CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007854
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 E3 ubiquitin-protein ligase NEDD4 
Protein Synonyms/Alias
 Neural precursor cell expressed developmentally down-regulated protein 4; NEDD-4 
Gene Name
 Nedd4 
Gene Synonyms/Alias
 Kiaa0093; Nedd-4; Nedd4-1; Nedd4a 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
83DTRVVRVKVIAGIGLubiquitination[1]
92IAGIGLAKKDILGASubiquitination[1]
93AGIGLAKKDILGASDubiquitination[1]
130IKKSLNPKWNEEILFacetylation[2]
130IKKSLNPKWNEEILFubiquitination[1]
186MERPYTFKDFVLHPRubiquitination[1]
206VKGYLRLKMTYLPKNubiquitination[1]
278ESRRTQWKRPSPDDDubiquitination[1]
429YYVDHNSKTTTWSKPubiquitination[1]
453IPAHLRGKTDSNDLGubiquitination[1]
484FFINHNIKKTQWEDPubiquitination[1]
529KQTDIPNKFEMKLRRacetylation[3]
734RFVNRIQKQMAAFKEacetylation[3]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
 [2] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
 Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
 Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337]
 [3] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441] 
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. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. Involved in ubiquitination of ERBB4 intracellular domain E4ICD1 (PubMed:19193720). Predominantly involved in ubiquitination of membrane bound forms of ERBB4 rather than processed precursors and intermediate membrane-anchored 80 kDa fragments (m80HER4), with a lesser role in ubiquitination of ERBB4 intracellular domain E4ICD1 (PubMed:19047365). Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. 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 (By similarity). 
Sequence Annotation
 DOMAIN 65 166 C2.
 DOMAIN 249 282 WW 1.
 DOMAIN 405 438 WW 2.
 DOMAIN 460 493 WW 3.
 DOMAIN 552 887 HECT.
 REGION 217 549 Mediates interaction with TNIK.
 ACT_SITE 854 854 Glycyl thioester intermediate.
 MOD_RES 287 287 Phosphothreonine.
 MOD_RES 309 309 Phosphoserine; by host.
 MOD_RES 385 385 Phosphoserine; by host (By similarity).  
Keyword
 3D-structure; Cell membrane; Complete proteome; Cytoplasm; Ligase; Membrane; Neurogenesis; Phosphoprotein; Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 887 AA 
Protein Sequence
MSSDMAADES EAPVLSEDEV WEFCLDKTED GGGSPGSDVT DTCEPPCGCW ELNPNSLEEE 60
HVLFTADPYL ELHNDDTRVV RVKVIAGIGL AKKDILGASD PYVRVTLYDP MSGILTSVQT 120
KTIKKSLNPK WNEEILFRVL PQRHRILFEV FDENRLTRDD FLGQVDVPLY PLPTENPRME 180
RPYTFKDFVL HPRSHKSRVK GYLRLKMTYL PKNGSEDENA DQAEELEPGW VVLDQPDAAT 240
HLPHPPEPSP LPPGWEERQD VLGRTYYVNH ESRRTQWKRP SPDDDLTDED NDDMQLQAQR 300
AFTTRRQISE DVDGPDNRES PENWEIVRED ENTEYSGQAV QSPPSGHIDV QTHLAEEFNT 360
RLAVCGNPAT SQPVTSSNHS SRGGSLQTCI FEEQPTLPVL LPTSSGLPPG WEEKQDDRGR 420
SYYVDHNSKT TTWSKPTMQD DPRSKIPAHL RGKTDSNDLG PLPPGWEERT HTDGRVFFIN 480
HNIKKTQWED PRLQNVAITG PAVPYSRDYK RKYEFFRRKL KKQTDIPNKF EMKLRRANIL 540
EDSYRRIMGV KRADLLKARL WIEFDGEKGL DYGGVAREWF FLISKEMFNP YYGLFEYSAT 600
DNYTLQINPN SGLCNEDHLS YFKFIGRVAG MAVYHGKLLD GFFIRPFYKM MLQKLITLHD 660
MESVDSEYYS SLRWILENDP TELDLRFIID EELFGQTHQH ELKTGGSEIV VTNKNKKEYI 720
YLVIQWRFVN RIQKQMAAFK EGFFELIPQD LIKIFDENEL ELLMCGLGDV DVNDWREHTK 780
YKNGYSMNHQ VIHWFWKAVW MMDSEKRIRL LQFVTGTSRV PMNGFAELYG SNGPQSFTVE 840
QWGTPDKLPR AHTCFNRLDL PPYESFDELW DKLQMAIENT QGFDGVD 887 
Gene Ontology
 GO:0005938; C:cell cortex; IEA:Compara.
 GO:0000785; C:chromatin; IEA:Compara.
 GO:0005829; C:cytosol; IDA:MGI.
 GO:0005794; C:Golgi apparatus; IEA:Compara.
 GO:0016020; C:membrane; IDA:MGI.
 GO:0005634; C:nucleus; IBA:RefGenome.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:Compara.
 GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
 GO:0000151; C:ubiquitin ligase complex; IPI:MGI.
 GO:0050815; F:phosphoserine binding; IDA:BHF-UCL.
 GO:0050816; F:phosphothreonine binding; IDA:BHF-UCL.
 GO:0019871; F:sodium channel inhibitor activity; IDA:MGI.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:MGI.
 GO:0002250; P:adaptive immune response; IMP:MGI.
 GO:0048514; P:blood vessel morphogenesis; IMP:MGI.
 GO:0044111; P:development involved in symbiotic interaction; IEA:Compara.
 GO:0003197; P:endocardial cushion development; IMP:MGI.
 GO:0042921; P:glucocorticoid receptor signaling pathway; IEA:Compara.
 GO:0010766; P:negative regulation of sodium ion transport; IDA:MGI.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:MGI.
 GO:0010768; P:negative regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage; IEA:Compara.
 GO:0030948; P:negative regulation of vascular endothelial growth factor receptor signaling pathway; IDA:UniProtKB.
 GO:0007528; P:neuromuscular junction development; IMP:MGI.
 GO:0031175; P:neuron projection development; IEA:Compara.
 GO:0003151; P:outflow tract morphogenesis; IMP:MGI.
 GO:0046824; P:positive regulation of nucleocytoplasmic transport; IEA:Compara.
 GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase cascade; IEA:Compara.
 GO:0045732; P:positive regulation of protein catabolic process; IDA:MGI.
 GO:0050847; P:progesterone receptor signaling pathway; IEA:Compara.
 GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
 GO:0006513; P:protein monoubiquitination; IDA:MGI.
 GO:0006622; P:protein targeting to lysosome; IEA:Compara.
 GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IMP:MGI.
 GO:0032801; P:receptor catabolic process; IEA:Compara.
 GO:0031623; P:receptor internalization; IEA:Compara.
 GO:0048814; P:regulation of dendrite morphogenesis; IMP:UniProtKB.
 GO:0042391; P:regulation of membrane potential; IEA:Compara.
 GO:1901016; P:regulation of potassium ion transmembrane transporter activity; IEA:Compara.
 GO:0050807; P:regulation of synapse organization; IMP:MGI.
 GO:0042110; P:T cell activation; IMP:MGI.
 GO:0019089; P:transmission of virus; IEA:Compara.
 GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IEA:Compara. 
Interpro
 IPR000008; C2_Ca-dep.
 IPR008973; C2_Ca/lipid-bd_dom_CaLB.
 IPR018029; C2_membr_targeting.
 IPR024928; E3_ub_ligase_SMURF1.
 IPR000569; HECT.
 IPR001202; WW_dom. 
Pfam
 PF00168; C2
 PF00632; HECT
 PF00397; WW 
SMART
 SM00239; C2
 SM00119; HECTc
 SM00456; WW 
PROSITE
 PS50004; C2
 PS50237; HECT
 PS01159; WW_DOMAIN_1
 PS50020; WW_DOMAIN_2 
PRINTS