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Protein

E3 ubiquitin-protein ligase NEDD4

Gene

NEDD4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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. Specifically ubiquitinates 'Lys-63' in target proteins (PubMed:23644597). 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. Promotes ubiquitination of RAPGEF2. 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. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046).9 Publications
(Microbial infection) Involved in the ubiquitination of Ebola virus protein VP40 which plays a role in viral budding.1 Publication

Miscellaneous

A cysteine residue is required for ubiquitin-thioester formation.

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Activated by NDFIP1- and NDFIP2-binding.By similarity

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.1 Publication
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei1286Glycyl thioester intermediatePROSITE-ProRule annotation1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionTransferase
Biological processHost-virus interaction, Neurogenesis, Ubl conjugation pathway

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.3.2.B9 2681
6.3.2.19 2681

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-1169408 ISG15 antiviral mechanism
R-HSA-1253288 Downregulation of ERBB4 signaling
R-HSA-8948747 Regulation of PTEN localization
R-HSA-8948751 Regulation of PTEN stability and activity
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...
SignaLinki
P46934

SIGNOR Signaling Network Open Resource

More...
SIGNORi
P46934

UniPathway: a resource for the exploration and annotation of metabolic pathways

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UniPathwayi
UPA00143

Protein family/group databases

Transport Classification Database

More...
TCDBi
8.A.30.1.2 the nedd4-family interacting protein-2 (nedd4) family

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
E3 ubiquitin-protein ligase NEDD4 (EC:2.3.2.262 Publications)
Alternative name(s):
Cell proliferation-inducing gene 53 protein
HECT-type E3 ubiquitin transferase NEDD4
Neural precursor cell expressed developmentally down-regulated protein 4
Short name:
NEDD-4
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:NEDD4
Synonyms:KIAA0093, NEDD4-1
ORF Names:PIG53
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 15

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000069869.15

Human Gene Nomenclature Database

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HGNCi
HGNC:7727 NEDD4

Online Mendelian Inheritance in Man (OMIM)

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MIMi
602278 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P46934

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi795W → A: Abolishes interaction with ARRDC3; when associated with A-868 and A-920. 1 Publication1
Mutagenesisi868W → A: Abolishes interaction with ARRDC3; when associated with A-795 and A-920. 1 Publication1
Mutagenesisi920W → A: Abolishes interaction with ARRDC3; when associated with A-795 and A-868. 1 Publication1

Organism-specific databases

DisGeNET

More...
DisGeNETi
4734

Open Targets

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OpenTargetsi
ENSG00000069869

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA31533

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL3621023

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
NEDD4

Domain mapping of disease mutations (DMDM)

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DMDMi
313104311

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001203191 – 1319E3 ubiquitin-protein ligase NEDD4Add BLAST1319
Isoform 4 (identifier: P46934-4)
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemovedCombined sources

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei576PhosphoserineBy similarity1
Modified residuei648PhosphothreonineBy similarity1
Modified residuei670PhosphoserineBy similarity1
Modified residuei742PhosphoserineCombined sources1
Modified residuei747PhosphoserineCombined sources1
Isoform 4 (identifier: P46934-4)
Modified residuei2N-acetylalanineCombined sources1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Auto-ubiquitinated.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
P46934

MaxQB - The MaxQuant DataBase

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MaxQBi
P46934

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P46934

PeptideAtlas

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PeptideAtlasi
P46934

PRoteomics IDEntifications database

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PRIDEi
P46934

ProteomicsDB human proteome resource

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ProteomicsDBi
55768
55769 [P46934-2]
55770 [P46934-3]
55771 [P46934-4]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P46934

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
P46934

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000069869 Expressed in 198 organ(s), highest expression level in biceps brachii

CleanEx database of gene expression profiles

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CleanExi
HS_NEDD4

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P46934 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P46934 HS

Organism-specific databases

Human Protein Atlas

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HPAi
CAB001991
CAB072833
HPA039883

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

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, PMEPAI and PRRG2 (By similarity). Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase and may induce its recruitment to exosomes (By similarity). Interaction with PTEN is questionable according to PubMed:18562292. Interacts (via C2 domain) with GRB10 (via SH2 domain). Interacts with ERBB4 (By similarity). 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). Interacts with OTUD7B. Interacts with ISG15. Interacts (via WW domain) with RAPGEF2; this interaction leads to ubiquitination and degradation via the proteasome pathway. Interacts (via WW domains) with ARRDC3 (via PPXY motifs) (PubMed:20559325, PubMed:24379409). Interacts with LAPTM4B; may play a role in the lysosomal sorting of LAPTM4B (PubMed:22096579). Interacts (via WW domains) with ARRDC1, ARRDC2 and ARRDC3 (PubMed:21191027). Interacts with ZBTB7B (By similarity).By similarity14 Publications
(Microbial infection) Interacts with viral proteins that contain a late-budding motif P-P-P-Y. This interaction is essential for viral particle budding of many retroviruses, like HTLV-1 Gag and MLV Gag. Interacts with Herpes simplex virus 2 (HHV-2) protein UL56; this interaction induces NEDD4 degradation (PubMed:18353951). Interacts with Ebola virus protein VP40 (PubMed:12559917).3 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
110811, 319 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
P46934

Database of interacting proteins

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DIPi
DIP-29815N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
P46934

Protein interaction database and analysis system

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IntActi
P46934, 38 interactors

Molecular INTeraction database

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MINTi
P46934

STRING: functional protein association networks

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STRINGi
9606.ENSP00000345530

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

11319
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
P46934

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P46934

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
P46934

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini610 – 643WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini767 – 800WW 2PROSITE-ProRule annotationAdd BLAST34
Domaini840 – 873WW 3PROSITE-ProRule annotationAdd BLAST34
Domaini892 – 925WW 4PROSITE-ProRule annotationAdd BLAST34
Domaini984 – 1318HECTPROSITE-ProRule annotationAdd BLAST335

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni578 – 981Mediates interaction with TNIKBy similarityAdd BLAST404

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi68 – 215Ser-richAdd BLAST148

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The WW domains mediate interaction with PPxY motif-containing proteins (PubMed:21191027). The WW domains mediate interaction with LITAF, RNF11, WBP1, WBP2, PMEPAI, NDFIP1 and PRRG2 (By similarity).By similarity1 Publication

Keywords - Domaini

Repeat

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG0940 Eukaryota
COG5021 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000158905

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG004134

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P46934

KEGG Orthology (KO)

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KOi
K10591

Identification of Orthologs from Complete Genome Data

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OMAi
FNSLKWI

Database of Orthologous Groups

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OrthoDBi
EOG091G0SS8

Database for complete collections of gene phylogenies

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PhylomeDBi
P46934

TreeFam database of animal gene trees

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TreeFami
TF323658

Family and domain databases

Conserved Domains Database

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CDDi
cd00078 HECTc, 1 hit
cd00201 WW, 4 hits

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
2.60.40.150, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR035892 C2_domain_sf
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR001202 WW_dom
IPR036020 WW_dom_sf

Pfam protein domain database

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Pfami
View protein in Pfam
PF00632 HECT, 1 hit
PF00397 WW, 4 hits

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00119 HECTc, 1 hit
SM00456 WW, 4 hits

Superfamily database of structural and functional annotation

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SUPFAMi
SSF51045 SSF51045, 4 hits
SSF56204 SSF56204, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS50237 HECT, 1 hit
PS01159 WW_DOMAIN_1, 4 hits
PS50020 WW_DOMAIN_2, 4 hits

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (4+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P46934-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAQSLRLHFA ARRSNTYPLS ETSGDDLDSH VHMCFKRPTR ISTSNVVQMK
60 70 80 90 100
LTPRQTALAP LIKENVQSQE RSSVPSSENV NKKSSCLQIS LQPTRYSGYL
110 120 130 140 150
QSSNVLADSD DASFTCILKD GIYSSAVVDN ELNAVNDGHL VSSPAICSGS
160 170 180 190 200
LSNFSTSDNG SYSSNGSDFG SCASITSGGS YTNSVISDSS SYTFPPSDDT
210 220 230 240 250
FLGGNLPSDS TSNRSVPNRN TTPCEIFSRS TSTDPFVQDD LEHGLEIMKL
260 270 280 290 300
PVSRNTKIPL KRYSSLVIFP RSPSTTRPTS PTSLCTLLSK GSYQTSHQFI
310 320 330 340 350
ISPSEIAHNE DGTSAKGFLS TAVNGLRLSK TICTPGEVRD IRPLHRKGSL
360 370 380 390 400
QKKIVLSNNT PRQTVCEKSS EGYSCVSVHF TQRKAATLDC ETTNGDCKPE
410 420 430 440 450
MSEIKLNSDS EYIKLMHRTS ACLPSSQNVD CQININGELE RPHSQMNKNH
460 470 480 490 500
GILRRSISLG GAYPNISCLS SLKHNCSKGG PSQLLIKFAS GNEGKVDNLS
510 520 530 540 550
RDSNRDCTNE LSNSCKTRDD FLGQVDVPLY PLPTENPRLE RPYTFKDFVL
560 570 580 590 600
HPRSHKSRVK GYLRLKMTYL PKTSGSEDDN AEQAEELEPG WVVLDQPDAA
610 620 630 640 650
CHLQQQQEPS PLPPGWEERQ DILGRTYYVN HESRRTQWKR PTPQDNLTDA
660 670 680 690 700
ENGNIQLQAQ RAFTTRRQIS EETESVDNRE SSENWEIIRE DEATMYSNQA
710 720 730 740 750
FPSPPPSSNL DVPTHLAEEL NARLTIFGNS AVSQPASSSN HSSRRGSLQA
760 770 780 790 800
YTFEEQPTLP VLLPTSSGLP PGWEEKQDER GRSYYVDHNS RTTTWTKPTV
810 820 830 840 850
QATVETSQLT SSQSSAGPQS QASTSDSGQQ VTQPSEIEQG FLPKGWEVRH
860 870 880 890 900
APNGRPFFID HNTKTTTWED PRLKIPAHLR GKTSLDTSND LGPLPPGWEE
910 920 930 940 950
RTHTDGRIFY INHNIKRTQW EDPRLENVAI TGPAVPYSRD YKRKYEFFRR
960 970 980 990 1000
KLKKQNDIPN KFEMKLRRAT VLEDSYRRIM GVKRADFLKA RLWIEFDGEK
1010 1020 1030 1040 1050
GLDYGGVARE WFFLISKEMF NPYYGLFEYS ATDNYTLQIN PNSGLCNEDH
1060 1070 1080 1090 1100
LSYFKFIGRV AGMAVYHGKL LDGFFIRPFY KMMLHKPITL HDMESVDSEY
1110 1120 1130 1140 1150
YNSLRWILEN DPTELDLRFI IDEELFGQTH QHELKNGGSE IVVTNKNKKE
1160 1170 1180 1190 1200
YIYLVIQWRF VNRIQKQMAA FKEGFFELIP QDLIKIFDEN ELELLMCGLG
1210 1220 1230 1240 1250
DVDVNDWREH TKYKNGYSAN HQVIQWFWKA VLMMDSEKRI RLLQFVTGTS
1260 1270 1280 1290 1300
RVPMNGFAEL YGSNGPQSFT VEQWGTPEKL PRAHTCFNRL DLPPYESFEE
1310
LWDKLQMAIE NTQGFDGVD
Note: No experimental confirmation available.
Length:1,319
Mass (Da):149,114
Last modified:November 30, 2010 - v4
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iD56EBBC50A34F13B
GO
Isoform 2 (identifier: P46934-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     589-604: Missing.

Note: No experimental confirmation available.
Show »
Length:1,303
Mass (Da):147,384
Checksum:iC40112E4C9BC8416
GO
Isoform 3 (identifier: P46934-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     517-588: Missing.

Note: No experimental confirmation available.
Show »
Length:1,247
Mass (Da):140,696
Checksum:i827AC55FB4AFB6A3
GO
Isoform 4 (identifier: P46934-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-419: Missing.
     420-516: SACLPSSQNV...CTNELSNSCK → MATCAVEVFG...LFEVFDENRL

