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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

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)
About This Section

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, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

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 essential hypertension, and liddle syndrome, and among its related super-pathways are Antigen processing: Ubiquitination & Proteasome degradation and HIV Life Cycle. GO annotations related to this gene include ubiquitin-protein ligase activity and sodium channel inhibitor activity. An important paralog of this gene is HERC1.

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 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000018.9  NT_025028.14  NC_018929.2  
Regulatory elements:
   SABiosciences 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 SABiosciences Chromatin IP Primers for NEDD4L

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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 UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB 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., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

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
Subcellular location: Cytoplasm. Note=May be recruited to exosomes by NDFIP1
Sequence caution: Sequence=BAA23711.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
Sequence=BAA23711.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact;
6/7 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:

  • UniProtKB: Phosphorylated by SGK1 or PKA; which impairs interaction with SCNN. Interaction with YWHAH inhibits
    dephosphorylation
  • UniProtKB: Auto-ubiquitinated
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_Q96PU5

  • 4/11 DME Specific Peptides for NEDD4L (Q96PU5) (see all 11)
     PLPPGWE  TQWEDPR  NPYYGLF  RLLQFVTG 

    NEDD4L Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    NEDD4L Protein Expression
    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
    Human Recombinant Protein Products for NEDD4L: 
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    Novus Biologicals NEDD4L Lysate
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    Cloud-Clone Corp. Proteins for NEDD4L 

    Gene Ontology (GO): 5/6 cellular component terms (GO ID links to tree view) (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



    NEDD4L Antibody Products: 
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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    5/7 InterPro protein domains (see all 7):
     IPR024928 E3_ub_ligase_SMURF1
     IPR018029 C2_membr_targeting
     IPR000569 HECT
     IPR008973 C2_Ca/lipid-bd_dom_CaLB
     IPR001202 WW_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,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    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): 5/7 molecular function terms (GO ID links to tree view) (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 

         10 MGI mutant phenotypes (inferred from 4 alleles(MGI details for Nedd4l):
     behavior/neurological  cardiovascular system  digestive/alimentary  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-out Nedd4ltm1.2Blyg for NEDD4L

       inGenious Targeting Laboratory - Custom generated mouse model solutions for NEDD4L 
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       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for NEDD4L 
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    miRNA
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    8/145 QIAGEN miScript miRNA 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
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NEDD4L


    (Pathways according to EMD Millipore, 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 SABiosciences, 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 Oct 2013 via Entrez Gene).
    About This Section

    SuperPaths for NEDD4L About   (see all 18)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Antigen processing: Ubiquitination & Proteasome degradation
    Antigen processing: Ubiquitination & Proteasome degradation0.83
    Ubiquitin mediated proteolysis0.36
    Class I MHC mediated antigen processing & presentation0.83
    2HIV Life Cycle
    HIV Life Cycle0.92
    HIV Infection0.61
    Late Phase of HIV Life Cycle0.92
    3Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
    Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer0.63
    Downregulation of SMAD2/3:SMAD4 transcriptional activity0.56
    Signaling by TGF-beta Receptor Complex0.61
    4TGF-beta receptor signaling activates SMADs
    Downregulation of TGF-beta receptor signaling0.90
    TGF-beta receptor signaling activates SMADs0.90
    5Immune System
    Immune System0.56
    Adaptive Immune System0.56

    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
        TGF-beta receptor signaling
    Neurotrophic factor-mediated Trk receptor signaling

    5/20        Reactome Pathways for NEDD4L (see all 20)
        TGF-beta receptor signaling activates SMADs
    Late Phase of HIV Life Cycle
    Stimuli-sensing channels
    Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
    Budding and maturation of HIV virion

    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

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for NEDD4L

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

    5/208 Interacting proteins for NEDD4L (Q96PU52, 3 ENSP000003831994) via UniProtKB, MINT, STRING, and/or I2D (see all 208)

    InteractantInteraction Details
    GeneCardExternal ID(s)
    LAPTM5Q135712, 3, ENSP000002945074MINT-62184 I2D: score=3 STRING: ENSP00000294507
    RNF11Q9Y3C52, 3, ENSP000002427194MINT-60888 I2D: score=3 STRING: ENSP00000242719
    SCNN1BP511682, 3, ENSP000003457514MINT-8290136 I2D: score=3 STRING: ENSP00000345751
    SMAD2Q157962, 3, ENSP000002621604MINT-61615 I2D: score=2 STRING: ENSP00000262160
    MED28Q9H2042, 3, ENSP000002373804MINT-7041937 I2D: score=1 STRING: ENSP00000237380
    About this table

