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FLASH GENE
Symbol ZFYVE9 contributors: mct/npt/pgu - updated : 15-02-2017
HGNC name zinc finger, FYVE domain containing 9
HGNC id 6775
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a FYVE-type zinc finger
  • a SMAD-binding domain, which interacts with SMAD2 and SMAD3, a SSID (SARA- and SMAD-interacting domain)
  • a ERBID (ERBIN-binding domain
  • a C-terminal, TbetaR complex-interacting region
  • conjugated MetalloP
    HOMOLOGY
    interspecies homolog to murine Zfyve9
    Homologene
    FAMILY
    CATEGORY regulatory , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    basic FUNCTION
  • involved in recruiting unphosphorylated SMAD2/SMAD3 proteins to the TGF beta receptor by controlling SMAD subcellular localization and by interacting with the TGFB receptor complex
  • playing an important functional role downstream of Rab5-regulated endosomal trafficking
  • facilitates TGFbeta and activin/nodal signaling by recruiting and presenting Smad2/3 to the receptor complex
  • ZFYVE9-regulated vesicular targeting underlies formation of the light-sensing organelle in mammalian rods
  • playing a role in presenting R-Smads to the receptor for phosphorylation
  • early endosomal protein, playing a key role in TGFB signalling
  • is dispensable for functional TGFB-mediated signaling
  • regulator of epithelial cell phenotype, with reduced expression during TGFB1-mediated epithelial-to-mesenchymal transition
  • RNF11 and ZFYVE9 participate structurally and functionally in the ESCRT-dependent lysosomal degradation of receptors
  • is an early endosomal protein facilitating TGFB1 signaling cascade
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    TGF beta signaling pathway
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, other,
  • phosphatidyl inositol-3-phosphate
  • Zn2+
  • protein
  • binding to SMAD2, SMAD3
  • TGF-beta receptor
  • interacting with LRP12
  • competes with SMAD2/3 for binding to ERBB2IP
  • although TGFB1 can induce epithelial-to-mesenchymal transition through reduction in ZFYVE9 expression, ZFYVE9 is also basally regulated by its interaction with PI3K
  • is a ZFYVE9-interacting protein residing on early and late endosomes, as well as the fast recycling compartment
  • ZFYVE9 interact with RNF11 (RING finger protein 11) and members of the ESCRT-0 (endosomal sorting complex required for transport) complex functionally participating in the degradation of EGFR
  • ZFYVE9, ZFYVE16 recruit the tumor supressor PTPN23, a master regulator of endosomal sorting and ESCRT-dependent receptor downregulation
  • regulates the TGFB1 signaling pathway by recruiting SMAD2/3 and accelerating their phosphorylation, thereby altering their susceptibility to TGFB1-mediated T cell suppression
  • cell & other
  • membrane
  • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    leads to a concomitant loss of SMAD2 expression, suggesting that its down-regulation might contribute to EMT (epithelial-to-mesenchymal transition) in part through indirect effects on SNAI1
    constitutional     --over  
    upregulation of ZFYVE9 and SMAD3 in cortex neurons might be involved in the development of intractable temporal lobe epilepsy
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS