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Aliases for NEDD4L Gene

Aliases for NEDD4L Gene

  • Neural Precursor Cell Expressed, Developmentally Down-Regulated 4-Like, E3 Ubiquitin Protein Ligase 2 3
  • KIAA0439 4 6
  • NEDD4-2 3 4
  • NEDD4.2 3 4
  • RSP5 3 6
  • Neural Precursor Cell Expressed, Developmentally Down-Regulated 4-Like 2
  • E3 Ubiquitin-Protein Ligase NEDD4-Like 3
  • Ubiquitin-Protein Ligase Rsp5 3
  • EC 6.3.2.- 4
  • HNEDD4-2 3
  • EC 6.3.2 63
  • NEDL3 4

External Ids for NEDD4L Gene

Previous GeneCards Identifiers for NEDD4L Gene

  • GC18P055746
  • GC18P055496
  • GC18P053860
  • GC18P053862
  • GC18P052421
  • GC18P055711

Summaries for NEDD4L Gene

Entrez Gene Summary for NEDD4L Gene

  • This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. The encoded protein mediates the ubiquitination of multiple target substrates and plays a critical role in epithelial sodium transport by regulating the cell surface expression of the epithelial sodium channel, ENaC. Single nucleotide polymorphisms in this gene may be associated with essential hypertension. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

GeneCards Summary for NEDD4L Gene

NEDD4L (Neural Precursor Cell Expressed, Developmentally Down-Regulated 4-Like, E3 Ubiquitin Protein Ligase) is a Protein Coding gene. Diseases associated with NEDD4L include liddle syndrome. Among its related pathways are Signaling by GPCR and Disease. GO annotations related to this gene include ubiquitin-protein transferase activity and potassium channel regulator activity. An important paralog of this gene is AREL1.

UniProtKB/Swiss-Prot for NEDD4L Gene

  • 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.

Gene Wiki entry for NEDD4L Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NEDD4L Gene

Genomics for NEDD4L Gene

Regulatory Elements for NEDD4L Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for NEDD4L Gene

Start:
58,044,355 bp from pter
End:
58,401,540 bp from pter
Size:
357,186 bases
Orientation:
Plus strand

Genomic View for NEDD4L Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for NEDD4L Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NEDD4L Gene

Proteins for NEDD4L Gene

  • Protein details for NEDD4L Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96PU5-NED4L_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase NEDD4-like
    Protein Accession:
    Q96PU5
    Secondary Accessions:
    • O43165
    • Q3LSM7
    • Q7Z5F1
    • Q7Z5F2
    • Q7Z5N3
    • Q8N5A7
    • Q8WUU9
    • Q9BW58
    • Q9H2W4
    • Q9NT88

    Protein attributes for NEDD4L Gene

    Size:
    975 amino acids
    Molecular mass:
    111932 Da
    Quaternary structure:
    • Interacts with UBE2E3 (By similarity). Interacts with NDFIP1 and NDFIP2 (By similarity); 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. Interacts (via C2 domain) with NPC2.
    SequenceCaution:
    • Sequence=BAA23711.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=BAA23711.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for NEDD4L Gene

    Alternative splice isoforms for NEDD4L Gene

neXtProt entry for NEDD4L Gene

Proteomics data for NEDD4L Gene at MOPED

Post-translational modifications for NEDD4L Gene

  • Auto-ubiquitinated.
  • Phosphorylated by SGK1 or PKA; which impairs interaction with SCNN. Interaction with YWHAH inhibits dephosphorylation.
  • Ubiquitination at Lys129, Lys471, Lys521, and Lys531
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for NEDD4L (NEDD4L)

Domains for NEDD4L Gene

Protein Domains for NEDD4L Gene

Suggested Antigen Peptide Sequences for NEDD4L Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q96PU5

UniProtKB/Swiss-Prot:

NED4L_HUMAN :
  • Q96PU5
Domain:
  • Contains 1 C2 domain.
  • Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.
  • Contains 4 WW domains.
genes like me logo Genes that share domains with NEDD4L: view

No data available for Gene Families for NEDD4L Gene

Function for NEDD4L Gene

Molecular function for NEDD4L Gene

GENATLAS Biochemistry: neural precursor cell expressed gene 4-like,developmentally down-regulated 4-like
UniProtKB/Swiss-Prot EnzymeRegulation: Activated by NDFIP1- and NDFIP2-binding
UniProtKB/Swiss-Prot Function: 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.
UniProtKB/Swiss-Prot Induction: By androgens in prostate, and by albumin in kidney.

