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FLASH GENE
Symbol VPS35 contributors: mct/ - updated : 15-09-2017
HGNC name vacuolar protein sorting 35 homolog (S. cerevisiae)
HGNC id 13487
Corresponding disease
PARK17 Parkinson disease 17
Location 16q11.2      Physical location : 46.693.590 - 46.723.144
Synonym name
  • vacuolar protein sorting 35 (yeast)
  • vesicle protein sorting 35
  • maternal-embryonic 3
  • Synonym symbol(s) FLJ10752, MEM3, FLJ13588, FLJ20388, DKFZp434E1211, DKFZp434P1672, PARK17
    DNA
    TYPE functioning gene
    STRUCTURE 29.56 kb     17 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
    17 - 3298 89 796 - 2000 11112353
    - polyA site 3600 89 796 brain, heart, testis, ovary, small intestine, spleen, skeletal muscle, placenta 2000
    - polyA site 3000 89 796 heart, testis, ovary, small intestine, spleen, skeletal muscle, placenta 2000 11112353
    - - 5500 - - widely 2000 11112353
    maybe cross-hybridization
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES globular Hydrophilic
    STRUCTURE
    motifs/domains
    HOMOLOGY
    interspecies homolog to yeast S.cerevisiae VPS35
    Homologene
    FAMILY
  • VPS35 family
  • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    text cytosolic and membrane associated
    basic FUNCTION
  • multimeric complex forming the core of the retromer coat involved in the retrograde transport of proteins from endosomes to the Golgi network
  • mediates vesicle transport between the mitochondria and peroxisomes (
  • role of VPS35 and NBEA in the retrieval and post-Golgi trafficking of synaptic GLYRs and possibly other neurotransmitter receptors
  • potential roles of VPS35 and NBEA in inhibitory receptor trafficking
  • major component of the retromer complex, that is important for endosome-to-Golgi retrieval of membrane proteins
  • essential role for VPS35 in suppression of Alzheimer disease neuropathology and in inhibition of BACE1 activation and Abeta production by promoting BACE1 endosome-to-Golgi retrieval
  • VPS29 and VPS35 form a biologically stable sub-complex
  • is involved in retrograde transport of proteins from endosomes to trans-Golgi network
  • retromer, including VPS35, VPS26A, and VPS29, is a protein complex responsible for recycling proteins within the endolysosomal pathway
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    PATHWAY
    metabolism
    signaling
    a component
  • cargo-selective VPS35/VPS29/VPS26A complex is catalysed by RAB7A and inhibited by the Rab-GAP protein, TBC1D5
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to the coiled-coil containing domain of SNX1
  • VPS26A, VPS29
  • displayed binding to gephyrin
  • GLRB binds the trafficking proteins VPS35 and Neurobeachin (NBEA)
  • endosomal localization of FAM21C is VPS35 dependent and relies on multivalency of FAM21C repeat elements
  • MAGEL2 was identified to interact with VPS35 and VPS26A two components of the endosomal retromer complex
  • VPS35 recruits MAGEL2-TRIM27 to retromer-positive endosomes by binding to MAGEL2
  • suppression of VPS35 led to mistrafficking of the melanogenic enzymes, tyrosinase and TYRP1, establishing that retromer acts in concert with ANKRD27 in this trafficking pathway
  • interactions between VPS35, EIF4G1, and SNCA
  • VPS35 works as the central subunit of retromer to recognize the cargos and binds with VPS29 and VPS26A via distinct domains
  • VPS35 has a role in the lysosomal degradation of parkin substrate AIMP2, of which accumulation leads to poly(ADP-ribose) polymerase-1 (PARP1)-dependent cell death
  • KLF7/VPS35 axis contributes to hepatocellular carcinoma progression through CCDC85C-activated CTNNB1 pathway
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) PARK17
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    VPS35 haploinsufficiencyincreases Alzheimer disease neuropathology
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS