Nf1 encodes neurofibromin, a large Ras GTPase-activating protein and tumor suppressor. Its core activity is stimulation of Ras GTP hydrolysis, converting active Ras-GTP to inactive Ras-GDP and thereby negatively regulating Ras-dependent intracellular signaling. SEC14/PH-like lipid-binding modules and nuclear or synaptic contexts may modulate localization or disease biology, but the central conserved function is RasGAP-mediated signal attenuation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005096 GTPase activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: Neurofibromin's GAP-related domain supplies an arginine finger (Arg1278) that stabilizes the RAS GTP-hydrolysis transition state; this RasGAP activity is the defining function of the protein. Reason: Defining biochemical activity (RasGAP); strongly supported by domain architecture and IMP/IGI/ISO evidence. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:1902531 regulation of intracellular signal transduction | IBA GO_REF:0000033 | MODIFY | Summary: This IBA-projected generic parent should be specialized to neurofibromin's actual role, negative regulation of RAS signal transduction via its RasGAP activity. Reason: Generic parent; specific RasGAP child term is the correct, more informative annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN008939999 SUPPORTS TRANSFER Node in PTHR10194, PANTHER family name "RAS GTPASE-ACTIVATING PROTEINS", the family UniProt also assigns to the target (PTHR10194:SF142 "NEUROFIBROMIN"). Every identified seed is a RasGAP-domain protein, spanning yeast, worm, fly, rodent and human, so the target is well inside the clade and the node placement is not at issue - the shared, informative claim across the seeds is GAP-mediated damping of Ras signalling, which the generic parent understates. MGI:MGI:97306 · mouse Nf1 (the review target itself) SUPPORTS TRANSFER The target's own MGI record is among the IBD seeds, the expected marker that experimental grounding exists on the target itself: Nf1 carries IMP/IGI annotations at GO:0005096 GTPase activator activity (PMID:8563750, PMID:11435472, PMID:16271875, PMID:17053831) and at GO:0007265 Ras protein signal transduction (PMID:10498620, PMID:10845775), which are among the descendant evidences behind the IBD. UniProtKB:P21359 · human NF1 (Neurofibromin) SUPPORTS TRANSFER The 1:1 human ortholog seed; its RasGAP activity is the same function the target inherits. FB:FBgn0015269 · Drosophila Nf1 (Neurofibromin 1) SUPPORTS TRANSFER Invertebrate ortholog seed; places the RasGAP role deep in the bilaterian tree rather than in vertebrates alone. MGI:MGI:1916851 · mouse Dab2ip (disabled 2 interacting protein) SUPPORTS TRANSFER A more distant RasGAP-family seed; like the others it acts as a negative regulator of Ras, which is what makes the signed child term the family-level claim. MGI:MGI:3039785 · mouse Syngap1 (synaptic Ras GTPase activating protein 1) SUPPORTS TRANSFER Further RasGAP-family seed with the same direction of effect on Ras. UniProtKB:Q5VWQ8 · human DAB2IP (Disabled homolog 2-interacting protein) SUPPORTS TRANSFER Human counterpart of the Dab2ip seed. UniProtKB:Q86YV0 · human RASAL3 (RAS protein activator like-3) SUPPORTS TRANSFER Human RasGAP-family seed. GO:0046580 is a genuine descendant of GO:1902531 (via GO:0046578 and GO:0051056), so the MODIFY is a parent-to-child narrowing onto the claim the seeds actually share, not a change of claim. Proposed replacements: negative regulation of Ras protein signal transduction Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0005096 GTPase activator activity | IEA GO_REF:0000120 | ACCEPT | Summary: Neurofibromin's GAP-related domain supplies an arginine finger (Arg1278) that stabilizes the RAS GTP-hydrolysis transition state; this RasGAP activity is the defining function of the protein. Reason: Defining biochemical activity (RasGAP); strongly supported by domain architecture and IMP/IGI/ISO evidence. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: An NLS in the C-terminal domain permits phosphorylation-regulated nuclear localization in some contexts; the dominant functional pool is cytoplasmic/membrane-proximal. Reason: Minor/context-dependent localization; non-core relative to membrane action. |
| GO:0005730 nucleolus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt SubCell-derived nucleolar localization reflects a minor nuclear pool and is not where the RasGAP function is exerted. Reason: Minor nuclear sub-compartment; IEA, non-core. |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Neurofibromin is a large cytoplasmic protein; the cytoplasm assignment is a generic compartment broader than the membrane-proximal site where it regulates RAS. Reason: Generic compartment; supportive but less informative than plasma-membrane localization. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Membrane recruitment (aided by SPRED binding) positions neurofibromin at the plasma membrane to act on prenylated, membrane-anchored RAS where RAS signalling originates. Reason: Site of RasGAP action on membrane-bound RAS; functionally core localization. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0008289 lipid binding | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: The CRAL-TRIO/Sec14-like domain binds glycerophospholipids, supporting membrane association and regulation but distinct from the catalytic RasGAP activity. Reason: Real Sec14-domain property supporting localization; ancillary to core RasGAP role. |
| GO:0014037 Schwann cell differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Schwann-cell differentiation depends on tightly controlled RAS signalling that neurofibromin enforces; the term is a downstream consequence of its RasGAP role. Reason: Downstream glial differentiation phenotype (IEA). |
| GO:0050793 regulation of developmental process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: This high-level developmental-regulation term reflects the many pleiotropic developmental roles downstream of neurofibromin's RAS control. Reason: Very generic downstream developmental term; IEA. |
| GO:0050807 regulation of synapse organization | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Neurofibromin influences synapse organization via its modulation of neuronal RAS/cAMP signalling; a downstream regulatory effect. Reason: Downstream synaptic-organization role; IEA. |
| GO:0098793 presynapse | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Presynaptic localization (GOC-inferred) is consistent with neurofibromin's role in neurotransmitter-secretion modulation, downstream of its signalling activity. Reason: Synaptic compartment; pleiotropic neuronal role, non-core. |
| GO:0005654 nucleoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Nucleoplasmic localization is an electronically projected refinement of the minor NLS-dependent nuclear pool of neurofibromin. Reason: Minor nuclear sub-compartment; IEA/ISO, non-core. |
| GO:0008429 phosphatidylethanolamine binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The CRAL-TRIO domain also binds phosphatidylethanolamine-headgroup glycerophospholipids, aiding membrane localization of neurofibromin. Reason: Specific Sec14 lipid preference; membrane-association role, non-core. |
| GO:0030424 axon | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal axonal localization reflects neurofibromin's distribution in neurons, consistent with its synaptic/neuronal roles but not its defining function. Reason: Neuronal sub-cellular distribution; pleiotropic/non-core. |
| GO:0030425 dendrite | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Dendritic localization is part of neurofibromin's neuronal distribution underpinning its synaptic-plasticity roles, downstream of RAS/cAMP regulation. Reason: Neuronal distribution supporting synaptic roles; non-core. |
| GO:0031210 phosphatidylcholine binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The Sec14-like CRAL-TRIO domain preferentially binds phosphatidylcholine-headgroup lipids, contributing to membrane targeting rather than to catalysis. Reason: Specific Sec14 lipid preference; supports membrane association, non-core. |
| GO:0043535 regulation of blood vessel endothelial cell migration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Endothelial migration during vessel formation is modulated downstream of neurofibromin's RAS signalling control; IEA/ISO-projected. Reason: Downstream vascular migration regulation; non-core. |
| GO:0045765 regulation of angiogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neurofibromin influences angiogenesis via its control of endothelial RAS signalling; a downstream vascular regulatory role. Reason: Downstream angiogenesis regulation. |
| GO:0050890 cognition | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cognitive function is impaired when RAS/cAMP signalling is dysregulated by NF1 loss; a high-level behavioural phenotype downstream of the molecular defect. Reason: Behavioural phenotype downstream of signalling dysregulation. |
| GO:0032991 protein-containing complex | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Bare 'protein-containing complex' membership adds no functional or compositional information about neurofibromin and is an ISO-projected generic term. Reason: Uninformative complex assignment; over-annotation. |
| GO:0043547 positive regulation of GTPase activity | ISO GO_REF:0000119 | ACCEPT | Summary: Direct readout of catalysis: neurofibromin accelerates the intrinsic GTPase activity of RAS, the molecular event that terminates active RAS-GTP signalling. Reason: Proximal consequence of RasGAP catalysis; core to neurofibromin function. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0001937 negative regulation of endothelial cell proliferation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Endothelial proliferation is restrained by neurofibromin through reduced RAS signalling, relevant to vascular phenotypes; downstream. Reason: Downstream vascular antiproliferative phenotype. |
| GO:0005096 GTPase activator activity | ISO GO_REF:0000096 | ACCEPT | Summary: Neurofibromin's GAP-related domain supplies an arginine finger (Arg1278) that stabilizes the RAS GTP-hydrolysis transition state; this RasGAP activity is the defining function of the protein. Reason: Defining biochemical activity (RasGAP); strongly supported by domain architecture and IMP/IGI/ISO evidence. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0005096 GTPase activator activity | ISO GO_REF:0000119 | ACCEPT | Summary: Neurofibromin's GAP-related domain supplies an arginine finger (Arg1278) that stabilizes the RAS GTP-hydrolysis transition state; this RasGAP activity is the defining function of the protein. Reason: Defining biochemical activity (RasGAP); strongly supported by domain architecture and IMP/IGI/ISO evidence. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0005634 nucleus | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: An NLS in the C-terminal domain permits phosphorylation-regulated nuclear localization in some contexts; the dominant functional pool is cytoplasmic/membrane-proximal. Reason: Minor/context-dependent localization; non-core relative to membrane action. |
| GO:0005654 nucleoplasm | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Nucleoplasmic localization is an electronically projected refinement of the minor NLS-dependent nuclear pool of neurofibromin. Reason: Minor nuclear sub-compartment; IEA/ISO, non-core. |
| GO:0005737 cytoplasm | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Neurofibromin is a large cytoplasmic protein; the cytoplasm assignment is a generic compartment broader than the membrane-proximal site where it regulates RAS. Reason: Generic compartment; supportive but less informative than plasma-membrane localization. |
| GO:0005886 plasma membrane | ISO GO_REF:0000119 | ACCEPT | Summary: Membrane recruitment (aided by SPRED binding) positions neurofibromin at the plasma membrane to act on prenylated, membrane-anchored RAS where RAS signalling originates. Reason: Site of RasGAP action on membrane-bound RAS; functionally core localization. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0008429 phosphatidylethanolamine binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: The CRAL-TRIO domain also binds phosphatidylethanolamine-headgroup glycerophospholipids, aiding membrane localization of neurofibromin. Reason: Specific Sec14 lipid preference; membrane-association role, non-core. |
| GO:0010976 positive regulation of neuron projection development | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: ISO-projected promotion of neurite outgrowth reflects neurofibromin's neuronal signalling role; downstream and electronically inferred. Reason: Downstream neuronal morphogenesis; ISO, non-core. |
| GO:0030424 axon | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Neuronal axonal localization reflects neurofibromin's distribution in neurons, consistent with its synaptic/neuronal roles but not its defining function. Reason: Neuronal sub-cellular distribution; pleiotropic/non-core. |
| GO:0030424 axon | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Neuronal axonal localization reflects neurofibromin's distribution in neurons, consistent with its synaptic/neuronal roles but not its defining function. Reason: Neuronal sub-cellular distribution; pleiotropic/non-core. |
| GO:0030425 dendrite | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Dendritic localization is part of neurofibromin's neuronal distribution underpinning its synaptic-plasticity roles, downstream of RAS/cAMP regulation. Reason: Neuronal distribution supporting synaptic roles; non-core. |
| GO:0030425 dendrite | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Dendritic localization is part of neurofibromin's neuronal distribution underpinning its synaptic-plasticity roles, downstream of RAS/cAMP regulation. Reason: Neuronal distribution supporting synaptic roles; non-core. |
| GO:0031210 phosphatidylcholine binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: The Sec14-like CRAL-TRIO domain preferentially binds phosphatidylcholine-headgroup lipids, contributing to membrane targeting rather than to catalysis. Reason: Specific Sec14 lipid preference; supports membrane association, non-core. |
| GO:0043535 regulation of blood vessel endothelial cell migration | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Endothelial migration during vessel formation is modulated downstream of neurofibromin's RAS signalling control; IEA/ISO-projected. Reason: Downstream vascular migration regulation; non-core. |
| GO:0045545 syndecan binding | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: ISO-projected syndecan binding implies a membrane/adhesion-associated partner interaction that is peripheral to the RasGAP catalytic role. Reason: Specific partner binding, electronically projected; ancillary. |
| GO:0045664 regulation of neuron differentiation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Neuronal differentiation is modulated by RAS-pathway tone that neurofibromin sets; an indirect downstream regulatory role. Reason: Downstream neuronal differentiation control; ISO. |
| GO:0045765 regulation of angiogenesis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Neurofibromin influences angiogenesis via its control of endothelial RAS signalling; a downstream vascular regulatory role. Reason: Downstream angiogenesis regulation. |
| GO:0050890 cognition | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Cognitive function is impaired when RAS/cAMP signalling is dysregulated by NF1 loss; a high-level behavioural phenotype downstream of the molecular defect. Reason: Behavioural phenotype downstream of signalling dysregulation. |
| GO:0098926 postsynaptic signal transduction | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Postsynaptic signal transduction involving neurofibromin reflects its synaptic localization and RAS/cAMP modulation; downstream and ISO-projected. Reason: Downstream synaptic signalling role; ISO. |
| GO:0098978 glutamatergic synapse | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: SynGO localization at glutamatergic synapses supports neurofibromin's modulation of synaptic transmission/plasticity, a downstream neuronal role. Reason: Synaptic localization tied to pleiotropic neuronal function. |
| GO:0099159 regulation of modification of postsynaptic structure | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: ISO-projected control of postsynaptic structural modification is part of neurofibromin's downstream synaptic-plasticity role. Reason: Downstream postsynaptic regulation; ISO. |
| GO:0098978 glutamatergic synapse | IMP PMID:22105171 Valosin-containing protein and neurofibromin interact to reg... | KEEP AS NON CORE | Summary: SynGO localization at glutamatergic synapses supports neurofibromin's modulation of synaptic transmission/plasticity, a downstream neuronal role. Reason: Synaptic localization tied to pleiotropic neuronal function. |
| GO:0098978 glutamatergic synapse | IDA PMID:22105171 Valosin-containing protein and neurofibromin interact to reg... | KEEP AS NON CORE | Summary: SynGO localization at glutamatergic synapses supports neurofibromin's modulation of synaptic transmission/plasticity, a downstream neuronal role. Reason: Synaptic localization tied to pleiotropic neuronal function. |
| GO:0099175 regulation of postsynapse organization | IMP PMID:22105171 Valosin-containing protein and neurofibromin interact to reg... | KEEP AS NON CORE | Summary: SynGO-supported regulation of postsynaptic organization reflects neurofibromin's synaptic signalling role downstream of RAS. Reason: Synaptic-structure regulation downstream of signalling. |
| GO:0099175 regulation of postsynapse organization | IDA PMID:22105171 Valosin-containing protein and neurofibromin interact to reg... | KEEP AS NON CORE | Summary: SynGO-supported regulation of postsynaptic organization reflects neurofibromin's synaptic signalling role downstream of RAS. Reason: Synaptic-structure regulation downstream of signalling. |
| GO:0005096 GTPase activator activity | IMP PMID:16271875 The HMG-CoA reductase inhibitor lovastatin reverses the lear... | ACCEPT | Summary: Neurofibromin's GAP-related domain supplies an arginine finger (Arg1278) that stabilizes the RAS GTP-hydrolysis transition state; this RasGAP activity is the defining function of the protein. Reason: Defining biochemical activity (RasGAP); strongly supported by domain architecture and IMP/IGI/ISO evidence. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0005096 GTPase activator activity | IGI PMID:16271875 The HMG-CoA reductase inhibitor lovastatin reverses the lear... | ACCEPT | Summary: Neurofibromin's GAP-related domain supplies an arginine finger (Arg1278) that stabilizes the RAS GTP-hydrolysis transition state; this RasGAP activity is the defining function of the protein. Reason: Defining biochemical activity (RasGAP); strongly supported by domain architecture and IMP/IGI/ISO evidence. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0060291 long-term synaptic potentiation | IMP PMID:16271875 The HMG-CoA reductase inhibitor lovastatin reverses the lear... | KEEP AS NON CORE | Summary: Altered LTP in Nf1 mutants arises from excess RAS/MAPK and cAMP signalling at synapses; a downstream plasticity phenotype. Reason: Synaptic plasticity phenotype downstream of signalling control. |
| GO:0060291 long-term synaptic potentiation | IGI PMID:16271875 The HMG-CoA reductase inhibitor lovastatin reverses the lear... | KEEP AS NON CORE | Summary: Altered LTP in Nf1 mutants arises from excess RAS/MAPK and cAMP signalling at synapses; a downstream plasticity phenotype. Reason: Synaptic plasticity phenotype downstream of signalling control. |
| GO:0070372 regulation of ERK1 and ERK2 cascade | IMP PMID:16271875 The HMG-CoA reductase inhibitor lovastatin reverses the lear... | KEEP AS NON CORE | Summary: ERK1/2 output is modulated as a downstream effect of neurofibromin lowering RAS-GTP levels; the regulation is exerted at the RAS node. Reason: Downstream effector regulation, secondary to the RasGAP role. |
| GO:0070372 regulation of ERK1 and ERK2 cascade | IGI PMID:16271875 The HMG-CoA reductase inhibitor lovastatin reverses the lear... | KEEP AS NON CORE | Summary: ERK1/2 output is modulated as a downstream effect of neurofibromin lowering RAS-GTP levels; the regulation is exerted at the RAS node. Reason: Downstream effector regulation, secondary to the RasGAP role. |
| GO:0001953 negative regulation of cell-matrix adhesion | IGI PMID:17053831 Hyperactivation of p21ras and PI3K cooperate to alter murine... | KEEP AS NON CORE | Summary: Cell-matrix adhesion is modulated downstream of neurofibromin's RAS/Rho signalling control; a downstream adhesion phenotype. Reason: Downstream adhesion regulation, IGI. |
| GO:0030336 negative regulation of cell migration | IGI PMID:17053831 Hyperactivation of p21ras and PI3K cooperate to alter murine... | KEEP AS NON CORE | Summary: Reduced cell migration with neurofibromin reflects its control of RAS/Rho-pathway-driven motility; a downstream cytoskeletal/signalling effect. Reason: Downstream motility regulation. |
| GO:0045671 negative regulation of osteoclast differentiation | IGI PMID:17053831 Hyperactivation of p21ras and PI3K cooperate to alter murine... | KEEP AS NON CORE | Summary: Neurofibromin restrains osteoclast differentiation via RAS signalling control, relevant to NF1 bone pathology; a downstream phenotype. Reason: Downstream osteoclast regulation, IGI. |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | IMP PMID:15039234 Loss of the nf1 tumor suppressor gene decreases fas antigen ... | KEEP AS NON CORE | Summary: Involvement in death-receptor apoptotic signalling is downstream of neurofibromin's broader survival-pathway modulation. Reason: Downstream apoptotic-signalling phenotype. |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | IGI PMID:15039234 Loss of the nf1 tumor suppressor gene decreases fas antigen ... | KEEP AS NON CORE | Summary: Involvement in death-receptor apoptotic signalling is downstream of neurofibromin's broader survival-pathway modulation. Reason: Downstream apoptotic-signalling phenotype. |
| GO:0048169 regulation of long-term neuronal synaptic plasticity | IMP PMID:11793011 Mechanism for the learning deficits in a mouse model of neur... | KEEP AS NON CORE | Summary: Long-term synaptic plasticity is modulated by neurofibromin via RAS/cAMP signalling; a downstream neuronal regulatory function. Reason: Downstream synaptic-plasticity regulation. |
| GO:0048169 regulation of long-term neuronal synaptic plasticity | IGI PMID:11793011 Mechanism for the learning deficits in a mouse model of neur... | KEEP AS NON CORE | Summary: Long-term synaptic plasticity is modulated by neurofibromin via RAS/cAMP signalling; a downstream neuronal regulatory function. Reason: Downstream synaptic-plasticity regulation. |
| GO:0042308 negative regulation of protein import into nucleus | IMP PMID:12469121 Nf1 has an essential role in endothelial cells. | KEEP AS NON CORE | Summary: A reported effect on nuclear protein import is a downstream/secondary role of neurofibromin and not its proximal RasGAP function. Reason: Downstream/secondary regulatory phenotype, IMP. |
| GO:0048820 hair follicle maturation | IMP PMID:25340873 Identification of genes important for cutaneous function rev... | KEEP AS NON CORE | Summary: Hair-follicle maturation is affected by NF1 loss via RAS-pathway dysregulation in skin appendages; a downstream developmental phenotype. Reason: Downstream skin-appendage developmental phenotype. |
| GO:0010468 regulation of gene expression | IGI PMID:25242307 Social learning and amygdala disruptions in Nf1 mice are res... | KEEP AS NON CORE | Summary: Effects on gene expression are distal transcriptional consequences of neurofibromin's control of RAS/MAPK signalling. Reason: Distal downstream transcriptional effect, IGI. |
| GO:0021764 amygdala development | IGI PMID:25242307 Social learning and amygdala disruptions in Nf1 mice are res... | KEEP AS NON CORE | Summary: Amygdala development is affected in Nf1 mutant mice, linking the RAS brake to limbic-circuit formation underlying behavioural phenotypes. Reason: Region-specific developmental phenotype, IGI. |
| GO:0043408 regulation of MAPK cascade | IGI PMID:25242307 Social learning and amygdala disruptions in Nf1 mice are res... | KEEP AS NON CORE | Summary: Generic regulation of the MAPK cascade reflects neurofibromin's indirect control of ERK signalling downstream of its action on RAS. Reason: Downstream/generic effector regulation, not the proximal function. |
| GO:0061534 gamma-aminobutyric acid secretion, neurotransmission | IGI PMID:25242307 Social learning and amygdala disruptions in Nf1 mice are res... | KEEP AS NON CORE | Summary: Neurofibromin modulates GABA release through RAS/cAMP-dependent control of inhibitory transmission; a downstream neuronal phenotype. Reason: Downstream neurotransmission phenotype, IGI. |
| GO:0061535 glutamate secretion, neurotransmission | IGI PMID:25242307 Social learning and amygdala disruptions in Nf1 mice are res... | KEEP AS NON CORE | Summary: Glutamate release is influenced by neurofibromin's RAS/cAMP signalling at synapses; a downstream excitatory-transmission role. Reason: Downstream neurotransmission phenotype, IGI. |
| GO:0098597 observational learning | IGI PMID:25242307 Social learning and amygdala disruptions in Nf1 mice are res... | KEEP AS NON CORE | Summary: Observational-learning deficits reflect neurofibromin's role in synaptic plasticity via RAS/cAMP signalling; a behavioural phenotype. Reason: Behavioural learning phenotype, IGI, downstream. |
| GO:1900271 regulation of long-term synaptic potentiation | IGI PMID:25242307 Social learning and amygdala disruptions in Nf1 mice are res... | KEEP AS NON CORE | Summary: Neurofibromin tunes LTP magnitude through its control of synaptic RAS/cAMP signalling, a downstream regulatory role. Reason: Downstream plasticity regulation, IGI. |
| GO:0034605 cellular response to heat | IDA PMID:20661302 Long-term potentiation in the CA1 hippocampus induced by NR2... | UNDECIDED | Summary: An IDA links neurofibromin to a cellular heat response; the mechanistic connection to its RasGAP role is unclear from the cached evidence, so the call is deferred. Reason: Experimental annotation whose mechanism is unclear; do not remove, defer per guidelines. |
| GO:0008429 phosphatidylethanolamine binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The CRAL-TRIO domain also binds phosphatidylethanolamine-headgroup glycerophospholipids, aiding membrane localization of neurofibromin. Reason: Specific Sec14 lipid preference; membrane-association role, non-core. |
| GO:0031210 phosphatidylcholine binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The Sec14-like CRAL-TRIO domain preferentially binds phosphatidylcholine-headgroup lipids, contributing to membrane targeting rather than to catalysis. Reason: Specific Sec14 lipid preference; supports membrane association, non-core. |
| GO:2001241 positive regulation of extrinsic apoptotic signaling pathway in absence of ligand | IMP PMID:15039234 Loss of the nf1 tumor suppressor gene decreases fas antigen ... | KEEP AS NON CORE | Summary: Sensitization to ligand-independent extrinsic apoptosis reflects altered survival signalling when RAS output changes; downstream. Reason: Downstream apoptotic-signalling phenotype, IMP. |
| GO:0005096 GTPase activator activity | IGI PMID:15665300 Glioma formation in neurofibromatosis 1 reflects preferentia... | ACCEPT | Summary: Neurofibromin's GAP-related domain supplies an arginine finger (Arg1278) that stabilizes the RAS GTP-hydrolysis transition state; this RasGAP activity is the defining function of the protein. Reason: Defining biochemical activity (RasGAP); strongly supported by domain architecture and IMP/IGI/ISO evidence. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0048147 negative regulation of fibroblast proliferation | IMP PMID:20154697 An oncogene-tumor suppressor cascade drives metastatic prost... | KEEP AS NON CORE | Summary: Fibroblast proliferation is curbed by neurofibromin lowering RAS-GTP; a downstream antiproliferative readout in mesenchymal cells. Reason: Downstream antiproliferative phenotype (experimental IMP; downgraded, not removed). |
| GO:0008542 visual learning | IMP PMID:11279521 Learning deficits, but normal development and tumor predispo... | KEEP AS NON CORE | Summary: Visual-learning deficits in Nf1+/- mice trace to excess RAS/cAMP-dependent synaptic signalling, a downstream behavioural readout. Reason: Behavioural learning phenotype downstream of RAS/cAMP. |
| GO:0001649 osteoblast differentiation | IMP PMID:16893911 Neurofibromin plays a critical role in modulating osteoblast... | KEEP AS NON CORE | Summary: Osteoblast differentiation is affected by NF1 loss through dysregulated RAS signalling, contributing to skeletal manifestations; downstream. Reason: Downstream skeletal-cell differentiation phenotype. |
| GO:0001666 response to hypoxia | IMP PMID:16288202 Nf1 haploinsufficiency augments angiogenesis. | KEEP AS NON CORE | Summary: Responsiveness to hypoxia in NF1 contexts is a downstream physiological phenotype connected to RAS/vascular signalling rather than a direct function. Reason: Downstream stress-response phenotype, IMP. |
| GO:0001937 negative regulation of endothelial cell proliferation | ISO GO_REF:0000008 | KEEP AS NON CORE | Summary: Endothelial proliferation is restrained by neurofibromin through reduced RAS signalling, relevant to vascular phenotypes; downstream. Reason: Downstream vascular antiproliferative phenotype. |
| GO:0001937 negative regulation of endothelial cell proliferation | IMP PMID:16288202 Nf1 haploinsufficiency augments angiogenesis. | KEEP AS NON CORE | Summary: Endothelial proliferation is restrained by neurofibromin through reduced RAS signalling, relevant to vascular phenotypes; downstream. Reason: Downstream vascular antiproliferative phenotype. |
| GO:0001938 positive regulation of endothelial cell proliferation | IGI PMID:16644864 Neurofibromin is a novel regulator of RAS-induced signals in... | KEEP AS NON CORE | Summary: A context-dependent positive effect on endothelial proliferation reflects complex vascular signalling outputs of neurofibromin; downstream and IGI. Reason: Context-dependent downstream vascular phenotype. |
| GO:0001952 regulation of cell-matrix adhesion | IMP PMID:16405917 Neurofibromin binds to caveolin-1 and regulates ras, FAK, an... | KEEP AS NON CORE | Summary: General regulation of cell-matrix adhesion by neurofibromin is an indirect downstream effect of its signalling role. Reason: Downstream adhesion regulation, IMP. |
| GO:0005096 GTPase activator activity | IMP PMID:17053831 Hyperactivation of p21ras and PI3K cooperate to alter murine... | ACCEPT | Summary: Neurofibromin's GAP-related domain supplies an arginine finger (Arg1278) that stabilizes the RAS GTP-hydrolysis transition state; this RasGAP activity is the defining function of the protein. Reason: Defining biochemical activity (RasGAP); strongly supported by domain architecture and IMP/IGI/ISO evidence. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0005515 protein binding | IPI PMID:16405917 Neurofibromin binds to caveolin-1 and regulates ras, FAK, an... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' conveys no functional specificity for neurofibromin; its informative partner interactions (SPRED, HTR6) are captured by dedicated terms. Reason: Uninformative MF; over-annotation. |
| GO:0006469 negative regulation of protein kinase activity | IMP PMID:16835260 Nf1+/- mast cells induce neurofibroma like phenotypes throug... | KEEP AS NON CORE | Summary: Reduced kinase (e.g. ERK) activity is an indirect downstream consequence of neurofibromin lowering RAS-GTP, not direct kinase inhibition. Reason: Indirect downstream kinase regulation. |
| GO:0006469 negative regulation of protein kinase activity | IGI PMID:17053831 Hyperactivation of p21ras and PI3K cooperate to alter murine... | KEEP AS NON CORE | Summary: Reduced kinase (e.g. ERK) activity is an indirect downstream consequence of neurofibromin lowering RAS-GTP, not direct kinase inhibition. Reason: Indirect downstream kinase regulation. |
| GO:0008285 negative regulation of cell population proliferation | IGI PMID:15665300 Glioma formation in neurofibromatosis 1 reflects preferentia... | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:15944386 Neurofibromin regulates neural stem cell proliferation, surv... | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0008542 visual learning | IGI PMID:16271875 The HMG-CoA reductase inhibitor lovastatin reverses the lear... | KEEP AS NON CORE | Summary: Visual-learning deficits in Nf1+/- mice trace to excess RAS/cAMP-dependent synaptic signalling, a downstream behavioural readout. Reason: Behavioural learning phenotype downstream of RAS/cAMP. |
| GO:0016525 negative regulation of angiogenesis | IGI PMID:16648142 Neurofibroma-associated growth factors activate a distinct s... | KEEP AS NON CORE | Summary: Neurofibromin can restrain angiogenesis by limiting endothelial RAS signalling; a downstream vascular phenotype. Reason: Downstream antiangiogenic phenotype, IGI. |
| GO:0021897 forebrain astrocyte development | IMP PMID:15944386 Neurofibromin regulates neural stem cell proliferation, surv... | KEEP AS NON CORE | Summary: Forebrain astrocyte development is perturbed when NF1 loss elevates RAS signalling; a region-specific downstream developmental phenotype. Reason: Region-specific downstream developmental phenotype. |
| GO:0030036 actin cytoskeleton organization | IGI PMID:15665300 Glioma formation in neurofibromatosis 1 reflects preferentia... | KEEP AS NON CORE | Summary: Effects on the actin cytoskeleton (via Rho/ROCK/LIMK/cofilin and PKA-Ena/VASP) are downstream of neurofibromin's signalling role rather than a direct structural function. Reason: Downstream cytoskeletal remodeling secondary to signalling regulation. |
| GO:0030036 actin cytoskeleton organization | IMP PMID:16405917 Neurofibromin binds to caveolin-1 and regulates ras, FAK, an... | KEEP AS NON CORE | Summary: Effects on the actin cytoskeleton (via Rho/ROCK/LIMK/cofilin and PKA-Ena/VASP) are downstream of neurofibromin's signalling role rather than a direct structural function. Reason: Downstream cytoskeletal remodeling secondary to signalling regulation. |
| GO:0030198 extracellular matrix organization | IMP PMID:16835260 Nf1+/- mast cells induce neurofibroma like phenotypes throug... | KEEP AS NON CORE | Summary: ECM organization is influenced by neurofibromin through its control of fibroblast RAS signalling; a downstream connective-tissue phenotype. Reason: Downstream ECM-organization phenotype. |
