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Protein Page:
NEDD4 iso4 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
NEDD4 iso4 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. 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. Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase and may induce its recruitment to exosomes. 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. 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). Activated by NDFIP1- and NDFIP2-binding. 4 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: EC 6.3.2.19; Ubiquitin conjugating system; Ubiquitin ligase; Nuclear receptor co-regulator; Ligase; EC 6.3.2.-
Cellular Component: Golgi apparatus; perinuclear region of cytoplasm; apicolateral plasma membrane; cytoplasm; plasma membrane; cell cortex; chromatin; nucleus; cytosol; ubiquitin ligase complex
Molecular Function: protein domain specific binding; sodium channel inhibitor activity; protein binding; ubiquitin binding; phosphothreonine binding; beta-2 adrenergic receptor binding; ubiquitin-protein ligase activity; phosphoserine binding; ligase activity
Biological Process: protein monoubiquitination; lysosomal transport; protein targeting to lysosome; progesterone receptor signaling pathway; T cell activation; transmission of virus; regulation of dendrite morphogenesis; protein ubiquitination during ubiquitin-dependent protein catabolic process; protein ubiquitination; positive regulation of nucleocytoplasmic transport; receptor internalization; receptor catabolic process; regulation of synapse organization and biogenesis; neuromuscular junction development; neurite development; adaptive immune response; negative regulation of vascular endothelial growth factor receptor signaling pathway; ubiquitin-dependent protein catabolic process via the multivesicular body pathway; cytokine and chemokine mediated signaling pathway; positive regulation of phosphoinositide 3-kinase cascade; regulation of membrane potential; glucocorticoid receptor signaling pathway; positive regulation of protein catabolic process; blood vessel morphogenesis; response to calcium ion
Reference #:  P46934-4 (UniProtKB)
Alt. Names/Synonyms: Cell proliferation-inducing gene 53 protein; E3 ubiquitin-protein ligase NEDD4; KIAA0093; MGC176705; NEDD-4; NEDD4; NEDD4-1; Neural precursor cell expressed developmentally down-regulated protein 4; neural precursor cell expressed, developmentally down-regulated 4; receptor-potentiating factor 1; RPF1
Gene Symbols: NEDD4
Molecular weight: 104,217 Da
Basal Isoelectric point: 5.67  Predict pI for various phosphorylation states
CST Pathways:  Notch Signaling
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

NEDD4 iso4

Protein Structure Not Found.


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Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

► Hide Isoforms
 
0 1 S20 RSNTYPLSETSGDDL
0 3 - gap
0 2 - gap
0 2 - gap
0 1 - gap
0 3 - gap
0 2 - gap
0 1 - gap
0 9 - gap
0 3 - gap
0 2 - gap
0 3 - gap
0 1 Y627 QDILGRTYYVNHESR
0 1 K639 ESRRTQWKRPTPQDN
0 5 T642 RTQWKRPTPQDNLTD
0 20 T648 PTPQDNLTDAENGNI
0 28 S670-p FTTRRQIsEETESVD
0 3 S681 ESVDNRESSENWEII
0 1 S703 YSNQAFPSPPPSSNL
0 7 F727 LNARLTIFGNSAVSQ
0 2 S742-p PASSSNHssRRGsLQ
0 3 S743-p ASSSNHssRRGsLQA
0 6 S747-p NHssRRGsLQAYTFE
0 1 A750 sRRGsLQAYTFEEQP
0 1 T758 YTFEEQPTLPVLLPT
0 3 Y785-p DERGRSYyVDHNSRT
0 1 R791 YyVDHNSRTTTWTKP
0 5 K882 IPAHLRGKTsLDTsN
0 1 S884-p AHLRGKTsLDTsNDL
0 1 S888-p GKTsLDTsNDLGPLP
1 0 T902 PPGWEERTHTDGRIF
0 2 K916 FYINHNIKRTQWEDP
0 2 Y976 ATVLEDSYRRIMGVK
0 1 K989 VKRADFLKARLWIEF
0 1 K1000 WIEFDGEKGLDYGGV
0 3 Y1004 DGEKGLDYGGVAREW
0 1 S1095 ITLHDMESVDSEYYN
  NEDD4 iso2  
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
Y555 QDILGRTYYVNHESR
K567 ESRRTQWKRPTPQDN
T570 RTQWKRPTPQDNLTD
T576 PTPQDNLTDAENGNI
S598-p FTTRRQIsEETESVD
S609 ESVDNRESSENWEII
S631 YSNQAFPSPPPSSNL
F655 LNARLTIFGNSAVSQ
S670 PASSSNHSSRRGSLQ
S671 ASSSNHSSRRGSLQA
S675 NHSSRRGSLQAYTFE
A678 SRRGSLQAYTFEEQP
T686 YTFEEQPTLPVLLPT
Y713 DERGRSYYVDHNSRT
R719 YYVDHNSRTTTWTKP
K810 IPAHLRGKTSLDTSN
S812 AHLRGKTSLDTSNDL
S816 GKTSLDTSNDLGPLP
T830 PPGWEERTHTDGRIF
K844 FYINHNIKRTQWEDP
Y904 ATVLEDSYRRIMGVK
K917 VKRADFLKARLWIEF
K928 WIEFDGEKGLDYGGV
Y932 DGEKGLDYGGVAREW
S1023 ITLHDMESVDSEYYN
  NEDD4 iso4  
- gap
R24 NSRIVRVRVIAGIGL
K33 IAGIGLAKKDILGAS
K34 AGIGLAKKDILGASD
Y43-p ILGASDPyVRVTLYD
K62 VLTSVQTKTIKKSLN
K65 SVQTKTIKKSLNPKW
K66 VQTKTIKKSLNPKWN
K71 IKKSLNPKWNEEILF
K127 LERPYTFKDFVLHPR
K147 VKGYLRLKMTYLPKT
S157 YLPKTSGSEDDNAEQ
Y208 QDILGRTYYVNHESR
K220 ESRRTQWKRPTPQDN
T223 RTQWKRPTPQDNLTD
T229 PTPQDNLTDAENGNI
S251-p FTTRRQIsEETESVD
S262 ESVDNRESSENWEII
S284 YSNQAFPSPPPSSNL
F308 LNARLTIFGNSAVSQ
S323 PASSSNHSsRRGsLQ
S324-p ASSSNHSsRRGsLQA
S328-p NHSsRRGsLQAYTFE
A331 sRRGsLQAYTFEEQP
T339 YTFEEQPTLPVLLPT
Y366-p DERGRSYyVDHNSRT
R372 YyVDHNSRTTTWTKP
K463-ub IPAHLRGkTSLDTSN
S465 AHLRGkTSLDTSNDL
S469 GkTSLDTSNDLGPLP
T483 PPGWEERTHTDGRIF
K497-ub FYINHNIkRTQWEDP
Y557-p ATVLEDSyRRIMGVK
K570 VKRADFLKARLWIEF
K581 WIEFDGEKGLDyGGV
Y585-p DGEKGLDyGGVAREW
S676 ITLHDMESVDSEYYN
  mouse

 
S16-p ESEAPVLsEDEVWEF
K83-ub DTRVVRVkVIAGIGL
K92-ub IAGIGLAkkDILGAS
K93-ub AGIGLAkkDILGASD
Y102 ILGASDPYVRVTLYD
K121-ub ILTSVQTkTIkkSLN
K124-ub SVQTkTIkkSLNPkW
K125-ub VQTkTIkkSLNPkWN
K130-ub IkkSLNPkWNEEILF
K186-ub MERPYTFkDFVLHPR
K206-ub VKGYLRLkMTYLPKN
S215-p TYLPKNGsEDENADQ
Y266 QDVLGRTYYVNHESR
K278-ub ESRRTQWkRPsPDDD
S281-p RTQWkRPsPDDDLtD
T287-p PsPDDDLtDEDNDDM
S309-p FTTRRQIsEDVDGPD
S320-p DGPDNREsPENWEIV
S342 YSGQAVQSPPSGHID
C365 FNTRLAVCGNPATSQ
S380 PVTSSNHSsRGGSLQ
S381-p VTSSNHSsRGGSLQT
S385 NHSsRGGSLQTCIFE
T388 sRGGSLQTCIFEEQP
T396 CIFEEQPTLPVLLPT
Y423 DDRGRSYYVDHNSkT
K429-ub YYVDHNSkTTTWSKP
K453-ub IPAHLRGkTDSNDLG
- gap
S456 HLRGkTDSNDLGPLP
T470-p PPGWEERtHTDGRVF
K484-ub FFINHNIkKTQWEDP
Y544 ANILEDSYRRIMGVK
K557-ub VKRADLLkARLWIEF
K568-ub WIEFDGEkGLDYGGV
Y572 DGEkGLDYGGVAREW
S663-p ITLHDMEsVDSEYYS
  rat

 
S12 DTEAPVLSEDEVWEF
K80 DTRVVRVKVIAGIGL
K89 IAGIGLAKKDILGAS
K90 AGIGLAKKDILGASD
Y99 ILGASDPYVRVTLYD
K118 VLTSVQTKTIKKSLN
K121 SVQTKTIKKSLNPKW
K122 VQTKTIKKSLNPKWN
K127 IKKSLNPKWNEEILF
K183 MERPYTFKDFVLHPR
K203 VKGYLRLKMTYLPKN
S212-p TYLPKNGsDDENADQ
Y263-p QDVLGRTyYVNHESR
K275 ESRTTQWKRPSPEDD
S278 TTQWKRPSPEDDLtD
T284-p PSPEDDLtDDENGDI
S306-p FTTRRQIsEDVDGPD
S317 DGPDNHESPENWEIV
S339-p YSGQAVQsPPSGHPD
Y362-p LDTRLTMyGNPATSQ
S377 PVTSSNHSSRGGSSQ
S378 VTSSNHSSRGGSSQt
S382 NHSSRGGSSQtCIFE
T385-p SRGGSSQtCIFEEQP
T393-p CIFEEQPtLPVLLPT
Y420 DDRGRSYYVDHNSKT
K426 YYVDHNSKTTTWSKP
K450 IPAHLRGKTPVDSND
- gap
S455 RGKTPVDSNDLGPLP
T469 PPGWEERTHTDGRVF
K483 FFINHNIKKTQWEDP
Y543-p ANILEDSyRRIMGVK
K556 VKRADFLKARLWIEF
K567 WIEFDGEKGLDyGGV
Y571-p DGEKGLDyGGVAREW
S663 ITLHDMESVDSEYYS
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