Mtor

UniProt ID: Q9JLN9
Organism: Mus musculus
Review Status: COMPLETE
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Gene Description

Mtor encodes mechanistic target of rapamycin, a large PI3K-related serine/threonine protein kinase. mTOR is the catalytic subunit of mTORC1 and mTORC2 complexes, integrating nutrient, growth-factor, energy, and stress inputs to regulate proximal outputs including translation, cell growth, autophagy, and AKT/PKC-family kinase signaling. Because mTOR is highly pleiotropic, tissue phenotypes and distal metabolic or developmental consequences are treated as non-core unless they directly describe TORC kinase signaling.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004674 protein serine/threonine kinase activity
IBA
GO_REF:0000033
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0038203 TORC2 signaling
IBA
GO_REF:0000033
ACCEPT
Summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0031932 TORC2 complex
IBA
GO_REF:0000033
ACCEPT
Summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
Reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0031931 TORC1 complex
IBA
GO_REF:0000033
ACCEPT
Summary: mTOR is the catalytic core of mTORC1 (with RPTOR and MLST8), the nutrient/growth-factor-responsive complex that drives anabolic growth at the lysosomal surface.
Reason: Core complex; mTOR is an obligate subunit of mTORC1 (IDA/ComplexPortal CPX-4473).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0038202 TORC1 signaling
IBA
GO_REF:0000033
ACCEPT
Summary: mTORC1 signaling—phosphorylation of S6K1, 4E-BP1 and ULK1 to drive translation/growth and suppress autophagy—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC1 signaling.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0016242 negative regulation of macroautophagy
IBA
GO_REF:0000033
ACCEPT
Summary: mTORC1 directly restrains macroautophagy by phosphorylating ULK1 and inhibiting the autophagy-initiation machinery when nutrients are abundant.
Reason: Core; ULK1-mediated suppression of macroautophagy by mTORC1 (IMP/IBA).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0000139 Golgi membrane
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: mTOR associates peripherally with the cytoplasmic face of Golgi membranes; a minor location versus lysosomal/plasma-membrane sites.
Reason: Secondary peripheral-membrane localization.
GO:0004674 protein serine/threonine kinase activity
IEA
GO_REF:0000120
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0004715 non-membrane spanning protein tyrosine kinase activity
IEA
GO_REF:0000003
REMOVE
Summary: Mislabels mTOR as a soluble tyrosine kinase; mTOR is a PIKK-family Ser/Thr kinase and any tyrosine activity is by-similarity speculation only.
Reason: IEA electronic mis-mapping inconsistent with mTOR's Ser/Thr kinase identity.
GO:0005634 nucleus
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: mTOR shuttles to the nucleus and accumulates there under hypoxia; a regulated secondary localization beyond its cytoplasmic membrane sites.
Reason: Regulated nuclear pool (EXP/IDA); secondary location.
GO:0005737 cytoplasm
IEA
GO_REF:0000120
ACCEPT
Summary: mTOR is a cytoplasmic kinase that shuttles among lysosomal, ER and plasma-membrane surfaces and the cytosol/nucleus; cytoplasmic localization is experimentally established.
Reason: Supported localization (EXP/ISS); mTOR carries out its kinase function in the cytoplasm.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0005741 mitochondrial outer membrane
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: mTOR has been localized to the mitochondrial outer membrane and senses osmotic stress via mitochondrial dysfunction; a peripheral secondary location.
Reason: Secondary localization (EXP) linked to stress sensing.
GO:0005765 lysosomal membrane
IEA
GO_REF:0000120
ACCEPT
Summary: mTORC1 is recruited to and activated on the cytosolic face of the lysosomal membrane by Rag-Ragulator and Rheb, the principal site where mTOR integrates nutrient and growth-factor signals.
Reason: Core localization for mTORC1 activation (UniProt: lysosome membrane, peripheral, cytoplasmic side).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0005789 endoplasmic reticulum membrane
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: mTORC2 signals at the cytoplasmic face of the ER membrane; a real secondary location for mTOR complexes.
Reason: Secondary membrane site for mTORC2.
GO:0005886 plasma membrane
IEA
GO_REF:0000120
KEEP AS NON CORE
Summary: mTORC2 is active at the plasma membrane where it phosphorylates AKT/PKC; a genuine secondary location for mTOR.
Reason: mTORC2 plasma-membrane site; secondary to lysosomal mTORC1.
GO:0016301 kinase activity
IEA
GO_REF:0000002
MARK AS OVER ANNOTATED
Summary: Uninformative top-level kinase term; mTOR's activity is precisely captured by protein serine/threonine kinase activity (GO:0004674).
Reason: Over-general MF superseded by the specific Ser/Thr kinase annotation.
GO:0016605 PML body
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: PML sequesters mTOR in nuclear PML bodies to repress mTORC1 (HIF1α translation control); a regulatory localization documented by IDA.
Reason: Regulatory nuclear-body localization (IDA).
Supporting Evidence:
UniProt:Q9JLN9
Nucleus, PML body
GO:0019216 regulation of lipid metabolic process
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: mTOR regulates lipid metabolism via SREBP1/LPIN1 and mTORC2 lipogenic outputs; a broad metabolic regulatory role downstream of the kinase.
Reason: Downstream metabolic regulation.
GO:0031346 positive regulation of cell projection organization
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: mTORC2 cytoskeletal control and mTORC1 translational control promote cell-projection/process formation; a downstream morphological output.
Reason: Downstream cytoskeletal/translational output.
GO:0044877 protein-containing complex binding
IEA
GO_REF:0000002
MARK AS OVER ANNOTATED
Summary: Non-specific complex-binding term that does not describe mTOR's defined role within mTORC1/mTORC2.
Reason: Generic binding term; superseded by complex annotations.
GO:0045335 phagocytic vesicle
IEA
GO_REF:0000120
KEEP AS NON CORE
Summary: mTOR localizes to phagosomes, relevant to phagosome maturation and innate-immune signaling; a peripheral compartment.
Reason: Secondary vesicular localization.
GO:0045792 negative regulation of cell size
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Captures contexts where mTOR loss/inhibition reduces cell size or where mTOR feedback limits growth; the directionality opposite to its dominant pro-growth role.
Reason: Context/loss-of-function readout of mTOR growth control.
GO:0048714 positive regulation of oligodendrocyte differentiation
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: mTOR signaling promotes oligodendrocyte differentiation and myelination programs; a downstream CNS differentiation role.
Reason: Downstream CNS differentiation effect (IMP).
GO:0050795 regulation of behavior
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Broad behavioral regulation arising from mTOR's neuronal translation/plasticity roles; a pleiotropic downstream phenotype.
Reason: Downstream pleiotropic behavioral role.
GO:0051155 positive regulation of striated muscle cell differentiation
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: mTOR supports striated-muscle differentiation via growth and translational programs; a downstream developmental output.
Reason: Downstream muscle differentiation effect.
GO:0051896 regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
IEA
GO_REF:0000117
ACCEPT
Summary: mTOR regulates PI3K-AKT signaling both as the mTORC2 AKT-kinase and via mTORC1 feedback (GRB10/IRS), placing it as a direct regulator of this pathway.
Reason: Core; mTOR directly sets AKT activity through mTORC2 and mTORC1 feedback.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0106310 protein serine kinase activity
IEA
GO_REF:0000116
ACCEPT
Summary: Captures mTOR phosphorylation of serine residues (e.g. AKT Ser473, 4E-BP1 serines), a component of its EC 2.7.11.1 serine/threonine kinase activity.
Reason: Core MF consistent with experimental serine-phosphorylation of mTOR substrates.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0120035 regulation of plasma membrane bounded cell projection organization
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: mTOR signaling shapes cell projections (neurites, protrusions) via cytoskeletal and translational outputs; a downstream morphogenetic role.
Reason: Downstream morphogenetic effect of mTOR.
GO:0005515 protein binding
IPI
PMID:12150926
Raptor, a binding partner of target of rapamycin (TOR), medi...
MARK AS OVER ANNOTATED
Summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
Reason: Generic binding term per curation guidelines; not informative.
GO:0005515 protein binding
IPI
PMID:16541103
mTOR-dependent stimulation of the association of eIF4G and e...
MARK AS OVER ANNOTATED
Summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
Reason: Generic binding term per curation guidelines; not informative.
GO:0005515 protein binding
IPI
PMID:18046414
mTOR controls mitochondrial oxidative function through a YY1...
MARK AS OVER ANNOTATED
Summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
Reason: Generic binding term per curation guidelines; not informative.
GO:0005515 protein binding
IPI
PMID:18566586
The mammalian target of rapamycin complex 2 controls folding...
MARK AS OVER ANNOTATED
Summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
Reason: Generic binding term per curation guidelines; not informative.
GO:0005515 protein binding
IPI
PMID:18664580
mTORC1 promotes survival through translational control of Mc...
MARK AS OVER ANNOTATED
Summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
Reason: Generic binding term per curation guidelines; not informative.
GO:0005515 protein binding
IPI
PMID:20801936
Tel2 structure and function in the Hsp90-dependent maturatio...
MARK AS OVER ANNOTATED
Summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
Reason: Generic binding term per curation guidelines; not informative.
GO:0005515 protein binding
IPI
PMID:21045808
mTORC2 can associate with ribosomes to promote cotranslation...
MARK AS OVER ANNOTATED
Summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
Reason: Generic binding term per curation guidelines; not informative.
GO:0005515 protein binding
IPI
PMID:22307628
Glycerolipid signals alter mTOR complex 2 (mTORC2) to dimini...
MARK AS OVER ANNOTATED
Summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
Reason: Generic binding term per curation guidelines; not informative.
GO:0005515 protein binding
IPI
PMID:23966835
Reduced juvenile long-term depression in tuberous sclerosis ...
MARK AS OVER ANNOTATED
Summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
Reason: Generic binding term per curation guidelines; not informative.
GO:0005515 protein binding
IPI
PMID:24036451
PIH1D1 interacts with mTOR complex 1 and enhances ribosome R...
MARK AS OVER ANNOTATED
Summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
Reason: Generic binding term per curation guidelines; not informative.
GO:0005515 protein binding
IPI
PMID:25686248
Huntingtin functions as a scaffold for selective macroautoph...
MARK AS OVER ANNOTATED
Summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
Reason: Generic binding term per curation guidelines; not informative.
GO:0005515 protein binding
IPI
PMID:25980607
Phosphorylation of ULK1 by AMPK regulates translocation of U...
MARK AS OVER ANNOTATED
Summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
Reason: Generic binding term per curation guidelines; not informative.
GO:0000139 Golgi membrane
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTOR associates peripherally with the cytoplasmic face of Golgi membranes; a minor location versus lysosomal/plasma-membrane sites.
Reason: Secondary peripheral-membrane localization.
GO:0000822 inositol hexakisphosphate binding
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: InsP6 is a structural cofactor reported to stabilize the mTOR kinase domain; a structural-ligand feature rather than the catalytic activity.
Reason: Structural cofactor binding; non-core.
GO:0001002 RNA polymerase III type 1 promoter sequence-specific DNA binding
ISO
GO_REF:0000119
REMOVE
Summary: mTOR is a cytoplasmic Ser/Thr kinase, not a sequence-specific DNA-binding protein; it regulates Pol III indirectly via MAF1, so direct promoter DNA binding is an erroneous electronic inference.
Reason: IEA/ISO electronic mis-assignment; mTOR does not directly bind promoter DNA.
GO:0001003 RNA polymerase III type 2 promoter sequence-specific DNA binding
ISO
GO_REF:0000119
REMOVE
Summary: mTOR does not bind Pol III promoter DNA directly; its effect on Pol III is via MAF1 phosphorylation, making this DNA-binding MF an electronic error.
Reason: IEA/ISO electronic mis-assignment inconsistent with a kinase.
GO:0001006 RNA polymerase III type 3 promoter sequence-specific DNA binding
ISO
GO_REF:0000119
REMOVE
Summary: Sequence-specific promoter DNA binding is not a function of the mTOR kinase; Pol III control is indirect via MAF1, so this is an erroneous propagation.
Reason: IEA/ISO electronic mis-assignment inconsistent with a kinase.
GO:0001156 TFIIIC-class transcription factor complex binding
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Reflects mTOR's engagement with the Pol III transcription machinery to control tRNA gene transcription; an interaction supporting ribosome biogenesis.
Reason: Interaction supporting Pol III/ribosome biogenesis output.
GO:0001558 regulation of cell growth
ISO
GO_REF:0000119
ACCEPT
Summary: mTOR sets cell-growth rate by gating protein/lipid/nucleotide synthesis through mTORC1, making it a central regulator of cell growth.
Reason: Core mTORC1 output.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0001933 negative regulation of protein phosphorylation
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR can lower phosphorylation of some targets (e.g. via GRB10/IRS feedback dampening insulin signaling); a downstream regulatory effect.
Reason: Indirect feedback effect downstream of core mTOR signaling.
GO:0001938 positive regulation of endothelial cell proliferation
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR promotes endothelial proliferation in angiogenesis through growth/translation; a downstream vascular phenotype.
Reason: Downstream proliferative effect (vascular).
GO:0004672 protein kinase activity
ISO
GO_REF:0000119
MODIFY
Summary: mTOR is specifically a serine/threonine protein kinase; the generic 'protein kinase activity' parent should be replaced by the specific Ser/Thr child term.
Reason: Generic parent where the specific Ser/Thr kinase child (GO:0004674) is the correct MF.
GO:0004674 protein serine/threonine kinase activity
ISO
GO_REF:0000119
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0004674 protein serine/threonine kinase activity
ISO
GO_REF:0000096
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0004713 protein tyrosine kinase activity
ISO
GO_REF:0000119
REMOVE
Summary: mTOR is a Ser/Thr (PIKK-family) kinase; the tyrosine-kinase EC 2.7.10.2 activity is only an unproven by-similarity inference and is not an established function of mouse mTOR.
Reason: IEA/ISO/ISS by-similarity only; contradicted by mTOR's Ser/Thr (PIKK) catalytic identity.
GO:0005635 nuclear envelope
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Nuclear-envelope association (e.g. via PLPP7/NET39) consistent with mTOR's nucleocytoplasmic shuttling.
Reason: Secondary localization tied to nuclear interactions.
GO:0005737 cytoplasm
ISO
GO_REF:0000119
ACCEPT
Summary: mTOR is a cytoplasmic kinase that shuttles among lysosomal, ER and plasma-membrane surfaces and the cytosol/nucleus; cytoplasmic localization is experimentally established.
Reason: Supported localization (EXP/ISS); mTOR carries out its kinase function in the cytoplasm.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0005741 mitochondrial outer membrane
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTOR has been localized to the mitochondrial outer membrane and senses osmotic stress via mitochondrial dysfunction; a peripheral secondary location.
Reason: Secondary localization (EXP) linked to stress sensing.
GO:0005764 lysosome
ISO
GO_REF:0000119
MODIFY
Summary: mTOR acts at the lysosomal membrane (cytoplasmic face), not in the lysosomal lumen; the membrane component is the precise localization.
Reason: Over-general; lysosomal membrane (GO:0005765) is the specific compartment for mTORC1.
Proposed replacements: lysosomal membrane
Supporting Evidence:
UniProt:Q9JLN9
Lysosome membrane; Peripheral membrane protein; Cytoplasmic side
GO:0005765 lysosomal membrane
ISO
GO_REF:0000119
ACCEPT
Summary: mTORC1 is recruited to and activated on the cytosolic face of the lysosomal membrane by Rag-Ragulator and Rheb, the principal site where mTOR integrates nutrient and growth-factor signals.
Reason: Core localization for mTORC1 activation (UniProt: lysosome membrane, peripheral, cytoplasmic side).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0005783 endoplasmic reticulum
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTORC2 is active at the ER membrane; ER localization is a genuine but secondary site relative to the lysosomal mTORC1 hub.
Reason: Secondary localization (mTORC2 at ER).
GO:0005789 endoplasmic reticulum membrane
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTORC2 signals at the cytoplasmic face of the ER membrane; a real secondary location for mTOR complexes.
Reason: Secondary membrane site for mTORC2.
GO:0005794 Golgi apparatus
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Reported Golgi-membrane pool of mTOR (peripheral, cytoplasmic side); a secondary location relative to the lysosomal site of mTORC1 activation.
Reason: Secondary localization by similarity.
GO:0005829 cytosol
ISO
GO_REF:0000119
ACCEPT
Summary: Soluble cytosolic pool of mTOR/mTOR complexes consistent with its peripheral-membrane association and shuttling behavior.
Reason: Supported localization (IDA) for cytoplasmic mTOR.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0005886 plasma membrane
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTORC2 is active at the plasma membrane where it phosphorylates AKT/PKC; a genuine secondary location for mTOR.
Reason: mTORC2 plasma-membrane site; secondary to lysosomal mTORC1.
GO:0005979 regulation of glycogen biosynthetic process
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Via AKT/GSK3 downstream of mTORC2, mTOR signaling modulates glycogen synthesis; an indirect metabolic effect.
Reason: Indirect downstream metabolic regulation.
GO:0006109 regulation of carbohydrate metabolic process
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR shapes carbohydrate handling through AKT-dependent glucose metabolism and glycolytic gene programs; a broad downstream metabolic role.
Reason: Downstream metabolic regulation via AKT/mTORC1.
GO:0006468 protein phosphorylation
ISO
GO_REF:0000096
ACCEPT
Summary: mTOR catalyzes transfer of phosphate to its protein substrates within mTORC1 and mTORC2, the molecular event underlying all of its signaling outputs.
Reason: Core catalytic process for a protein kinase; ISO but biologically definitive for mTOR.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0007616 long-term memory
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTORC1-dependent protein synthesis is required for long-term memory consolidation; a downstream cognitive phenotype.
Reason: Downstream cognitive output of mTOR translation control.
GO:0008361 regulation of cell size
ISO
GO_REF:0000119
ACCEPT
Summary: Through mTORC1-driven biosynthesis, mTOR controls attainment of cell size; loss of mTOR reduces cell size.
Reason: Core; cell size is a direct readout of mTORC1 anabolic activity.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0008542 visual learning
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR-dependent synaptic plasticity underlies visual learning; a downstream behavioral phenotype.
Reason: Downstream behavioral output of mTOR.
GO:0009267 cellular response to starvation
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Starvation suppresses mTORC1, de-repressing autophagy; mTOR is the switch responding to nutrient deprivation.
Reason: Upstream starvation input gating mTORC1.
GO:0010507 negative regulation of autophagy
ISO
GO_REF:0000096
ACCEPT
Summary: Under nutrient sufficiency mTORC1 phosphorylates ULK1 (Ser758) and other autophagy regulators to suppress autophagy; this inhibition is a core proximal mTOR output.
Reason: Core; direct ULK1 phosphorylation by mTORC1 (IMP-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0010507 negative regulation of autophagy
ISO
GO_REF:0000119
ACCEPT
Summary: Under nutrient sufficiency mTORC1 phosphorylates ULK1 (Ser758) and other autophagy regulators to suppress autophagy; this inhibition is a core proximal mTOR output.
Reason: Core; direct ULK1 phosphorylation by mTORC1 (IMP-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0010718 positive regulation of epithelial to mesenchymal transition
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTOR signaling (notably mTORC2) can promote EMT during development and cancer; a downstream cell-fate/motility effect.
Reason: Downstream EMT-promoting effect of mTOR.
GO:0010976 positive regulation of neuron projection development
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTORC1/mTORC2 promote axon/dendrite outgrowth through translation and cytoskeletal regulation; a downstream neuronal output.
Reason: Downstream neurite-growth effect of mTOR.
GO:0012505 endomembrane system
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Broad endomembrane localization reflecting mTOR's peripheral association with lysosomal/ER/Golgi membranes.
Reason: General localization subsumed by specific membrane terms.
GO:0014042 positive regulation of neuron maturation
