Tumor Necrosis Factor Receptor Superfamily Member 6 Protein (FAS) Human 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: 10q23.31

Cellular Component: CD95 death-inducing signaling complex; cell surface; cytosol; integral to plasma membrane; lipid raft; mitochondrion; nuclear body; plasma membrane

Molecular Function: calmodulin binding; identical protein binding; kinase binding; protein binding; signal transducer activity; tumor necrosis factor binding; tumor necrosis factor receptor activity

Biological Process: apoptosis; caspase activation; cellular response to amino acid starvation; immune response; inflammatory response; multicellular organismal development; negative regulation of apoptosis; positive regulation of apoptosis; positive regulation of protein amino acid phosphorylation; protein complex assembly; regulation of apoptosis; regulation of cell proliferation; regulation of stress-activated MAPK cascade; response to lipopolysaccharide; signal transduction

Disease: Autoimmune Lymphoproliferative Syndrome