FAS Receptor, Soluble (FAS receptor) 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]

Function: 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). Ref.4 Ref.28

Subunit structure: Binds DAXX. Interacts with HIPK3. Part of a complex containing HIPK3 and FADD

By similarity. Binds RIPK1 and FAIM2. Interacts with BRE and FEM1B. Interacts with FADD. Ref.15 Ref.16 Ref.17 Ref.19 Ref.23 Ref.28

Subcellular location: Isoform 1: Cell membrane; Single-pass type I membrane protein Ref.28. Isoform 2: Secreted Ref.28. Isoform 3: Secreted Ref.28. Isoform 4: Secreted Ref.28. Isoform 5: Secreted Ref.28. Isoform 6: Secreted Ref.28.

Tissue specificity: 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. Ref.3

Domain: Contains a death domain involved in the binding of FADD, and maybe to other cytosolic adapter proteins.

Post-translational modification: N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. Ref.26

Involvement in disease: Autoimmune lymphoproliferative syndrome 1A (ALPS1A) [MIM:601859]: 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.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.41 Ref.42

Sequence similarities: Contains 1 death domain.Contains 3 TNFR-Cys repeats.