NEDD4

Details:

UniProt Entry: P46934

Gene: NEDD4

Class: HECT

Family: HECT1

Protein length: 1319

Database confidence: 0.875

InterPro: InterPro Entry

Mode of Action: Standalone

AlphaFold Model: Link

PDB Structures: 2kpz, 2kq0, 2m3o, 2xbb, 2xbf, 3b7y, 4bbn, 4be8, 4n7f, 4n7h, 5aht, 5c7j, 5c91, 9h9o, 9h9t

Protein Sequence ▾

Domain Architecture (From InterPro) ▾

Protein functions ▾

Start	End	Type	Name	InterPro	Source
500	607	Homologous_superfamily	C2 domain superfamily	IPR035892	G3DSA:2.60.40.150
601	644	Homologous_superfamily	WW domain superfamily	IPR036020	SSF51045
610	643	Domain	WW domain	IPR001202	PS50020
611	643	Domain	WW domain	IPR001202	SM00456
612	641	Domain	WW domain	IPR001202	PF00397
613	643	Domain	WW domain	IPR001202	cd00201
616	641	Domain	WW domain	IPR001202	PS01159
761	801	Homologous_superfamily	WW domain superfamily	IPR036020	SSF51045
767	800	Domain	WW domain	IPR001202	PS50020
768	800	Domain	WW domain	IPR001202	SM00456
769	798	Domain	WW domain	IPR001202	PF00397
770	799	Domain	WW domain	IPR001202	cd00201
773	798	Domain	WW domain	IPR001202	PS01159
840	874	Homologous_superfamily	WW domain superfamily	IPR036020	SSF51045
840	873	Domain	WW domain	IPR001202	PS50020
841	873	Domain	WW domain	IPR001202	SM00456
842	871	Domain	WW domain	IPR001202	PF00397
843	873	Domain	WW domain	IPR001202	cd00201
846	871	Domain	WW domain	IPR001202	PS01159
888	927	Homologous_superfamily	WW domain superfamily	IPR036020	SSF51045
892	925	Domain	WW domain	IPR001202	PS50020
893	925	Domain	WW domain	IPR001202	SM00456
894	923	Domain	WW domain	IPR001202	PF00397
895	925	Domain	WW domain	IPR001202	cd00201
898	923	Domain	WW domain	IPR001202	PS01159
943	1312	Homologous_superfamily	HECT, E3 ligase catalytic domain	IPR035983	SSF56204
962	1316	Domain	HECT domain	IPR000569	cd00078
982	1318	Domain	HECT domain	IPR000569	SM00119
984	1318	Domain	HECT domain	IPR000569	PS50237
1014	1316	Domain	HECT domain	IPR000569	PF00632

GO term	Name	Ontology	Evidence	Reference
GO:0006511	ubiquitin-dependent protein catabolic process	Biological Process	IEA	GO_REF:0000117
GO:0006955	immune response	Biological Process	IEA	GO_REF:0000117
GO:0007399	nervous system development	Biological Process	IEA	GO_REF:0000043
GO:0010646	regulation of cell communication	Biological Process	IEA	GO_REF:0000117
GO:0016567	protein ubiquitination	Biological Process	IEA	GO_REF:0000120
GO:0023051	regulation of signaling	Biological Process	IEA	GO_REF:0000117
GO:0042176	regulation of protein catabolic process	Biological Process	IEA	GO_REF:0000117
GO:0065008	regulation of biological quality	Biological Process	IEA	GO_REF:0000117
GO:0006814	sodium ion transport	Biological Process	IEA	GO_REF:0000107
GO:0046755	viral budding	Biological Process	IMP	PMID:15126635
GO:0051649	establishment of localization in cell	Biological Process	IEA	GO_REF:0000107
GO:0000122	negative regulation of transcription by RNA polymerase II	Biological Process	IEA	GO_REF:0000107
GO:0002250	adaptive immune response	Biological Process	IEA	GO_REF:0000107
GO:0003151	outflow tract morphogenesis	Biological Process	IEA	GO_REF:0000107
GO:0003197	endocardial cushion development	Biological Process	IEA	GO_REF:0000107
GO:0006366	transcription by RNA polymerase II	Biological Process	IDA	PMID:9852112
GO:0006513	protein monoubiquitination	Biological Process	IEA	GO_REF:0000107
GO:0007528	neuromuscular junction development	Biological Process	IEA	GO_REF:0000107
GO:0010766	negative regulation of sodium ion transport	Biological Process	IEA	GO_REF:0000107
GO:0042110	T cell activation	Biological Process	IEA	GO_REF:0000107
GO:0045732	positive regulation of protein catabolic process	Biological Process	IEA	GO_REF:0000107
GO:0048514	blood vessel morphogenesis	Biological Process	IEA	GO_REF:0000107
GO:0050807	regulation of synapse organization	Biological Process	IEA	GO_REF:0000107
GO:0045087	innate immune response	Biological Process	IDA	PMID:23951545
GO:0006622	protein targeting to lysosome	Biological Process	IPI	PMID:17116753
GO:0006974	DNA damage response	Biological Process	IEP	PMID:17996703
GO:0007041	lysosomal transport	Biological Process	IDA	PMID:18544533
GO:0016241	regulation of macroautophagy	Biological Process	TAS	PMID:25809873
GO:0030948	negative regulation of vascular endothelial growth factor receptor signaling pathway	Biological Process	ISS	GO_REF:0000024
GO:0031175	neuron projection development	Biological Process	IBA	GO_REF:0000033
GO:0031623	receptor internalization	Biological Process	IBA	GO_REF:0000033
GO:0032801	receptor catabolic process	Biological Process	IBA	GO_REF:0000033
GO:0034644	cellular response to UV	Biological Process	IMP	PMID:17996703
GO:0042391	regulation of membrane potential	Biological Process	IDA	PMID:17289006
GO:0042921	nuclear receptor-mediated glucocorticoid signaling pathway	Biological Process	IDA	PMID:8649367
GO:0043162	ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	Biological Process	IMP	PMID:20086093
GO:0044111	formation of structure involved in a symbiotic process	Biological Process	IMP	PMID:15126635
