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NEDD4L Gene

protein-coding   GIFtS: 66
GCID: GC18P055711

Neural Precursor Cell Expressed, Developmentally Down-Regulated...

(Previous names: neural precursor cell expressed, developmentally down-regulated...)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Neural Precursor Cell Expressed, Developmentally Down-Regulated 4-Like,
E3 Ubiquitin Protein Ligase1 2
     hNEDD4-22
NEDD4.22 3     Ubiquitin-Protein Ligase Rsp52
RSP52 5     EC 6.3.2.-3
KIAA04393 5     NEDL33
Neural Precursor Cell Expressed, Developmentally Down-Regulated 4-Like1     Nedd4-23
NEDD4-22     EC 6.3.28
E3 Ubiquitin-Protein Ligase NEDD4-Like2     

External Ids:    HGNC: 77281   Entrez Gene: 233272   Ensembl: ENSG000000497597   OMIM: 6063845   UniProtKB: Q96PU53   

Export aliases for NEDD4L gene to outside databases

Previous GC identifers: GC18P055746 GC18P055496 GC18P053860 GC18P053862 GC18P052421


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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, and essential hypertension. GO annotations related to this gene include ubiquitin-protein ligase activity and potassium channel regulator activity. An important paralog of this gene is HECW2.

UniProtKB/Swiss-Prot: NED4L_HUMAN, Q96PU5
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

Gene Wiki entry for NEDD4L Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000018.10  NT_010966.15  NC_018929.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the NEDD4L gene promoter:
         HEN1   POU2F1   c-Myb   Hand1   Evi-1   RSRFC4   E47   GATA-1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidNEDD4L promoter sequence
   Search Chromatin IP Primers for NEDD4L

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat NEDD4L


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 18q21   Ensembl cytogenetic band:  18q21.31   HGNC cytogenetic band: 18q21

NEDD4L Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NEDD4L gene location

GeneLoc information about chromosome 18         GeneLoc Exon Structure

GeneLoc location for GC18P055711:  view genomic region     (about GC identifiers)

Start:
55,711,599 bp from pter      End:
56,068,772 bp from pter
Size:
357,174 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: NED4L_HUMAN, Q96PU5 (See protein sequence)
Recommended Name: E3 ubiquitin-protein ligase NEDD4-like  
Size: 975 amino acids; 111932 Da
Subunit: 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
Sequence caution: Sequence=BAA23711.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
Sequence=BAA23711.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact;
Selected PDB 3D structures from and Proteopedia for NEDD4L (see all 7):
2LAJ (3D)        2LB2 (3D)        2LTY (3D)        2NSQ (3D)        2ONI (3D)        3JVZ (3D)    
Secondary accessions: O43165 Q3LSM7 Q7Z5F1 Q7Z5F2 Q7Z5N3 Q8N5A7 Q8WUU9 Q9BW58 Q9H2W4 Q9NT88
Alternative splicing: 8 isoforms:  Q96PU5-1   Q96PU5-2   Q96PU5-3   Q96PU5-4   Q96PU5-5   Q96PU5-6   Q96PU5-7   Q96PU5-9   
(No experimental confirmation available)

Explore the universe of human proteins at neXtProt for NEDD4L: NX_Q96PU5

Explore proteomics data for NEDD4L at MOPED

Post-translational modifications: 

  • Phosphorylated by SGK1 or PKA; which impairs interaction with SCNN. Interaction with YWHAH inhibits
    dephosphorylation1
  • Auto-ubiquitinated1
  • Ubiquitination2 at Lys129, Lys471, Lys521, Lys531
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for NEDD4L (Q96PU5) (see all 11)
     PLPPGWE  TQWEDPR  NPYYGLF  RLLQFVTG 


    See NEDD4L Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (10 alternative transcripts): 
    NP_001138436.1  NP_001138437.1  NP_001138438.1  NP_001138439.1  NP_001138440.1  NP_001138441.1  NP_001138442.1  NP_001138443.1  
    NP_001230889.1  NP_056092.2  

    ENSEMBL proteins: 
     ENSP00000348847   ENSP00000383199   ENSP00000465669   ENSP00000372301   ENSP00000256830  
     ENSP00000466776   ENSP00000393395   ENSP00000350569   ENSP00000468546   ENSP00000405440  
     ENSP00000466789   ENSP00000389406   ENSP00000467072   ENSP00000467768   ENSP00000468332  
     ENSP00000256832   ENSP00000411947  
    Reactome Protein details: Q96PU5

