FAS

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005031 tumor necrosis factor receptor activity	IBA GO_REF:0000033	ACCEPT	Summary: CORE FUNCTION of FAS. FAS/CD95 is a type I transmembrane death receptor that binds FASLG (FasL/CD95L) and mediates apoptotic signaling. FAS is a bona fide member of the TNF receptor superfamily (TNFRSF6), containing three cysteine-rich domains (CRDs) in its extracellular region characteristic of this family [PMID:1375228]. Note: This annotation applies primarily to membrane-bound isoform 1 (P25445-1); soluble isoforms retain ligand binding but lack signaling capacity. Reason: This is a core molecular function of FAS. The deep research confirms FAS is TNFRSF6 with characteristic cysteine-rich domains that mediate FasL binding. IBA inference is appropriate as this function is highly conserved across the TNFR family. 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: ISOFORM-SPECIFIC (membrane-bound isoform 1 only). FAS localizes to cholesterol- and sphingolipid-rich membrane rafts, which is important for efficient DISC assembly and apoptotic signaling. Caveolin-1 regulates Fas localization and DISC formation in membrane rafts [PMID:21382479]. The deep research confirms membrane raft localization facilitates FAS clustering upon FasL binding. Reason: Well-supported localization for membrane-bound FAS isoform 1. IBA inference is consistent with direct experimental evidence (IDA PMID:21382479). Note: Does not apply to soluble isoforms 2-6 which are secreted. 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: ISOFORM-SPECIFIC (membrane-bound isoform 1 only). The extracellular domain of membrane-bound FAS is exposed on the external side of the plasma membrane where it binds FasL. FAS is a type I transmembrane protein with the N-terminal CRD-containing ligand-binding domain facing the extracellular space [PMID:1375228]. Reason: Correct localization for the canonical membrane-bound isoform 1. This is essential for FasL binding and receptor function. Note: Soluble isoforms 2-6 are secreted and do not have this localization. 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: CORE FUNCTION of membrane-bound FAS. Activation-induced cell death (AICD) is a critical mechanism for T cell homeostasis where repeated TCR stimulation induces FAS and FasL expression, creating an autocrine/paracrine death signal that terminates immune responses. The deep research (FAS-deep-research-perplexity.md) confirms FAS-FasL interactions participate in AICD of mature T-cells. Reason: Well-established core function of FAS in immune regulation. AICD via FAS-FasL is essential for peripheral tolerance and termination of immune responses. Defects in this pathway cause ALPS (autoimmune lymphoproliferative syndrome). 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 2014–Jan 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: ISOFORM-SPECIFIC (membrane-bound isoform 1 only). FAS is a core component of the CD95 death-inducing signaling complex (DISC), which forms upon FasL binding and consists of FAS, FADD, and procaspase-8. The Fas-FADD death domain complex forms an asymmetric oligomeric structure of 5-7 Fas DD and 5 FADD DD [PMID:20935634]. This is the defining functional complex for FAS-mediated apoptosis. Reason: DISC localization is the core functional context for membrane-bound FAS. Structural studies confirm the oligomeric Fas-FADD complex architecture. Note: Soluble FAS isoforms cannot form DISC as they lack the transmembrane domain needed for membrane anchoring and proper DISC assembly. 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 activates stress-activated protein kinases including ASK1 and JNK/SAPK under certain conditions, particularly glutamine deprivation [PMID:11096076]. This represents a non-apoptotic signaling output of FAS activation that can modulate cellular stress responses. Reason: FAS can regulate MAPK cascades but this is not its primary function. The deep research confirms non-apoptotic signaling pathways exist but the core function remains apoptosis induction. This annotation reflects ancillary signaling. 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-κB, 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-κB 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	ACCEPT	Summary: ISOFORM-SPECIFIC annotation for SOLUBLE FAS isoforms (P25445-2 to P25445-6). Soluble FAS isoforms lacking the transmembrane domain act as decoy receptors that bind FasL and block apoptosis. This is the OPPOSITE function of membrane-bound isoform 1. PMID:7510905 demonstrates soluble FAS blocks Fas-mediated apoptosis. Reason: Correct annotation but ONLY for soluble isoforms 2-6. UniProt explicitly states that secreted isoforms 2 to 6 block apoptosis in vitro. This IBA annotation likely reflects phylogenetic inference that includes soluble forms. 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 mediate motor neuron apoptosis. The deep research mentions FAS expression in the developing nervous system and its role in neuronal cell death. However, this represents a tissue-specific manifestation of FAS apoptotic function rather than a distinct mechanism. Reason: While FAS can mediate motor neuron apoptosis, this is a context-specific application of its general apoptotic function. The core function is death receptor activity and apoptosis induction, which applies across cell types. Motor neuron apoptosis is one of many cellular contexts where FAS functions. 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 trigger necroptotic cell death through RIP1 (RIPK1) when caspase activity is inhibited. FAS interacts with RIP1 via death domain interactions [PMID:7538908]. RIP-mediated necrosis involves inhibition of ADP/ATP exchange [PMID:16507998]. This represents an alternative cell death pathway downstream of FAS activation. Reason: Necroptosis is a secondary pathway activated when apoptosis is blocked. The primary function of FAS is apoptosis induction; necroptosis occurs under specific conditions (caspase inhibition). This is a valid but non-core function. 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	ACCEPT	Summary: FAS is a member of the TNF receptor superfamily (TNFRSF6) and mediates signaling analogous to other TNFR family members. However, FAS specifically responds to FasL (FASLG/TNFSF6), not TNF itself. The term may be overly broad. Reason: While FAS does not directly respond to TNF, it is part of the broader TNF receptor superfamily and uses similar death domain-mediated signaling mechanisms. The IEA annotation based on logical inference is acceptable as a general categorization of this signaling pathway family.
GO:0004888 transmembrane signaling receptor activity	IEA GO_REF:0000002	ACCEPT	Summary: ISOFORM-SPECIFIC (membrane-bound isoform 1 only). FAS isoform 1 is a type I transmembrane receptor that binds FasL extracellularly and transduces signals intracellularly via its death domain. This is a valid parent term of the more specific GO:0005031 (tumor necrosis factor receptor activity). Reason: Correct general molecular function for membrane-bound FAS. This IEA based on InterPro domain mapping is appropriate. Note: Does not apply to soluble isoforms 2-6 which lack the transmembrane domain.
GO:0005516 calmodulin binding	IEA GO_REF:0000043	ACCEPT	Summary: FAS binds calmodulin in a region overlapping its death domain (residues 230-254). This interaction has been structurally characterized by X-ray crystallography [PMID:24914971 cited in UniProt]. Calmodulin binding may modulate FAS signaling. Reason: UniProt documents interaction with CALM based on structural evidence. IEA from keyword mapping is consistent with direct experimental data. This represents a regulatory interaction that modulates FAS function.
GO:0005576 extracellular region	IEA GO_REF:0000044	ACCEPT	Summary: ISOFORM-SPECIFIC annotation for SOLUBLE FAS isoforms (P25445-2 to P25445-6). UniProt explicitly states that isoforms 2-6 are secreted. Soluble FAS lacking the transmembrane domain is released into the extracellular space where it acts as a decoy receptor. Reason: Correct localization for soluble FAS isoforms. IEA from UniProt subcellular location mapping is appropriate for the secreted isoforms. Note: Does not apply to membrane-bound isoform 1.
GO:0005886 plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: ISOFORM-SPECIFIC (membrane-bound isoform 1 only). FAS isoform 1 is a type I transmembrane protein localized to the plasma membrane where it functions as a death receptor. UniProt confirms cell membrane localization for isoform 1. Reason: Correct localization for membrane-bound FAS. IEA from UniProt subcellular location is appropriate. Note: Does not apply to soluble isoforms 2-6 which are secreted.
GO:0006915 apoptotic process	IEA GO_REF:0000120	ACCEPT	Summary: CORE FUNCTION of membrane-bound FAS. Apoptosis is the primary biological process mediated by FAS activation. Upon FasL binding, FAS recruits FADD and caspase-8 to form the DISC, initiating the caspase cascade leading to cell death. Reason: This is the core biological process for FAS. IEA from combined automated methods is consistent with extensive experimental evidence. Note: Soluble isoforms have the opposite effect, blocking apoptosis.
GO:0006955 immune response	IEA GO_REF:0000002	ACCEPT	Summary: FAS plays a critical role in immune homeostasis through elimination of autoreactive lymphocytes and termination of immune responses via AICD. Defects in FAS cause ALPS, an autoimmune disorder. The deep research confirms FAS-FasL is essential for peripheral tolerance and immune regulation. Reason: While overly broad, FAS does function in immune response contexts. The term encompasses FAS roles in lymphocyte homeostasis, peripheral tolerance, and immune response termination. IEA from InterPro mapping is acceptable.
GO:0007165 signal transduction	IEA GO_REF:0000002	ACCEPT	Summary: FAS is a signaling receptor that transduces extracellular FasL binding into intracellular signals. The signal transduction involves death domain-mediated recruitment of FADD and caspase-8, leading to DISC formation and caspase activation. Reason: Correct but very general term. FAS is indeed a signal transducing receptor. More specific terms (e.g., Fas signaling pathway, extrinsic apoptotic signaling) better capture its function.
GO:0009986 cell surface	IEA GO_REF:0000117	ACCEPT	Summary: ISOFORM-SPECIFIC (membrane-bound isoform 1 only). FAS isoform 1 is expressed on the cell surface where it can engage FasL on neighboring cells. Cell surface expression is essential for FAS-mediated apoptosis. Reason: Correct localization for membrane-bound FAS. IEA from ARBA machine learning is consistent with experimental evidence. Note: Does not apply to soluble isoforms.
GO:0016020 membrane	IEA GO_REF:0000002	ACCEPT	Summary: ISOFORM-SPECIFIC (membrane-bound isoform 1 only). FAS isoform 1 is an integral membrane protein. This is a very general parent term of plasma membrane. Reason: Correct but overly general term. More specific terms (plasma membrane, membrane raft) are more informative. IEA from InterPro mapping is appropriate.
GO:0031265 CD95 death-inducing signaling complex	IEA GO_REF:0000117	ACCEPT	Summary: ISOFORM-SPECIFIC (membrane-bound isoform 1 only). Duplicate of IBA annotation for DISC localization. FAS is a core component of the CD95 DISC along with FADD and caspase-8. Reason: Correct localization. This IEA annotation is consistent with the IBA annotation and extensive experimental evidence. Duplicates are acceptable with different evidence codes.
GO:0042981 regulation of apoptotic process	IEA GO_REF:0000117	ACCEPT	Summary: FAS regulates apoptosis - membrane-bound isoform 1 positively regulates it by triggering cell death, while soluble isoforms 2-6 negatively regulate it by blocking FasL. This general term encompasses both activities. Reason: Correct but imprecise. The more specific child terms (positive/negative regulation of apoptotic process) better capture the isoform-specific functions. IEA is acceptable as a general categorization.
GO:0045121 membrane raft	IEA GO_REF:0000044	ACCEPT	Summary: ISOFORM-SPECIFIC (membrane-bound isoform 1 only). Duplicate of IBA annotation. FAS localizes to membrane rafts which facilitates DISC assembly. Reason: Correct localization. Consistent with IBA annotation and experimental evidence. IEA from UniProt confirms this localization.
GO:0097191 extrinsic apoptotic signaling pathway	IEA GO_REF:0000117	ACCEPT	Summary: CORE FUNCTION of membrane-bound FAS. FAS is the defining death receptor of the extrinsic apoptotic signaling pathway. Upon FasL binding, FAS recruits FADD via death domain interactions, forming the DISC that activates caspase-8. Reason: This is the core biological process for FAS. The extrinsic pathway is initiated by death receptors like FAS, in contrast to the intrinsic (mitochondrial) pathway. IEA from ARBA is consistent with extensive experimental evidence.
GO:0005515 protein binding	IPI PMID:10918185 Negative regulation of Fas-mediated apoptosis by FAP-1 in hu...	MODIFY	Summary: Generic protein binding term. FAS interacts with many proteins including FADD, CASP8, RIPK1, DAXX, and others. This term is uninformative and should be replaced with more specific molecular function terms. Reason: Per curation guidelines, 'protein binding' is too vague and does not provide useful information about FAS function. More specific terms should be used. Proposed replacements: tumor necrosis factor receptor activity identical protein binding Supporting Evidence: PMID:10918185 Negative regulation of Fas-mediated apoptosis by FAP-1 in human cancer cells.
GO:0005515 protein binding	IPI PMID:11003656 Inhibition of Daxx-mediated apoptosis by heat shock protein ...	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. More specific molecular function terms should be used. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:11003656 Inhibition of Daxx-mediated apoptosis by heat shock protein 27.
GO:0005515 protein binding	IPI PMID:11495919 Apoptosis signal-regulating kinase 1 controls the proapoptot...	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:11495919 2001 Aug 8. Apoptosis signal-regulating kinase 1 controls the proapoptotic function of death-associated protein (Daxx) in the cytoplasm.
GO:0005515 protein binding	IPI PMID:11606059 Apoptosis-linked gene 2 binds to the death domain of Fas and...	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:11606059 Apoptosis-linked gene 2 binds to the death domain of Fas and dissociates from Fas during Fas-mediated apoptosis in Jurkat cells.
GO:0005515 protein binding	IPI PMID:11717445 Caspase-10 is an initiator caspase in death receptor signali...	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:11717445 Caspase-10 is an initiator caspase in death receptor signaling.
GO:0005515 protein binding	IPI PMID:12724420 FAP-1 association with Fas (Apo-1) inhibits Fas expression o...	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:12724420 FAP-1 association with Fas (Apo-1) inhibits Fas expression on the cell surface.
GO:0005515 protein binding	IPI PMID:12887920 Induction of TNF receptor I-mediated apoptosis via two seque...	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:12887920 Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes.
GO:0005515 protein binding	IPI PMID:16498403 The role of receptor internalization in CD95 signaling.	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:16498403 The role of receptor internalization in CD95 signaling.
GO:0005515 protein binding	IPI PMID:17047155 Caspase-8 prevents sustained activation of NF-kappaB in mono...	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:17047155 2006 Oct 17. Caspase-8 prevents sustained activation of NF-kappaB in monocytes undergoing macrophagic differentiation.
GO:0005515 protein binding	IPI PMID:17159907 Palmitoylation of CD95 facilitates formation of SDS-stable r...	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:17159907 Palmitoylation of CD95 facilitates formation of SDS-stable receptor aggregates that initiate apoptosis signaling.
GO:0005515 protein binding	IPI PMID:18328427 Yes and PI3K bind CD95 to signal invasion of glioblastoma.	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:18328427 Yes and PI3K bind CD95 to signal invasion of glioblastoma.
GO:0005515 protein binding	IPI PMID:21382479 Caveolin-1 mediates Fas-BID signaling in hyperoxia-induced a...	MODIFY	Summary: FAS-Caveolin-1 interaction study. Cav-1 regulates Fas signaling and DISC formation. Generic protein binding term is uninformative. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity 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:21625644 Modulation of the CD95-induced apoptosis: the role of CD95 N...	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:21625644 Modulation of the CD95-induced apoptosis: the role of CD95 N-glycosylation.
GO:0005515 protein binding	IPI PMID:21803845 PMLRARα binds to Fas and suppresses Fas-mediated apoptosis t...	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:21803845 2011 Jul 29. PMLRARα binds to Fas and suppresses Fas-mediated apoptosis through recruiting c-FLIP in vivo.
GO:0005515 protein binding	IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ...	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:25241761 Oct 9. Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005515 protein binding	IPI PMID:35922511 A physical wiring diagram for the human immune system.	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:35922511 Aug 3. A physical wiring diagram for the human immune system.
GO:0005515 protein binding	IPI PMID:7536190 A novel protein that interacts with the death domain of Fas/...	MODIFY	Summary: FAS-FADD interaction. This study identified FADD as binding the FAS death domain. More specific term needed. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity 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...	MODIFY	Summary: FAS-FADD interaction via death domains. More specific term needed. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity 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/multimerization. FAS forms multimers upon activation which is required for DISC assembly. This is a valid more specific term than generic protein binding. Reason: FAS self-association is well-documented and important for signaling. The Fas-FADD death domain complex contains 5-7 FAS molecules, demonstrating FAS homo-oligomerization. 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. The death domain mediates FAS-FAS interactions. Reason: FAS self-association via death domains is well-established. Required for DISC assembly. 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: FAS self-association identified in yeast two-hybrid screen. Reason: FAS-FAS interaction documented by RIP study. Consistent with DISC architecture. 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: ISOFORM-SPECIFIC (membrane-bound isoform 1 only). Direct experimental evidence (HPA immunohistochemistry) for plasma membrane localization. Reason: Correct localization for membrane-bound FAS. IDA from HPA data is strong evidence. Note: Does not apply to soluble isoforms.
