Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol ZFYVE9 contributors: mct/npt/pgu - updated : 15-02-2017
HGNC name zinc finger, FYVE domain containing 9
HGNC id 6775
Location 1p32.3      Physical location : 52.608.045 - 52.812.357
Synonym name
  • Smad anchor for receptor activation
  • MAD, mothers against decapentaplegic homolog (Drosophila) interacting protein, receptor activation anchor
  • Synonym symbol(s) SMADIP, SARA, MADHIP, NSP
    DNA
    TYPE functioning gene
    STRUCTURE 204.31 kb     18 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 4753 150 1366 ubiquitous 2007 17356069
  • variant 1 lacks an in frame exon compared to variant 3 (18 exons)
  • isoform 1 lacks an internal segment compared to isoform 3
  • 5 - 2625 83 762 ubiquitous 2007 17356069
    lacks several exons in the coding region compared to variant 1 and variant 3 (five exons)
    18 - 4930 156 1425 ubiquitous 2007 17356069
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivefemale systemuteruscervix highly
     male systemprostate  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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