FAS

Domain

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

Function

Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase CASP8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs CASP8 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).

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

(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.

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.

Cellular localization

• Isoform 1
• Cell membrane
• Single-pass type I membrane protein
• Membrane raft
• Isoform 2
• Secreted
• Isoform 3
• Secreted
• Isoform 4
• Secreted
• Isoform 5
• Secreted
• Isoform 6
• Secreted

Alternative names

CD95, APT1, FAS1, TNFRSF6, FAS, Tumor necrosis factor receptor superfamily member 6, Apo-1 antigen, Apoptosis-mediating surface antigen FAS, FASLG receptor

Database links

swissprot:P25445 entrezGene:355 omim:134637

Other research areas

• Oncology