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Protein Page:
NEDD4L (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
NEDD4L 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. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, Nav1.2, Nav1.3, Nav1.5, Nav1.7, Nav1.8, Kv1.3, EAAT1 or CLC5. Promotes ubiquitination and degradation of SGK1 and TNK2. Interacts with UBE2E3. Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase. Interacts via its WW domains with SCNN1A, SCNN1B, SCNN1G, SCN1A, SCN2A, SCN3A, SCN5A, SCN8A, SCN9A, SCN10A and CLCN5. Interacts with SMAD2, SMAD3, SMAD6 and SMAD7. The phosphorylated form interacts with 14-3-3 proteins. Interacts with Epstein-Barr virus LMP2A. Interacts with TNK2. Interacts with WNK1. Interacts with SGK1. By androgens in prostate, and by albumin in kidney. Ubiquitously expressed, with highest levels in prostate, pancreas and kidney. Activated by NDFIP1- and NDFIP2-binding. 9 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; Ligase; Ubiquitin conjugating system; EC 6.3.2.-; Ubiquitin ligase
Cellular Component: nucleoplasm; cytoplasm; plasma membrane; intracellular; cytosol; nucleus
Molecular Function: sodium channel inhibitor activity; protein binding; potassium channel regulator activity; sodium channel regulator activity; ubiquitin-protein ligase activity; potassium channel inhibitor activity; ligase activity
Biological Process: protein monoubiquitination; proteasomal ubiquitin-dependent protein catabolic process; response to metal ion; viral reproduction; protein ubiquitination during ubiquitin-dependent protein catabolic process; sodium ion transport; protein ubiquitination; positive regulation of endocytosis; negative regulation of transcription from RNA polymerase II promoter; viral infectious cycle; excretion; response to salt stress; water homeostasis; transforming growth factor beta receptor signaling pathway; transmembrane transport; transcription initiation from RNA polymerase II promoter; cellular sodium ion homeostasis; ubiquitin-dependent protein catabolic process via the multivesicular body pathway; transcription, DNA-dependent; negative regulation of systemic arterial blood pressure; regulation of membrane potential; positive regulation of protein catabolic process; regulation of protein catabolic process; gene expression; negative regulation of transforming growth factor beta receptor signaling pathway
Reference #:  Q96PU5 (UniProtKB)
Alt. Names/Synonyms: E3 ubiquitin-protein ligase NEDD4-like; FLJ33870; hNedd4-2; KIAA0439; NED4L; Nedd4-2; NEDD4.2; NEDD4L; NEDL3; neural precursor cell expressed, developmentally down-regulated 4-like; neural precursor cell expressed, developmentally down-regulated gene 4-like; RSP5; ubiquitin-protein ligase NEDD4-like; ubiquitin-protein ligase Rsp5
Gene Symbols: NEDD4L
Molecular weight: 111,932 Da
Basal Isoelectric point: 5.56  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

NEDD4L

Protein Structure Not Found.


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Sites Implicated In
activity, inhibited: S342‑p, S428‑p
molecular association, regulation: S342‑p, S448‑p
phosphorylation: S342‑p, T367‑p, S448‑p