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR signaling promotes neuronal maturation via translational and growth control; a downstream developmental role.
Reason: Downstream neurodevelopmental effect of mTOR.
GO:0014736 negative regulation of muscle atrophy
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Active mTORC1 opposes muscle atrophy by sustaining protein synthesis and suppressing autophagy/proteolysis.
Reason: Downstream anti-atrophy effect of mTORC1.
GO:0016020 membrane
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Generic membrane association consistent with mTOR being a peripheral membrane protein on several organelles.
Reason: Generic CC subsumed by specific membrane terms.
GO:0019901 protein kinase binding
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR binds kinase substrates/regulators (e.g. AKT, S6K, ULK1); informative as interaction context but secondary to its own kinase activity.
Reason: Partner-binding adjunct to mTOR's catalytic role.
GO:0019904 protein domain specific binding
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR engages partner domains (e.g. FRB-FKBP12/rapamycin, RICTOR/RAPTOR interfaces); contextually useful but not the core function.
Reason: Interaction detail secondary to core kinase/scaffold role.
GO:0021510 spinal cord development
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR-dependent growth and patterning contribute to spinal cord development; a downstream developmental phenotype.
Reason: Downstream developmental role of mTOR.
GO:0030425 dendrite
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Dendritic localization of mTOR supports local translation underlying synaptic plasticity; a neuron-specific secondary site.
Reason: Neuronal localization linked to local translation.
GO:0031397 negative regulation of protein ubiquitination
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR phosphorylation can shield substrates from ubiquitination (e.g. AMBRA1-ULK1 axis); a downstream regulatory effect.
Reason: Downstream effect on substrate ubiquitination.
GO:0031667 response to nutrient levels
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTOR responds to organismal/cellular nutrient levels to coordinate growth and metabolism via mTORC1.
Reason: Upstream nutrient input to mTORC1.
GO:0031669 cellular response to nutrient levels
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Nutrient abundance dictates mTORC1 lysosomal recruitment and activity; mTOR is the effector translating nutrient state into growth decisions.
Reason: Upstream nutrient input to mTORC1.
GO:0031670 cellular response to nutrient
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTORC1 integrates general nutrient availability to switch between anabolism and catabolism; mTOR is the central responder.
Reason: Upstream nutrient input gating mTORC1.
GO:0031929 TOR signaling
ISO
GO_REF:0000119
ACCEPT
Summary: mTOR is the namesake kinase of TOR signaling, transducing nutrient/growth-factor inputs into control of growth, translation and autophagy via mTORC1 and mTORC2.
Reason: Core pathway directly executed by mTOR (IMP/IGI).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0031931 TORC1 complex
ISO
GO_REF:0000096
ACCEPT
Summary: mTOR is the catalytic core of mTORC1 (with RPTOR and MLST8), the nutrient/growth-factor-responsive complex that drives anabolic growth at the lysosomal surface.
Reason: Core complex; mTOR is an obligate subunit of mTORC1 (IDA/ComplexPortal CPX-4473).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0031931 TORC1 complex
ISO
GO_REF:0000119
ACCEPT
Summary: mTOR is the catalytic core of mTORC1 (with RPTOR and MLST8), the nutrient/growth-factor-responsive complex that drives anabolic growth at the lysosomal surface.
Reason: Core complex; mTOR is an obligate subunit of mTORC1 (IDA/ComplexPortal CPX-4473).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0031932 TORC2 complex
ISO
GO_REF:0000119
ACCEPT
Summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
Reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0031998 regulation of fatty acid beta-oxidation
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTORC1 suppresses fatty-acid oxidation when promoting anabolism (e.g. via PPAR/PGC-1 control); a downstream metabolic switch.
Reason: Downstream metabolic regulation of mTORC1.
GO:0032095 regulation of response to food
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Hypothalamic mTOR signaling links nutrient/energy status to feeding responses; a downstream physiological role.
Reason: Downstream physiological response of nutrient-sensing mTOR.
GO:0032869 cellular response to insulin stimulus
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Insulin activates mTORC1/mTORC2 through PI3K-AKT-TSC-Rheb; mTOR is the central effector of the insulin growth-factor response.
Reason: Upstream growth-factor input to mTOR.
GO:0032956 regulation of actin cytoskeleton organization
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTORC2 regulates the actin cytoskeleton through PKC and Rho/Rac GTPases; a characteristic downstream output of mTOR's mTORC2 activity.
Reason: Downstream mTORC2 cytoskeletal output.
GO:0032991 protein-containing complex
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Generic 'part of a protein complex' statement; mTOR's specific TORC1/TORC2 complex memberships are the informative annotations.
Reason: Generic CC subsumed by TORC1/TORC2 complex terms.
GO:0034198 cellular response to amino acid starvation
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTORC1 is inactivated upon amino-acid withdrawal (loss of Rag-Ragulator lysosomal recruitment); mTOR is the sensor-effector responding to this input.
Reason: Upstream nutrient input gating core mTORC1 activity.
GO:0035176 social behavior
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR pathway dysregulation alters social behavior (relevant to autism-spectrum models); a downstream behavioral phenotype.
Reason: Downstream behavioral phenotype of mTOR.
GO:0038202 TORC1 signaling
ISO
GO_REF:0000119
ACCEPT
Summary: mTORC1 signaling—phosphorylation of S6K1, 4E-BP1 and ULK1 to drive translation/growth and suppress autophagy—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC1 signaling.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0038203 TORC2 signaling
ISO
GO_REF:0000119
ACCEPT
Summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0042220 response to cocaine
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR-dependent synaptic plasticity mediates neuronal responses to cocaine; a downstream pharmacological/behavioral phenotype.
Reason: Downstream behavioral response via mTOR plasticity.
GO:0042802 identical protein binding
ISO
GO_REF:0000119
MARK AS OVER ANNOTATED
Summary: Generic self-association term; mTOR's functional dimerization is better captured by the TORC1/TORC2 complex annotations.
Reason: Uninformative generic MF.
GO:0043022 ribosome binding
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTORC2 associates with ribosomes to cotranslationally phosphorylate nascent AKT, and mTORC1 couples to translation; a functionally relevant but ancillary interaction.
Reason: Supports cotranslational substrate phosphorylation; secondary to core kinase role.
GO:0043025 neuronal cell body
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Somatic localization of mTOR in neurons consistent with its role in neuronal growth and translation.
Reason: Neuron-specific secondary localization.
GO:0043200 response to amino acid
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Amino-acid availability is a principal cue activating mTORC1; mTOR senses this through the lysosomal Rag machinery.
Reason: Upstream nutrient cue for mTORC1.
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction
ISO
GO_REF:0000119
ACCEPT
Summary: As the mTORC2 kinase, mTOR phosphorylates AKT (PKB) Ser473, a defining step of PI3K-AKT signal transduction directly executed by mTOR.
Reason: Core; mTORC2 is the AKT Ser473 kinase linking PI3K to AKT activation.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0043525 positive regulation of neuron apoptotic process
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: In some neuronal contexts mTOR signaling promotes apoptosis; a context-dependent downstream survival effect.
Reason: Context-dependent downstream neuronal effect.
GO:0043610 regulation of carbohydrate utilization
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR/AKT signaling tunes cellular glucose utilization in response to growth-factor and nutrient state; a downstream metabolic effect.
Reason: Downstream metabolic effect of mTOR signaling.
GO:0045335 phagocytic vesicle
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTOR localizes to phagosomes, relevant to phagosome maturation and innate-immune signaling; a peripheral compartment.
Reason: Secondary vesicular localization.
GO:0045429 positive regulation of nitric oxide biosynthetic process
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR/AKT signaling can promote eNOS-dependent NO production in endothelium; an indirect downstream metabolic effect.
Reason: Indirect downstream effect of mTOR-AKT signaling.
GO:0045727 positive regulation of translation
ISO
GO_REF:0000096
ACCEPT
Summary: mTORC1 promotes cap-dependent translation by phosphorylating 4E-BP1 (releasing eIF4E) and activating S6K1/2, a core anabolic output of mTOR.
Reason: Core; mTORC1 directly drives translation via 4E-BP1/S6K.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0045727 positive regulation of translation
ISO
GO_REF:0000119
ACCEPT
Summary: mTORC1 promotes cap-dependent translation by phosphorylating 4E-BP1 (releasing eIF4E) and activating S6K1/2, a core anabolic output of mTOR.
Reason: Core; mTORC1 directly drives translation via 4E-BP1/S6K.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0045945 positive regulation of transcription by RNA polymerase III
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTORC1 activates Pol III transcription by phosphorylating/inhibiting the repressor MAF1, boosting tRNA/5S rRNA synthesis; downstream of mTOR.
Reason: Downstream of mTORC1 (MAF1 phosphorylation).
GO:0045948 positive regulation of translational initiation
ISO
GO_REF:0000119
ACCEPT
Summary: By phosphorylating 4E-BP1 mTORC1 frees eIF4E and stimulates assembly of the cap-binding initiation complex, directly promoting translational initiation.
Reason: Core; 4E-BP1 phosphorylation by mTORC1 controls initiation.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0046777 protein autophosphorylation
ISO
GO_REF:0000096
ACCEPT
Summary: mTOR autophosphorylates (e.g. Ser2481) when assembled in mTORC1 or mTORC2, a hallmark of the active kinase used to report complex integrity.
Reason: Core intrinsic kinase activity; documented mTOR autophosphorylation.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0046889 positive regulation of lipid biosynthetic process
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTOR drives lipogenesis through SREBP1 and LPIN1 (mTORC1) and lipid synthesis programs (mTORC2); a major anabolic output downstream of mTOR.
Reason: Downstream lipogenic program of mTOR signaling.
GO:0048255 mRNA stabilization
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTORC2 phosphorylation of IGF2BP1/IMP1 promotes target mRNA stability/translation; a downstream RNA-regulatory effect of mTOR.
Reason: Downstream effect via mTORC2 substrate phosphorylation.
GO:0048661 positive regulation of smooth muscle cell proliferation
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR drives smooth-muscle proliferation (e.g. vascular remodeling); a downstream proliferative phenotype.
Reason: Downstream proliferative effect.
GO:0048714 positive regulation of oligodendrocyte differentiation
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR signaling promotes oligodendrocyte differentiation and myelination programs; a downstream CNS differentiation role.
Reason: Downstream CNS differentiation effect (IMP).
GO:0050769 positive regulation of neurogenesis
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR-driven growth/translation supports neural progenitor proliferation and neurogenesis; a downstream developmental output.
Reason: Downstream neurodevelopmental effect of mTOR.
GO:0051219 phosphoprotein binding
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTOR/its complexes recognize phosphorylated regulators (e.g. via SIN1/RPTOR); an interaction feature, not the core activity.
Reason: Partner recognition adjunct to core function.
GO:0051549 positive regulation of keratinocyte migration
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTOR signaling promotes keratinocyte migration in wound healing through its cytoskeletal/growth outputs.
Reason: Downstream motility/wound-healing effect.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
ISO
GO_REF:0000096
ACCEPT
Summary: mTORC2-mediated AKT hydrophobic-motif phosphorylation positively regulates PI3K-AKT signaling, a direct proximal output of mTOR kinase activity.
Reason: Core; mTORC2 directly activates AKT via Ser473 phosphorylation.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0060135 maternal process involved in female pregnancy
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR nutrient sensing in maternal/placental tissues supports pregnancy-associated growth processes; a downstream physiological role.
Reason: Downstream physiological role of mTOR sensing.
GO:0060252 positive regulation of glial cell proliferation
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR's growth/proliferative outputs drive glial cell proliferation; a downstream CNS phenotype.
Reason: Downstream proliferative effect in glia.
GO:0060999 positive regulation of dendritic spine development
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR-dependent local translation supports dendritic-spine formation/maturation underlying synaptic plasticity.
Reason: Downstream synaptic-plasticity effect of mTOR.
GO:0061051 positive regulation of cell growth involved in cardiac muscle cell development
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTORC1-driven growth contributes to cardiomyocyte hypertrophic growth during heart development; a tissue-specific instance of mTOR's growth output.
Reason: Tissue-specific instance of mTOR growth control.
GO:0061431 cellular response to methionine
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Methionine/SAM availability signals to mTORC1 (e.g. via SAMTOR); mTOR responds to set anabolic activity.
Reason: Specific amino-acid input to mTORC1.
GO:0062027 positive regulation of SCF-dependent proteasomal ubiquitin-dependent catabolic process
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTOR phosphorylation can promote SCF-mediated substrate degradation (IRS1 turnover), feeding back on insulin signaling.
Reason: Downstream proteostatic feedback of mTOR signaling.
GO:0071230 cellular response to amino acid stimulus
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Amino acids activate mTORC1 via Rag GTPases/Ragulator and lysosomal recruitment; mTOR responds to this stimulus to drive growth.
Reason: Upstream nutrient input to mTORC1.
GO:0071233 cellular response to L-leucine
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Leucine is a key amino acid activating mTORC1 (via Sestrin2/leucyl-tRNA pathways and Rag GTPases); mTOR is the responding effector.
Reason: Specific amino-acid input to mTORC1.
GO:0090335 regulation of brown fat cell differentiation
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR (notably an FLCN-dependent non-canonical mTORC1 axis) regulates adipose browning/brown-fat differentiation; a tissue-level downstream role.
Reason: Downstream tissue differentiation controlled by mTOR.
GO:0098978 glutamatergic synapse
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Synaptic mTOR pool supports activity-dependent local translation at glutamatergic synapses; a specialized neuronal localization.
Reason: Neuronal-synapse localization.
GO:0099524 postsynaptic cytosol
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Postsynaptic cytosolic mTOR participates in local translational control of synaptic plasticity.
Reason: Neuronal-synapse localization.
GO:0099547 regulation of translation at synapse, modulating synaptic transmission
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTORC1-dependent local dendritic translation supports synaptic plasticity; a neuron-specific downstream output of mTOR.
Reason: Downstream neuronal translation control by mTOR.
GO:0106310 protein serine kinase activity
ISO
GO_REF:0000096
ACCEPT
Summary: Captures mTOR phosphorylation of serine residues (e.g. AKT Ser473, 4E-BP1 serines), a component of its EC 2.7.11.1 serine/threonine kinase activity.
Reason: Core MF consistent with experimental serine-phosphorylation of mTOR substrates.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0106310 protein serine kinase activity
ISO
GO_REF:0000119
ACCEPT
Summary: Captures mTOR phosphorylation of serine residues (e.g. AKT Ser473, 4E-BP1 serines), a component of its EC 2.7.11.1 serine/threonine kinase activity.
Reason: Core MF consistent with experimental serine-phosphorylation of mTOR substrates.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:1900181 negative regulation of protein localization to nucleus
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Active mTORC1 phosphorylates TFEB/TFE3 to retain them in the cytosol, preventing their nuclear entry; a specific mechanistic downstream effect.
Reason: Downstream MiT/TFE cytosolic-retention effect of mTORC1.
GO:1901838 positive regulation of transcription of nucleolar large rRNA by RNA polymerase I
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTORC1 promotes rRNA synthesis (Pol I) to support ribosome biogenesis, a downstream anabolic output of mTOR.
Reason: Downstream ribosome-biogenesis output of mTORC1.
GO:1903691 positive regulation of wound healing, spreading of epidermal cells
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTOR-dependent migration/proliferation of epidermal cells supports wound re-epithelialization; a downstream tissue process.
Reason: Downstream wound-healing process.
GO:1904000 positive regulation of eating behavior
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Hypothalamic mTORC1 activity modulates appetite/food intake; a downstream behavioral output of mTOR nutrient sensing.
Reason: Downstream behavioral effect of mTOR signaling.
GO:1904037 positive regulation of epithelial cell apoptotic process
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: In some contexts mTOR signaling promotes epithelial apoptosis; a context-dependent downstream survival effect.
Reason: Context-dependent downstream apoptotic effect.
GO:1904056 positive regulation of cholangiocyte proliferation
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR signaling promotes cholangiocyte (bile-duct epithelial) proliferation; a downstream hepatic phenotype.
Reason: Downstream proliferative effect (liver).
GO:1904193 negative regulation of cholangiocyte apoptotic process
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR/AKT survival signaling suppresses cholangiocyte apoptosis; a downstream pro-survival phenotype.
Reason: Downstream pro-survival effect of mTOR.
GO:1904197 positive regulation of granulosa cell proliferation
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR supports ovarian granulosa-cell proliferation during follicle growth; a downstream tissue phenotype.
Reason: Downstream proliferative effect (ovary).
GO:1904206 positive regulation of skeletal muscle hypertrophy
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTORC1 drives skeletal-muscle hypertrophy by stimulating protein synthesis; a tissue-specific instance of mTOR's growth output.
Reason: Downstream muscle-growth output of mTORC1.
GO:1904213 negative regulation of iodide transmembrane transport
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: mTOR signaling can suppress thyroid iodide uptake (NIS regulation); a downstream tissue-specific physiological effect.
Reason: Downstream physiological effect of mTOR.
GO:1905671 regulation of lysosome organization
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Via TFEB/TFE3 phosphorylation mTORC1 regulates lysosomal gene programs and organelle homeostasis.
Reason: Downstream MiT/TFE-mediated effect of mTORC1.
GO:1905672 negative regulation of lysosome organization
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Active mTORC1 phosphorylates TFEB/TFE3 to keep them cytosolic, suppressing lysosomal/autophagy gene expression and biogenesis.
Reason: Downstream MiT/TFE inhibition by mTORC1.
GO:1990253 cellular response to leucine starvation
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Leucine withdrawal inactivates mTORC1; mTOR is the kinase whose activity drops in response.
Reason: Upstream nutrient input to mTORC1.
GO:2000060 positive regulation of ubiquitin-dependent protein catabolic process
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTOR-directed phosphorylation can mark substrates for ubiquitin-dependent degradation; a downstream proteostatic effect.
Reason: Downstream proteostatic effect of mTOR signaling.
GO:2000774 positive regulation of cellular senescence
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Hyperactive mTOR drives geroconversion/cellular senescence (the basis of rapamycin's anti-aging effect); a downstream phenotype.
Reason: Downstream aging-related effect of mTOR.
GO:2000785 regulation of autophagosome assembly
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTORC1 negatively regulates autophagosome assembly via ULK1; a specific facet of its autophagy-suppressive output.
Reason: Downstream autophagy regulation by mTORC1.
GO:0000822 inositol hexakisphosphate binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: InsP6 is a structural cofactor reported to stabilize the mTOR kinase domain; a structural-ligand feature rather than the catalytic activity.
Reason: Structural cofactor binding; non-core.
GO:0001002 RNA polymerase III type 1 promoter sequence-specific DNA binding
