FAS (CD95/APO-1/TNFRSF6) is a type I transmembrane death receptor for FAS ligand. Its extracellular region engages FASLG, while the intracellular death domain recruits FADD to assemble a death-inducing signaling complex and activate initiator caspases. This receptor pathway drives extrinsic apoptosis and contributes to the removal of activated lymphocytes. FAS signaling can also engage ASK1/JNK under glutamine deprivation in human HeLa cells. Alternative splicing yields products with different extracellular and intracellular sequences, including secreted variants reported to inhibit FAS-triggered apoptosis in cell assays and a reported tumor-associated membrane-containing variant lacking the death domain.
Curated functional classes representing distinct biological activities. These may be splice variants, cleavage products, or other forms with different functions.
FAS_MEMBRANEFAS_SOLUBLEFAS_DELTA_DEATH_DOMAINDefinition: Combining with extracellular FAS ligand (FASLG) and transmitting the signal across the plasma membrane to initiate apoptotic or necrotic cell death.
Justification: The live QuickGO term and child records checked on 2026-10-26 contain death receptor activity and ligand-specific TNF and TRAIL receptor children, but the Fas, CD95 and FASLG searches returned no equivalent FASLG-specific receptor molecular function. FAS is not the TNF-binding receptor defined by GO:0005031. The proposal distinguishes ligand specificity while retaining the current death receptor term; no GO identifier or NEW annotation is invented. Original FASLG-stimulated receptor-complex experiments support this receptor specificity. Reciprocal primary-screen signals from recombinant human FAS and FASLG ectodomain constructs provide direct interaction evidence for the ligand-specificity proposal (PMID:35922511). This screen does not supply a newly measured FAS-specific SPR affinity or a target-specific secondary-matrix validation.
Parent term: death receptor activity
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005031 tumor necrosis factor receptor activity | IBA GO_REF:0000033 | MODIFY | Summary: FAS is an inherited death receptor in the experimentally grounded FAS clade; the literal TNF-cytokine specificity of this term is inappropriate. Reason: The actual PTHR46874 tree places human P25445 below IBD node PTN002930185; its target alignment matches the canonical sequence and no family NOT was found. Human self-WITH is expected experimental grounding, not circularity. GO:0005031 specifies binding the TNF cytokine, whereas the inspected human PMID:12221075 Methods/Results use anti-CD95 to initiate receptor-dependent death. Rat PMID:16154149 concerns Fas/FasL-dependent Kupffer-cell apoptosis and does not establish TNF binding to FAS in its accessible abstract. The inherited death-receptor mechanism is sound; refine the ancestral functional scope to GO:0005035, which includes ligand-initiated apoptotic or necrotic death. The retained superfamily/provider quotations establish identity/context, not literal TNF ligand specificity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002930185 Β· PTN002930185 UNRESOLVED Actual ancestral IBD is on the human target path, with experimentally grounded human self-WITH and rat descendant evidence. The inherited death-receptor mechanism is supported, but literal TNF-cytokine specificity of this node assertion is not established by the inspected human assay or accessible rat abstract; refine the term scope, not the orthology. Proposed replacements: death receptor activity Supporting Evidence: PMID:1375228 The deduced amino acid sequence of APO-1 showed sequence identity with the Fas antigen, a cysteine-rich transmembrane protein of 335 amino acids with significant similarity to the members of the tumor necrosis factor/nerve growth factor receptor superfamily. file:human/FAS/FAS-deep-research-perplexity.md provider: perplexity file:human/FAS/FAS-deep-research-falcon.md The gene symbol **FAS** here refers to the human cell-surface death receptor **CD95/APO-1**, a **type I transmembrane** member of the TNF receptor superfamily (TNFRSF6) with extracellular **cysteine-rich domains (CRDs)** and a cytosolic **death domain (DD)** that recruits the adaptor **FADD** to assemble a **death-inducing signaling complex (DISC)**, consistent with UniProt accession **P25445**. |
| GO:0045121 membrane raft | IBA GO_REF:0000033 | ACCEPT | Summary: FAS has a regulated membrane-raft-associated pool. Reason: The target descends from the actual PTN002930185 IBD node and the human self-WITH has direct grounding. PMID:21382479 fractionates human BEAS-2B cells using detergent-free sucrose gradients and detects FAS in raft fractions, with redistribution during prolonged hyperoxia. PMID:25301068 independently detects a FAS pool in detergent-resistant membrane fractions of human SW480 cells. These assays support raft association, not exclusive or permanent raft residence, and do not distinguish all natural isoforms. Supporting Evidence: PMID:21382479 We found that Cav-1 regulated Fas signaling and mediated the communication between extrinsic and intrinsic pathways. Shortly after hyperoxia (4 h), the colocalization and interaction of Cav-1 and Fas increased, followed by Fas multimer and DISC formation. |
| GO:0009897 external side of plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: The extracellular portion of membrane FAS is exposed at the cell surface. Reason: The actual PTN002930185 assertion lies on the human target ancestry; the mouse and rat donor mappings were recovered. Rat PMID:17195944 was read only at abstract level and is not treated as a complete topology assay. Independent human intact-cell antibody staining and cold surface biotinylation in PMID:25301068, together with the official type-I FAS topology, support external exposure. The term describes the exposed receptor portion, not an assertion that its intracellular death domain is extracellular or that every natural product has this location. Supporting Evidence: PMID:1375228 The APO-1 antigen as defined by the mouse monoclonal antibody anti-APO-1 was previously found to be expressed on the cell surface of activated human T and B lymphocytes and a variety of malignant human lymphoid cell lines. |
| GO:0006924 activation-induced cell death of T cells | IBA GO_REF:0000033 | ACCEPT | Summary: FAS participates in activation-induced death of T cells through death-receptor signaling. Reason: The actual PTN002930185 IBD is ancestral to human FAS, with mouse experimental descendants. The accessible donor abstracts PMID:12702495, PMID:7602121 and PMID:8640868 have distinct compartment, age and BCL2 contexts; they are not universal T-cell homeostasis experiments. The independently identified human PMID:7530335 abstract reports activated T-cell/Jurkat FasL induction and inhibition of activation-induced death by FAS blockade or soluble receptor. This well-established receptor role supports retention of the phylogenetic assertion despite incomplete donor full-text access; no target-specific loss is established. Supporting Evidence: PMID:7538907 Overexpression of FADD in MCF7 and BJAB cells induces apoptosis, which, like Fas-induced apoptosis, is blocked by CrmA, a specific inhibitor of the interleukin-1 beta-converting enzyme. PMID:39060684 Autoimmune lymphoproliferative syndrome (ALPS) is a rare primary immunodeficiency disorder of defective Fas-mediated apoptosis (restimulation-induced cell death), featuring chronic lymphadenopathy, splenomegaly, cytopenias, and increased lymphoma risk. file:human/FAS/FAS-deep-research-falcon.md A large 2024 cohort study of **802** individuals referred for ALPS NGS testing (May 2014βJan 2023) provides quantitative, clinically grounded evidence linking FAS to immune homeostasis via apoptosis regulation |
| GO:0031265 CD95 death-inducing signaling complex | IBA GO_REF:0000033 | ACCEPT | Summary: FAS is the receptor component of the CD95 death-inducing signaling complex. Reason: The human target lies below the actual PTN002930185 IBD; self-WITH is legitimate. PMID:20935634 examines reconstituted human FAS-DD/FADD-DD assemblies and interface-dependent signaling in human cells, while its crystal uses mouse FAS-DD with human FADD-DD. The actual Reactome entities independently contain P25445 in the FASL:FAS:FADD/procaspase complex. Retain DISC membership without imposing one fixed oligomeric stoichiometry or treating the receptor as a caspase enzyme. Rat PMID:16493077 was only abstract-read and is not used as a fully verified independent assembly experiment. Supporting Evidence: PMID:20935634 The death-inducing signaling complex (DISC) formed by the death receptor Fas, the adaptor protein FADD and caspase-8 mediates the extrinsic apoptotic program PMID:40330016 Upon binding to mFASL, FAS recruits the adaptor protein FAS-associated death domain (FADD), which recruits procaspase-8, procaspase-10, and cellular FLICE inhibitory protein (c-FLIP) via their homotypic death effector domain (DED), forming a membrane-bound death-inducing signaling complex (DISC) file:human/FAS/FAS-deep-research-falcon.md Upon ligand binding, conformational changes allow FAS DD engagement with **FADD**, which then recruits DED-containing proteins **procaspase-8/10** and **c-FLIP** isoforms to form the membrane-associated **DISC**; this supports procaspase-8 activation, which then activates effector caspases (e.g., caspase-3/-7) to execute apoptosis. |
| GO:0032872 regulation of stress-activated MAPK cascade | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: FAS ligation can regulate stress-activated MAPK signaling in a conditional apoptotic setting. Reason: The actual ancestral IBD includes human experimental self-WITH. Original Methods/Results and Figure 2 caption of PMID:11096076 show anti-FAS stimulation of human HeLa cells activates ASK1 and JNK/SAPK during glutamine deprivation; p42/p44 MAPK responds in both glutamine conditions, whereas p38 phosphorylation was not detected. This is a conditional signaling output, not FAS kinase activity or a general non-apoptotic function. Retain as non-core. Supporting Evidence: PMID:11096076 Fas ligation activated apoptosis signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK; also known as stress-activated protein kinase (SAPK)) in Gln-deprived cells PMID:40330016 Upon activation, FAS triggers signaling pathways such as NF-ΞΊB, MAPK, and PI3K/AKT through different mechanisms. These pathways regulate immune responses and promote cell proliferation, migration, and invasion by inducing the production of inflammatory factors and chemokines file:human/FAS/FAS-deep-research-falcon.md A key contemporary view is that CD95 can also act as a **multifunctional signaling receptor**, activating programs such as **NF-ΞΊB** and **MAPK (ERK/JNK/p38)**, supporting outcomes including chemokine release and cellular migration/invasion in certain contexts. |
| GO:0043066 negative regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Soluble FAS products can inhibit FAS-triggered apoptosis in defined experimental settings. Reason: The actual PTN002930185 ancestry is sound, but the donor assay is product-sensitive. The recovered original PMID:7595210 Methods, Results and Figure 2 caption describe murine FasB-expressing P815 clones and conditioned medium protecting against FasL-expressing 3T3 cells while surface FasA remains. Murine FasB has a distinct truncated architecture; it is not an assay of human isoforms 2β6. The preserved human PMID:7510905 evidence and official UniProt soluble-product annotation corroborate negative regulation at gene level. Retain this non-core output without claiming direct ligand sequestration was measured in the mouse experiment, identical mechanisms for every human product, or loss of the death domain from every soluble isoform. Supporting Evidence: PMID:7510905 Supernatants from cells transfected with the variant messenger RNA blocked apoptosis induced by the antibody to Fas |
| GO:0097049 motor neuron apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: FAS can contribute to injury-associated motor-neuron apoptosis. Reason: The actual PTN002930185 IBD is inherited by human FAS. Full original PMID:13679421 Methods/Results show Fas-mutant/deficient mouse motoneuron cultures and partial protection after neonatal facial-nerve axotomy; normal developmental motoneuron numbers were not altered in the tested mutants. FADD-DN also affects other death-receptor signaling, so the FAS-specific mutant experiments are distinguished from that broader perturbation. Retain the conserved, context-dependent output as non-core; this is not direct human motor-neuron evidence or a universal developmental requirement. The inherited PMID:7538907 quotation concerns FADD in other cell types and is not motor-neuron proof. Supporting Evidence: PMID:7538907 Overexpression of FADD in MCF7 and BJAB cells induces apoptosis, which, like Fas-induced apoptosis, is blocked by CrmA |
| GO:0097527 necroptotic signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: FAS can initiate necroptotic signaling when the cellular death machinery favors this route. Reason: The actual PTN002930185 IBD includes legitimate human and mouse-descendant evidence. Original PMID:21052097 Results, Figure 1 caption and Methods specify mouse L929sA cells engineered to express human FAS: anti-human FAS plus zVAD induces necrotic death sensitive to necrostatin-1. This is human-receptor evidence in a mouse host, not an endogenous mouse-Fas assay. Retain a conditional non-core output, separately from ordinary caspase-dependent apoptosis. The preserved PMID:7538908 quotation establishes RIP association and does not alone establish necroptosis; PMID:16507998 remains separate human-source corroboration with its direct-lane access limits. Supporting Evidence: PMID:7538908 Using a genetic selection based on protein-protein interaction in yeast, we have identified two gene products that associate with the intracellular domain of Fas: Fas itself, and a novel 74 kDa protein we have named RIP |
| GO:0033209 tumor necrosis factor-mediated signaling pathway | IEA GO_REF:0000108 | MODIFY | Summary: The electronic pathway inference carries literal TNF specificity from an overly specific molecular-function premise. Reason: GO_REF:0000108 describes logical MF-to-BP propagation and this source explicitly uses GO:0005031. GO:0033209 is initiated by the TNF cytokine binding its receptor; membership in the TNF receptor superfamily does not establish that ligand specificity. Human anti-CD95 receptor assays in PMID:12221075 and FAS/FADD signaling in PMID:20935634 support the verified GO:0036337 Fas signaling pathway. Preserve the imported source fields and refine its biological assertion. Proposed replacements: Fas signaling pathway |
| GO:0004888 transmembrane signaling receptor activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: A supported receptor annotation subsumed by death receptor activity. Reason: The target InterPro mapping and human receptor experiments support transmembrane signaling receptor activity. This broad claim is true but adds no functional coverage beyond death receptor activity (GO:0005035), retained by the reviewed phylogenetic and experimental replacements. Current QuickGO places GO:0005035 under GO:0004888. TOO_GENERAL preserves the positive source claim; it does not allege an erroneous domain mapping. |
| GO:0005516 calmodulin binding | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: FAS can bind calmodulin, with direct peptide-level structural and binding evidence. Reason: PMID:24914971 Figure 1c reports FAS-peptide binding by SPR; deposited structure 3EWT contains human calmodulin and a synthetic 25-residue human FAS peptide. The main Methods/Results body was not accessible, so this does not establish full-receptor stoichiometry, a unique site, or a universal physiological regulatory mechanism. Retain the binding assertion as non-core. This inherited keyword-mapping source is absent from the fresh GOA snapshot, and the official GO_REF:0000043 description now restricts its pipeline to viruses; source lifecycle is assessed separately from this positive biological judgment. Historical source retained; retired only from the pinned current GOA active set (see the source guide), not judged biologically false or officially withdrawn. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: FAS has extracellular soluble products in addition to its membrane receptor form. Reason: The electronic source SL-0243 maps the official UniProt secreted-product annotation to extracellular region. Human soluble FAS evidence supports gene-level extracellular localization; the canonical membrane receptor should not be redescribed as freely soluble. UniProt lists isoforms 2β6 as secreted, but this mapping is not an independent secretion assay for each product. In particular, isoform 6 lacks the transmembrane segment while retaining the death-domain sequence; no universal intracellular-domain deletion is implied. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Membrane FAS localizes to the plasma membrane. Reason: The official UniProt SL-0039 mapping agrees with human intact-cell FAS flow cytometry and surface biotinylation in PMID:25301068 and HPA immunofluorescence. Retain the cellular location without asserting that only natural isoform 1 can be membrane-associated: isoform 7 retains the transmembrane sequence, while its measured localization requires separate evidence. |
| GO:0006915 apoptotic process | IEA GO_REF:0000120 | ACCEPT | Summary: FAS receptor signaling participates in apoptosis. Reason: The historical combined electronic source integrated InterPro IPR008063 and apoptosis keyword KW-0053. The biological process is supported by human FAS-dependent death and DISC assays; the receptor supplies the signaling step rather than catalyzing proteolysis. Fresh context 62 now carries the same GO:0006915 assertion directly through InterPro. That source replacement is a lifecycle question, not evidence against apoptosis or a reason to alter the imported source fields. Historical source retained; retired only from the pinned current GOA active set (see the source guide), not judged biologically false or officially withdrawn. |
| GO:0006955 immune response | IEA GO_REF:0000002 | ACCEPT | Summary: FAS receptor signaling contributes to immune responses and activated-lymphocyte homeostasis. Reason: The official IPR008063-to-GO:0006955 mapping is broad but biologically appropriate for a receptor that mediates activated T-cell death. Human activation-induced death evidence in PMID:7530335 supports an actual signaling role, rather than deriving function solely from disease association. This does not imply an indispensable role in every immune compartment. |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | TOO GENERAL | Summary: Broad signal transduction is subsumed by the retained Fas signaling pathway. Reason: The target InterPro entries IPR008063 and IPR000488 correctly support a signaling role. GO:0007165 is an ancestor of the retained Fas signaling pathway (GO:0036337), independently supported by human receptor stimulation in PMID:12221075 and PMID:11096076. The broad mapping adds no separate process coverage. TOO_GENERAL does not attribute kinase or caspase activity to FAS or claim that the domain mapping is false. |
| GO:0009986 cell surface | IEA GO_REF:0000117 | ACCEPT | Summary: The membrane receptor has experimentally supported cell-surface exposure. Reason: Historical ARBA00027349 still contains a matching clause (zero-based 29: FunFam 2.10.50.10:FF:000021 plus Euteleostomi); the official FAS sequence record supplies both conditions. Human intact-cell labeling and surface biotinylation in PMID:25301068 support the location. Its absence from the fresh GOA export does not demonstrate withdrawal of the rule or a false biological claim. Keep the historical source intact pending explicit lifecycle reconciliation. Historical source retained; retired only from the pinned current GOA active set (see the source guide), not judged biologically false or officially withdrawn. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: FAS includes membrane-associated receptor products. Reason: The actual IPR008063 family and InterPro2GO mapping support this broad CC and agree with direct human surface measurements. Retain the broad electronic annotation without treating it as an assertion about all seven natural products or exclusive localization of isoform 1. |
| GO:0031265 CD95 death-inducing signaling complex | IEA GO_REF:0000117 | ACCEPT | Summary: FAS is part of the CD95 DISC. Reason: The actual ARBA00086566 rule has a matching zero-based clause 0 requiring FunFam 2.10.50.10:FF:000021 and Eukaryota, both present in the official target record. Human FAS/FADD assembly evidence and recursively resolved Reactome FAS-containing complexes support this assertion. Retain complex membership without a fixed oligomeric stoichiometry or a universal isoform assignment. |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000117 | ACCEPT | Summary: FAS receptor signaling regulates apoptosis, with product-dependent inhibitory effects also reported. Reason: Historical ARBA00027086 still contains a matching zero-based clause 54 for FunFam 2.10.50.10:FF:000021. Human receptor activation and soluble-product evidence support the broad regulatory term. This does not require every soluble isoform to have the same architecture or inhibitory mechanism. Current GOA absence alone is insufficient to call this rule withdrawn; historical source lifecycle remains separate. Historical source retained; retired only from the pinned current GOA active set (see the source guide), not judged biologically false or officially withdrawn. |
| GO:0045121 membrane raft | IEA GO_REF:0000044 | ACCEPT | Summary: FAS has a regulated membrane-raft-associated pool. Reason: The official UniProt SL-0370 mapping is consistent with actual human raft fractionation in PMID:21382479 and detergent-resistant membrane fractionation in PMID:25301068. The pool is dynamic and not the exclusive receptor location; neither assay establishes a natural-isoform-specific restriction. |
| GO:0097191 extrinsic apoptotic signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: FAS initiates the extrinsic apoptotic signaling pathway. Reason: The actual ARBA00028297 rule has matching zero-based clause 1 requiring the target FunFam and Eukaryota. FAS-dependent human death and FAS/FADD complex experiments directly support the receptor signaling step. FAS recruits the signaling machinery; downstream caspases execute proteolysis. |
| GO:0005515 protein binding | IPI PMID:10918185 Negative regulation of Fas-mediated apoptosis by FAP-1 in hu... | KEEP AS NON CORE | Summary: FAS association with PTPN13/FAP-1 is supported in the specified assay context. Reason: The original abstract explicitly reports FASβFAP-1 association in human 293T cells and loss of association after mutation of the FAS C-terminal tPLV motif. Full Methods/Results remain inaccessible; retain the explicit positive interaction without assigning phosphatase activity to FAS. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. |
| GO:0005515 protein binding | IPI PMID:11003656 Inhibition of Daxx-mediated apoptosis by heat shock protein ... | KEEP AS NON CORE | Summary: FAS association with DAXX is supported in the specified assay context. Reason: Original Methods and Results/Figures1/3 show GST-FAS death domain retaining DAXX from transfected 293-cell lysates. This is a positive association assay, not evidence that FAS has DAXX adaptor activity or that two purified proteins alone bind. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. |
| GO:0005515 protein binding | IPI PMID:11495919 Apoptosis signal-regulating kinase 1 controls the proapoptot... | KEEP AS NON CORE | Summary: FAS association with DAXX is supported in the specified assay context. Reason: Original Results and Figure3 show conditional FASβDAXX co-immunoprecipitation in human 293 cells expressing ASK1. ASK1-dependent redistribution and DAXX signaling do not establish an additional FAS molecular activity. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. |
| GO:0005515 protein binding | IPI PMID:11606059 Apoptosis-linked gene 2 binds to the death domain of Fas and... | KEEP AS NON CORE | Summary: FAS association with mouse Pdcd6/ALG2 is supported in the specified assay context. Reason: Human FAS death-domain two-hybrid and GST-ALG2 pull-down assays are positive. The imported P12815 partner is mouse Pdcd6, as recorded by IntAct; human Jurkat FASβPDCD6 co-IP is separate corroboration. Preserve this cross-species source context without attributing calcium-binding activity to FAS. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. |
| GO:0005515 protein binding | IPI PMID:11717445 Caspase-10 is an initiator caspase in death receptor signali... | KEEP AS NON CORE | Summary: FAS association with FADD is supported in the specified assay context. Reason: Original Figure2B and Methods show FADD in anti-FAS immunoprecipitates from stimulated primary human T cells. Retain this historical positive complex-association record; its absence from fresh imports does not invalidate it. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Historical source retained; retired only from the pinned current GOA active set (see the source guide), not judged biologically false or officially withdrawn. Supporting Evidence: PMID:11717445 Fas crosslinking in primary human T cells leads to the recruitment and activation of caspase-10. |
| GO:0005515 protein binding | IPI PMID:12724420 FAP-1 association with Fas (Apo-1) inhibits Fas expression o... | KEEP AS NON CORE | Summary: FAS association with PTPN13/FAP-1 is supported in the specified assay context. Reason: Original Methods and Figure1D show reciprocal endogenous FASβFAP-1 co-immunoprecipitation in human melanoma cells, with C-terminal FAS-motif experiments providing context. The association does not make FAS a phosphatase. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. |
| GO:0005515 protein binding | IPI PMID:12887920 Induction of TNF receptor I-mediated apoptosis via two seque... | KEEP AS NON CORE | Summary: FAS association with FASLG is supported in the specified assay context. Reason: The actual original Figure2C and accompanying Results include Flag-FASL stimulation and immunoprecipitation in human HT1080 cells. This positive FAS control supports the FASβFASLG association despite the TNFR1-focused title; it does not transfer TNFR1 complex-I/II biology to FAS. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. |
| GO:0005515 protein binding | IPI PMID:16498403 The role of receptor internalization in CD95 signaling. | KEEP AS NON CORE | Summary: FAS association with FADD is supported in the specified assay context. Reason: Original Results/Figures1/3 show FADD in ligand-isolated FAS complexes in human BJAB cells; Figure6 additionally examines FAS intracellular-domain/FADD death-domain interaction. The supported association is retained; a cellular-component DISC term is not a replacement molecular function. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:16498403 Recruitment of DISC components to the activated receptor predominantly occurs after the receptor has moved into an endosomal compartment |
| GO:0005515 protein binding | IPI PMID:17047155 Caspase-8 prevents sustained activation of NF-kappaB in mono... | KEEP AS NON CORE | Summary: FAS association with CASP8 is supported in the specified assay context. Reason: Original Figure3B identifies FAS in caspase8 immunoprecipitates from human U937 cells after CH11/CHX treatment. The monocyte-differentiation emphasis of the title does not negate this positive FAS assay. Co-complex recovery is not purified binary binding. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. |
| GO:0005515 protein binding | IPI PMID:17159907 Palmitoylation of CD95 facilitates formation of SDS-stable r... | KEEP AS NON CORE | Summary: FAS association with FADD is supported in the specified assay context. Reason: Original Figure1C detects FAS in FADD immunoprecipitates after LzCD95L stimulation of human SKW6.4/H9 cells. The independently inspected original Methods and Figure4 establish the receptor-complex context; no natural isoform or exclusive raft localization is inferred. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:17159907 these SDS-stable forms of CD95 correspond to very high molecular weight DISC complexes (hiDISC) and are the sites of caspase-8 activation. |
| GO:0005515 protein binding | IPI PMID:18328427 Yes and PI3K bind CD95 to signal invasion of glioblastoma. | UNDECIDED | Summary: The imported FASβSRC/P12931 association remains unresolved from accessible original evidence. Reason: The genuine repository file contains only the article summary; operative Methods/Results for this exact partner were not recovered. IntAct records the source pair, but the YES/PI3K-focused abstract cannot verify or refute it. P12931 denotes SRC, whereas YES1 is P07947; preserve the machine source accession and do not infer curator error from the title. |
| GO:0005515 protein binding | IPI PMID:21382479 Caveolin-1 mediates Fas-BID signaling in hyperoxia-induced a... | KEEP AS NON CORE | Summary: FAS association with CAV1 is supported in the specified assay context. Reason: Original Figure3A/B supports FASβCAV1 colocalization and co-immunoprecipitation in human BEAS-2B cells. Primary mouse Cav1-deletion experiments are separate. Retain association without claiming purified binary binding or making FAS a caveolar scaffold. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. |
| GO:0005515 protein binding | IPI PMID:21625644 Modulation of the CD95-induced apoptosis: the role of CD95 N... | KEEP AS NON CORE | Summary: FAS association with FADD is supported in the specified assay context. Reason: Original Figure7 and Methods show FADD in anti-FAS immunoprecipitates from human HeLa cells expressing wild-type or engineered glycosylation-site mutants. These constructs are not natural isoform-specific annotations. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. |
| GO:0005515 protein binding | IPI PMID:21803845 PMLRARΞ± binds to Fas and suppresses Fas-mediated apoptosis t... | KEEP AS NON CORE | Summary: FAS association with PML is supported in the specified assay context. Reason: Original Figure1B and related Methods support native PMLβFAS association in human HL60 and transfected HEK cells. This is distinct from the PMLβRARalpha fusion context and does not establish an extra FAS molecular activity. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | KEEP AS NON CORE | Summary: FAS association with FASLG is supported in the specified assay context. Reason: The authentic original PLA supplement lists FASβFASLG among the557 positive HeLa-cell pairs (TableS1 page8), with the exact antibody pair in TableS7 page89. This establishes cellular proximity under the published thresholds, not purified binary binding or a new activity inferred from the partner. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: FAS association with FADD is supported in the specified assay context. Reason: The original BioPlex293T table directly joins FAS/Gene355 to FADD/Gene8772 (line43744; pInt0.999970081167744). Original Methods describe tagged ORFeome AP-MS and aggregation to gene identifiers. Retain co-complex association; displayed accession suffixes do not establish a natural FAS isoform6 function. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. |
| GO:0005515 protein binding | IPI PMID:35922511 A physical wiring diagram for the human immune system. | KEEP AS NON CORE | Summary: FAS association with FASLG is supported in the specified assay context. Reason: The original leukocyte-screen matrix has positive reciprocal FAS/FASLG cells (1.92865 and0.3917; combined2.32035), with construct metadata verified. This target pair is not a new confirmatory SPR measurement in this paper; the cited1.6nM value comes from earlier work. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. |
| GO:0005515 protein binding | IPI PMID:7536190 A novel protein that interacts with the death domain of Fas/... | KEEP AS NON CORE | Summary: FAS association with FADD is supported in the specified assay context. Reason: The complete original abstract explicitly reports death-domain-dependent FASβFADD interaction and a negative FAS loss-of-function mutant. Full Methods/Results are inaccessible, but this partner interaction is directly stated. DISC membership is not a molecular-function replacement. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:7536190 A novel protein that specifically binds to the death domain of Fas/APO1 but not to Fas/APO1 molecules with a loss of function point mutation |
| GO:0005515 protein binding | IPI PMID:7538907 FADD, a novel death domain-containing protein, interacts wit... | KEEP AS NON CORE | Summary: FAS association with FADD is supported in the specified assay context. Reason: The original abstract explicitly reports a FAS-tail yeast two-hybrid interaction with FADD, including wild-type/FD5 versus lpr/FD8 specificity. FADD overexpression phenotypes do not make FAS an adaptor; full Methods/Results remain inaccessible. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:7538907 FADD, which binds Fas and Fas-FD5, a mutant of Fas possessing enhanced killing activity, but not the functionally inactive mutants Fas-LPR and Fas-FD8 |
| GO:0042802 identical protein binding | IPI PMID:21382479 Caveolin-1 mediates Fas-BID signaling in hyperoxia-induced a... | ACCEPT | Summary: FAS self-association is supported in human epithelial cells. Reason: Original Figure3C measures FAS multimerization in human BEAS-2B cells during the hyperoxia/CAV1 experiments. This supports receptor self-association without asserting that every receptor oligomer is an active DISC. Supporting Evidence: PMID:21382479 the colocalization and interaction of Cav-1 and Fas increased, followed by Fas multimer and DISC formation |
| GO:0042802 identical protein binding | IPI PMID:7536190 A novel protein that interacts with the death domain of Fas/... | ACCEPT | Summary: FAS self-association is supported by the exact curated FASβFAS interaction record. Reason: The saved IntAct record EBI-494924 is an exact positive human FASβFAS two-hybrid association for PMID:7536190: both participants are UniProtKB:P25445 and both species are human. Together with the independently supported FAS self-association in PMID:21382479 and PMID:7538908, this supports the gene-level identical-protein-binding claim. The original operative paper experiment and figure pixels were not recovered, so its construct details are not independently certified here. The inherited quotation describes FADD self-association and is preserved only as an inherited anchor; it does not support this FASβFAS row. That misplaced review anchor is not evidence of an upstream IntAct source defect. Supporting Evidence: PMID:7536190 the region upstream to the death domain prompts self-association of the protein |
| GO:0042802 identical protein binding | IPI PMID:7538908 RIP: a novel protein containing a death domain that interact... | ACCEPT | Summary: The original abstract explicitly supports FAS self-association. Reason: The yeast two-hybrid study reports association of the FAS intracellular domain with itself and with RIP, with loss in the lpr mutant. Full Methods/Results are inaccessible; retain the explicit positive original result and defer to the experimental curation. Supporting Evidence: PMID:7538908 we have identified two gene products that associate with the intracellular domain of Fas: Fas itself, and a novel 74 kDa protein we have named RIP |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: HPA cell-line immunofluorescence supports plasma-membrane localization of FAS. Reason: The actual HPA FAS XML and subcellular page report supported plasma-membrane staining with antibody HPA027444 in A-431 and U-251 MG cells; the corresponding images were inspected. Cytosolic and nuclear-body signals are also recorded, so the assay does not establish exclusive membrane localization. The antigen is an N-terminal FAS region and does not resolve natural isoforms. This is cell-line immunofluorescence evidence, not a claim that only isoform 1 was assayed. |
| GO:0005031 tumor necrosis factor receptor activity | IDA PMID:12221075 Glutathione peroxidase-1 protects from CD95-induced apoptosi... | MODIFY | Summary: FAS has death-receptor activity; literal TNF receptor activity is too specific in the wrong ligand direction. Reason: Official GO:0005031 requires binding the TNF cytokine. Original human-cell CH11 activation, surface staining and apoptosis/caspase assays establish CD95/FAS receptor signaling, not TNF binding. Refine to GO:0005035 death receptor activity, consistent with FASL biology and the parallel phylogenetic review. Proposed replacements: death receptor activity Supporting Evidence: PMID:12221075 Through the induction of apoptosis, CD95 plays a crucial role in the immune response and the elimination of cancer cells |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | IDA PMID:12221075 Glutathione peroxidase-1 protects from CD95-induced apoptosi... | ACCEPT | Summary: FAS directly initiates death-domain-dependent extrinsic apoptosis. Reason: Original Methods/Results show CH11-activated human FAS signaling with caspase activation and apoptosis in T47D, MCF7/CD95 and Jurkat contexts. GPX1 modulates downstream susceptibility; FAS remains the initiating receptor. Supporting Evidence: PMID:12221075 Ligation of CD95 receptor activates a complex signaling network that appears to implicate the generation of reactive oxygen species (ROS) file:human/FAS/FAS-deep-research-falcon.md FAS/CD95 is a multifunctional receptor best known for initiating the **extrinsic apoptosis pathway** following engagement by its cognate ligand **FASLG/CD95L**, but it can also signal through **non-apoptotic** programs (e.g., NF-ΞΊB/MAPK) depending on stimulus strength, ligand form, and DISC composition. PMID:39513921 Upon activation with its cognate ligand or with agonistic antibodies, CD95 DD interacts with DD of Fas-associated protein with death domain (FADD) to initiate DR signaling via the formation of the death-inducing signaling complex (DISC) |
| GO:0036337 Fas signaling pathway | IDA PMID:12221075 Glutathione peroxidase-1 protects from CD95-induced apoptosi... | ACCEPT | Summary: The original human-cell experiments directly assay FAS signaling. Reason: CH11 receptor stimulation and downstream death/caspase measurements establish FAS signaling in the tested human cells. Mouse Jo2 experiments provide separate corroboration and are not redescribed as human assays. Supporting Evidence: PMID:12221075 Ligation of CD95 receptor activates a complex signaling network |
| GO:1903428 positive regulation of reactive oxygen species biosynthetic process | IDA PMID:12221075 Glutathione peroxidase-1 protects from CD95-induced apoptosi... | KEEP AS NON CORE | Summary: Reactive-oxygen production is a conditional downstream FAS response. Reason: The original human-cell assays connect CD95 stimulation to ROS accumulation and GPX1-dependent protection. This is a downstream apoptotic output, not a ROS-generating enzymatic activity of FAS or a universal receptor response. Supporting Evidence: PMID:12221075 Anti-CD95 antibodies triggered an early generation of ROS in human breast cancer T47D cells |
| GO:0005515 protein binding | IPI PMID:15917238 CD47 augments Fas/CD95-mediated apoptosis. | KEEP AS NON CORE | Summary: FAS association with CD47 is supported in the specified assay context. Reason: Actual original Methods and Figure7 describe CH11-associated FAS/CD47 recovery and reciprocal immunoprecipitation in human Jurkat cells, with deficient-cell controls. The authors allow an intervening protein; retain the association without claiming an isolated direct contact. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | IDA PMID:9333124 Fas and Fas ligand interaction is necessary for human osteob... | ACCEPT | Summary: FAS activation triggers extrinsic apoptosis in human osteoblast models. Reason: The original abstract explicitly describes anti-FAS-induced apoptosis in MG63 and primary human osteoblast cultures, with FASL/activated-PBMC effects blocked by FAS chimeric protein. Full Methods/Results remain inaccessible; the positive receptor-death context is directly stated. Supporting Evidence: PMID:9333124 Fas and Fas ligand interaction is necessary for human osteoblast apoptosis. |
| GO:0005515 protein binding | IPI PMID:18846110 Identification of an antiapoptotic protein complex at death ... | KEEP AS NON CORE | Summary: FAS association with DDX3X is supported in the specified assay context. Reason: Original Figure7f and associated human Jurkat experiments recover DDX3X with FAS in an inhibitory signaling complex. The interaction does not confer RNA-helicase or translational activity on FAS. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. |
| GO:0032872 regulation of stress-activated MAPK cascade | IMP PMID:11096076 Glutamine-dependent antiapoptotic interaction of human gluta... | KEEP AS NON CORE | Summary: FAS conditionally regulates stress-activated MAPK signaling during glutamine deprivation. Reason: Original HeLa assays show anti-FAS-induced ASK1/JNK activation under glutamine starvation; ERK is activated in both conditions and p38 phosphorylation is not detected. Retain the demonstrated conditional signaling output without assigning kinase activity to FAS. Supporting Evidence: PMID:11096076 Fas ligation activated apoptosis signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK; also known as stress-activated protein kinase (SAPK)) in Gln-deprived cells |
| GO:0034198 cellular response to amino acid starvation | IMP PMID:11096076 Glutamine-dependent antiapoptotic interaction of human gluta... | KEEP AS NON CORE | Summary: FAS participates in the apoptotic response under amino-acid starvation conditions. Reason: Original HeLa experiments compare glutamine deprivation and repletion before CH11 stimulation, with differential ASK1/JNK and death responses. This supports the tested response context, not direct nutrient sensing by FAS. Supporting Evidence: PMID:11096076 HeLa cells were susceptible to Fas-mediated apoptosis under the condition of glutamine deprivation |
| GO:0036337 Fas signaling pathway | IMP PMID:11096076 Glutamine-dependent antiapoptotic interaction of human gluta... | ACCEPT | Summary: Anti-FAS stimulation directly activates the FAS signaling pathway. Reason: The original HeLa study follows receptor stimulation through signaling and apoptotic endpoints, including starvation/repletion comparisons. QRSβASK1 interaction experiments concern other proteins and are not FAS binding or catalytic evidence. Supporting Evidence: PMID:11096076 HeLa cells were susceptible to Fas-mediated apoptosis |
| GO:2001235 positive regulation of apoptotic signaling pathway | IMP PMID:11096076 Glutamine-dependent antiapoptotic interaction of human gluta... | ACCEPT | Summary: FAS activation promotes apoptotic signaling in the tested human cells. Reason: Original CH11-treated HeLa experiments measure downstream signaling, caspase activation, morphology and DNA fragmentation. The receptor initiates this pathway; glutamine availability changes the response magnitude. Supporting Evidence: PMID:11096076 HeLa cells were susceptible to Fas-mediated apoptosis |
| GO:0005516 calmodulin binding | IDA PMID:24914971 Structural insights into the mechanism of calmodulin binding... | KEEP AS NON CORE | Summary: A human FAS peptide binds calmodulin in primary biophysical experiments. Reason: The original Figure1c SPR caption and deposited 3EWT complex support binding of a synthetic human FAS peptide to human calmodulin. Main Methods/Results remain inaccessible. Retain this auxiliary interaction without inferring full-receptor stoichiometry, a unique site or universal physiological regulation. Supporting Evidence: PMID:24914971 Structural insights into the mechanism of calmodulin binding to death receptors. |
| GO:0031264 death-inducing signaling complex | IDA PMID:21803845 PMLRARΞ± binds to Fas and suppresses Fas-mediated apoptosis t... | MODIFY | Summary: FAS is a component of the CD95 death-inducing signaling complex. Reason: Original human-cell anti-FAS immunoprecipitation in Figure6A recovers FADD/caspase8 and examines the effect of PMLβRARalpha. The CD95-specific child better captures this receptor complex than the broader DISC term. No natural isoform-specific assignment is made. Proposed replacements: CD95 death-inducing signaling complex Supporting Evidence: PMID:21803845 2011 Jul 29. PMLRARΞ± binds to Fas and suppresses Fas-mediated apoptosis through recruiting c-FLIP in vivo. |
| GO:0097527 necroptotic signaling pathway | IMP PMID:16507998 Inhibition of ADP/ATP exchange in receptor-interacting prote... | KEEP AS NON CORE | Summary: FAS can initiate a conditional necroptotic signaling response. Reason: Original anti-FAS/zVAD experiments in human U937/THP1 cells support caspase-inhibited death with RIP-associated sensitivity; the independent primary RIP-null/rescue experiments in PMID:11101870 strengthen the receptor/RIP context. Official GO:0097527 includes RIPK1 and/or RIPK3 signaling. Do not infer an assayed FASβRIPK3βMLKL complex or make this the principal receptor outcome. Supporting Evidence: PMID:16507998 These observations demonstrate a novel mechanism initiated through death receptor ligation and mediated by RIP that results in the suppression of ANT activity and necrosis |
| GO:0005886 plasma membrane | IMP PMID:21625644 Modulation of the CD95-induced apoptosis: the role of CD95 N... | ACCEPT | Summary: The tested human FAS receptor is present at the plasma membrane. Reason: Original human HeLa flow-cytometry/confocal experiments directly examine surface FAS and engineered glycosylation mutants. These constructs do not establish an exclusive natural isoform1 localization or exclude other membrane products. Supporting Evidence: PMID:21625644 Modulation of the CD95-induced apoptosis: the role of CD95 N-glycosylation. |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:21625644 Modulation of the CD95-induced apoptosis: the role of CD95 N... | ACCEPT | Summary: FAS positively regulates apoptosis through receptor activation. Reason: Original human HeLa FAS stimulation/death experiments and DISC analyses support the proapoptotic receptor role. Glycosylation-site substitutions are experimental mutants, not evidence of natural isoform-specific function. Supporting Evidence: PMID:21625644 Modulation of the CD95-induced apoptosis: the role of CD95 N-glycosylation. |
| GO:0009986 cell surface | IDA PMID:22891283 Vesicles released by activated T cells induce both Fas-media... | ACCEPT | Summary: FAS is experimentally detected at the human-cell surface. Reason: Original Methods describe nonpermeabilized PE-DX2 FAS surface staining on ice, and Results/Figure2 compare human Jurkat derivatives. This directly supports the cell-surface annotation. Supporting Evidence: PMID:22891283 2012 Aug 13. Vesicles released by activated T cells induce both Fas-mediated RIP-dependent apoptotic and Fas-independent nonapoptotic cell deaths. |
| GO:0097191 extrinsic apoptotic signaling pathway | IMP PMID:22891283 Vesicles released by activated T cells induce both Fas-media... | ACCEPT | Summary: FAS mediates an extrinsic apoptotic response to activated-T-cell vesicles. Reason: Original human Jurkat deficiency/reconstitution comparisons distinguish FAS-dependent apoptosis from a separate FAS-independent nonapoptotic vesicle effect. Only the former supports the FAS apoptotic annotation. Supporting Evidence: PMID:22891283 2012 Aug 13. Vesicles released by activated T cells induce both Fas-mediated RIP-dependent apoptotic and Fas-independent nonapoptotic cell deaths. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | UNDECIDED | Summary: The specific proteomic FAS exosome identification remains unverified. Reason: The original main Methods establish human B-cell exosome isolation and proteomic thresholds, but the FAS target entry in supplemental TableS1 was not recovered. The main-text FASN label is a different protein. Preserve the curated HDA assertion without treating inaccessible target evidence as contamination or absence. Supporting Evidence: PMID:20458337 2010 May 11. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-139952 | ACCEPT | Summary: Reactome explicitly models FAS at the plasma membrane in this event. Reason: The event 'Caspase-8 processing in the DISC' reaches the actual FAS entity by 139952 β input β 2671813 β hasMember β 2671811 β hasComponent β 43124 β hasComponent β 76195 β hasComponent β 76564 β hasComponent β 66248. Entity 66248 is P25445, modeled residues 26β335, with GO:0005886 compartment. This validates the CC assertion through the modeled participant, even when the event title foregrounds another molecule. It does not assign that other molecule's activity to FAS or establish a universal natural-isoform location. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-141310 | ACCEPT | Summary: Reactome explicitly models FAS at the plasma membrane in this event. Reason: The event 'FASL:FAS Receptor Trimer:FADD complex binds procaspase-10' reaches the actual FAS entity by 141310 β input β 43124 β hasComponent β 76195 β hasComponent β 76564 β hasComponent β 66248. Entity 66248 is P25445, modeled residues 26β335, with GO:0005886 compartment. This validates the CC assertion through the modeled participant, even when the event title foregrounds another molecule. It does not assign that other molecule's activity to FAS or establish a universal natural-isoform location. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-3465429 | ACCEPT | Summary: Reactome explicitly models FAS at the plasma membrane in this event. Reason: The event 'FLIP(S) and procaspase-8 form heterodimer' reaches the actual FAS entity by 3465429 β input β 3465443 β hasComponent β 2671814 β hasMember β 43124 β hasComponent β 76195 β hasComponent β 76564 β hasComponent β 66248. Entity 66248 is P25445, modeled residues 26β335, with GO:0005886 compartment. This validates the CC assertion through the modeled participant, even when the event title foregrounds another molecule. It does not assign that other molecule's activity to FAS or establish a universal natural-isoform location. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-3465448 | ACCEPT | Summary: Reactome explicitly models FAS at the plasma membrane in this event. Reason: The event 'Caspase-8 and FLIP(L) processing at DISC' reaches the actual FAS entity by 3465448 β input β 3371381 β hasComponent β 3465443 β hasComponent β 2671814 β hasMember β 43124 β hasComponent β 76195 β hasComponent β 76564 β hasComponent β 66248. Entity 66248 is P25445, modeled residues 26β335, with GO:0005886 compartment. This validates the CC assertion through the modeled participant, even when the event title foregrounds another molecule. It does not assign that other molecule's activity to FAS or establish a universal natural-isoform location. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-3465459 | ACCEPT | Summary: Reactome explicitly models FAS at the plasma membrane in this event. Reason: The event 'FLIP(L) and procaspase-8 form heterodimer in FasL/CD95 signaling' reaches the actual FAS entity by 3465459 β input β 75114 β hasComponent β 43124 β hasComponent β 76195 β hasComponent β 76564 β hasComponent β 66248. Entity 66248 is P25445, modeled residues 26β335, with GO:0005886 compartment. This validates the CC assertion through the modeled participant, even when the event title foregrounds another molecule. It does not assign that other molecule's activity to FAS or establish a universal natural-isoform location. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5675456 | ACCEPT | Summary: Reactome explicitly models FAS at the plasma membrane in this event. Reason: The event 'FLIP(L) and procaspase-8 form heterodimer' reaches the actual FAS entity by 5675456 β input β 3465443 β hasComponent β 2671814 β hasMember β 43124 β hasComponent β 76195 β hasComponent β 76564 β hasComponent β 66248. Entity 66248 is P25445, modeled residues 26β335, with GO:0005886 compartment. This validates the CC assertion through the modeled participant, even when the event title foregrounds another molecule. It does not assign that other molecule's activity to FAS or establish a universal natural-isoform location. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6800001 | ACCEPT | Summary: Reactome explicitly models FAS at the plasma membrane in this event. Reason: The event 'TP53 family members stimulate FAS gene expression' reaches the actual FAS entity by 6800001 β output β 66248. Entity 66248 is P25445, modeled residues 26β335, with GO:0005886 compartment. This validates the CC assertion through the modeled participant, even when the event title foregrounds another molecule. It does not assign that other molecule's activity to FAS or establish a universal natural-isoform location. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-71050 | ACCEPT | Summary: Reactome explicitly models FAS at the plasma membrane in this event. Reason: The event 'Trimerization of the FASL:FAS receptor complex' reaches the actual FAS entity by 71050 β input β 76564 β hasComponent β 66248. Entity 66248 is P25445, modeled residues 26β335, with GO:0005886 compartment. This validates the CC assertion through the modeled participant, even when the event title foregrounds another molecule. It does not assign that other molecule's activity to FAS or establish a universal natural-isoform location. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-73945 | ACCEPT | Summary: Reactome explicitly models FAS at the plasma membrane in this event. Reason: The event 'FAS-mediated dimerization of procaspase-8' reaches the actual FAS entity by 73945 β input β 75114 β hasComponent β 43124 β hasComponent β 76195 β hasComponent β 76564 β hasComponent β 66248. Entity 66248 is P25445, modeled residues 26β335, with GO:0005886 compartment. This validates the CC assertion through the modeled participant, even when the event title foregrounds another molecule. It does not assign that other molecule's activity to FAS or establish a universal natural-isoform location. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-75244 | ACCEPT | Summary: Reactome explicitly models FAS at the plasma membrane in this event. Reason: The event 'FASL binds FAS Receptor' reaches the actual FAS entity by 75244 β input β 66248. Entity 66248 is P25445, modeled residues 26β335, with GO:0005886 compartment. This validates the CC assertion through the modeled participant, even when the event title foregrounds another molecule. It does not assign that other molecule's activity to FAS or establish a universal natural-isoform location. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-83586 | ACCEPT | Summary: Reactome explicitly models FAS at the plasma membrane in this event. Reason: The event 'FASL:FAS Receptor Trimer:FADD complex binds pro-Caspase-8' reaches the actual FAS entity by 83586 β input β 43124 β hasComponent β 76195 β hasComponent β 76564 β hasComponent β 66248. Entity 66248 is P25445, modeled residues 26β335, with GO:0005886 compartment. This validates the CC assertion through the modeled participant, even when the event title foregrounds another molecule. It does not assign that other molecule's activity to FAS or establish a universal natural-isoform location. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-83650 | ACCEPT | Summary: Reactome explicitly models FAS at the plasma membrane in this event. Reason: The event 'FasL:Fas binds FADD' reaches the actual FAS entity by 83650 β input β 76195 β hasComponent β 76564 β hasComponent β 66248. Entity 66248 is P25445, modeled residues 26β335, with GO:0005886 compartment. This validates the CC assertion through the modeled participant, even when the event title foregrounds another molecule. It does not assign that other molecule's activity to FAS or establish a universal natural-isoform location. |
| GO:0071455 cellular response to hyperoxia | IMP PMID:21382479 Caveolin-1 mediates Fas-BID signaling in hyperoxia-induced a... | KEEP AS NON CORE | Summary: FAS contributes to a hyperoxia-associated epithelial-cell response. Reason: Original human BEAS-2B experiments measure FAS clustering, FADD/CAV1 association and compartment redistribution during hyperoxia. Mouse Cav1-deletion experiments are separate. Retain the conditional response without assigning oxygen-sensor activity to FAS. Supporting Evidence: PMID:21382479 We found that Cav-1 regulated Fas signaling and mediated the communication between extrinsic and intrinsic pathways |
| GO:0031265 CD95 death-inducing signaling complex | IDA PMID:20935634 The Fas-FADD death domain complex structure reveals the basi... | ACCEPT | Summary: FAS contributes the receptor death domain to the CD95 DISC. Reason: Original reconstitution, interface mutagenesis, human-cell FRET and Jurkat death assays support FASβFADD complex assembly. The crystal uses mouse FAS death domain with human FADD; human biochemical/cellular experiments provide separate target evidence. Exact stoichiometry is assay-specific. Supporting Evidence: PMID:20935634 The death-inducing signaling complex (DISC) formed by the death receptor Fas, the adaptor protein FADD and caspase-8 mediates the extrinsic apoptotic program |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:20935634 The Fas-FADD death domain complex structure reveals the basi... | ACCEPT | Summary: FAS receptor signaling promotes apoptosis. Reason: Original human Jurkat anti-FAS/FASL-LZ assays connect FAS death-domain interface mutations to altered cell death, with human biochemical/FRET evidence. The mixed-species crystal alone is not represented as a human-cell phenotype. Supporting Evidence: PMID:20935634 Mutations in Fas that disrupt the DISC cause autoimmune lymphoproliferative syndrome (ALPS) |
| GO:0045121 membrane raft | IDA PMID:21382479 Caveolin-1 mediates Fas-BID signaling in hyperoxia-induced a... | ACCEPT | Summary: A dynamic fraction of human FAS occupies membrane rafts. Reason: Original human BEAS-2B fractionation and Figure3D show FAS in raft fractions with time-dependent redistribution under hyperoxia. Retain the supported raft pool without claiming exclusive or permanent localization. Supporting Evidence: PMID:21382479 the colocalization and interaction of Cav-1 and Fas increased, followed by Fas multimer and DISC formation |
| GO:0005515 protein binding | IPI PMID:21109225 Whole-exome-sequencing-based discovery of human FADD deficie... | KEEP AS NON CORE | Summary: FAS association with FADD is supported in the specified assay context. Reason: Original Results/Figure1H show recombinant His-FAS death domain retaining FADD, including the C105W comparison under specified salt conditions. The FADD-focused title does not invalidate the positive FAS-binding assay. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. |
| GO:0071260 cellular response to mechanical stimulus | IEP PMID:19593445 Expression of the Bcl-2 protein BAD promotes prostate cancer... | UNDECIDED | Summary: The cited original does not resolve FAS involvement in mechanical-stimulus response. Reason: The complete cached original main Methods/Results concern regulation of BAD and apoptosis; no operative FAS mechanical-stimulus assay was identified. PMID identity and the official GO definition were verified. Flag the reference mismatch while leaving the imported experimental assertion undecided; no replacement PMID is guessed. Supporting Evidence: PMID:19593445 Expression of the Bcl-2 protein BAD promotes prostate cancer growth. |
| GO:0031264 death-inducing signaling complex | IDA PMID:11101870 Fas triggers an alternative, caspase-8-independent cell deat... | MODIFY | Summary: The original isolates the CD95-specific death-inducing signaling complex. Reason: Original human Jurkat Flag-FASL immunoprecipitation (Figure3g and Methods) recovers FAS, FADD, procaspase8 and RIP, with a nonagonistic ZB4 control. Refine the broad DISC component to CD95 DISC; the separate RIP-dependent death phenotype does not imply direct binary contacts. Proposed replacements: CD95 death-inducing signaling complex Supporting Evidence: PMID:11101870 Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. |
| GO:0019900 kinase binding | IPI PMID:7538908 RIP: a novel protein containing a death domain that interact... | KEEP AS NON CORE | Summary: FAS binds the RIP kinase in the original interaction assay. Reason: The original abstract explicitly reports a FAS-intracellular-domain/RIP yeast two-hybrid interaction. Full Methods/Results remain inaccessible. Retain this auxiliary kinase-binding context; kinase catalytic activity belongs to RIP, not FAS. Supporting Evidence: PMID:7538908 RIP contains an N-terminal region with homology to protein kinases and a C-terminal region containing a cytoplasmic motif (death domain) |
| GO:0006915 apoptotic process | IDA PMID:9681877 Effect of age and apoptosis on the mouse homologue of the hu... | ACCEPT | Summary: Human patient-derived lymphoid cells undergo FAS-triggered apoptosis. Reason: The original abstract explicitly reports enhanced anti-FAS-induced apoptosis in human Werner-syndrome lymphoid cells. Mouse WRN cloning in the same paper does not invalidate the human receptor assay, and does not establish a FAS helicase or aging function. Supporting Evidence: PMID:9681877 Effect of age and apoptosis on the mouse homologue of the huWRN gene. |
| GO:0005515 protein binding | IPI PMID:15465831 A death receptor-associated anti-apoptotic protein, BRE, inh... | KEEP AS NON CORE | Summary: FAS association with BRE/BABAM2 is supported in the specified assay context. Reason: Original Figures4/6 and Methods support reciprocal association between FAS and BRE in human HeLa cells. The authors allow indirect association; the partner context does not establish a new FAS enzymatic or adaptor activity. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. |
| GO:0042981 regulation of apoptotic process | NAS PMID:7533181 Three functional soluble forms of the human apoptosis-induci... | ACCEPT | Summary: FAS products regulate apoptosis in the reported expression experiments. Reason: The original abstract reports human soluble FAS variants expressed in COS cells that inhibit apoptosis, complementing the established proapoptotic membrane-receptor role. Retain the broad regulation term without assigning identical effects to every alternative product. Supporting Evidence: PMID:7533181 Three functional soluble forms of the human apoptosis-inducing Fas molecule are produced by alternative splicing. |
