Fas/CD95 (FAS) Active Protein

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. [provided by RefSeq, Mar 2011]

FAS: 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). Binds DAXX. Interacts with HIPK3. Part of a complex containing HIPK3 and FADD. Binds RIPK1 and FAIM2. Interacts with BRE and FEM1B. Interacts with FADD. Isoform 1 and isoform 6 are expressed at equal levels in resting peripheral blood mononuclear cells. After activation there is an increase in isoform 1 and decrease in the levels of isoform 6. 6 isoforms of the human protein are produced by alternative splicing.

Protein type: Apoptosis; Cell surface; Membrane protein, integral; Receptor, cytokine

Chromosomal Location of Human Ortholog: 10q24.1

Cellular Component: cell surface; cytoplasm; integral to membrane; plasma membrane; CD95 death-inducing signaling complex; nucleus; cytosol; external side of plasma membrane; lipid raft

Molecular Function: identical protein binding; signal transducer activity; protein binding; transmembrane receptor activity; receptor activity; kinase binding

Biological Process: spleen development; circadian rhythm; caspase activation; regulation of myeloid cell differentiation; renal system process; transformed cell apoptosis; positive regulation of apoptosis; apoptosis; positive regulation of protein homooligomerization; regulation of lymphocyte differentiation; response to toxin; response to glucocorticoid stimulus; negative regulation of B cell activation; signal transduction; negative thymic T cell selection; regulation of apoptosis; inflammatory cell apoptosis; B cell mediated immunity; induction of apoptosis via death domain receptors; gene expression; protein complex assembly; immunoglobulin production; activated T cell apoptosis; protein homooligomerization; negative regulation of apoptosis

Disease: Autoimmune Lymphoproliferative Syndrome