GO:0005031 tumor necrosis factor receptor activity	IDA PMID:12221075 Glutathione peroxidase-1 protects from CD95-induced apoptosi...	ACCEPT	Summary: CORE FUNCTION. Direct experimental demonstration of TNF receptor activity. FAS binds FasL and activates downstream apoptotic signaling. Reason: This is the core molecular function of FAS. IDA evidence from direct assay confirms receptor activity. Consistent with IBA annotation. 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: CORE FUNCTION of membrane-bound FAS. FAS is the canonical death domain receptor that initiates the extrinsic apoptotic pathway. This is a highly specific and accurate term for FAS function. Reason: This is the defining biological process for FAS. The term precisely describes FAS-mediated apoptosis through death domain interactions with FADD. 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-κB/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: CORE FUNCTION. The Fas signaling pathway is the specific pathway initiated by FAS/CD95 ligation. This is the most precise process term for FAS function. Reason: This is the defining signaling pathway for FAS. Highly specific and accurate. 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: FAS activation triggers early ROS production. This study demonstrated that anti-CD95 antibodies triggered early generation of ROS in T47D cells. Reason: ROS production is a documented downstream effect of FAS signaling but is not the core function. The primary function is apoptosis induction. 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.	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:15917238 2005 May 24. CD47 augments Fas/CD95-mediated apoptosis.
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: CORE FUNCTION. Duplicate annotation for extrinsic apoptotic signaling via death domain receptors from different publication. Reason: Core biological process for FAS. Consistent with other annotations. 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 ...	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:18846110 2008 Oct 10. Identification of an antiapoptotic protein complex at death receptors.
GO:0032872 regulation of stress-activated MAPK cascade	IMP PMID:11096076 Glutamine-dependent antiapoptotic interaction of human gluta...	KEEP AS NON CORE	Summary: FAS ligation activates ASK1 and JNK/SAPK under glutamine deprivation conditions. Duplicate of IBA annotation with experimental evidence. Reason: MAPK regulation is a secondary signaling output, not the core function of 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-mediated apoptosis is enhanced under glutamine starvation conditions. This reflects context-dependent modulation of FAS signaling. Reason: Amino acid starvation modulates FAS sensitivity but is not a core function. 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: CORE FUNCTION. Duplicate annotation for Fas signaling pathway with IMP evidence. Reason: Core signaling pathway for FAS. Consistent with IDA annotation. 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: CORE FUNCTION of membrane-bound FAS. FAS positively regulates apoptotic signaling by initiating the caspase cascade. Reason: Core function of membrane-bound FAS isoform 1. Note: Soluble isoforms have opposite effect. 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...	ACCEPT	Summary: FAS binds calmodulin in a region overlapping its death domain (residues 230-254). Direct experimental evidence from structural studies. Reason: IDA evidence supports calmodulin binding. This may modulate FAS signaling. Consistent with IEA annotation. Supporting Evidence: PMID:24914971 Structural insights into the mechanism of calmodulin binding to death receptors.