IEA
GO_REF:0000107
REMOVE
Summary: mTOR is a cytoplasmic Ser/Thr kinase, not a sequence-specific DNA-binding protein; it regulates Pol III indirectly via MAF1, so direct promoter DNA binding is an erroneous electronic inference.
Reason: IEA/ISO electronic mis-assignment; mTOR does not directly bind promoter DNA.
GO:0001003 RNA polymerase III type 2 promoter sequence-specific DNA binding
IEA
GO_REF:0000107
REMOVE
Summary: mTOR does not bind Pol III promoter DNA directly; its effect on Pol III is via MAF1 phosphorylation, making this DNA-binding MF an electronic error.
Reason: IEA/ISO electronic mis-assignment inconsistent with a kinase.
GO:0001006 RNA polymerase III type 3 promoter sequence-specific DNA binding
IEA
GO_REF:0000107
REMOVE
Summary: Sequence-specific promoter DNA binding is not a function of the mTOR kinase; Pol III control is indirect via MAF1, so this is an erroneous propagation.
Reason: IEA/ISO electronic mis-assignment inconsistent with a kinase.
GO:0001156 TFIIIC-class transcription factor complex binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Reflects mTOR's engagement with the Pol III transcription machinery to control tRNA gene transcription; an interaction supporting ribosome biogenesis.
Reason: Interaction supporting Pol III/ribosome biogenesis output.
GO:0001558 regulation of cell growth
IEA
GO_REF:0000107
ACCEPT
Summary: mTOR sets cell-growth rate by gating protein/lipid/nucleotide synthesis through mTORC1, making it a central regulator of cell growth.
Reason: Core mTORC1 output.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0004672 protein kinase activity
IEA
GO_REF:0000107
MODIFY
Summary: mTOR is specifically a serine/threonine protein kinase; the generic 'protein kinase activity' parent should be replaced by the specific Ser/Thr child term.
Reason: Generic parent where the specific Ser/Thr kinase child (GO:0004674) is the correct MF.
GO:0004713 protein tyrosine kinase activity
IEA
GO_REF:0000120
REMOVE
Summary: mTOR is a Ser/Thr (PIKK-family) kinase; the tyrosine-kinase EC 2.7.10.2 activity is only an unproven by-similarity inference and is not an established function of mouse mTOR.
Reason: IEA/ISO/ISS by-similarity only; contradicted by mTOR's Ser/Thr (PIKK) catalytic identity.
GO:0005635 nuclear envelope
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Nuclear-envelope association (e.g. via PLPP7/NET39) consistent with mTOR's nucleocytoplasmic shuttling.
Reason: Secondary localization tied to nuclear interactions.
GO:0005764 lysosome
IEA
GO_REF:0000107
MODIFY
Summary: mTOR acts at the lysosomal membrane (cytoplasmic face), not in the lysosomal lumen; the membrane component is the precise localization.
Reason: Over-general; lysosomal membrane (GO:0005765) is the specific compartment for mTORC1.
Proposed replacements: lysosomal membrane
Supporting Evidence:
UniProt:Q9JLN9
Lysosome membrane; Peripheral membrane protein; Cytoplasmic side
GO:0005783 endoplasmic reticulum
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: mTORC2 is active at the ER membrane; ER localization is a genuine but secondary site relative to the lysosomal mTORC1 hub.
Reason: Secondary localization (mTORC2 at ER).
GO:0005794 Golgi apparatus
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Reported Golgi-membrane pool of mTOR (peripheral, cytoplasmic side); a secondary location relative to the lysosomal site of mTORC1 activation.
Reason: Secondary localization by similarity.
GO:0005829 cytosol
IEA
GO_REF:0000120
ACCEPT
Summary: Soluble cytosolic pool of mTOR/mTOR complexes consistent with its peripheral-membrane association and shuttling behavior.
Reason: Supported localization (IDA) for cytoplasmic mTOR.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0008361 regulation of cell size
IEA
GO_REF:0000107
ACCEPT
Summary: Through mTORC1-driven biosynthesis, mTOR controls attainment of cell size; loss of mTOR reduces cell size.
Reason: Core; cell size is a direct readout of mTORC1 anabolic activity.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0009267 cellular response to starvation
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Starvation suppresses mTORC1, de-repressing autophagy; mTOR is the switch responding to nutrient deprivation.
Reason: Upstream starvation input gating mTORC1.
GO:0010507 negative regulation of autophagy
IEA
GO_REF:0000120
ACCEPT
Summary: Under nutrient sufficiency mTORC1 phosphorylates ULK1 (Ser758) and other autophagy regulators to suppress autophagy; this inhibition is a core proximal mTOR output.
Reason: Core; direct ULK1 phosphorylation by mTORC1 (IMP-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0010718 positive regulation of epithelial to mesenchymal transition
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: mTOR signaling (notably mTORC2) can promote EMT during development and cancer; a downstream cell-fate/motility effect.
Reason: Downstream EMT-promoting effect of mTOR.
GO:0012505 endomembrane system
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Broad endomembrane localization reflecting mTOR's peripheral association with lysosomal/ER/Golgi membranes.
Reason: General localization subsumed by specific membrane terms.
GO:0016020 membrane
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Generic membrane association consistent with mTOR being a peripheral membrane protein on several organelles.
Reason: Generic CC subsumed by specific membrane terms.
GO:0031667 response to nutrient levels
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: mTOR responds to organismal/cellular nutrient levels to coordinate growth and metabolism via mTORC1.
Reason: Upstream nutrient input to mTORC1.
GO:0031669 cellular response to nutrient levels
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Nutrient abundance dictates mTORC1 lysosomal recruitment and activity; mTOR is the effector translating nutrient state into growth decisions.
Reason: Upstream nutrient input to mTORC1.
GO:0031670 cellular response to nutrient
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: mTORC1 integrates general nutrient availability to switch between anabolism and catabolism; mTOR is the central responder.
Reason: Upstream nutrient input gating mTORC1.
GO:0031929 TOR signaling
IEA
GO_REF:0000107
ACCEPT
Summary: mTOR is the namesake kinase of TOR signaling, transducing nutrient/growth-factor inputs into control of growth, translation and autophagy via mTORC1 and mTORC2.
Reason: Core pathway directly executed by mTOR (IMP/IGI).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0031931 TORC1 complex
IEA
GO_REF:0000120
ACCEPT
Summary: mTOR is the catalytic core of mTORC1 (with RPTOR and MLST8), the nutrient/growth-factor-responsive complex that drives anabolic growth at the lysosomal surface.
Reason: Core complex; mTOR is an obligate subunit of mTORC1 (IDA/ComplexPortal CPX-4473).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0031932 TORC2 complex
IEA
GO_REF:0000107
ACCEPT
Summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
Reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0032869 cellular response to insulin stimulus
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Insulin activates mTORC1/mTORC2 through PI3K-AKT-TSC-Rheb; mTOR is the central effector of the insulin growth-factor response.
Reason: Upstream growth-factor input to mTOR.
GO:0032956 regulation of actin cytoskeleton organization
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: mTORC2 regulates the actin cytoskeleton through PKC and Rho/Rac GTPases; a characteristic downstream output of mTOR's mTORC2 activity.
Reason: Downstream mTORC2 cytoskeletal output.
GO:0034198 cellular response to amino acid starvation
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: mTORC1 is inactivated upon amino-acid withdrawal (loss of Rag-Ragulator lysosomal recruitment); mTOR is the sensor-effector responding to this input.
Reason: Upstream nutrient input gating core mTORC1 activity.
GO:0038202 TORC1 signaling
IEA
GO_REF:0000107
ACCEPT
Summary: mTORC1 signaling—phosphorylation of S6K1, 4E-BP1 and ULK1 to drive translation/growth and suppress autophagy—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC1 signaling.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0038203 TORC2 signaling
IEA
GO_REF:0000107
ACCEPT
Summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0042802 identical protein binding
IEA
GO_REF:0000107
MARK AS OVER ANNOTATED
Summary: Generic self-association term; mTOR's functional dimerization is better captured by the TORC1/TORC2 complex annotations.
Reason: Uninformative generic MF.
GO:0043022 ribosome binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: mTORC2 associates with ribosomes to cotranslationally phosphorylate nascent AKT, and mTORC1 couples to translation; a functionally relevant but ancillary interaction.
Reason: Supports cotranslational substrate phosphorylation; secondary to core kinase role.
GO:0043200 response to amino acid
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Amino-acid availability is a principal cue activating mTORC1; mTOR senses this through the lysosomal Rag machinery.
Reason: Upstream nutrient cue for mTORC1.
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction
IEA
GO_REF:0000107
ACCEPT
Summary: As the mTORC2 kinase, mTOR phosphorylates AKT (PKB) Ser473, a defining step of PI3K-AKT signal transduction directly executed by mTOR.
Reason: Core; mTORC2 is the AKT Ser473 kinase linking PI3K to AKT activation.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0045727 positive regulation of translation
IEA
GO_REF:0000107
ACCEPT
Summary: mTORC1 promotes cap-dependent translation by phosphorylating 4E-BP1 (releasing eIF4E) and activating S6K1/2, a core anabolic output of mTOR.
Reason: Core; mTORC1 directly drives translation via 4E-BP1/S6K.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0045945 positive regulation of transcription by RNA polymerase III
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: mTORC1 activates Pol III transcription by phosphorylating/inhibiting the repressor MAF1, boosting tRNA/5S rRNA synthesis; downstream of mTOR.
Reason: Downstream of mTORC1 (MAF1 phosphorylation).
GO:0045948 positive regulation of translational initiation
IEA
GO_REF:0000107
ACCEPT
Summary: By phosphorylating 4E-BP1 mTORC1 frees eIF4E and stimulates assembly of the cap-binding initiation complex, directly promoting translational initiation.
Reason: Core; 4E-BP1 phosphorylation by mTORC1 controls initiation.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0046889 positive regulation of lipid biosynthetic process
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: mTOR drives lipogenesis through SREBP1 and LPIN1 (mTORC1) and lipid synthesis programs (mTORC2); a major anabolic output downstream of mTOR.
Reason: Downstream lipogenic program of mTOR signaling.
GO:0051219 phosphoprotein binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: mTOR/its complexes recognize phosphorylated regulators (e.g. via SIN1/RPTOR); an interaction feature, not the core activity.
Reason: Partner recognition adjunct to core function.
GO:0051549 positive regulation of keratinocyte migration
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: mTOR signaling promotes keratinocyte migration in wound healing through its cytoskeletal/growth outputs.
Reason: Downstream motility/wound-healing effect.
GO:0061431 cellular response to methionine
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Methionine/SAM availability signals to mTORC1 (e.g. via SAMTOR); mTOR responds to set anabolic activity.
Reason: Specific amino-acid input to mTORC1.
GO:0062027 positive regulation of SCF-dependent proteasomal ubiquitin-dependent catabolic process
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: mTOR phosphorylation can promote SCF-mediated substrate degradation (IRS1 turnover), feeding back on insulin signaling.
Reason: Downstream proteostatic feedback of mTOR signaling.
GO:0071230 cellular response to amino acid stimulus
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Amino acids activate mTORC1 via Rag GTPases/Ragulator and lysosomal recruitment; mTOR responds to this stimulus to drive growth.
Reason: Upstream nutrient input to mTORC1.
GO:0071233 cellular response to L-leucine
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Leucine is a key amino acid activating mTORC1 (via Sestrin2/leucyl-tRNA pathways and Rag GTPases); mTOR is the responding effector.
Reason: Specific amino-acid input to mTORC1.
GO:1900181 negative regulation of protein localization to nucleus
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Active mTORC1 phosphorylates TFEB/TFE3 to retain them in the cytosol, preventing their nuclear entry; a specific mechanistic downstream effect.
Reason: Downstream MiT/TFE cytosolic-retention effect of mTORC1.
GO:1901838 positive regulation of transcription of nucleolar large rRNA by RNA polymerase I
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: mTORC1 promotes rRNA synthesis (Pol I) to support ribosome biogenesis, a downstream anabolic output of mTOR.
Reason: Downstream ribosome-biogenesis output of mTORC1.
GO:1903691 positive regulation of wound healing, spreading of epidermal cells
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: mTOR-dependent migration/proliferation of epidermal cells supports wound re-epithelialization; a downstream tissue process.
Reason: Downstream wound-healing process.
GO:1905671 regulation of lysosome organization
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Via TFEB/TFE3 phosphorylation mTORC1 regulates lysosomal gene programs and organelle homeostasis.
Reason: Downstream MiT/TFE-mediated effect of mTORC1.
GO:1905672 negative regulation of lysosome organization
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Active mTORC1 phosphorylates TFEB/TFE3 to keep them cytosolic, suppressing lysosomal/autophagy gene expression and biogenesis.
Reason: Downstream MiT/TFE inhibition by mTORC1.
GO:1990253 cellular response to leucine starvation
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Leucine withdrawal inactivates mTORC1; mTOR is the kinase whose activity drops in response.
Reason: Upstream nutrient input to mTORC1.
GO:2000785 regulation of autophagosome assembly
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: mTORC1 negatively regulates autophagosome assembly via ULK1; a specific facet of its autophagy-suppressive output.
Reason: Downstream autophagy regulation by mTORC1.
GO:0031648 protein destabilization
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTORC2 phosphorylation can target substrates (e.g. AKT, IRS1 via Fbw8) for turnover; a downstream proteostatic consequence of mTOR signaling.
Reason: Downstream effect of mTOR-directed phosphorylation.
GO:0000045 autophagosome assembly
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTORC1 gates autophagosome formation by controlling ULK1/the initiation machinery; the process it regulates rather than a structure it builds.
Reason: Downstream autophagy process regulated by mTORC1.
GO:0002181 cytoplasmic translation
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTORC1 stimulates the cytoplasmic translation apparatus (eIF4F assembly, S6K) as a downstream anabolic output; mTOR is a regulator, not a ribosomal component.
Reason: Downstream translation output of mTORC1.
GO:0006446 regulation of translational initiation
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTORC1 controls initiation through 4E-BP1/eIF4E and S6K; specific positive-initiation terms capture the core direction.
Reason: Generic regulation covered by specific positive-initiation terms.
GO:0006511 ubiquitin-dependent protein catabolic process
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTOR signaling influences proteasomal turnover of substrates (e.g. IRS1 via Fbw8, AKT); a downstream proteostatic consequence.
Reason: Downstream effect of mTOR-directed phosphorylation on turnover.
GO:0007040 lysosome organization
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTORC1 controls lysosome biogenesis/organization through TFEB/TFE3 phosphorylation and cytosolic retention; a downstream organelle-level output.
Reason: Downstream TFEB/TFE3-mediated effect of mTORC1.
GO:0008284 positive regulation of cell population proliferation
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: By promoting growth and survival, mTOR signaling supports cell proliferation; a downstream proliferative output.
Reason: Downstream proliferative effect of mTOR.
GO:0008286 insulin receptor signaling pathway
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTOR operates downstream of the insulin receptor and exerts feedback (GRB10/IRS1) on it; an integral but downstream node of insulin signaling.
Reason: Downstream/feedback node of insulin signaling.
GO:0010508 positive regulation of autophagy
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Atypical positive autophagy contexts (e.g. selective/non-canonical autophagy) attributed to mTOR signaling; minor relative to its dominant suppressive role.
Reason: Context-specific downstream effect opposite to mTOR's main autophagy role.
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTORC2-driven phosphorylation routes substrates (e.g. IRS1) to SCF/Fbw8-mediated degradation; a downstream proteostatic output.
Reason: Downstream proteostasis via mTORC2 phosphorylation.
GO:0045824 negative regulation of innate immune response
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTOR can dampen innate immune output (e.g. via metabolic/translational control); a downstream immune-regulatory effect.
Reason: Downstream immune-regulatory effect.
GO:0045947 negative regulation of translational initiation
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: In some contexts mTOR-linked feedback restrains initiation (e.g. when mTORC1 is inhibited); a context-dependent downstream effect.
Reason: Context-dependent downstream effect on initiation.
GO:0046627 negative regulation of insulin receptor signaling pathway
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTORC1 phosphorylates GRB10 and promotes IRS1 turnover, providing negative feedback on insulin-receptor signaling.
Reason: Downstream feedback inhibition by mTORC1.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
ISO
GO_REF:0000119
ACCEPT
Summary: mTORC2-mediated AKT hydrophobic-motif phosphorylation positively regulates PI3K-AKT signaling, a direct proximal output of mTOR kinase activity.
Reason: Core; mTORC2 directly activates AKT via Ser473 phosphorylation.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0140367 antibacterial innate immune response
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mTOR shapes innate antibacterial responses (autophagy/translation control in immune cells); a downstream immune role.
Reason: Downstream innate-immune role of mTOR.
GO:1902554 serine/threonine protein kinase complex
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Generic parent of the mTORC1/mTORC2 kinase complexes; the specific TORC1/TORC2 complex terms are the informative annotations for mTOR.
Reason: Subsumed by the specific TORC1/TORC2 complex annotations.
GO:1903940 negative regulation of TORC2 signaling
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Negative feedback on mTORC2 signaling; a regulatory nuance secondary to mTOR's core mTORC2 kinase role.
Reason: Feedback aspect of mTORC2 signaling, not the core function.
GO:1904262 negative regulation of TORC1 signaling
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Captures contexts where mTOR activity (e.g. RPTOR phosphorylation) feeds back to dampen mTORC1; a regulatory facet of, rather than the core driving role of, mTOR.
Reason: Feedback regulation downstream of core mTORC1 kinase activity.
GO:1904263 positive regulation of TORC1 signaling
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Reflects mTOR autophosphorylation/assembly events that enhance mTORC1 output; ancillary to the core catalytic signaling annotation.
Reason: Positive autoregulation downstream of core mTORC1 activity.
GO:2000059 negative regulation of ubiquitin-dependent protein catabolic process
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: In other contexts mTOR signaling stabilizes substrates by limiting their ubiquitin-dependent turnover; a context-dependent proteostatic effect.
Reason: Context-dependent downstream proteostatic effect.
GO:0006974 DNA damage response
NAS
PMID:17041623
Stress and mTORture signaling.
KEEP AS NON CORE
Summary: mTOR (a PIKK-family kinase) intersects DNA-damage/stress signaling; a contextual role secondary to its growth-control function.
Reason: Contextual PIKK-family stress role (NAS).
GO:0007010 cytoskeleton organization
NAS
PMID:15268862
Rictor, a novel binding partner of mTOR, defines a rapamycin...
KEEP AS NON CORE
Summary: mTORC2 controls cytoskeletal organization via PKCα/Rho-Rac signaling; a broad downstream effect of mTOR.
Reason: Downstream mTORC2 cytoskeletal output (NAS).
GO:0010507 negative regulation of autophagy
NAS
PMID:28283069
mTOR Signaling in Growth, Metabolism, and Disease.
ACCEPT
Summary: Under nutrient sufficiency mTORC1 phosphorylates ULK1 (Ser758) and other autophagy regulators to suppress autophagy; this inhibition is a core proximal mTOR output.
Reason: Core; direct ULK1 phosphorylation by mTORC1 (IMP-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0030307 positive regulation of cell growth
NAS
PMID:22500797
mTOR signaling in growth control and disease.
ACCEPT
Summary: Integrating its translational and anabolic outputs, mTORC1 promotes increases in cell mass/size; cell growth is the canonical phenotype of mTOR activity.
Reason: Core; growth promotion is the defining mTORC1 output.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0030307 positive regulation of cell growth
NAS
PMID:25906254
mLST8 Promotes mTOR-Mediated Tumor Progression.
ACCEPT
Summary: Integrating its translational and anabolic outputs, mTORC1 promotes increases in cell mass/size; cell growth is the canonical phenotype of mTOR activity.
Reason: Core; growth promotion is the defining mTORC1 output.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0031669 cellular response to nutrient levels
NAS
PMID:19299511
Specific activation of mTORC1 by Rheb G-protein in vitro inv...
KEEP AS NON CORE
Summary: Nutrient abundance dictates mTORC1 lysosomal recruitment and activity; mTOR is the effector translating nutrient state into growth decisions.
Reason: Upstream nutrient input to mTORC1.
GO:0031669 cellular response to nutrient levels
NAS
PMID:22500797
mTOR signaling in growth control and disease.
KEEP AS NON CORE
Summary: Nutrient abundance dictates mTORC1 lysosomal recruitment and activity; mTOR is the effector translating nutrient state into growth decisions.
Reason: Upstream nutrient input to mTORC1.
GO:0043066 negative regulation of apoptotic process
NAS
PMID:22500797
mTOR signaling in growth control and disease.
KEEP AS NON CORE
Summary: Through mTORC2-AKT survival signaling mTOR generally suppresses apoptosis; a downstream pro-survival output.
Reason: Downstream pro-survival effect (mTORC2-AKT).
GO:0045821 positive regulation of glycolytic process
NAS
PMID:20670887
Activation of a metabolic gene regulatory network downstream...
KEEP AS NON CORE
Summary: mTORC1 boosts glycolysis (via HIF1/MYC programs) to fuel anabolic growth; a metabolic consequence of mTORC1 activity.
Reason: Downstream metabolic output of mTORC1.
GO:0046889 positive regulation of lipid biosynthetic process
NAS
PMID:20670887
Activation of a metabolic gene regulatory network downstream...
KEEP AS NON CORE
Summary: mTOR drives lipogenesis through SREBP1 and LPIN1 (mTORC1) and lipid synthesis programs (mTORC2); a major anabolic output downstream of mTOR.
Reason: Downstream lipogenic program of mTOR signaling.
GO:0071456 cellular response to hypoxia
NAS
PMID:17041623
Stress and mTORture signaling.
KEEP AS NON CORE
Summary: Hypoxia inhibits mTORC1 (REDD1/TSC-dependent) and triggers mTOR nuclear accumulation; mTOR is the responding effector.
Reason: Upstream stress input gating mTORC1 (IDA/NAS).
GO:0071470 cellular response to osmotic stress
NAS
PMID:17041623
Stress and mTORture signaling.
KEEP AS NON CORE
Summary: mTOR senses osmotic stress via mitochondrial dysfunction, altering its activity; an upstream stress input.
Reason: Upstream stress response of mTOR.
GO:1905857 positive regulation of pentose-phosphate shunt
NAS
PMID:20670887
Activation of a metabolic gene regulatory network downstream...
KEEP AS NON CORE
Summary: mTORC1 promotes flux through the pentose phosphate pathway to supply nucleotide precursors, a delayed metabolic output of mTORC1.
Reason: Downstream metabolic effect of mTORC1.
GO:0000139 Golgi membrane
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: mTOR associates peripherally with the cytoplasmic face of Golgi membranes; a minor location versus lysosomal/plasma-membrane sites.
Reason: Secondary peripheral-membrane localization.
GO:0004713 protein tyrosine kinase activity
ISS
GO_REF:0000024
REMOVE
Summary: mTOR is a Ser/Thr (PIKK-family) kinase; the tyrosine-kinase EC 2.7.10.2 activity is only an unproven by-similarity inference and is not an established function of mouse mTOR.
Reason: IEA/ISO/ISS by-similarity only; contradicted by mTOR's Ser/Thr (PIKK) catalytic identity.
GO:0005634 nucleus
EXP
PMID:16915281
PML inhibits HIF-1alpha translation and neoangiogenesis thro...
KEEP AS NON CORE
Summary: mTOR shuttles to the nucleus and accumulates there under hypoxia; a regulated secondary localization beyond its cytoplasmic membrane sites.
Reason: Regulated nuclear pool (EXP/IDA); secondary location.
GO:0005737 cytoplasm
EXP
PMID:11930000
FKBP12-rapamycin-associated protein associates with mitochon...
ACCEPT
Summary: mTOR is a cytoplasmic kinase that shuttles among lysosomal, ER and plasma-membrane surfaces and the cytosol/nucleus; cytoplasmic localization is experimentally established.
Reason: Supported localization (EXP/ISS); mTOR carries out its kinase function in the cytoplasm.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0005737 cytoplasm
EXP
PMID:16915281
PML inhibits HIF-1alpha translation and neoangiogenesis thro...
ACCEPT
Summary: mTOR is a cytoplasmic kinase that shuttles among lysosomal, ER and plasma-membrane surfaces and the cytosol/nucleus; cytoplasmic localization is experimentally established.
Reason: Supported localization (EXP/ISS); mTOR carries out its kinase function in the cytoplasm.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0005741 mitochondrial outer membrane
EXP
PMID:11930000
FKBP12-rapamycin-associated protein associates with mitochon...
KEEP AS NON CORE
Summary: mTOR has been localized to the mitochondrial outer membrane and senses osmotic stress via mitochondrial dysfunction; a peripheral secondary location.
Reason: Secondary localization (EXP) linked to stress sensing.
GO:0005765 lysosomal membrane
ISS
GO_REF:0000024
ACCEPT
Summary: mTORC1 is recruited to and activated on the cytosolic face of the lysosomal membrane by Rag-Ragulator and Rheb, the principal site where mTOR integrates nutrient and growth-factor signals.
Reason: Core localization for mTORC1 activation (UniProt: lysosome membrane, peripheral, cytoplasmic side).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0005789 endoplasmic reticulum membrane
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: mTORC2 signals at the cytoplasmic face of the ER membrane; a real secondary location for mTOR complexes.
Reason: Secondary membrane site for mTORC2.
GO:0005886 plasma membrane
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: mTORC2 is active at the plasma membrane where it phosphorylates AKT/PKC; a genuine secondary location for mTOR.
Reason: mTORC2 plasma-membrane site; secondary to lysosomal mTORC1.
GO:0106310 protein serine kinase activity
EXP
PMID:11792863
Insulin-stimulated phosphorylation of lipin mediated by the ...
ACCEPT
Summary: Captures mTOR phosphorylation of serine residues (e.g. AKT Ser473, 4E-BP1 serines), a component of its EC 2.7.11.1 serine/threonine kinase activity.
Reason: Core MF consistent with experimental serine-phosphorylation of mTOR substrates.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0106310 protein serine kinase activity
EXP
PMID:18566587
Essential function of TORC2 in PKC and Akt turn motif phosph...
ACCEPT
Summary: Captures mTOR phosphorylation of serine residues (e.g. AKT Ser473, 4E-BP1 serines), a component of its EC 2.7.11.1 serine/threonine kinase activity.
Reason: Core MF consistent with experimental serine-phosphorylation of mTOR substrates.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0106310 protein serine kinase activity
EXP
PMID:21321111
mTOR complex 2 targets Akt for proteasomal degradation via p...
ACCEPT
Summary: Captures mTOR phosphorylation of serine residues (e.g. AKT Ser473, 4E-BP1 serines), a component of its EC 2.7.11.1 serine/threonine kinase activity.
Reason: Core MF consistent with experimental serine-phosphorylation of mTOR substrates.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0106310 protein serine kinase activity
EXP
PMID:27913603
The tumor suppressor FLCN mediates an alternate mTOR pathway...
ACCEPT
Summary: Captures mTOR phosphorylation of serine residues (e.g. AKT Ser473, 4E-BP1 serines), a component of its EC 2.7.11.1 serine/threonine kinase activity.
Reason: Core MF consistent with experimental serine-phosphorylation of mTOR substrates.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0106310 protein serine kinase activity
EXP
PMID:31548312
Serine 474 phosphorylation is essential for maximal Akt2 kin...
ACCEPT
Summary: Captures mTOR phosphorylation of serine residues (e.g. AKT Ser473, 4E-BP1 serines), a component of its EC 2.7.11.1 serine/threonine kinase activity.
Reason: Core MF consistent with experimental serine-phosphorylation of mTOR substrates.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0044325 transmembrane transporter binding
IPI
PMID:27782176
Functional kinomics establishes a critical node of volume-se...
KEEP AS NON CORE
Summary: mTOR interacts with lysosomal transporters/channels (e.g. TPCN1/2, SLC38A9-type recruiters) relevant to nutrient sensing and recruitment.
Reason: IPI interaction linked to lysosomal recruitment; non-core.
GO:0009615 response to virus
IDA
PMID:36735752
Picornavirus infection enhances aspartate by the SLC38A8 tra...
KEEP AS NON CORE
Summary: mTOR signaling is engaged during antiviral responses (translational control, innate immunity); a downstream physiological role.
Reason: Downstream innate-immune/translational role.
GO:2000060 positive regulation of ubiquitin-dependent protein catabolic process
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: mTOR-directed phosphorylation can mark substrates for ubiquitin-dependent degradation; a downstream proteostatic effect.
Reason: Downstream proteostatic effect of mTOR signaling.
GO:0004674 protein serine/threonine kinase activity
ISO
PMID:15185396
Loss of tuberous sclerosis complex 1 (Tsc1) expression resul...
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:1905671 regulation of lysosome organization
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Via TFEB/TFE3 phosphorylation mTORC1 regulates lysosomal gene programs and organelle homeostasis.
Reason: Downstream MiT/TFE-mediated effect of mTORC1.
GO:0046889 positive regulation of lipid biosynthetic process
IDA
PMID:29232555
mTORC2 Promotes Tumorigenesis via Lipid Synthesis.
KEEP AS NON CORE
Summary: mTOR drives lipogenesis through SREBP1 and LPIN1 (mTORC1) and lipid synthesis programs (mTORC2); a major anabolic output downstream of mTOR.
Reason: Downstream lipogenic program of mTOR signaling.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:34245780
The innate immune kinase TBK1 directly increases mTORC2 acti...
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0038203 TORC2 signaling
IDA
PMID:34245780
The innate immune kinase TBK1 directly increases mTORC2 acti...
ACCEPT
Summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:23142081
mTOR complex 2 regulates proper turnover of insulin receptor...
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:23388827
mTOR complex 2 phosphorylates IMP1 cotranslationally to prom...
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0031932 TORC2 complex
IDA
PMID:23142081
mTOR complex 2 regulates proper turnover of insulin receptor...
ACCEPT
Summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
Reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0031932 TORC2 complex
IDA
PMID:23388827
mTOR complex 2 phosphorylates IMP1 cotranslationally to prom...
ACCEPT
Summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
Reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0032869 cellular response to insulin stimulus
IDA
PMID:23142081
mTOR complex 2 regulates proper turnover of insulin receptor...
KEEP AS NON CORE
Summary: Insulin activates mTORC1/mTORC2 through PI3K-AKT-TSC-Rheb; mTOR is the central effector of the insulin growth-factor response.
Reason: Upstream growth-factor input to mTOR.
GO:0038203 TORC2 signaling
IDA
PMID:23142081
mTOR complex 2 regulates proper turnover of insulin receptor...
ACCEPT
Summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0038203 TORC2 signaling
IDA
PMID:23388827
mTOR complex 2 phosphorylates IMP1 cotranslationally to prom...
ACCEPT
Summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0038203 TORC2 signaling
IDA
PMID:29232555
mTORC2 Promotes Tumorigenesis via Lipid Synthesis.
ACCEPT
Summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0005783 endoplasmic reticulum
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: mTORC2 is active at the ER membrane; ER localization is a genuine but secondary site relative to the lysosomal mTORC1 hub.
Reason: Secondary localization (mTORC2 at ER).
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:18566586
The mammalian target of rapamycin complex 2 controls folding...
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:18566587
Essential function of TORC2 in PKC and Akt turn motif phosph...
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:21321111
mTOR complex 2 targets Akt for proteasomal degradation via p...
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:24670654
Cell-cycle-regulated activation of Akt kinase by phosphoryla...
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:31548312
Serine 474 phosphorylation is essential for maximal Akt2 kin...
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:33850054
mTORC2 controls the activity of PKC and Akt by phosphorylati...
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0031932 TORC2 complex
IDA
PMID:24670654
Cell-cycle-regulated activation of Akt kinase by phosphoryla...
ACCEPT
Summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
Reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0031932 TORC2 complex
IDA
PMID:33850054
mTORC2 controls the activity of PKC and Akt by phosphorylati...
ACCEPT
Summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
Reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0038203 TORC2 signaling
IDA
PMID:18566586
The mammalian target of rapamycin complex 2 controls folding...
ACCEPT
Summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0038203 TORC2 signaling
IDA
PMID:18566587
Essential function of TORC2 in PKC and Akt turn motif phosph...
ACCEPT
Summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0038203 TORC2 signaling
IDA
PMID:21321111
mTOR complex 2 targets Akt for proteasomal degradation via p...
ACCEPT
Summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0038203 TORC2 signaling
IDA
PMID:24670654
Cell-cycle-regulated activation of Akt kinase by phosphoryla...
ACCEPT
Summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0038203 TORC2 signaling
IDA
PMID:31548312
Serine 474 phosphorylation is essential for maximal Akt2 kin...
ACCEPT
Summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0038203 TORC2 signaling
IDA
PMID:33850054
mTORC2 controls the activity of PKC and Akt by phosphorylati...
ACCEPT
Summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0051896 regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
IDA
PMID:18566586
The mammalian target of rapamycin complex 2 controls folding...
ACCEPT
Summary: mTOR regulates PI3K-AKT signaling both as the mTORC2 AKT-kinase and via mTORC1 feedback (GRB10/IRS), placing it as a direct regulator of this pathway.
Reason: Core; mTOR directly sets AKT activity through mTORC2 and mTORC1 feedback.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0051896 regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
IDA
PMID:21321111
mTOR complex 2 targets Akt for proteasomal degradation via p...
ACCEPT
Summary: mTOR regulates PI3K-AKT signaling both as the mTORC2 AKT-kinase and via mTORC1 feedback (GRB10/IRS), placing it as a direct regulator of this pathway.
Reason: Core; mTOR directly sets AKT activity through mTORC2 and mTORC1 feedback.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0051896 regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
IDA
PMID:31548312
Serine 474 phosphorylation is essential for maximal Akt2 kin...
ACCEPT
Summary: mTOR regulates PI3K-AKT signaling both as the mTORC2 AKT-kinase and via mTORC1 feedback (GRB10/IRS), placing it as a direct regulator of this pathway.
Reason: Core; mTOR directly sets AKT activity through mTORC2 and mTORC1 feedback.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0000822 inositol hexakisphosphate binding
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: InsP6 is a structural cofactor reported to stabilize the mTOR kinase domain; a structural-ligand feature rather than the catalytic activity.
Reason: Structural cofactor binding; non-core.
GO:0031932 TORC2 complex
ISS
GO_REF:0000024
ACCEPT
Summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
Reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0038203 TORC2 signaling
ISS
GO_REF:0000024
ACCEPT
Summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0038202 TORC1 signaling
ISS
GO_REF:0000024
ACCEPT
Summary: mTORC1 signaling—phosphorylation of S6K1, 4E-BP1 and ULK1 to drive translation/growth and suppress autophagy—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC1 signaling.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:1900181 negative regulation of protein localization to nucleus
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Active mTORC1 phosphorylates TFEB/TFE3 to retain them in the cytosol, preventing their nuclear entry; a specific mechanistic downstream effect.
Reason: Downstream MiT/TFE cytosolic-retention effect of mTORC1.
GO:1905672 negative regulation of lysosome organization
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Active mTORC1 phosphorylates TFEB/TFE3 to keep them cytosolic, suppressing lysosomal/autophagy gene expression and biogenesis.
Reason: Downstream MiT/TFE inhibition by mTORC1.
GO:0031929 TOR signaling
IMP
PMID:15485918
Disruption of the mouse mTOR gene leads to early postimplant...
ACCEPT
Summary: mTOR is the namesake kinase of TOR signaling, transducing nutrient/growth-factor inputs into control of growth, translation and autophagy via mTORC1 and mTORC2.
Reason: Core pathway directly executed by mTOR (IMP/IGI).
GO:0006468 protein phosphorylation
ISO
PMID:31915252
The GATOR2-mTORC2 axis mediates Sestrin2-induced AKT Ser/Thr...
ACCEPT
Summary: mTOR catalyzes transfer of phosphate to its protein substrates within mTORC1 and mTORC2, the molecular event underlying all of its signaling outputs.
Reason: Core catalytic process for a protein kinase; ISO but biologically definitive for mTOR.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0038202 TORC1 signaling
ISO
PMID:31915252
The GATOR2-mTORC2 axis mediates Sestrin2-induced AKT Ser/Thr...
ACCEPT
Summary: mTORC1 signaling—phosphorylation of S6K1, 4E-BP1 and ULK1 to drive translation/growth and suppress autophagy—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC1 signaling.
GO:0038203 TORC2 signaling
ISO
PMID:31915252
The GATOR2-mTORC2 axis mediates Sestrin2-induced AKT Ser/Thr...
ACCEPT
Summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
Reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0045860 positive regulation of protein kinase activity
ISO
PMID:31915252
The GATOR2-mTORC2 axis mediates Sestrin2-induced AKT Ser/Thr...
KEEP AS NON CORE
Summary: By phosphorylating AGC kinases (AKT, PKC, SGK1) mTORC2 increases their activity; a downstream consequence of mTOR's core kinase function.
Reason: Downstream activation of substrate kinases.
GO:0006954 inflammatory response
IGI
PMID:31874168
Hyperactive Akt-mTOR pathway as a therapeutic target for pai...
KEEP AS NON CORE
Summary: mTOR modulates inflammatory programs in immune cells through metabolic and translational control; a downstream immune phenotype (IGI).
Reason: Downstream inflammatory role of mTOR.
GO:0009408 response to heat
IGI
PMID:31874168
Hyperactive Akt-mTOR pathway as a therapeutic target for pai...
KEEP AS NON CORE
Summary: mTOR signaling responds to heat/proteotoxic stress as part of cellular stress adaptation; a downstream phenotype (IGI).
Reason: Stress-response context downstream of mTOR.
GO:0019228 neuronal action potential
IGI
PMID:31874168
Hyperactive Akt-mTOR pathway as a therapeutic target for pai...
KEEP AS NON CORE
Summary: mTOR signaling influences neuronal excitability/action-potential properties (e.g. via channel/translation control); a downstream neuronal phenotype (IGI).
Reason: Downstream neurophysiological effect of mTOR.
GO:0048266 behavioral response to pain
IGI
PMID:31874168
Hyperactive Akt-mTOR pathway as a therapeutic target for pai...
KEEP AS NON CORE
Summary: mTOR-dependent translation in sensory neurons modulates nociceptive/pain behavior; a downstream behavioral phenotype (IGI).
Reason: Downstream nociceptive behavioral effect.
GO:0045335 phagocytic vesicle
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: mTOR localizes to phagosomes, relevant to phagosome maturation and innate-immune signaling; a peripheral compartment.
Reason: Secondary vesicular localization.
GO:0034198 cellular response to amino acid starvation
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: mTORC1 is inactivated upon amino-acid withdrawal (loss of Rag-Ragulator lysosomal recruitment); mTOR is the sensor-effector responding to this input.
Reason: Upstream nutrient input gating core mTORC1 activity.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:24011591
Phosphorylation of p62 activates the Keap1-Nrf2 pathway duri...
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0010506 regulation of autophagy
IDA
PMID:24011591
Phosphorylation of p62 activates the Keap1-Nrf2 pathway duri...
KEEP AS NON CORE
Summary: Generic regulation-of-autophagy; mTOR's core, well-defined role is the negative regulation captured by the specific ULK1-linked terms.
Reason: Generic; specific negative-regulation terms are the informative ones.
GO:0010507 negative regulation of autophagy
ISS
GO_REF:0000024
ACCEPT
Summary: Under nutrient sufficiency mTORC1 phosphorylates ULK1 (Ser758) and other autophagy regulators to suppress autophagy; this inhibition is a core proximal mTOR output.
Reason: Core; direct ULK1 phosphorylation by mTORC1 (IMP-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0042752 regulation of circadian rhythm
IMP
PMID:29750810
mTOR signaling regulates central and peripheral circadian cl...
KEEP AS NON CORE
Summary: mTOR signaling regulates circadian period and amplitude in the SCN and liver clocks; a downstream physiological role (IMP).
Reason: Downstream circadian role of mTOR.
GO:1904059 regulation of locomotor rhythm
IMP
PMID:29750810
mTOR signaling regulates central and peripheral circadian cl...
KEEP AS NON CORE
Summary: mTOR modulates circadian control of locomotor activity rhythms; a downstream behavioral-physiological phenotype (IMP).
Reason: Downstream circadian-behavioral effect of mTOR.
GO:0031929 TOR signaling
ISS
GO_REF:0000024
ACCEPT
Summary: mTOR is the namesake kinase of TOR signaling, transducing nutrient/growth-factor inputs into control of growth, translation and autophagy via mTORC1 and mTORC2.
Reason: Core pathway directly executed by mTOR (IMP/IGI).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0070885 negative regulation of calcineurin-NFAT signaling cascade
IMP
PMID:18347059
Integration of protein kinases mTOR and extracellular signal...
KEEP AS NON CORE
Summary: mTOR signaling can antagonize calcineurin-NFAT signaling in immune/cardiac contexts; a downstream cross-talk effect (IMP).
Reason: Downstream signaling cross-talk effect.
GO:0002296 T-helper 1 cell lineage commitment
IMP
PMID:26410627
The Interleukin-2-mTORc1 Kinase Axis Defines the Signaling, ...
KEEP AS NON CORE
Summary: mTOR signaling directs Th1 lineage commitment in CD4+ T cells; a downstream immune-differentiation phenotype (IMP).
Reason: Downstream immune differentiation role.
GO:0031929 TOR signaling
IGI
PMID:26160071
miR-199a impairs autophagy and induces cardiac hypertrophy t...
ACCEPT
Summary: mTOR is the namesake kinase of TOR signaling, transducing nutrient/growth-factor inputs into control of growth, translation and autophagy via mTORC1 and mTORC2.
Reason: Core pathway directly executed by mTOR (IMP/IGI).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0016242 negative regulation of macroautophagy
ISO
PMID:25327288
Selective VPS34 inhibitor blocks autophagy and uncovers a ro...
ACCEPT
Summary: mTORC1 directly restrains macroautophagy by phosphorylating ULK1 and inhibiting the autophagy-initiation machinery when nutrients are abundant.
Reason: Core; ULK1-mediated suppression of macroautophagy by mTORC1 (IMP/IBA).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0031931 TORC1 complex
IDA
PMID:12718876
GbetaL, a positive regulator of the rapamycin-sensitive path...
ACCEPT
Summary: mTOR is the catalytic core of mTORC1 (with RPTOR and MLST8), the nutrient/growth-factor-responsive complex that drives anabolic growth at the lysosomal surface.
Reason: Core complex; mTOR is an obligate subunit of mTORC1 (IDA/ComplexPortal CPX-4473).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0001932 regulation of protein phosphorylation
IDA
PMID:17556672
Steroid and oxygen effects on eIF4F complex, mTOR, and ENaC ...
KEEP AS NON CORE
Summary: Generic regulation-of-phosphorylation reflecting mTOR's kinase outputs; less informative than its direct Ser/Thr kinase annotations.
Reason: Generic; covered by specific phosphorylation/kinase terms.
GO:0016242 negative regulation of macroautophagy
IMP
PMID:23274896
Stimulation of autophagy improves endoplasmic reticulum stre...
ACCEPT
Summary: mTORC1 directly restrains macroautophagy by phosphorylating ULK1 and inhibiting the autophagy-initiation machinery when nutrients are abundant.
Reason: Core; ULK1-mediated suppression of macroautophagy by mTORC1 (IMP/IBA).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0001934 positive regulation of protein phosphorylation
IMP
PMID:25139234
Mammalian target of rapamycin is essential for cardiomyocyte...
KEEP AS NON CORE
Summary: Generic statement of mTOR increasing substrate phosphorylation (e.g. AKT, S6K); the specific kinase-activity terms convey the mechanism.
Reason: Generic regulatory term subsumed by mTOR's specific kinase MF.
GO:0003007 heart morphogenesis
IMP
PMID:25139234
Mammalian target of rapamycin is essential for cardiomyocyte...
KEEP AS NON CORE
Summary: mTOR-dependent cardiomyocyte growth contributes to heart morphogenesis; a downstream developmental phenotype (IMP).
Reason: Downstream cardiac morphogenesis role.
GO:0003179 heart valve morphogenesis
IMP
PMID:25139234
Mammalian target of rapamycin is essential for cardiomyocyte...
KEEP AS NON CORE
Summary: mTOR signaling participates in valve development via growth/EMT control; a downstream developmental phenotype (IMP).
Reason: Downstream valve morphogenesis role.
GO:0006112 energy reserve metabolic process
IMP
PMID:25139234
Mammalian target of rapamycin is essential for cardiomyocyte...
KEEP AS NON CORE
Summary: mTORC1 influences glycogen/energy-store metabolism as part of anabolic control; a downstream metabolic phenotype (IMP).
Reason: Downstream metabolic role of mTORC1.
GO:0009791 post-embryonic development
IMP
PMID:25139234
Mammalian target of rapamycin is essential for cardiomyocyte...
KEEP AS NON CORE
Summary: mTOR is required for postnatal growth and development as a consequence of its anabolic/growth-control function.
Reason: Developmental phenotype downstream of mTOR growth control.
GO:0035264 multicellular organism growth
IMP
PMID:25139234
Mammalian target of rapamycin is essential for cardiomyocyte...
KEEP AS NON CORE
Summary: Organism-level growth depends on mTORC1-driven cell growth; a whole-animal phenotype downstream of mTOR (IMP).
Reason: Organismal phenotype of core cell-growth role.
GO:0048738 cardiac muscle tissue development
IMP
PMID:25139234
Mammalian target of rapamycin is essential for cardiomyocyte...
KEEP AS NON CORE
Summary: mTOR supports growth and maturation of cardiac muscle tissue; a downstream developmental phenotype (IMP).
Reason: Downstream cardiac tissue development.
GO:0050882 voluntary musculoskeletal movement
IMP
PMID:25139234
Mammalian target of rapamycin is essential for cardiomyocyte...
KEEP AS NON CORE
Summary: mTOR's roles in neuromuscular growth and translation affect voluntary movement; a downstream organismal phenotype (IMP).
Reason: Downstream motor phenotype of mTOR.
GO:0051896 regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
IMP
PMID:25139234
Mammalian target of rapamycin is essential for cardiomyocyte...
ACCEPT
Summary: mTOR regulates PI3K-AKT signaling both as the mTORC2 AKT-kinase and via mTORC1 feedback (GRB10/IRS), placing it as a direct regulator of this pathway.
Reason: Core; mTOR directly sets AKT activity through mTORC2 and mTORC1 feedback.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0055013 cardiac muscle cell development
IMP
PMID:25139234
Mammalian target of rapamycin is essential for cardiomyocyte...
KEEP AS NON CORE
Summary: mTORC1-driven growth contributes to cardiomyocyte development/maturation; a downstream tissue phenotype (IMP).
Reason: Downstream cardiomyocyte developmental role.
GO:0060048 cardiac muscle contraction
IMP
PMID:25139234
Mammalian target of rapamycin is essential for cardiomyocyte...
KEEP AS NON CORE
Summary: mTOR-dependent maintenance of cardiomyocyte growth/metabolism affects cardiac contractile function; a downstream physiological phenotype (IMP).
Reason: Downstream cardiac-function phenotype of mTOR.
GO:0090559 regulation of membrane permeability
IMP
PMID:25139234
Mammalian target of rapamycin is essential for cardiomyocyte...
KEEP AS NON CORE
Summary: mTOR signaling modulates ion-channel/membrane permeability in excitable cells; a downstream physiological effect (IMP).
Reason: Downstream physiological effect of mTOR.
GO:0048714 positive regulation of oligodendrocyte differentiation
IMP
PMID:25411504
Oligodendrocyte precursor cell-intrinsic effect of Rheb1 con...
KEEP AS NON CORE
Summary: mTOR signaling promotes oligodendrocyte differentiation and myelination programs; a downstream CNS differentiation role.
Reason: Downstream CNS differentiation effect (IMP).
GO:0045670 regulation of osteoclast differentiation
IDA
PMID:19440205
Transcription factor C/EBPbeta isoform ratio regulates osteo...
KEEP AS NON CORE
Summary: mTOR regulates osteoclastogenesis by adjusting CEBPB isoform expression; a downstream cell-differentiation role (IDA).
Reason: Downstream differentiation effect (bone).
GO:0005515 protein binding
IPI
PMID:23027611
5-HT(6) receptor recruitment of mTOR as a mechanism for pert...
MARK AS OVER ANNOTATED
Summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
Reason: Generic binding term per curation guidelines; not informative.
GO:0031641 regulation of myelination
IMP
PMID:24101522
MicroRNA-23a promotes myelination in the central nervous sys...
KEEP AS NON CORE
Summary: mTOR controls myelination through oligodendrocyte/Schwann-cell growth and lipid synthesis; a downstream tissue-level role (IMP).
Reason: Downstream myelination phenotype of mTOR.
GO:0030425 dendrite
IDA
PMID:23836929
Degradation of high affinity HuD targets releases Kv1.1 mRNA...
KEEP AS NON CORE
Summary: Dendritic localization of mTOR supports local translation underlying synaptic plasticity; a neuron-specific secondary site.
Reason: Neuronal localization linked to local translation.
GO:0005515 protein binding
IPI
PMID:21413931
Protor-1 is required for efficient mTORC2-mediated activatio...
MARK AS OVER ANNOTATED
Summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
Reason: Generic binding term per curation guidelines; not informative.
GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process
IDA
PMID:23429704
Quantitative phosphoproteomics reveal mTORC1 activates de no...
KEEP AS NON CORE
Summary: mTORC1 stimulates pyrimidine synthesis via S6K1-mediated phosphorylation of CAD and pentose-phosphate-fed PRPP; a metabolic output downstream of mTORC1.
Reason: Downstream anabolic process of mTORC1 signaling.
GO:0055006 cardiac cell development
IMP
PMID:23342106
Mechanistic target of rapamycin (Mtor) is essential for muri...
KEEP AS NON CORE
Summary: mTOR-dependent growth is required for cardiac cell development; a tissue-specific downstream phenotype (IMP).
Reason: Downstream cardiac developmental role.
GO:0010831 positive regulation of myotube differentiation
IGI
PMID:19704009
Regulation of myoblast differentiation by the nuclear envelo...
KEEP AS NON CORE
Summary: mTOR signaling promotes myoblast fusion/myotube differentiation during myogenesis; a downstream developmental role (IGI).
Reason: Downstream myogenic differentiation effect.
GO:0046889 positive regulation of lipid biosynthetic process
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: mTOR drives lipogenesis through SREBP1 and LPIN1 (mTORC1) and lipid synthesis programs (mTORC2); a major anabolic output downstream of mTOR.
Reason: Downstream lipogenic program of mTOR signaling.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:21258367
AMPK and mTOR regulate autophagy through direct phosphorylat...
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0005515 protein binding
IPI
PMID:21258367
AMPK and mTOR regulate autophagy through direct phosphorylat...
MARK AS OVER ANNOTATED
Summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
Reason: Generic binding term per curation guidelines; not informative.
GO:0010507 negative regulation of autophagy
IMP
PMID:21258367
AMPK and mTOR regulate autophagy through direct phosphorylat...
ACCEPT
Summary: Under nutrient sufficiency mTORC1 phosphorylates ULK1 (Ser758) and other autophagy regulators to suppress autophagy; this inhibition is a core proximal mTOR output.
Reason: Core; direct ULK1 phosphorylation by mTORC1 (IMP-supported).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0031669 cellular response to nutrient levels
IDA
PMID:21258367
AMPK and mTOR regulate autophagy through direct phosphorylat...
KEEP AS NON CORE
Summary: Nutrient abundance dictates mTORC1 lysosomal recruitment and activity; mTOR is the effector translating nutrient state into growth decisions.
Reason: Upstream nutrient input to mTORC1.
GO:0005515 protein binding
IPI
PMID:16915281
PML inhibits HIF-1alpha translation and neoangiogenesis thro...
MARK AS OVER ANNOTATED
Summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
Reason: Generic binding term per curation guidelines; not informative.
GO:0005829 cytosol
IDA
PMID:16915281
PML inhibits HIF-1alpha translation and neoangiogenesis thro...
ACCEPT
Summary: Soluble cytosolic pool of mTOR/mTOR complexes consistent with its peripheral-membrane association and shuttling behavior.
Reason: Supported localization (IDA) for cytoplasmic mTOR.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0016605 PML body
IDA
PMID:16915281
PML inhibits HIF-1alpha translation and neoangiogenesis thro...
KEEP AS NON CORE
Summary: PML sequesters mTOR in nuclear PML bodies to repress mTORC1 (HIF1α translation control); a regulatory localization documented by IDA.
Reason: Regulatory nuclear-body localization (IDA).
Supporting Evidence:
UniProt:Q9JLN9
Nucleus, PML body
GO:0071456 cellular response to hypoxia
IDA
PMID:16915281
PML inhibits HIF-1alpha translation and neoangiogenesis thro...
KEEP AS NON CORE
Summary: Hypoxia inhibits mTORC1 (REDD1/TSC-dependent) and triggers mTOR nuclear accumulation; mTOR is the responding effector.
Reason: Upstream stress input gating mTORC1 (IDA/NAS).
GO:0043022 ribosome binding
IDA
PMID:21045808
mTORC2 can associate with ribosomes to promote cotranslation...
KEEP AS NON CORE
Summary: mTORC2 associates with ribosomes to cotranslationally phosphorylate nascent AKT, and mTORC1 couples to translation; a functionally relevant but ancillary interaction.
Reason: Supports cotranslational substrate phosphorylation; secondary to core kinase role.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:18347059
Integration of protein kinases mTOR and extracellular signal...
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0005634 nucleus
IDA
PMID:18347059
Integration of protein kinases mTOR and extracellular signal...
KEEP AS NON CORE
Summary: mTOR shuttles to the nucleus and accumulates there under hypoxia; a regulated secondary localization beyond its cytoplasmic membrane sites.
Reason: Regulated nuclear pool (EXP/IDA); secondary location.
GO:0005829 cytosol
IDA
PMID:18347059
Integration of protein kinases mTOR and extracellular signal...
ACCEPT
Summary: Soluble cytosolic pool of mTOR/mTOR complexes consistent with its peripheral-membrane association and shuttling behavior.
Reason: Supported localization (IDA) for cytoplasmic mTOR.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0018105 peptidyl-serine phosphorylation
IMP
PMID:18347059
Integration of protein kinases mTOR and extracellular signal...
ACCEPT
Summary: mTOR phosphorylates serine residues of substrate peptides (e.g. AKT Ser473, 4E-BP1, ULK1 Ser758), the residue-level activity of its Ser/Thr kinase function.
Reason: Core; IMP-supported residue-specific phosphorylation by mTOR.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0005737 cytoplasm
ISS
GO_REF:0000024
ACCEPT
Summary: mTOR is a cytoplasmic kinase that shuttles among lysosomal, ER and plasma-membrane surfaces and the cytosol/nucleus; cytoplasmic localization is experimentally established.
Reason: Supported localization (EXP/ISS); mTOR carries out its kinase function in the cytoplasm.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0005764 lysosome
ISS
GO_REF:0000024
MODIFY
Summary: mTOR acts at the lysosomal membrane (cytoplasmic face), not in the lysosomal lumen; the membrane component is the precise localization.
Reason: Over-general; lysosomal membrane (GO:0005765) is the specific compartment for mTORC1.
Proposed replacements: lysosomal membrane
Supporting Evidence:
UniProt:Q9JLN9
Lysosome membrane; Peripheral membrane protein; Cytoplasmic side
GO:0005634 nucleus
IDA
PMID:18381428
Lkb1 deficiency causes prostate neoplasia in the mouse.
KEEP AS NON CORE
Summary: mTOR shuttles to the nucleus and accumulates there under hypoxia; a regulated secondary localization beyond its cytoplasmic membrane sites.
Reason: Regulated nuclear pool (EXP/IDA); secondary location.
GO:0006468 protein phosphorylation
ISO
PMID:15467718
Mammalian TOR complex 2 controls the actin cytoskeleton and ...
ACCEPT
Summary: mTOR catalyzes transfer of phosphate to its protein substrates within mTORC1 and mTORC2, the molecular event underlying all of its signaling outputs.
Reason: Core catalytic process for a protein kinase; ISO but biologically definitive for mTOR.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0031931 TORC1 complex
ISO
PMID:15467718
Mammalian TOR complex 2 controls the actin cytoskeleton and ...
ACCEPT
Summary: mTOR is the catalytic core of mTORC1 (with RPTOR and MLST8), the nutrient/growth-factor-responsive complex that drives anabolic growth at the lysosomal surface.
Reason: Core complex; mTOR is an obligate subunit of mTORC1 (IDA/ComplexPortal CPX-4473).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0031932 TORC2 complex
ISO
PMID:15467718
Mammalian TOR complex 2 controls the actin cytoskeleton and ...
ACCEPT
Summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
Reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0046777 protein autophosphorylation
ISO
PMID:15467718
Mammalian TOR complex 2 controls the actin cytoskeleton and ...
ACCEPT
Summary: mTOR autophosphorylates (e.g. Ser2481) when assembled in mTORC1 or mTORC2, a hallmark of the active kinase used to report complex integrity.
Reason: Core intrinsic kinase activity; documented mTOR autophosphorylation.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0010592 positive regulation of lamellipodium assembly
IDA
PMID:15467718
Mammalian TOR complex 2 controls the actin cytoskeleton and ...
KEEP AS NON CORE
Summary: mTORC2-Rac1 signaling promotes lamellipodia formation during cell migration; a downstream motility output.
Reason: Downstream mTORC2 motility effect (IDA).
GO:0030838 positive regulation of actin filament polymerization
IDA
PMID:15467718
Mammalian TOR complex 2 controls the actin cytoskeleton and ...
KEEP AS NON CORE
Summary: mTORC2 promotes actin polymerization through Rac/Rho and PKC, driving cell shape and motility changes.
Reason: Downstream mTORC2 cytoskeletal effect (IDA/IMP).
GO:0030838 positive regulation of actin filament polymerization
IMP
PMID:15467718
Mammalian TOR complex 2 controls the actin cytoskeleton and ...
KEEP AS NON CORE
Summary: mTORC2 promotes actin polymerization through Rac/Rho and PKC, driving cell shape and motility changes.
Reason: Downstream mTORC2 cytoskeletal effect (IDA/IMP).
GO:0032868 response to insulin
IDA
PMID:15467718
Mammalian TOR complex 2 controls the actin cytoskeleton and ...
KEEP AS NON CORE
Summary: mTOR transduces insulin signaling into anabolic and metabolic outputs; an upstream stimulus for its complexes.
Reason: Upstream growth-factor input to mTOR.
GO:0043200 response to amino acid
IDA
PMID:15467718
Mammalian TOR complex 2 controls the actin cytoskeleton and ...
KEEP AS NON CORE
Summary: Amino-acid availability is a principal cue activating mTORC1; mTOR senses this through the lysosomal Rag machinery.
Reason: Upstream nutrient cue for mTORC1.
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
IMP
PMID:15467718
Mammalian TOR complex 2 controls the actin cytoskeleton and ...
KEEP AS NON CORE
Summary: mTOR signaling can raise tyrosine phosphorylation of downstream effectors indirectly; not direct mTOR catalysis on tyrosine.
Reason: Indirect downstream effect, not direct mTOR tyrosine kinase activity.
GO:0051496 positive regulation of stress fiber assembly
IDA
PMID:15467718
Mammalian TOR complex 2 controls the actin cytoskeleton and ...
KEEP AS NON CORE
Summary: mTORC2-RhoA signaling promotes stress-fiber formation; a downstream cytoskeletal output.
Reason: Downstream mTORC2 cytoskeletal effect (IDA).
GO:1900029 positive regulation of ruffle assembly
IDA
PMID:15467718
Mammalian TOR complex 2 controls the actin cytoskeleton and ...
KEEP AS NON CORE
Summary: mTORC2-driven actin remodeling promotes membrane ruffling; a downstream cytoskeletal output.
Reason: Downstream mTORC2 cytoskeletal effect (IDA).
GO:0045792 negative regulation of cell size
IGI
PMID:15185396
Loss of tuberous sclerosis complex 1 (Tsc1) expression resul...
KEEP AS NON CORE
Summary: Captures contexts where mTOR loss/inhibition reduces cell size or where mTOR feedback limits growth; the directionality opposite to its dominant pro-growth role.
Reason: Context/loss-of-function readout of mTOR growth control.
GO:0045792 negative regulation of cell size
ISO
PMID:16286931
Regulation of neuronal morphology and function by the tumor ...
KEEP AS NON CORE
Summary: Captures contexts where mTOR loss/inhibition reduces cell size or where mTOR feedback limits growth; the directionality opposite to its dominant pro-growth role.
Reason: Context/loss-of-function readout of mTOR growth control.
GO:0045792 negative regulation of cell size
IGI
PMID:16286931
Regulation of neuronal morphology and function by the tumor ...
KEEP AS NON CORE
Summary: Captures contexts where mTOR loss/inhibition reduces cell size or where mTOR feedback limits growth; the directionality opposite to its dominant pro-growth role.
Reason: Context/loss-of-function readout of mTOR growth control.
GO:0045859 regulation of protein kinase activity
IGI
PMID:15185396
Loss of tuberous sclerosis complex 1 (Tsc1) expression resul...
KEEP AS NON CORE
Summary: mTOR modulates activity of downstream kinases through phosphorylation; regulatory consequence of its catalytic role.
Reason: Downstream of core kinase activity.
GO:0016242 negative regulation of macroautophagy
IMP
PMID:16714284
Autophagy is disrupted in a knock-in mouse model of juvenile...
ACCEPT
Summary: mTORC1 directly restrains macroautophagy by phosphorylating ULK1 and inhibiting the autophagy-initiation machinery when nutrients are abundant.
Reason: Core; ULK1-mediated suppression of macroautophagy by mTORC1 (IMP/IBA).
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:11707573
FRAP/mTOR is required for proliferation and patterning durin...
ACCEPT
Summary: mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates.
Reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0018107 peptidyl-threonine phosphorylation
IDA
PMID:11707573
FRAP/mTOR is required for proliferation and patterning durin...
ACCEPT
Summary: mTOR phosphorylates threonine residues of substrates (e.g. AKT Thr450 turn motif), part of its Ser/Thr kinase catalytic repertoire.
Reason: Core; IDA-supported threonine phosphorylation by mTOR.
Supporting Evidence:
UniProt:Q9JLN9
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
file:mouse/Mtor/Mtor-deep-research-falcon.md
Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
GO:0007281 germ cell development
IDA
PMID:12140361
Dissection of the c-Kit signaling pathway in mouse primordia...
KEEP AS NON CORE
Summary: mTOR-dependent growth/translation supports germ-cell development; a downstream developmental phenotype (IDA).
Reason: Downstream developmental role of mTOR.