    NEDD4L Human Recombinant Protein Products:

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    Novus Biologicals NEDD4L Proteins
    Novus Biologicals NEDD4L Lysate
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    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for NEDD4L

    NEDD4L Antibody Products:

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    Search for Antibodies for NEDD4L at Abcam
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    LSBio Antibodies in human, mouse, rat for NEDD4L

    NEDD4L Assay Products:

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    Cloud-Clone Corp. ELISAs for NEDD4L
    Cloud-Clone Corp. CLIAs for NEDD4L


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    4 InterPro protein domains:
     IPR024928 E3_ub_ligase_SMURF1
     IPR000569 HECT
     IPR001202 WW_dom
     IPR000008 C2_dom

    Graphical View of Domain Structure for InterPro Entry Q96PU5

    ProtoNet protein and cluster: Q96PU5

    3 Blocks protein domains:
    IPB000008 C2 domain
    IPB000569 HECT domain (Ubiquitin-protein ligase)
    IPB002349 WW domain signature


    UniProtKB/Swiss-Prot: NED4L_HUMAN, Q96PU5
    Similarity: Contains 1 C2 domain
    Similarity: Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain
    Similarity: Contains 4 WW domains


    NEDD4L for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: NED4L_HUMAN, Q96PU5
    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
    Enzyme regulation: Activated by NDFIP1- and NDFIP2-binding
    Induction: By androgens in prostate, and by albumin in kidney

         Genatlas biochemistry entry for NEDD4L:
    neural precursor cell expressed gene 4-like,developmentally down-regulated 4-like

         Enzyme Numbers (IUBMB): EC 6.3.2.-1 EC 6.3.22

         Gene Ontology (GO): Selected molecular function terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004842ubiquitin-protein ligase activity TAS--
    GO:0005515protein binding IPI11244092
    GO:0015459potassium channel regulator activity IDA17289006
    GO:0017080sodium channel regulator activity IDA11244092
    GO:0019870potassium channel inhibitor activity IDA--
         
    NEDD4L for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for NEDD4L:
     Synthetic lethal with Ras 

         12 MGI mutant phenotypes (inferred from 5 alleles(MGI details for Nedd4l):
     behavior/neurological  cardiovascular system  cellular  digestive/alimentary  hematopoietic system 
     homeostasis/metabolism  immune system  mortality/aging  muscle  no phenotypic analysis 
     renal/urinary system  respiratory system 

    NEDD4L for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for NEDD4L: Nedd4ltm1Shkr Nedd4ltm1.2Blyg

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for NEDD4L
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for NEDD4L

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for NEDD4L
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for NEDD4L

    miRNA
    Products:
        
    miRTarBase miRNAs that target NEDD4L:
    hsa-mir-1296-5p (MIRT036071), hsa-mir-24-3p (MIRT030590), hsa-mir-423-5p (MIRT038151)

    Block miRNA regulation of human, mouse, rat NEDD4L using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate NEDD4L (see all 145):
    hsa-miR-579 hsa-miR-26a-2* hsa-miR-193a-3p hsa-miR-106a hsa-miR-519a hsa-miR-200b hsa-miR-92b hsa-miR-130b
    SwitchGear 3'UTR luciferase reporter plasmidNEDD4L 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for NEDD4L
    Predesigned siRNA for gene silencing in human, mouse, rat NEDD4L

    Gene Editing
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    Clone
    Products:
         
    OriGene clones in human, mouse for NEDD4L (see all 49)
    OriGene ORF clones in mouse, rat for NEDD4L
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 9): NEDD4L (NM_001144965)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for NEDD4L
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NEDD4L

    Cell Line
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    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NEDD4L


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    NED4L_HUMAN, Q96PU5: Cytoplasm. Note=May be recruited to exosomes by NDFIP1
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol4
    nucleus4
    endosome2
    lysosome2
    plasma membrane2
    vacuole2

    Gene Ontology (GO): Selected cellular component terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005622intracellular IC11244092
    GO:0005634nucleus IBA--
    GO:0005654nucleoplasm TAS--
    GO:0005737cytoplasm IBA--
    GO:0005829cytosol TAS--

    NEDD4L for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for NEDD4L About   (see all 17)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Class I MHC mediated antigen processing and presentation
    Class I MHC mediated antigen processing and presentation0.84
    Adaptive Immune System0.41
    Antigen processing- Ubiquitination and Proteasome degradation0.84
    Ubiquitin mediated proteolysis0.35
    2Loss of Function of SMAD2/3 in Cancer
    Transcriptional activity of SMAD2/SMAD3-SMAD4 heterotrimer0.72
    TGFBR1 KD Mutants in Cancer0.60
    Loss of Function of SMAD2/3 in Cancer0.60
    SMAD2/3 MH2 Domain Mutants in Cancer0.60
    Loss of Function of SMAD4 in Cancer0.60
    SMAD2/3 Phosphorylation Motif Mutants in Cancer0.60
    TGFBR2 MSI Frameshift Mutants in Cancer0.60
    SMAD4 MH2 Domain Mutants in Cancer0.60
    3HIV Life Cycle
    HIV Life Cycle0.91
    HIV Infection0.62
    Late Phase of HIV Life Cycle0.91
    4TGF-beta receptor signaling activates SMADs
    Downregulation of TGF-beta receptor signaling0.82
    TGF-beta receptor signaling activates SMADs0.82
    5Ion channel transport
    Ion channel transport0.58
    Stimuli-sensing channels0.58

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    2 Cell Signaling Technology (CST) Pathways for NEDD4L
        TGF-beta/Smad Signaling
    Protein Stability

    2 BioSystems Pathways for NEDD4L
        Neurotrophic factor-mediated Trk receptor signaling
    TGF-beta receptor signaling

    5 Reactome Pathways for NEDD4L
        Antigen processing: Ubiquitination & Proteasome degradation
    Stimuli-sensing channels
    Downregulation of SMAD2/3:SMAD4 transcriptional activity
    Budding and maturation of HIV virion
    Downregulation of TGF-beta receptor signaling

    1 PharmGKB Pathway for NEDD4L
        Diuretics Pathway, Pharmacodynamics

    3 Kegg Pathways  (Kegg details for NEDD4L):
        Ubiquitin mediated proteolysis
    Endocytosis
    Aldosterone-regulated sodium reabsorption

    UniProtKB/Swiss-Prot: NED4L_HUMAN, Q96PU5
    Pathway: Protein modification; protein ubiquitination


    NEDD4L for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Array including NEDD4L: 

              Ubiquitin Ligases in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for NEDD4L

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for NEDD4L (Q96PU52, 3 ENSP000003831994) via UniProtKB, MINT, STRING, and/or I2D (see all 283)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ARHGDIAP525652, 3, ENSP000002693214MINT-63860 I2D: score=6 STRING: ENSP00000269321
    LAPTM5Q135712, 3, ENSP000002945074MINT-62184 I2D: score=3 STRING: ENSP00000294507
    SMAD2Q157962, 3, ENSP000002621604MINT-61615 I2D: score=2 STRING: ENSP00000262160
    MED28Q9H2042, 3, ENSP000002373804MINT-7041937 I2D: score=1 STRING: ENSP00000237380
    RAPGEF2Q9Y4G82, 3, ENSP000002644314MINT-8290088 I2D: score=1 STRING: ENSP00000264431
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 43):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000122negative regulation of transcription from RNA polymerase II promoter TAS--
    GO:0003085negative regulation of systemic arterial blood pressure IEA--
    GO:0003254regulation of membrane depolarization IDA15217910
    GO:0006351transcription, DNA-templated TAS--
    GO:0006367transcription initiation from RNA polymerase II promoter TAS--

    NEDD4L for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for NEDD4L (NED4L)

    4 HMDB Compounds for NEDD4L    About this table
    CompoundSynonyms CAS #PubMed Ids
    Adenosine monophosphate5'-AMP (see all 28)61-19-8--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--
    Phosphoric acidacide phosphorique (FRENCH) (see all 20)7664-38-2--
    Pyrophosphate(4-)Diphosphoric acid ion (see all 10)14000-31-8--

    3 Novoseek inferred chemical compound relationships for NEDD4L gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    sodium 64.4 23 16338225 (5), 18687683 (3), 12522688 (2), 18498246 (1) (see all 12)
    glutamate 0 1 12911626 (1)
    cysteine 0 1 10066826 (1)

