| Feature | Human FAS/CD95 annotation | Evidence note | Citation |
|---|---|---|---|
| Protein type / identity | Type I transmembrane death receptor of the TNF receptor superfamily; also called CD95, APO-1, TNFRSF6; human FAS corresponds to UniProt P25445 | Recent reviews explicitly match human FAS with CD95/APO-1 and describe it as a cell-surface TNFR-family death receptor mediating apoptotic and non-apoptotic signaling | (pqac-00000002, pqac-00000007) |
| Extracellular cysteine-rich domains (CRDs) | N-terminal extracellular region contains three cysteine-rich domains; CRD2 and part of CRD3 contribute to ligand recognition | Structural summary identifies 3 CRDs and maps ligand-binding activity mainly to CRD2 plus part of CRD3, consistent with TNFR-family architecture | (pqac-00000005, pqac-00000007) |
| PLAD (pre-ligand assembly domain) | PLAD spans residues 59–82 and supports receptor pre-association/oligomerization before ligand binding | CD95 pre-oligomerization at the plasma membrane is highlighted as a signaling-facilitating feature, with PLAD specifically assigned to residues 59–82 | (pqac-00000005, pqac-00000007) |
| Transmembrane region | Single-pass transmembrane segment (~17 aa); intramembrane interactions contribute to receptor trimerization/clustering | Reviews describe a 17-aa TM region and note a proline-containing TM motif/intramembrane trimerization that helps organize signaling-competent receptor assemblies | (pqac-00000005, pqac-00000007) |
| Cytoplasmic death domain | Intracellular death domain (~80 aa) composed of six antiparallel α-helices; binds FADD through homotypic DD interactions | This domain is the core signaling module that converts ligand-induced receptor conformational changes into DISC assembly | (pqac-00000005, pqac-00000007) |
| Main ligand(s) | FAS ligand/CD95L is the cognate ligand; exists as membrane-bound (mFASL) and soluble (sFASL) forms | mFASL is emphasized as the potent apoptosis-inducing form, whereas sFASL more often favors non-apoptotic outputs such as NF-κB-linked signaling | (pqac-00000002, pqac-00000001) |
| DISC adaptor proteins | FADD is the central adaptor; DISC recruits procaspase-8, procaspase-10, and c-FLIP isoforms | After FAS activation, FADD bridges the receptor death domain to DED-containing effectors/regulators, forming the membrane-bound DISC | (pqac-00000002, pqac-00000005, pqac-00000014) |
| Apoptotic signaling branch | Canonical extrinsic apoptosis via caspase-8 activation; type I cells rely mainly on direct effector caspase activation, type II cells amplify through mitochondria/BID/apoptosome | Figure-based and text evidence show DISC-driven caspase-8 activation followed by direct caspase-3/7 activation or mitochondrial amplification depending on cellular context | (pqac-00000005, pqac-00000014) |
| Non-apoptotic signaling branch | Can activate NF-κB and MAPK pathways (ERK, JNK, p38), supporting inflammation, migration, survival, regeneration, and tumor-promoting programs in some contexts | Current understanding is that FAS is multifunctional: low/altered stimulation or modified DISC composition can redirect signaling away from apoptosis toward survival/inflammatory programs | (pqac-00000001, pqac-00000005, pqac-00000014) |
| Typical cellular localization | Primarily plasma membrane/cell surface receptor; signaling platforms include pre-associated oligomers and membrane microdomains; DISC assembles at the membrane | Reviews describe ubiquitous surface expression, especially on immune cells, with signaling initiated at membrane-associated receptor clusters | (pqac-00000002, pqac-00000005, pqac-00000007) |
| Key intracellular signaling compartments | Membrane-associated DISC for apoptotic signaling; non-apoptotic complexes including FADDosome/MISC have been proposed for NF-κB/MAPK signaling | Figure summary distinguishes DISC from non-apoptotic FADDosome-like assemblies containing FADD, RIPK1, c-FLIP, and caspases-8/10 | (pqac-00000005, pqac-00000014) |
| Ligand-form checkpoint | mFASL generally drives robust apoptotic signaling; sFASL preferentially supports non-apoptotic signaling | Ligand biochemical form is repeatedly cited as a major determinant of life/death outcome downstream of FAS | (pqac-00000002, pqac-00000001) |
| c-FLIP checkpoint | c-FLIPL, c-FLIPS, and c-FLIPR modulate procaspase-8 activation; short isoforms inhibit caspase-8 activation, while c-FLIPL can be pro- or anti-apoptotic depending on abundance/ratio | DISC composition and especially c-FLIP level are presented as central switches controlling whether CD95 signaling remains apoptotic or becomes non-apoptotic | (pqac-00000007, pqac-00000001) |
| PTM / receptor regulation checkpoint | Glycosylation of CD95 and PTMs of DISC proteins influence signaling outcome; nitrosylation and ubiquitination control c-FLIP stability and apoptosis resistance | Reviews highlight PTMs as major checkpoints, though effects are context dependent and often act by reshaping DISC assembly or turnover of regulators | (pqac-00000007, pqac-00000001) |


*Table: This table summarizes the verified identity, domain architecture, signaling mechanisms, localization, and major regulatory checkpoints of human FAS/CD95 (UniProt P25445). It is useful as a compact functional annotation linking receptor structure to apoptotic versus non-apoptotic outcomes.*