GO:0031264 death-inducing signaling complex	IDA PMID:21803845 PMLRARα binds to Fas and suppresses Fas-mediated apoptosis t...	ACCEPT	Summary: ISOFORM-SPECIFIC (membrane-bound isoform 1 only). FAS is a core component of the DISC. This is a more general term than GO:0031265 (CD95 DISC). Reason: Correct localization. DISC is the functional context for FAS-mediated apoptosis. Supporting Evidence: PMID:21803845 2011 Jul 29. PMLRARα 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 trigger necroptosis via RIP1 when caspases are inhibited. IMP evidence from study showing RIP-dependent necrosis downstream of death receptor ligation. Reason: Necroptosis is a secondary pathway activated when apoptosis is blocked. Consistent with IBA annotation. 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: ISOFORM-SPECIFIC (membrane-bound isoform 1 only). IMP evidence for plasma membrane localization. Reason: Correct localization for membrane-bound FAS. Consistent with IDA and IEA annotations. 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: CORE FUNCTION of membrane-bound FAS (isoform 1, P25445-1). FAS is the death receptor that initiates extrinsic apoptosis by forming the DISC (Death-Inducing Signaling Complex) with FADD and CASP8 upon FasL binding. Note: This function is OPPOSITE to soluble FAS isoforms (P25445-2 to P25445-6) which BLOCK apoptosis. Reason: Core pro-apoptotic function of canonical membrane-bound FAS. Should ideally be isoform-specific to P25445-1 to distinguish from the anti-apoptotic soluble isoforms. 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: ISOFORM-SPECIFIC (membrane-bound isoform 1 only). Direct experimental evidence for cell surface localization. Reason: Correct localization for membrane-bound FAS. Consistent with other annotations. 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: CORE FUNCTION. IMP evidence for extrinsic apoptotic signaling pathway. Consistent with IEA annotation. Reason: Core biological process for FAS. 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...	KEEP AS NON CORE	Summary: FAS has been detected in extracellular exosomes. High-throughput data analysis. Reason: Exosomal localization may reflect secretion of soluble FAS isoforms or membrane FAS in exosomes. Not a core localization. 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: ISOFORM-SPECIFIC. TAS from Reactome for plasma membrane localization. Reason: Correct localization for membrane-bound FAS. Consistent with other annotations.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-141310	ACCEPT	Summary: ISOFORM-SPECIFIC. TAS from Reactome for plasma membrane localization. Reason: Correct localization for membrane-bound FAS. Duplicate from different pathway.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-3465429	ACCEPT	Summary: ISOFORM-SPECIFIC. TAS from Reactome for plasma membrane localization. Reason: Correct localization for membrane-bound FAS. Duplicate from different pathway.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-3465448	ACCEPT	Summary: ISOFORM-SPECIFIC. TAS from Reactome for plasma membrane localization. Reason: Correct localization for membrane-bound FAS. Duplicate from different pathway.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-3465459	ACCEPT	Summary: ISOFORM-SPECIFIC. TAS from Reactome for plasma membrane localization. Reason: Correct localization for membrane-bound FAS. Duplicate from different pathway.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5675456	ACCEPT	Summary: ISOFORM-SPECIFIC. TAS from Reactome for plasma membrane localization. Reason: Correct localization for membrane-bound FAS. Duplicate from different pathway.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6800001	ACCEPT	Summary: ISOFORM-SPECIFIC. TAS from Reactome for plasma membrane localization. Reason: Correct localization for membrane-bound FAS. Duplicate from different pathway.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-71050	ACCEPT	Summary: ISOFORM-SPECIFIC. TAS from Reactome for plasma membrane localization. Reason: Correct localization for membrane-bound FAS. Duplicate from different pathway.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-73945	ACCEPT	Summary: ISOFORM-SPECIFIC. TAS from Reactome for plasma membrane localization. Reason: Correct localization for membrane-bound FAS. Duplicate from different pathway.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-75244	ACCEPT	Summary: ISOFORM-SPECIFIC. TAS from Reactome for plasma membrane localization. Reason: Correct localization for membrane-bound FAS. Duplicate from different pathway.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-83586	ACCEPT	Summary: ISOFORM-SPECIFIC. TAS from Reactome for plasma membrane localization. Reason: Correct localization for membrane-bound FAS. Duplicate from different pathway.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-83650	ACCEPT	Summary: ISOFORM-SPECIFIC. TAS from Reactome for plasma membrane localization. Reason: Correct localization for membrane-bound FAS. Duplicate from different pathway.
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-mediated apoptosis is induced by hyperoxia. Study showed Cav-1 regulates Fas signaling in hyperoxia-induced apoptosis. Reason: Hyperoxia response is a specific context where FAS is activated. Not a core function. 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: ISOFORM-SPECIFIC. Direct structural evidence for FAS in the CD95 DISC. This study solved the Fas-FADD death domain complex structure showing 5-7 Fas DD and 5 FADD DD. Reason: Core localization for membrane-bound FAS. Strong structural evidence. 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: CORE FUNCTION of membrane-bound FAS. IMP evidence from structure-function studies showing that ALPS mutations disrupt FAS-FADD interaction and apoptosis. Reason: Core pro-apoptotic function. Consistent with other annotations. 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: ISOFORM-SPECIFIC. Direct experimental evidence for FAS localization in membrane rafts. Cav-1 interaction facilitates FAS clustering in rafts. Reason: Correct localization for membrane-bound FAS. IDA evidence is strong. 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...	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:21109225 Epub 2010 Nov 25. Whole-exome-sequencing-based discovery of human FADD deficiency.