| GO:0006915 apoptotic process | TAS PMID:10871852 p38 protects human melanoma cells from UV-induced apoptosis ... | ACCEPT | Summary: FAS contributes to apoptosis in human melanoma cells. Reason: Original Results/Figure4D show that antagonistic anti-FAS reduces UV-induced apoptosis in parental LU1205 cells, with IΞΊB-DN and TNFR1-blockade comparisons. Here NF-kappaB regulates FAS expression; these data do not establish FAS as a transcription factor. Supporting Evidence: PMID:10871852 p38 protects human melanoma cells from UV-induced apoptosis through down-regulation of NF-kappaB activity and Fas expression. |
| GO:0006915 apoptotic process | TAS PMID:1375228 Purification and molecular cloning of the APO-1 cell surface... | ACCEPT | Summary: Antibody activation of expressed human FAS triggers apoptosis. Reason: Original BL60-P7 transfection, surface staining and DNA-fragmentation assays distinguish APO-1-positive cloneK50 from negative cloneK04. This directly supports apoptosis downstream of the expressed human receptor. Supporting Evidence: PMID:1375228 Cross-linking of the APO-1 antigen by anti-APO-1 induced programmed cell death, apoptosis, of APO-1 positive cells |
| GO:0007165 signal transduction | TAS PMID:9360929 Requirement for the CD95 receptor-ligand pathway in c-Myc-in... | TOO GENERAL | Summary: A positive FAS signaling context is already represented more specifically. Reason: The accessible original abstract describes cell-surface FASβFASL-dependent apoptosis and MYC-dependent sensitization downstream of receptor activation. Signal transduction is true but subsumed by the retained GO:0036337 Fas signaling pathway. This specificity judgment uses the positive abstract and independent receptor evidence; it does not claim access to the original full Methods/Results, a particular natural isoform, or a transcriptional activity of FAS. Supporting Evidence: PMID:9360929 Requirement for the CD95 receptor-ligand pathway in c-Myc-induced apoptosis. |
| GO:0038023 signaling receptor activity | TAS PMID:1375228 Purification and molecular cloning of the APO-1 cell surface... | MODIFY | Summary: The measured receptor function is death-receptor activity. Reason: Original surface-expression and antibody-triggered death assays establish signaling by human APO-1/FAS. GO:0005035 captures this specific receptor function. The physiological ligand was unknown in this paper; TNFR-family sequence membership is not a TNF ligand-binding assay. Proposed replacements: death receptor activity Supporting Evidence: PMID:1375228 The APO-1 antigen as defined by the mouse monoclonal antibody anti-APO-1 was previously found to be expressed on the cell surface |
| GO:0043066 negative regulation of apoptotic process | TAS PMID:7510905 Protection from Fas-mediated apoptosis by a soluble form of ... | KEEP AS NON CORE | Summary: A soluble FAS-product context inhibits apoptosis. Reason: The original abstract reports inhibition of anti-FAS-induced apoptosis by a transmembrane-deletion FAS product/conditioned medium. This is an alternative-product antagonistic effect rather than the principal membrane-receptor activity. Full Methods/Results remain inaccessible; neither universal soluble-product inhibition nor a proven sequestration mechanism is asserted. Supporting Evidence: PMID:7510905 Supernatants from cells transfected with the variant messenger RNA blocked apoptosis induced by the antibody to Fas |
| GO:0065003 protein-containing complex assembly | TAS PMID:10875918 Fas preassociation required for apoptosis signaling and domi... | ACCEPT | Summary: FAS assembles into receptor complexes before ligand stimulation. Reason: Original human293T FRET/co-immunoprecipitation, CRD1 perturbations and endogenous H9 crosslinking support preassociation. Unstimulated complexes lack the reported caspase8/PARP cleavage response; preassociation alone is not an active DISC. Supporting Evidence: PMID:10875918 Preassociated Fas complexes were found in living cells by means of fluorescence resonance energy transfer between variants of green fluorescent protein |
| GO:0005829 cytosol | NAS PMID:7533181 Three functional soluble forms of the human apoptosis-induci... | UNDECIDED | Summary: Cytosolic FAS localization is unresolved from the accessible source. Reason: The original abstract describes soluble FAS variants, but soluble or secreted protein is not equivalent to cytosolic localization. Operative localization evidence in the full paper was not recovered. Preserve the imported assertion without removing it from abstract-only evidence. Supporting Evidence: PMID:7533181 transcripts are expressed as soluble Fas proteins |
| GO:0038023 signaling receptor activity | NAS PMID:7533181 Three functional soluble forms of the human apoptosis-induci... | MODIFY | Summary: The gene-level signaling-receptor assertion is refined to death receptor activity. Reason: The complete original PMID:7533181 abstract explicitly introduces Fas/Apo-1 as an apoptosis-signaling cell-surface antigen. This NAS row has no isoform restriction, so its gene-level signaling-receptor claim is refined to the independently established death receptor activity (GO:0005035), consistent with the other receptor context. The same abstract studies human FasTMDel, FasDel2 and FasDel3 transcripts, COS-cell expression and soluble-product inhibition; those observations do not establish death-receptor signaling by every soluble product. Full operative Methods/Results remain unavailable. No natural isoform is assigned, and no membrane-receptor assay is represented as an assay of a soluble product. Proposed replacements: death receptor activity Supporting Evidence: PMID:7533181 Three functional soluble forms of the human apoptosis-inducing Fas molecule are produced by alternative splicing. |
| GO:0005515 protein binding | IPI PMID:11717445 Caspase-10 is an initiator caspase in death receptor signali... | KEEP AS NON CORE | Summary: FAS association with CASP8 is supported in the specified assay context. Reason: Original Figure2B detects caspase8 in stimulated primary-human-T-cell FAS immunoprecipitates. Retain this historical complex-association record without claiming purified binary FASβcaspase8 contact, without interpreting snapshot absence as biological invalidity or official withdrawal. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Historical source retained; retired only from the pinned current GOA active set (see the source guide), not judged biologically false or officially withdrawn. Supporting Evidence: PMID:11717445 Fas crosslinking in primary human T cells leads to the recruitment and activation of caspase-10. |
| GO:0005515 protein binding | IPI PMID:12887920 Induction of TNF receptor I-mediated apoptosis via two seque... | KEEP AS NON CORE | Summary: FAS association with CASP8 is supported in the specified assay context. Reason: Original Figure2C and Results explicitly detect caspase8 in Flag-FASL-isolated receptor complexes in human HT1080 cells. This positive-control experiment supports the source context despite the TNFR1-focused title; it is co-complex evidence, not purified binary binding. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:12887920 Apoptosis induced by TNF-receptor I (TNFR1) is thought to proceed via recruitment of the adaptor FADD and caspase-8 to the receptor complex. |
| GO:0005515 protein binding | IPI PMID:16498403 The role of receptor internalization in CD95 signaling. | KEEP AS NON CORE | Summary: FAS association with CASP8 is supported in the specified assay context. Reason: Original ligand-isolated FAS complexes in human BJAB cells contain caspase8 (Figures1/3). Endosomal experiments are separately described. Retain the supported complex association without replacing the molecular function with a cellular-component term. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:16498403 Recruitment of DISC components to the activated receptor predominantly occurs after the receptor has moved into an endosomal compartment and blockade of CD95 internalization impairs DISC formation and apoptosis. |
| GO:0005515 protein binding | IPI PMID:17159907 Palmitoylation of CD95 facilitates formation of SDS-stable r... | KEEP AS NON CORE | Summary: FAS association with CASP8 is supported in the specified assay context. Reason: Original Figure1A/B detects FAS in caspase8 immunoprecipitates after LzCD95L stimulation of human SKW6.4/H9 cells; Figure4 depletion/gradient experiments support the complex. Purified binary FASβcaspase8 binding is not established. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:17159907 these SDS-stable forms of CD95 correspond to very high molecular weight DISC complexes (hiDISC) and are the sites of caspase-8 activation. |
| GO:0005515 protein binding | IPI PMID:18328427 Yes and PI3K bind CD95 to signal invasion of glioblastoma. | UNDECIDED | Summary: The imported FASβFADD association remains unresolved from accessible original evidence. Reason: The genuine repository file contains only the article summary; operative Methods/Results for the exact FASβFADD association were not recovered. IntAct records the source pair, but the YES/PI3K-focused abstract cannot verify or refute it. Preserve the curated source context without inferring an experimental attribution error from the title. Supporting Evidence: PMID:18328427 Binding of CD95 Ligand to CD95 on glioblastoma cells recruits the Src family member Yes and the p85 subunit of phosphatidylinositol 3-kinase to CD95 |
| GO:0005515 protein binding | IPI PMID:18328427 Yes and PI3K bind CD95 to signal invasion of glioblastoma. | UNDECIDED | Summary: The imported FASβCASP8 association remains unresolved from accessible original evidence. Reason: The genuine repository file contains only the article summary; operative Methods/Results for the exact FASβcaspase-8 association were not recovered. IntAct records the source pair, but the YES/PI3K-focused abstract cannot verify or refute it. Preserve the curated source context without inferring an experimental attribution error from the title. Supporting Evidence: PMID:18328427 Our results uncover CD95 as an activator of PI3K and, most importantly, as a crucial trigger of basal invasion of glioblastoma in vivo. |
