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FLASH GENE
Symbol GAS6 contributors: mct/npt - updated : 25-01-2016
HGNC name growth arrest-specific 6
HGNC id 4168
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