GO:0071260 cellular response to mechanical stimulus	IEP PMID:19593445 Expression of the Bcl-2 protein BAD promotes prostate cancer...	KEEP AS NON CORE	Summary: FAS expression is modulated by mechanical stimulus. IEP (expression pattern) evidence suggests FAS is involved in cellular response to mechanical stress. Reason: Mechanical stimulus response is a specific context. IEP evidence is weaker than direct functional evidence. 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...	ACCEPT	Summary: ISOFORM-SPECIFIC. Direct experimental evidence for FAS in the DISC. Consistent with other DISC annotations. Reason: Core localization for membrane-bound FAS. 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...	ACCEPT	Summary: FAS binds RIP1 (RIPK1), a serine/threonine kinase. RIP contains a kinase domain and interacts with FAS death domain. Reason: Valid molecular function annotation. RIP1 kinase binding is well-documented. 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: CORE FUNCTION. Direct experimental evidence for FAS-mediated apoptosis. Reason: Core biological process for membrane-bound FAS. Consistent with other annotations. 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...	MODIFY	Summary: Generic protein binding term. Uninformative about FAS function. Reason: Per curation guidelines, 'protein binding' is too vague. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: PMID:15465831 2004 Oct 1. A death receptor-associated anti-apoptotic protein, BRE, inhibits mitochondrial apoptotic pathway.
GO:0042981 regulation of apoptotic process	NAS PMID:7533181 Three functional soluble forms of the human apoptosis-induci...	ACCEPT	Summary: FAS regulates apoptosis - membrane-bound form triggers it, soluble forms block it. NAS evidence from review article. Reason: Correct general term. Consistent with IEA annotation. 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: CORE FUNCTION. TAS evidence for apoptotic process involvement. Reason: Core biological process for FAS. Consistent with other annotations. 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: CORE FUNCTION. Original characterization of APO-1/Fas showing apoptosis induction. Reason: Core biological process. Seminal paper identifying APO-1/Fas as apoptosis inducer. 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...	ACCEPT	Summary: FAS is a signaling receptor. TAS evidence for signal transduction. Reason: Correct but general term. Consistent with IEA annotation. 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...	ACCEPT	Summary: CORE FUNCTION. FAS is a cell surface signaling receptor. Reason: Correct molecular function. Consistent with other annotations. 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 ...	ACCEPT	Summary: ISOFORM-SPECIFIC ANNOTATION. This annotation refers to SOLUBLE FAS isoforms (P25445-2 to P25445-6), NOT the canonical membrane-bound form. PMID:7510905 explicitly demonstrates that "a human Fas messenger RNA variant capable of encoding a soluble Fas molecule lacking the transmembrane domain" produces a protein where "Supernatants from cells transfected with the variant messenger RNA blocked apoptosis induced by the antibody to Fas." Reason: Correct annotation for soluble FAS isoforms. This is the antagonistic function of the TMdel isoforms that act as decoy receptors. Should ideally be annotated to specific isoforms P25445-2/6, not the canonical membrane-bound P25445-1. 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 forms preassociated complexes before ligand binding. This study showed that FAS preassociation in the PRELIGAND assembly domain is required for signaling. Reason: Valid biological process. FAS preassociation and DISC assembly are well-documented. 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 localization may refer to the intracellular death domain portion of membrane-bound FAS or to cleaved/soluble forms. NAS evidence is weak. Reason: Unclear what cytosolic localization refers to. FAS is primarily a membrane protein. May refer to cleaved forms or ICD. NAS evidence insufficient for confident assessment. Supporting Evidence: PMID:7533181 Three functional soluble forms of the human apoptosis-inducing Fas molecule are produced by alternative splicing.
GO:0038023 signaling receptor activity	NAS PMID:7533181 Three functional soluble forms of the human apoptosis-induci...	ACCEPT	Summary: CORE FUNCTION. FAS is a signaling receptor. NAS evidence from review article. Reason: Correct molecular function. Consistent with TAS annotation. Supporting Evidence: PMID:7533181 Three functional soluble forms of the human apoptosis-inducing Fas molecule are produced by alternative splicing.

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

Perplexity

📚 Additional Documentation

Notes

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