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FLASH GENE
Symbol VAV2 contributors: mct - updated : 11-01-2017
HGNC name vav 2 guanine nucleotide exchange factor
HGNC id 12658
Location 9q34.2      Physical location : 136.627.016 - 136.857.446
Synonym name
  • vav 2 oncogene
  • guanine nucleotide exchange factor VAV2
  • oncogene VAV2
    • Synonym symbol(s) VAV-2
    DNA
    TYPE functioning gene
    STRUCTURE 230.43 kb     30 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    regionally located duplicated exons or pseudogene(s), in the same region
    RNA
    TRANSCRIPTS type messenger
    text alternative splicing isoforms leading to isoforms neuronal specific (exon 6 and 16), also alternative splicing of exon 28
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    27 - 4748 - 839 - 2017 28270555
  • isoform 2
    • 30 - 4865 - 878 - 2017 28270555
  • isoform 1
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunethymus    
    Respiratoryrespiratory tractlarynx   
    Urinarybladder    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one CH (calponin-homology) domain
  • one DH (DBL-homology) domain
  • one PH domain
  • an atypical C1 domain, which possesses close structural homology to the typical C1 domains of protein kinase C but which fails to bind the second messenger diacylglycerol or the potent analogs, the phorbol esters
  • one phorbol-ester/DAG-type zinc finger
  • one SH2 domain
  • two SH3 domains
    • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to rattus Vav2 (95.0pc)
    homolog to murine Vav2 (95.9pc)
    intraspecies homolog to VAV proto-oncogene 2
    Homologene
    FAMILY
  • DBL family of GDP-GTP exchange factors, VAV family proto-oncogenes
    • CATEGORY protooncogene , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    text integral to membrane
    basic FUNCTION
  • GDP-GTP exchange factor for small Ras-related GTPases like ARHB, ARHG, RAC1
  • playing an important role in angiogenesis
  • regulator of Ephrin/Ephrin receptor endocytosis and determining repulsive signaling during axon guidance (Cowan 2005)
  • regulating VEGF-induced RAC1 activation in endothelial cells (Garrett 2007)
  • VAV2 expression delays EGFR internalization and degradation and enhances its phosphorylation (Thalappilly 2010)
  • can regulate growth factors receptor signaling by slowing receptor internalization and degradation (Thalappilly 2010)
  • VAV2/VAV3 guanine nucleotide exchange factors play a critical role in host-mediated tumor progression and angiogenesis, particularly in tumor endothelium
  • regulates processes including cell migration, neuronal development and phagocytosis through interactions with different proteins
  • coordination between GIT2/VAV2 signaling and GIT2/ARHGEF7 signaling during cell migration
  • VAV2 and VAV3 favor skin tumor initiation and promotion by engaging extracellular signaling loops
  • VAV2 is implicated in glucose-induced RAC1 activation, actin remodelling and glucose-stimulated insulin secretion (GSIS) in pancreatic beta cells
  • might promote invasion and metastasis of gastric cancer by regulating some invasion and metastasis-related genes
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • ions Zn2+
    • protein
  • interacting with EPHA2
  • interaction with FLNB, a scaffolding protein connecting also KDR and RAC1 proteins for endothelial cell motility (Del Valle-Pérez 2010)
  • SSX2IP mediates the activation of RAC1 through VAV2
  • CENTD3 is an interaction partner for VAV2
  • GIT2 is required for VAV2 activation downstream of integrin engagement and epidermal growth factor (EGF) stimulation
  • interaction between TXNIP and VAV2
  • guanine nucleotide exchange factor VAV2 gene is a direct target for CUX1
    • cell & other
    REGULATION
    Other activity on EGFR stability is modulated by the interaction between VAV2 and two endosom-associated proteins (Thalappilly 2010)
    recruitment by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
  • to obesity, and HTA
    • Variant & Polymorphism other
  • carrier of the T allele in VAV2 rs602990 polymorphism is associated with an increased risk of obesity, reduced levels of ankle-brachial index and diastolic blood pressure and reduced retinal artery caliber
    • Candidate gene
  • EGFR/VAV2 signaling is involved in cell invasion in head and neck squamous cell carcinoma (Patel 2007)
    • Marker
    Therapy target
    ANIMAL & CELL MODELS