| GO:0005515 protein binding | IPI PMID:18846110 Identification of an antiapoptotic protein complex at death ... | KEEP AS NON CORE | Summary: FAS association with GSK3B is supported in the specified assay context. Reason: Original Figure7f detects GSK3B in FAS-associated inhibitory complexes in human Jurkat cells. Retain the association without assigning kinase activity to FAS or deriving a separate function from the partner label. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:18846110 We identified an antiapoptotic protein complex associated with death receptors that contains glycogen synthase kinase-3 (GSK3), DDX3 and cellular inhibitor of apoptosis protein-1 (cIAP-1). |
| GO:0005515 protein binding | IPI PMID:18846110 Identification of an antiapoptotic protein complex at death ... | KEEP AS NON CORE | Summary: FAS association with BIRC2/cIAP1 is supported in the specified assay context. Reason: Original Figure7f supports cIAP1 in FAS-associated inhibitory complexes in human Jurkat cells. Association with an inhibitor-of-apoptosis protein does not establish an ubiquitin-ligase activity of FAS. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:18846110 an antiapoptotic complex of GSK3, DDX3 and cIAP-1 caps death receptors, providing a checkpoint to counterbalance apoptotic signaling. |
| GO:0005515 protein binding | IPI PMID:21382479 Caveolin-1 mediates Fas-BID signaling in hyperoxia-induced a... | KEEP AS NON CORE | Summary: FAS association with FADD is supported in the specified assay context. Reason: Original Figure2B shows FASβFADD association in human BEAS-2B cells with CAV1-expression comparisons; mouse Cav1-knockout experiments are separate. The molecular association is retained without substituting a DISC cellular-component term. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:21382479 Fas, the Fas-associated death domain, and caspase 8 form the death-inducing signaling complex (DISC). |
| GO:0005515 protein binding | IPI PMID:21625644 Modulation of the CD95-induced apoptosis: the role of CD95 N... | KEEP AS NON CORE | Summary: FAS association with CASP8 is supported in the specified assay context. Reason: Original Figure7 detects caspase8 in anti-FAS immunoprecipitates from human HeLa cells in the FAS glycosylation study. The co-complex result is positive but does not establish purified binary binding or natural isoform specificity. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:21625644 The DISC consists of oligomerized CD95, the adaptor molecule FADD, two isoforms of procaspase-8 |
| GO:0005515 protein binding | IPI PMID:21803845 PMLRARΞ± binds to Fas and suppresses Fas-mediated apoptosis t... | KEEP AS NON CORE | Summary: FAS association with FASLG is supported in the specified assay context. Reason: Original Figures5B/C examine FASLβFAS association in human-cell experiments. Retain the supported ligandβreceptor association; the separate PMLβRARalpha perturbation context does not invalidate it. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:21803845 PMLRARΞ± binds to Fas and suppresses Fas-mediated apoptosis through recruiting c-FLIP in vivo. |
| GO:0005515 protein binding | IPI PMID:21803845 PMLRARΞ± binds to Fas and suppresses Fas-mediated apoptosis t... | KEEP AS NON CORE | Summary: FAS association with FADD is supported in the specified assay context. Reason: Original Figure6A detects FADD in anti-FAS immunoprecipitates from human U937-PR9 cells. PMLβRARalpha-dependent inhibition changes complex composition but does not eliminate the positive association context. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:21803845 Binding of PMLRARΞ± to Fas was mapped to the B-box domain of PML moiety and death domain of Fas. |
| GO:0005515 protein binding | IPI PMID:21803845 PMLRARΞ± binds to Fas and suppresses Fas-mediated apoptosis t... | KEEP AS NON CORE | Summary: FAS association with CASP8 is supported in the specified assay context. Reason: Original Figure6A detects caspase8 in anti-FAS immunoprecipitates from human U937-PR9 cells. Retain the complex association without claiming purified binary binding or deriving protease activity for FAS. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:21803845 PMLRARΞ± recruited c-FLIP(L/S) and excluded procaspase 8 from Fas death signaling complex. |
| GO:0005515 protein binding | IPI PMID:21803845 PMLRARΞ± binds to Fas and suppresses Fas-mediated apoptosis t... | KEEP AS NON CORE | Summary: FAS association with PMLβRARalpha fusion is supported in the specified assay context. Reason: The exact Q15156 source is the PMLβRARalpha fusion, not CFLAR. Original human-cell co-immunoprecipitation and domain experiments support its association with FAS. Retain this cancer-context interaction without assigning the fusion or recruited c-FLIP activities to FAS. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:21803845 Taken together, PMLRARΞ± binds to Fas and blocks Fas-mediated apoptosis in APL by forming an apoptotic inhibitory complex with c-FLIP. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | KEEP AS NON CORE | Summary: FAS association with FADD is supported in the specified assay context. Reason: Authentic original PLA TableS1 page8 lists FADDβFAS as positive, with the exact antibodies in TableS7 page89. The HeLa-cell proximity result meets the published criteria; it is not a purified two-protein binding measurement or a new functional assignment. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:25241761 Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | KEEP AS NON CORE | Summary: FAS association with DAXX is supported in the specified assay context. Reason: Authentic original PLA TableS1 page4 lists FASβDAXX as positive; TableS7 page76 identifies the target assay kit. Retain this proximity observation without inferring a transcriptional or adaptor activity for FAS. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:25241761 we collected βΌ 700 primary antibodies and employed a highly sensitive and specific technique, an in situ proximity ligation assay, to investigate 1204 endogenous PPIs in HeLa cells |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: FAS association with CASP8 is supported in the specified assay context. Reason: The original BioPlex293T table directly joins FAS/Gene355 to CASP8/Gene841 (line43745; pInt0.99999988038695). Tagged AP-MS supports co-complex association. The Methods aggregate proteins to gene identifiers, so accession suffixes alone do not establish a natural isoform-specific function. Retain as non-core under the project binding policy; no more specific molecular activity is established by this interaction. Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. |
| GO:0005886 plasma membrane | EXP PMID:1713127 The polypeptide encoded by the cDNA for human cell surface a... | ACCEPT | Summary: Human FAS is a plasma-membrane death receptor. Reason: The original abstract reports human FAS expression conferring anti-FAS sensitivity in mouse recipient cells, with transmembrane receptor architecture. Human receptor identity and mouse assay host are distinguished; no natural isoform or processing coordinate is inferred. |
| GO:0005886 plasma membrane | EXP PMID:25301068 Fas palmitoylation by the palmitoyl acyltransferase DHHC7 re... | ACCEPT | Summary: Human FAS is a plasma-membrane death receptor. Reason: Original human SW480 surface-flow/biotinylation assays establish plasma-membrane FAS; Brij98/sucrose fractionation shows a raft-associated pool reduced by DHHC7 depletion. FAS is the palmitoylation substrate, not the acyltransferase; engineered C199V is not a natural isoform assignment. Supporting Evidence: |
| GO:0006915 apoptotic process | IEA GO_REF:0000002 | ACCEPT | Summary: The current InterPro source supports FAS participation in apoptosis. Reason: The actual target IPR008063 family maps to GO:0006915. Human receptor activation and DISC-dependent signaling support the apoptotic process (PMID:12221075; PMID:20935634). This is a fresh imported context, distinct from historical combined-method old14; preserve the exact machine source while reconciling its lifecycle separately. |
| GO:0045121 membrane raft | EXP PMID:25301068 Fas palmitoylation by the palmitoyl acyltransferase DHHC7 re... | ACCEPT | Summary: Human FAS has a dynamic detergent-resistant membrane pool. Reason: Original human SW480 surface-flow/biotinylation assays establish plasma-membrane FAS; Brij98/sucrose fractionation shows a raft-associated pool reduced by DHHC7 depletion. FAS is the palmitoylation substrate, not the acyltransferase; engineered C199V is not a natural isoform assignment. Supporting Evidence: |
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Download this section (compressed HTML)Q: In the human soluble-product expression contexts studied in PMID:7533181 and PMID:8648105, how does the retained downstream death-domain sequence of TMdel/isoform 6 contribute, if at all, to inhibition compared with the shorter ectodomain products? Sequence retention alone does not establish that contribution.
Q: Does the dominant-negative FasExo8Del phenotype reported in mutation-bearing HUT78 clones (PMID:8598453) extend to other defined human cellular contexts at endogenous abundance? This question concerns generalization of that tumor-cell result, not a claim that the product is uncharacterized or normally expressed in every tissue.
Experiment: Compare sequence-verified TMdel/isoform 6 with the shorter soluble products and with a matched deletion of its retained death-domain region. In the human-cell expression context being tested, measure expression, secretion, receptor surface abundance, agonist binding and FASLG-triggered FADD/caspase-8 recruitment and apoptosis separately. Normalize soluble-product abundance and distinguish antibody inhibition from natural-ligand inhibition; the historical expression phenotypes do not by themselves identify a common inhibitory mechanism.
Hypothesis: The protective phenotype of TMdel/isoform 6 may depend on features beyond simply lacking most of the membrane anchor.
Type: Controlled isoform comparison with localization, interaction and signaling readouts
Experiment: Compare the sequence-verified FasExo8Del variant and full-length receptor at matched, measured expression ratios in HUT78 and a second defined human lymphoid cell context. Measure surface localization, receptor association, FADD recruitment and caspase activation after FASLG stimulation. Use the reported resistant HUT78 phenotype as a positive comparator, without presuming normal-tissue expression or a universal mechanism.
Hypothesis: FasExo8Del inhibition may depend on expression ratio and cellular context.
Type: Context and dose comparison of an established tumor-associated variant
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