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FLASH GENE
Symbol FAS contributors: mct/ - updated : 05-03-2016
HGNC name Fas (TNF receptor superfamily, member 6)
HGNC id 11920
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver    
 pharynx    
Endocrineadrenal gland    
Lymphoid/Immunethymus   highly
Reproductivefemale systemuterus   
Respiratorylung    
Urinarybladder    
 kidney    
Visualeye   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadipose  highly
cell lineage
cell lines
fluid/secretion blood
at STAGE
physiological period fetal
Text muscle
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • three extracytoplasmic cysteine-rich pseudo-repeats CRD1, CRD2, CRD3 typical for the TNFR superfamily
  • a preligand assembly domain (PLAD) in CRD1 mediating ligand-independent receptor assembly and signaling
  • a small cytoplasmic domain
  • a DEATH domain, associating under activation with the DEATH domain of FADD and CASP8
  • conjugated GlycoP
    mono polymer homomer , trimer
    HOMOLOGY
    Homologene
    FAMILY
  • tumor necrosis factor receptor superfamily
  • CATEGORY antigen , receptor membrane
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    text isoforms lacking the transmembrane domain are secreted
    basic FUNCTION
  • mediating apoptosis of inactivated T cells for instance in negative regulation of erythropoiesis through sequential activation of ICE-like (CASP4, CASP5 and CPP32-like (CASP3)) caspases
  • blocking after stimulation T lymphocyte calcium channels through the activation of acidic sphingomyelinase (SMPD1) and ceramide release
  • involved in extra-thymic self-tolerance and tumor immune escape
  • playing a central role in the physiological regulation of programmed cell death, and involved in the pathogenesis of various malignancies and diseases of the immune system
  • activating NF-kappaB, MAPK3/ERK1, and MAPK8/JNK, and is found to be involved in transducing the proliferating signals in normal diploid fibroblast and T cells
  • isoforms lacking the transmembrane domain may negatively regulate the apoptosis mediated by the full length isoform
  • its stimulation results in the formation of a novel death effector domain protein-containing complex
  • death receptor whose stimulation by either the physiologic ligand FASL or the agonistic antibodies leads to the formation of a multi-molecular complex termed DISC (death-inducing signaling complex)
  • death receptor that regulates tissue homeostasis mainly in the immune system through the induction of apoptosis
  • could actually promote the growth of tumours through its non-apoptotic activities
  • having a role in the tumorigenesis of ovarian cancer
  • induces a potent apoptotic signal
  • promotes apoptosis through well-defined signalling pathway
  • FAS/FASLG system plays a central role in maintaining peripheral immune tolerance
  • the site-specific FAS mRNA editing mutation may play a critical role in human immune responses and in the pathogenesis of human chronic inflammatory diseases
  • plays a pivotal role in immune surveillance and immune tolerance
  • induces invasion by stimulating the expression of extracellular matrix (ECM)-degrading proteases, and by stimulating the formation of actin-driven cell protrusions through Rac and the cofilin pathway
  • FAS-stimulation triggers localized Ca2+ influx through the redistribution of STIM1/ORAI1 into the FAS-Cap, and this influx inhibits the initial steps of the FAS signaling pathway
  • FAS-mediated Ca2+ response controls the initial steps in the receptor signaling pathway to promote the transmission of nonapoptotic signals
  • rotative stress has a significant effect on CA2, FAS, FASLG, OSCAR, and TRAP gene expression in osteoclasts
  • FAS and NFKB play a role in the initiation and development of breast cancer, while VEGFC appears to promote lymph node metastasis
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • trimerization may be dependent of TNFSF6 or independent
  • FAS/FASLG induces erythroblast apoptosis
  • FAS/FADD/caspase-8 complex is known as the death-inducing signaling complex (DISC)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding DAXX, RIPK1, FAIM2
  • interacting with HIPK3, BRE
  • interacting with CASP8AP2
  • interacting with CFL1 (cofilin activation is required for FAS-stimulated formation of membrane protrusions and increased tumour cell invasion)
  • biological role of Ca2+ and the ORAI1 channel that drives a transient negative feedback loop, introducing a lag phase in the early steps of the FAS signal (
  • hyperoxia-induced MAP1LC3B activation regulates the FAS apoptotic pathway and thus confers cytoprotection in lung epithelial cells (interaction of MAP1LC3B and FAS pathways requires CAV1)
  • LAT is proteolytically cleaved following FAS engagement in a tyrosine phosphorylation-dependent fashion
  • FAS-CALM1 interactions, and CALM1 antagonists greatly inhibit FAS-CALM1 interactions by blocking the FAS-binding site on CALM1
  • identification of ZDHHC7 as a FAS-palmitoylating enzyme
  • role for MOAP1 in FAS signaling in the liver by promoting MTCH2-mediated BID recruitment to mitochondria
  • FAS, a mediator of extrinsic apoptotic pathway, is a novel CERS6 binding partner
  • cell & other
    REGULATION
    activated by its natural ligand FASL (leads to the formation of the death-inducing signaling complex)
    induced by TP53-responsive elements, and TP63, TP73
    ASSOCIATED DISORDERS
    corresponding disease(s) CSS1 , TAL4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    fusion with ESR1 in several cancer lines (prostate, breast cervical, bladder)
    tumoral somatic mutation      
    mutated in the death domain in the non small cell lung cancer, in non lymphoid malignancie, T cell lymphoma and Hodgkin's disease, thyroid lymphoma, nasal NK/T cell lymphoma
    tumoral       loss of function
  • retention of intron 5 and encodes a dysfunctional protein
  • impairment of Fas-induced apoptosis resulting from aberrant splicing potentially contributes to the development and progression of cutaneous T-cell lymphoma
  • tumoral somatic mutation      
    in nodal diffuse large B-cell lymphoma
    tumoral     --over  
    in epithelial ovarian cancer
    Susceptibility
  • implicated early-onset Alzheimer with inconsistant results
  • to autoimmune diabetes
  • systemic lupus erythematous with loss of regulation of B lymphocytes
  • to acute myeloid leukemia (AML)
  • to myocardial infarction (MI)
  • Variant & Polymorphism SNP , other
  • promoter playing a role in Alzheimer disease
  • increased risk of AML associated with heterozygotes (GA) and homozygote variants (AA) at position -1377 bp
  • SNP (-670G/A), may be a risk factor of MI occurrence
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    locking FAS in apoptosis-mode may be a more promising anti-cancer strategy than simply inhibiting or stimulating FAS
    ANIMAL & CELL MODELS