Show »
Length:900
Mass (Da):104,217
Checksum:i4303287D3133B1C7
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0Y8X6H0Y8X6_HUMAN
E3 ubiquitin-protein ligase NEDD4
NEDD4
910Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0YA37H0YA37_HUMAN
E3 ubiquitin-protein ligase NEDD4
NEDD4
401Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0Y8H4H0Y8H4_HUMAN
E3 ubiquitin-protein ligase NEDD4
NEDD4
35Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0Y9L1H0Y9L1_HUMAN
E3 ubiquitin-protein ligase NEDD4
NEDD4
39Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence BAA07655 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti59A → T in AL832063 (PubMed:17974005).Curated1
Sequence conflicti407N → H in AL832063 (PubMed:17974005).Curated1
Sequence conflicti620Q → R in AAT52215 (Ref. 4) Curated1
Sequence conflicti620Q → R in AAI44285 (PubMed:15489334).Curated1
Sequence conflicti863T → I in AAI36606 (PubMed:15489334).Curated1
Sequence conflicti863T → I in AAI44285 (PubMed:15489334).Curated1
Sequence conflicti1199L → P in BAG65229 (PubMed:14702039).Curated1
Sequence conflicti1268S → L in AL832063 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_06198533M → V. Corresponds to variant dbSNP:rs1912403Ensembl.1
Natural variantiVAR_036472627Y → H in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_047909679R → Q5 PublicationsCorresponds to variant dbSNP:rs2303580Ensembl.1
Natural variantiVAR_047910698N → S5 PublicationsCorresponds to variant dbSNP:rs2303579Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0382561 – 419Missing in isoform 4. 4 PublicationsAdd BLAST419
Alternative sequenceiVSP_038257420 – 516SACLP…SNSCK → MATCAVEVFGLLEDEENSRI VRVRVIAGIGLAKKDILGAS DPYVRVTLYDPMNGVLTSVQ TKTIKKSLNPKWNEEILFRV HPQQHRLLFEVFDENRL in isoform 4. 4 PublicationsAdd BLAST97
Alternative sequenceiVSP_038258517 – 588Missing in isoform 3. 1 PublicationAdd BLAST72
Alternative sequenceiVSP_038259589 – 604Missing in isoform 2. 1 PublicationAdd BLAST16

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
D42055 mRNA Translation: BAA07655.1 Different initiation.
AK304394 mRNA Translation: BAG65229.1
AY550969 mRNA Translation: AAT52215.1
AL832063 Genomic DNA No translation available.
AC009997 Genomic DNA No translation available.
AC039057 Genomic DNA No translation available.
CH471082 Genomic DNA Translation: EAW77495.1
BC136605 mRNA Translation: AAI36606.1
BC144284 mRNA Translation: AAI44285.1
BC144285 mRNA Translation: AAI44286.1
BC152452 mRNA Translation: AAI52453.1
BC152562 mRNA Translation: AAI52563.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS10156.1 [P46934-3]
CCDS45265.1 [P46934-4]
CCDS61643.1 [P46934-2]
CCDS61644.1 [P46934-1]

NCBI Reference Sequences

More...
RefSeqi
NP_001271267.1, NM_001284338.1 [P46934-1]
NP_001271268.1, NM_001284339.1 [P46934-2]
NP_001271269.1, NM_001284340.1
NP_001316141.1, NM_001329212.1
NP_006145.2, NM_006154.3 [P46934-4]
NP_940682.2, NM_198400.3 [P46934-3]

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.1565

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000338963; ENSP00000345530; ENSG00000069869 [P46934-3]
ENST00000435532; ENSP00000410613; ENSG00000069869 [P46934-4]
ENST00000506154; ENSP00000422705; ENSG00000069869 [P46934-2]
ENST00000508342; ENSP00000424827; ENSG00000069869 [P46934-1]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
4734

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:4734

UCSC genome browser

More...
UCSCi
uc002adi.5 human [P46934-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D42055 mRNA Translation: BAA07655.1 Different initiation.
AK304394 mRNA Translation: BAG65229.1
AY550969 mRNA Translation: AAT52215.1
AL832063 Genomic DNA No translation available.
AC009997 Genomic DNA No translation available.
AC039057 Genomic DNA No translation available.
CH471082 Genomic DNA Translation: EAW77495.1
BC136605 mRNA Translation: AAI36606.1
BC144284 mRNA Translation: AAI44285.1
BC144285 mRNA Translation: AAI44286.1
BC152452 mRNA Translation: AAI52453.1
BC152562 mRNA Translation: AAI52563.1
CCDSiCCDS10156.1 [P46934-3]
CCDS45265.1 [P46934-4]
CCDS61643.1 [P46934-2]
CCDS61644.1 [P46934-1]
RefSeqiNP_001271267.1, NM_001284338.1 [P46934-1]
NP_001271268.1, NM_001284339.1 [P46934-2]
NP_001271269.1, NM_001284340.1
NP_001316141.1, NM_001329212.1
NP_006145.2, NM_006154.3 [P46934-4]
NP_940682.2, NM_198400.3 [P46934-3]
UniGeneiHs.1565