Enzyme Numbers (IUBMB) for NEDD4L Gene

Gene Ontology (GO) - Molecular Function for NEDD4L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 ubiquitin-protein transferase activity TAS --
GO:0005515 protein binding IPI 11244092
GO:0015459 potassium channel regulator activity IDA 17289006
GO:0016874 ligase activity IEA --
GO:0017080 sodium channel regulator activity IDA 11244092
genes like me logo Genes that share ontologies with NEDD4L: view
genes like me logo Genes that share phenotypes with NEDD4L: view

Animal Models for NEDD4L Gene

MGI Knock Outs for NEDD4L:

Animal Model Products

CRISPR Products

miRNA for NEDD4L Gene

miRTarBase miRNAs that target NEDD4L

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for NEDD4L

In Situ Assay Products

Flow Cytometry Products

No data available for Transcription Factor Targeting and HOMER Transcription for NEDD4L Gene

Localization for NEDD4L Gene

Subcellular locations from UniProtKB/Swiss-Prot for NEDD4L Gene

Cytoplasm. Note=May be recruited to exosomes by NDFIP1.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NEDD4L Gene COMPARTMENTS Subcellular localization image for NEDD4L gene
Compartment Confidence
cytosol 4
nucleus 4
endosome 2
lysosome 2
plasma membrane 2
vacuole 2

Gene Ontology (GO) - Cellular Components for NEDD4L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular IC 11244092
GO:0005634 nucleus IBA --
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IBA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with NEDD4L: view

Pathways for NEDD4L Gene

genes like me logo Genes that share pathways with NEDD4L: view

Pathways by source for NEDD4L Gene

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays

UniProtKB/Swiss-Prot Q96PU5-NED4L_HUMAN

  • Pathway: Protein modification; protein ubiquitination

Gene Ontology (GO) - Biological Process for NEDD4L Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription from RNA polymerase II promoter TAS --
GO:0003085 negative regulation of systemic arterial blood pressure IEA --
GO:0003254 regulation of membrane depolarization IDA 15217910
GO:0006351 transcription, DNA-templated TAS --
GO:0006367 transcription initiation from RNA polymerase II promoter TAS --
genes like me logo Genes that share ontologies with NEDD4L: view

Compounds for NEDD4L Gene

(4) HMDB Compounds for NEDD4L Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine monophosphate
  • 5'-AMP
61-19-8
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
Phosphoric acid
  • acide phosphorique (FRENCH)
7664-38-2
Pyrophosphate
  • (4-)Diphosphoric acid ion
14000-31-8

(3) Novoseek inferred chemical compound relationships for NEDD4L Gene

Compound -log(P) Hits PubMed IDs
sodium 64.4 19
glutamate 0 1
cysteine 0 1

(2) PharmGKB related drug/compound annotations for NEDD4L Gene

Drug/compound Annotation
diuretics CA
hydrochlorothiazide CA
genes like me logo Genes that share compounds with NEDD4L: view

Transcripts for NEDD4L Gene

Unigene Clusters for NEDD4L Gene

Neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase:
Representative Sequences:

CRISPR Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for NEDD4L

Primer Products

  • OriGene qSTAR qPCR primer pairs in human,mouse,rat for NEDD4L

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for NEDD4L Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19a · 19b ^ 20 ^
SP1: - - - -
SP2: - -
SP3: - - -
SP4: - - - - - - - - -
SP5: - - - - - - -
SP6: - - - -
SP7: -
SP8: - - - - - - - - -
SP9: - -
SP10: - - - - - - - - -
SP11:
SP12: - - - - -
SP13:
SP14: - - - - - - - - - - - - - - - - - - - - - - -
SP15:
SP16:
SP17:
SP18:
SP19:
SP20: - - -