GO:0046824	positive regulation of nucleocytoplasmic transport	Biological Process	IDA	PMID:17218261
GO:0048814	regulation of dendrite morphogenesis	Biological Process	ISS	GO_REF:0000024
GO:0050847	progesterone receptor signaling pathway	Biological Process	IDA	PMID:8649367
GO:0051592	response to calcium ion	Biological Process	TAS	PMID:9405440
GO:0051897	positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	Biological Process	IMP	PMID:17218260
GO:0070534	protein K63-linked ubiquitination	Biological Process	ISS	GO_REF:0000024
GO:1903765	negative regulation of potassium ion export across plasma membrane	Biological Process	IDA	PMID:17289006
GO:0005634	nucleus	Cellular Component	IEA	GO_REF:0000120
GO:0005654	nucleoplasm	Cellular Component	IDA	GO_REF:0000052
GO:0005737	cytoplasm	Cellular Component	IEA	GO_REF:0000044
GO:0005829	cytosol	Cellular Component	IDA	GO_REF:0000052
GO:0005886	plasma membrane	Cellular Component	IEA	GO_REF:0000044
GO:0098978	glutamatergic synapse	Cellular Component	IEA	GO_REF:0000107
GO:0099524	postsynaptic cytosol	Cellular Component	IEA	GO_REF:0000107
GO:0000785	chromatin	Cellular Component	IDA	PMID:17996703
GO:0005794	Golgi apparatus	Cellular Component	IDA	PMID:16118794
GO:0005938	cell cortex	Cellular Component	IDA	PMID:9990509
GO:0016020	membrane	Cellular Component	IEA	GO_REF:0000120
GO:0016327	apicolateral plasma membrane	Cellular Component	TAS	PMID:9405440
GO:0048471	perinuclear region of cytoplasm	Cellular Component	IDA	PMID:9990509
GO:0070062	extracellular exosome	Cellular Component	HDA	PMID:23533145
GO:0000151	ubiquitin ligase complex	Cellular Component	ISS	GO_REF:0000024
GO:0032991	protein-containing complex	Cellular Component	IDA	PMID:17116753
GO:0004842	ubiquitin-protein transferase activity	Molecular Function	IEA	GO_REF:0000002
GO:0016740	transferase activity	Molecular Function	IEA	GO_REF:0000043
GO:0019871	sodium channel inhibitor activity	Molecular Function	IEA	GO_REF:0000117
GO:0061630	ubiquitin protein ligase activity	Molecular Function	IEA	GO_REF:0000120
GO:0005515	protein binding	Molecular Function	IPI	PMID:10642508
GO:0016248	channel inhibitor activity	Molecular Function	IDA	PMID:10642508
GO:0019870	potassium channel inhibitor activity	Molecular Function	IDA	PMID:17289006
GO:0019899	enzyme binding	Molecular Function	IPI	PMID:26006083
GO:0019904	protein domain specific binding	Molecular Function	IPI	PMID:12907594
GO:0031698	beta-2 adrenergic receptor binding	Molecular Function	IDA	PMID:18544533
GO:0035255	ionotropic glutamate receptor binding	Molecular Function	IEA	GO_REF:0000107
GO:0043130	ubiquitin binding	Molecular Function	IDA	PMID:9990509
GO:0044325	transmembrane transporter binding	Molecular Function	IPI	PMID:17289006
GO:0050815	phosphoserine residue binding	Molecular Function	ISS	GO_REF:0000024
GO:0050816	phosphothreonine residue binding	Molecular Function	ISS	GO_REF:0000024
GO:0070063	RNA polymerase binding	Molecular Function	IPI	PMID:17996703
GO:0070064	proline-rich region binding	Molecular Function	IEA	GO_REF:0000107

Enzyme–Substrate Interactions ▾

Substrate	Name	Known ESI (UbiBrowser)	Known ESI (UbiNet)	PPI (IntAct direct) PSI-MI score ≥ 0.5	PPI (IntAct indirect) PSI-MI scores ≥ 0.5 for both PPIs	PubMed Ref.	IntAct Ref.	Substrate Specificity
A8MYT4	A8MYT4	Yes	No	No	No	—	No	E3-specific
O15431	COPT1	Yes	No	No	No	—	No	E3-specific
Q5MJ70	SPDYA	Yes	Yes	No	No	—	No	E3-specific
Q99755	PI51A	Yes	Yes	No	No	—	No	E3-specific
P01116	RASK	Yes	Yes	No	No	—	No	E3-specific
Q16655	MAR1	Yes	Yes	Yes	No	37219487, 20491914	EBI-42494149	Cluster-specific
Q9UJM3	ERRFI	Yes	Yes	No	No	—	No	E3-specific
P17302	CXA1	Yes	Yes	No	No	—	No	E3-specific
P10114	RAP2A	Yes	No	No	No	—	No	E3-specific
P10523	ARRS	Yes	Yes	No	No	—	No	E3-specific
Q13571	LAPM5	Yes	Yes	No	No	15231748	EBI-7266025	Cluster-specific
P25116	PAR1	Yes	Yes	No	No	—	No	E3-specific
Q9Y4H2	IRS2	Yes	Yes	No	No	—	No	E3-specific
Q969T9	WBP2	Yes	Yes	No	No	—	No	E3-specific
Q6PJG6	BRAT1	Yes	Yes	No	No	—	No	Cluster-specific
Q9H4B6	SAV1	Yes	Yes	No	No	—	No	E3-specific
O75113	N4BP1	Yes	Yes	No	No	—	No	E3-specific
Q9BSA4	TTYH2	Yes	Yes	No	No	—	No	Cluster-specific
Q92734	TFG	Yes	No	No	No	—	No	E3-specific
Q96NT3	GUCD1	Yes	Yes	No	No	—	No	E3-specific
P51170	SCNNG	Yes	Yes	No	No	11359767	EBI-7845524	Cluster-specific
Q14524	SCN5A	Yes	Yes	No	No	—	No	Cluster-specific
P46934	NEDD4	Yes	Yes	No	No	—	No	E3-specific
Q9BXB1	LGR4	Yes	Yes	No	No	—	No	Cluster-specific
Q9NYA4	MTMR4	Yes	Yes	No	No	—	No	E3-specific
Q01959	SC6A3	Yes	Yes	No	No	—	No	Cluster-specific
Q9UKG1	DP13A	Yes	Yes	No	No	—	No	E3-specific
Q15012	LAP4A	Yes	No	No	No	—	No	E3-specific
O15399	NMDE4	Yes	Yes	No	No	—	No	E3-specific
Q9Y4G8	RPGF2	Yes	Yes	No	No	21765395	EBI-7026879	E3-specific
O75444	MAF	Yes	No	No	No	—	No	E3-specific
O43490	PROM1	Yes	No	No	No	—	No	E3-specific
Q9BT67	NFIP1	Yes	Yes	No	No	—	No	E3-specific
P23759	PAX7	Yes	Yes	No	No	—	No	E3-specific
Q9NV92	NFIP2	Yes	Yes	No	No	—	No	Cluster-specific
P01112	RASH	Yes	Yes	No	No	—	No	E3-specific
P42261	GRIA1	Yes	Yes	No	No	—	No	E3-specific
Q2KJY2	KI26B	Yes	Yes	No	No	—	No	E3-specific
Q96FV9	THOC1	Yes	Yes	No	No	—	No	E3-specific
P19634	SL9A1	Yes	Yes	No	No	—	No	E3-specific
Q9UIH9	KLF15	Yes	No	No	No	—	No	E3-specific
P08183	MDR1	Yes	Yes	No	No	—	No	E3-specific
Q4VCS5	AMOT	Yes	Yes	No	No	—	No	Cluster-specific
P01111	RASN	Yes	Yes	No	No	—	No	E3-specific
P43005	EAA3	Yes	Yes	No	No	—	No	E3-specific
O75473	LGR5	Yes	Yes	No	No	—	No	Cluster-specific
O14980	XPO1	Yes	No	No	No	—	No	E3-specific
Q96BF3	TMIG2	Yes	No	No	No	—	No	E3-specific
Q9Y5U5	TNR18	Yes	No	No	No	—	No	E3-specific
O75843	AP1G2	Yes	Yes	No	No	—	No	E3-specific
O95835	LATS1	Yes	Yes	No	No	—	No	Cluster-specific
Q01628	IFM3	Yes	Yes	No	No	—	No	E3-specific
P07550	ADRB2	Yes	Yes	No	No	—	No	E3-specific
Q96GG9	DCNL1	Yes	Yes	No	No	—	No	E3-specific
P27216	ANX13	Yes	Yes	No	No	—	No	E3-specific
P51168	SCNNB	Yes	Yes	Yes	No	21765395, 11359767	EBI-7845369	Cluster-specific
Q9UBF6	RBX2	Yes	Yes	No	No	—	No	E3-specific

Small Molecule Interactions ▾

Type	ChEMBL Compound ID	Source	pChEMBL	PDB Compound ID	PDB Codes	SMILES
E3 Binder	CHEMBL3621955	ChEMBL	6.3	—	—	Cc1nc2ccccc2nc1SCC(=O)NC(=O)Nc1ccccc1
E3 Binder	CHEMBL3621954	ChEMBL	6.3	—	—	Cc1nn(-c2ccccc2)c(C)c1NC(=O)CN1CCCC(c2nc3ccccc3s2)C1

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The E3 Ligome database, including all associated data, metadata, and documentation, is the intellectual property of Goethe University (PROXIDRUGs consortium) under the InnoDATA project.
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If you use or refer to the Database in your publications, reports, or presentations, you must cite the paper: Dutta, A., Cristiani, A., Nikte, S.V. et al. Multi-scale classification decodes the complexity of the human E3 ligome. Nat Commun 16, 11382 (2025).

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For inquiries, permissions, or support regarding the Database, please contact: Dr. Ramachandra M. Bhaskara, Goethe University Frankfurt.
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