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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
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