ExUns: 21a · 21b ^ 22a · 22b ^ 23 ^ 24 ^ 25a · 25b ^ 26 ^ 27 ^ 28 ^ 29 ^ 30 ^ 31 ^ 32 ^ 33 ^ 34 ^ 35 ^ 36 ^ 37a · 37b ^ 38a · 38b ^ 39 ^ 40a · 40b ·
SP1: - - - - -
SP2: - - - - - -
SP3: - - - - -
SP4: - - - - -
SP5: - - - - -
SP6: - - - - - -
SP7: - - - - -
SP8: - - - - - -
SP9: - - - - - -
SP10: - - - - - - -
SP11: - - - - - - - -
SP12:
SP13:
SP14: - - - - - - - - - - - - - - - - - - - - - -
SP15: -
SP16:
SP17:
SP18:
SP19:
SP20:

ExUns: 40c · 40d · 40e · 40f
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:
SP14:
SP15:
SP16:
SP17:
SP18:
SP19:
SP20:

Relevant External Links for NEDD4L Gene

GeneLoc Exon Structure for
NEDD4L
ECgene alternative splicing isoforms for
NEDD4L

Expression for NEDD4L Gene

mRNA expression in normal human tissues for NEDD4L Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for NEDD4L Gene

SOURCE GeneReport for Unigene cluster for NEDD4L Gene Hs.185677

mRNA Expression by UniProt/SwissProt for NEDD4L Gene

Q96PU5-NED4L_HUMAN
Tissue specificity: Ubiquitously expressed, with highest levels in prostate, pancreas and kidney.
genes like me logo Genes that share expressions with NEDD4L: view

In Situ Assay Products

No data available for mRNA differential expression in normal tissues for NEDD4L Gene

Orthologs for NEDD4L Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for NEDD4L Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NEDD4L 35
  • 99.66 (n)
  • 100 (a)
NEDD4L 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia NEDD4L 35
  • 90.37 (n)
  • 98.06 (a)
NEDD4L 36
  • 98 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NEDD4L 35
  • 92.12 (n)
  • 97.75 (a)
NEDD4L 36
  • 98 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Nedd4l 35
  • 89.71 (n)
  • 97.95 (a)
Nedd4l 16
Nedd4l 36
  • 98 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NEDD4L 36
  • 96 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NEDD4L 36
  • 93 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Nedd4l 35
  • 89.39 (n)
  • 97.92 (a)
chicken
(Gallus gallus)
Aves NEDD4L 35
  • 82.15 (n)
  • 93.54 (a)
NEDD4L 36
  • 93 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NEDD4L 36
  • 93 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.206 35
tropical clawed frog
(Silurana tropicalis)
Amphibia nedd4l 35
  • 78.46 (n)
  • 89.97 (a)
Str.10684 35
zebrafish
(Danio rerio)
Actinopterygii Dr.26117 35
nedd4l 35
  • 73.46 (n)
  • 82.9 (a)
nedd4l 36
  • 79 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000787 35
  • 54.09 (n)
  • 54.09 (a)
fruit fly
(Drosophila melanogaster)
Insecta Nedd4 35
  • 64.64 (n)
  • 67.3 (a)
Nedd4 36
  • 46 (a)
OneToMany
Nedd4 37
  • 46 (a)
worm
(Caenorhabditis elegans)
Secernentea Y92H12A.2 35
  • 57.05 (n)
  • 56.46 (a)
Y92H12A.2 36
  • 50 (a)
OneToMany
Y92H12A.2 37
  • 47 (a)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ADL055C 35
  • 57.56 (n)
  • 52.86 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes RSP5 35
  • 55.5 (n)
  • 52.13 (a)
RSP5 36
  • 40 (a)
OneToMany
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0E13575g 35
  • 55.91 (n)
  • 54.19 (a)
bread mold
(Neurospora crassa)
Ascomycetes NCU03947 35
  • 53.42 (n)
  • 49.6 (a)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes pub1 35
  • 54 (n)
  • 49.86 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 62 (a)
OneToMany
Species with no ortholog for NEDD4L:
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for NEDD4L Gene

ENSEMBL:
Gene Tree for NEDD4L (if available)
TreeFam:
Gene Tree for NEDD4L (if available)

