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FLASH GENE
Symbol VAPB contributors: mct/npt/pgu - updated : 05-01-2017
HGNC name VAMP (vesicle-associated membrane protein)-associated protein B and C
HGNC id 12649
Corresponding disease
ALS8 familial amyotrophic lateral sclerosis 8
SMAPA spinal muscular atrophy proximal, adult type
Location 20q13.32      Physical location : 56.964.244 - 57.021.961
Synonym name
  • VAMP-associated protein B
  • VAMP-associated protein C
  • VAMP-associated 33 kDa protein
  • Synonym symbol(s) VAPC, VAP-B, VAMP-B/VAMP-C, VAP-B/VAP-C
    DNA
    TYPE functioning gene
    STRUCTURE 61.98 kb     6 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
    6 - 3689 27.2 243 - 2008 18555774
    3 splicing 1833 11.1 99 - 2010 20227395
  • truncated
  • lacking exons 35,
  • plays an important role in the propagation of hepatitis C virus
  • 3 - 7587 - 99 - 2010 20227395
    VAPB-2
    5 - - - - - 2010 20227395
    lacking exon 3
    4 - - - - - 2010 20227395
    Lacking exons 3-4
    4 - - - - - 2010 20227395
    Lacking exons 4-5
    3 - - - - - 2010 20227395
    Lacking exons 2-3-4
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal gland   highly
    Nervousspinal cord   predominantly
    Reproductivefemale systemovary  highly
     male systemprostate   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal predominantly
    Nervouscentral   
    cell lineage
    cell lines lymphoma
    fluid/secretion
    at STAGE
    physiological period embryo
    Text
  • expressed early in development in pluripotent stem cells
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal MSP (major sperm protein) domain, containing an FFAT-motif binding site (correct distribution of the proline residues would be critical for the correct fold of the MSP domain which is required for recognition of the FFAT motif of its partner), and a VAP consensus sequence (VCS) (
  • a transmembrane domain
  • an amphipathic helical structure
  • a central coiled-coil protein- protein interaction motif
  • a hydrophobic C-terminus acting as a membrane-anchor
  • (endoplasmatic reticulum membrane anchored C-terminal domain)
    mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies homolog to Drosophila DVAP-33A
    homolog to C. elegans VPR-1
    intraspecies homolog to VAPA (60 p100)
    Homologene
    FAMILY
    CATEGORY secretory , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,lysosome
    intracellular,cytoplasm,cytosolic,vesicle
    text
  • type IV membrane protein
  • is an integral endoplasmic reticulum (ER) protein whose amino-terminus projects into the cytosol
  • is an integral membrane protein localized to the endoplasmic reticulum (ER)
  • basic FUNCTION
  • may be involved in vesicle trafficking
  • playing a a possible role in synaptic homeostasis, by coordinating structural remodeling and post-synaptic sensitivity to neurotransmitter to ensure synaptic efficacy
  • may act as docking sites for cytoplasmic factors to interact with the ER
  • may have structural and regulatory functions based on interactions of the MSP domain
  • plays an important role in the replication of the hepatitis C virus genome
  • can bind to lipid-binding proteins
  • VAPB function is required for transport to the nuclear envelope
  • role of VAPB in tumor promotion in human breast cancer
  • both VAPB and YIF1A are important for ER-to-Golgi transport and missorting of YIF1A may contribute to VAPB-associated motor neuron disease
  • VAPB and the related protein VAPA form homo- and heterodimers that are anchored in the endoplasmic reticulum membrane and can interact with protein partners carrying a FFAT motif
  • is a tail-anchored protein in the endoplasmic reticulum (ER)
  • functions as an adaptor protein to recruit target proteins to the ER and execute various cellular functions, lipid transport, membrane traffic, ER stress
  • binding of VAPB to RAB3GAP1 is implicated in the regulation of nuclear envelope formation through ERGIC
  • VAPB and RMND3 localise and form contacts at synapses, and stimulating neuronal activity increases ER-mitochondria contacts and the VAPB-RMND3 interaction
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimer with VAPA
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interact with VAMP1 and VAMP2
  • interact directly with components of ER homeostatic and stress signaling systems and may therefore be parts of a previously unidentified regulatory pathway (mis-function of such regulatory systems may contribute to the pathological mechanisms of degenerative motor neuron disease)
  • interact with lipid-binding proteins carrying a short motif containing two phenylalanines in an acidic tract (FFAT motif) and targets them to the cytosolic surface of the endoplasmic reticulum (ER)
  • VAPB interacts with the outer mitochondrial membrane protein, protein tyrosine phosphatase-interacting protein 51 (RMDN3)
  • VAPB strongly affects the distribution of YIF1A and is required for intracellular membrane trafficking into dendrites and normal dendritic morphology
  • VAPB/ALS8 interacts with FFAT-like proteins including the VCP cofactor FAF1 and the ASNA1 ATPase
  • directly binds to RAB3 GTPase activating protein 1 (RAB3GAP1), the catalytic subunit of RAB3GAP, through the two phenylalanines (FF) in an acidic tract (FFAT)-like motif of RAB3GAP1
  • VAPB-RMDN3 tethers regulate macroautophagy/autophagy
  • VAPA, VAPB are endoplasmic reticulum (ER)-resident integral membrane protein that controls a nonvesicular mode of ceramide and cholesterol transfer from the ER to the Golgi complex by interacting with COL4A3BP and oxysterol-binding protein (OSBP), respectively
  • the mechanism by which the VAPB-RMDN3 tethers regulate autophagy involves their role in mediating delivery of Ca2+ to mitochondria from ER stores
  • VAPB and RMND3 localise and form contacts at synapses, and stimulating neuronal activity increases ER-mitochondria contacts and the VAPB-RMND3 interaction
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) ALS8 , SMAPA
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    reduced levels of VAP family proteins result in decreased ER anchoring of lipid-binding proteins and cause motor neuron degeneration
    constitutional     --low  
    reduced levels of VAPB might be an initial defect leading to ALS8 pathogenesis
    constitutional     --low  
    loss of either VAPB or RMDN3 perturbs uptake of Ca(2+) by mitochondria following release from ER stores
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerative 
    optimal levels of VAPB may play a central role in the pathogenesis of ALS8, in agreement with the observed reduction of VAPB in sporadic ALS
    ANIMAL & CELL MODELS