    1 PharmGKB related drug/compound annotation for NEDD4L gene    About this table
    Drug/compound PharmGKB Annotation
    hydrochlorothiazideCA  



    NEDD4L for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for NEDD4L gene (10 alternative transcripts): 
    NM_001144964.1  NM_001144965.1  NM_001144966.2  NM_001144967.2  NM_001144968.1  NM_001144969.1  NM_001144970.2  NM_001144971.1  
    NM_001243960.1  NM_015277.5  

    Unigene Cluster for NEDD4L:

    Neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase
    Hs.185677  [show with all ESTs]
    Unigene Representative Sequence: NM_001144967
    Selected Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 37):
    ENST00000356462(uc002lgz.3) ENST00000400345(uc002lgy.3) ENST00000589054
    ENST00000382850(uc002lgx.3) ENST00000256830(uc002lha.1 uc002lhh.2 uc010dpm.1)
    ENST00000590694 ENST00000591989 ENST00000591579 ENST00000592846 ENST00000585363
    ENST00000588516 ENST00000585594 ENST00000587547 ENST00000435432(uc002lhb.2)
    ENST00000357895(uc002lhc.2 uc002lhd.2 uc002lhe.2) ENST00000586263
    ENST00000456173(uc002lhf.3) ENST00000588494
    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate NEDD4L (see all 145):
    hsa-miR-579 hsa-miR-26a-2* hsa-miR-193a-3p hsa-miR-106a hsa-miR-519a hsa-miR-200b hsa-miR-92b hsa-miR-130b
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    Inhib. RNA
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    GenScript: all cDNA clones in your preferred vector (see all 9): NEDD4L (NM_001144965)
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    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat NEDD4L
      QuantiTect SYBR Green Assays in human, mouse, rat NEDD4L
      QuantiFast Probe-based Assays in human, mouse, rat NEDD4L

    Additional mRNA sequence: 

    AB007899.1 AB071179.1 AF070601.1 AF210730.1 AF385931.1 AK091189.1 AK096812.1 AK130420.1 
    AK294963.1 AK300444.1 AL137469.1 AY112983.1 AY112984.2 AY112985.2 AY243313.1 AY243314.1 
    AY243316.1 AY243317.1 AY243318.1 AY243319.1 AY243321.1 AY243322.1 AY256662.1 AY312514.1 
    AY751751.1 BC000621.2 BC019345.1 BC032597.1 DQ181796.1 

    Selected DOTS entries (see all 39):

    DT.100820119  DT.121086464  DT.117979  DT.95113158  DT.101977753  DT.100820117  DT.40206821  DT.100820114 
    DT.212759  DT.100820116  DT.100820113  DT.101984926  DT.101969416  DT.75193154  DT.40246153  DT.100000871 
    DT.101960611  DT.101964807  DT.40189222  DT.100805131  DT.92432739  DT.75147786  DT.91849864  DT.102833453 

    Selected AceView cDNA sequences (see all 284):

    AU119079 CA312089 AA807359 AA775172 AB071179 BM694251 CA441492 BX642806 
    AA327282 AA838301 BX486688 AK130420 AI805240 AI264097 BQ220579 CB108717 
    AF210730 AF385931 AA026694 BU680215 BM714998 CF528594 CD655521 AI248492 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for NEDD4L (see all 20)    About this scheme

    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:                                -     -     -     -                 -     -     -                                                                           

    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:        -     -                                               -                                                     -           -                           

    ExUns: 40c · 40d · 40e · 40f
    SP1:                        
    SP2:                        
    SP3:                        
    SP4:                        
    SP5:                        


    ECgene alternative splicing isoforms for NEDD4L

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    NEDD4L expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    NEDD4L Expression
    About this image


    NEDD4L expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 7) fully expand
     
     Gut Tube (Gastrointestinal Tract)    fully expand to see all 3 entries
             Hindgut
     
     Kidney (Urinary System)
             Metanephros
     
     Neurons
             nGnG Amacrine Cells Inner Nuclear Layer
     
     Inner Cell Mass (Early Embryonic Tissues)
             Inner Cell Mass Cells Inner Cell Mass
     
     Eye (Sensory Organs)
             nGnG Amacrine Cells Inner Nuclear Layer
    NEDD4L Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    NEDD4L Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.185677

    UniProtKB/Swiss-Prot: NED4L_HUMAN, Q96PU5
    Tissue specificity: Ubiquitously expressed, with highest levels in prostate, pancreas and kidney

        Pathway & Disease-focused RT2 Profiler PCR Array including NEDD4L: 
              Ubiquitin Ligases in human mouse rat

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    In Situ
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NEDD4L

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of eukaryotes.

    Orthologs for NEDD4L gene from Selected species (see all 22)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Nedd4l1 , 5 neural precursor cell expressed, developmentally down-regulated more1, 5 89.71(n)1
    97.95(a)1
      18 (37.57 cM)5
    838141  NM_001114386.11  NP_001107858.11 
     648877565 
    chicken
    (Gallus gallus)
    Aves NEDD4L1 neural precursor cell expressed, developmentally down-regulated more 82.15(n)
    93.54(a)
      374119  XM_004948998.1  XP_004949055.1 
    lizard
    (Anolis carolinensis)
    Reptilia NEDD4L6
    neural precursor cell expressed, developmentally d...
    93(a)
    1 ↔ 1
    GL343213.1(2382440-2655715)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.2062 Xenopus laevis mRNA for Nedd4 protein 79.02(n)    AJ000085.1 
    zebrafish
    (Danio rerio)
    Actinopterygii Dr.261172 Transcribed sequence with moderate similarity to protein more 77.48(n)    CD605190.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Nedd41 , 3 protein ubiquitination
    ubiquitin-protein ligase3
    Nedd41
    46(a)3
    64.64(n)1
    67.3(a)1
      399581  NM_168738.41  NP_730284.21 
    worm
    (Caenorhabditis elegans)
    Secernentea Y92H12A.21 , 3 Y92H12A.21 47(a)3
    57.05(n)1
    56.46(a)1
      I(1543634-1555890)3
    1717191  NM_058464.61  NP_490865.31 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes RSP51 RSP5 55.5(n)
    52.13(a)
      856862   NP_011051.3 
    soybean
    (Glycine max)
    eudicotyledons 467664452   -- 69.22(n)  


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for NEDD4L gene
    HECW22  AREL12  UBR52  WWP22  SMURF22  HECW12  SMURF12  HUWE12  
    NEDD42  WWP12  ITCH2  
    15 SIMAP similar genes for NEDD4L using alignment to 9 protein entries:     NED4L_HUMAN (see all proteins):
    DKFZp564H223    HUWE1    SMURF2    WWP1    NEDD4    UBE3A
    WWC2    HECTD1    HECW1    SMURF1    AREL1    WWP2
    ITCH    HECTD2    HACE1

    NEDD4L for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for NEDD4L (see all 8301)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 18 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs581871251,2
    C--52419621(+) GTGTG-/TGTGTG
            
    TGAGA
    3 -- us2k11Minor allele frequency- TGTGTG:0.00NA 2
    rs1125930001,2
    C--55563215(+) AATGCGTGTGT/-
            
    GTGTG
    3 -- us2k11Minor allele frequency- -:0.50CSA 2
    rs50214191,2
    C--55563232(+) gtgtgA/Tgtgtg 3 -- us2k11Minor allele frequency- T:0.00NA 2
    rs58252551,2
    C--55563238(+) GTGTGA/TGAGAG 3 -- us2k13Minor allele frequency- T:0.20WA CSA 5
    rs1919542541,2
    --55563365(+) GGAGTA/GCAGTG 3 -- us2k10--------
    rs1410998091,2
    --55563394(+) GCAACA/CTCCGC 3 -- us2k10--------
    rs1838684611,2
    --55563558(+) CGCCCA/GCCTCA 3 -- us2k10--------
    rs1874118271,2
    --55563686(+) ATAGTC/TCTCCA 3 -- us2k10--------
    rs111520561,2
    C,F,H--55563735(+) CTGTGG/CACTTG 3 -- us2k15Minor allele frequency- C:0.04NS EA 532
    rs1919480691,2
    --55563968(+) CGGGTC/TACGCG 3 -- us2k10--------

