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FLASH GENE
Symbol VAPA contributors: mct/npt - updated : 24-03-2016
HGNC name VAMP (vesicle-associated membrane protein)-associated protein A, 33kDa
HGNC id 12648
Location 18p11.22      Physical location : 9.913.954 - 9.960.017
Synonym name 33 kDa Vamp-associated protein
Synonym symbol(s) VAP33, VAP-A, VAP-33, MGC3745, hVAP-33
DNA
TYPE functioning gene
STRUCTURE 46.06 kb     7 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
PTPRM 18p11.2 protein tyrosine phosphatase, receptor type, M FLJ11996 18p11.22 hypothetical protein FLJ11996 LOC125831 18p11.22 similar to constitutive photomorphogenic protein LOC390829 18 similar to Aldose reductase (AR) (Aldehyde reductase) LOC201475 18p11.22 similar to Rab12 protein KIAA0802 18p11.21 similar to Rab12 protein LOC390830 18 similar to ribosomal protein S4, X-linked NDUFV2 18p11.22-p11.21 NADH dehydrogenase (ubiquinone) flavoprotein 2, 24kDa KIAA0874 TWSG1 18p11.3-p11.2 twisted gastrulation homolog 1 (Drosophila) RALBP1 18p11.3 ralA binding protein 1 PPP4R1 18p11.22 protein phosphatase 4, regulatory subunit 1 LOC125242 18p11.22 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) RAB31 18p11.31-p11.22 RAB31, member RAS oncogene family TXNDC2 18p11.31-p11.2 thioredoxin domain containing 2 (spermatozoa) VAPA 18p11.21 VAMP (vesicle-associated membrane protein)-associated protein A, 33kDa APCDD1 18p11.21 adenomatosis polyposis coli down-regulated 1 NAPG 18p11.21 N-ethylmaleimide-sensitive factor attachment protein, gamma LOC390831 18 similar to Phosphomannomutase 2 (PMM 2) FLJ23403 18p11.21 hypothetical protein FLJ23403 LOC342843 18p11.21 similar to hypothetical protein LOC284221 18p11.21 hypothetical protein LOC284221 FLJ34907 18p11.21 hypothetical protein FLJ34907 LOC388463 18 similar to acyl-malonyl condensing enzyme LOC388464 18 hypothetical gene supported by D86974 GNAL 18p11.31 guanine nucleotide binding protein (G protein), alpha activating activity polypeptide, olfactory type CHMP1.5 18p11.21 CHMP1.5 protein MPPE1 18p11.21-p11.1 CHMP1.5 protein IMPA2 18p11.22-p11.21 inositol(myo)-1(or 4)-monophosphatase 2 LOC284226 18p11.21 similar to Kinesin-like protein KIF1C LOC284227 18p11.21 similar to single stranded DNA binding protein 4 LOC162835 18p11.21 similar to G protein-coupled receptor 124 LOC342850 18p11.21 similar to KIAA1074 protein LOC390832 18 similar to Phosphomannomutase 2 (PMM 2) CIDEA 18p11.21 cell death-inducing DFFA-like effector a MGC4083 18p11.21 tubulin beta MGC4083
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
7 - 6994 - 294 - 2004 15016871
6 - 6859 27 249 - 2004 15016871
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrineneuroendocrinepituitary  highly
Nervousnerve   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivebone  highly
cell lineage
cell lines
fluid/secretion
at STAGE
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) ( )
  • an intermediate domain
  • the central domain is amphipathic and predicted to form a coiled-coil structure
  • a transmembrane domain (TMD)
  • eight potential phosphorylation sites
  • the C-terminal 20 amino acids hydrophobic and acting as an intracellular membrane anchor
  • secondary structure an alpha-helical coiled-coil domain
    HOMOLOGY
    interspecies homolog to murine Vapa
    homolog to yeast VAP Scs2p
    intraspecies homolog to VAPB (60 p100)
    Homologene
    FAMILY
    CATEGORY secretory , transport
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,cytoplasm,cytoskeleton,microtubule
    basic FUNCTION
  • playing a role in vesicle trafficking
  • 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
  • playing an important role in the replication of the hepatitis C virus genome
  • is an integral membrane protein that plays an important role in membrane trafficking, endoplasmic reticulum homeostasis, and the stress-signaling system
  • VAPA with an altered proline distribution can phenocopy amyotrophic lateral sclerosis-associated VAPB
  • 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
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS exocytosis transport , endocytosis transport
    text vesicle trafficking
    PATHWAY
    metabolism
    signaling
    a component
  • dimerizing with VAPB
  • chaperone complex comprising HSP90AA1 and TTC1 that is recruited to the membrane protein VAPA, and regulates intracellular vesicle transport
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • VAMP1, VAMP2
  • interacting with VAPB and ATF6
  • interact directly with components of ER homeostatic and stress signalling 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)
  • GLTP interacting with VAPA
  • SLC26A5 appears to modify the expression of VAPA protein in outer hair cells (OHC), and VAPA could be involved in SLC26A5 transportation inside OHCs and may facilitate the targeting of this abundant OHC protein to the plasma membrane
  • partners of CLN8 are VAPA, C14orf1/hERG28, STX8, GABARAPL2, BNIP3 and BNIP3L proteins and are associated with biologically relevant processes such as synthesis and transport of lipids, vesicular/membrane trafficking, autophagy/mitophagy and apoptosis
  • 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
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    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 (Teuling 2007)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS