Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0043066 negative regulation of apoptotic process	IBA GO_REF:0000033	ACCEPT	Summary: ACCEPT: negative regulation of apoptotic process is a recurrent GAS6/TAM signaling output in several cell types, including fibroblasts and oligodendrocytes. Reason: Gas6 protects cells from serum deprivation, TNF-alpha, and growth factor withdrawal through AXL/TAM signaling. Supporting Evidence: PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase.
GO:0005615 extracellular space	IBA GO_REF:0000033	ACCEPT	Summary: ACCEPT: extracellular space is the correct functional location for the mature secreted GAS6 ligand. Reason: GAS6 has a signal peptide, is annotated by UniProt as secreted, and acts extracellularly on cell-surface TAM receptors. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0007166 cell surface receptor signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: ACCEPT: GAS6 is directly involved in cell-surface receptor signaling through TAM receptor tyrosine kinases. Reason: Ligand binding to AXL/TYRO3/MERTK initiates receptor activation and downstream signaling at the cell surface. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IBA GO_REF:0000033	ACCEPT	Summary: ACCEPT: positive regulation of PI3K/protein kinase B signaling is a well-supported GAS6/TAM output in oligodendrocytes, erythroblasts, and platelets. Reason: Multiple mouse-relevant experiments show Gas6/TAM signaling activates PI3K-Akt survival or platelet signaling pathways. Supporting Evidence: PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. PMID:15650770 Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying outside-in signaling via alphaIIbbeta3. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0048018 receptor ligand activity	IBA GO_REF:0000033	ACCEPT	Summary: ACCEPT: receptor ligand activity is the clearest existing MF term for GAS6. Mouse GAS6 is a secreted vitamin K-dependent ligand for TAM receptor tyrosine kinases, especially AXL, and ligand binding activates receptor phosphorylation and downstream signaling. Reason: This term captures the core molecular role of GAS6 better than generic receptor-binding terms. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0005509 calcium ion binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: calcium binding is supported by the Gla and calcium-binding EGF-like domains and is important for the carboxylated extracellular ligand, but it is an enabling structural property rather than the main biological function. Reason: Retain as an ancillary molecular property of GAS6, not as the curated core function. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding.
GO:0005576 extracellular region	IEA GO_REF:0000120	ACCEPT	Summary: ACCEPT: extracellular region is a broader but correct location for secreted GAS6. Reason: The mature protein is secreted and functions outside the cell. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0016477 cell migration	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: cell migration is a known downstream outcome of GAS6/TAM signaling but is broad and cell-context dependent. Reason: Retain as a non-core downstream process. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:18787040 Silencing studies evaluated the role of Tyro3 and Axl in NLT GnRH neuronal cells and suggest that both play a role in Gas6 stimulation of GnRH neuronal survival and migration.
GO:0030154 cell differentiation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: cell differentiation reflects context-specific immune or hematopoietic consequences of GAS6/TAM signaling rather than a primary GAS6 function. Reason: Retain as a broad non-core process. Supporting Evidence: PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0031669 cellular response to nutrient levels	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: cellular response to nutrient levels describes a context that can affect GAS6 expression or vitamin K-dependent modification, not the function executed by the GAS6 protein. Reason: Do not treat upstream expression or modification context as a core Gas6 biological process. Supporting Evidence: PMID:8336730 This finding thus defines a new member of vitamin K-dependent proteins that is expressed in many human and mouse tissues and may be involved in the regulation of a protease cascade relevant in growth regulation. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0046872 metal ion binding	IEA GO_REF:0000043	MODIFY	Summary: MODIFY: metal ion binding is too generic. GAS6 has specific calcium-binding Gla and EGF-like domains that support its vitamin K-dependent extracellular ligand function. Reason: Replace the generic metal-binding annotation with calcium ion binding. Proposed replacements: calcium ion binding Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding.
GO:0050878 regulation of body fluid levels	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: regulation of body fluid levels is too broad and physiologically remote for the evidence reviewed. Reason: The direct function is secreted TAM ligand signaling, not general body-fluid regulation. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses.
GO:0001786 phosphatidylserine binding	IEA GO_REF:0000107	ACCEPT	Summary: ACCEPT: phosphatidylserine binding is a core biochemical property of vitamin K-carboxylated GAS6, allowing it to bridge PtdSer-exposed apoptotic or activated membranes to TAM receptors. Reason: The Gla-domain PtdSer interaction is central to GAS6-dependent TAM activation and efferocytosis. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon highlights efferocytosis as a central GAS6/TAM function, with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on phagocytes.
GO:0001961 positive regulation of cytokine-mediated signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: GAS6/TAM signaling can tune cytokine-mediated pathways, including Epo-associated erythroid survival and immune signaling, but this is context-dependent. Reason: The annotation is plausible as a downstream regulatory effect rather than the core function. Supporting Evidence: PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0003104 positive regulation of glomerular filtration	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: glomerular filtration is a high-level renal physiological phenotype and is too indirect for mouse Gas6 as a core GO process. Reason: The curated mechanism is extracellular TAM ligand signaling; renal filtration effects should be supported with narrower contextual evidence before retention as a core-like process. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0005102 signaling receptor binding	IEA GO_REF:0000107	MODIFY	Summary: MODIFY: signaling receptor binding is true but too generic for GAS6. The more informative annotation is receptor ligand activity for TAM receptor tyrosine kinases. Reason: Receptor ligand activity captures both binding and receptor activation. Proposed replacements: receptor ligand activity Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0005615 extracellular space	IEA GO_REF:0000120	ACCEPT	Summary: ACCEPT: extracellular space is the correct functional location for the mature secreted GAS6 ligand. Reason: GAS6 has a signal peptide, is annotated by UniProt as secreted, and acts extracellularly on cell-surface TAM receptors. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0005737 cytoplasm	IEA GO_REF:0000107	REMOVE	Summary: REMOVE: cytoplasm is not the functional location of mature GAS6. The reviewed protein is secreted and acts extracellularly on cell-surface TAM receptors. Reason: Any cytoplasmic signal would reflect biosynthesis or transfer noise rather than the active mature protein location. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0006909 phagocytosis	IEA GO_REF:0000107	MODIFY	Summary: MODIFY: generic phagocytosis is too broad. GAS6 most specifically promotes apoptotic-cell clearance/efferocytosis via TAM receptors. Reason: Replace broad phagocytosis with apoptotic cell clearance for this ligand mechanism. Proposed replacements: apoptotic cell clearance Supporting Evidence: PMID:18159085 The phagocytic ability of Sertoli cells increased by five times in the presence of Gas6 in serum-free medium when compared with controls. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon highlights efferocytosis as a central GAS6/TAM function, with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on phagocytes.
GO:0007165 signal transduction	IEA GO_REF:0000120	MODIFY	Summary: MODIFY: signal transduction is too broad. GAS6 specifically acts in cell-surface receptor signaling through TAM receptor tyrosine kinases. Reason: Replace with a more specific receptor-signaling process already supported for GAS6. Proposed replacements: cell surface receptor signaling pathway Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6.
GO:0007166 cell surface receptor signaling pathway	IEA GO_REF:0000120	ACCEPT	Summary: ACCEPT: GAS6 is directly involved in cell-surface receptor signaling through TAM receptor tyrosine kinases. Reason: Ligand binding to AXL/TYRO3/MERTK initiates receptor activation and downstream signaling at the cell surface. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0010628 positive regulation of gene expression	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: positive regulation of gene expression is an indirect downstream consequence of receptor signaling and is too broad for Gas6 curation. Reason: Use signaling pathway terms rather than generic gene-expression outcomes for GAS6. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0010804 negative regulation of tumor necrosis factor-mediated signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: negative regulation of TNF-mediated signaling is consistent with GAS6/TAM anti-inflammatory and survival signaling, but it is a context-specific output. Reason: Retain as non-core because the primary molecular role is TAM receptor activation. Supporting Evidence: PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0019064 fusion of virus membrane with host plasma membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: enveloped viruses can exploit GAS6/TAM phosphatidylserine bridging for apoptotic mimicry, but this host-factor role is not an evolved core function of mouse Gas6. Reason: Retain as a pathogen-context annotation, explicitly non-core. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0019079 viral genome replication	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: viral genome replication is an indirect pathogen-context consequence of GAS6/TAM-mediated viral entry or signaling and is not a core host function. Reason: Retain only as a non-core host-factor annotation. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0030674 protein-macromolecule adaptor activity	IEA GO_REF:0000107	ACCEPT	Summary: ACCEPT: GAS6 functions as an extracellular bridging/adaptor ligand by engaging phosphatidylserine-containing membranes through its Gla domain and TAM receptor ectodomains through its C-terminal LG domains. The term is imperfectly broad but captures this bridging role better than generic protein binding. Reason: The annotation represents a core bridging function, although a more specific PtdSer-dependent TAM receptor bridging MF would be preferable. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon highlights efferocytosis as a central GAS6/TAM function, with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on phagocytes. PMID:18159085 The phagocytic ability of Sertoli cells increased by five times in the presence of Gas6 in serum-free medium when compared with controls.
GO:0030971 receptor tyrosine kinase binding	IEA GO_REF:0000107	ACCEPT	Summary: ACCEPT: receptor tyrosine kinase binding is directly supported because GAS6 binds and activates the TAM receptor tyrosine kinases AXL, TYRO3, and MER/MERTK. Reason: This specific binding term is mechanistically correct for the GAS6 receptor-ligand interaction. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0031100 animal organ regeneration	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: organ regeneration is noted in UniProt/Falcon summaries for GAS6/TAM signaling, but it is a physiological outcome rather than a direct core function. Reason: Retain as a non-core tissue-repair outcome. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0032008 positive regulation of TOR signaling	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: TOR signaling can lie downstream of PI3K/AKT, but this is a secondary pathway branch rather than the primary GAS6 function. Reason: Retain as non-core downstream signaling. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0032689 negative regulation of type II interferon production	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: suppression of interferon-gamma/type II interferon production is consistent with reported GAS6/TAM immunoregulatory programs but is a downstream immune-context effect. Reason: Retain as non-core immunoregulation rather than primary GAS6 function. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0032692 negative regulation of interleukin-1 production	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: reduced interleukin-1 production is consistent with TAM-mediated anti-inflammatory feedback but is not the primary molecular function of GAS6. Reason: Retain as non-core immunoregulatory output. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0032715 negative regulation of interleukin-6 production	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: reduced interleukin-6 production is consistent with GAS6/TAM anti-inflammatory signaling but is context-specific. Reason: Retain as non-core immunoregulatory output. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0032720 negative regulation of tumor necrosis factor production	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: reduced tumor necrosis factor production is consistent with GAS6/TAM anti-inflammatory feedback but is not the core ligand function. Reason: Retain as non-core immunoregulatory output. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0032825 positive regulation of natural killer cell differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: natural killer cell differentiation is noted as a GAS6/TAM-associated immune outcome, but it is downstream and cell-context specific. Reason: Retain as non-core because the core role is extracellular TAM receptor activation. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0035457 cellular response to interferon-alpha	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: cellular response to interferon-alpha is a plausible immune-context annotation for TAM signaling crosstalk, but it is not a defining function of GAS6. Reason: Retain as non-core immune signaling context. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0035754 B cell chemotaxis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: B cell chemotaxis may reflect immune-cell responses to GAS6/TAM signaling, but it is a downstream context rather than the core molecular role. Reason: Retain as non-core pending more specific direct mouse evidence. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process	IEA GO_REF:0000107	MODIFY	Summary: MODIFY: GAS6 does not directly inhibit cysteine-type endopeptidases/caspases. It reduces apoptosis through TAM receptor signaling and downstream survival pathways. Reason: Replace the incorrect molecular-function term with the supported biological-process term for anti-apoptotic signaling. Proposed replacements: negative regulation of apoptotic process Supporting Evidence: PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6.
GO:0043066 negative regulation of apoptotic process	IEA GO_REF:0000107	ACCEPT	Summary: ACCEPT: negative regulation of apoptotic process is a recurrent GAS6/TAM signaling output in several cell types, including fibroblasts and oligodendrocytes. Reason: Gas6 protects cells from serum deprivation, TNF-alpha, and growth factor withdrawal through AXL/TAM signaling. Supporting Evidence: PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase.
GO:0043277 apoptotic cell clearance	IEA GO_REF:0000120	ACCEPT	Summary: ACCEPT: apoptotic cell clearance is a core cellular role of GAS6/TAM signaling. GAS6 promotes recognition and phagocytosis of apoptotic cells by TAM-expressing phagocytes. Reason: The Sertoli-cell study and broader TAM literature support GAS6 as an efferocytosis ligand. Supporting Evidence: PMID:18159085 The phagocytic ability of Sertoli cells increased by five times in the presence of Gas6 in serum-free medium when compared with controls. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon highlights efferocytosis as a central GAS6/TAM function, with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on phagocytes.
GO:0045892 negative regulation of DNA-templated transcription	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: negative regulation of DNA-templated transcription is an indirect downstream signaling consequence and not a direct function of GAS6. Reason: This term overstates downstream transcriptional effects as a Gas6 process. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0046718 symbiont entry into host cell	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: symbiont/virus entry annotations reflect pathogen exploitation of GAS6/TAM phosphatidylserine bridging rather than physiological GAS6 function. Reason: Retain as non-core pathogen-context annotation. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0046813 receptor-mediated virion attachment to host cell	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: receptor-mediated virion attachment can occur through GAS6/TAM apoptotic mimicry, but it is a pathogen-context use of the normal PtdSer/TAM bridging mechanism. Reason: Retain as non-core pathogen-context annotation. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0046827 positive regulation of protein export from nucleus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: positive regulation of protein export from nucleus is too indirect and not part of the established GAS6/TAM ligand mechanism. Reason: No reviewed mouse evidence makes nuclear export a direct or central Gas6 function. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0048018 receptor ligand activity	IEA GO_REF:0000120	ACCEPT	Summary: ACCEPT: receptor ligand activity is the clearest existing MF term for GAS6. Mouse GAS6 is a secreted vitamin K-dependent ligand for TAM receptor tyrosine kinases, especially AXL, and ligand binding activates receptor phosphorylation and downstream signaling. Reason: This term captures the core molecular role of GAS6 better than generic receptor-binding terms. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0050766 positive regulation of phagocytosis	IEA GO_REF:0000107	ACCEPT	Summary: ACCEPT: positive regulation of phagocytosis is supported by Gas6-enhanced phagocytic uptake of apoptotic cells, especially in TAM receptor contexts. Reason: This is a core cellular consequence of the GAS6 phosphatidylserine/TAM bridging mechanism. Supporting Evidence: PMID:18159085 The phagocytic ability of Sertoli cells increased by five times in the presence of Gas6 in serum-free medium when compared with controls. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon highlights efferocytosis as a central GAS6/TAM function, with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on phagocytes.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA GO_REF:0000120	ACCEPT	Summary: ACCEPT: positive regulation of PI3K/protein kinase B signaling is a well-supported GAS6/TAM output in oligodendrocytes, erythroblasts, and platelets. Reason: Multiple mouse-relevant experiments show Gas6/TAM signaling activates PI3K-Akt survival or platelet signaling pathways. Supporting Evidence: PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. PMID:15650770 Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying outside-in signaling via alphaIIbbeta3. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0070168 negative regulation of biomineral tissue development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: negative regulation of biomineral tissue development may reflect GAS6/AXL effects on survival/calcification contexts, but it is peripheral to the core ligand mechanism. Reason: Retain as non-core because the direct role is TAM receptor signaling. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0070588 calcium ion transmembrane transport	IEA GO_REF:0000107	REMOVE	Summary: REMOVE: GAS6 binds calcium as a vitamin K-dependent Gla/EGF-domain protein but is not a calcium transporter and does not mediate calcium transmembrane transport. Reason: The term confuses calcium binding with transport activity. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding.
GO:0071307 cellular response to vitamin K	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: vitamin K is required for GAS6 gamma-carboxylation, but GAS6 is a vitamin K-dependent protein rather than a mediator of cellular response to vitamin K. Reason: Post-translational dependence should not be represented as a protein-level response process. Supporting Evidence: PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding.
GO:0071333 cellular response to glucose stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: cellular response to glucose stimulus is too far upstream or contextual for the reviewed Gas6 evidence. Reason: The direct Gas6 role is extracellular TAM receptor signaling, not glucose-response execution. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0071466 cellular response to xenobiotic stimulus	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: xenobiotic-response annotations likely reflect warfarin sensitivity of GAS6 carboxylation rather than a function performed by GAS6. Reason: Warfarin affects GAS6 maturation; GAS6 itself should not be curated as mediating a xenobiotic response without direct evidence. Supporting Evidence: PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding.
GO:0072659 protein localization to plasma membrane	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: protein localization to plasma membrane is a downstream or inferred cellular effect and is not a precise annotation for secreted GAS6. Reason: The appropriate direct annotation is extracellular TAM receptor ligand/signaling activity. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses.
GO:0085029 extracellular matrix assembly	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: extracellular matrix assembly is likely an indirect fibroblast/secretome-context association and not a direct Gas6 function. Reason: Retain the extracellular-location evidence but do not curate ECM assembly as a core or direct process. Supporting Evidence: PMID:24006456 Mouse cardiac fibroblasts were transfected with pre-/anti-miR of miR-29b and miR-30c, and their conditioned medium was analyzed by mass spectrometry.
GO:0097028 dendritic cell differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: dendritic-cell differentiation is plausible within GAS6/TAM immune regulation, but it is a downstream immune-context annotation. Reason: Retain as non-core. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0097241 hematopoietic stem cell migration to bone marrow	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: hematopoietic stem cell migration to bone marrow is a specific hematopoietic context and not the main molecular function of GAS6. Reason: Retain as non-core pending direct mouse-specific support. Supporting Evidence: PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells.
GO:1900142 negative regulation of oligodendrocyte apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: protection of oligodendrocytes from apoptosis is experimentally supported but is a specific cellular context of the broader GAS6/TAM survival pathway. Reason: Retain as non-core cell-type-specific survival output. Supporting Evidence: PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death.
GO:2000270 negative regulation of fibroblast apoptotic process	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: Gas6 supports fibroblast survival under starvation, but the cell-type-specific anti-apoptotic term is a downstream outcome. Reason: Retain as non-core survival output. Supporting Evidence: PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase.
GO:2000352 negative regulation of endothelial cell apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: endothelial-cell survival is consistent with UniProt-described GAS6/AXL function, but this cell-type-specific survival outcome is non-core. Reason: Retain as non-core survival output. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:2000510 positive regulation of dendritic cell chemotaxis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: dendritic-cell chemotaxis is a context-specific immune-cell response and not the defining role of GAS6. Reason: Retain as non-core immune-cell outcome. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:2000533 negative regulation of renal albumin absorption	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: renal albumin absorption is a very specific renal outcome transferred from orthologous/automated evidence and is not established as a direct mouse Gas6 function here. Reason: This appears downstream and context-specific relative to the conserved TAM ligand role. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:2000669 negative regulation of dendritic cell apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: dendritic-cell survival regulation is plausible for GAS6/TAM immune signaling but is a cell-context-specific outcome. Reason: Retain as non-core immune-cell survival output. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0001934 positive regulation of protein phosphorylation	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: positive regulation of protein phosphorylation is broadly correct for GAS6/TAM signaling but less specific than positive regulation of protein kinase activity and PI3K/AKT signaling. Reason: Retain as a broad downstream signaling consequence, not as a primary core annotation. Supporting Evidence: PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0001934 positive regulation of protein phosphorylation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: positive regulation of protein phosphorylation is broadly correct for GAS6/TAM signaling but less specific than positive regulation of protein kinase activity and PI3K/AKT signaling. Reason: Retain as a broad downstream signaling consequence, not as a primary core annotation. Supporting Evidence: PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0006468 protein phosphorylation	ISO GO_REF:0000119	MODIFY	Summary: MODIFY: protein phosphorylation incorrectly suggests GAS6 participates in the phosphorylation process itself. GAS6 is the extracellular ligand that activates receptor and downstream protein kinases. Reason: Replace with positive regulation of protein kinase activity, which accurately describes ligand-mediated kinase activation. Proposed replacements: positive regulation of protein kinase activity Supporting Evidence: PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0032148 activation of protein kinase B activity	ISO GO_REF:0000096	ACCEPT	Summary: ACCEPT: activation of protein kinase B activity is supported as a direct downstream effect of GAS6/Axl signaling. Reason: The term captures the AKT activation branch of GAS6/TAM signaling. Supporting Evidence: PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. PMID:15650770 Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying outside-in signaling via alphaIIbbeta3.
GO:0045860 positive regulation of protein kinase activity	ISO GO_REF:0000119	ACCEPT	Summary: ACCEPT: GAS6 positively regulates protein kinase activity by activating TAM receptor tyrosine kinases and downstream kinases such as AKT and ERK. Reason: This regulatory BP accurately describes ligand-driven activation without implying that GAS6 itself is a kinase. Supporting Evidence: PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0001786 phosphatidylserine binding	ISO GO_REF:0000119	ACCEPT	Summary: ACCEPT: phosphatidylserine binding is a core biochemical property of vitamin K-carboxylated GAS6, allowing it to bridge PtdSer-exposed apoptotic or activated membranes to TAM receptors. Reason: The Gla-domain PtdSer interaction is central to GAS6-dependent TAM activation and efferocytosis. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon highlights efferocytosis as a central GAS6/TAM function, with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on phagocytes.
GO:0001961 positive regulation of cytokine-mediated signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: GAS6/TAM signaling can tune cytokine-mediated pathways, including Epo-associated erythroid survival and immune signaling, but this is context-dependent. Reason: The annotation is plausible as a downstream regulatory effect rather than the core function. Supporting Evidence: PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0003104 positive regulation of glomerular filtration	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: glomerular filtration is a high-level renal physiological phenotype and is too indirect for mouse Gas6 as a core GO process. Reason: The curated mechanism is extracellular TAM ligand signaling; renal filtration effects should be supported with narrower contextual evidence before retention as a core-like process. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0005102 signaling receptor binding	ISO GO_REF:0000119	MODIFY	Summary: MODIFY: signaling receptor binding is true but too generic for GAS6. The more informative annotation is receptor ligand activity for TAM receptor tyrosine kinases. Reason: Receptor ligand activity captures both binding and receptor activation. Proposed replacements: receptor ligand activity Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0005615 extracellular space	ISO GO_REF:0000096	ACCEPT	Summary: ACCEPT: extracellular space is the correct functional location for the mature secreted GAS6 ligand. Reason: GAS6 has a signal peptide, is annotated by UniProt as secreted, and acts extracellularly on cell-surface TAM receptors. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0005615 extracellular space	ISO GO_REF:0000119	ACCEPT	Summary: ACCEPT: extracellular space is the correct functional location for the mature secreted GAS6 ligand. Reason: GAS6 has a signal peptide, is annotated by UniProt as secreted, and acts extracellularly on cell-surface TAM receptors. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0005737 cytoplasm	ISO GO_REF:0000119	REMOVE	Summary: REMOVE: cytoplasm is not the functional location of mature GAS6. The reviewed protein is secreted and acts extracellularly on cell-surface TAM receptors. Reason: Any cytoplasmic signal would reflect biosynthesis or transfer noise rather than the active mature protein location. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0006909 phagocytosis	ISO GO_REF:0000119	MODIFY	Summary: MODIFY: generic phagocytosis is too broad. GAS6 most specifically promotes apoptotic-cell clearance/efferocytosis via TAM receptors. Reason: Replace broad phagocytosis with apoptotic cell clearance for this ligand mechanism. Proposed replacements: apoptotic cell clearance Supporting Evidence: PMID:18159085 The phagocytic ability of Sertoli cells increased by five times in the presence of Gas6 in serum-free medium when compared with controls. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon highlights efferocytosis as a central GAS6/TAM function, with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on phagocytes.
GO:0007165 signal transduction	ISO GO_REF:0000096	MODIFY	Summary: MODIFY: signal transduction is too broad. GAS6 specifically acts in cell-surface receptor signaling through TAM receptor tyrosine kinases. Reason: Replace with a more specific receptor-signaling process already supported for GAS6. Proposed replacements: cell surface receptor signaling pathway Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6.
GO:0007165 signal transduction	ISO GO_REF:0000119	MODIFY	Summary: MODIFY: signal transduction is too broad. GAS6 specifically acts in cell-surface receptor signaling through TAM receptor tyrosine kinases. Reason: Replace with a more specific receptor-signaling process already supported for GAS6. Proposed replacements: cell surface receptor signaling pathway Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6.
GO:0007166 cell surface receptor signaling pathway	ISO GO_REF:0000119	ACCEPT	Summary: ACCEPT: GAS6 is directly involved in cell-surface receptor signaling through TAM receptor tyrosine kinases. Reason: Ligand binding to AXL/TYRO3/MERTK initiates receptor activation and downstream signaling at the cell surface. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0010628 positive regulation of gene expression	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: positive regulation of gene expression is an indirect downstream consequence of receptor signaling and is too broad for Gas6 curation. Reason: Use signaling pathway terms rather than generic gene-expression outcomes for GAS6. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0010804 negative regulation of tumor necrosis factor-mediated signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: negative regulation of TNF-mediated signaling is consistent with GAS6/TAM anti-inflammatory and survival signaling, but it is a context-specific output. Reason: Retain as non-core because the primary molecular role is TAM receptor activation. Supporting Evidence: PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0019064 fusion of virus membrane with host plasma membrane	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: enveloped viruses can exploit GAS6/TAM phosphatidylserine bridging for apoptotic mimicry, but this host-factor role is not an evolved core function of mouse Gas6. Reason: Retain as a pathogen-context annotation, explicitly non-core. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0019079 viral genome replication	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: viral genome replication is an indirect pathogen-context consequence of GAS6/TAM-mediated viral entry or signaling and is not a core host function. Reason: Retain only as a non-core host-factor annotation. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0030674 protein-macromolecule adaptor activity	ISO GO_REF:0000119	ACCEPT	Summary: ACCEPT: GAS6 functions as an extracellular bridging/adaptor ligand by engaging phosphatidylserine-containing membranes through its Gla domain and TAM receptor ectodomains through its C-terminal LG domains. The term is imperfectly broad but captures this bridging role better than generic protein binding. Reason: The annotation represents a core bridging function, although a more specific PtdSer-dependent TAM receptor bridging MF would be preferable. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon highlights efferocytosis as a central GAS6/TAM function, with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on phagocytes. PMID:18159085 The phagocytic ability of Sertoli cells increased by five times in the presence of Gas6 in serum-free medium when compared with controls.
GO:0030971 receptor tyrosine kinase binding	ISO GO_REF:0000119	ACCEPT	Summary: ACCEPT: receptor tyrosine kinase binding is directly supported because GAS6 binds and activates the TAM receptor tyrosine kinases AXL, TYRO3, and MER/MERTK. Reason: This specific binding term is mechanistically correct for the GAS6 receptor-ligand interaction. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0032008 positive regulation of TOR signaling	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: TOR signaling can lie downstream of PI3K/AKT, but this is a secondary pathway branch rather than the primary GAS6 function. Reason: Retain as non-core downstream signaling. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0032689 negative regulation of type II interferon production	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: suppression of interferon-gamma/type II interferon production is consistent with reported GAS6/TAM immunoregulatory programs but is a downstream immune-context effect. Reason: Retain as non-core immunoregulation rather than primary GAS6 function. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0032692 negative regulation of interleukin-1 production	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: reduced interleukin-1 production is consistent with TAM-mediated anti-inflammatory feedback but is not the primary molecular function of GAS6. Reason: Retain as non-core immunoregulatory output. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0032715 negative regulation of interleukin-6 production	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: reduced interleukin-6 production is consistent with GAS6/TAM anti-inflammatory signaling but is context-specific. Reason: Retain as non-core immunoregulatory output. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0032720 negative regulation of tumor necrosis factor production	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: reduced tumor necrosis factor production is consistent with GAS6/TAM anti-inflammatory feedback but is not the core ligand function. Reason: Retain as non-core immunoregulatory output. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0032825 positive regulation of natural killer cell differentiation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: natural killer cell differentiation is noted as a GAS6/TAM-associated immune outcome, but it is downstream and cell-context specific. Reason: Retain as non-core because the core role is extracellular TAM receptor activation. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0035457 cellular response to interferon-alpha	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: cellular response to interferon-alpha is a plausible immune-context annotation for TAM signaling crosstalk, but it is not a defining function of GAS6. Reason: Retain as non-core immune signaling context. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0035754 B cell chemotaxis	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: B cell chemotaxis may reflect immune-cell responses to GAS6/TAM signaling, but it is a downstream context rather than the core molecular role. Reason: Retain as non-core pending more specific direct mouse evidence. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process	ISO GO_REF:0000119	MODIFY	Summary: MODIFY: GAS6 does not directly inhibit cysteine-type endopeptidases/caspases. It reduces apoptosis through TAM receptor signaling and downstream survival pathways. Reason: Replace the incorrect molecular-function term with the supported biological-process term for anti-apoptotic signaling. Proposed replacements: negative regulation of apoptotic process Supporting Evidence: PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6.
GO:0043066 negative regulation of apoptotic process	ISO GO_REF:0000119	ACCEPT	Summary: ACCEPT: negative regulation of apoptotic process is a recurrent GAS6/TAM signaling output in several cell types, including fibroblasts and oligodendrocytes. Reason: Gas6 protects cells from serum deprivation, TNF-alpha, and growth factor withdrawal through AXL/TAM signaling. Supporting Evidence: PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase.
GO:0043277 apoptotic cell clearance	ISO GO_REF:0000119	ACCEPT	Summary: ACCEPT: apoptotic cell clearance is a core cellular role of GAS6/TAM signaling. GAS6 promotes recognition and phagocytosis of apoptotic cells by TAM-expressing phagocytes. Reason: The Sertoli-cell study and broader TAM literature support GAS6 as an efferocytosis ligand. Supporting Evidence: PMID:18159085 The phagocytic ability of Sertoli cells increased by five times in the presence of Gas6 in serum-free medium when compared with controls. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon highlights efferocytosis as a central GAS6/TAM function, with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on phagocytes.
GO:0045892 negative regulation of DNA-templated transcription	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: negative regulation of DNA-templated transcription is an indirect downstream signaling consequence and not a direct function of GAS6. Reason: This term overstates downstream transcriptional effects as a Gas6 process. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0046718 symbiont entry into host cell	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: symbiont/virus entry annotations reflect pathogen exploitation of GAS6/TAM phosphatidylserine bridging rather than physiological GAS6 function. Reason: Retain as non-core pathogen-context annotation. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0046813 receptor-mediated virion attachment to host cell	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: receptor-mediated virion attachment can occur through GAS6/TAM apoptotic mimicry, but it is a pathogen-context use of the normal PtdSer/TAM bridging mechanism. Reason: Retain as non-core pathogen-context annotation. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0046827 positive regulation of protein export from nucleus	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: positive regulation of protein export from nucleus is too indirect and not part of the established GAS6/TAM ligand mechanism. Reason: No reviewed mouse evidence makes nuclear export a direct or central Gas6 function. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0048018 receptor ligand activity	ISO GO_REF:0000119	ACCEPT	Summary: ACCEPT: receptor ligand activity is the clearest existing MF term for GAS6. Mouse GAS6 is a secreted vitamin K-dependent ligand for TAM receptor tyrosine kinases, especially AXL, and ligand binding activates receptor phosphorylation and downstream signaling. Reason: This term captures the core molecular role of GAS6 better than generic receptor-binding terms. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0048146 positive regulation of fibroblast proliferation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: Gas6 stimulates cardiac fibroblast proliferation through vitamin K-dependent Axl/ERK signaling, but fibroblast proliferation is a tissue-specific outcome. Reason: Retain as a supported non-core biological effect. Supporting Evidence: PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase.
GO:0050766 positive regulation of phagocytosis	ISO GO_REF:0000119	ACCEPT	Summary: ACCEPT: positive regulation of phagocytosis is supported by Gas6-enhanced phagocytic uptake of apoptotic cells, especially in TAM receptor contexts. Reason: This is a core cellular consequence of the GAS6 phosphatidylserine/TAM bridging mechanism. Supporting Evidence: PMID:18159085 The phagocytic ability of Sertoli cells increased by five times in the presence of Gas6 in serum-free medium when compared with controls. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon highlights efferocytosis as a central GAS6/TAM function, with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on phagocytes.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO GO_REF:0000096	ACCEPT	Summary: ACCEPT: positive regulation of PI3K/protein kinase B signaling is a well-supported GAS6/TAM output in oligodendrocytes, erythroblasts, and platelets. Reason: Multiple mouse-relevant experiments show Gas6/TAM signaling activates PI3K-Akt survival or platelet signaling pathways. Supporting Evidence: PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. PMID:15650770 Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying outside-in signaling via alphaIIbbeta3. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO GO_REF:0000119	ACCEPT	Summary: ACCEPT: positive regulation of PI3K/protein kinase B signaling is a well-supported GAS6/TAM output in oligodendrocytes, erythroblasts, and platelets. Reason: Multiple mouse-relevant experiments show Gas6/TAM signaling activates PI3K-Akt survival or platelet signaling pathways. Supporting Evidence: PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. PMID:15650770 Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying outside-in signaling via alphaIIbbeta3. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0070168 negative regulation of biomineral tissue development	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: negative regulation of biomineral tissue development may reflect GAS6/AXL effects on survival/calcification contexts, but it is peripheral to the core ligand mechanism. Reason: Retain as non-core because the direct role is TAM receptor signaling. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0070588 calcium ion transmembrane transport	ISO GO_REF:0000119	REMOVE	Summary: REMOVE: GAS6 binds calcium as a vitamin K-dependent Gla/EGF-domain protein but is not a calcium transporter and does not mediate calcium transmembrane transport. Reason: The term confuses calcium binding with transport activity. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding.
GO:0071307 cellular response to vitamin K	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: vitamin K is required for GAS6 gamma-carboxylation, but GAS6 is a vitamin K-dependent protein rather than a mediator of cellular response to vitamin K. Reason: Post-translational dependence should not be represented as a protein-level response process. Supporting Evidence: PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding.
GO:0071333 cellular response to glucose stimulus	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: cellular response to glucose stimulus is too far upstream or contextual for the reviewed Gas6 evidence. Reason: The direct Gas6 role is extracellular TAM receptor signaling, not glucose-response execution. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0071466 cellular response to xenobiotic stimulus	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: xenobiotic-response annotations likely reflect warfarin sensitivity of GAS6 carboxylation rather than a function performed by GAS6. Reason: Warfarin affects GAS6 maturation; GAS6 itself should not be curated as mediating a xenobiotic response without direct evidence. Supporting Evidence: PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding.
GO:0071466 cellular response to xenobiotic stimulus	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: xenobiotic-response annotations likely reflect warfarin sensitivity of GAS6 carboxylation rather than a function performed by GAS6. Reason: Warfarin affects GAS6 maturation; GAS6 itself should not be curated as mediating a xenobiotic response without direct evidence. Supporting Evidence: PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding.
GO:0072659 protein localization to plasma membrane	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: protein localization to plasma membrane is a downstream or inferred cellular effect and is not a precise annotation for secreted GAS6. Reason: The appropriate direct annotation is extracellular TAM receptor ligand/signaling activity. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses.
GO:0097241 hematopoietic stem cell migration to bone marrow	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: hematopoietic stem cell migration to bone marrow is a specific hematopoietic context and not the main molecular function of GAS6. Reason: Retain as non-core pending direct mouse-specific support. Supporting Evidence: PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells.
GO:1900142 negative regulation of oligodendrocyte apoptotic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: protection of oligodendrocytes from apoptosis is experimentally supported but is a specific cellular context of the broader GAS6/TAM survival pathway. Reason: Retain as non-core cell-type-specific survival output. Supporting Evidence: PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death.
GO:2000270 negative regulation of fibroblast apoptotic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: Gas6 supports fibroblast survival under starvation, but the cell-type-specific anti-apoptotic term is a downstream outcome. Reason: Retain as non-core survival output. Supporting Evidence: PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase.
GO:2000352 negative regulation of endothelial cell apoptotic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: endothelial-cell survival is consistent with UniProt-described GAS6/AXL function, but this cell-type-specific survival outcome is non-core. Reason: Retain as non-core survival output. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:2000510 positive regulation of dendritic cell chemotaxis	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: dendritic-cell chemotaxis is a context-specific immune-cell response and not the defining role of GAS6. Reason: Retain as non-core immune-cell outcome. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:2000669 negative regulation of dendritic cell apoptotic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: dendritic-cell survival regulation is plausible for GAS6/TAM immune signaling but is a cell-context-specific outcome. Reason: Retain as non-core immune-cell survival output. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0048018 receptor ligand activity	ISS GO_REF:0000024	ACCEPT	Summary: ACCEPT: receptor ligand activity is the clearest existing MF term for GAS6. Mouse GAS6 is a secreted vitamin K-dependent ligand for TAM receptor tyrosine kinases, especially AXL, and ligand binding activates receptor phosphorylation and downstream signaling. Reason: This term captures the core molecular role of GAS6 better than generic receptor-binding terms. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0030674 protein-macromolecule adaptor activity	ISS GO_REF:0000024	ACCEPT	Summary: ACCEPT: GAS6 functions as an extracellular bridging/adaptor ligand by engaging phosphatidylserine-containing membranes through its Gla domain and TAM receptor ectodomains through its C-terminal LG domains. The term is imperfectly broad but captures this bridging role better than generic protein binding. Reason: The annotation represents a core bridging function, although a more specific PtdSer-dependent TAM receptor bridging MF would be preferable. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon highlights efferocytosis as a central GAS6/TAM function, with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on phagocytes. PMID:18159085 The phagocytic ability of Sertoli cells increased by five times in the presence of Gas6 in serum-free medium when compared with controls.
GO:0005615 extracellular space	HDA PMID:24006456 Extracellular matrix secretion by cardiac fibroblasts: role ...	ACCEPT	Summary: ACCEPT: extracellular space is the correct functional location for the mature secreted GAS6 ligand. Reason: GAS6 has a signal peptide, is annotated by UniProt as secreted, and acts extracellularly on cell-surface TAM receptors. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0046827 positive regulation of protein export from nucleus	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: positive regulation of protein export from nucleus is too indirect and not part of the established GAS6/TAM ligand mechanism. Reason: No reviewed mouse evidence makes nuclear export a direct or central Gas6 function. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0005737 cytoplasm	ISS GO_REF:0000024	REMOVE	Summary: REMOVE: cytoplasm is not the functional location of mature GAS6. The reviewed protein is secreted and acts extracellularly on cell-surface TAM receptors. Reason: Any cytoplasmic signal would reflect biosynthesis or transfer noise rather than the active mature protein location. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0045860 positive regulation of protein kinase activity	ISS GO_REF:0000024	ACCEPT	Summary: ACCEPT: GAS6 positively regulates protein kinase activity by activating TAM receptor tyrosine kinases and downstream kinases such as AKT and ERK. Reason: This regulatory BP accurately describes ligand-driven activation without implying that GAS6 itself is a kinase. Supporting Evidence: PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0048146 positive regulation of fibroblast proliferation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: Gas6 stimulates cardiac fibroblast proliferation through vitamin K-dependent Axl/ERK signaling, but fibroblast proliferation is a tissue-specific outcome. Reason: Retain as a supported non-core biological effect. Supporting Evidence: PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase.
GO:0032715 negative regulation of interleukin-6 production	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: reduced interleukin-6 production is consistent with GAS6/TAM anti-inflammatory signaling but is context-specific. Reason: Retain as non-core immunoregulatory output. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0019064 fusion of virus membrane with host plasma membrane	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: enveloped viruses can exploit GAS6/TAM phosphatidylserine bridging for apoptotic mimicry, but this host-factor role is not an evolved core function of mouse Gas6. Reason: Retain as a pathogen-context annotation, explicitly non-core. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0046813 receptor-mediated virion attachment to host cell	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: receptor-mediated virion attachment can occur through GAS6/TAM apoptotic mimicry, but it is a pathogen-context use of the normal PtdSer/TAM bridging mechanism. Reason: Retain as non-core pathogen-context annotation. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0001786 phosphatidylserine binding	ISS GO_REF:0000024	ACCEPT	Summary: ACCEPT: phosphatidylserine binding is a core biochemical property of vitamin K-carboxylated GAS6, allowing it to bridge PtdSer-exposed apoptotic or activated membranes to TAM receptors. Reason: The Gla-domain PtdSer interaction is central to GAS6-dependent TAM activation and efferocytosis. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon highlights efferocytosis as a central GAS6/TAM function, with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on phagocytes.
GO:0001961 positive regulation of cytokine-mediated signaling pathway	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: GAS6/TAM signaling can tune cytokine-mediated pathways, including Epo-associated erythroid survival and immune signaling, but this is context-dependent. Reason: The annotation is plausible as a downstream regulatory effect rather than the core function. Supporting Evidence: PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0006909 phagocytosis	ISS GO_REF:0000024	MODIFY	Summary: MODIFY: generic phagocytosis is too broad. GAS6 most specifically promotes apoptotic-cell clearance/efferocytosis via TAM receptors. Reason: Replace broad phagocytosis with apoptotic cell clearance for this ligand mechanism. Proposed replacements: apoptotic cell clearance Supporting Evidence: PMID:18159085 The phagocytic ability of Sertoli cells increased by five times in the presence of Gas6 in serum-free medium when compared with controls. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon highlights efferocytosis as a central GAS6/TAM function, with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on phagocytes.
GO:0010628 positive regulation of gene expression	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: positive regulation of gene expression is an indirect downstream consequence of receptor signaling and is too broad for Gas6 curation. Reason: Use signaling pathway terms rather than generic gene-expression outcomes for GAS6. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0010804 negative regulation of tumor necrosis factor-mediated signaling pathway	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: negative regulation of TNF-mediated signaling is consistent with GAS6/TAM anti-inflammatory and survival signaling, but it is a context-specific output. Reason: Retain as non-core because the primary molecular role is TAM receptor activation. Supporting Evidence: PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0019079 viral genome replication	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: viral genome replication is an indirect pathogen-context consequence of GAS6/TAM-mediated viral entry or signaling and is not a core host function. Reason: Retain only as a non-core host-factor annotation. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0032689 negative regulation of type II interferon production	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: suppression of interferon-gamma/type II interferon production is consistent with reported GAS6/TAM immunoregulatory programs but is a downstream immune-context effect. Reason: Retain as non-core immunoregulation rather than primary GAS6 function. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0032692 negative regulation of interleukin-1 production	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: reduced interleukin-1 production is consistent with TAM-mediated anti-inflammatory feedback but is not the primary molecular function of GAS6. Reason: Retain as non-core immunoregulatory output. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0032720 negative regulation of tumor necrosis factor production	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: reduced tumor necrosis factor production is consistent with GAS6/TAM anti-inflammatory feedback but is not the core ligand function. Reason: Retain as non-core immunoregulatory output. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0032825 positive regulation of natural killer cell differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: natural killer cell differentiation is noted as a GAS6/TAM-associated immune outcome, but it is downstream and cell-context specific. Reason: Retain as non-core because the core role is extracellular TAM receptor activation. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0035457 cellular response to interferon-alpha	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: cellular response to interferon-alpha is a plausible immune-context annotation for TAM signaling crosstalk, but it is not a defining function of GAS6. Reason: Retain as non-core immune signaling context. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0035754 B cell chemotaxis	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: B cell chemotaxis may reflect immune-cell responses to GAS6/TAM signaling, but it is a downstream context rather than the core molecular role. Reason: Retain as non-core pending more specific direct mouse evidence. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process	ISS GO_REF:0000024	MODIFY	Summary: MODIFY: GAS6 does not directly inhibit cysteine-type endopeptidases/caspases. It reduces apoptosis through TAM receptor signaling and downstream survival pathways. Reason: Replace the incorrect molecular-function term with the supported biological-process term for anti-apoptotic signaling. Proposed replacements: negative regulation of apoptotic process Supporting Evidence: PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6.
GO:0045892 negative regulation of DNA-templated transcription	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: negative regulation of DNA-templated transcription is an indirect downstream signaling consequence and not a direct function of GAS6. Reason: This term overstates downstream transcriptional effects as a Gas6 process. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0046718 symbiont entry into host cell	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: symbiont/virus entry annotations reflect pathogen exploitation of GAS6/TAM phosphatidylserine bridging rather than physiological GAS6 function. Reason: Retain as non-core pathogen-context annotation. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0050766 positive regulation of phagocytosis	ISS GO_REF:0000024	ACCEPT	Summary: ACCEPT: positive regulation of phagocytosis is supported by Gas6-enhanced phagocytic uptake of apoptotic cells, especially in TAM receptor contexts. Reason: This is a core cellular consequence of the GAS6 phosphatidylserine/TAM bridging mechanism. Supporting Evidence: PMID:18159085 The phagocytic ability of Sertoli cells increased by five times in the presence of Gas6 in serum-free medium when compared with controls. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon highlights efferocytosis as a central GAS6/TAM function, with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on phagocytes.
GO:0070168 negative regulation of biomineral tissue development	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: negative regulation of biomineral tissue development may reflect GAS6/AXL effects on survival/calcification contexts, but it is peripheral to the core ligand mechanism. Reason: Retain as non-core because the direct role is TAM receptor signaling. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0097241 hematopoietic stem cell migration to bone marrow	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: hematopoietic stem cell migration to bone marrow is a specific hematopoietic context and not the main molecular function of GAS6. Reason: Retain as non-core pending direct mouse-specific support. Supporting Evidence: PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells.
GO:2000669 negative regulation of dendritic cell apoptotic process	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: dendritic-cell survival regulation is plausible for GAS6/TAM immune signaling but is a cell-context-specific outcome. Reason: Retain as non-core immune-cell survival output. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0001934 positive regulation of protein phosphorylation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: positive regulation of protein phosphorylation is broadly correct for GAS6/TAM signaling but less specific than positive regulation of protein kinase activity and PI3K/AKT signaling. Reason: Retain as a broad downstream signaling consequence, not as a primary core annotation. Supporting Evidence: PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0003104 positive regulation of glomerular filtration	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: glomerular filtration is a high-level renal physiological phenotype and is too indirect for mouse Gas6 as a core GO process. Reason: The curated mechanism is extracellular TAM ligand signaling; renal filtration effects should be supported with narrower contextual evidence before retention as a core-like process. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0005102 signaling receptor binding	ISS GO_REF:0000024	MODIFY	Summary: MODIFY: signaling receptor binding is true but too generic for GAS6. The more informative annotation is receptor ligand activity for TAM receptor tyrosine kinases. Reason: Receptor ligand activity captures both binding and receptor activation. Proposed replacements: receptor ligand activity Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0006468 protein phosphorylation	ISS GO_REF:0000024	MODIFY	Summary: MODIFY: protein phosphorylation incorrectly suggests GAS6 participates in the phosphorylation process itself. GAS6 is the extracellular ligand that activates receptor and downstream protein kinases. Reason: Replace with positive regulation of protein kinase activity, which accurately describes ligand-mediated kinase activation. Proposed replacements: positive regulation of protein kinase activity Supporting Evidence: PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0032008 positive regulation of TOR signaling	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: TOR signaling can lie downstream of PI3K/AKT, but this is a secondary pathway branch rather than the primary GAS6 function. Reason: Retain as non-core downstream signaling. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0032148 activation of protein kinase B activity	ISS GO_REF:0000024	ACCEPT	Summary: ACCEPT: activation of protein kinase B activity is supported as a direct downstream effect of GAS6/Axl signaling. Reason: The term captures the AKT activation branch of GAS6/TAM signaling. Supporting Evidence: PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. PMID:15650770 Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying outside-in signaling via alphaIIbbeta3.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISS GO_REF:0000024	ACCEPT	Summary: ACCEPT: positive regulation of PI3K/protein kinase B signaling is a well-supported GAS6/TAM output in oligodendrocytes, erythroblasts, and platelets. Reason: Multiple mouse-relevant experiments show Gas6/TAM signaling activates PI3K-Akt survival or platelet signaling pathways. Supporting Evidence: PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. PMID:15650770 Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying outside-in signaling via alphaIIbbeta3. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0071307 cellular response to vitamin K	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: vitamin K is required for GAS6 gamma-carboxylation, but GAS6 is a vitamin K-dependent protein rather than a mediator of cellular response to vitamin K. Reason: Post-translational dependence should not be represented as a protein-level response process. Supporting Evidence: PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding.
GO:0071333 cellular response to glucose stimulus	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: cellular response to glucose stimulus is too far upstream or contextual for the reviewed Gas6 evidence. Reason: The direct Gas6 role is extracellular TAM receptor signaling, not glucose-response execution. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0071466 cellular response to xenobiotic stimulus	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: xenobiotic-response annotations likely reflect warfarin sensitivity of GAS6 carboxylation rather than a function performed by GAS6. Reason: Warfarin affects GAS6 maturation; GAS6 itself should not be curated as mediating a xenobiotic response without direct evidence. Supporting Evidence: PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding.
GO:0072659 protein localization to plasma membrane	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: protein localization to plasma membrane is a downstream or inferred cellular effect and is not a precise annotation for secreted GAS6. Reason: The appropriate direct annotation is extracellular TAM receptor ligand/signaling activity. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses.
GO:0085029 extracellular matrix assembly	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: extracellular matrix assembly is likely an indirect fibroblast/secretome-context association and not a direct Gas6 function. Reason: Retain the extracellular-location evidence but do not curate ECM assembly as a core or direct process. Supporting Evidence: PMID:24006456 Mouse cardiac fibroblasts were transfected with pre-/anti-miR of miR-29b and miR-30c, and their conditioned medium was analyzed by mass spectrometry.
GO:2000270 negative regulation of fibroblast apoptotic process	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: Gas6 supports fibroblast survival under starvation, but the cell-type-specific anti-apoptotic term is a downstream outcome. Reason: Retain as non-core survival output. Supporting Evidence: PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase.
GO:2000352 negative regulation of endothelial cell apoptotic process	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: endothelial-cell survival is consistent with UniProt-described GAS6/AXL function, but this cell-type-specific survival outcome is non-core. Reason: Retain as non-core survival output. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:2000533 negative regulation of renal albumin absorption	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: renal albumin absorption is a very specific renal outcome transferred from orthologous/automated evidence and is not established as a direct mouse Gas6 function here. Reason: This appears downstream and context-specific relative to the conserved TAM ligand role. Supporting Evidence: file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0043066 negative regulation of apoptotic process	IDA PMID:16723520 Gas6/Axl signaling activates the phosphatidylinositol 3-kina...	ACCEPT	Summary: ACCEPT: negative regulation of apoptotic process is a recurrent GAS6/TAM signaling output in several cell types, including fibroblasts and oligodendrocytes. Reason: Gas6 protects cells from serum deprivation, TNF-alpha, and growth factor withdrawal through AXL/TAM signaling. Supporting Evidence: PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase.
GO:0001764 neuron migration	IGI PMID:18787040 Axl and Tyro3 modulate female reproduction by influencing go...	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: GnRH neuron migration/survival depends on Axl and Tyro3 and is stimulated by Gas6 in the cited system, but it is a developmental consequence of TAM signaling rather than the main GAS6 function. Reason: Retain as a supported developmental phenotype-level annotation, non-core. Supporting Evidence: PMID:18787040 Silencing studies evaluated the role of Tyro3 and Axl in NLT GnRH neuronal cells and suggest that both play a role in Gas6 stimulation of GnRH neuronal survival and migration.
GO:0005615 extracellular space	IDA PMID:18188450 Role of Gas6 in erythropoiesis and anemia in mice.	ACCEPT	Summary: ACCEPT: extracellular space is the correct functional location for the mature secreted GAS6 ligand. Reason: GAS6 has a signal peptide, is annotated by UniProt as secreted, and acts extracellularly on cell-surface TAM receptors. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0031589 cell-substrate adhesion	IMP PMID:18188450 Role of Gas6 in erythropoiesis and anemia in mice.	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: erythroid or stromal adhesion effects may occur in the anemia/Epo context, but they are downstream of Gas6 signaling and not the defining molecular function. Reason: Retain as a context-specific non-core outcome. Supporting Evidence: PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells.
GO:0043066 negative regulation of apoptotic process	IMP PMID:18188450 Role of Gas6 in erythropoiesis and anemia in mice.	ACCEPT	Summary: ACCEPT: negative regulation of apoptotic process is a recurrent GAS6/TAM signaling output in several cell types, including fibroblasts and oligodendrocytes. Reason: Gas6 protects cells from serum deprivation, TNF-alpha, and growth factor withdrawal through AXL/TAM signaling. Supporting Evidence: PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase.
GO:0043277 apoptotic cell clearance	IDA PMID:18159085 Gas6 and the Tyro 3 receptor tyrosine kinase subfamily regul...	ACCEPT	Summary: ACCEPT: apoptotic cell clearance is a core cellular role of GAS6/TAM signaling. GAS6 promotes recognition and phagocytosis of apoptotic cells by TAM-expressing phagocytes. Reason: The Sertoli-cell study and broader TAM literature support GAS6 as an efferocytosis ligand. Supporting Evidence: PMID:18159085 The phagocytic ability of Sertoli cells increased by five times in the presence of Gas6 in serum-free medium when compared with controls. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon highlights efferocytosis as a central GAS6/TAM function, with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on phagocytes.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP PMID:18188450 Role of Gas6 in erythropoiesis and anemia in mice.	ACCEPT	Summary: ACCEPT: positive regulation of PI3K/protein kinase B signaling is a well-supported GAS6/TAM output in oligodendrocytes, erythroblasts, and platelets. Reason: Multiple mouse-relevant experiments show Gas6/TAM signaling activates PI3K-Akt survival or platelet signaling pathways. Supporting Evidence: PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. PMID:15650770 Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying outside-in signaling via alphaIIbbeta3. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0071363 cellular response to growth factor stimulus	IMP PMID:18188450 Role of Gas6 in erythropoiesis and anemia in mice.	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: Gas6 participates in cellular responses to growth-factor contexts such as Epo and serum-starvation/growth stimulation, but this term is broad and context-dependent. Reason: Retain as non-core because it describes the biological context, not the primary molecular activity. Supporting Evidence: PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. PMID:8336730 This finding thus defines a new member of vitamin K-dependent proteins that is expressed in many human and mouse tissues and may be involved in the regulation of a protease cascade relevant in growth regulation.
GO:0007596 blood coagulation	IMP PMID:15184064 Vitamin K-dependent Gas6 activates ERK kinase and stimulates...	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: Gas6 influences platelet signaling and thrombus stabilization, but blood coagulation is too broad and can imply direct participation in the coagulation cascade. Reason: Gas6-deficient or TAM-blocked mice have impaired thrombus stabilization without the protein acting as a coagulation enzyme or core cascade component. Supporting Evidence: PMID:15650770 Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying outside-in signaling via alphaIIbbeta3. file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses.
GO:0043066 negative regulation of apoptotic process	IMP PMID:15184064 Vitamin K-dependent Gas6 activates ERK kinase and stimulates...	ACCEPT	Summary: ACCEPT: negative regulation of apoptotic process is a recurrent GAS6/TAM signaling output in several cell types, including fibroblasts and oligodendrocytes. Reason: Gas6 protects cells from serum deprivation, TNF-alpha, and growth factor withdrawal through AXL/TAM signaling. Supporting Evidence: PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase.
GO:0048018 receptor ligand activity	ISO GO_REF:0000008	ACCEPT	Summary: ACCEPT: receptor ligand activity is the clearest existing MF term for GAS6. Mouse GAS6 is a secreted vitamin K-dependent ligand for TAM receptor tyrosine kinases, especially AXL, and ligand binding activates receptor phosphorylation and downstream signaling. Reason: This term captures the core molecular role of GAS6 better than generic receptor-binding terms. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0048146 positive regulation of fibroblast proliferation	ISO GO_REF:0000008	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: Gas6 stimulates cardiac fibroblast proliferation through vitamin K-dependent Axl/ERK signaling, but fibroblast proliferation is a tissue-specific outcome. Reason: Retain as a supported non-core biological effect. Supporting Evidence: PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IGI PMID:15650770 Role of Gas6 receptors in platelet signaling during thrombus...	ACCEPT	Summary: ACCEPT: positive regulation of PI3K/protein kinase B signaling is a well-supported GAS6/TAM output in oligodendrocytes, erythroblasts, and platelets. Reason: Multiple mouse-relevant experiments show Gas6/TAM signaling activates PI3K-Akt survival or platelet signaling pathways. Supporting Evidence: PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. PMID:15650770 Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying outside-in signaling via alphaIIbbeta3. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0070374 positive regulation of ERK1 and ERK2 cascade	ISO GO_REF:0000008	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: ERK1/ERK2 activation is experimentally supported in cardiac fibroblasts but is one context-specific signaling branch downstream of the TAM receptor-ligand interaction. Reason: Retain as a supported downstream outcome, but do not treat it as the defining GAS6 function. Supporting Evidence: PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
GO:0007167 enzyme-linked receptor protein signaling pathway	IGI PMID:9395235 Signaling through the ARK tyrosine kinase receptor protects ...	ACCEPT	Summary: ACCEPT: enzyme-linked receptor protein signaling pathway is appropriate because GAS6 activates TAM receptor tyrosine kinases. Reason: The primary signaling receptors for GAS6 are enzyme-linked receptor tyrosine kinases. Supporting Evidence: PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses.
GO:0043066 negative regulation of apoptotic process	IDA PMID:9395235 Signaling through the ARK tyrosine kinase receptor protects ...	ACCEPT	Summary: ACCEPT: negative regulation of apoptotic process is a recurrent GAS6/TAM signaling output in several cell types, including fibroblasts and oligodendrocytes. Reason: Gas6 protects cells from serum deprivation, TNF-alpha, and growth factor withdrawal through AXL/TAM signaling. Supporting Evidence: PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase.
GO:0043066 negative regulation of apoptotic process	IGI PMID:9395235 Signaling through the ARK tyrosine kinase receptor protects ...	ACCEPT	Summary: ACCEPT: negative regulation of apoptotic process is a recurrent GAS6/TAM signaling output in several cell types, including fibroblasts and oligodendrocytes. Reason: Gas6 protects cells from serum deprivation, TNF-alpha, and growth factor withdrawal through AXL/TAM signaling. Supporting Evidence: PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:16723520 We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase.
GO:0048018 receptor ligand activity	IDA PMID:9395235 Signaling through the ARK tyrosine kinase receptor protects ...	ACCEPT	Summary: ACCEPT: receptor ligand activity is the clearest existing MF term for GAS6. Mouse GAS6 is a secreted vitamin K-dependent ligand for TAM receptor tyrosine kinases, especially AXL, and ligand binding activates receptor phosphorylation and downstream signaling. Reason: This term captures the core molecular role of GAS6 better than generic receptor-binding terms. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses. PMID:9395235 Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6. PMID:15184064 Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0005615 extracellular space	ISO PMID:8336730 The protein encoded by a growth arrest-specific gene (gas6) ...	ACCEPT	Summary: ACCEPT: extracellular space is the correct functional location for the mature secreted GAS6 ligand. Reason: GAS6 has a signal peptide, is annotated by UniProt as secreted, and acts extracellularly on cell-surface TAM receptors. Supporting Evidence: file:mouse/Gas6/Gas6-uniprot.txt UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding. file:mouse/Gas6/Gas6-deep-research-falcon.md Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
GO:0009267 cellular response to starvation	IDA PMID:8336730 The protein encoded by a growth arrest-specific gene (gas6) ...	MARK AS OVER ANNOTATED	Summary: MARK_AS_OVER_ANNOTATED: serum starvation induces gas6 expression, but expression context is not the same as a function of the GAS6 protein in cellular response to starvation. Reason: Avoid conflating gene expression regulation with gene product function. Supporting Evidence: PMID:8336730 This finding thus defines a new member of vitamin K-dependent proteins that is expressed in many human and mouse tissues and may be involved in the regulation of a protease cascade relevant in growth regulation.
GO:0071363 cellular response to growth factor stimulus	IDA PMID:8336730 The protein encoded by a growth arrest-specific gene (gas6) ...	KEEP AS NON CORE	Summary: KEEP_AS_NON_CORE: Gas6 participates in cellular responses to growth-factor contexts such as Epo and serum-starvation/growth stimulation, but this term is broad and context-dependent. Reason: Retain as non-core because it describes the biological context, not the primary molecular activity. Supporting Evidence: PMID:18188450 Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. PMID:8336730 This finding thus defines a new member of vitamin K-dependent proteins that is expressed in many human and mouse tissues and may be involved in the regulation of a protease cascade relevant in growth regulation.

Core Functions

Extracellular receptor ligand for TAM receptor tyrosine kinases. Vitamin K-carboxylated GAS6 binds AXL, TYRO3, and MER/MERTK at the cell surface, promoting receptor activation and downstream kinase signaling including PI3K/AKT and ERK/MAPK pathways that support survival, proliferation, adhesion, migration, and platelet/thrombus-stabilization responses in specific tissues.

Molecular Function:

receptor ligand activity

Directly Involved In:

cell surface receptor signaling pathway positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of protein kinase activity negative regulation of apoptotic process

Cellular Locations:

extracellular space

Supporting Evidence:

file:mouse/Gas6/Gas6-uniprot.txt
UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses.
PMID:9395235
Activation of ARK phosphorylation and a weak but significant induction of MAP kinase activity accompanied the increased survival of cells treated with Gas6.
PMID:16723520
We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death.
PMID:15184064
Gas6 stimulated tyrosine phosphorylation of Axl as well as phosphorylation of ERK kinase.
PMID:18188450
Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells.
PMID:15650770
Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying outside-in signaling via alphaIIbbeta3.
file:mouse/Gas6/Gas6-deep-research-falcon.md
Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
file:mouse/Gas6/Gas6-deep-research-falcon.md
Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.

Phosphatidylserine-dependent bridging ligand for apoptotic-cell clearance. The carboxylated Gla domain binds phosphatidylserine-exposed apoptotic or activated membranes, while the C-terminal receptor-binding region engages TAM receptors on phagocytes, thereby promoting apoptotic-cell recognition and efferocytosis.

Molecular Function:

phosphatidylserine binding

Directly Involved In:

apoptotic cell clearance positive regulation of phagocytosis

Cellular Locations:

extracellular space

Supporting Evidence:

PMID:18159085
The phagocytic ability of Sertoli cells increased by five times in the presence of Gas6 in serum-free medium when compared with controls.
file:mouse/Gas6/Gas6-deep-research-falcon.md
Falcon highlights efferocytosis as a central GAS6/TAM function, with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on phagocytes.
file:mouse/Gas6/Gas6-deep-research-falcon.md
Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation.
file:mouse/Gas6/Gas6-uniprot.txt
UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000008

Gene Ontology annotation by the MGI curatorial staff, curated orthology

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000096

Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000119

Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:15184064

Vitamin K-dependent Gas6 activates ERK kinase and stimulates growth of cardiac fibroblasts.

PMID:15650770

Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy.

PMID:16723520

Gas6/Axl signaling activates the phosphatidylinositol 3-kinase/Akt1 survival pathway to protect oligodendrocytes from tumor necrosis factor alpha-induced apoptosis.

PMID:18159085

Gas6 and the Tyro 3 receptor tyrosine kinase subfamily regulate the phagocytic function of Sertoli cells.

PMID:18188450

Role of Gas6 in erythropoiesis and anemia in mice.

PMID:18787040

Axl and Tyro3 modulate female reproduction by influencing gonadotropin-releasing hormone neuron survival and migration.

PMID:24006456

Extracellular matrix secretion by cardiac fibroblasts: role of microRNA-29b and microRNA-30c.

PMID:8336730

The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade.

PMID:9395235

Signaling through the ARK tyrosine kinase receptor protects from apoptosis in the absence of growth stimulation.

file:mouse/Gas6/Gas6-uniprot.txt

UniProtKB Q61592 mouse GAS6 record

Mouse GAS6 is a secreted ligand for TAM receptor tyrosine kinases AXL, TYRO3, and MER/MERTK.

"UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER receptor tyrosine kinases, with roles in cell growth, survival, adhesion, migration, platelet activation, and thrombotic responses."
GAS6 has vitamin K-dependent gamma-carboxyglutamate residues essential for calcium binding and is annotated as secreted.

"UniProt annotates the mature mouse GAS6 protein as secreted and notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium binding."

file:mouse/Gas6/Gas6-deep-research-falcon.md

Falcon deep research report for mouse Gas6

Falcon synthesizes GAS6 as a secreted TAM ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor kinase signaling.

"Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and triggers receptor dimerization and kinase activation."
Falcon identifies efferocytosis, inflammatory regulation, and PI3K-AKT/ERK signaling as major GAS6/TAM functional outputs.

"Falcon highlights efferocytosis as a central GAS6/TAM function, with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on phagocytes."

Suggested Experiments

Experiment: Compare fully carboxylated recombinant mouse GAS6 with warfarin-produced/non-carboxylated GAS6 in matched AXL-, TYRO3-, and MERTK-expressing phagocyte assays measuring receptor phosphorylation, apoptotic-cell binding, and engulfment.

Hypothesis: Gamma-carboxylated mouse GAS6 activates TAM receptors and promotes apoptotic-cell clearance more effectively than non-carboxylated GAS6.

Type: biochemical receptor activation and efferocytosis assay

Experiment: Use tissue-specific Gas6 perturbation or rescue models with direct TAM signaling readouts to determine whether these high-level phenotypes persist after controlling for general survival/efferocytosis effects.

Hypothesis: Renal, biomineralization, and nuclear-export annotations are secondary context effects rather than direct conserved GAS6 functions.

Type: conditional mouse genetics with pathway readouts

📚 Additional Documentation

Deep Research Falcon

(Gas6-deep-research-falcon.md)

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gene_info: Name=Gas6;
organism_full: Mus musculus (Mouse).
protein_family: Not specified in UniProt
protein_domains: cEGF. (IPR026823); Coagulation_fac-like_Gla_dom. (IPR017857); ConA-like_dom_sf.
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q61592
Protein Description: RecName: Full=Growth arrest-specific protein 6; Short=GAS-6; AltName: Full=AXL receptor tyrosine kinase ligand; Flags: Precursor;
Gene Information: Name=Gas6;
Organism (full): Mus musculus (Mouse).
Protein Family: Not specified in UniProt
Key Domains: cEGF. (IPR026823); Coagulation_fac-like_Gla_dom. (IPR017857); ConA-like_dom_sf. (IPR013320); EGF-like_Ca-bd_dom. (IPR001881); EGF-like_dom. (IPR000742)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "Gas6" matches the protein description above
Verify the organism is correct: Mus musculus (Mouse).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'Gas6' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene Gas6 (gene ID: Gas6, UniProt: Q61592) in mouse.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q61592
Protein Description: RecName: Full=Growth arrest-specific protein 6; Short=GAS-6; AltName: Full=AXL receptor tyrosine kinase ligand; Flags: Precursor;
Gene Information: Name=Gas6;
Organism (full): Mus musculus (Mouse).
Protein Family: Not specified in UniProt
Key Domains: cEGF. (IPR026823); Coagulation_fac-like_Gla_dom. (IPR017857); ConA-like_dom_sf. (IPR013320); EGF-like_Ca-bd_dom. (IPR001881); EGF-like_dom. (IPR000742)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "Gas6" matches the protein description above
Verify the organism is correct: Mus musculus (Mouse).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Please provide a comprehensive research report on the gene Gas6 (gene ID: Gas6, UniProt: Q61592) in mouse.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Comprehensive research report: Mouse Gas6 (UniProt Q61592) functional annotation

Executive summary

Mouse Gas6 encodes growth arrest-specific protein 6 (GAS6), a secreted, vitamin K–dependent, multi-domain ligand of the TAM receptor tyrosine kinases (TYRO3, AXL, MERTK). Its core biochemical role is to bridge phosphatidylserine (PtdSer)-bearing membranes (e.g., apoptotic cells, activated platelets, extracellular vesicles, viral envelopes) to TAM receptors and trigger receptor dimerization and kinase activation, thereby controlling efferocytosis, inflammatory resolution, vascular biology, and tissue repair programs. Key signaling outputs include PI3K–AKT, MEK–ERK/MAPK, SRC/GRB2, and context-specific JAK/STAT and SOCS1/3-mediated negative feedback on inflammatory pathways. Recent mouse studies (2023–2024) demonstrate GAS6-dependent regulation of blood–brain barrier integrity in infectious/sepsis models, macrophage efferocytosis and protection in hepatic ischemia–reperfusion injury, and therapeutic benefit of local rmGAS6 delivery in osteoarthritis models. Translationally, the GAS6/TAM axis is actively targeted by small-molecule inhibitors, decoy receptors/ligand traps, antibodies/ADCs, and aptamers, with numerous registered clinical trials and detailed potency metrics in 2024 authoritative reviews. (miao2024therapeutictargetingof pages 1-3, prouse2024functionsoftam pages 3-4, miao2024extracellularvesiclescontaining pages 2-4, li2023gas6exertsneuroprotective pages 1-2, miao2024therapeutictargetingof pages 9-11)

1) Mandatory verification: correct gene/protein identity

1.1 UniProt accession-to-gene/protein mapping

A UniProt-linked proteomics dataset table explicitly lists UniProt accession Q61592 aligned with “Growth-arrest-specific protein 6 precursor (GAS-6)”, supporting the mapping of Q61592 to mouse GAS6 precursor. (keene2009massspectrometricand pages 23-24)

1.2 Definition

GAS6 is described in recent authoritative reviews as a secreted, vitamin K-dependent ligand of the TAM receptors (TYRO3, AXL, MERTK). (zhai2023gas6axlpathwayimmunological pages 1-2, miao2024therapeutictargetingof pages 1-3)

1.3 Domain architecture (aligns with user-provided UniProt domain list)

Multiple recent sources converge on the canonical GAS6 modular organization:
- N-terminal Gla (γ-carboxyglutamate) domain (vitamin K-dependent),
- Four EGF-like domains,
- C-terminal SHBG-like region composed of two laminin G-like (LG) domains. (zhai2023gas6axlpathwayimmunological pages 1-2, apostolo2024couldgas6tamaxis pages 4-6)

This matches the user-provided UniProt domain expectations (Gla/coagulation-factor-like domain; EGF-like repeats including Ca-binding EGF; ConA-like/LG modules). (zhai2023gas6axlpathwayimmunological pages 1-2, apostolo2024couldgas6tamaxis pages 6-7)

2) Key concepts & definitions (current understanding)

2.1 TAM receptors and their ligands

The TAM receptor family comprises TYRO3, AXL, and MERTK, receptor tyrosine kinases that regulate immune homeostasis, efferocytosis, and tissue repair. (miao2024therapeutictargetingof pages 1-3)
The two primary vitamin K-dependent TAM ligands are GAS6 and PROS1 (Protein S); GAS6 can bind all three TAM receptors, while PROS1 has different receptor selectivity. (miao2024therapeutictargetingof pages 1-3, prieto2024thetamsubfamily pages 8-9)

2.2 Ligand specificity/affinity and physiological context

GAS6 activates TAM receptors with a reported receptor preference AXL > TYRO3 > MERTK (highest affinity for AXL). (miao2024therapeutictargetingof pages 1-3, prouse2024functionsoftam pages 3-4)
Review-level quantitative context: plasma GAS6 ~0.25 nM vs protein S ~350 nM (much more abundant). (prouse2024functionsoftam pages 3-4)

2.3 Core biochemical mechanism: PtdSer bridging

GAS6’s vitamin K–dependent Gla domain binds membrane phospholipids including PtdSer, while its C-terminal LG/SHBG region engages TAM receptor immunoglobulin domains; this tripartite interaction (PtdSer–ligand–receptor) is central to TAM activation in contexts like apoptotic-cell recognition. (miao2024therapeutictargetingof pages 1-3, prouse2024functionsoftam pages 3-4, prieto2024thetamsubfamily pages 8-9)

2.4 Receptor activation model (stoichiometry)

A 2024 Nature Reviews Drug Discovery synthesis describes an activation path where initial 1:1 GAS6–AXL binding progresses to a 2:2 GAS6–AXL assembly, driving receptor homodimerization and kinase activation. (miao2024therapeutictargetingof pages 1-3)

2.5 Efferocytosis

Efferocytosis is the phagocytic clearance of apoptotic cells. GAS6 supports efferocytosis by acting as a bridging ligand between apoptotic-cell PtdSer and TAM receptors on phagocytes, promoting anti-inflammatory resolution programs. (apostolo2024couldgas6tamaxis pages 6-7, tanim2024mertkinhibitionas pages 2-4)

3) Molecular function, pathways, and cellular localization

3.1 Molecular function (functional annotation)

Primary molecular function: extracellular ligand activity that triggers TAM receptor activation.
- GAS6 is a secreted ligand that binds TAM receptors and initiates RTK signaling. (zhai2023gas6axlpathwayimmunological pages 1-2, miao2024therapeutictargetingof pages 1-3)
- GAS6 requires vitamin K–dependent γ-carboxylation of its Gla domain for full function; inhibiting γ-carboxylation blocks effective TAM activation. (prouse2024functionsoftam pages 3-4, miao2024therapeutictargetingof pages 1-3)

3.2 Post-translational modification: γ-carboxylation in vivo (mouse-relevant)

A 2024 study demonstrates that a functional vitamin K cycle exists in rodent brain tissue/cells and that warfarin can abolish/restores (with vitamin K1) endogenous GAS6 γ-carboxylation in ex vivo/in vitro settings, linking nutrient status and inflammatory state to GAS6 functionality. (aydin2024modificationofgas6 pages 14-16)

3.3 Downstream signaling pathways

Across reviews, GAS6/TAM signaling is repeatedly linked to:
- PI3K–AKT signaling (survival, metabolism, anti-apoptosis), (prouse2024functionsoftam pages 3-4, apostolo2024couldgas6tamaxis pages 6-7)
- MEK–ERK/MAPK signaling (growth, migration, differentiation), (miao2024therapeutictargetingof pages 1-3, apostolo2024couldgas6tamaxis pages 6-7)
- adaptor recruitment including p85-PI3K, SRC family, and GRB2, (miao2024therapeutictargetingof pages 1-3)
- context-specific JAK/STAT engagement and immunoregulatory transcriptional feedback. (apostolo2024couldgas6tamaxis pages 4-6)

3.4 Immunoregulatory outputs (SOCS, cytokine suppression)

GAS6/TAM signaling can induce SOCS1/SOCS3 and suppress inflammatory cytokine programs and TLR outputs in macrophage-centric contexts, consistent with a gatekeeping role in innate immune regulation. (apostolo2024couldgas6tamaxis pages 6-7, prouse2024functionsoftama pages 5-6)

3.5 Subcellular/extracellular localization

GAS6 is primarily extracellular/secreted, acting in soluble form or associated with PtdSer-bearing membranes/vesicles to activate TAM receptors on adjacent cells. (zhai2023gas6axlpathwayimmunological pages 1-2, miao2024therapeutictargetingof pages 1-3)
TAM receptor ectodomains can be shed, generating soluble sAXL/sMERTK that still bind GAS6, functioning as ligand “traps” that modulate pathway activity. (apostolo2024couldgas6tamaxis pages 6-7, apostolo2024couldgas6tamaxis pages 4-6)

4) Expression patterns and mouse-relevant localization

4.1 Broad tissue/cell-type expression (mouse-relevant summaries)

A 2024 synthesis reports GAS6 as broadly expressed, including vascular endothelial cells (heart/kidney/lung), platelets, and immune cells, with earlier work noting expression in hematopoietic tissue. (miao2024therapeutictargetingof pages 26-28)
Another 2024 review emphasizes GAS6 expression in vascular smooth muscle cells, kidney, lung, intestine, heart, and monocytes. (apostolo2024couldgas6tamaxis pages 6-7)

4.2 CNS expression and TAM partitioning

A 2024 study in Cells reports GAS6 expression in microglia and astrocytes and cell-type-partitioned TAM expression: microglia show strong Mertk and Axl but little Tyro3, while astrocytes express Tyro3 and Axl (and Tyro3 is abundant in neurons). (aydin2024modificationofgas6 pages 14-16)

5) Recent developments and latest research (2023–2024 prioritized)

5.1 2024: EV-delivered GAS6 drives MerTK-dependent efferocytosis and hepatoprotection in mouse hepatic ischemia–reperfusion injury

A 2024 Cell Death Discovery primary study shows MSC-derived extracellular vesicles (MSC-EVs) enriched in GAS6 reduce liver injury after ischemia–reperfusion, localize to liver macrophages, and enhance MerTK–ERK–COX2 signaling and macrophage efferocytosis; GAS6 knockdown in EVs reduces MerTK/ERK activation, efferocytosis, and hepatoprotection (with multiple quantitative endpoints and n=5 per group reported for some analyses). (miao2024extracellularvesiclescontaining pages 2-4)

Figure-based evidence from this study directly supports: (i) GAS6 enrichment in EVs; (ii) reduced MerTK/ERK/COX2 activation with GAS6 knockdown; and (iii) worsening liver injury endpoints (ALT/AST, Suzuki score) and efferocytosis quantification when GAS6 is depleted from EVs. (miao2024extracellularvesiclescontaining media dc397bc7, miao2024extracellularvesiclescontaining media d099de7d)

5.2 2024: GAS6 deficiency worsens outcomes in mouse Japanese encephalitis; GAS6 delivery improves BBB integrity and resistance

A 2024 Journal of Neuroinflammation mouse study reports that brain GAS6 decreases during JEV infection, inversely correlating with viral load and neuronal loss, and that GAS6/TAM signaling deficiency increases mortality and BBB breakdown; delivering/overexpressing GAS6 increases resistance and improves BBB integrity. (bian2024gas6asa pages 1-2)

5.3 2023: Exogenous GAS6 restores BBB integrity in a mouse sepsis-associated encephalopathy model

A 2023 mouse study using CLP sepsis reports that a single i.v. 6 μg GAS6 dose (given immediately after CLP; n=20 per group) improved neurological scores and reduced BBB permeability/brain edema; tight junction proteins occludin and ZO-1 were restored by GAS6 treatment. (li2023gas6exertsneuroprotective pages 1-2)

5.4 2023: Local rmGAS6 administration in mouse OA models

A 2023 eLife study provides a detailed mouse protocol in which intra-articular recombinant mouse GAS6 (rmGAS6) was administered weekly at 50 ng/g (~5 µl), n=6 per group post-DMM surgery (harvested 4–8 weeks), with efferocytosis assays in RAW264.7/BMDM systems and histologic scoring (OARSI; synovitis scales). (yao2023downregulatedgas6impairs pages 14-15)

5.5 2024: Mechanistic update on endogenous vitamin K–dependent GAS6 modification in brain

A 2024 Cells paper provides evidence of an endogenous vitamin K cycle within rodent brain and demonstrates GAS6 γ-carboxylation is sensitive to warfarin and can be restored with vitamin K1, connecting metabolism/nutrient state to GAS6 signaling capacity in CNS contexts. (aydin2024modificationofgas6 pages 14-16)

6) Current applications and real-world implementations

6.1 Biomarkers and disease monitoring

Reviews emphasize soluble TAM system components (e.g., soluble receptors produced by shedding) and altered GAS6/TAM axis states as candidate biomarkers across inflammatory, fibrotic, and oncologic contexts, driven by the pathway’s extracellular accessibility and measurable circulating components. (apostolo2024couldgas6tamaxis pages 6-7, miao2024therapeutictargetingof pages 16-18)

6.2 Therapeutic targeting: modalities and rationale (expert synthesis, 2024)

A 2024 Nature Reviews Drug Discovery article provides an authoritative overview of real-world intervention strategies targeting the GAS6/TAM axis:
- Small-molecule kinase inhibitors (AXL-, MERTK-, or pan-TAM),
- Biologics disrupting GAS6–receptor binding (e.g., soluble decoys/ligand traps),
- Antibodies and antibody–drug conjugates (ADCs) targeting AXL,
- Aptamers against AXL.
It notes that ~20 TAM inhibitors have entered clinical trials and provides potency metrics and multiple NCT identifiers. (miao2024therapeutictargetingof pages 9-11, miao2024therapeutictargetingof pages 13-15, miao2024therapeutictargetingof pages 18-20)

6.3 Quantitative therapeutic parameters (examples)

Bemcentinib (AXL inhibitor) is summarized with IC50 14 nM and multiple phase I/II programs (including COVID-19 testing). (miao2024therapeutictargetingof pages 9-11)
Native GAS6–AXL binding is exceptionally high affinity (reported KD ~32 pM), shaping the engineering requirements for competitive biologic inhibitors/decoys. (miao2024therapeutictargetingof pages 13-15)
An affinity-matured anti-AXL antibody is reported with picomolar–nanomolar binding (example values include KD 1 nM human and 545 pM mouse in the review). (miao2024therapeutictargetingof pages 13-15)

7) Clinical trials snapshot (examples from ClinicalTrials.gov records retrieved)

The clinical-trial landscape is heavily AXL/MERTK-focused, consistent with GAS6 as an upstream ligand.

7.1 MERTK/TAM-axis inhibitor: MRX-2843

NCT04872478 (posted 2022): Phase 1 dose-escalation PK/safety study of MRX-2843 in adolescents and adults with relapsed/refractory AML/ALL/MPAL; estimated enrollment 50. (NCT04872478 chunk 1)
NCT04946890 (posted 2021): Phase I/II study of MRX2843 in relapsed/refractory AML; estimated enrollment 104, oral dosing with planned dose levels including 80/120/180 mg/day; prior MerTK/FLT3-targeting therapy excluded. (NCT04946890 chunk 1)

7.2 AXL-targeted ADC: mecobotamab vedotin (CAB-AXL-ADC; BA3011)

NCT03425279 (start 2018-02-15): Phase 1/2 study of mecbotamab vedotin (BA3011) ± nivolumab in advanced solid tumors including sarcoma; actual enrollment 245; completed with completion date 2025-01-08; outcomes include ORR (RECIST), PK, PFS, OS. (NCT03425279 chunk 1)
NCT04681131 (start 2021-03-17): Phase 2 study of CAB-AXL-ADC (BA3011) alone or with a PD-1 inhibitor in metastatic NSCLC; actual enrollment 85; completed with primary/completion date 2025-07-09. (NCT04681131 chunk 1)

7.3 Additional trial mapping from recent oncology review literature

A 2023 Frontiers in Oncology review aggregates multiple AXL-targeting trial IDs (examples include NCT03425279 for BA3011, and other AXL/MET/multikinase programs), illustrating broad clinical interest in the AXL/GAS6 axis across cancers. (pidkovka2023alteredexpressionof pages 8-9)

8) Expert opinions and analysis (authoritative sources)

8.1 Why GAS6/TAM is considered a high-value therapeutic axis

A 2024 Nature Reviews Drug Discovery synthesis emphasizes that TAM receptors are rarely mutated (pathology often arises through expression changes and microenvironmental activation), potentially reducing classical mutation-driven resistance and motivating both ligand–receptor blockade and kinase inhibition strategies. (miao2024therapeutictargetingof pages 1-3)

8.2 Key translational challenge: extremely high GAS6–AXL affinity

The same 2024 review highlights that the picomolar native affinity of GAS6 for AXL can limit the efficacy of weaker binders and creates a strong engineering constraint for biologics meant to neutralize the interaction. (miao2024therapeutictargetingof pages 13-15, miao2024therapeutictargetingof pages 18-20)

8.3 Safety/physiology considerations

Reviews note that MERTK has essential homeostatic roles (efferocytosis, tissue maintenance), implying possible liabilities for indiscriminate inhibition—supporting careful target selection (AXL vs pan-TAM) and context-specific strategies. (miao2024therapeutictargetingof pages 15-16)

9) Key statistics and recent data highlights

Circulating abundance contrast: GAS6 ~0.25 nM vs protein S ~350 nM (review-level values; human-centric but mechanistically informative). (prouse2024functionsoftam pages 3-4)
Mouse study sample sizes/dosing:
CLP sepsis model: n=20 per group, 6 μg i.v. GAS6 immediate treatment. (li2023gas6exertsneuroprotective pages 1-2)
OA DMM model: intra-articular rmGAS6 50 ng/g weekly, n=6 per group, harvest 4–8 weeks. (yao2023downregulatedgas6impairs pages 14-15)
HIRI model with MSC-EVs: histology/serum endpoints reported with n=5 per group in the excerpted methods/results. (miao2024extracellularvesiclescontaining pages 2-4)
Figure-derived quantitative validation of GAS6 dependence in HIRI protection (ALT/AST, Suzuki score, efferocytosis quantification) is available in the retrieved image panels. (miao2024extracellularvesiclescontaining media dc397bc7, miao2024extracellularvesiclescontaining media d099de7d)

10) Consolidated evidence map

The following table provides a structured “at-a-glance” annotation linking major functional claims to sources.

Category	Key points	Key evidence	Primary citations
Identity / verification	Mouse Gas6 encodes growth arrest-specific protein 6 (GAS6), a secreted vitamin K-dependent TAM ligand; UniProt-linked evidence maps Q61592 to GAS-6 precursor.	Q61592 mapped to GAS-6 precursor in proteomics table; GAS6 described as secreted TAM ligand	(keene2009massspectrometricand pages 23-24, zhai2023gas6axlpathwayimmunological pages 1-2)
Domain architecture	GAS6 has an N-terminal Gla (γ-carboxyglutamate) domain, 4 EGF-like domains, and a C-terminal SHBG-like / 2 laminin G-like (LG) domains that mediate receptor binding.	Canonical Gla–EGF–LG/SHBG organization	(zhai2023gas6axlpathwayimmunological pages 1-2, apostolo2024couldgas6tamaxis pages 6-7, apostolo2024couldgas6tamaxis pages 4-6)
Ligand–receptor specificity	GAS6 activates all three TAM receptors (AXL, TYRO3, MERTK) with highest affinity for AXL; PROS1 differs by favoring TYRO3/MERTK and not AXL.	Affinity hierarchy AXL > TYRO3 > MERTK	(miao2024therapeutictargetingof pages 1-3, prouse2024functionsoftam pages 3-4)
Post-translational requirement	GAS6 requires vitamin K-dependent γ-carboxylation of the Gla domain for full activity; blocking γ-carboxylation prevents effective TAM activation.	Gla modification required; warfarin reduces Gla-GAS6 in brain tissue	(miao2024therapeutictargetingof pages 1-3, prouse2024functionsoftam pages 3-4, aydin2024modificationofgas6 pages 14-16)
Biochemical mechanism	The Gla domain binds Ca2+ and phosphatidylserine (PtdSer) on apoptotic cells/activated platelets, while the LG/SHBG region binds TAM Ig domains, enabling ligand-mediated receptor activation.	PtdSer bridging plus receptor engagement by LG domains	(miao2024therapeutictargetingof pages 1-3, prouse2024functionsoftam pages 3-4, tanim2024mertkinhibitionas pages 2-4)
Receptor activation model	GAS6–AXL binding proceeds from 1:1 complex to 2:2 assembly, driving receptor homodimerization, kinase activation, and adaptor recruitment.	1:1 → 2:2 GAS6–AXL assembly	(miao2024therapeutictargetingof pages 1-3)
Core downstream pathways	Activated TAM signaling engages PI3K/p85–AKT, MEK/ERK-MAPK, SRC/GRB2, and context-dependent JAK/STAT signaling.	Autophosphorylation recruits PI3K, SRC, GRB2; downstream AKT/ERK/JAK-STAT	(miao2024therapeutictargetingof pages 1-3, prouse2024functionsoftam pages 3-4, apostolo2024couldgas6tamaxis pages 4-6)
Immune regulation / efferocytosis	GAS6 functions as a bridging molecule for efferocytosis, promotes anti-inflammatory signaling, induces SOCS1/SOCS3, and suppresses inflammatory cytokine programs including IFNAR-STAT1/TLR outputs.	Efferocytosis, SOCS induction, cytokine suppression	(apostolo2024couldgas6tamaxis pages 6-7, prouse2024functionsoftama pages 3-5, prouse2024functionsoftama pages 5-6)
Extracellular localization	GAS6 acts mainly outside the cell as a secreted extracellular ligand; soluble sAXL/sMERTK ectodomains can bind and sequester GAS6.	Secreted ligand; soluble receptor traps	(zhai2023gas6axlpathwayimmunological pages 1-2, apostolo2024couldgas6tamaxis pages 6-7, apostolo2024couldgas6tamaxis pages 4-6, miao2024therapeutictargetingof pages 4-6)
Tissue / cell-type expression in mouse-relevant literature	Broad expression reported in vascular smooth muscle, kidney, lung, intestine, heart, monocytes; also in vascular endothelial cells, platelets, hematopoietic tissue, and CNS glia.	Broad tissue distribution; immune and vascular compartments	(apostolo2024couldgas6tamaxis pages 6-7, apostolo2024couldgas6tamaxis pages 4-6, miao2024therapeutictargetingof pages 26-28)
CNS localization	In mouse brain, GAS6 is expressed in microglia and astrocytes; Mertk/Axl are strong in microglia, Tyro3/Axl in astrocytes, with Tyro3 abundant in neurons.	CNS glial expression and TAM partitioning	(aydin2024modificationofgas6 pages 14-16)
Mouse phenotype: thrombosis / vascular homeostasis	Gas6−/− mice are largely normal at baseline but form smaller thrombi on challenge, indicating context-dependent roles in thrombosis rather than constitutive developmental necessity.	Normal baseline, reduced thrombus formation under challenge	(miao2024therapeutictargetingof pages 4-6)
Mouse phenotype: Japanese encephalitis	In mouse JEV models, brain GAS6 decreases and inversely correlates with viral load/neuronal loss; GAS6/TAM deficiency worsens mortality, neuroinflammation, and BBB breakdown, while GAS6 supplementation/overexpression improves resistance.	Higher mortality with deficiency; BBB protection with GAS6	(bian2024gas6asa pages 1-2)
Mouse phenotype: sepsis-associated encephalopathy	In CLP sepsis mice, a single 6 μg i.v. GAS6 dose reduced neurologic deficits, brain edema, BBB leakage, and restored occludin/ZO-1 expression.	n=20/group; BBB and neurologic benefit	(li2023gas6exertsneuroprotective pages 1-2)
Mouse phenotype: liver ischemia-reperfusion	In murine HIRI, MSC-derived EVs enriched in GAS6 localize to liver macrophages and enhance MerTK–ERK–COX2 signaling, efferocytosis, and hepatoprotection; GAS6 knockdown in EVs weakens these effects.	n=5/group; lower ALT/AST, Suzuki score, apoptosis; Figure supports mechanism	(miao2024extracellularvesiclescontaining pages 2-4, miao2024extracellularvesiclescontaining media dc397bc7, miao2024extracellularvesiclescontaining media d099de7d)
Mouse phenotype: osteoarthritis / synovium	In DMM OA models using C57BL/6 and Apoe−/− mice, reduced GAS6 is linked to impaired synovial macrophage efferocytosis; recombinant mouse GAS6 given intra-articularly (50 ng/g weekly, ~5 μl, n=6/group) improved pathology.	rmGAS6 dosing defined; restored phagocytic capacity, reduced apoptotic-cell burden	(yao2023downregulatedgas6impairs pages 1-2, yao2023downregulatedgas6impairs pages 14-15)
Recent mechanistic update (2024)	Mouse brain contains a functional vitamin K cycle capable of modifying endogenous GAS6; inflammatory stimulation downregulates key vitamin K cycle genes in microglia, linking nutrient/PTM state to GAS6 function.	Endogenous GGCX/VKORC1 machinery; warfarin-sensitive Gla-GAS6	(aydin2024modificationofgas6 pages 14-16)
Quantitative recent stats	Review-level quantitative parameters: circulating GAS6 ~0.25 nM versus PROS1 ~350 nM; native GAS6–AXL affinity is very high (KD ~32 pM).	Plasma abundance contrast; picomolar AXL binding	(prouse2024functionsoftam pages 3-4, miao2024therapeutictargetingof pages 13-15)
Translational applications	The GAS6/TAM axis is being targeted via small-molecule inhibitors, decoy receptors/ligand traps (e.g., batiraxcept), antibodies, ADCs, and aptamers; >20 TAM inhibitors have entered clinical development.	Bemcentinib, MRX-2843, sitravatinib, CAB-AXL-ADC, batiraxcept, GL21 aptamer	(miao2024therapeutictargetingof pages 9-11, miao2024therapeutictargetingof pages 16-18, miao2024therapeutictargetingof pages 13-15, miao2024therapeutictargetingof pages 18-20)
Example clinical implementations	Trial-linked examples include bemcentinib (AXL inhibitor; phase I/II programs), MRX-2843 (MERTK/FLT3 inhibitor), CAB-AXL-ADC, and batiraxcept/AVB-500 combinations; clinical records include NCT03184571, NCT04890509, NCT03510104, NCT04872478, NCT04946890, NCT04681131, NCT03425279, NCT04019288, NCT05826015.	Multiple registered trials and enrollment-defined studies	(miao2024therapeutictargetingof pages 9-11, miao2024therapeutictargetingof pages 15-16, miao2024therapeutictargetingof pages 13-15, miao2024therapeutictargetingof pages 18-20)

Table: This table summarizes functional annotation for mouse GAS6 (UniProt Q61592), covering molecular structure, mechanism, localization, mouse phenotypes, and translational relevance. It is designed as a compact evidence map with direct citation IDs for rapid integration into the final report.

References (URLs and publication dates for key sources)

Miao YR, Rankin EB, Giaccia AJ. Therapeutic targeting of the functionally elusive TAM receptor family. Nat Rev Drug Discov (Issue 3; e-pub 2023; print Dec 2024). https://doi.org/10.1038/s41573-023-00846-8 (miao2024therapeutictargetingof pages 1-3, miao2024therapeutictargetingof pages 9-11)
Tutusaus A, Morales A, García de Frutos P, Marí M. GAS6/TAM Axis as Therapeutic Target in Liver Diseases. Semin Liver Dis Feb 2024. https://doi.org/10.1055/a-2275-0408 (tutusaus2024gas6tamaxisas pages 1-3)
Apostolo D et al. Could Gas6/TAM Axis Provide Valuable Insights into the Pathogenesis of Systemic Sclerosis? Curr Issues Mol Biol Jul 2024. https://doi.org/10.3390/cimb46070444 (apostolo2024couldgas6tamaxis pages 6-7)
Aydin N et al. Modification of Gas6 Protein in the Brain by a Functional Endogenous Tissue Vitamin K Cycle. Cells May 2024. https://doi.org/10.3390/cells13100873 (aydin2024modificationofgas6 pages 14-16)
Miao L et al. Extracellular vesicles containing GAS6 protect the liver from ischemia-reperfusion injury… Cell Death Discovery Sep 2024. https://doi.org/10.1038/s41420-024-02169-y (miao2024extracellularvesiclescontaining pages 2-4, miao2024extracellularvesiclescontaining media dc397bc7)
Yao Z et al. Down-regulated GAS6 impairs synovial macrophage efferocytosis and promotes obesity-associated osteoarthritis. eLife May 2023. https://doi.org/10.7554/elife.83069 (yao2023downregulatedgas6impairs pages 14-15)
Bian P et al. GAS6 as a potential target to alleviate neuroinflammation during Japanese encephalitis in mouse models. J Neuroinflammation Sep 2024. https://doi.org/10.1186/s12974-024-03225-1 (bian2024gas6asa pages 1-2)
ClinicalTrials.gov records: NCT04872478 (posted 2022), NCT04946890 (posted 2021), NCT03425279 (start 2018-02-15), NCT04681131 (start 2021-03-17). (NCT04872478 chunk 1, NCT04946890 chunk 1, NCT03425279 chunk 1, NCT04681131 chunk 1)

Notes on scope and evidence strength

Many mechanistic details (domains, PS-bridging, stoichiometry, adaptor recruitment) are supported strongly by 2023–2024 authoritative reviews that integrate extensive primary literature; mouse-specific in vivo functional roles are supported by multiple 2023–2024 primary studies in distinct tissues and disease models. (miao2024therapeutictargetingof pages 1-3, miao2024extracellularvesiclescontaining pages 2-4, li2023gas6exertsneuroprotective pages 1-2)
Some quantitative values (e.g., plasma concentrations) are primarily human-derived review estimates but are included because they constrain interpretation of ligand availability and therapeutic competition at the GAS6–AXL interface. (prouse2024functionsoftam pages 3-4, miao2024therapeutictargetingof pages 13-15)

References

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(miao2024extracellularvesiclescontaining pages 2-4): Longyu Miao, Chaoqun Yu, Ge Guan, Xiaoyu Luan, Xiaoshuang Jin, Meiqi Pan, Yuzhen Yang, Jiaoyang Yan, Peng Chen, and Guohu Di. Extracellular vesicles containing gas6 protect the liver from ischemia-reperfusion injury by enhancing macrophage efferocytosis via mertk-erk-cox2 signaling. Cell Death Discovery, Sep 2024. URL: https://doi.org/10.1038/s41420-024-02169-y, doi:10.1038/s41420-024-02169-y. This article has 33 citations and is from a peer-reviewed journal.
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(prouse2024functionsoftama pages 5-6): Teagan Prouse, Samarpan Majumder, and Rinku Majumder. Functions of tam receptors and their ligands protein s and gas6 in atherosclerosis and cardiovascular disease. Oct 2024. URL: https://doi.org/10.20944/preprints202410.0083.v1, doi:10.20944/preprints202410.0083.v1.
(miao2024therapeutictargetingof pages 26-28): Yu Rebecca Miao, Erinn B. Rankin, and Amato J. Giaccia. Therapeutic targeting of the functionally elusive tam receptor family. Nature reviews. Drug discovery, 23:201-217, Dec 2024. URL: https://doi.org/10.1038/s41573-023-00846-8, doi:10.1038/s41573-023-00846-8. This article has 67 citations.
(miao2024extracellularvesiclescontaining media dc397bc7): Longyu Miao, Chaoqun Yu, Ge Guan, Xiaoyu Luan, Xiaoshuang Jin, Meiqi Pan, Yuzhen Yang, Jiaoyang Yan, Peng Chen, and Guohu Di. Extracellular vesicles containing gas6 protect the liver from ischemia-reperfusion injury by enhancing macrophage efferocytosis via mertk-erk-cox2 signaling. Cell Death Discovery, Sep 2024. URL: https://doi.org/10.1038/s41420-024-02169-y, doi:10.1038/s41420-024-02169-y. This article has 33 citations and is from a peer-reviewed journal.
(miao2024extracellularvesiclescontaining media d099de7d): Longyu Miao, Chaoqun Yu, Ge Guan, Xiaoyu Luan, Xiaoshuang Jin, Meiqi Pan, Yuzhen Yang, Jiaoyang Yan, Peng Chen, and Guohu Di. Extracellular vesicles containing gas6 protect the liver from ischemia-reperfusion injury by enhancing macrophage efferocytosis via mertk-erk-cox2 signaling. Cell Death Discovery, Sep 2024. URL: https://doi.org/10.1038/s41420-024-02169-y, doi:10.1038/s41420-024-02169-y. This article has 33 citations and is from a peer-reviewed journal.
(bian2024gas6asa pages 1-2): Peiyu Bian, Haijun Zhang, Chuantao Ye, Chuanyu Luo, Hong Jiang, Yuan Wang, Yangchao Dong, Jing Yang, Fanglin Zhang, Xiaoming Wang, Ying Zhang, Zhansheng Jia, and Yingfeng Lei. Gas6 as a potential target to alleviate neuroinflammation during japanese encephalitis in mouse models. Journal of Neuroinflammation, Sep 2024. URL: https://doi.org/10.1186/s12974-024-03225-1, doi:10.1186/s12974-024-03225-1. This article has 5 citations and is from a peer-reviewed journal.
(yao2023downregulatedgas6impairs pages 14-15): Zihao Yao, Weizhong Qi, Hongbo Zhang, Zhicheng Zhang, Liangliang Liu, Yan Shao, Hua Zeng, Jianbin Yin, Haoyan Pan, Xiongtian Guo, Anling Liu, Daozhang Cai, Xiaochun Bai, and Haiyan Zhang. Down-regulated gas6 impairs synovial macrophage efferocytosis and promotes obesity-associated osteoarthritis. eLife, May 2023. URL: https://doi.org/10.7554/elife.83069, doi:10.7554/elife.83069. This article has 72 citations and is from a domain leading peer-reviewed journal.
(miao2024therapeutictargetingof pages 16-18): Yu Rebecca Miao, Erinn B. Rankin, and Amato J. Giaccia. Therapeutic targeting of the functionally elusive tam receptor family. Nature reviews. Drug discovery, 23:201-217, Dec 2024. URL: https://doi.org/10.1038/s41573-023-00846-8, doi:10.1038/s41573-023-00846-8. This article has 67 citations.
(miao2024therapeutictargetingof pages 13-15): Yu Rebecca Miao, Erinn B. Rankin, and Amato J. Giaccia. Therapeutic targeting of the functionally elusive tam receptor family. Nature reviews. Drug discovery, 23:201-217, Dec 2024. URL: https://doi.org/10.1038/s41573-023-00846-8, doi:10.1038/s41573-023-00846-8. This article has 67 citations.
(miao2024therapeutictargetingof pages 18-20): Yu Rebecca Miao, Erinn B. Rankin, and Amato J. Giaccia. Therapeutic targeting of the functionally elusive tam receptor family. Nature reviews. Drug discovery, 23:201-217, Dec 2024. URL: https://doi.org/10.1038/s41573-023-00846-8, doi:10.1038/s41573-023-00846-8. This article has 67 citations.
(NCT04872478 chunk 1): Pharmacokinetic and Safety Study of MRX-2843 in Adolescents and Adults With Relapsed/Refractory AML, ALL, or MPAL. Meryx, Inc.. 2022. ClinicalTrials.gov Identifier: NCT04872478
(NCT04946890 chunk 1): A Study of MRX2843 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia. Betta Pharmaceuticals Co., Ltd.. 2021. ClinicalTrials.gov Identifier: NCT04946890
(NCT03425279 chunk 1): CAB-AXL-ADC Safety and Efficacy Study in Adult and Adolescent Patients With Sarcoma. BioAtla, Inc.. 2018. ClinicalTrials.gov Identifier: NCT03425279
(NCT04681131 chunk 1): CAB-AXL-ADC Safety and Efficacy Study in Adults With NSCLC. BioAtla, Inc.. 2021. ClinicalTrials.gov Identifier: NCT04681131
(pidkovka2023alteredexpressionof pages 8-9): Nataliya Pidkovka and Abbes Belkhiri. Altered expression of axl receptor tyrosine kinase in gastrointestinal cancers: a promising therapeutic target. Frontiers in Oncology, Jul 2023. URL: https://doi.org/10.3389/fonc.2023.1079041, doi:10.3389/fonc.2023.1079041. This article has 9 citations.
(miao2024therapeutictargetingof pages 15-16): Yu Rebecca Miao, Erinn B. Rankin, and Amato J. Giaccia. Therapeutic targeting of the functionally elusive tam receptor family. Nature reviews. Drug discovery, 23:201-217, Dec 2024. URL: https://doi.org/10.1038/s41573-023-00846-8, doi:10.1038/s41573-023-00846-8. This article has 67 citations.
(prouse2024functionsoftama pages 3-5): Teagan Prouse, Samarpan Majumder, and Rinku Majumder. Functions of tam receptors and their ligands protein s and gas6 in atherosclerosis and cardiovascular disease. Oct 2024. URL: https://doi.org/10.20944/preprints202410.0083.v1, doi:10.20944/preprints202410.0083.v1.
(miao2024therapeutictargetingof pages 4-6): Yu Rebecca Miao, Erinn B. Rankin, and Amato J. Giaccia. Therapeutic targeting of the functionally elusive tam receptor family. Nature reviews. Drug discovery, 23:201-217, Dec 2024. URL: https://doi.org/10.1038/s41573-023-00846-8, doi:10.1038/s41573-023-00846-8. This article has 67 citations.
(yao2023downregulatedgas6impairs pages 1-2): Zihao Yao, Weizhong Qi, Hongbo Zhang, Zhicheng Zhang, Liangliang Liu, Yan Shao, Hua Zeng, Jianbin Yin, Haoyan Pan, Xiongtian Guo, Anling Liu, Daozhang Cai, Xiaochun Bai, and Haiyan Zhang. Down-regulated gas6 impairs synovial macrophage efferocytosis and promotes obesity-associated osteoarthritis. eLife, May 2023. URL: https://doi.org/10.7554/elife.83069, doi:10.7554/elife.83069. This article has 72 citations and is from a domain leading peer-reviewed journal.
(tutusaus2024gas6tamaxisas pages 1-3): Anna Tutusaus, Albert Morales, Pablo García de Frutos, and Montserrat Marí. Gas6/tam axis as therapeutic target in liver diseases. Seminars in Liver Disease, 44:99-114, Feb 2024. URL: https://doi.org/10.1055/a-2275-0408, doi:10.1055/a-2275-0408. This article has 7 citations and is from a peer-reviewed journal.

Citations

keene2009massspectrometricand pages 23-24
miao2024therapeutictargetingof pages 1-3
prouse2024functionsoftam pages 3-4
miao2024therapeutictargetingof pages 26-28
miao2024extracellularvesiclescontaining pages 2-4
miao2024therapeutictargetingof pages 9-11
miao2024therapeutictargetingof pages 13-15
pidkovka2023alteredexpressionof pages 8-9
miao2024therapeutictargetingof pages 15-16
miao2024therapeutictargetingof pages 4-6
prieto2024thetamsubfamily pages 8-9
tanim2024mertkinhibitionas pages 2-4
prouse2024functionsoftama pages 5-6
miao2024therapeutictargetingof pages 16-18
miao2024therapeutictargetingof pages 18-20
prouse2024functionsoftama pages 3-5
https://doi.org/10.1038/s41573-023-00846-8
https://doi.org/10.1055/a-2275-0408
https://doi.org/10.3390/cimb46070444
https://doi.org/10.3390/cells13100873
https://doi.org/10.1038/s41420-024-02169-y
https://doi.org/10.7554/elife.83069
https://doi.org/10.1186/s12974-024-03225-1
https://doi.org/10.1038/s41573-023-00846-8,
https://doi.org/10.3390/ijms252312736,
https://doi.org/10.1038/s41420-024-02169-y,
https://doi.org/10.1002/pmic.200800385,
https://doi.org/10.3389/fonc.2023.1121130,
https://doi.org/10.3390/cimb46070444,
https://doi.org/10.3390/ijms25063369,
https://doi.org/10.3390/ijms25147660,
https://doi.org/10.3390/cells13100873,
https://doi.org/10.20944/preprints202410.0083.v1,
https://doi.org/10.1186/s12974-024-03225-1,
https://doi.org/10.7554/elife.83069,
https://doi.org/10.3389/fonc.2023.1079041,
https://doi.org/10.1055/a-2275-0408,

📄 View Raw YAML

id: Q61592
gene_symbol: Gas6
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
description: 'Growth arrest-specific protein 6 (Gas6) encodes a secreted, vitamin K-dependent
  extracellular ligand for TAM receptor tyrosine kinases AXL, TYRO3, and MER/MERTK. Carboxylated
  GAS6 binds phosphatidylserine-bearing membranes through its Gla domain and TAM receptor
  ectodomains through its C-terminal laminin G-like domains, promoting receptor activation,
  PI3K/AKT and ERK signaling, apoptotic-cell clearance, cell survival, and context-specific
  immune, vascular, platelet, and hematopoietic responses.'
existing_annotations:
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'ACCEPT: negative regulation of apoptotic process is a recurrent GAS6/TAM signaling
      output in several cell types, including fibroblasts and oligodendrocytes.'
    action: ACCEPT
    reason: Gas6 protects cells from serum deprivation, TNF-alpha, and growth factor
      withdrawal through AXL/TAM signaling.
    supported_by:
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'ACCEPT: extracellular space is the correct functional location for the mature
      secreted GAS6 ligand.'
    action: ACCEPT
    reason: GAS6 has a signal peptide, is annotated by UniProt as secreted, and acts
      extracellularly on cell-surface TAM receptors.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0007166
    label: cell surface receptor signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'ACCEPT: GAS6 is directly involved in cell-surface receptor signaling through
      TAM receptor tyrosine kinases.'
    action: ACCEPT
    reason: Ligand binding to AXL/TYRO3/MERTK initiates receptor activation and
      downstream signaling at the cell surface.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'ACCEPT: positive regulation of PI3K/protein kinase B signaling is a well-supported
      GAS6/TAM output in oligodendrocytes, erythroblasts, and platelets.'
    action: ACCEPT
    reason: Multiple mouse-relevant experiments show Gas6/TAM signaling activates
      PI3K-Akt survival or platelet signaling pathways.
    supported_by:
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
    - reference_id: PMID:15650770
      supporting_text: Gas6, through its receptors, activates PI3K and Akt and
        stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying
        outside-in signaling via alphaIIbbeta3.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'ACCEPT: receptor ligand activity is the clearest existing MF term for GAS6.
      Mouse GAS6 is a secreted vitamin K-dependent ligand for TAM receptor tyrosine kinases,
      especially AXL, and ligand binding activates receptor phosphorylation and downstream
      signaling.'
    action: ACCEPT
    reason: This term captures the core molecular role of GAS6 better than generic
      receptor-binding terms.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: 'KEEP_AS_NON_CORE: calcium binding is supported by the Gla and calcium-binding
      EGF-like domains and is important for the carboxylated extracellular ligand, but it
      is an enabling structural property rather than the main biological function.'
    action: KEEP_AS_NON_CORE
    reason: Retain as an ancillary molecular property of GAS6, not as the curated core
      function.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'ACCEPT: extracellular region is a broader but correct location for secreted
      GAS6.'
    action: ACCEPT
    reason: The mature protein is secreted and functions outside the cell.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0016477
    label: cell migration
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'KEEP_AS_NON_CORE: cell migration is a known downstream outcome of GAS6/TAM signaling
      but is broad and cell-context dependent.'
    action: KEEP_AS_NON_CORE
    reason: Retain as a non-core downstream process.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:18787040
      supporting_text: Silencing studies evaluated the role of Tyro3 and Axl in NLT GnRH
        neuronal cells and suggest that both play a role in Gas6 stimulation of GnRH
        neuronal survival and migration.
- term:
    id: GO:0030154
    label: cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'KEEP_AS_NON_CORE: cell differentiation reflects context-specific immune or hematopoietic
      consequences of GAS6/TAM signaling rather than a primary GAS6 function.'
    action: KEEP_AS_NON_CORE
    reason: Retain as a broad non-core process.
    supported_by:
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0031669
    label: cellular response to nutrient levels
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: cellular response to nutrient levels describes a context
      that can affect GAS6 expression or vitamin K-dependent modification, not the function
      executed by the GAS6 protein.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not treat upstream expression or modification context as a core Gas6
      biological process.
    supported_by:
    - reference_id: PMID:8336730
      supporting_text: This finding thus defines a new member of vitamin K-dependent
        proteins that is expressed in many human and mouse tissues and may be involved
        in the regulation of a protease cascade relevant in growth regulation.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: 'MODIFY: metal ion binding is too generic. GAS6 has specific calcium-binding
      Gla and EGF-like domains that support its vitamin K-dependent extracellular ligand function.'
    action: MODIFY
    reason: Replace the generic metal-binding annotation with calcium ion binding.
    proposed_replacement_terms:
    - id: GO:0005509
      label: calcium ion binding
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
- term:
    id: GO:0050878
    label: regulation of body fluid levels
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: regulation of body fluid levels is too broad and physiologically
      remote for the evidence reviewed.'
    action: MARK_AS_OVER_ANNOTATED
    reason: The direct function is secreted TAM ligand signaling, not general body-fluid
      regulation.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
- term:
    id: GO:0001786
    label: phosphatidylserine binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'ACCEPT: phosphatidylserine binding is a core biochemical property of vitamin
      K-carboxylated GAS6, allowing it to bridge PtdSer-exposed apoptotic or activated membranes
      to TAM receptors.'
    action: ACCEPT
    reason: The Gla-domain PtdSer interaction is central to GAS6-dependent TAM
      activation and efferocytosis.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon highlights efferocytosis as a central GAS6/TAM function,
        with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on
        phagocytes.
- term:
    id: GO:0001961
    label: positive regulation of cytokine-mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: GAS6/TAM signaling can tune cytokine-mediated pathways, including
      Epo-associated erythroid survival and immune signaling, but this is context-dependent.'
    action: KEEP_AS_NON_CORE
    reason: The annotation is plausible as a downstream regulatory effect rather than
      the core function.
    supported_by:
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0003104
    label: positive regulation of glomerular filtration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: glomerular filtration is a high-level renal physiological
      phenotype and is too indirect for mouse Gas6 as a core GO process.'
    action: MARK_AS_OVER_ANNOTATED
    reason: The curated mechanism is extracellular TAM ligand signaling; renal
      filtration effects should be supported with narrower contextual evidence before
      retention as a core-like process.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0005102
    label: signaling receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'MODIFY: signaling receptor binding is true but too generic for GAS6. The more
      informative annotation is receptor ligand activity for TAM receptor tyrosine kinases.'
    action: MODIFY
    reason: Receptor ligand activity captures both binding and receptor activation.
    proposed_replacement_terms:
    - id: GO:0048018
      label: receptor ligand activity
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'ACCEPT: extracellular space is the correct functional location for the mature
      secreted GAS6 ligand.'
    action: ACCEPT
    reason: GAS6 has a signal peptide, is annotated by UniProt as secreted, and acts
      extracellularly on cell-surface TAM receptors.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'REMOVE: cytoplasm is not the functional location of mature GAS6. The reviewed
      protein is secreted and acts extracellularly on cell-surface TAM receptors.'
    action: REMOVE
    reason: Any cytoplasmic signal would reflect biosynthesis or transfer noise rather
      than the active mature protein location.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0006909
    label: phagocytosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'MODIFY: generic phagocytosis is too broad. GAS6 most specifically promotes apoptotic-cell
      clearance/efferocytosis via TAM receptors.'
    action: MODIFY
    reason: Replace broad phagocytosis with apoptotic cell clearance for this ligand
      mechanism.
    proposed_replacement_terms:
    - id: GO:0043277
      label: apoptotic cell clearance
    supported_by:
    - reference_id: PMID:18159085
      supporting_text: The phagocytic ability of Sertoli cells increased by five times
        in the presence of Gas6 in serum-free medium when compared with controls.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon highlights efferocytosis as a central GAS6/TAM function,
        with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on
        phagocytes.
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'MODIFY: signal transduction is too broad. GAS6 specifically acts in cell-surface
      receptor signaling through TAM receptor tyrosine kinases.'
    action: MODIFY
    reason: Replace with a more specific receptor-signaling process already supported
      for GAS6.
    proposed_replacement_terms:
    - id: GO:0007166
      label: cell surface receptor signaling pathway
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
- term:
    id: GO:0007166
    label: cell surface receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'ACCEPT: GAS6 is directly involved in cell-surface receptor signaling through
      TAM receptor tyrosine kinases.'
    action: ACCEPT
    reason: Ligand binding to AXL/TYRO3/MERTK initiates receptor activation and
      downstream signaling at the cell surface.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: positive regulation of gene expression is an indirect
      downstream consequence of receptor signaling and is too broad for Gas6 curation.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Use signaling pathway terms rather than generic gene-expression outcomes for
      GAS6.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0010804
    label: negative regulation of tumor necrosis factor-mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: negative regulation of TNF-mediated signaling is consistent
      with GAS6/TAM anti-inflammatory and survival signaling, but it is a context-specific
      output.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because the primary molecular role is TAM receptor
      activation.
    supported_by:
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0019064
    label: fusion of virus membrane with host plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: enveloped viruses can exploit GAS6/TAM phosphatidylserine
      bridging for apoptotic mimicry, but this host-factor role is not an evolved core function
      of mouse Gas6.'
    action: KEEP_AS_NON_CORE
    reason: Retain as a pathogen-context annotation, explicitly non-core.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0019079
    label: viral genome replication
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: viral genome replication is an indirect pathogen-context consequence
      of GAS6/TAM-mediated viral entry or signaling and is not a core host function.'
    action: KEEP_AS_NON_CORE
    reason: Retain only as a non-core host-factor annotation.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'ACCEPT: GAS6 functions as an extracellular bridging/adaptor ligand by engaging
      phosphatidylserine-containing membranes through its Gla domain and TAM receptor ectodomains
      through its C-terminal LG domains. The term is imperfectly broad but captures this bridging
      role better than generic protein binding.'
    action: ACCEPT
    reason: The annotation represents a core bridging function, although a more specific
      PtdSer-dependent TAM receptor bridging MF would be preferable.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon highlights efferocytosis as a central GAS6/TAM function,
        with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on
        phagocytes.
    - reference_id: PMID:18159085
      supporting_text: The phagocytic ability of Sertoli cells increased by five times
        in the presence of Gas6 in serum-free medium when compared with controls.
- term:
    id: GO:0030971
    label: receptor tyrosine kinase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'ACCEPT: receptor tyrosine kinase binding is directly supported because GAS6
      binds and activates the TAM receptor tyrosine kinases AXL, TYRO3, and MER/MERTK.'
    action: ACCEPT
    reason: This specific binding term is mechanistically correct for the GAS6
      receptor-ligand interaction.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0031100
    label: animal organ regeneration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: organ regeneration is noted in UniProt/Falcon summaries for
      GAS6/TAM signaling, but it is a physiological outcome rather than a direct core function.'
    action: KEEP_AS_NON_CORE
    reason: Retain as a non-core tissue-repair outcome.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0032008
    label: positive regulation of TOR signaling
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: TOR signaling can lie downstream of PI3K/AKT, but this is
      a secondary pathway branch rather than the primary GAS6 function.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core downstream signaling.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0032689
    label: negative regulation of type II interferon production
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: suppression of interferon-gamma/type II interferon production
      is consistent with reported GAS6/TAM immunoregulatory programs but is a downstream immune-context
      effect.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immunoregulation rather than primary GAS6 function.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0032692
    label: negative regulation of interleukin-1 production
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: reduced interleukin-1 production is consistent with TAM-mediated
      anti-inflammatory feedback but is not the primary molecular function of GAS6.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immunoregulatory output.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0032715
    label: negative regulation of interleukin-6 production
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: reduced interleukin-6 production is consistent with GAS6/TAM
      anti-inflammatory signaling but is context-specific.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immunoregulatory output.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0032720
    label: negative regulation of tumor necrosis factor production
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: reduced tumor necrosis factor production is consistent with
      GAS6/TAM anti-inflammatory feedback but is not the core ligand function.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immunoregulatory output.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0032825
    label: positive regulation of natural killer cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: natural killer cell differentiation is noted as a GAS6/TAM-associated
      immune outcome, but it is downstream and cell-context specific.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because the core role is extracellular TAM receptor
      activation.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0035457
    label: cellular response to interferon-alpha
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: cellular response to interferon-alpha is a plausible immune-context
      annotation for TAM signaling crosstalk, but it is not a defining function of GAS6.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immune signaling context.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0035754
    label: B cell chemotaxis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: B cell chemotaxis may reflect immune-cell responses to GAS6/TAM
      signaling, but it is a downstream context rather than the core molecular role.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core pending more specific direct mouse evidence.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0043027
    label: cysteine-type endopeptidase inhibitor activity involved in apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'MODIFY: GAS6 does not directly inhibit cysteine-type endopeptidases/caspases.
      It reduces apoptosis through TAM receptor signaling and downstream survival pathways.'
    action: MODIFY
    reason: Replace the incorrect molecular-function term with the supported
      biological-process term for anti-apoptotic signaling.
    proposed_replacement_terms:
    - id: GO:0043066
      label: negative regulation of apoptotic process
    supported_by:
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'ACCEPT: negative regulation of apoptotic process is a recurrent GAS6/TAM signaling
      output in several cell types, including fibroblasts and oligodendrocytes.'
    action: ACCEPT
    reason: Gas6 protects cells from serum deprivation, TNF-alpha, and growth factor
      withdrawal through AXL/TAM signaling.
    supported_by:
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
- term:
    id: GO:0043277
    label: apoptotic cell clearance
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'ACCEPT: apoptotic cell clearance is a core cellular role of GAS6/TAM signaling.
      GAS6 promotes recognition and phagocytosis of apoptotic cells by TAM-expressing phagocytes.'
    action: ACCEPT
    reason: The Sertoli-cell study and broader TAM literature support GAS6 as an
      efferocytosis ligand.
    supported_by:
    - reference_id: PMID:18159085
      supporting_text: The phagocytic ability of Sertoli cells increased by five times
        in the presence of Gas6 in serum-free medium when compared with controls.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon highlights efferocytosis as a central GAS6/TAM function,
        with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on
        phagocytes.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: negative regulation of DNA-templated transcription is
      an indirect downstream signaling consequence and not a direct function of GAS6.'
    action: MARK_AS_OVER_ANNOTATED
    reason: This term overstates downstream transcriptional effects as a Gas6 process.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0046718
    label: symbiont entry into host cell
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: symbiont/virus entry annotations reflect pathogen exploitation
      of GAS6/TAM phosphatidylserine bridging rather than physiological GAS6 function.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core pathogen-context annotation.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0046813
    label: receptor-mediated virion attachment to host cell
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: receptor-mediated virion attachment can occur through GAS6/TAM
      apoptotic mimicry, but it is a pathogen-context use of the normal PtdSer/TAM bridging
      mechanism.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core pathogen-context annotation.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0046827
    label: positive regulation of protein export from nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: positive regulation of protein export from nucleus is
      too indirect and not part of the established GAS6/TAM ligand mechanism.'
    action: MARK_AS_OVER_ANNOTATED
    reason: No reviewed mouse evidence makes nuclear export a direct or central Gas6
      function.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'ACCEPT: receptor ligand activity is the clearest existing MF term for GAS6.
      Mouse GAS6 is a secreted vitamin K-dependent ligand for TAM receptor tyrosine kinases,
      especially AXL, and ligand binding activates receptor phosphorylation and downstream
      signaling.'
    action: ACCEPT
    reason: This term captures the core molecular role of GAS6 better than generic
      receptor-binding terms.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0050766
    label: positive regulation of phagocytosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'ACCEPT: positive regulation of phagocytosis is supported by Gas6-enhanced phagocytic
      uptake of apoptotic cells, especially in TAM receptor contexts.'
    action: ACCEPT
    reason: This is a core cellular consequence of the GAS6 phosphatidylserine/TAM
      bridging mechanism.
    supported_by:
    - reference_id: PMID:18159085
      supporting_text: The phagocytic ability of Sertoli cells increased by five times
        in the presence of Gas6 in serum-free medium when compared with controls.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon highlights efferocytosis as a central GAS6/TAM function,
        with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on
        phagocytes.
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'ACCEPT: positive regulation of PI3K/protein kinase B signaling is a well-supported
      GAS6/TAM output in oligodendrocytes, erythroblasts, and platelets.'
    action: ACCEPT
    reason: Multiple mouse-relevant experiments show Gas6/TAM signaling activates
      PI3K-Akt survival or platelet signaling pathways.
    supported_by:
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
    - reference_id: PMID:15650770
      supporting_text: Gas6, through its receptors, activates PI3K and Akt and
        stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying
        outside-in signaling via alphaIIbbeta3.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0070168
    label: negative regulation of biomineral tissue development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: negative regulation of biomineral tissue development may reflect
      GAS6/AXL effects on survival/calcification contexts, but it is peripheral to the core
      ligand mechanism.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because the direct role is TAM receptor signaling.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0070588
    label: calcium ion transmembrane transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'REMOVE: GAS6 binds calcium as a vitamin K-dependent Gla/EGF-domain protein but
      is not a calcium transporter and does not mediate calcium transmembrane transport.'
    action: REMOVE
    reason: The term confuses calcium binding with transport activity.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
- term:
    id: GO:0071307
    label: cellular response to vitamin K
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: vitamin K is required for GAS6 gamma-carboxylation,
      but GAS6 is a vitamin K-dependent protein rather than a mediator of cellular response
      to vitamin K.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Post-translational dependence should not be represented as a protein-level
      response process.
    supported_by:
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
- term:
    id: GO:0071333
    label: cellular response to glucose stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: cellular response to glucose stimulus is too far upstream
      or contextual for the reviewed Gas6 evidence.'
    action: MARK_AS_OVER_ANNOTATED
    reason: The direct Gas6 role is extracellular TAM receptor signaling, not
      glucose-response execution.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0071466
    label: cellular response to xenobiotic stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: xenobiotic-response annotations likely reflect warfarin
      sensitivity of GAS6 carboxylation rather than a function performed by GAS6.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Warfarin affects GAS6 maturation; GAS6 itself should not be curated as
      mediating a xenobiotic response without direct evidence.
    supported_by:
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
- term:
    id: GO:0072659
    label: protein localization to plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: protein localization to plasma membrane is a downstream
      or inferred cellular effect and is not a precise annotation for secreted GAS6.'
    action: MARK_AS_OVER_ANNOTATED
    reason: The appropriate direct annotation is extracellular TAM receptor
      ligand/signaling activity.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
- term:
    id: GO:0085029
    label: extracellular matrix assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: extracellular matrix assembly is likely an indirect
      fibroblast/secretome-context association and not a direct Gas6 function.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Retain the extracellular-location evidence but do not curate ECM assembly as
      a core or direct process.
    supported_by:
    - reference_id: PMID:24006456
      supporting_text: Mouse cardiac fibroblasts were transfected with pre-/anti-miR of
        miR-29b and miR-30c, and their conditioned medium was analyzed by mass
        spectrometry.
- term:
    id: GO:0097028
    label: dendritic cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: dendritic-cell differentiation is plausible within GAS6/TAM
      immune regulation, but it is a downstream immune-context annotation.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0097241
    label: hematopoietic stem cell migration to bone marrow
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: hematopoietic stem cell migration to bone marrow is a specific
      hematopoietic context and not the main molecular function of GAS6.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core pending direct mouse-specific support.
    supported_by:
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
- term:
    id: GO:1900142
    label: negative regulation of oligodendrocyte apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: protection of oligodendrocytes from apoptosis is experimentally
      supported but is a specific cellular context of the broader GAS6/TAM survival pathway.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core cell-type-specific survival output.
    supported_by:
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
- term:
    id: GO:2000270
    label: negative regulation of fibroblast apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'KEEP_AS_NON_CORE: Gas6 supports fibroblast survival under starvation, but the
      cell-type-specific anti-apoptotic term is a downstream outcome.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core survival output.
    supported_by:
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
- term:
    id: GO:2000352
    label: negative regulation of endothelial cell apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: endothelial-cell survival is consistent with UniProt-described
      GAS6/AXL function, but this cell-type-specific survival outcome is non-core.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core survival output.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:2000510
    label: positive regulation of dendritic cell chemotaxis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: dendritic-cell chemotaxis is a context-specific immune-cell
      response and not the defining role of GAS6.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immune-cell outcome.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:2000533
    label: negative regulation of renal albumin absorption
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: renal albumin absorption is a very specific renal outcome
      transferred from orthologous/automated evidence and is not established as a direct mouse
      Gas6 function here.'
    action: MARK_AS_OVER_ANNOTATED
    reason: This appears downstream and context-specific relative to the conserved TAM
      ligand role.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:2000669
    label: negative regulation of dendritic cell apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'KEEP_AS_NON_CORE: dendritic-cell survival regulation is plausible for GAS6/TAM
      immune signaling but is a cell-context-specific outcome.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immune-cell survival output.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0001934
    label: positive regulation of protein phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'KEEP_AS_NON_CORE: positive regulation of protein phosphorylation is broadly
      correct for GAS6/TAM signaling but less specific than positive regulation of protein
      kinase activity and PI3K/AKT signaling.'
    action: KEEP_AS_NON_CORE
    reason: Retain as a broad downstream signaling consequence, not as a primary core
      annotation.
    supported_by:
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0001934
    label: positive regulation of protein phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: positive regulation of protein phosphorylation is broadly
      correct for GAS6/TAM signaling but less specific than positive regulation of protein
      kinase activity and PI3K/AKT signaling.'
    action: KEEP_AS_NON_CORE
    reason: Retain as a broad downstream signaling consequence, not as a primary core
      annotation.
    supported_by:
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'MODIFY: protein phosphorylation incorrectly suggests GAS6 participates in the
      phosphorylation process itself. GAS6 is the extracellular ligand that activates receptor
      and downstream protein kinases.'
    action: MODIFY
    reason: Replace with positive regulation of protein kinase activity, which
      accurately describes ligand-mediated kinase activation.
    proposed_replacement_terms:
    - id: GO:0045860
      label: positive regulation of protein kinase activity
    supported_by:
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0032148
    label: activation of protein kinase B activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'ACCEPT: activation of protein kinase B activity is supported as a direct downstream
      effect of GAS6/Axl signaling.'
    action: ACCEPT
    reason: The term captures the AKT activation branch of GAS6/TAM signaling.
    supported_by:
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
    - reference_id: PMID:15650770
      supporting_text: Gas6, through its receptors, activates PI3K and Akt and
        stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying
        outside-in signaling via alphaIIbbeta3.
- term:
    id: GO:0045860
    label: positive regulation of protein kinase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'ACCEPT: GAS6 positively regulates protein kinase activity by activating TAM
      receptor tyrosine kinases and downstream kinases such as AKT and ERK.'
    action: ACCEPT
    reason: This regulatory BP accurately describes ligand-driven activation without
      implying that GAS6 itself is a kinase.
    supported_by:
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0001786
    label: phosphatidylserine binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'ACCEPT: phosphatidylserine binding is a core biochemical property of vitamin
      K-carboxylated GAS6, allowing it to bridge PtdSer-exposed apoptotic or activated membranes
      to TAM receptors.'
    action: ACCEPT
    reason: The Gla-domain PtdSer interaction is central to GAS6-dependent TAM
      activation and efferocytosis.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon highlights efferocytosis as a central GAS6/TAM function,
        with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on
        phagocytes.
- term:
    id: GO:0001961
    label: positive regulation of cytokine-mediated signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: GAS6/TAM signaling can tune cytokine-mediated pathways, including
      Epo-associated erythroid survival and immune signaling, but this is context-dependent.'
    action: KEEP_AS_NON_CORE
    reason: The annotation is plausible as a downstream regulatory effect rather than
      the core function.
    supported_by:
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0003104
    label: positive regulation of glomerular filtration
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: glomerular filtration is a high-level renal physiological
      phenotype and is too indirect for mouse Gas6 as a core GO process.'
    action: MARK_AS_OVER_ANNOTATED
    reason: The curated mechanism is extracellular TAM ligand signaling; renal
      filtration effects should be supported with narrower contextual evidence before
      retention as a core-like process.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0005102
    label: signaling receptor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'MODIFY: signaling receptor binding is true but too generic for GAS6. The more
      informative annotation is receptor ligand activity for TAM receptor tyrosine kinases.'
    action: MODIFY
    reason: Receptor ligand activity captures both binding and receptor activation.
    proposed_replacement_terms:
    - id: GO:0048018
      label: receptor ligand activity
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'ACCEPT: extracellular space is the correct functional location for the mature
      secreted GAS6 ligand.'
    action: ACCEPT
    reason: GAS6 has a signal peptide, is annotated by UniProt as secreted, and acts
      extracellularly on cell-surface TAM receptors.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'ACCEPT: extracellular space is the correct functional location for the mature
      secreted GAS6 ligand.'
    action: ACCEPT
    reason: GAS6 has a signal peptide, is annotated by UniProt as secreted, and acts
      extracellularly on cell-surface TAM receptors.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'REMOVE: cytoplasm is not the functional location of mature GAS6. The reviewed
      protein is secreted and acts extracellularly on cell-surface TAM receptors.'
    action: REMOVE
    reason: Any cytoplasmic signal would reflect biosynthesis or transfer noise rather
      than the active mature protein location.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0006909
    label: phagocytosis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'MODIFY: generic phagocytosis is too broad. GAS6 most specifically promotes apoptotic-cell
      clearance/efferocytosis via TAM receptors.'
    action: MODIFY
    reason: Replace broad phagocytosis with apoptotic cell clearance for this ligand
      mechanism.
    proposed_replacement_terms:
    - id: GO:0043277
      label: apoptotic cell clearance
    supported_by:
    - reference_id: PMID:18159085
      supporting_text: The phagocytic ability of Sertoli cells increased by five times
        in the presence of Gas6 in serum-free medium when compared with controls.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon highlights efferocytosis as a central GAS6/TAM function,
        with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on
        phagocytes.
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'MODIFY: signal transduction is too broad. GAS6 specifically acts in cell-surface
      receptor signaling through TAM receptor tyrosine kinases.'
    action: MODIFY
    reason: Replace with a more specific receptor-signaling process already supported
      for GAS6.
    proposed_replacement_terms:
    - id: GO:0007166
      label: cell surface receptor signaling pathway
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'MODIFY: signal transduction is too broad. GAS6 specifically acts in cell-surface
      receptor signaling through TAM receptor tyrosine kinases.'
    action: MODIFY
    reason: Replace with a more specific receptor-signaling process already supported
      for GAS6.
    proposed_replacement_terms:
    - id: GO:0007166
      label: cell surface receptor signaling pathway
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
- term:
    id: GO:0007166
    label: cell surface receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'ACCEPT: GAS6 is directly involved in cell-surface receptor signaling through
      TAM receptor tyrosine kinases.'
    action: ACCEPT
    reason: Ligand binding to AXL/TYRO3/MERTK initiates receptor activation and
      downstream signaling at the cell surface.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: positive regulation of gene expression is an indirect
      downstream consequence of receptor signaling and is too broad for Gas6 curation.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Use signaling pathway terms rather than generic gene-expression outcomes for
      GAS6.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0010804
    label: negative regulation of tumor necrosis factor-mediated signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: negative regulation of TNF-mediated signaling is consistent
      with GAS6/TAM anti-inflammatory and survival signaling, but it is a context-specific
      output.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because the primary molecular role is TAM receptor
      activation.
    supported_by:
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0019064
    label: fusion of virus membrane with host plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: enveloped viruses can exploit GAS6/TAM phosphatidylserine
      bridging for apoptotic mimicry, but this host-factor role is not an evolved core function
      of mouse Gas6.'
    action: KEEP_AS_NON_CORE
    reason: Retain as a pathogen-context annotation, explicitly non-core.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0019079
    label: viral genome replication
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: viral genome replication is an indirect pathogen-context consequence
      of GAS6/TAM-mediated viral entry or signaling and is not a core host function.'
    action: KEEP_AS_NON_CORE
    reason: Retain only as a non-core host-factor annotation.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'ACCEPT: GAS6 functions as an extracellular bridging/adaptor ligand by engaging
      phosphatidylserine-containing membranes through its Gla domain and TAM receptor ectodomains
      through its C-terminal LG domains. The term is imperfectly broad but captures this bridging
      role better than generic protein binding.'
    action: ACCEPT
    reason: The annotation represents a core bridging function, although a more specific
      PtdSer-dependent TAM receptor bridging MF would be preferable.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon highlights efferocytosis as a central GAS6/TAM function,
        with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on
        phagocytes.
    - reference_id: PMID:18159085
      supporting_text: The phagocytic ability of Sertoli cells increased by five times
        in the presence of Gas6 in serum-free medium when compared with controls.
- term:
    id: GO:0030971
    label: receptor tyrosine kinase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'ACCEPT: receptor tyrosine kinase binding is directly supported because GAS6
      binds and activates the TAM receptor tyrosine kinases AXL, TYRO3, and MER/MERTK.'
    action: ACCEPT
    reason: This specific binding term is mechanistically correct for the GAS6
      receptor-ligand interaction.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0032008
    label: positive regulation of TOR signaling
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'KEEP_AS_NON_CORE: TOR signaling can lie downstream of PI3K/AKT, but this is
      a secondary pathway branch rather than the primary GAS6 function.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core downstream signaling.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0032689
    label: negative regulation of type II interferon production
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: suppression of interferon-gamma/type II interferon production
      is consistent with reported GAS6/TAM immunoregulatory programs but is a downstream immune-context
      effect.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immunoregulation rather than primary GAS6 function.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0032692
    label: negative regulation of interleukin-1 production
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: reduced interleukin-1 production is consistent with TAM-mediated
      anti-inflammatory feedback but is not the primary molecular function of GAS6.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immunoregulatory output.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0032715
    label: negative regulation of interleukin-6 production
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: reduced interleukin-6 production is consistent with GAS6/TAM
      anti-inflammatory signaling but is context-specific.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immunoregulatory output.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0032720
    label: negative regulation of tumor necrosis factor production
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: reduced tumor necrosis factor production is consistent with
      GAS6/TAM anti-inflammatory feedback but is not the core ligand function.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immunoregulatory output.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0032825
    label: positive regulation of natural killer cell differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: natural killer cell differentiation is noted as a GAS6/TAM-associated
      immune outcome, but it is downstream and cell-context specific.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because the core role is extracellular TAM receptor
      activation.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0035457
    label: cellular response to interferon-alpha
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: cellular response to interferon-alpha is a plausible immune-context
      annotation for TAM signaling crosstalk, but it is not a defining function of GAS6.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immune signaling context.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0035754
    label: B cell chemotaxis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: B cell chemotaxis may reflect immune-cell responses to GAS6/TAM
      signaling, but it is a downstream context rather than the core molecular role.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core pending more specific direct mouse evidence.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0043027
    label: cysteine-type endopeptidase inhibitor activity involved in apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'MODIFY: GAS6 does not directly inhibit cysteine-type endopeptidases/caspases.
      It reduces apoptosis through TAM receptor signaling and downstream survival pathways.'
    action: MODIFY
    reason: Replace the incorrect molecular-function term with the supported
      biological-process term for anti-apoptotic signaling.
    proposed_replacement_terms:
    - id: GO:0043066
      label: negative regulation of apoptotic process
    supported_by:
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'ACCEPT: negative regulation of apoptotic process is a recurrent GAS6/TAM signaling
      output in several cell types, including fibroblasts and oligodendrocytes.'
    action: ACCEPT
    reason: Gas6 protects cells from serum deprivation, TNF-alpha, and growth factor
      withdrawal through AXL/TAM signaling.
    supported_by:
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
- term:
    id: GO:0043277
    label: apoptotic cell clearance
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'ACCEPT: apoptotic cell clearance is a core cellular role of GAS6/TAM signaling.
      GAS6 promotes recognition and phagocytosis of apoptotic cells by TAM-expressing phagocytes.'
    action: ACCEPT
    reason: The Sertoli-cell study and broader TAM literature support GAS6 as an
      efferocytosis ligand.
    supported_by:
    - reference_id: PMID:18159085
      supporting_text: The phagocytic ability of Sertoli cells increased by five times
        in the presence of Gas6 in serum-free medium when compared with controls.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon highlights efferocytosis as a central GAS6/TAM function,
        with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on
        phagocytes.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: negative regulation of DNA-templated transcription is
      an indirect downstream signaling consequence and not a direct function of GAS6.'
    action: MARK_AS_OVER_ANNOTATED
    reason: This term overstates downstream transcriptional effects as a Gas6 process.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0046718
    label: symbiont entry into host cell
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: symbiont/virus entry annotations reflect pathogen exploitation
      of GAS6/TAM phosphatidylserine bridging rather than physiological GAS6 function.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core pathogen-context annotation.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0046813
    label: receptor-mediated virion attachment to host cell
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: receptor-mediated virion attachment can occur through GAS6/TAM
      apoptotic mimicry, but it is a pathogen-context use of the normal PtdSer/TAM bridging
      mechanism.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core pathogen-context annotation.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0046827
    label: positive regulation of protein export from nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: positive regulation of protein export from nucleus is
      too indirect and not part of the established GAS6/TAM ligand mechanism.'
    action: MARK_AS_OVER_ANNOTATED
    reason: No reviewed mouse evidence makes nuclear export a direct or central Gas6
      function.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'ACCEPT: receptor ligand activity is the clearest existing MF term for GAS6.
      Mouse GAS6 is a secreted vitamin K-dependent ligand for TAM receptor tyrosine kinases,
      especially AXL, and ligand binding activates receptor phosphorylation and downstream
      signaling.'
    action: ACCEPT
    reason: This term captures the core molecular role of GAS6 better than generic
      receptor-binding terms.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0048146
    label: positive regulation of fibroblast proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: Gas6 stimulates cardiac fibroblast proliferation through vitamin
      K-dependent Axl/ERK signaling, but fibroblast proliferation is a tissue-specific outcome.'
    action: KEEP_AS_NON_CORE
    reason: Retain as a supported non-core biological effect.
    supported_by:
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
- term:
    id: GO:0050766
    label: positive regulation of phagocytosis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'ACCEPT: positive regulation of phagocytosis is supported by Gas6-enhanced phagocytic
      uptake of apoptotic cells, especially in TAM receptor contexts.'
    action: ACCEPT
    reason: This is a core cellular consequence of the GAS6 phosphatidylserine/TAM
      bridging mechanism.
    supported_by:
    - reference_id: PMID:18159085
      supporting_text: The phagocytic ability of Sertoli cells increased by five times
        in the presence of Gas6 in serum-free medium when compared with controls.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon highlights efferocytosis as a central GAS6/TAM function,
        with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on
        phagocytes.
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'ACCEPT: positive regulation of PI3K/protein kinase B signaling is a well-supported
      GAS6/TAM output in oligodendrocytes, erythroblasts, and platelets.'
    action: ACCEPT
    reason: Multiple mouse-relevant experiments show Gas6/TAM signaling activates
      PI3K-Akt survival or platelet signaling pathways.
    supported_by:
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
    - reference_id: PMID:15650770
      supporting_text: Gas6, through its receptors, activates PI3K and Akt and
        stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying
        outside-in signaling via alphaIIbbeta3.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'ACCEPT: positive regulation of PI3K/protein kinase B signaling is a well-supported
      GAS6/TAM output in oligodendrocytes, erythroblasts, and platelets.'
    action: ACCEPT
    reason: Multiple mouse-relevant experiments show Gas6/TAM signaling activates
      PI3K-Akt survival or platelet signaling pathways.
    supported_by:
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
    - reference_id: PMID:15650770
      supporting_text: Gas6, through its receptors, activates PI3K and Akt and
        stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying
        outside-in signaling via alphaIIbbeta3.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0070168
    label: negative regulation of biomineral tissue development
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: negative regulation of biomineral tissue development may reflect
      GAS6/AXL effects on survival/calcification contexts, but it is peripheral to the core
      ligand mechanism.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because the direct role is TAM receptor signaling.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0070588
    label: calcium ion transmembrane transport
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'REMOVE: GAS6 binds calcium as a vitamin K-dependent Gla/EGF-domain protein but
      is not a calcium transporter and does not mediate calcium transmembrane transport.'
    action: REMOVE
    reason: The term confuses calcium binding with transport activity.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
- term:
    id: GO:0071307
    label: cellular response to vitamin K
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: vitamin K is required for GAS6 gamma-carboxylation,
      but GAS6 is a vitamin K-dependent protein rather than a mediator of cellular response
      to vitamin K.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Post-translational dependence should not be represented as a protein-level
      response process.
    supported_by:
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
- term:
    id: GO:0071333
    label: cellular response to glucose stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: cellular response to glucose stimulus is too far upstream
      or contextual for the reviewed Gas6 evidence.'
    action: MARK_AS_OVER_ANNOTATED
    reason: The direct Gas6 role is extracellular TAM receptor signaling, not
      glucose-response execution.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0071466
    label: cellular response to xenobiotic stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: xenobiotic-response annotations likely reflect warfarin
      sensitivity of GAS6 carboxylation rather than a function performed by GAS6.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Warfarin affects GAS6 maturation; GAS6 itself should not be curated as
      mediating a xenobiotic response without direct evidence.
    supported_by:
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
- term:
    id: GO:0071466
    label: cellular response to xenobiotic stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: xenobiotic-response annotations likely reflect warfarin
      sensitivity of GAS6 carboxylation rather than a function performed by GAS6.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Warfarin affects GAS6 maturation; GAS6 itself should not be curated as
      mediating a xenobiotic response without direct evidence.
    supported_by:
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
- term:
    id: GO:0072659
    label: protein localization to plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: protein localization to plasma membrane is a downstream
      or inferred cellular effect and is not a precise annotation for secreted GAS6.'
    action: MARK_AS_OVER_ANNOTATED
    reason: The appropriate direct annotation is extracellular TAM receptor
      ligand/signaling activity.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
- term:
    id: GO:0097241
    label: hematopoietic stem cell migration to bone marrow
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: hematopoietic stem cell migration to bone marrow is a specific
      hematopoietic context and not the main molecular function of GAS6.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core pending direct mouse-specific support.
    supported_by:
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
- term:
    id: GO:1900142
    label: negative regulation of oligodendrocyte apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: protection of oligodendrocytes from apoptosis is experimentally
      supported but is a specific cellular context of the broader GAS6/TAM survival pathway.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core cell-type-specific survival output.
    supported_by:
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
- term:
    id: GO:2000270
    label: negative regulation of fibroblast apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: Gas6 supports fibroblast survival under starvation, but the
      cell-type-specific anti-apoptotic term is a downstream outcome.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core survival output.
    supported_by:
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
- term:
    id: GO:2000352
    label: negative regulation of endothelial cell apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: endothelial-cell survival is consistent with UniProt-described
      GAS6/AXL function, but this cell-type-specific survival outcome is non-core.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core survival output.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:2000510
    label: positive regulation of dendritic cell chemotaxis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: dendritic-cell chemotaxis is a context-specific immune-cell
      response and not the defining role of GAS6.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immune-cell outcome.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:2000669
    label: negative regulation of dendritic cell apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'KEEP_AS_NON_CORE: dendritic-cell survival regulation is plausible for GAS6/TAM
      immune signaling but is a cell-context-specific outcome.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immune-cell survival output.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'ACCEPT: receptor ligand activity is the clearest existing MF term for GAS6.
      Mouse GAS6 is a secreted vitamin K-dependent ligand for TAM receptor tyrosine kinases,
      especially AXL, and ligand binding activates receptor phosphorylation and downstream
      signaling.'
    action: ACCEPT
    reason: This term captures the core molecular role of GAS6 better than generic
      receptor-binding terms.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'ACCEPT: GAS6 functions as an extracellular bridging/adaptor ligand by engaging
      phosphatidylserine-containing membranes through its Gla domain and TAM receptor ectodomains
      through its C-terminal LG domains. The term is imperfectly broad but captures this bridging
      role better than generic protein binding.'
    action: ACCEPT
    reason: The annotation represents a core bridging function, although a more specific
      PtdSer-dependent TAM receptor bridging MF would be preferable.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon highlights efferocytosis as a central GAS6/TAM function,
        with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on
        phagocytes.
    - reference_id: PMID:18159085
      supporting_text: The phagocytic ability of Sertoli cells increased by five times
        in the presence of Gas6 in serum-free medium when compared with controls.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: HDA
  original_reference_id: PMID:24006456
  review:
    summary: 'ACCEPT: extracellular space is the correct functional location for the mature
      secreted GAS6 ligand.'
    action: ACCEPT
    reason: GAS6 has a signal peptide, is annotated by UniProt as secreted, and acts
      extracellularly on cell-surface TAM receptors.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0046827
    label: positive regulation of protein export from nucleus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: positive regulation of protein export from nucleus is
      too indirect and not part of the established GAS6/TAM ligand mechanism.'
    action: MARK_AS_OVER_ANNOTATED
    reason: No reviewed mouse evidence makes nuclear export a direct or central Gas6
      function.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'REMOVE: cytoplasm is not the functional location of mature GAS6. The reviewed
      protein is secreted and acts extracellularly on cell-surface TAM receptors.'
    action: REMOVE
    reason: Any cytoplasmic signal would reflect biosynthesis or transfer noise rather
      than the active mature protein location.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0045860
    label: positive regulation of protein kinase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'ACCEPT: GAS6 positively regulates protein kinase activity by activating TAM
      receptor tyrosine kinases and downstream kinases such as AKT and ERK.'
    action: ACCEPT
    reason: This regulatory BP accurately describes ligand-driven activation without
      implying that GAS6 itself is a kinase.
    supported_by:
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0048146
    label: positive regulation of fibroblast proliferation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: Gas6 stimulates cardiac fibroblast proliferation through vitamin
      K-dependent Axl/ERK signaling, but fibroblast proliferation is a tissue-specific outcome.'
    action: KEEP_AS_NON_CORE
    reason: Retain as a supported non-core biological effect.
    supported_by:
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
- term:
    id: GO:0032715
    label: negative regulation of interleukin-6 production
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: reduced interleukin-6 production is consistent with GAS6/TAM
      anti-inflammatory signaling but is context-specific.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immunoregulatory output.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0019064
    label: fusion of virus membrane with host plasma membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: enveloped viruses can exploit GAS6/TAM phosphatidylserine
      bridging for apoptotic mimicry, but this host-factor role is not an evolved core function
      of mouse Gas6.'
    action: KEEP_AS_NON_CORE
    reason: Retain as a pathogen-context annotation, explicitly non-core.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0046813
    label: receptor-mediated virion attachment to host cell
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: receptor-mediated virion attachment can occur through GAS6/TAM
      apoptotic mimicry, but it is a pathogen-context use of the normal PtdSer/TAM bridging
      mechanism.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core pathogen-context annotation.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0001786
    label: phosphatidylserine binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'ACCEPT: phosphatidylserine binding is a core biochemical property of vitamin
      K-carboxylated GAS6, allowing it to bridge PtdSer-exposed apoptotic or activated membranes
      to TAM receptors.'
    action: ACCEPT
    reason: The Gla-domain PtdSer interaction is central to GAS6-dependent TAM
      activation and efferocytosis.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon highlights efferocytosis as a central GAS6/TAM function,
        with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on
        phagocytes.
- term:
    id: GO:0001961
    label: positive regulation of cytokine-mediated signaling pathway
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: GAS6/TAM signaling can tune cytokine-mediated pathways, including
      Epo-associated erythroid survival and immune signaling, but this is context-dependent.'
    action: KEEP_AS_NON_CORE
    reason: The annotation is plausible as a downstream regulatory effect rather than
      the core function.
    supported_by:
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0006909
    label: phagocytosis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'MODIFY: generic phagocytosis is too broad. GAS6 most specifically promotes apoptotic-cell
      clearance/efferocytosis via TAM receptors.'
    action: MODIFY
    reason: Replace broad phagocytosis with apoptotic cell clearance for this ligand
      mechanism.
    proposed_replacement_terms:
    - id: GO:0043277
      label: apoptotic cell clearance
    supported_by:
    - reference_id: PMID:18159085
      supporting_text: The phagocytic ability of Sertoli cells increased by five times
        in the presence of Gas6 in serum-free medium when compared with controls.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon highlights efferocytosis as a central GAS6/TAM function,
        with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on
        phagocytes.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: positive regulation of gene expression is an indirect
      downstream consequence of receptor signaling and is too broad for Gas6 curation.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Use signaling pathway terms rather than generic gene-expression outcomes for
      GAS6.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0010804
    label: negative regulation of tumor necrosis factor-mediated signaling pathway
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: negative regulation of TNF-mediated signaling is consistent
      with GAS6/TAM anti-inflammatory and survival signaling, but it is a context-specific
      output.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because the primary molecular role is TAM receptor
      activation.
    supported_by:
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0019079
    label: viral genome replication
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: viral genome replication is an indirect pathogen-context consequence
      of GAS6/TAM-mediated viral entry or signaling and is not a core host function.'
    action: KEEP_AS_NON_CORE
    reason: Retain only as a non-core host-factor annotation.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0032689
    label: negative regulation of type II interferon production
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: suppression of interferon-gamma/type II interferon production
      is consistent with reported GAS6/TAM immunoregulatory programs but is a downstream immune-context
      effect.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immunoregulation rather than primary GAS6 function.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0032692
    label: negative regulation of interleukin-1 production
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: reduced interleukin-1 production is consistent with TAM-mediated
      anti-inflammatory feedback but is not the primary molecular function of GAS6.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immunoregulatory output.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0032720
    label: negative regulation of tumor necrosis factor production
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: reduced tumor necrosis factor production is consistent with
      GAS6/TAM anti-inflammatory feedback but is not the core ligand function.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immunoregulatory output.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0032825
    label: positive regulation of natural killer cell differentiation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: natural killer cell differentiation is noted as a GAS6/TAM-associated
      immune outcome, but it is downstream and cell-context specific.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because the core role is extracellular TAM receptor
      activation.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0035457
    label: cellular response to interferon-alpha
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: cellular response to interferon-alpha is a plausible immune-context
      annotation for TAM signaling crosstalk, but it is not a defining function of GAS6.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immune signaling context.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0035754
    label: B cell chemotaxis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: B cell chemotaxis may reflect immune-cell responses to GAS6/TAM
      signaling, but it is a downstream context rather than the core molecular role.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core pending more specific direct mouse evidence.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0043027
    label: cysteine-type endopeptidase inhibitor activity involved in apoptotic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'MODIFY: GAS6 does not directly inhibit cysteine-type endopeptidases/caspases.
      It reduces apoptosis through TAM receptor signaling and downstream survival pathways.'
    action: MODIFY
    reason: Replace the incorrect molecular-function term with the supported
      biological-process term for anti-apoptotic signaling.
    proposed_replacement_terms:
    - id: GO:0043066
      label: negative regulation of apoptotic process
    supported_by:
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: negative regulation of DNA-templated transcription is
      an indirect downstream signaling consequence and not a direct function of GAS6.'
    action: MARK_AS_OVER_ANNOTATED
    reason: This term overstates downstream transcriptional effects as a Gas6 process.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0046718
    label: symbiont entry into host cell
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: symbiont/virus entry annotations reflect pathogen exploitation
      of GAS6/TAM phosphatidylserine bridging rather than physiological GAS6 function.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core pathogen-context annotation.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0050766
    label: positive regulation of phagocytosis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'ACCEPT: positive regulation of phagocytosis is supported by Gas6-enhanced phagocytic
      uptake of apoptotic cells, especially in TAM receptor contexts.'
    action: ACCEPT
    reason: This is a core cellular consequence of the GAS6 phosphatidylserine/TAM
      bridging mechanism.
    supported_by:
    - reference_id: PMID:18159085
      supporting_text: The phagocytic ability of Sertoli cells increased by five times
        in the presence of Gas6 in serum-free medium when compared with controls.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon highlights efferocytosis as a central GAS6/TAM function,
        with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on
        phagocytes.
- term:
    id: GO:0070168
    label: negative regulation of biomineral tissue development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: negative regulation of biomineral tissue development may reflect
      GAS6/AXL effects on survival/calcification contexts, but it is peripheral to the core
      ligand mechanism.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because the direct role is TAM receptor signaling.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0097241
    label: hematopoietic stem cell migration to bone marrow
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: hematopoietic stem cell migration to bone marrow is a specific
      hematopoietic context and not the main molecular function of GAS6.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core pending direct mouse-specific support.
    supported_by:
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
- term:
    id: GO:2000669
    label: negative regulation of dendritic cell apoptotic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: dendritic-cell survival regulation is plausible for GAS6/TAM
      immune signaling but is a cell-context-specific outcome.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core immune-cell survival output.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0001934
    label: positive regulation of protein phosphorylation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: positive regulation of protein phosphorylation is broadly
      correct for GAS6/TAM signaling but less specific than positive regulation of protein
      kinase activity and PI3K/AKT signaling.'
    action: KEEP_AS_NON_CORE
    reason: Retain as a broad downstream signaling consequence, not as a primary core
      annotation.
    supported_by:
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0003104
    label: positive regulation of glomerular filtration
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: glomerular filtration is a high-level renal physiological
      phenotype and is too indirect for mouse Gas6 as a core GO process.'
    action: MARK_AS_OVER_ANNOTATED
    reason: The curated mechanism is extracellular TAM ligand signaling; renal
      filtration effects should be supported with narrower contextual evidence before
      retention as a core-like process.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0005102
    label: signaling receptor binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'MODIFY: signaling receptor binding is true but too generic for GAS6. The more
      informative annotation is receptor ligand activity for TAM receptor tyrosine kinases.'
    action: MODIFY
    reason: Receptor ligand activity captures both binding and receptor activation.
    proposed_replacement_terms:
    - id: GO:0048018
      label: receptor ligand activity
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'MODIFY: protein phosphorylation incorrectly suggests GAS6 participates in the
      phosphorylation process itself. GAS6 is the extracellular ligand that activates receptor
      and downstream protein kinases.'
    action: MODIFY
    reason: Replace with positive regulation of protein kinase activity, which
      accurately describes ligand-mediated kinase activation.
    proposed_replacement_terms:
    - id: GO:0045860
      label: positive regulation of protein kinase activity
    supported_by:
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0032008
    label: positive regulation of TOR signaling
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: TOR signaling can lie downstream of PI3K/AKT, but this is
      a secondary pathway branch rather than the primary GAS6 function.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core downstream signaling.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0032148
    label: activation of protein kinase B activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'ACCEPT: activation of protein kinase B activity is supported as a direct downstream
      effect of GAS6/Axl signaling.'
    action: ACCEPT
    reason: The term captures the AKT activation branch of GAS6/TAM signaling.
    supported_by:
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
    - reference_id: PMID:15650770
      supporting_text: Gas6, through its receptors, activates PI3K and Akt and
        stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying
        outside-in signaling via alphaIIbbeta3.
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'ACCEPT: positive regulation of PI3K/protein kinase B signaling is a well-supported
      GAS6/TAM output in oligodendrocytes, erythroblasts, and platelets.'
    action: ACCEPT
    reason: Multiple mouse-relevant experiments show Gas6/TAM signaling activates
      PI3K-Akt survival or platelet signaling pathways.
    supported_by:
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
    - reference_id: PMID:15650770
      supporting_text: Gas6, through its receptors, activates PI3K and Akt and
        stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying
        outside-in signaling via alphaIIbbeta3.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0071307
    label: cellular response to vitamin K
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: vitamin K is required for GAS6 gamma-carboxylation,
      but GAS6 is a vitamin K-dependent protein rather than a mediator of cellular response
      to vitamin K.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Post-translational dependence should not be represented as a protein-level
      response process.
    supported_by:
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
- term:
    id: GO:0071333
    label: cellular response to glucose stimulus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: cellular response to glucose stimulus is too far upstream
      or contextual for the reviewed Gas6 evidence.'
    action: MARK_AS_OVER_ANNOTATED
    reason: The direct Gas6 role is extracellular TAM receptor signaling, not
      glucose-response execution.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0071466
    label: cellular response to xenobiotic stimulus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: xenobiotic-response annotations likely reflect warfarin
      sensitivity of GAS6 carboxylation rather than a function performed by GAS6.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Warfarin affects GAS6 maturation; GAS6 itself should not be curated as
      mediating a xenobiotic response without direct evidence.
    supported_by:
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
- term:
    id: GO:0072659
    label: protein localization to plasma membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: protein localization to plasma membrane is a downstream
      or inferred cellular effect and is not a precise annotation for secreted GAS6.'
    action: MARK_AS_OVER_ANNOTATED
    reason: The appropriate direct annotation is extracellular TAM receptor
      ligand/signaling activity.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
- term:
    id: GO:0085029
    label: extracellular matrix assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: extracellular matrix assembly is likely an indirect
      fibroblast/secretome-context association and not a direct Gas6 function.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Retain the extracellular-location evidence but do not curate ECM assembly as
      a core or direct process.
    supported_by:
    - reference_id: PMID:24006456
      supporting_text: Mouse cardiac fibroblasts were transfected with pre-/anti-miR of
        miR-29b and miR-30c, and their conditioned medium was analyzed by mass
        spectrometry.
- term:
    id: GO:2000270
    label: negative regulation of fibroblast apoptotic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: Gas6 supports fibroblast survival under starvation, but the
      cell-type-specific anti-apoptotic term is a downstream outcome.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core survival output.
    supported_by:
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
- term:
    id: GO:2000352
    label: negative regulation of endothelial cell apoptotic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'KEEP_AS_NON_CORE: endothelial-cell survival is consistent with UniProt-described
      GAS6/AXL function, but this cell-type-specific survival outcome is non-core.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core survival output.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:2000533
    label: negative regulation of renal albumin absorption
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: renal albumin absorption is a very specific renal outcome
      transferred from orthologous/automated evidence and is not established as a direct mouse
      Gas6 function here.'
    action: MARK_AS_OVER_ANNOTATED
    reason: This appears downstream and context-specific relative to the conserved TAM
      ligand role.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IDA
  original_reference_id: PMID:16723520
  review:
    summary: 'ACCEPT: negative regulation of apoptotic process is a recurrent GAS6/TAM signaling
      output in several cell types, including fibroblasts and oligodendrocytes.'
    action: ACCEPT
    reason: Gas6 protects cells from serum deprivation, TNF-alpha, and growth factor
      withdrawal through AXL/TAM signaling.
    supported_by:
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
- term:
    id: GO:0001764
    label: neuron migration
  evidence_type: IGI
  original_reference_id: PMID:18787040
  review:
    summary: 'KEEP_AS_NON_CORE: GnRH neuron migration/survival depends on Axl and Tyro3 and
      is stimulated by Gas6 in the cited system, but it is a developmental consequence of
      TAM signaling rather than the main GAS6 function.'
    action: KEEP_AS_NON_CORE
    reason: Retain as a supported developmental phenotype-level annotation, non-core.
    supported_by:
    - reference_id: PMID:18787040
      supporting_text: Silencing studies evaluated the role of Tyro3 and Axl in NLT GnRH
        neuronal cells and suggest that both play a role in Gas6 stimulation of GnRH
        neuronal survival and migration.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: IDA
  original_reference_id: PMID:18188450
  review:
    summary: 'ACCEPT: extracellular space is the correct functional location for the mature
      secreted GAS6 ligand.'
    action: ACCEPT
    reason: GAS6 has a signal peptide, is annotated by UniProt as secreted, and acts
      extracellularly on cell-surface TAM receptors.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0031589
    label: cell-substrate adhesion
  evidence_type: IMP
  original_reference_id: PMID:18188450
  review:
    summary: 'KEEP_AS_NON_CORE: erythroid or stromal adhesion effects may occur in the anemia/Epo
      context, but they are downstream of Gas6 signaling and not the defining molecular function.'
    action: KEEP_AS_NON_CORE
    reason: Retain as a context-specific non-core outcome.
    supported_by:
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:18188450
  review:
    summary: 'ACCEPT: negative regulation of apoptotic process is a recurrent GAS6/TAM signaling
      output in several cell types, including fibroblasts and oligodendrocytes.'
    action: ACCEPT
    reason: Gas6 protects cells from serum deprivation, TNF-alpha, and growth factor
      withdrawal through AXL/TAM signaling.
    supported_by:
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
- term:
    id: GO:0043277
    label: apoptotic cell clearance
  evidence_type: IDA
  original_reference_id: PMID:18159085
  review:
    summary: 'ACCEPT: apoptotic cell clearance is a core cellular role of GAS6/TAM signaling.
      GAS6 promotes recognition and phagocytosis of apoptotic cells by TAM-expressing phagocytes.'
    action: ACCEPT
    reason: The Sertoli-cell study and broader TAM literature support GAS6 as an
      efferocytosis ligand.
    supported_by:
    - reference_id: PMID:18159085
      supporting_text: The phagocytic ability of Sertoli cells increased by five times
        in the presence of Gas6 in serum-free medium when compared with controls.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon highlights efferocytosis as a central GAS6/TAM function,
        with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on
        phagocytes.
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction
  evidence_type: IMP
  original_reference_id: PMID:18188450
  review:
    summary: 'ACCEPT: positive regulation of PI3K/protein kinase B signaling is a well-supported
      GAS6/TAM output in oligodendrocytes, erythroblasts, and platelets.'
    action: ACCEPT
    reason: Multiple mouse-relevant experiments show Gas6/TAM signaling activates
      PI3K-Akt survival or platelet signaling pathways.
    supported_by:
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
    - reference_id: PMID:15650770
      supporting_text: Gas6, through its receptors, activates PI3K and Akt and
        stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying
        outside-in signaling via alphaIIbbeta3.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0071363
    label: cellular response to growth factor stimulus
  evidence_type: IMP
  original_reference_id: PMID:18188450
  review:
    summary: 'KEEP_AS_NON_CORE: Gas6 participates in cellular responses to growth-factor contexts
      such as Epo and serum-starvation/growth stimulation, but this term is broad and context-dependent.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because it describes the biological context, not the
      primary molecular activity.
    supported_by:
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
    - reference_id: PMID:8336730
      supporting_text: This finding thus defines a new member of vitamin K-dependent
        proteins that is expressed in many human and mouse tissues and may be involved
        in the regulation of a protease cascade relevant in growth regulation.
- term:
    id: GO:0007596
    label: blood coagulation
  evidence_type: IMP
  original_reference_id: PMID:15184064
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: Gas6 influences platelet signaling and thrombus stabilization,
      but blood coagulation is too broad and can imply direct participation in the coagulation
      cascade.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Gas6-deficient or TAM-blocked mice have impaired thrombus stabilization
      without the protein acting as a coagulation enzyme or core cascade component.
    supported_by:
    - reference_id: PMID:15650770
      supporting_text: Gas6, through its receptors, activates PI3K and Akt and
        stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying
        outside-in signaling via alphaIIbbeta3.
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:15184064
  review:
    summary: 'ACCEPT: negative regulation of apoptotic process is a recurrent GAS6/TAM signaling
      output in several cell types, including fibroblasts and oligodendrocytes.'
    action: ACCEPT
    reason: Gas6 protects cells from serum deprivation, TNF-alpha, and growth factor
      withdrawal through AXL/TAM signaling.
    supported_by:
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000008
  review:
    summary: 'ACCEPT: receptor ligand activity is the clearest existing MF term for GAS6.
      Mouse GAS6 is a secreted vitamin K-dependent ligand for TAM receptor tyrosine kinases,
      especially AXL, and ligand binding activates receptor phosphorylation and downstream
      signaling.'
    action: ACCEPT
    reason: This term captures the core molecular role of GAS6 better than generic
      receptor-binding terms.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0048146
    label: positive regulation of fibroblast proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000008
  review:
    summary: 'KEEP_AS_NON_CORE: Gas6 stimulates cardiac fibroblast proliferation through vitamin
      K-dependent Axl/ERK signaling, but fibroblast proliferation is a tissue-specific outcome.'
    action: KEEP_AS_NON_CORE
    reason: Retain as a supported non-core biological effect.
    supported_by:
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction
  evidence_type: IGI
  original_reference_id: PMID:15650770
  review:
    summary: 'ACCEPT: positive regulation of PI3K/protein kinase B signaling is a well-supported
      GAS6/TAM output in oligodendrocytes, erythroblasts, and platelets.'
    action: ACCEPT
    reason: Multiple mouse-relevant experiments show Gas6/TAM signaling activates
      PI3K-Akt survival or platelet signaling pathways.
    supported_by:
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
    - reference_id: PMID:15650770
      supporting_text: Gas6, through its receptors, activates PI3K and Akt and
        stimulates tyrosine phosphorylation of the beta3 integrin, thereby amplifying
        outside-in signaling via alphaIIbbeta3.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0070374
    label: positive regulation of ERK1 and ERK2 cascade
  evidence_type: ISO
  original_reference_id: GO_REF:0000008
  review:
    summary: 'KEEP_AS_NON_CORE: ERK1/ERK2 activation is experimentally supported in cardiac
      fibroblasts but is one context-specific signaling branch downstream of the TAM receptor-ligand
      interaction.'
    action: KEEP_AS_NON_CORE
    reason: Retain as a supported downstream outcome, but do not treat it as the
      defining GAS6 function.
    supported_by:
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and
        SOCS-linked inflammatory feedback as major GAS6/TAM signaling outputs.
- term:
    id: GO:0007167
    label: enzyme-linked receptor protein signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:9395235
  review:
    summary: 'ACCEPT: enzyme-linked receptor protein signaling pathway is appropriate because
      GAS6 activates TAM receptor tyrosine kinases.'
    action: ACCEPT
    reason: The primary signaling receptors for GAS6 are enzyme-linked receptor tyrosine
      kinases.
    supported_by:
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IDA
  original_reference_id: PMID:9395235
  review:
    summary: 'ACCEPT: negative regulation of apoptotic process is a recurrent GAS6/TAM signaling
      output in several cell types, including fibroblasts and oligodendrocytes.'
    action: ACCEPT
    reason: Gas6 protects cells from serum deprivation, TNF-alpha, and growth factor
      withdrawal through AXL/TAM signaling.
    supported_by:
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IGI
  original_reference_id: PMID:9395235
  review:
    summary: 'ACCEPT: negative regulation of apoptotic process is a recurrent GAS6/TAM signaling
      output in several cell types, including fibroblasts and oligodendrocytes.'
    action: ACCEPT
    reason: Gas6 protects cells from serum deprivation, TNF-alpha, and growth factor
      withdrawal through AXL/TAM signaling.
    supported_by:
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:16723520
      supporting_text: We conclude that gas6 signaling through the Axl receptor and the
        PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
        withdrawal and TNFalpha-mediated cell death.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: IDA
  original_reference_id: PMID:9395235
  review:
    summary: 'ACCEPT: receptor ligand activity is the clearest existing MF term for GAS6.
      Mouse GAS6 is a secreted vitamin K-dependent ligand for TAM receptor tyrosine kinases,
      especially AXL, and ligand binding activates receptor phosphorylation and downstream
      signaling.'
    action: ACCEPT
    reason: This term captures the core molecular role of GAS6 better than generic
      receptor-binding terms.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
        receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
        migration, platelet activation, and thrombotic responses.
    - reference_id: PMID:9395235
      supporting_text: Activation of ARK phosphorylation and a weak but significant
        induction of MAP kinase activity accompanied the increased survival of cells
        treated with Gas6.
    - reference_id: PMID:15184064
      supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
        phosphorylation of ERK kinase.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0005615
    label: extracellular space
  evidence_type: ISO
  original_reference_id: PMID:8336730
  review:
    summary: 'ACCEPT: extracellular space is the correct functional location for the mature
      secreted GAS6 ligand.'
    action: ACCEPT
    reason: GAS6 has a signal peptide, is annotated by UniProt as secreted, and acts
      extracellularly on cell-surface TAM receptors.
    supported_by:
    - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
      supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
        notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
        binding.
    - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
      supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
        ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
        triggers receptor dimerization and kinase activation.
- term:
    id: GO:0009267
    label: cellular response to starvation
  evidence_type: IDA
  original_reference_id: PMID:8336730
  review:
    summary: 'MARK_AS_OVER_ANNOTATED: serum starvation induces gas6 expression, but expression
      context is not the same as a function of the GAS6 protein in cellular response to starvation.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Avoid conflating gene expression regulation with gene product function.
    supported_by:
    - reference_id: PMID:8336730
      supporting_text: This finding thus defines a new member of vitamin K-dependent
        proteins that is expressed in many human and mouse tissues and may be involved
        in the regulation of a protease cascade relevant in growth regulation.
- term:
    id: GO:0071363
    label: cellular response to growth factor stimulus
  evidence_type: IDA
  original_reference_id: PMID:8336730
  review:
    summary: 'KEEP_AS_NON_CORE: Gas6 participates in cellular responses to growth-factor contexts
      such as Epo and serum-starvation/growth stimulation, but this term is broad and context-dependent.'
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because it describes the biological context, not the
      primary molecular activity.
    supported_by:
    - reference_id: PMID:18188450
      supporting_text: Here, we report that murine erythroblasts released Gas6 in
        response to Epo and that Gas6 enhanced Epo receptor signaling by activating the
        serine-threonine kinase Akt in these cells.
    - reference_id: PMID:8336730
      supporting_text: This finding thus defines a new member of vitamin K-dependent
        proteins that is expressed in many human and mouse tissues and may be involved
        in the regulation of a protease cascade relevant in growth regulation.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000008
  title: Gene Ontology annotation by the MGI curatorial staff, curated orthology
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to
    orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000096
  title: Automated transfer of experimentally-verified manual GO annotation data to
    mouse-rat orthologs
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000119
  title: Automated transfer of experimentally-verified manual GO annotation data to
    mouse-human orthologs
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:15184064
  title: Vitamin K-dependent Gas6 activates ERK kinase and stimulates growth of cardiac
    fibroblasts.
  findings: []
- id: PMID:15650770
  title: Role of Gas6 receptors in platelet signaling during thrombus stabilization and
    implications for antithrombotic therapy.
  findings: []
- id: PMID:16723520
  title: Gas6/Axl signaling activates the phosphatidylinositol 3-kinase/Akt1 survival
    pathway to protect oligodendrocytes from tumor necrosis factor alpha-induced
    apoptosis.
  findings: []
- id: PMID:18159085
  title: Gas6 and the Tyro 3 receptor tyrosine kinase subfamily regulate the phagocytic
    function of Sertoli cells.
  findings: []
- id: PMID:18188450
  title: Role of Gas6 in erythropoiesis and anemia in mice.
  findings: []
- id: PMID:18787040
  title: Axl and Tyro3 modulate female reproduction by influencing
    gonadotropin-releasing hormone neuron survival and migration.
  findings: []
- id: PMID:24006456
  title: 'Extracellular matrix secretion by cardiac fibroblasts: role of microRNA-29b and
    microRNA-30c.'
  findings: []
- id: PMID:8336730
  title: The protein encoded by a growth arrest-specific gene (gas6) is a new member of
    the vitamin K-dependent proteins related to protein S, a negative coregulator in the
    blood coagulation cascade.
  findings: []
- id: PMID:9395235
  title: Signaling through the ARK tyrosine kinase receptor protects from apoptosis in
    the absence of growth stimulation.
  findings: []
- id: file:mouse/Gas6/Gas6-uniprot.txt
  title: UniProtKB Q61592 mouse GAS6 record
  findings:
  - statement: Mouse GAS6 is a secreted ligand for TAM receptor tyrosine kinases AXL,
      TYRO3, and MER/MERTK.
    supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
      receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
      migration, platelet activation, and thrombotic responses.
  - statement: GAS6 has vitamin K-dependent gamma-carboxyglutamate residues essential
      for calcium binding and is annotated as secreted.
    supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
      notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
      binding.
- id: file:mouse/Gas6/Gas6-deep-research-falcon.md
  title: Falcon deep research report for mouse Gas6
  findings:
  - statement: Falcon synthesizes GAS6 as a secreted TAM ligand that bridges
      phosphatidylserine-bearing membranes to TAM receptors and triggers receptor kinase
      signaling.
    supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
      ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
      triggers receptor dimerization and kinase activation.
  - statement: Falcon identifies efferocytosis, inflammatory regulation, and
      PI3K-AKT/ERK signaling as major GAS6/TAM functional outputs.
    supporting_text: Falcon highlights efferocytosis as a central GAS6/TAM function,
      with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on
      phagocytes.
core_functions:
- description: Extracellular receptor ligand for TAM receptor tyrosine kinases. Vitamin
    K-carboxylated GAS6 binds AXL, TYRO3, and MER/MERTK at the cell surface, promoting
    receptor activation and downstream kinase signaling including PI3K/AKT and ERK/MAPK
    pathways that support survival, proliferation, adhesion, migration, and
    platelet/thrombus-stabilization responses in specific tissues.
  molecular_function:
    id: GO:0048018
    label: receptor ligand activity
  directly_involved_in:
  - id: GO:0007166
    label: cell surface receptor signaling pathway
  - id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal
      transduction
  - id: GO:0045860
    label: positive regulation of protein kinase activity
  - id: GO:0043066
    label: negative regulation of apoptotic process
  locations:
  - id: GO:0005615
    label: extracellular space
  supported_by:
  - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
    supporting_text: UniProt describes mouse GAS6 as a ligand for AXL, TYRO3 and MER
      receptor tyrosine kinases, with roles in cell growth, survival, adhesion,
      migration, platelet activation, and thrombotic responses.
  - reference_id: PMID:9395235
    supporting_text: Activation of ARK phosphorylation and a weak but significant
      induction of MAP kinase activity accompanied the increased survival of cells
      treated with Gas6.
  - reference_id: PMID:16723520
    supporting_text: We conclude that gas6 signaling through the Axl receptor and the
      PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor
      withdrawal and TNFalpha-mediated cell death.
  - reference_id: PMID:15184064
    supporting_text: Gas6 stimulated tyrosine phosphorylation of Axl as well as
      phosphorylation of ERK kinase.
  - reference_id: PMID:18188450
    supporting_text: Here, we report that murine erythroblasts released Gas6 in response
      to Epo and that Gas6 enhanced Epo receptor signaling by activating the
      serine-threonine kinase Akt in these cells.
  - reference_id: PMID:15650770
    supporting_text: Gas6, through its receptors, activates PI3K and Akt and stimulates
      tyrosine phosphorylation of the beta3 integrin, thereby amplifying outside-in
      signaling via alphaIIbbeta3.
  - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
    supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
      ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
      triggers receptor dimerization and kinase activation.
  - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
    supporting_text: Falcon identifies PI3K-AKT, MEK-ERK/MAPK, SRC/GRB2, and SOCS-linked
      inflammatory feedback as major GAS6/TAM signaling outputs.
- description: Phosphatidylserine-dependent bridging ligand for apoptotic-cell
    clearance. The carboxylated Gla domain binds phosphatidylserine-exposed apoptotic or
    activated membranes, while the C-terminal receptor-binding region engages TAM
    receptors on phagocytes, thereby promoting apoptotic-cell recognition and
    efferocytosis.
  molecular_function:
    id: GO:0001786
    label: phosphatidylserine binding
  directly_involved_in:
  - id: GO:0043277
    label: apoptotic cell clearance
  - id: GO:0050766
    label: positive regulation of phagocytosis
  locations:
  - id: GO:0005615
    label: extracellular space
  supported_by:
  - reference_id: PMID:18159085
    supporting_text: The phagocytic ability of Sertoli cells increased by five times in
      the presence of Gas6 in serum-free medium when compared with controls.
  - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
    supporting_text: Falcon highlights efferocytosis as a central GAS6/TAM function,
      with GAS6 bridging apoptotic-cell phosphatidylserine to TAM receptors on
      phagocytes.
  - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
    supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
      ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
      triggers receptor dimerization and kinase activation.
  - reference_id: file:mouse/Gas6/Gas6-uniprot.txt
    supporting_text: UniProt annotates the mature mouse GAS6 protein as secreted and
      notes vitamin K-dependent gamma-carboxyglutamate residues required for calcium
      binding.
proposed_new_terms:
- proposed_name: phosphatidylserine-dependent TAM receptor bridging activity
  proposed_definition: Binding phosphatidylserine-containing membranes and a TAM-family
    receptor tyrosine kinase to bridge the membrane surface to the receptor-bearing cell
    and promote TAM receptor activation.
  justification: GAS6 is currently split across receptor ligand activity,
    phosphatidylserine binding, and broad adaptor activity. A single MF term would more
    precisely capture the vitamin K-dependent bridging mechanism used by GAS6 and
    related TAM ligands during efferocytosis and activated-membrane signaling.
  proposed_parent:
    id: GO:0048018
    label: receptor ligand activity
  supported_by:
  - reference_id: file:mouse/Gas6/Gas6-deep-research-falcon.md
    supporting_text: Falcon summarizes mouse GAS6 as a secreted vitamin K-dependent
      ligand that bridges phosphatidylserine-bearing membranes to TAM receptors and
      triggers receptor dimerization and kinase activation.
  - reference_id: PMID:18159085
    supporting_text: The phagocytic ability of Sertoli cells increased by five times in
      the presence of Gas6 in serum-free medium when compared with controls.
suggested_questions:
- question: Should GAS6 viral-entry annotations be retained as host-factor annotations
    for pathogen exploitation of the PtdSer/TAM mechanism, or moved out of core
    gene-function curation?
- question: Would GO prefer a new molecular-function term for
    phosphatidylserine-dependent TAM receptor bridging activity, or should this
    mechanism be represented with receptor ligand activity plus annotation extensions?
suggested_experiments:
- hypothesis: Gamma-carboxylated mouse GAS6 activates TAM receptors and promotes
    apoptotic-cell clearance more effectively than non-carboxylated GAS6.
  description: Compare fully carboxylated recombinant mouse GAS6 with
    warfarin-produced/non-carboxylated GAS6 in matched AXL-, TYRO3-, and
    MERTK-expressing phagocyte assays measuring receptor phosphorylation, apoptotic-cell
    binding, and engulfment.
  experiment_type: biochemical receptor activation and efferocytosis assay
- hypothesis: Renal, biomineralization, and nuclear-export annotations are secondary
    context effects rather than direct conserved GAS6 functions.
  description: Use tissue-specific Gas6 perturbation or rescue models with direct TAM
    signaling readouts to determine whether these high-level phenotypes persist after
    controlling for general survival/efferocytosis effects.
  experiment_type: conditional mouse genetics with pathway readouts

Gas6

Gene Description

Proposed New Ontology Terms

phosphatidylserine-dependent TAM receptor bridging activity

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Deep Research Falcon

Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Output

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Comprehensive research report: Mouse Gas6 (UniProt Q61592) functional annotation

Executive summary

1) Mandatory verification: correct gene/protein identity

1.1 UniProt accession-to-gene/protein mapping

1.2 Definition

1.3 Domain architecture (aligns with user-provided UniProt domain list)

2) Key concepts & definitions (current understanding)

2.1 TAM receptors and their ligands

2.2 Ligand specificity/affinity and physiological context

2.3 Core biochemical mechanism: PtdSer bridging

2.4 Receptor activation model (stoichiometry)

2.5 Efferocytosis

3) Molecular function, pathways, and cellular localization

3.1 Molecular function (functional annotation)

3.2 Post-translational modification: γ-carboxylation in vivo (mouse-relevant)

3.3 Downstream signaling pathways

3.4 Immunoregulatory outputs (SOCS, cytokine suppression)

3.5 Subcellular/extracellular localization

4) Expression patterns and mouse-relevant localization

4.1 Broad tissue/cell-type expression (mouse-relevant summaries)

4.2 CNS expression and TAM partitioning

5) Recent developments and latest research (2023–2024 prioritized)

5.1 2024: EV-delivered GAS6 drives MerTK-dependent efferocytosis and hepatoprotection in mouse hepatic ischemia–reperfusion injury

5.2 2024: GAS6 deficiency worsens outcomes in mouse Japanese encephalitis; GAS6 delivery improves BBB integrity and resistance

5.3 2023: Exogenous GAS6 restores BBB integrity in a mouse sepsis-associated encephalopathy model

5.4 2023: Local rmGAS6 administration in mouse OA models

5.5 2024: Mechanistic update on endogenous vitamin K–dependent GAS6 modification in brain

6) Current applications and real-world implementations

6.1 Biomarkers and disease monitoring

6.2 Therapeutic targeting: modalities and rationale (expert synthesis, 2024)

6.3 Quantitative therapeutic parameters (examples)

7) Clinical trials snapshot (examples from ClinicalTrials.gov records retrieved)

7.1 MERTK/TAM-axis inhibitor: MRX-2843

7.2 AXL-targeted ADC: mecobotamab vedotin (CAB-AXL-ADC; BA3011)

7.3 Additional trial mapping from recent oncology review literature

8) Expert opinions and analysis (authoritative sources)

8.1 Why GAS6/TAM is considered a high-value therapeutic axis

8.2 Key translational challenge: extremely high GAS6–AXL affinity

8.3 Safety/physiology considerations

9) Key statistics and recent data highlights

10) Consolidated evidence map

References (URLs and publication dates for key sources)

Notes on scope and evidence strength

Citations

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