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 K25 ESRILRVKVVSGIDL
0 3 Y79 PKWNEEFYFRVNPSN
0 1 K129-ub MERPYTFkDFLLRPR
0 1 S251 AAHRRFRSRRHISED
0 1 S297-p ALPPPPAsPGsRTsP
0 1 S300-p PPPAsPGsRTsPQEL
0 1 T302 PAsPGsRTsPQELSE
0 6 S303-p AsPGsRTsPQELSEE
0 1 S312-p QELSEELsRRLQItP
0 6 T318-p LsRRLQItPDSNGEQ
0 14 S335-p SLIQREPssRLRsCs
0 5 S336-p LIQREPssRLRsCsV
0 19 S340-p EPssRLRsCsVtDAV
10 66 S342-p ssRLRsCsVtDAVAE
0 7 T344-p RLRsCsVtDAVAEQG
0 5 S365-p APAGRARsstVTGGE
0 6 S366-p PAGRARsstVTGGEE
4 16 T367-p AGRARsstVTGGEEP
0 1 S377-p GGEEPTPsVAyVHtT
0 2 Y380-p EPTPsVAyVHtTPGL
0 1 T383-p PsVAyVHtTPGLPSG
1 0 S428-p AEDGASGsATNSNNH
0 33 S446-p PQIRRPRsLssPTVT
10 75 S448-p IRRPRsLssPTVTLS
0 23 S449-p RRPRsLssPTVTLSA
0 2 T451 PRsLssPTVTLSAPL
0 1 T453 sLssPTVTLSAPLEG
0 3 K462-ub SAPLEGAkDsPVRRA
0 4 S464-p PLEGAkDsPVRRAVk
0 2 K471-ub sPVRRAVkDtLsNPQ
0 7 T473-p VRRAVkDtLsNPQsP
0 25 S475-p RAVkDtLsNPQsPQP
0 78 S479-p DtLsNPQsPQPsPyN
0 55 S483-p NPQsPQPsPyNsPKP
0 27 Y485-p QsPQPsPyNsPKPQH
0 69 S487-p PQPsPyNsPKPQHKV
0 1 K489 PsPyNsPKPQHKVTQ
0 1 K521-ub FFIDHNTkTTTWEDP
0 1 K531-ub TWEDPRLkFPVHMRS
0 2 K539-ub FPVHMRSkTSLNPND
0 2 Y593 ITGPAVPYSREFKQK
0 1 Y601 SREFKQKYDYFRKKL
0 2 K656-ub WIEFESEkGLDyGGV
0 3 Y660-p ESEkGLDyGGVAREW
1 0 S795-p VDLKPNGsEIMVTNE
0 7 Y951 NRLDLPPYETFEDLR
4080 : Phospho-NEDD4L (Ser342) Antibody
12146 : Phospho-NEDD4L (Ser342) (D16D6) Rabbit mAb
8063 : Phospho-NEDD4L (Ser448) Antibody
  NEDD4L iso5  
K25 ESRILRVKVVSGIDL
Y79 PKWNEEFYFRVNPSN
K129 MERPYTFKDFLLRPR
S251 AAHRRFRSRRHISED
S297 ALPPPPASPGSRTSP
S300 PPPASPGSRTSPQEL
T302 PASPGSRTSPQELSE
S303 ASPGSRTSPQELSEE
S312 QELSEELSRRLQITP
T318 LSRRLQITPDSNGEQ
S335 SLIQREPSSRLRsCs
S336 LIQREPSSRLRsCsV
S340-p EPSSRLRsCsVtDAV
S342-p SSRLRsCsVtDAVAE
T344-p RLRsCsVtDAVAEQG
- gap
- gap
- gap
S357 QGHLPPPSVAYVHTT
Y360 LPPPSVAYVHTTPGL
T363 PSVAYVHTTPGLPSG
S408 AEDGASGSATNSNNH
S426 PQIRRPRSLSSPTVT
S428 IRRPRSLSSPTVTLS
S429 RRPRSLSSPTVTLSA
T431 PRSLSSPTVTLSAPL
T433 SLSSPTVTLSAPLEG
K442 SAPLEGAKDSPVRRA
S444 PLEGAKDSPVRRAVK
K451 SPVRRAVKDTLSNPQ
T453 VRRAVKDTLSNPQSP
S455 RAVKDTLSNPQSPQP
S459 DTLSNPQSPQPSPYN
S463 NPQSPQPSPYNSPKP
Y465 QSPQPSPYNSPKPQH
S467 PQPSPYNSPKPQHKV
K469 PSPYNSPKPQHKVTQ
K501 FFIDHNTKTTTWEDP
K511 TWEDPRLKFPVHMRS
K519 FPVHMRSKTSLNPND
Y573 ITGPAVPYSREFKQK
Y581 SREFKQKYDYFRKKL
K636 WIEFESEKGLDYGGV
Y640 ESEKGLDYGGVAREW
S775 VDLKPNGSEIMVTNE
Y931 NRLDLPPYETFEDLR
4080 : Phospho-NEDD4L (Ser342) Antibody
12146 : Phospho-NEDD4L (Ser342) (D16D6) Rabbit mAb
8063 : Phospho-NEDD4L (Ser448) Antibody
  mouse

► Hide Isoforms
 
K53-ub ESRILRVkVVSGIDL
Y107 PKWNEEFYFRVNPSN
K157 MERPYTFKDFLLRPR
S279-p AAHRRFRsRRHISED
S326 ALPPPPASPVSRtsP
S329 PPPASPVSRtsPQEL
T331-p PASPVSRtsPQELSE
S332-p ASPVSRtsPQELSEE
S341 QELSEEVSRRLQItP
T347-p VSRRLQItPDSNGEQ
S364-p SLIQREPsSRLRsCs
S365 LIQREPsSRLRsCsV
S369-p EPsSRLRsCsVTDTV
S371-p sSRLRsCsVTDTVAE
T373 RLRsCsVTDTVAEQA
S394 TPTRRARSStVTGGE
S395 PTRRARSStVTGGEE
T396-p TRRARSStVTGGEEP
S406 GGEEPTPSVAYVHTT
Y409 EPTPSVAYVHTTPGL
T412 PSVAYVHTTPGLPSG
S457 AEDGASGSATNSNNH
S475-p PQIRRPRsLssPtVt
S477-p IRRPRsLssPtVtLS
S478-p RRPRsLssPtVtLSA
T480-p PRsLssPtVtLSAPL
T482-gl sLssPtVtLSAPLEG
K491-ub SAPLEGAkDsPIRRA
S493-p PLEGAkDsPIRRAVK
K500 sPIRRAVKDtLsNPQ
T502-p IRRAVKDtLsNPQsP
S504-p RAVKDtLsNPQsPQP
S508-p DtLsNPQsPQPsPyN
S512-p NPQsPQPsPyNsPkP
Y514-p QsPQPsPyNsPkPQH
S516-p PQPsPyNsPkPQHKV
K518-ub PsPyNsPkPQHKVTQ
K550 FFIDHNTKTTTWEDP
K560 TWEDPRLKFPVHMRS
K568-ub FPVHMRSkASLNPND
Y622 ITGPAVPYSREFKQK
Y630 SREFKQKYDYFRKKL
K685-ub WIEFESEkGLDYGGV
Y689 ESEkGLDYGGVAREW
S824 VDLKPNGSEIMVTNE
Y980 NRLDLPPYETFEDLR
4080 : Phospho-NEDD4L (Ser342) Antibody
12146 : Phospho-NEDD4L (Ser342) (D16D6) Rabbit mAb
8063 : Phospho-NEDD4L (Ser448) Antibody
  NEDD4L iso3  
K53 ESRILRVKVVSGIDL
Y107 PKWNEEFYFRVNPSN
K157 MERPYTFKDFLLRPR
S279 AAHRRFRSRRHISED
S326 ALPPPPASPVSRTSP
S329 PPPASPVSRTSPQEL
T331 PASPVSRTSPQELSE
S332 ASPVSRTSPQELSEE
S341 QELSEEVSRRLQITP
T347 VSRRLQITPDSNGEQ
S364 SLIQREPSSRLRSCs
S365 LIQREPSSRLRSCsV
S369 EPSSRLRSCsVTDTV
S371-p SSRLRSCsVTDTVAE
T373 RLRSCsVTDTVAEQA
- gap
- gap
- gap
S386 QAHLPPPSVAYVHTT
Y389 LPPPSVAYVHTTPGL
T392 PSVAYVHTTPGLPSG
S437 AEDGASGSATNSNNH
S455 PQIRRPRSLSSPTVT
S457 IRRPRSLSSPTVTLS
S458 RRPRSLSSPTVTLSA
T460 PRSLSSPTVTLSAPL
T462 SLSSPTVTLSAPLEG
K471 SAPLEGAKDSPIRRA
S473 PLEGAKDSPIRRAVK
K480 SPIRRAVKDTLSNPQ
T482 IRRAVKDTLSNPQSP
S484 RAVKDTLSNPQSPQP
S488 DTLSNPQSPQPSPYN
S492 NPQSPQPSPYNSPKP
Y494 QSPQPSPYNSPKPQH
S496 PQPSPYNSPKPQHKV
K498 PSPYNSPKPQHKVTQ
K530 FFIDHNTKTTTWEDP
K540 TWEDPRLKFPVHMRS
K548 FPVHMRSKASLNPND
Y602 ITGPAVPYSREFKQK
Y610 SREFKQKYDYFRKKL
K665 WIEFESEKGLDYGGV
Y669 ESEKGLDYGGVAREW
S804 VDLKPNGSEIMVTNE
Y960 NRLDLPPYETFEDLR
4080 : Phospho-NEDD4L (Ser342) Antibody
12146 : Phospho-NEDD4L (Ser342) (D16D6) Rabbit mAb
8063 : Phospho-NEDD4L (Ser448) Antibody
  rat

