CD95; Fas antigen; tumor necrosis factor receptor superfamily member 6; apo-1 antigen; apoptosis-mediating surface antigen FAS; FASLG receptor (FAS, APT1, FAS1, TNFRSF6)
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Function
- mediates apoptosis
- ligand for Fas is a transmembrane glycoprotein FasL
- 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 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
- secreted isoforms 2-6 block apoptosis (in vitro)
- Fas/FasL & perforin/granzyme systems account for cytotoxic T-cell induced apoptosis[9]
- Ca+2-independent killing by cytotoxic T-cells is mediated via fas/Apo1
- genes for Fas & FasL may be considered tumor suppressor genes
- under certain circumstances, Fas activation has been reported to stimulate lymphocyte proliferation rather than apoptosis[5]
- Fas antigen-induced apoptosis is initiated by receptor clustering
- downstream effectors of Fas antigen include members of the interleukin-1 beta converting enzyme (ICE)
- binds DAXX
- interacts with HIPK3
- part of a complex containing HIPK3 & FADD (putative)
- binds RIPK1 & FAIM2
- interacts with BRE & FEM1B
- interacts with FADD
Structure
- N-glycosylated & O-glycosylated
- O-glycosylated with core 1 or possibly core 8 glycans
- member of the TNF receptor family
- the FasL signal is transduced through the Fas antigen cytoplasmic 'death domain'
- contains 1 death domain
- contains 3 TNFR-Cys repeats
Compartment
- isoform 1:
- cell membrane, single-pass type 1 membrane protein
- isoform 2: secreted
- isoform 3: secreted
- isoform 4: secreted
- isoform 5: secreted
- isoform 6: secreted
- at least one isoform may be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay
Alternative splicing
named isoforms=6
Expression
- activated B cells
- activated T cells
- resting T cells (low levels)
- breast
- vaginal, endometrial & ovarian epithelium
- isoform 1 & isoform 6 are expressed at equal levels in resting peripheral blood mononuclear cells
Pathology
More general terms
- tumor necrosis factor [TNF] receptor family
- CD antigen
- pro apoptotic protein
- human longevity protein
More specific terms
Additional terms
- apoptosis
- Fas ligand; tumor necrosis factor ligand superfamily member 6; Fas antigen ligand; CD95L protein; apoptosis antigen ligand; APTL; CD178 (FASLG, APT1LG1, FASL, TNFSF6)
- protein tyrosine phosphatase 13, non-receptor type; Fas-associated phosphatase-1; FAP-1, protein-tyrosine phosphatase 1E (PTPN13, PNP1, PTP1E, PTPL1)
References
- ↑ Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992 Mar 26;356(6367):314-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1372394
- ↑ Taga T & Kishimoto T Cytokine receptors and signal transduction FASEB J 6:3387 1992 PMID: https://www.ncbi.nlm.nih.gov/pubmed/1334470
- ↑ Cory S. Apoptosis. Fascinating death factor. Nature. 1994 Jan 27;367(6461):317-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7509455
- ↑ Nagata S, Golstein P. The Fas death factor. Science. 1995 Mar 10;267(5203):1449-56. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7533326
- ↑ 5.0 5.1 Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science. 1995 Mar 10;267(5203):1456-62. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7878464
- ↑ 6.0 6.1 Rieux-Laucat F, Le Deist F, Hivroz C, Roberts IA, Debatin KM, Fischer A, de Villartay JP. Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science. 1995 Jun 2;268(5215):1347-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7539157
- ↑ 7.0 7.1 Fisher GH, Rosenberg FJ, Straus SE, Dale JK, Middleton LA, Lin AY, Strober W, Lenardo MJ, Puck JM. Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell. 1995 Jun 16;81(6):935-46. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7540117
- ↑ Lacronique V, Mignon A, Fabre M, Viollet B, Rouquet N, Molina T, Porteu A, Henrion A, Bouscary D, Varlet P, Joulin V, Kahn A. Bcl-2 protects from lethal hepatic apoptosis induced by an anti-Fas antibody in mice. Nat Med. 1996 Jan;2(1):80-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8564847
- ↑ 9.0 9.1 Kagi D, Vignaux F, Ledermann B et al Fas and perforin pathways as major mechanisms of T cell- mediated cytotoxicity. Science. 1994 Jul 22;265(5171):528-30. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/7518614
- ↑ <Internet> http://www.pathologyoutlines.com/cdmarkers.html 11 June 2005
Database
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=355
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:355
- Kegg: http://www.genome.jp/dbget-bin/www_bget?
- OMIM: https://mirror.omim.org/entry/134637
- OMIM: https://mirror.omim.org/entry/601859
- UniProt: http://www.uniprot.org/uniprot/P25445.html