    HapMap Linkage Disequilibrium report for NEDD4L (55711599 - 55961599 bp, first 250kb of NEDD4L)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for NEDD4L (see all 35):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2717155CNV Deletion23290073
    esv2657059CNV Deletion23128226
    esv2138002CNV Deletion18987734
    esv3030CNV Deletion18987735
    esv2717157CNV Deletion23290073
    esv1499259CNV Deletion17803354
    esv2717158CNV Deletion23290073
    esv2673951CNV Deletion23128226
    esv2572802CNV Deletion19546169
    esv2717159CNV Deletion23290073

    Human Gene Mutation Database (HGMD): NEDD4L
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing NEDD4L
    DNA2.0 Custom Variant and Variant Library Synthesis for NEDD4L

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 606384    OMIM disorders: --

    17 diseases for NEDD4L:    
    About MalaCards
    liddle syndrome    essential hypertension    hypertension    gallbladder cancer
    pulmonary function    malignant glioma    diabetic nephropathy    ischemia
    obesity    asthma    cerebritis    sarcoma
    hiv-1    prostate cancer    prostatitis    neuronitis
    malaria

    2 diseases from the University of Copenhagen DISEASES database for NEDD4L:
    Liddle syndrome     Hypertension

    NEDD4L for disorders           About GeneDecksing

    3 Novoseek inferred disease relationships for NEDD4L gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    liddles syndrome 90.6 4 19007435 (1), 18691017 (1), 16477034 (1)
    essential hypertension 51.8 3 16103266 (2), 18293164 (1)
    hypotension orthostatic 30.2 3 16103266 (2)

    Genetic Association Database (GAD): NEDD4L
    Human Genome Epidemiology (HuGE) Navigator: NEDD4L (13 documents)

    Export disorders for NEDD4L gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for NEDD4L gene, integrated from 10 sources (see all 217):
    (articles sorted by number of sources associating them with NEDD4L)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. NEDD4L on human chromosome 18q21 has multiple forms of transcripts and is a homologue of the mouse Nedd4-2 gene. (PubMed id 11840194)1, 2, 9 Chen H.... McInnis M.G. (Eur. J. Hum. Genet. 2001)
    2. Nedd4-2 phosphorylation induces serum and glucocorticoid-regulated kinase (SGK) ubiquitination and degradation. (PubMed id 15576372)1, 2, 9 Zhou R. and Snyder P.M. (J. Biol. Chem. 2005)
    3. cAMP and serum and glucocorticoid-inducible kinase (SGK) regulate the epithelial Na(+) channel through convergent phosphorylation of Nedd4- 2. (PubMed id 15328345)1, 2, 9 Snyder P.M.... Steines J.C. (J. Biol. Chem. 2004)
    4. Nedd4-2 isoforms ubiquitinate individual epithelial sodium channel subunits and reduce surface expression and function of the epithelial sodium channel. (PubMed id 18322022)1, 3, 9 Raikwar N.S. and Thomas C.P. (Am. J. Physiol. Renal Physiol. 2008)
    5. Association of NEDD4L ubiquitin ligase with essential hypertension. (PubMed id 16103266)1, 4, 9 Russo C.J....Baldwin C.T. (Hypertension 2005)
    6. Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel. (PubMed id 11696533)1, 2, 9 Snyder P.M.... Thomas B.C. (J. Biol. Chem. 2002)
    7. Identification of NPC2 protein as interaction molecule with C2 domain of human Nedd4L. (PubMed id 19664597)1, 2, 9 Araki N.... Umemura S. (Biochem. Biophys. Res. Commun. 2009)
    8. A naturally occurring human Nedd4-2 variant displays impaired ENaC regulation in Xenopus laevis oocytes. (PubMed id 15140763)1, 2, 9 Fouladkou F....Staub O. (Am. J. Physiol. 2004)
    9. Two polymorphisms in NEDD4L gene and essential hypertension in Chinese Hans - a population-based case-control study. (PubMed id 18293164)1, 4, 9 Wen H....Wang X. (Clin. Exp. Hypertens. 2008)
    10. 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. (PubMed id 12911626)1, 2, 9 Boehmer C.... Lang F. (J. Neurochem. 2003)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 23327 HGNC: 7728 AceView: NEDD4L Ensembl:ENSG00000049759 euGenes: HUgn23327
    ECgene: NEDD4L Kegg: 23327 H-InvDB: NEDD4L

    (According to HUGE)
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    HUGE: KIAA0439

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for NEDD4L Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for NEDD4L gene:
    Search GeneIP for patents involving NEDD4L

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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