interpro
 IPR000569; HECT.
 IPR001202; WW_dom. 
Pfam
 PF00632; HECT
 PF00397; WW 
SMART
 SM00119; HECTc
 SM00456; WW 
PROSITE
 PS50237; HECT
 PS01159; WW_DOMAIN_1
 PS50020; WW_DOMAIN_2 
PRINTS