 
K12 ESRILRVKVVSGIDL
Y66-p PKWNEEFyFRVNPSN
K116 MERPYTFKDFLLRPR
S238 AAHRRFRSRRHISED
S285 ALPPPPASPVSRTSP
S288 PPPASPVSRTSPQEL
T290 PASPVSRTSPQELSE
S291 ASPVSRTSPQELSEE
S300 QELSEELSRRLQITP
T306 LSRRLQITPDSNGEQ
S323 ALIQREPSSRLRSCS
S324 LIQREPSSRLRSCSV
S328 EPSSRLRSCSVTDTV
S330 SSRLRSCSVTDTVAE
T332 RLRSCSVTDTVAEQA
S353 TPTRRARSSTVTGGE
S354 PTRRARSSTVTGGEE
T355 TRRARSSTVTGGEES
S365 GGEESTPSVAYVHTT
Y368 ESTPSVAYVHTTPGL
T371 PSVAYVHTTPGLPSG
S416 AEDGASGSATNSNNH
S434 PQIRRPRSLssPtVT
S436-p IRRPRSLssPtVTLS
S437-p RRPRSLssPtVTLSA
T439-p PRSLssPtVTLSAPL
T441 SLssPtVTLSAPLEG
K450 SAPLEGAKDSPIRRA
S452 PLEGAKDSPIRRAVK
K459 SPIRRAVKDTLSNPQ
T461 IRRAVKDTLSNPQsP
S463 RAVKDTLSNPQsPQP
S467-p DTLSNPQsPQPsPyN
S471-p NPQsPQPsPyNsPKP
Y473-p QsPQPsPyNsPKPQH
S475-p PQPsPyNsPKPQHKV
K477 PsPyNsPKPQHKVTQ
K509 FFIDHNTKTTTWEDP
K519 TWEDPRLKFPVHMRS
K527 FPVHMRSKASLNPND
Y581-p ITGPAVPySREFKQK
Y589-p SREFKQKyDYFRKKL
K644 WIEFESEKGLDyGGV
Y648-p ESEKGLDyGGVAREW
S783 VDLKPNGSEIMVTNE
Y939-p NRLDLPPyETFEDLR
4080 : Phospho-NEDD4L (Ser342) Antibody
12146 : Phospho-NEDD4L (Ser342) (D16D6) Rabbit mAb
8063 : Phospho-NEDD4L (Ser448) Antibody
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