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FLASH GENE
Symbol NDFIP1 contributors: mct/ - updated : 21-09-2018
HGNC name Nedd4 family interacting protein 1
HGNC id 17592
Location 5q31.3      Physical location : 141.488.323 - 141.534.006
Synonym name
  • Nedd4 WW domain-binding protein 5
  • putative NF-kappa-B-activating protein 164
  • breast cancer-associated protein SGA-1M
    • Synonym symbol(s) N4WBP5, MGC10924
    DNA
    TYPE functioning gene
    STRUCTURE 45.69 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 3599 24.7 221 - 2015 26363003
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
    Endocrineparathyroid   predominantly
    Nervousbrainhindbraincerebellum highly
     braindiencephalonthalamus highly
     brainforebraincerebral cortex   Homo sapiens
    Reproductivemale systemtestis   
    Respiratorylung    
    Urinarykidney    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    cell lineage
    cell lines embryonic kidney cell line HEK 293T
    fluid/secretion
    at STAGE
    physiological period fetal
    Text brain, kidney, lung
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three transmembrane domains
  • two PPXY motifs
  • PY motifs by which they bind NEDD4 family members and bring them close to target proteins
    • HOMOLOGY
    interspecies homolog to murine Ndfip1
    Homologene
    FAMILY
    CATEGORY adaptor , transport carrier
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,nuclear envelope
    text
  • golgi-associated protein
  • is primarily localized in the Golgi apparatus where it recruits NEDD4L to mediate the degradation of mature KCNH2 during channel trafficking to the plasma membrane
    • basic FUNCTION
  • may act as an adaptor for NEDD4-like proteins and their putative targets to control ubiquitin-dependent protein sorting and trafficking
  • a role in positive regulation of I-kappa B kinase/NF-kappa B cascade
  • may be involved in the structural maintenance of the Golgi complex
  • expression of NDFIP1 results in recruitment of NEDD4, NEDD4L, ITCH proteins into exosomes (important role for protein trafficking via exosomes)
  • may play a major role in mediating exosomal transfer of other ubiquitinated proteins
  • exosomal transport of NDFIP1 and its associated cargo proteins would provide an additional and rapid route for removal of unwanted proteins to enhance neuronal survival
  • regulating SLC11A2, and playing a critical role for in regulating metal transport in neurons
  • promote ubiquitination both of Jun proteins, which have a PY motif, and of endophilin, which does not
  • related endosomal membrane proteins that bind to and activate members of the NEDD4 family of E3 ubiquitin ligases
  • appears to be a key regulator of the Nedd4-like Itch protein in T cells, acting to dampen signaling from the T-cell receptor
  • is an adaptor and activator for NEDD4-family ubiquitin ligases for increasing substrate specificity
  • promotes death of pancreatic beta cells
  • NDFIP1/NDFIP2 regulate the cross talk between the T-cell receptor and cytokine signalling pathways to limit inappropriate T-cell responses
  • NDFIP1 restricts production of the proinflammatory cytokines in Th17 cells
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • important component of the signaling machinery, with the ability to modulate the relative activities of different pathways emanating from a single growth factor
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds NEDD4 WW domains (positive roles of NDFIP1/NEDD4 in improving neuronal survival during brain injury)
  • can interact with WW domains of a number of NEDD4 family members
  • activate the catalytic activity of ITCH and of several other HECT ligases by binding to them
  • interacting with SLC11A2 (interacts with 2 WW domain-interacting proteins, NDFIP1 and NDFIP2)
  • physically and functionally associated with multiple components of the EGF signaling cascade, and their levels modulate the relative output of different signaling pathways
  • NDFIP1 is a critical mediator of SLC11A2 regulation particularly under iron restricted conditions
  • is an adaptor for the E3 ubiquitin ligase ITCH
  • PTEN secretion in exosomes required NDFIP1, an adaptor protein for members of the NEDD4 family of E3 ubiquitin ligases
  • enforces a requirement for CD28 costimulation by limiting IL2 production
  • nuclear trafficking of PTEN required both RAB5A as well as the E3 ligase adaptor protein NDFIP1
  • NDFIP1 acts as an adaptor for UBE2L3 and ITCH
  • NDFIP1 is a sensor protein during cell injury and NDFIP1 up-regulation as a cue for BRAT1 ubiquitination by Nedd4 E3 ligases, followed by nuclear translocation of BRAT1
  • NDFIP1 is primarily localized in the Golgi apparatus where it recruits NEDD4L to mediate the degradation of mature KCNH2 proteins during channel trafficking to the plasma membrane
  • important negative regulatory function for NEDD4L and NDFIP1 in IgE-dependent mast cell activity
  • NDFIP1 mediates the ubiquitination of NTRK2, resulting in receptor trafficking predominantly on RAB7A containing late endosomes, highlighting a pathway for NTRK2 degradation at the lysosome
    • cell & other
    REGULATION
    Other a potential target for ubiquitination by the Nedd4 family of proteins
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    with NEDD4 proteins are up-regulated in stressed neurons during brain injury
    constitutional     --over  
    in cortical neurons following traumatic brain injury, and this over-expression is protective against neuronal apoptosis
    constitutional     --over  
    in the substantia nigra of Parkinsonian brains is associated with elevated iron levels
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mice lacking Ndfip1 have increased numbers of Th17 cells, and this increase is cell intrinsic
  • Th2 inflammation, such as that observed in Ndfip1(-/-) mice, can increase Th17 differentiation by recruiting Il6-producing eosinophils into secondary lymphoid organs and tissues