Core Functions

Acts as the catalytic kinase of mTORC1, integrating nutrient and growth-factor inputs at lysosomal membranes to regulate translation, cell growth, and autophagy.

Supporting Evidence:
  • UniProt:Q9JLN9
    Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
  • file:mouse/Mtor/Mtor-deep-research-falcon.md
    Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.

Acts as the catalytic kinase of mTORC2, phosphorylating AGC-family kinase substrates including AKT and supporting PI3K-AKT pathway output.

Supporting Evidence:
  • UniProt:Q9JLN9
    Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
  • file:mouse/Mtor/Mtor-deep-research-falcon.md
    Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.

References

Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on Enzyme Commission mapping
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Automatic Gene Ontology annotation based on Rhea mapping
Electronic Gene Ontology annotations created by ARBA machine learning models
Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs
Combined Automated Annotation using Multiple IEA Methods
FRAP/mTOR is required for proliferation and patterning during embryonic development in the mouse.
Insulin-stimulated phosphorylation of lipin mediated by the mammalian target of rapamycin.
FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction.
Dissection of the c-Kit signaling pathway in mouse primordial germ cells by retroviral-mediated gene transfer.
Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action.
GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR.
Loss of tuberous sclerosis complex 1 (Tsc1) expression results in increased Rheb/S6K pathway signaling important for astrocyte cell size regulation.
Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton.
Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive.
Disruption of the mouse mTOR gene leads to early postimplantation lethality and prohibits embryonic stem cell development.
Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2.
mTOR-dependent stimulation of the association of eIF4G and eIF3 by insulin.
Autophagy is disrupted in a knock-in mouse model of juvenile neuronal ceroid lipofuscinosis.
PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR.
Stress and mTORture signaling.
Steroid and oxygen effects on eIF4F complex, mTOR, and ENaC translation in fetal lung epithelia.
mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex.
Integration of protein kinases mTOR and extracellular signal-regulated kinase 5 in regulating nucleocytoplasmic localization of NFATc4.
Lkb1 deficiency causes prostate neoplasia in the mouse.
The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C.
Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling.
mTORC1 promotes survival through translational control of Mcl-1.
Specific activation of mTORC1 by Rheb G-protein in vitro involves enhanced recruitment of its substrate protein.
Transcription factor C/EBPbeta isoform ratio regulates osteoclastogenesis through MafB.
Regulation of myoblast differentiation by the nuclear envelope protein NET39.
Activation of a metabolic gene regulatory network downstream of mTOR complex 1.
Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes.
mTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide.
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1.
mTOR complex 2 targets Akt for proteasomal degradation via phosphorylation at the hydrophobic motif.
Protor-1 is required for efficient mTORC2-mediated activation of SGK1 in the kidney.
Glycerolipid signals alter mTOR complex 2 (mTORC2) to diminish insulin signaling.
mTOR signaling in growth control and disease.
5-HT(6) receptor recruitment of mTOR as a mechanism for perturbed cognition in schizophrenia.
mTOR complex 2 regulates proper turnover of insulin receptor substrate-1 via the ubiquitin ligase subunit Fbw8.
Stimulation of autophagy improves endoplasmic reticulum stress-induced diabetes.
Mechanistic target of rapamycin (Mtor) is essential for murine embryonic heart development and growth.
mTOR complex 2 phosphorylates IMP1 cotranslationally to promote IGF2 production and the proliferation of mouse embryonic fibroblasts.
Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis.
Degradation of high affinity HuD targets releases Kv1.1 mRNA from miR-129 repression by mTORC1.
Reduced juvenile long-term depression in tuberous sclerosis complex is mitigated in adults by compensatory recruitment of mGluR5 and Erk signaling.
Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy.
PIH1D1 interacts with mTOR complex 1 and enhances ribosome RNA transcription.
MicroRNA-23a promotes myelination in the central nervous system.
Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus.
Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice.
Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo.
Oligodendrocyte precursor cell-intrinsic effect of Rheb1 controls differentiation and mediates mTORC1-dependent myelination in brain.
Huntingtin functions as a scaffold for selective macroautophagy.
mLST8 Promotes mTOR-Mediated Tumor Progression.
Phosphorylation of ULK1 by AMPK regulates translocation of ULK1 to mitochondria and mitophagy.
miR-199a impairs autophagy and induces cardiac hypertrophy through mTOR activation.
The Interleukin-2-mTORc1 Kinase Axis Defines the Signaling, Differentiation, and Metabolism of T Helper 1 and Follicular B Helper T Cells.
Functional kinomics establishes a critical node of volume-sensitive cation-Cl(-) cotransporter regulation in the mammalian brain.
The tumor suppressor FLCN mediates an alternate mTOR pathway to regulate browning of adipose tissue.
mTOR Signaling in Growth, Metabolism, and Disease.
mTORC2 Promotes Tumorigenesis via Lipid Synthesis.
mTOR signaling regulates central and peripheral circadian clock function.
Serine 474 phosphorylation is essential for maximal Akt2 kinase activity in adipocytes.
Hyperactive Akt-mTOR pathway as a therapeutic target for pain hypersensitivity in Cntnap2-deficient mice.
The GATOR2-mTORC2 axis mediates Sestrin2-induced AKT Ser/Thr kinase activation.
mTORC2 controls the activity of PKC and Akt by phosphorylating a conserved TOR interaction motif.
The innate immune kinase TBK1 directly increases mTORC2 activity and downstream signaling to Akt.
Picornavirus infection enhances aspartate by the SLC38A8 transporter to promote viral replication.
UniProt:Q9JLN9
UniProtKB record for mouse Mtor (Q9JLN9)
file:mouse/Mtor/Mtor-deep-research-falcon.md
Falcon deep research synthesis for mouse Mtor

Deep Research

Falcon

(Mtor-deep-research-falcon.md)
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 41 citations 2026-05-03T20:38:52.520084

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.

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Research report: Mouse Mtor (UniProt Q9JLN9) — functional annotation, pathways, localization, and applications

Executive summary

Mouse Mtor encodes mechanistic/mammalian target of rapamycin (mTOR), a PI3K-related serine/threonine kinase that nucleates two signaling complexes, mTORC1 and mTORC2, which coordinate growth-factor, nutrient, and energy-stress information to regulate translation, metabolism, autophagy, and cytoskeletal programs. The most current mechanistic model places mTORC1 activation on the cytosolic face of lysosomal membranes, where Rag–Ragulator (nutrient/amino-acid arm) and Rheb (growth-factor arm downstream of TSC1/2) converge to recruit and catalytically activate mTORC1. Recent (2024) cryo-EM reconstitution studies quantify this synergy and provide a structural rationale for signal integration at the lysosome. Translationally, partial pathway coverage by first-generation rapalogs has motivated development of ATP-competitive mTORC1/2 inhibitors and bi-steric mTORC1-selective inhibitors, with measurable (but toxicity-limited) clinical activity; in parallel, mTOR inhibition is now being implemented in aging/metabolism and even dermatologic trials.

1) Key concepts and definitions (current understanding)

1.1 Gene/protein identity verification

Multiple 2024 reviews explicitly define mTOR as the “mammalian target of rapamycin” and describe it as a PI3K-related protein kinase, aligning with the UniProt entry for mouse Mtor (UniProt Q9JLN9). (marafie2024mtoritscritical pages 1-3, basnet2024mammaliantargetof pages 7-8)

1.2 Enzymatic function and complex architecture

mTOR is the catalytic kinase within:
- mTORC1: includes mTOR, Raptor, mLST8, and regulatory subunits such as PRAS40 and DEPTOR (with some reviews also listing assembly/stability factors like Tel2/Tti1). (marafie2024mtoritscritical pages 1-3, chen2024targetingthemtorautophagy pages 2-4)
- mTORC2: includes mTOR, Rictor, mSIN1, mLST8, and DEPTOR (some reviews also note Protor). (marafie2024mtoritscritical pages 1-3, basnet2024mammaliantargetof pages 2-4)

Canonical outputs:
- mTORC1 phosphorylates S6K1/2 and 4E-BP1/2 (translation/growth control). (marafie2024mtoritscritical pages 1-3, basnet2024mammaliantargetof pages 2-4, cui2024structuralbasisfor pages 23-28)
- mTORC2 promotes Akt Ser473 phosphorylation, supporting survival and other downstream programs. (marafie2024mtoritscritical pages 1-3, basnet2024mammaliantargetof pages 2-4, subbiah2024phaseistudy pages 1-2)

1.3 Pathway-level positioning

A widely used pathway abstraction is that growth-factor/PI3K signaling activates Akt, which inhibits TSC1/2, allowing Rheb to stimulate mTORC1. (marafie2024mtoritscritical pages 1-3, basnet2024mammaliantargetof pages 2-4)

2) Recent developments and latest research (prioritizing 2023–2024)

2.1 Lysosomal membrane signal integration by mTORC1 (structural and quantitative 2024 evidence)

A 2024 cryo-EM and biochemical reconstitution study (Cui et al., bioRxiv; publication date Nov 2024, https://doi.org/10.1101/2024.11.15.623810) reconstructed an mTORC1–Rheb–Rag–Ragulator–4EBP1 complex on membranes and quantified the synergy between nutrient and growth-factor arms:
- >35-fold activation of mTORC1 kinase activity with liposomes + Rag–Ragulator + Rheb-GTP (vs baseline), while Rheb-GTP alone on vesicles produced ~3-fold activation in the reported conditions. (cui2024structuralbasisfor pages 4-7)
- Physiologic reconstitution conditions in the excerpt include 250 nM Rheb and 300 nM RagA/C–Ragulator. (cui2024structuralbasisfor pages 4-7)
- Membrane geometry mattered: small 30–50 nm liposomes reduced activity by ~65%, indicating a potential role for membrane curvature/shape in mTORC1 activation efficiency. (cui2024structuralbasisfor pages 4-7)
- The authors propose a three-step proximity/engagement model: Rag–Ragulator recruitment brings mTORC1 within ~100 Å of the membrane; Rheb recruitment brings it within ~40 Å; then direct mTOR/Raptor membrane engagement completes maximal activation. (cui2024structuralbasisfor pages 4-7)
- Cell-based validation in Raptor KO MEFs quantified decreased pS6K and p4EBP1 after perturbations, reporting n=3 experiments and P < 0.0001 in a two-way ANOVA framework. (cui2024structuralbasisfor pages 23-28)

These results strengthen the current view that mTORC1 is activated at lysosomal membranes via coordinated, multi-component recruitment and membrane engagement. (cui2024structuralbasisfor pages 7-10, cui2024structuralbasisfor pages 23-28)

2.2 Energy stress control via AXIN and AMPK at lysosomes (2023)

A 2023 study in Life Metabolism (publication date Mar 2023, https://doi.org/10.1093/lifemeta/load005) supports a hierarchical inhibition model in which glucose starvation triggers AXIN lysosomal translocation to inactivate/sunder mTORC1 from lysosomes via Rag inhibition, and AMPK further inhibits mTORC1 through phosphorylation of Raptor and TSC2, particularly under severe stress. (li2023hierarchicalinhibitionof pages 12-13)

3) Cellular localization and where mTOR acts

3.1 Lysosomal surface as an operational hub for mTORC1

Multiple sources converge on the lysosome as a key spatial node for mTORC1 regulation:
- Structural reconstitution directly places the activating complex on membranes with Ragulator and lipidated Rheb providing membrane anchoring and shows direct membrane-contacting features in mTOR and Raptor. (cui2024structuralbasisfor pages 7-10, cui2024structuralbasisfor pages 23-28)
- A 2024 review notes Raptor’s role in mTORC1 stability/substrate recognition and explicitly links it to localization to lysosomal surfaces. (chen2024targetingthemtorautophagy pages 2-4)

3.2 Beyond lysosomes

The gathered evidence set is strongest on lysosomal recruitment/activation; it does not exclude additional pools (e.g., cytoplasmic, other organelles). A recent conceptual advance (not fully quantified in the retrieved excerpts) is that different amino-acid sources may produce spatially separated mTORC1 signaling, implying non-lysosomal mTORC1 substrate phosphorylation can occur under some nutrient contexts. (fernandes2024spatialandfunctional, retrieved but not evidence-extracted here)

4) Regulation and biochemical pathway roles (precision emphasis)

4.1 Nutrient arm (Rag GTPases / Ragulator)

Amino-acid sensing is mediated through Rag GTPases and Ragulator, which recruit/organize mTORC1 on lysosomal membranes; this architecture is explicitly reconstituted structurally and biochemically in the 2024 membrane cryo-EM system. (cui2024structuralbasisfor pages 4-7, cui2024structuralbasisfor pages 23-28)

4.2 Growth-factor arm (TSC1/2 → Rheb)

Akt-dependent inhibition of TSC1/2 is a standard mechanism for permitting Rheb activation of mTORC1, and structural work references TSC2 as the opposing GAP for Rheb. (marafie2024mtoritscritical pages 1-3, cui2024structuralbasisfor pages 23-28)

4.3 Energy-stress arm (AXIN/AMPK)

Glucose starvation and energetic stress inhibit mTORC1 through AXIN and AMPK, including Rag-dependent lysosomal mechanisms and AMPK phosphorylation of Raptor/TSC2. (li2023hierarchicalinhibitionof pages 12-13)

5) Current applications and real-world implementations

5.1 Oncology: evolution of mTOR inhibitors and resistance considerations

Therapeutic targeting has progressed from rapamycin/rapalogs to catalytic inhibitors because rapalogs can yield incomplete pathway suppression (notably limited 4E-BP1 effects) and allow compensatory signaling (including via mTORC2/Akt). (du2023bistericmtorc1inhibitors pages 1-2, subbiah2024phaseistudy pages 1-2, marafie2024mtoritscritical pages 8-9)

A key quantitative clinical example is a Phase I trial of dual mTORC1/2 inhibition:
- Sapanisertib (TAK-228/MLN0128) + metformin in 30 heavily pretreated patients showed 4/30 partial responses, 15/30 stable disease, and 63% disease control; Grade 3–5 treatment-related AEs included hyperglycemia 13% and fatigue 7%; MTD was 4 mg sapanisertib + 1,000 mg metformin (publication date Dec 2024, https://doi.org/10.1158/2767-9764.crc-22-0260). (subbiah2024phaseistudy pages 1-2)

Preclinical benchmarking and mechanistic translation:
- In a 2023 JCI study (publication date Nov 2023, https://doi.org/10.1172/jci167861), rapamycin had no effect on p-4EBP1 even at 100 nM, whereas MLN0128 reduced phospho-sites at 10–30 nM and inhibited p-AKT Ser473 at 100 nM; bi-steric mTORC1-selective inhibitors nearly abolished mTORC1 activity at 0.3 nM and increased apoptosis compared with rapamycin or MLN0128. (du2023bistericmtorc1inhibitors pages 1-2)

5.2 Aging/metabolism: controlled mTOR inhibition in humans

ClinicalTrials.gov records show ongoing implementation of mTOR modulation in aging/metabolism:
- NCT05835999 (Everolimus Aging Study): Phase 2, randomized, placebo-controlled trial (start 2023-03-24) testing everolimus 0.5 mg/day vs 5 mg/week vs placebo for 24 weeks in adults 55–80 with insulin resistance/prediabetes; primary endpoint is insulin sensitivity during a dual-tracer 75 g OGTT. URL: https://clinicaltrials.gov/study/NCT05835999. (NCT05835999 chunk 1)
- NCT06658093 (RESTOR): early-phase interventional PK/PD dose-optimization of sirolimus and everolimus in healthy older adults (estimated enrollment 194, start 2025-08-13, recruiting). URL: https://clinicaltrials.gov/study/NCT06658093. (NCT06658093 chunk 1)

5.3 Dermatology implementation (example of pathway broadening)

  • NCT07166354: Phase 1/2 randomized, quadruple-masked study of topical mTOR inhibitor CS-002 for grey hair (canities), estimated enrollment 100, status not-yet-recruiting (start 2025-10-01). URL: https://clinicaltrials.gov/NCT07166354. (NCT07166354 chunk 1)

6) Expert opinions / analysis synthesized from authoritative sources

Across 2024 reviews and 2023–2024 primary studies, a consistent expert-level interpretation emerges:
1. Spatial control is central: mTORC1’s lysosomal recruitment and membrane engagement are not incidental but mechanistically required for robust signal integration (nutrients + growth factors). (cui2024structuralbasisfor pages 7-10, cui2024structuralbasisfor pages 23-28)
2. Therapeutic depth vs tolerability trade-off: deeper blockade (catalytic inhibitors, dual mTORC1/2) can address rapalog escape but introduces toxicity constraints; hence renewed interest in mTORC1-selective but mechanistically complete inhibitors (e.g., bi-steric agents) to suppress 4E-BP1 while limiting mTORC2-associated liabilities. (du2023bistericmtorc1inhibitors pages 1-2, subbiah2024phaseistudy pages 1-2)

7) Statistics and data highlights from recent studies

  • >35-fold activation of reconstituted mTORC1 by combined Rag–Ragulator + Rheb-GTP on membranes; ~65% activity reduction on small (30–50 nm) liposomes (Nov 2024 preprint). (cui2024structuralbasisfor pages 4-7)
  • In cell experiments, quantification of mTORC1 outputs (pS6K, p4EBP1) reported n=3 and P < 0.0001 for specific comparisons in Raptor KO MEFs (Nov 2024 preprint). (cui2024structuralbasisfor pages 23-28)
  • Phase I clinical activity of dual mTORC1/2 inhibitor sapanisertib + metformin: 4/30 PR, 15/30 SD, 63% DCR; hyperglycemia 13% and fatigue 7% grade 3–5 TRAEs (Dec 2024). (subbiah2024phaseistudy pages 1-2)
  • Preclinical potency comparisons: rapamycin fails to suppress p-4EBP1 at 100 nM, while bi-steric inhibitors suppress mTORC1 activity at 0.3 nM (Nov 2023). (du2023bistericmtorc1inhibitors pages 1-2)

Figures and tables for functional annotation

The following artifacts and evidence figure crops summarize key mechanistic aspects:

Aspect Current understanding (concise) Key evidence (include paper title, year, and DOI URL) Notes/limitations
Verified identity Mouse Mtor (UniProt Q9JLN9) corresponds to mechanistic/mammalian target of rapamycin (mTOR), a PI3K-related serine/threonine protein kinase. The retrieved literature aligns with the UniProt description and known synonyms “mammalian target of rapamycin” and “mTOR”. (marafie2024mtoritscritical pages 1-3, basnet2024mammaliantargetof pages 7-8) mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process (2024), DOI: https://doi.org/10.3390/ijms25116141; Mammalian Target of Rapamycin (mTOR) Signalling Pathway—A Potential Target for Cancer Intervention: A Short Overview (2024), DOI: https://doi.org/10.2174/1874467217666230331081959 Evidence here is largely mammalian-review level rather than mouse-only biochemistry, but it matches UniProt Q9JLN9 and canonical mTOR biology.
Kinase type / enzyme function mTOR is the catalytic kinase in mTOR complexes and functions as a serine/threonine kinase of the PIKK family; recent structural work further indicates that activation is conformational and membrane-dependent. (cui2024structuralbasisfor pages 7-10, marafie2024mtoritscritical pages 1-3, basnet2024mammaliantargetof pages 2-4) Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mTORC1 (2024 preprint), DOI: https://doi.org/10.1101/2024.11.15.623810; mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process (2024), DOI: https://doi.org/10.3390/ijms25116141; Mammalian Target of Rapamycin (mTOR) Signalling Pathway—A Potential Target for Cancer Intervention: A Short Overview (2024), DOI: https://doi.org/10.2174/1874467217666230331081959 UniProt notes EC 2.7.11.1 with historical evidence; retrieved sources emphasize serine/threonine kinase activity.
Complexes / core subunits mTOR assembles into mTORC1 and mTORC2. Retrieved sources list mTORC1 with Raptor, mLST8, PRAS40, and DEPTOR and mTORC2 with Rictor, mSIN1, mLST8, and DEPTOR; some reviews also include Tel2/Tti1 and Protor in broader subunit summaries. (marafie2024mtoritscritical pages 1-3, basnet2024mammaliantargetof pages 2-4, chen2024targetingthemtorautophagy pages 2-4) mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process (2024), DOI: https://doi.org/10.3390/ijms25116141; Mammalian Target of Rapamycin (mTOR) Signalling Pathway—A Potential Target for Cancer Intervention: A Short Overview (2024), DOI: https://doi.org/10.2174/1874467217666230331081959; Targeting the mTOR-Autophagy Axis: Unveiling Therapeutic Potentials in Osteoporosis (2024), DOI: https://doi.org/10.3390/biom14111452 Subunit lists vary slightly by review because some include assembly/stability cofactors whereas others emphasize core signaling subunits.
Canonical substrates / outputs mTORC1 phosphorylates S6K1/2 and 4E-BP1/2, promoting translation and cell growth; mTORC2 promotes AKT Ser473 phosphorylation. Recent structural and functional work directly assays mTORC1 outputs using 4EBP1 and S6K. (cui2024structuralbasisfor pages 4-7, marafie2024mtoritscritical pages 1-3, basnet2024mammaliantargetof pages 2-4, cui2024structuralbasisfor pages 23-28) Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mTORC1 (2024 preprint), DOI: https://doi.org/10.1101/2024.11.15.623810; mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process (2024), DOI: https://doi.org/10.3390/ijms25116141; Mammalian Target of Rapamycin (mTOR) Signalling Pathway—A Potential Target for Cancer Intervention: A Short Overview (2024), DOI: https://doi.org/10.2174/1874467217666230331081959 Retrieved evidence is strongest for canonical mammalian substrates; substrate scope is broader in the full literature than summarized here.
Regulation by Rheb Rheb-GTP is a direct activator of mTORC1; recent cryo-EM and reconstitution work shows strong activation when lipidated Rheb-GTP is presented on membranes and resolves a direct Rheb–mTOR interface. Rheb-GDP does not equivalently activate. (cui2024structuralbasisfor pages 4-7, cui2024structuralbasisfor pages 7-10, cui2024structuralbasisfor pages 23-28) Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mTORC1 (2024 preprint), DOI: https://doi.org/10.1101/2024.11.15.623810 Preprint evidence is highly mechanistic but not yet peer reviewed.
Regulation by Rag GTPases and Ragulator Amino-acid signaling to mTORC1 occurs through Rag GTPases and Ragulator, which recruit and organize mTORC1 on lysosomal membranes; recent structural work reconstitutes an mTORC1–Rheb–Rag–Ragulator membrane complex and prior cited mechanisms support Rag–Raptor interaction. (cui2024structuralbasisfor pages 4-7, li2023hierarchicalinhibitionof pages 12-13, cui2024structuralbasisfor pages 23-28) Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mTORC1 (2024 preprint), DOI: https://doi.org/10.1101/2024.11.15.623810; Hierarchical inhibition of mTORC1 by glucose starvation-triggered AXIN lysosomal translocation and by AMPK (2023), DOI: https://doi.org/10.1093/lifemeta/load005 The 2023 AXIN/AMPK source supports the Ragulator and Rag framework mainly through cited mechanistic context rather than direct new structural data in the excerpt.
Regulation by TSC1/2 and Akt Growth-factor and PI3K signaling activate Akt, which inhibits the TSC1/2 complex, thereby permitting Rheb-dependent mTORC1 activation. TSC2 is also referenced as the GAP opposing Rheb in structural and mechanistic context. (marafie2024mtoritscritical pages 1-3, basnet2024mammaliantargetof pages 2-4, cui2024structuralbasisfor pages 23-28) mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process (2024), DOI: https://doi.org/10.3390/ijms25116141; Mammalian Target of Rapamycin (mTOR) Signalling Pathway—A Potential Target for Cancer Intervention: A Short Overview (2024), DOI: https://doi.org/10.2174/1874467217666230331081959; Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mTORC1 (2024 preprint), DOI: https://doi.org/10.1101/2024.11.15.623810 Reviews summarize the pathway clearly; direct mouse-specific biochemical dissection in the retrieved set is limited.
Regulation by AMPK and AXIN Energy stress inhibits mTORC1 through AXIN lysosomal translocation and AMPK. In the 2023 study, AXIN-mediated lysosomal events act early or primarily under glucose starvation, whereas AMPK additionally inhibits via Raptor and TSC2 phosphorylation, especially under severe stress. (li2023hierarchicalinhibitionof pages 12-13) Hierarchical inhibition of mTORC1 by glucose starvation-triggered AXIN lysosomal translocation and by AMPK (2023), DOI: https://doi.org/10.1093/lifemeta/load005 Excerpted evidence is summary-level; precise quantitative results from that study were not available in the retrieved passage.
Subcellular localization A key operational localization for mTORC1 is the cytosolic face of the lysosomal membrane, where nutrient and growth-factor inputs converge. Raptor contributes to lysosomal surface localization and stability, and recent structural work maps direct membrane contacts by both mTOR and Raptor. (cui2024structuralbasisfor pages 7-10, chen2024targetingthemtorautophagy pages 2-4, cui2024structuralbasisfor pages 23-28) Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mTORC1 (2024 preprint), DOI: https://doi.org/10.1101/2024.11.15.623810; Targeting the mTOR-Autophagy Axis: Unveiling Therapeutic Potentials in Osteoporosis (2024), DOI: https://doi.org/10.3390/biom14111452 Retrieved evidence strongly supports lysosomal localization for mTORC1; it does not exclude additional cytoplasmic or other compartmental pools.
Quantitative finding: membrane reconstitution synergy In Cui et al. 2024, liposomes plus Rag-Ragulator plus Rheb-GTP increased mTORC1 activity by more than 35-fold; Rheb-GTP on large unilamellar vesicles alone produced about a 3-fold increase. Experimental concentrations cited in the excerpt were 250 nM Rheb and 300 nM RagA/C-Ragulator. (cui2024structuralbasisfor pages 4-7) Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mTORC1 (2024 preprint), DOI: https://doi.org/10.1101/2024.11.15.623810 Strong quantitative mechanistic support, but from a preprint.
Quantitative finding: membrane geometry and distances Cui et al. report a three-step lysosomal activation model in which Rag-Ragulator recruitment brings mTORC1 to within about 100 Å of the membrane, Rheb recruitment to within about 40 Å, and direct mTOR and Raptor membrane engagement completes activation; Rheb was positioned about 13 Å above the membrane in the structure. Smaller 30 to 50 nm liposomes reduced activity by about 65%. (cui2024structuralbasisfor pages 4-7, cui2024structuralbasisfor pages 23-28) Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mTORC1 (2024 preprint), DOI: https://doi.org/10.1101/2024.11.15.623810 Distances are structural-model estimates from membrane reconstitution, not direct in vivo intracellular distance measurements.
Quantitative finding: structural states and cell-based validation Cui et al. resolved intermediate and active membrane-bound states at 3.61 Å and 3.16 Å. In inducible Raptor KO MEFs, rescue and perturbation experiments quantified pS6K and p4EBP1 with n = 3 experiments, reporting P < 0.0001 by two-way ANOVA with Dunnett’s multiple-comparisons test. (cui2024structuralbasisfor pages 7-10, cui2024structuralbasisfor pages 23-28) Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mTORC1 (2024 preprint), DOI: https://doi.org/10.1101/2024.11.15.623810 Useful for confidence in mechanistic conclusions, but still centered on mTORC1 rather than full Mtor biology across all tissues and contexts.

Table: This table verifies that UniProt Q9JLN9 is mouse Mtor/mTOR and summarizes its core biochemical function, complex membership, regulation, localization, and key recent quantitative mechanistic findings. It is useful as a concise evidence map for functional annotation focused on the primary molecular role of the gene product.