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KPZNMR-A834-878[»]
2KQ0NMR-A834-878[»]
2M3ONMR-W838-877[»]
2XBBX-ray2.68A/B938-1319[»]
2XBFX-ray2.50A938-1319[»]
3B7YX-ray1.80A/B517-571[»]
4BBNX-ray2.51A938-1319[»]
4BE8X-ray3.00A938-1319[»]
4N7FX-ray1.10A/B841-874[»]
4N7HX-ray1.70A840-872[»]
5AHTNMR-A838-877[»]
5C7JX-ray3.00A/B939-1319[»]
5C91X-ray2.44A938-1312[»]
ProteinModelPortaliP46934
SMRiP46934
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110811, 319 interactors
CORUMiP46934
DIPiDIP-29815N
ELMiP46934
IntActiP46934, 38 interactors
MINTiP46934
STRINGi9606.ENSP00000345530

Chemistry databases

ChEMBLiCHEMBL3621023

Protein family/group databases

TCDBi8.A.30.1.2 the nedd4-family interacting protein-2 (nedd4) family

PTM databases

iPTMnetiP46934
PhosphoSitePlusiP46934

Polymorphism and mutation databases

BioMutaiNEDD4
DMDMi313104311

Proteomic databases

EPDiP46934
MaxQBiP46934
PaxDbiP46934
PeptideAtlasiP46934
PRIDEiP46934
ProteomicsDBi55768
55769 [P46934-2]
55770 [P46934-3]
55771 [P46934-4]

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
4734
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000338963; ENSP00000345530; ENSG00000069869 [P46934-3]
ENST00000435532; ENSP00000410613; ENSG00000069869 [P46934-4]
ENST00000506154; ENSP00000422705; ENSG00000069869 [P46934-2]
ENST00000508342; ENSP00000424827; ENSG00000069869 [P46934-1]
GeneIDi4734
KEGGihsa:4734
UCSCiuc002adi.5 human [P46934-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
4734
DisGeNETi4734
EuPathDBiHostDB:ENSG00000069869.15

GeneCards: human genes, protein and diseases

More...
GeneCardsi
NEDD4
HGNCiHGNC:7727 NEDD4
HPAiCAB001991
CAB072833
HPA039883
MIMi602278 gene
neXtProtiNX_P46934
OpenTargetsiENSG00000069869
PharmGKBiPA31533

Human Unidentified Gene-Encoded large proteins database

More...
HUGEi
Search...

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG0940 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00940000158905
HOVERGENiHBG004134
InParanoidiP46934
KOiK10591
OMAiFNSLKWI
OrthoDBiEOG091G0SS8
PhylomeDBiP46934
TreeFamiTF323658

Enzyme and pathway databases

UniPathwayi
UPA00143

BRENDAi2.3.2.B9 2681
6.3.2.19 2681
ReactomeiR-HSA-1169408 ISG15 antiviral mechanism
R-HSA-1253288 Downregulation of ERBB4 signaling
R-HSA-8948747 Regulation of PTEN localization
R-HSA-8948751 Regulation of PTEN stability and activity
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiP46934
SIGNORiP46934

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
NEDD4 human
EvolutionaryTraceiP46934

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
NEDD4

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
4734

Protein Ontology

More...
PROi
PR:P46934

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000069869 Expressed in 198 organ(s), highest expression level in biceps brachii
CleanExiHS_NEDD4
ExpressionAtlasiP46934 baseline and differential
GenevisibleiP46934 HS

Family and domain databases

CDDicd00078 HECTc, 1 hit
cd00201 WW, 4 hits
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR035892 C2_domain_sf
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR001202 WW_dom
IPR036020 WW_dom_sf
PfamiView protein in Pfam
PF00632 HECT, 1 hit
PF00397 WW, 4 hits
SMARTiView protein in SMART
SM00119 HECTc, 1 hit
SM00456 WW, 4 hits
SUPFAMiSSF51045 SSF51045, 4 hits
SSF56204 SSF56204, 1 hit
PROSITEiView protein in PROSITE
PS50237 HECT, 1 hit
PS01159 WW_DOMAIN_1, 4 hits
PS50020 WW_DOMAIN_2, 4 hits

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiNEDD4_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P46934
Secondary accession number(s): A1KY35
, A6ND72, A7MD29, B4E2R7, B7ZM59, B7ZM60, B9EGN5, D6RF89
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 30, 2010
Last modified: December 5, 2018
This is version 197 of the entry and version 4 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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