| GO:0030336 negative regulation of cell migration | ISO GO_REF:0000008 | KEEP AS NON CORE | Summary: Reduced cell migration with neurofibromin reflects its control of RAS/Rho-pathway-driven motility; a downstream cytoskeletal/signalling effect. Reason: Downstream motility regulation. |
| GO:0030336 negative regulation of cell migration | IGI PMID:16644864 Neurofibromin is a novel regulator of RAS-induced signals in... | KEEP AS NON CORE | Summary: Reduced cell migration with neurofibromin reflects its control of RAS/Rho-pathway-driven motility; a downstream cytoskeletal/signalling effect. Reason: Downstream motility regulation. |
| GO:0035021 negative regulation of Rac protein signal transduction | IGI PMID:15665300 Glioma formation in neurofibromatosis 1 reflects preferentia... | KEEP AS NON CORE | Summary: Reduced Rac signalling is reported downstream of NF1 loss; this lies in a Rho-family arm secondary to neurofibromin's primary RAS-directed GAP function. Reason: Downstream/secondary signalling effect, not the canonical RAS GAP activity. |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:15944386 Neurofibromin regulates neural stem cell proliferation, surv... | KEEP AS NON CORE | Summary: Pro-apoptotic effects of neurofibromin in some cell types are downstream of its modulation of RAS-pathway survival signalling. Reason: Downstream apoptotic-balance phenotype. |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:17053831 Hyperactivation of p21ras and PI3K cooperate to alter murine... | KEEP AS NON CORE | Summary: Pro-apoptotic effects of neurofibromin in some cell types are downstream of its modulation of RAS-pathway survival signalling. Reason: Downstream apoptotic-balance phenotype. |
| GO:0043407 negative regulation of MAP kinase activity | IMP PMID:12409258 Glycogen stored in skeletal but not in cardiac muscle in aci... | KEEP AS NON CORE | Summary: Lowered ERK/MAPK activity results indirectly from neurofibromin reducing RAS-GTP; it acts on RAS, not directly on the MAP kinase. Reason: Indirect downstream effect of RasGAP activity on RAS. |
| GO:0043407 negative regulation of MAP kinase activity | IGI PMID:12409258 Glycogen stored in skeletal but not in cardiac muscle in aci... | KEEP AS NON CORE | Summary: Lowered ERK/MAPK activity results indirectly from neurofibromin reducing RAS-GTP; it acts on RAS, not directly on the MAP kinase. Reason: Indirect downstream effect of RasGAP activity on RAS. |
| GO:0043409 negative regulation of MAPK cascade | ISO GO_REF:0000008 | KEEP AS NON CORE | Summary: Dampening of the RAF-MEK-ERK cascade follows from reduced RAS activation; neurofibromin's direct target is RAS-GTP, upstream of the cascade. Reason: Downstream consequence of negative regulation of RAS. |
| GO:0043409 negative regulation of MAPK cascade | IMP PMID:16644864 Neurofibromin is a novel regulator of RAS-induced signals in... | KEEP AS NON CORE | Summary: Dampening of the RAF-MEK-ERK cascade follows from reduced RAS activation; neurofibromin's direct target is RAS-GTP, upstream of the cascade. Reason: Downstream consequence of negative regulation of RAS. |
| GO:0043547 positive regulation of GTPase activity | ISO GO_REF:0000008 | ACCEPT | Summary: Direct readout of catalysis: neurofibromin accelerates the intrinsic GTPase activity of RAS, the molecular event that terminates active RAS-GTP signalling. Reason: Proximal consequence of RasGAP catalysis; core to neurofibromin function. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0045124 regulation of bone resorption | IMP PMID:17053831 Hyperactivation of p21ras and PI3K cooperate to alter murine... | KEEP AS NON CORE | Summary: Bone resorption is modulated by neurofibromin through its effects on osteoclast RAS signalling; a downstream skeletal phenotype. Reason: Downstream bone-remodeling phenotype, IMP. |
| GO:0045762 positive regulation of adenylate cyclase activity | IMP PMID:11788835 Neurofibromin regulates G protein-stimulated adenylyl cyclas... | KEEP AS NON CORE | Summary: Neurofibromin promotes cAMP production via G-protein-dependent adenylyl cyclase regulation, a distinct downstream signalling arm beyond RasGAP catalysis. Reason: Real but distinct cAMP-modulatory role; pleiotropic/non-core. |
| GO:0045765 regulation of angiogenesis | IMP PMID:16288202 Nf1 haploinsufficiency augments angiogenesis. | KEEP AS NON CORE | Summary: Neurofibromin influences angiogenesis via its control of endothelial RAS signalling; a downstream vascular regulatory role. Reason: Downstream angiogenesis regulation. |
| GO:0046580 negative regulation of Ras protein signal transduction | IMP PMID:15665300 Glioma formation in neurofibromatosis 1 reflects preferentia... | ACCEPT | Summary: By converting RAS-GTP to RAS-GDP neurofibromin is the principal brake on RAS pathway output; loss elevates RAS signalling and drives the NF1 phenotype. Reason: Direct, proximal biological role of the RasGAP; core function. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0046580 negative regulation of Ras protein signal transduction | IGI PMID:15665300 Glioma formation in neurofibromatosis 1 reflects preferentia... | ACCEPT | Summary: By converting RAS-GTP to RAS-GDP neurofibromin is the principal brake on RAS pathway output; loss elevates RAS signalling and drives the NF1 phenotype. Reason: Direct, proximal biological role of the RasGAP; core function. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0046580 negative regulation of Ras protein signal transduction | IMP PMID:15944386 Neurofibromin regulates neural stem cell proliferation, surv... | ACCEPT | Summary: By converting RAS-GTP to RAS-GDP neurofibromin is the principal brake on RAS pathway output; loss elevates RAS signalling and drives the NF1 phenotype. Reason: Direct, proximal biological role of the RasGAP; core function. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0046580 negative regulation of Ras protein signal transduction | IMP PMID:16835260 Nf1+/- mast cells induce neurofibroma like phenotypes throug... | ACCEPT | Summary: By converting RAS-GTP to RAS-GDP neurofibromin is the principal brake on RAS pathway output; loss elevates RAS signalling and drives the NF1 phenotype. Reason: Direct, proximal biological role of the RasGAP; core function. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0046580 negative regulation of Ras protein signal transduction | IMP PMID:16893911 Neurofibromin plays a critical role in modulating osteoblast... | ACCEPT | Summary: By converting RAS-GTP to RAS-GDP neurofibromin is the principal brake on RAS pathway output; loss elevates RAS signalling and drives the NF1 phenotype. Reason: Direct, proximal biological role of the RasGAP; core function. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0046580 negative regulation of Ras protein signal transduction | IGI PMID:17053831 Hyperactivation of p21ras and PI3K cooperate to alter murine... | ACCEPT | Summary: By converting RAS-GTP to RAS-GDP neurofibromin is the principal brake on RAS pathway output; loss elevates RAS signalling and drives the NF1 phenotype. Reason: Direct, proximal biological role of the RasGAP; core function. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0046929 negative regulation of neurotransmitter secretion | IMP PMID:16298082 Stimulus-evoked release of neuropeptides is enhanced in sens... | KEEP AS NON CORE | Summary: Neurofibromin can dampen neurotransmitter release via its synaptic signalling role; a downstream regulatory effect on transmission. Reason: Downstream neurotransmission regulation. |
| GO:0046929 negative regulation of neurotransmitter secretion | IGI PMID:16298082 Stimulus-evoked release of neuropeptides is enhanced in sens... | KEEP AS NON CORE | Summary: Neurofibromin can dampen neurotransmitter release via its synaptic signalling role; a downstream regulatory effect on transmission. Reason: Downstream neurotransmission regulation. |
| GO:0048715 negative regulation of oligodendrocyte differentiation | IMP PMID:15944386 Neurofibromin regulates neural stem cell proliferation, surv... | KEEP AS NON CORE | Summary: Oligodendrocyte differentiation is sensitive to RAS tone; neurofibromin's restraint of RAS underlies this negative-regulation phenotype. Reason: Downstream glial differentiation control. |
| GO:0000165 MAPK cascade | IMP PMID:14724565 Role of TC21/R-Ras2 in enhanced migration of neurofibromin-d... | KEEP AS NON CORE | Summary: The MAPK (RAF-MEK-ERK) cascade is the principal effector arm downstream of RAS that neurofibromin restrains; involvement here is a consequence of its RasGAP role. Reason: Downstream effector pathway of the RAS brake; not the proximal function. |
| GO:0007265 Ras protein signal transduction | IMP PMID:12469121 Nf1 has an essential role in endothelial cells. | KEEP AS NON CORE | Summary: Neurofibromin participates in RAS signalling specifically as its negative regulator; the broad 'Ras protein signal transduction' term is less precise than the negative-regulation term. Reason: Subsumed by the more specific negative-regulation-of-Ras core term; kept as supporting context. |
| GO:0007507 heart development | IMP PMID:12469121 Nf1 has an essential role in endothelial cells. | KEEP AS NON CORE | Summary: Nf1-null embryos show cardiovascular defects and mid-gestation lethality because controlled RAS/MAPK and PI3K signalling is required for cardiac morphogenesis. Reason: Downstream organ-development phenotype (well documented in mouse). |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:11246230 Neurofibromatosis 1 (NF1) heterozygosity results in a cell-a... | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0008285 negative regulation of cell population proliferation | IGI PMID:11246230 Neurofibromatosis 1 (NF1) heterozygosity results in a cell-a... | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:14982883 Somatic inactivation of Nf1 in hematopoietic cells results i... | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0030336 negative regulation of cell migration | IMP PMID:14724565 Role of TC21/R-Ras2 in enhanced migration of neurofibromin-d... | KEEP AS NON CORE | Summary: Reduced cell migration with neurofibromin reflects its control of RAS/Rho-pathway-driven motility; a downstream cytoskeletal/signalling effect. Reason: Downstream motility regulation. |
| GO:0030336 negative regulation of cell migration | IGI PMID:14724565 Role of TC21/R-Ras2 in enhanced migration of neurofibromin-d... | KEEP AS NON CORE | Summary: Reduced cell migration with neurofibromin reflects its control of RAS/Rho-pathway-driven motility; a downstream cytoskeletal/signalling effect. Reason: Downstream motility regulation. |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:14724565 Role of TC21/R-Ras2 in enhanced migration of neurofibromin-d... | KEEP AS NON CORE | Summary: PI3K/AKT is a second major RAS effector arm engaged when neurofibromin is lost; its regulation is a downstream consequence of altered RAS-GTP. Reason: Downstream RAS effector pathway; pleiotropic, not proximal. |
| GO:0043547 positive regulation of GTPase activity | IMP PMID:11435472 Hyperactivation of p21(ras) and the hematopoietic-specific R... | ACCEPT | Summary: Direct readout of catalysis: neurofibromin accelerates the intrinsic GTPase activity of RAS, the molecular event that terminates active RAS-GTP signalling. Reason: Proximal consequence of RasGAP catalysis; core to neurofibromin function. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0043547 positive regulation of GTPase activity | IMP PMID:8563750 Nf1 deficiency causes Ras-mediated granulocyte/macrophage co... | ACCEPT | Summary: Direct readout of catalysis: neurofibromin accelerates the intrinsic GTPase activity of RAS, the molecular event that terminates active RAS-GTP signalling. Reason: Proximal consequence of RasGAP catalysis; core to neurofibromin function. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0046580 negative regulation of Ras protein signal transduction | IMP PMID:11246230 Neurofibromatosis 1 (NF1) heterozygosity results in a cell-a... | ACCEPT | Summary: By converting RAS-GTP to RAS-GDP neurofibromin is the principal brake on RAS pathway output; loss elevates RAS signalling and drives the NF1 phenotype. Reason: Direct, proximal biological role of the RasGAP; core function. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0005096 GTPase activator activity | IMP PMID:11435472 Hyperactivation of p21(ras) and the hematopoietic-specific R... | ACCEPT | Summary: Neurofibromin's GAP-related domain supplies an arginine finger (Arg1278) that stabilizes the RAS GTP-hydrolysis transition state; this RasGAP activity is the defining function of the protein. Reason: Defining biochemical activity (RasGAP); strongly supported by domain architecture and IMP/IGI/ISO evidence. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0007265 Ras protein signal transduction | IMP PMID:11435472 Hyperactivation of p21(ras) and the hematopoietic-specific R... | KEEP AS NON CORE | Summary: Neurofibromin participates in RAS signalling specifically as its negative regulator; the broad 'Ras protein signal transduction' term is less precise than the negative-regulation term. Reason: Subsumed by the more specific negative-regulation-of-Ras core term; kept as supporting context. |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:11401406 Analysis of melanocyte precursors in Nf1 mutants reveals tha... | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0008285 negative regulation of cell population proliferation | IGI PMID:11401406 Analysis of melanocyte precursors in Nf1 mutants reveals tha... | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0008285 negative regulation of cell population proliferation | IGI PMID:11435472 Hyperactivation of p21(ras) and the hematopoietic-specific R... | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0008542 visual learning | IMP PMID:11793011 Mechanism for the learning deficits in a mouse model of neur... | KEEP AS NON CORE | Summary: Visual-learning deficits in Nf1+/- mice trace to excess RAS/cAMP-dependent synaptic signalling, a downstream behavioural readout. Reason: Behavioural learning phenotype downstream of RAS/cAMP. |
| GO:0008542 visual learning | IGI PMID:11793011 Mechanism for the learning deficits in a mouse model of neur... | KEEP AS NON CORE | Summary: Visual-learning deficits in Nf1+/- mice trace to excess RAS/cAMP-dependent synaptic signalling, a downstream behavioural readout. Reason: Behavioural learning phenotype downstream of RAS/cAMP. |
| GO:0032228 regulation of synaptic transmission, GABAergic | IGI PMID:11793011 Mechanism for the learning deficits in a mouse model of neur... | KEEP AS NON CORE | Summary: GABAergic transmission is regulated by neurofibromin through RAS/cAMP signalling, contributing to learning phenotypes; downstream and pleiotropic. Reason: Downstream inhibitory-transmission regulation, IGI. |
| GO:0043065 positive regulation of apoptotic process | IGI PMID:15039234 Loss of the nf1 tumor suppressor gene decreases fas antigen ... | KEEP AS NON CORE | Summary: Pro-apoptotic effects of neurofibromin in some cell types are downstream of its modulation of RAS-pathway survival signalling. Reason: Downstream apoptotic-balance phenotype. |
| GO:0007265 Ras protein signal transduction | IGI PMID:10845775 Neurofibromin negatively regulates neurotrophin signaling th... | KEEP AS NON CORE | Summary: Neurofibromin participates in RAS signalling specifically as its negative regulator; the broad 'Ras protein signal transduction' term is less precise than the negative-regulation term. Reason: Subsumed by the more specific negative-regulation-of-Ras core term; kept as supporting context. |
| GO:0008285 negative regulation of cell population proliferation | IGI PMID:10620616 Genetic and biochemical evidence that haploinsufficiency of ... | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0008285 negative regulation of cell population proliferation | IGI PMID:10973261 Nf1;Trp53 mutant mice develop glioblastoma with evidence of ... | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0008285 negative regulation of cell population proliferation | IGI PMID:9001241 Nf1-deficient mouse Schwann cells are angiogenic and invasiv... | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0021987 cerebral cortex development | IMP PMID:11297510 Ablation of NF1 function in neurons induces abnormal develop... | KEEP AS NON CORE | Summary: Cortical development is impaired by RAS dysregulation in NF1-deficient mice; a region-specific downstream developmental phenotype. Reason: Region-specific CNS developmental phenotype. |
| GO:0022011 myelination in peripheral nervous system | IMP PMID:10586246 Neurofibromin, the neurofibromatosis type 1 Ras-GAP, is requ... | KEEP AS NON CORE | Summary: PNS myelination by Schwann cells is sensitive to RAS dosage controlled by neurofibromin, so myelination defects are a downstream effect of NF1 loss. Reason: Downstream PNS phenotype of dysregulated RAS in Schwann cells. |
| GO:0042127 regulation of cell population proliferation | IGI PMID:10678181 Nf1 and Gmcsf interact in myeloid leukemogenesis. | KEEP AS NON CORE | Summary: General control of proliferation by neurofibromin follows from its modulation of RAS mitogenic signalling. Reason: Downstream/generic proliferation control, IGI. |
| GO:0043407 negative regulation of MAP kinase activity | IGI PMID:10620616 Genetic and biochemical evidence that haploinsufficiency of ... | KEEP AS NON CORE | Summary: Lowered ERK/MAPK activity results indirectly from neurofibromin reducing RAS-GTP; it acts on RAS, not directly on the MAP kinase. Reason: Indirect downstream effect of RasGAP activity on RAS. |
| GO:0043407 negative regulation of MAP kinase activity | IMP PMID:11297510 Ablation of NF1 function in neurons induces abnormal develop... | KEEP AS NON CORE | Summary: Lowered ERK/MAPK activity results indirectly from neurofibromin reducing RAS-GTP; it acts on RAS, not directly on the MAP kinase. Reason: Indirect downstream effect of RasGAP activity on RAS. |
| GO:0043473 pigmentation | IMP PMID:10844550 The neurofibromatosis type 1 (Nf1) tumor suppressor is a mod... | KEEP AS NON CORE | Summary: Pigmentation phenotypes (cafe-au-lait-like) arise because melanocyte RAS signalling, normally restrained by neurofibromin, is dysregulated on NF1 loss. Reason: Downstream melanocyte phenotype. |
| GO:0043525 positive regulation of neuron apoptotic process | IGI PMID:10845775 Neurofibromin negatively regulates neurotrophin signaling th... | KEEP AS NON CORE | Summary: Promotion of neuronal apoptosis in NF1 contexts reflects altered RAS/PI3K survival signalling; a downstream neuronal phenotype. Reason: Downstream neuronal apoptosis phenotype. |
| GO:0043525 positive regulation of neuron apoptotic process | IMP PMID:11297510 Ablation of NF1 function in neurons induces abnormal develop... | KEEP AS NON CORE | Summary: Promotion of neuronal apoptosis in NF1 contexts reflects altered RAS/PI3K survival signalling; a downstream neuronal phenotype. Reason: Downstream neuronal apoptosis phenotype. |
| GO:0043525 positive regulation of neuron apoptotic process | IMP PMID:7671302 Loss of neurofibromin results in neurotrophin-independent su... | KEEP AS NON CORE | Summary: Promotion of neuronal apoptosis in NF1 contexts reflects altered RAS/PI3K survival signalling; a downstream neuronal phenotype. Reason: Downstream neuronal apoptosis phenotype. |
| GO:0048712 negative regulation of astrocyte differentiation | IMP PMID:11297510 Ablation of NF1 function in neurons induces abnormal develop... | KEEP AS NON CORE | Summary: By limiting RAS/MAPK signalling neurofibromin restrains astrocyte fate; loss promotes astrogliogenesis, a downstream developmental effect. Reason: Downstream gliogenesis phenotype of elevated RAS. |
| GO:0048853 forebrain morphogenesis | IMP PMID:11297510 Ablation of NF1 function in neurons induces abnormal develop... | KEEP AS NON CORE | Summary: Forebrain morphogenesis depends on properly tuned RAS signalling enforced by neurofibromin; defects are a downstream developmental consequence. Reason: Downstream forebrain morphogenesis phenotype. |
| GO:0007265 Ras protein signal transduction | IMP PMID:10498620 In vitro and in vivo effects of a farnesyltransferase inhibi... | KEEP AS NON CORE | Summary: Neurofibromin participates in RAS signalling specifically as its negative regulator; the broad 'Ras protein signal transduction' term is less precise than the negative-regulation term. Reason: Subsumed by the more specific negative-regulation-of-Ras core term; kept as supporting context. |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:10498620 In vitro and in vivo effects of a farnesyltransferase inhibi... | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0008285 negative regulation of cell population proliferation | IGI PMID:10591652 Mouse models of tumor development in neurofibromatosis type ... | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0008285 negative regulation of cell population proliferation | IGI PMID:10591653 Mouse tumor model for neurofibromatosis type 1. | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0043473 pigmentation | IMP PMID:10594763 Induction of melanogenic abnormalities in NF1+/- mutant mice... | KEEP AS NON CORE | Summary: Pigmentation phenotypes (cafe-au-lait-like) arise because melanocyte RAS signalling, normally restrained by neurofibromin, is dysregulated on NF1 loss. Reason: Downstream melanocyte phenotype. |
| GO:0043473 pigmentation | IGI PMID:10620616 Genetic and biochemical evidence that haploinsufficiency of ... | KEEP AS NON CORE | Summary: Pigmentation phenotypes (cafe-au-lait-like) arise because melanocyte RAS signalling, normally restrained by neurofibromin, is dysregulated on NF1 loss. Reason: Downstream melanocyte phenotype. |
| GO:0007154 cell communication | IMP PMID:10442636 Haploinsufficiency for the neurofibromatosis 1 (NF1) tumor s... | KEEP AS NON CORE | Summary: Generic 'cell communication' captures neurofibromin's signalling involvement at a very high level and is far less informative than its RasGAP terms. Reason: Generic high-level signalling process; non-core. |
| GO:0007420 brain development | IMP PMID:10419687 Neurofibromin deficiency in mice causes exencephaly and is a... | KEEP AS NON CORE | Summary: Broad brain development is affected because neurofibromin's control of RAS/MAPK is required for normal neural proliferation and patterning. Reason: Broad downstream CNS developmental phenotype. |
| GO:0007422 peripheral nervous system development | IMP PMID:10419687 Neurofibromin deficiency in mice causes exencephaly and is a... | KEEP AS NON CORE | Summary: Broad PNS development is affected via Schwann-cell and neural-crest derivatives whose RAS signalling neurofibromin restrains. Reason: Broad downstream developmental process. |
| GO:0007507 heart development | IMP PMID:10419687 Neurofibromin deficiency in mice causes exencephaly and is a... | KEEP AS NON CORE | Summary: Nf1-null embryos show cardiovascular defects and mid-gestation lethality because controlled RAS/MAPK and PI3K signalling is required for cardiac morphogenesis. Reason: Downstream organ-development phenotype (well documented in mouse). |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:10383727 The Nf1 tumor suppressor regulates mouse skin wound healing,... | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:10442636 Haploinsufficiency for the neurofibromatosis 1 (NF1) tumor s... | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0021915 neural tube development | IGI PMID:10419687 Neurofibromin deficiency in mice causes exencephaly and is a... | KEEP AS NON CORE | Summary: Neural-tube development is among the embryonic processes sensitive to RAS dosage controlled by neurofibromin. Reason: Embryonic CNS developmental phenotype, IGI. |
| GO:0030199 collagen fibril organization | IMP PMID:10383727 The Nf1 tumor suppressor regulates mouse skin wound healing,... | KEEP AS NON CORE | Summary: Altered collagen fibril organization reflects effects of NF1 loss on fibroblast/ECM behaviour downstream of RAS signalling. Reason: Downstream ECM/connective-tissue phenotype. |
| GO:0042060 wound healing | IMP PMID:10383727 The Nf1 tumor suppressor regulates mouse skin wound healing,... | KEEP AS NON CORE | Summary: Wound-healing defects reflect altered proliferation/migration/ECM behaviour downstream of neurofibromin's RAS signalling control. Reason: Downstream integrative physiological phenotype. |
| GO:0048593 camera-type eye morphogenesis | IMP PMID:7926784 Targeted disruption of the neurofibromatosis type-1 gene lea... | KEEP AS NON CORE | Summary: Eye morphogenesis defects in Nf1 mutants reflect the requirement for controlled RAS signalling during ocular development. Reason: Organ-development phenotype downstream of RAS control. |
| GO:0048712 negative regulation of astrocyte differentiation | IMP PMID:10442636 Haploinsufficiency for the neurofibromatosis 1 (NF1) tumor s... | KEEP AS NON CORE | Summary: By limiting RAS/MAPK signalling neurofibromin restrains astrocyte fate; loss promotes astrogliogenesis, a downstream developmental effect. Reason: Downstream gliogenesis phenotype of elevated RAS. |
| GO:0048712 negative regulation of astrocyte differentiation | IMP PMID:9878702 Region-specific astrogliosis in brains of mice heterozygous ... | KEEP AS NON CORE | Summary: By limiting RAS/MAPK signalling neurofibromin restrains astrocyte fate; loss promotes astrogliogenesis, a downstream developmental effect. Reason: Downstream gliogenesis phenotype of elevated RAS. |
| GO:0001656 metanephros development | IMP PMID:7926784 Targeted disruption of the neurofibromatosis type-1 gene lea... | KEEP AS NON CORE | Summary: Metanephric kidney development is affected in Nf1 mutants secondary to dysregulated RAS signalling in developing tissues. Reason: Organ-development phenotype, IMP. |
| GO:0001889 liver development | IMP PMID:7926784 Targeted disruption of the neurofibromatosis type-1 gene lea... | KEEP AS NON CORE | Summary: Liver development is among the organogenesis processes perturbed by NF1 loss via altered RAS signalling. Reason: Organ-development phenotype, IMP. |
| GO:0005096 GTPase activator activity | IMP PMID:8563750 Nf1 deficiency causes Ras-mediated granulocyte/macrophage co... | ACCEPT | Summary: Neurofibromin's GAP-related domain supplies an arginine finger (Arg1278) that stabilizes the RAS GTP-hydrolysis transition state; this RasGAP activity is the defining function of the protein. Reason: Defining biochemical activity (RasGAP); strongly supported by domain architecture and IMP/IGI/ISO evidence. Supporting Evidence: UniProt:Q04690 Stimulates the GTPase activity of Ras (By similarity). NF1 shows greater affinity for Ras GAP, but lower specific activity (By similarity). May be a regulator of Ras activity (By similarity). file:mouse/Nf1/Nf1-deep-research-falcon.md Neurofibromin is a **RAS GTPase-activating protein** that accelerates RAS GTP hydrolysis (RAS-GTP -> RAS-GDP), thereby negatively regulating Ras signaling. |
| GO:0007265 Ras protein signal transduction | IMP PMID:8563750 Nf1 deficiency causes Ras-mediated granulocyte/macrophage co... | KEEP AS NON CORE | Summary: Neurofibromin participates in RAS signalling specifically as its negative regulator; the broad 'Ras protein signal transduction' term is less precise than the negative-regulation term. Reason: Subsumed by the more specific negative-regulation-of-Ras core term; kept as supporting context. |
| GO:0007265 Ras protein signal transduction | IMP PMID:9001241 Nf1-deficient mouse Schwann cells are angiogenic and invasiv... | KEEP AS NON CORE | Summary: Neurofibromin participates in RAS signalling specifically as its negative regulator; the broad 'Ras protein signal transduction' term is less precise than the negative-regulation term. Reason: Subsumed by the more specific negative-regulation-of-Ras core term; kept as supporting context. |
| GO:0007406 negative regulation of neuroblast proliferation | IMP PMID:7926784 Targeted disruption of the neurofibromatosis type-1 gene lea... | KEEP AS NON CORE | Summary: Neurofibromin limits neuroblast proliferation by restraining RAS-driven cell-cycle entry; a downstream antiproliferative role in the nervous system. Reason: Downstream antiproliferative phenotype of the RAS brake. |
| GO:0007507 heart development | IMP PMID:7920653 Tumour predisposition in mice heterozygous for a targeted mu... | KEEP AS NON CORE | Summary: Nf1-null embryos show cardiovascular defects and mid-gestation lethality because controlled RAS/MAPK and PI3K signalling is required for cardiac morphogenesis. Reason: Downstream organ-development phenotype (well documented in mouse). |
| GO:0007507 heart development | IMP PMID:7926784 Targeted disruption of the neurofibromatosis type-1 gene lea... | KEEP AS NON CORE | Summary: Nf1-null embryos show cardiovascular defects and mid-gestation lethality because controlled RAS/MAPK and PI3K signalling is required for cardiac morphogenesis. Reason: Downstream organ-development phenotype (well documented in mouse). |
| GO:0007519 skeletal muscle tissue development | IMP PMID:7926784 Targeted disruption of the neurofibromatosis type-1 gene lea... | KEEP AS NON CORE | Summary: Skeletal-muscle development is influenced by NF1 loss through altered RAS/MAPK signalling; a downstream tissue-development phenotype. Reason: Tissue-development phenotype, IMP. |
| GO:0008017 microtubule binding | ISO GO_REF:0000008 | KEEP AS NON CORE | Summary: ISO-projected microtubule binding has been linked to neurofibromin in mitotic/tubulin contexts but is peripheral to its core membrane-proximal RasGAP role. Reason: Ancillary, electronically projected binding; not core function. |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:8563750 Nf1 deficiency causes Ras-mediated granulocyte/macrophage co... | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:9001241 Nf1-deficient mouse Schwann cells are angiogenic and invasiv... | KEEP AS NON CORE | Summary: Neurofibromin restrains proliferation by lowering RAS-driven mitogenic signalling; its tumour-suppressor antiproliferative output is downstream of the RasGAP step. Reason: Downstream antiproliferative (tumour-suppressor) phenotype. |
| GO:0008542 visual learning | IGI PMID:9054942 A mouse model for the learning and memory deficits associate... | KEEP AS NON CORE | Summary: Visual-learning deficits in Nf1+/- mice trace to excess RAS/cAMP-dependent synaptic signalling, a downstream behavioural readout. Reason: Behavioural learning phenotype downstream of RAS/cAMP. |
| GO:0014044 Schwann cell development | IMP PMID:9001241 Nf1-deficient mouse Schwann cells are angiogenic and invasiv... | KEEP AS NON CORE | Summary: Schwann-cell development is disrupted by NF1 loss because hyperactive RAS deregulates glial proliferation/differentiation; a downstream developmental phenotype. Reason: Developmental phenotype downstream of the RAS brake. |
| GO:0048485 sympathetic nervous system development | IMP PMID:7926784 Targeted disruption of the neurofibromatosis type-1 gene lea... | KEEP AS NON CORE | Summary: Sympathetic (neural-crest-derived) development is perturbed by elevated RAS in NF1-deficient cells, a downstream developmental phenotype. Reason: Neural-crest-derived developmental phenotype. |
| GO:0048745 smooth muscle tissue development | IMP PMID:7926784 Targeted disruption of the neurofibromatosis type-1 gene lea... | KEEP AS NON CORE | Summary: Smooth-muscle development, relevant to vascular phenotypes, is perturbed downstream of neurofibromin's RAS control. Reason: Tissue-development phenotype, IMP. |
| GO:0048844 artery morphogenesis | IMP PMID:7926784 Targeted disruption of the neurofibromatosis type-1 gene lea... | KEEP AS NON CORE | Summary: Artery morphogenesis is disrupted by NF1 loss through dysregulated RAS signalling in vascular cells; a downstream cardiovascular phenotype. Reason: Downstream vascular developmental phenotype. |
| GO:0005737 cytoplasm | IDA PMID:15133494 JCV T-antigen interacts with the neurofibromatosis type 2 ge... | KEEP AS NON CORE | Summary: Neurofibromin is a large cytoplasmic protein; the cytoplasm assignment is a generic compartment broader than the membrane-proximal site where it regulates RAS. Reason: Generic compartment; supportive but less informative than plasma-membrane localization. |
| GO:0007265 Ras protein signal transduction | IMP PMID:16906226 The neurofibromin GAP-related domain rescues endothelial but... | KEEP AS NON CORE | Summary: Neurofibromin participates in RAS signalling specifically as its negative regulator; the broad 'Ras protein signal transduction' term is less precise than the negative-regulation term. Reason: Subsumed by the more specific negative-regulation-of-Ras core term; kept as supporting context. |
| GO:0007507 heart development | IMP PMID:16906226 The neurofibromin GAP-related domain rescues endothelial but... | KEEP AS NON CORE | Summary: Nf1-null embryos show cardiovascular defects and mid-gestation lethality because controlled RAS/MAPK and PI3K signalling is required for cardiac morphogenesis. Reason: Downstream organ-development phenotype (well documented in mouse). |
| GO:0021510 spinal cord development | IMP PMID:16906226 The neurofibromin GAP-related domain rescues endothelial but... | KEEP AS NON CORE | Summary: Spinal cord development is affected by NF1 loss through dysregulated RAS signalling in neural progenitors. Reason: Region-specific CNS developmental phenotype. |
| GO:0030325 adrenal gland development | IMP PMID:16906226 The neurofibromin GAP-related domain rescues endothelial but... | KEEP AS NON CORE | Summary: Adrenal (neural-crest-derived) development is affected in Nf1 mutants through dysregulated RAS signalling; a downstream developmental phenotype. Reason: Organ-development phenotype, IMP. |
| GO:0045685 regulation of glial cell differentiation | IMP PMID:12904481 Aberrant growth and differentiation of oligodendrocyte proge... | KEEP AS NON CORE | Summary: Glial differentiation is steered by RAS-pathway tone, so its regulation is an indirect consequence of neurofibromin's RasGAP activity. Reason: Downstream glial regulation secondary to RAS control. |
| GO:0048485 sympathetic nervous system development | IMP PMID:16906226 The neurofibromin GAP-related domain rescues endothelial but... | KEEP AS NON CORE | Summary: Sympathetic (neural-crest-derived) development is perturbed by elevated RAS in NF1-deficient cells, a downstream developmental phenotype. Reason: Neural-crest-derived developmental phenotype. |
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