    Gene Ontology (GO): 5/40 biological process terms (GO ID links to tree view) (see all 40):    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-dependent 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 HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    NEDD4L for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
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    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  

    Search CenterWatch for drugs/clinical trials and news about NEDD4L / NED4L

    (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,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
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    About This Section

    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
    18/37 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
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    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 

    24/39 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 

    24/284 AceView cDNA sequences (see all 284):

    BQ000605 H06012 AF385931 BM674388 CF528594 CB152874 BX486688 BQ220579 
    BG496356 AA775172 AW613877 AI377528 BM714998 BX282031 AY312514 BC019345 
    AK096812 AK091189 BM931700 AY243319 AW195564 AK130420 CD655521 BP340588 

    GeneLoc Exon Structure

    5/20 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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    NEDD4L expression in normal human tissues (normalized intensities)      NEDD4L embryonic expression: see
    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 
     5/13 selected tissues (see all 13) fully expand
     
     Gut Tube (Gastrointestinal Tract)    fully expand to see all 3 entries
             Hindgut
     
     Brain (Nervous System)    fully expand to see all 2 entries
             superior temporal gyrus   
     
     Colon (Gastrointestinal Tract)
             colonic mucosal (ibs)   
     
     Nose (Sensory Organs)
             sensory organ/nose/nasal cavity   
     
     Kidney (Urinary System)
             Metanephros

    See NEDD4L Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for NEDD4L

    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

        SABiosciences Expression via Pathway-Focused PCR Array including NEDD4L: 
              Ubiquitin Ligases in human mouse rat

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    (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)
    About This Section

    This gene was present in the common ancestor of eukaryotes.

    Orthologs for NEDD4L gene from 8/22 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 82.36(n)
    94.05(a)
      374119  XM_424462.3  XP_424462.3 
    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 Nedd43 protein ubiquitination
    ubiquitin-protein ligase
    46(a)     --
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes RSP51 Rsp5p 51.97(n)
    46.6(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)
    About This Section
    Paralogs for NEDD4L gene
    HERC12  HECW22  HERC22  HECTD32  WWP22  HECW12  SMURF22  SMURF12  
    HUWE12  NEDD42  WWP12  ITCH2  
    16 SIMAP similar genes for NEDD4L using alignment to 9 protein entries:     NED4L_HUMAN (see all proteins):
    DKFZp564H223    HUWE1    SMURF2    UBE3A    WWP1    NEDD4
    WWC2    HECTD1    HECW1    SMURF1    UBE3B    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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/8301 SNPs in NEDD4L are shown (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
    ----------
    VAR_0234164
    ----see VAR_0234162 S R mis40--------
    VAR_0234154
    ----see VAR_0234152 P L mis40--------
    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--------

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

    Structural Variations
         Database of Genomic Variants (DGV) 10/35 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
    SABiosciences Cancer Mutation PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 606384    OMIM disorders: --

    12 diseases for NEDD4L:    About MalaCards
    essential hypertension    liddle syndrome    hypertension    gallbladder cancer
    malignant glioma    ischemia    obesity    sarcoma
    cerebritis    prostate cancer    prostatitis    neuronitis

    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)
    About This Section

    PubMed articles for NEDD4L gene, integrated from 9 sources (see all 211):
    (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. (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. (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. (2004)
    4. Nedd4-2 isoforms ubiquitinate individual epithelial s odium channel subunits and reduce surface expression and function of the epithe lial sodium channel. (PubMed id 18322022)1, 3, 9 Raikwar N.S. and Thomas C.P. (2008)
    5. Association of NEDD4L ubiquitin ligase with essential hypertension. (PubMed id 16103266)1, 4, 9 Russo C.J....Baldwin C.T. (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. (2002)
    7. Identification of NPC2 protein as interaction molecul e with C2 domain of human Nedd4L. (PubMed id 19664597)1, 2, 9 Araki N....Umemura S. (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. (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. (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. (2003)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     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)
    About This Section
    Entrez Gene: 23327 HGNC: 7728 AceView: NEDD4L Ensembl:ENSG00000049759 euGenes: HUgn23327
    ECgene: NEDD4L Kegg: 23327 H-InvDB: NEDD4L

    (According to HUGE)
    About This Section
    HUGE: KIAA0439

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