FAS

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains a death domain. It has been shown to play a central role in the physiological regulation of programmed cell death, and has been implicated in the pathogenesis of various malignancies and diseases of the immune system. The interaction of this receptor with its ligand allows the formation of a death-inducing signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10. The autoproteolytic processing of the caspases in the complex triggers a downstream caspase cascade, and leads to apoptosis. This receptor has been also shown to activate 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. Several alternatively spliced transcript variants have been described, some of which are candidates for nonsense-mediated mRNA decay (NMD). The isoforms lacking the transmembrane domain may negatively regulate the apoptosis mediated by the full length isoform.

Full Name

Fas Cell Surface Death Receptor

Alternative Names

Fas Cell Surface Death Receptor; Tumor Necrosis Factor Receptor Superfamily, Member 6; Fas (TNF Receptor Superfamily, Member 6); Apoptosis-Mediating Surface Antigen FAS; TNF Receptor Superfamily Member 6; FASLG Receptor; CD95 Antigen; TNFRSF6; APT1; FAS1; Mutant Tumor Necrosis Receptor Superfamily Member 6;

Research Area

Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. The secreted isoforms 2 to 6 block apoptosis (in vitro).

Biological Process

Activation-induced cell death of T cells Source: GO_Central
Apoptotic process Source: MGI
Cellular response to amino acid starvation Source: CAFA
Cellular response to hyperoxia Source: UniProtKB
Cellular response to mechanical stimulus Source: UniProtKB
Extrinsic apoptotic signaling pathway Source: UniProtKB
Extrinsic apoptotic signaling pathway in absence of ligand Source: GO_Central
Fas signaling pathway Source: CAFA
Immune response Source: InterPro
Motor neuron apoptotic process Source: GO_Central
Necroptotic signaling pathway Source: BHF-UCL
Negative regulation of apoptotic process Source: GO_Central
Positive regulation of apoptotic process Source: UniProtKB
Positive regulation of apoptotic signaling pathway Source: CAFA
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: CAFA
Positive regulation of protein phosphorylation Source: CAFA
Protein-containing complex assembly Source: ProtInc
Regulation of apoptotic process Source: UniProtKB
Regulation of stress-activated MAPK cascade Source: CAFA
Signal transduction Source: ProtInc

Cellular Location

Isoform 1: Cell membrane; Membrane raft
Isoform 2&3&4&5&6: Secreted

Involvement in disease

Autoimmune lymphoproliferative syndrome 1A (ALPS1A):
A disorder of apoptosis that manifests in early childhood and results in the accumulation of autoreactive lymphocytes. It is characterized by non-malignant lymphadenopathy with hepatosplenomegaly, and autoimmune hemolytic anemia, thrombocytopenia and neutropenia.

Topology

Extracellular: 26-173
Helical: 174-190
Cytoplasmic: 191-335

PTM

(Microbial infection) Glycosylated at Arg-250 by enteropathogenic E.coli protein NleB1: arginine GlcNAcylation prevents homotypic/heterotypic death domain interactions.
Palmitoylated (PubMed:25301068). Palmitoylation by ZDHHC7 prevents the lysosomal degradation of FAS regulating its expression at the plasma membrane (PubMed:25301068).
N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans.

Anti-FAS antibodies

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FAS Matched Antibody Pair (410) (APMAB-410LY)

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Target: FAS

Specificity: Human

FAS

Anti-FAS antibodies

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