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FLASH GENE
Symbol GAS6 contributors: mct/npt - updated : 25-01-2016
HGNC name growth arrest-specific 6
HGNC id 4168
Location 13q34      Physical location : 114.523.523 - 114.567.046
Synonym name
  • AXL stimulatory factor
  • AXL receptor tyrosine kinase ligand
    • Synonym symbol(s) AXLLG, AXSF, FLJ34709, DKFZp666G247, GAS-6
    DNA
    TYPE functioning gene
    STRUCTURE 43.52 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   HRE
    text structure promoter contain an ERE (estrogen response element) interacting with ESR1
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 2521 - 678 - 2007 17174935
    9 - 2188 - 405 - 2007 17174935
    7 - 2523 - 379 - 2007 17174935
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
    Nervousbrain    
     nerve   highly
     nervecranial nerve  highly
    Reproductivefemale systemuterus  highly
    Respiratorylung    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte Homo sapiens
    Blood/Hematopoieticplatelet
    Cardiovascularendothelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four EGF-like domains and gamma carboxylglutamic residues (GLA domain)
  • two laminin A/neurexin/sex hormone-binding globulin repeats (LNS)
  • one GAS specific domain
  • isoforms Precursor proteolytically processed in two secreted fragments, a 30 kDa N terminal and a 50 kDa C terminal protein
    HOMOLOGY
    interspecies homolog to murine Gas6
    intraspecies paralog to PROS1
    Homologene
    FAMILY
  • vitamin K-dependent family of protein
    • CATEGORY regulatory , secretory , signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus
    basic FUNCTION
  • vitamine-K dependent protein involved in the stimulation of cell proliferation, cell growth and survival, cell adhesion and migration
  • estrogen target gene in mammary epithelial cells
  • may be one of the factors involved in the estrogen-stimulated ductal growth of mammary glands
  • GAS6/AXL-mediated signaling regulates dendritic cell activities, and identifies GAS6/AXL as a new dendritic cell chemotaxis pathway (Scutera 2009)
  • GAS6 synthesis is likely to be a regulatory mechanism during systemic inflammation
  • is an important regulator of both CNS demyelination and remyelination
  • Vitamin K-dependent protein GAS6 playing a role in vascular smooth muscle cell (VSMC) survival and migration, as well as in endothelium and leukocyte activation, and that could therefore be involved in atherosclerosis
  • acts as a protective factor, in part by reducing the pro-inflammatory phenotype of VSMC
  • implicated in both anti-inflammatory response as well as platelet/leukocytes activation
  • increased tissue factor mRNA and protein expression in endothelial cells
  • key regulator of the vascular system, which is linked to a number of cardiovascular diseases
  • likely activates the AKT1 signaling pathway, which, in turn, promotes the proliferation and migration of endothelial progenitor cells (EPCs)
  • cytokine that can be synthesized by a variety of cell types and secreted into the extracellular matrix
  • vitamin K-dependent protein involved in cell survival, migration, and proliferation in response to inflammatory processes
  • may represent a novel independent risk factor for primary Sjögren syndrome (pSS), with a potential role in salivary gland inflammation and dysfunction
    • CELLULAR PROCESS cell life, proliferation/growth
    cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS coagulation/hemostasis
    text enhancing platelet degranulation and aggregation responses through its receptors promoting platelet activation and mediating thrombus formation
    PATHWAY
    metabolism
    signaling
  • GAS6/AXL signaling plays an important role in vascular biology by modulating survival and migration of vascular smooth muscle cells and endothelial cells (Li 2009)
  • GAS6/AXL signaling is essential for delaying the cellular senescence process regulated by the PI3K/AKT1/FOXO1 signaling pathway
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
  • Ca++ binding
    • protein
  • ligand for TYRO3/AXL ,SKY and MER family of receptor tyrosine kinases
  • GAS6 in circulation is bound to AXL suggesting circulating GAS6 to be inhibited and incapable of stimulating the TAM receptors
  • THBD is a novel molecule that promotes apoptosis and vascular calcification by regulation of GAS6, presumably via EGF receptor/ERK axis
  • interact with AXL in endothelial cells, inducing several signaling pathways involved in cell survival and proliferation
  • GAS6-induced AXL signaling is a critical driver of pancreatic cancer progression
  • GAS6-FOXO1 signaling axis plays an important role in VCAM1 expression in the context of venous thromboembolism (VTE)
    • cell & other
    REGULATION
    inhibited by estrogen in ER positive breast cancer cells
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in both glioma and vascular cells and predict poor prognosis in glioblastoma multiformis patients (Hutterer 2008)
    constitutional     --over  
    in patients with RPL (recurrent pregnancy loss)
    constitutional     --over  
    in systemic lupus erythematosus, with lupus nephritis or cutaneous vasculitis
    constitutional     --over  
    GAS6 serum concentrations are significantly increased in Preeclampsia (PE) during pregnancy
    constitutional     --over  
    associated with venous thromboembolic disease
    Susceptibility to atherothrombotic disease
    Variant & Polymorphism SNP SNP c834+7G>A in intron 8 increasing the risk of atherothrombotic disease
    Candidate gene
    Marker
  • potential to serve as a SLE disease activity marker
    • Therapy target
    SystemTypeDisorderPubmed
    cancerendocrinethyroid
    TYRO3/AXL-GAS6 autocrine circuit sustains the malignant features of thyroid cancer cells and targeting the circuit could offer a novel therapeutic approach in this cancer
    cancerbrainglioma/neuroblstoma
    specific targeting of the Axl/Gas6 signaling pathway may represent a potential new approach for glioma treatment
    cancerdigestivecolon
    unique inhibitory role during the progression of intestinal tumors associated with suppression of stromal immune reactions, suggesting a novel therapeutic approach for colorectal cancer patients
    cancerendocrinepancreas
    GAS6 inhibition with low-dose warfarin or other AXL-targeting agents may improve outcome in patients with AXL-expressing tumors
    ANIMAL & CELL MODELS