CD95

CD95 (APO-1/Fas) is an important inducer of the extrinsic apoptosis signaling pathway and therapy induced apoptosis of many tumor cells has been linked to the activity of CD95. is a prototype death receptor characterized by the presence of an 80 amino acid death domain in its cytoplasmic tail. This domain is essential for the recruitment of a number of signaling components upon activation by either agonistic anti-CD95 antibodies or cognate CD95 ligand that initiate apoptosis. The complex of proteins that forms upon triggering of CD95 is called the death-inducting signaling complex (DISC). The DISC consists of an adaptor protein and initiator caspases and is essential for induction of apoptosis. CD95 is also crucial for the negative selection of B cells within the germinal center (GC). Impairment of CD95-mediated apoptosis results in defective affinity maturation and the persistence of autoreactive B-cell clones.

CD95 Related Areas

Immunology>>Adaptive Immunity>>T Cell>>Regulatory T Cell>>CD95/APO-1/TNFRSF6

Immunology>>Cytokine & Receptor>>TNF Superfamily>>CD95/APO-1/TNFRSF6

Immunology>>Innate Immunity>>Natural Killer Cell (NK Cell)>>CD95/APO-1/TNFRSF6

Immunology>>Cluster of Differentiation>>B Cell CD Antigen>>CD95/APO-1/TNFRSF6

Immunology>>Cluster of Differentiation>>Granulocyte CD Antigen>>Neutrophils>>CD95/APO-1/TNFRSF6

Immunology>>Cluster of Differentiation>>Monocyte/Macrophage CD Antigen>>Other>>CD95/APO-1/TNFRSF6

Immunology>>Cluster of Differentiation>>T Cell CD Antigen>>Helper T Cells / Regulatory T Cells>>CD95/APO-1/TNFRSF6

CD95 Alternative Names

CD95, APO-1, FAS, TNFRSF6, APT1, FAS1, FASTM, ALPS1A

Summaries for CD95

Entrez Gene summary for FAS:

The CD95 protein encoded by this FAS gene is a member of the TNF-receptor superfamily. This CD95 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 CD95 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 CD95 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.

Wikipedia summary for CD95:

The FAS receptor (FasR) also known as apoptosis antigen 1 (APO-1 or APT), cluster of differentiation 95 (CD95) or tumor necrosis factor receptor superfamily member 6 (TNFRSF6) is a protein that in humans is encoded by the TNFRSF6 gene.The CD95 is a death receptor on the surface of cells that leads to programmed cell death (apoptosis). It is one of two apoptosis pathways, the other being the mitochondrial pathway. CD95 is located on chromosome 10 in humans and 19 in mice. Similar sequences related by evolution (orthologs) are found in most mammals.

Human CD95 Protein General Information

 

• Protein names: CD_antigen, Short Name=CD95
• Sequence length: 335 AA.
• Domain: CD95 contains a death domain involved in the binding of FADD, and maybe to other cytosolic adapter proteins.
• Sequence similarities: Contains 1 death domain. Contains 3 TNFR-Cys repeats.
• Subunit structure: CD95 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.
• Subcellular location: Isoform 1: Cell membrane; Single-pass type I membrane protein Ref.23. Isoform 2: Secreted Ref.23. Isoform 3: Secreted Ref.23. Isoform 4: Secreted Ref.23. Isoform 5: Secreted Ref.23. Isoform 6: Secreted Ref.23.n
• 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.
• Involvement in disease: Defects in CD95 are the cause of autoimmune lymphoproliferative syndrome type 1A (ALPS1A) [MIM:601859]; also known as Canale-Smith syndrome (CSS). ALPS is a childhood syndrome involving hemolytic anemia and thrombocytopenia with massive lymphadenopathy and splenomegaly.

General information above from UniProt

Function for CD95 Protein

UniProtKB:

CD95 protein is 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).

Genatlas:

• CD95 mediates apoptosis of inactivated T cells for instance in negative regulation of erythropoiesis through sequential activation of ICE-like (CASP4, CASP5 and CPP32-like (CASP3)) caspases
• CD95 blocks after stimulation T lymphocyte calcium channels through the activation of acidic sphingomyelinase (SMPD1) and ceramide release
• CD95 is involved in extra-thymic self-tolerance and tumor immune escape
• CD95 plays a central role in the physiological regulation of programmed cell death, and involved in the pathogenesis of various malignancies and diseases of the immune system
• CD95 activates 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
• isoforms lacking the transmembrane domain may negatively regulate the apoptosis mediated by the full length isoform
• stimulation results of CD95 in the formation of a novel death effector domain protein-containing complex
• death receptor that regulates tissue homeostasis mainly in the immune system through the induction of apoptosis
• CD95 could actually promote the growth of tumours through its non-apoptotic activities (Pubmed 20505730)
• CD95 has a role in the tumorigenesis of ovarian cancer (Pubmed 20505730)

Phenotype Information for CD95

• Gene/Locus: TNFRSF6, APT1, FAS, CD95, ALPS1A
• Phenotype: Autoimmune lymphoproliferative syndrome, type IA
  Squamous cell carcinoma, burn scar-related, somatic
  {Autoimmune lymphoproliferative syndrome}

Phenotype Information for CD95 from OMIM (Online Mendelian Inheritance in Man)