Paralogs for NEDD4L Gene

Paralogs for NEDD4L Gene

genes like me logo Genes that share paralogs with NEDD4L: view

Variants for NEDD4L Gene

Sequence variations from dbSNP and Humsavar for NEDD4L Gene

SNP ID Clin Chr 18 pos Sequence Context AA Info Type MAF
rs1672 -- 58,094,773(-) AAGGT(A/G)CCGCC intron-variant
rs1675 -- 58,094,762(-) ACCTA(C/T)GCAGT intron-variant
rs45448 -- 58,107,843(-) cccaa(A/T)tactt intron-variant
rs48000 -- 58,176,512(-) ATAAA(A/G)ATTTT intron-variant
rs150377 -- 58,246,055(-) AACTT(C/T)TAGAT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for NEDD4L Gene

Variant ID Type Subtype PubMed ID
nsv523158 CNV Gain 19592680
nsv2322 CNV Insertion 18451855
esv2717155 CNV Deletion 23290073
esv2658465 CNV Deletion 23128226
esv1752057 CNV Insertion 17803354
esv1432973 CNV Deletion 17803354
esv2426857 CNV Deletion 19546169
esv2006464 CNV Deletion 18987734
esv3030 CNV Deletion 18987735
esv2717156 CNV Deletion 23290073
esv1499259 CNV Deletion 17803354
nsv131445 CNV Loss 16902084
esv7213 CNV Loss 19470904
nsv510459 CNV Loss 20534489
esv2572802 CNV Deletion 19546169
esv2677246 CNV Deletion 23128226
nsv2323 CNV Insertion 18451855
esv2643904 CNV Insertion 19546169
nsv518049 CNV Loss 19592680
esv2717157 CNV Deletion 23290073
esv2673951 CNV Deletion 23128226
esv29895 CNV Loss 19812545
nsv528313 CNV Loss 19592680
dgv1029e1 CNV Complex 17122850
essv18552 CNV CNV 17122850
dgv1030e1 CNV Complex 17122850
nsv442442 CNV CNV 18776908
esv2657059 CNV Deletion 23128226
esv29817 CNV Loss 19812545
nsv514875 CNV Loss 21397061
nsv516529 CNV Loss 19592680
nsv817794 CNV Loss 17921354
esv2717158 CNV Deletion 23290073
esv2138002 CNV Deletion 18987734
esv2717159 CNV Deletion 23290073

Relevant External Links for NEDD4L Gene

HapMap Linkage Disequilibrium report
NEDD4L
Human Gene Mutation Database (HGMD)
NEDD4L

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NEDD4L Gene

Disorders for NEDD4L Gene

MalaCards: The human disease database

MalaCards: The human disease database. (1) Diseases for NEDD4L Gene including...

Search for NEDD4L Gene in MalaCards »

(2) University of Copenhagen DISEASES for NEDD4L Gene

(3) Novoseek inferred disease relationships for NEDD4L Gene

Disease -log(P) Hits PubMed IDs
liddles syndrome 90.6 3
essential hypertension 51.8 3
hypotension orthostatic 30.2 2

Relevant External Links for NEDD4L

Genetic Association Database (GAD)
NEDD4L
Human Genome Epidemiology (HuGE) Navigator
NEDD4L
genes like me logo Genes that share disorders with NEDD4L: view

No data available for UniProtKB/Swiss-Prot for NEDD4L Gene

Publications for NEDD4L Gene

  1. The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial sodium channel. (PMID: 11244092) Harvey K.F. … Kumar S. (J. Biol. Chem. 2001) 2 3 23
  2. NEDD4L on human chromosome 18q21 has multiple forms of transcripts and is a homologue of the mouse Nedd4-2 gene. (PMID: 11840194) Chen H. … McInnis M.G. (Eur. J. Hum. Genet. 2001) 3 4 23
  3. Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel. (PMID: 11696533) Snyder P.M. … Thomas B.C. (J. Biol. Chem. 2002) 3 4 23
  4. Regulation of the glutamate transporter EAAT1 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid-inducible kinase isoforms SGK1/3 and protein kinase B. (PMID: 12911626) Boehmer C. … Lang F. (J. Neurochem. 2003) 3 4 23
  5. Identification of new partners of the epithelial sodium channel alpha subunit. (PMID: 14556380) Malbert-Colas L. … Dhermy D. (C. R. Biol. 2003) 3 4 23

Products for NEDD4L Gene

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