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FLASH GENE
Symbol NDFIP1 contributors: mct/ - updated : 21-09-2018
HGNC name Nedd4 family interacting protein 1
HGNC id 17592
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 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