A schematic figure set showing mTORC1 on membranes (Rheb, Rag, Ragulator; three-step activation model) was extracted from Cui et al. 2024 and can be cited directly. (cui2024structuralbasisfor media 2962e450, cui2024structuralbasisfor media b885f8f5, cui2024structuralbasisfor media b9f8adb3, cui2024structuralbasisfor media 1bcd6393)

Modality Example agent(s) Mechanistic rationale (mTORC1 vs mTORC2, substrates) Key quantitative findings Source (paper/trial, year, URL/DOI/NCT)
Rapalog / allosteric mTOR inhibitor Rapamycin (sirolimus), everolimus, temsirolimus First-generation FKBP12-dependent inhibitors that primarily suppress mTORC1; incomplete suppression of some outputs, especially weak effect on 4E-BP1 in some settings, while mTORC2-AKT Ser473 signaling can persist or rebound, contributing to feedback resistance (marafie2024mtoritscritical pages 8-9, du2023bistericmtorc1inhibitors pages 1-2, mehta2024unveilingtherole pages 1-2) In glioblastoma, everolimus + temozolomide + radiation in 18 patients produced 4 partial responses and 9 patients with advanced toxicities; a separate 100-patient study found no survival benefit versus standard therapy. Rapamycin had no effect on p-4EBP1 even at 100 nM in the JCI preclinical comparison (marafie2024mtoritscritical pages 8-9, du2023bistericmtorc1inhibitors pages 1-2) Marafie et al., 2024, https://doi.org/10.3390/ijms25116141; Du et al., 2023, https://doi.org/10.1172/jci167861; Mehta et al., 2024, https://doi.org/10.1021/acsptsci.4c00530 (marafie2024mtoritscritical pages 8-9, du2023bistericmtorc1inhibitors pages 1-2, mehta2024unveilingtherole pages 1-2)
ATP-competitive dual mTORC1/2 inhibitor Sapanisertib / TAK-228 / MLN0128 Designed to inhibit catalytic activity of both mTORC1 and mTORC2, aiming to overcome rapalog-mediated escape through persistent AKT Ser473 phosphorylation and incomplete blockade of translational outputs (marafie2024mtoritscritical pages 8-9, subbiah2024phaseistudy pages 1-2, du2023bistericmtorc1inhibitors pages 1-2) Phase I combination study: 30 heavily pretreated patients; 4/30 partial responses, 15/30 stable disease, 63% disease-control rate; responders enriched for PTEN alterations (3/4 PRs, 3/5 PTEN-mutant patients had PR). Grade 3-5 treatment-related AEs included hyperglycemia 13% and fatigue 7%; MTD was 4 mg sapanisertib + 1,000 mg metformin. Preclinically, MLN0128 reduced phospho-sites at 10-30 nM and inhibited p-AKT S473 at 100 nM (subbiah2024phaseistudy pages 1-2, du2023bistericmtorc1inhibitors pages 1-2) Subbiah et al., 2024, https://doi.org/10.1158/2767-9764.crc-22-0260; Du et al., 2023, https://doi.org/10.1172/jci167861; Marafie et al., 2024, https://doi.org/10.3390/ijms25116141 (subbiah2024phaseistudy pages 1-2, du2023bistericmtorc1inhibitors pages 1-2, marafie2024mtoritscritical pages 8-9)
Bi-steric mTORC1-selective inhibitor RMC-6272; related bi-steric mTORC1 inhibitors Engineered to more completely inhibit mTORC1 outputs, including 4E-BP1, while avoiding full mTORC2 inhibition-associated toxicity; intended for tumors with hyperactivated mTORC1 (du2023bistericmtorc1inhibitors pages 1-2, mehta2024unveilingtherole pages 1-2) In tumor models, bi-steric inhibitors eliminated phosphorylated 4EBP1, induced more apoptosis than rapamycin or MLN0128, and 0.3 nM nearly abolished mTORC1 activity; RMC-6272 at 1 nM for 24 h induced G0/G1 arrest and reduced clonogenic growth. Pathway relevance: PI3K/AKT/mTOR alterations noted in 4,689/10,800 (43%) cancers in the cited study background (du2023bistericmtorc1inhibitors pages 1-2) Du et al., 2023, https://doi.org/10.1172/jci167861; Mehta et al., 2024, https://doi.org/10.1021/acsptsci.4c00530 (du2023bistericmtorc1inhibitors pages 1-2, mehta2024unveilingtherole pages 1-2)
Rapalog implementation in presurgical pharmacodynamic oncology study Temsirolimus 25 mg IV weekly Clinical pharmacodynamic implementation of mTOR pathway inhibition to test target engagement in tumor tissue using p4EBP1 and S6K1 as readouts, directly linking drug exposure to canonical mTORC1 substrate modulation (NCT02093598 chunk 1) Phase IIa POEM study enrolled 10 actual participants with endometrial carcinoma; regimen was 25 mg IV weekly for 28 days (4 doses); completed study with biomarker endpoints in tumor tissue after four weeks (NCT02093598 chunk 1) ClinicalTrials.gov NCT02093598, 2012 registry record, https://clinicaltrials.gov/study/NCT02093598 (NCT02093598 chunk 1)
Aging/metabolism trial using rapalog dosing strategies Everolimus 0.5 mg/day or 5 mg/week Tests whether controlled mTOR modulation in adults with insulin resistance/prediabetes can alter metabolic phenotypes; includes molecular assessments of mTORC1/mTORC2 signaling to compare continuous versus intermittent dosing (NCT05835999 chunk 1) Phase 2, randomized, placebo-controlled trial; 106 participants; oral everolimus for 24 weeks with 0.5 mg/day or 5 mg/week regimens versus placebo; primary endpoint is change in peripheral insulin sensitivity during dual-tracer 75 g OGTT (NCT05835999 chunk 1) ClinicalTrials.gov NCT05835999, 2023 registry record, https://clinicaltrials.gov/study/NCT05835999 (NCT05835999 chunk 1)
Aging trial comparing rapamycin vs everolimus PK/PD Rapamycin (sirolimus), everolimus Translational PK/PD implementation comparing two clinically available mTOR inhibitors in older adults; mechanistic endpoints include blood, adipose, and muscle p-rpS6, pS6K, Akt to optimize daily versus intermittent inhibition (NCT06658093 chunk 1, NCT06658093 chunk 2) Early Phase 1, recruiting; estimated enrollment 194; healthy adults mainly 65-90 years; adaptive dose-finding followed by blinded placebo-controlled phase; PK/PD endpoints include whole-blood inhibition and tissue biomarkers over about 12 weeks to 12 months depending on sub-study (NCT06658093 chunk 1, NCT06658093 chunk 2) ClinicalTrials.gov NCT06658093, 2025 registry record, https://clinicaltrials.gov/study/NCT06658093 (NCT06658093 chunk 1, NCT06658093 chunk 2)
Human physiology / muscle aging implementation Rapamune (sirolimus) Tests whether mTOR inhibition modulates muscle size, function, and protein turnover in older humans, connecting canonical mTOR growth-control biology to sarcopenia-related physiology (NCT05414292 chunk 1) Recruiting study with estimated enrollment 16 healthy men >50 years; about 16 weeks total intervention including 14 weeks unilateral resistance exercise; outcomes include MRI, ultrasound, strength testing, tracers, and bilateral muscle biopsies (NCT05414292 chunk 1) ClinicalTrials.gov NCT05414292, 2021 registry record, https://clinicaltrials.gov/study/NCT05414292 (NCT05414292 chunk 1)
Topical/local mTOR inhibition CS-002 topical mTOR inhibitor Local mTOR pathway modulation for a non-oncology indication (grey hair/canities), illustrating expansion of mTOR targeting beyond cancer and immunosuppression into dermatologic implementation (NCT07166354 chunk 1) Randomized Phase 1/2, quadruple-masked study; estimated enrollment 100 adults aged 30-65; placebo-controlled; primary endpoint is Greying Severity Score over 24 weeks; status not yet recruiting (NCT07166354 chunk 1) ClinicalTrials.gov NCT07166354, 2025 registry record, https://clinicaltrials.gov/NCT07166354 (NCT07166354 chunk 1)
Formulation / PK-improved rapalog and broader translational evolution Temsirolimus, everolimus, RapaLinks, newer dual inhibitors Reviews emphasize progression from rapamycin to more drug-like rapalogs and next-generation inhibitors to improve solubility, bioavailability, depth of pathway blockade, and resistance control; RapaLinks are highlighted as more potent hybrid approaches (mehta2024unveilingtherole pages 8-10, mehta2024unveilingtherole pages 1-2) Temsirolimus improves solubility but is IV-only and rapidly cleared; everolimus has ~30 h half-life, whereas rapamycin has biological half-life >50 h. Reviews describe RapaLinks as more potent in preclinical studies, though specific response numbers were not given in the retrieved excerpt (mehta2024unveilingtherole pages 8-10, mehta2024unveilingtherole pages 1-2) Mehta et al., 2024, https://doi.org/10.1021/acsptsci.4c00530 (mehta2024unveilingtherole pages 8-10, mehta2024unveilingtherole pages 1-2)

Table: This table summarizes recent translational and clinical implementations of mTOR pathway modulation, spanning rapalogs, catalytic inhibitors, bi-steric inhibitors, and emerging aging and topical applications. It highlights how mechanism, substrate coverage, and feedback biology translate into measurable efficacy, toxicity, and trial design choices.

Limitations of this report

  • The strongest mechanistic localization/activation evidence in this evidence set is for mTORC1 and comes from a 2024 bioRxiv preprint; although detailed and quantitative, it is not yet peer-reviewed in the retrieved form. (cui2024structuralbasisfor pages 4-7, cui2024structuralbasisfor pages 23-28)
  • Several complex subunit lists come from narrative reviews; while consistent with consensus, subunit inclusion criteria (core vs assembly factors) vary across sources. (marafie2024mtoritscritical pages 1-3, chen2024targetingthemtorautophagy pages 2-4)

Key URLs (publication dates)

  • Cui et al. Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mTORC1 (bioRxiv, Nov 2024): https://doi.org/10.1101/2024.11.15.623810 (cui2024structuralbasisfor pages 4-7)
  • Li et al. Hierarchical inhibition of mTORC1 by glucose starvation-triggered AXIN lysosomal translocation and by AMPK (Life Metabolism, Mar 2023): https://doi.org/10.1093/lifemeta/load005 (li2023hierarchicalinhibitionof pages 12-13)
  • Marafie et al. mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process (IJMS, Jun 2024): https://doi.org/10.3390/ijms25116141 (marafie2024mtoritscritical pages 1-3)
  • Subbiah et al. Phase I study of mTORC1/2 inhibitor sapanisertib + metformin (Cancer Research Communications, Dec 2024): https://doi.org/10.1158/2767-9764.crc-22-0260 (subbiah2024phaseistudy pages 1-2)
  • Du et al. Bi-steric mTORC1 inhibitors induce apoptotic cell death… (JCI, Nov 2023): https://doi.org/10.1172/jci167861 (du2023bistericmtorc1inhibitors pages 1-2)
  • ClinicalTrials.gov NCT05835999 (start 2023-03-24): https://clinicaltrials.gov/study/NCT05835999 (NCT05835999 chunk 1)
  • ClinicalTrials.gov NCT06658093 (start 2025-08-13): https://clinicaltrials.gov/study/NCT06658093 (NCT06658093 chunk 1)
  • ClinicalTrials.gov NCT07166354 (start 2025-10-01): https://clinicaltrials.gov/NCT07166354 (NCT07166354 chunk 1)

References

  1. (marafie2024mtoritscritical pages 1-3): Sulaiman K. Marafie, Fahd Al-Mulla, and Jehad Abubaker. Mtor: its critical role in metabolic diseases, cancer, and the aging process. International Journal of Molecular Sciences, 25:6141, Jun 2024. URL: https://doi.org/10.3390/ijms25116141, doi:10.3390/ijms25116141. This article has 98 citations.

  2. (basnet2024mammaliantargetof pages 7-8): Rajesh Basnet, Buddha Bahadur Basnet, Radheshyam Gupta, TilBahadur Basnet, Sandhya Khadka, and Md Shan Alam. Mammalian target of rapamycin (mtor) signalling pathway-a potential target for cancer intervention: a short overview. Current Molecular Pharmacology, Aug 2024. URL: https://doi.org/10.2174/1874467217666230331081959, doi:10.2174/1874467217666230331081959. This article has 18 citations and is from a peer-reviewed journal.

  3. (chen2024targetingthemtorautophagy pages 2-4): Rongjin Chen, Chenhui Yang, Fei Yang, Ao Yang, Hefang Xiao, Bo Peng, Changshun Chen, Bin Geng, and Yayi Xia. Targeting the mtor-autophagy axis: unveiling therapeutic potentials in osteoporosis. Biomolecules, 14:1452, Nov 2024. URL: https://doi.org/10.3390/biom14111452, doi:10.3390/biom14111452. This article has 22 citations.

  4. (basnet2024mammaliantargetof pages 2-4): Rajesh Basnet, Buddha Bahadur Basnet, Radheshyam Gupta, TilBahadur Basnet, Sandhya Khadka, and Md Shan Alam. Mammalian target of rapamycin (mtor) signalling pathway-a potential target for cancer intervention: a short overview. Current Molecular Pharmacology, Aug 2024. URL: https://doi.org/10.2174/1874467217666230331081959, doi:10.2174/1874467217666230331081959. This article has 18 citations and is from a peer-reviewed journal.

  5. (cui2024structuralbasisfor pages 23-28): Zhicheng Cui, Alessandra Esposito, Gennaro Napolitano, Andrea Ballabio, and James H. Hurley. Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mtorc1. bioRxiv, Nov 2024. URL: https://doi.org/10.1101/2024.11.15.623810, doi:10.1101/2024.11.15.623810. This article has 5 citations.

  6. (subbiah2024phaseistudy pages 1-2): V. Subbiah, Niamh Coleman, S. Piha-Paul, A. Tsimberidou, F. Janku, J. Rodón, Shubham Pant, E. Dumbrava, S. Fu, David S Hong, Shizhen Zhang, Ming Sun, Yunfang Jiang, J. Roszik, Juhee Song, Ying Yuan, F. Meric-Bernstam, and A. Naing. Phase i study of mtorc1/2 inhibitor sapanisertib (cb-228/tak-228) in combination with metformin in patients with mtor/akt/pi3k pathway alterations and advanced solid malignancies. Cancer Research Communications, 4:378-387, Dec 2024. URL: https://doi.org/10.1158/2767-9764.crc-22-0260, doi:10.1158/2767-9764.crc-22-0260. This article has 37 citations and is from a peer-reviewed journal.

  7. (cui2024structuralbasisfor pages 4-7): Zhicheng Cui, Alessandra Esposito, Gennaro Napolitano, Andrea Ballabio, and James H. Hurley. Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mtorc1. bioRxiv, Nov 2024. URL: https://doi.org/10.1101/2024.11.15.623810, doi:10.1101/2024.11.15.623810. This article has 5 citations.

  8. (cui2024structuralbasisfor pages 7-10): Zhicheng Cui, Alessandra Esposito, Gennaro Napolitano, Andrea Ballabio, and James H. Hurley. Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mtorc1. bioRxiv, Nov 2024. URL: https://doi.org/10.1101/2024.11.15.623810, doi:10.1101/2024.11.15.623810. This article has 5 citations.

  9. (li2023hierarchicalinhibitionof pages 12-13): Mengqi Li, Xiaoyan Wei, Jinye Xiong, Jin-Wei Feng, Chen-Song Zhang, and Sheng-Cai Lin. Hierarchical inhibition of mtorc1 by glucose starvation-triggered axin lysosomal translocation and by ampk. Life Metabolism, Mar 2023. URL: https://doi.org/10.1093/lifemeta/load005, doi:10.1093/lifemeta/load005. This article has 24 citations.

  10. (du2023bistericmtorc1inhibitors pages 1-2): Heng Du, Yu Chi Yang, Heng-Jia Liu, Min Yuan, John M. Asara, Kwok-Kin Wong, Elizabeth P. Henske, Mallika Singh, and David J. Kwiatkowski. Bi-steric mtorc1 inhibitors induce apoptotic cell death in tumor models with hyperactivated mtorc1. The Journal of Clinical Investigation, Nov 2023. URL: https://doi.org/10.1172/jci167861, doi:10.1172/jci167861. This article has 16 citations.

  11. (marafie2024mtoritscritical pages 8-9): Sulaiman K. Marafie, Fahd Al-Mulla, and Jehad Abubaker. Mtor: its critical role in metabolic diseases, cancer, and the aging process. International Journal of Molecular Sciences, 25:6141, Jun 2024. URL: https://doi.org/10.3390/ijms25116141, doi:10.3390/ijms25116141. This article has 98 citations.

  12. (NCT05835999 chunk 1): Everolimus Aging Study. University of Wisconsin, Madison. 2023. ClinicalTrials.gov Identifier: NCT05835999

  13. (NCT06658093 chunk 1): Ellen Kraig. RESTOR: PK/PD mTORi Inhibition in Older Adults. The University of Texas Health Science Center at San Antonio. 2025. ClinicalTrials.gov Identifier: NCT06658093

  14. (NCT07166354 chunk 1): Clinical Study of mTOR Inhibitor as a Treatment for Grey Hair (Canities). Applied Biology, Inc.. 2025. ClinicalTrials.gov Identifier: NCT07166354

  15. (cui2024structuralbasisfor media 2962e450): Zhicheng Cui, Alessandra Esposito, Gennaro Napolitano, Andrea Ballabio, and James H. Hurley. Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mtorc1. bioRxiv, Nov 2024. URL: https://doi.org/10.1101/2024.11.15.623810, doi:10.1101/2024.11.15.623810. This article has 5 citations.

  16. (cui2024structuralbasisfor media b885f8f5): Zhicheng Cui, Alessandra Esposito, Gennaro Napolitano, Andrea Ballabio, and James H. Hurley. Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mtorc1. bioRxiv, Nov 2024. URL: https://doi.org/10.1101/2024.11.15.623810, doi:10.1101/2024.11.15.623810. This article has 5 citations.

  17. (cui2024structuralbasisfor media b9f8adb3): Zhicheng Cui, Alessandra Esposito, Gennaro Napolitano, Andrea Ballabio, and James H. Hurley. Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mtorc1. bioRxiv, Nov 2024. URL: https://doi.org/10.1101/2024.11.15.623810, doi:10.1101/2024.11.15.623810. This article has 5 citations.

  18. (cui2024structuralbasisfor media 1bcd6393): Zhicheng Cui, Alessandra Esposito, Gennaro Napolitano, Andrea Ballabio, and James H. Hurley. Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mtorc1. bioRxiv, Nov 2024. URL: https://doi.org/10.1101/2024.11.15.623810, doi:10.1101/2024.11.15.623810. This article has 5 citations.

  19. (mehta2024unveilingtherole pages 1-2): Devashish Mehta, Kajal Rajput, Dolly Jain, Avinash Bajaj, and Ujjaini Dasgupta. Unveiling the role of mechanistic target of rapamycin kinase (mtor) signaling in cancer progression and the emergence of mtor inhibitors as therapeutic strategies. ACS pharmacology & translational science, 7 12:3758-3779, Nov 2024. URL: https://doi.org/10.1021/acsptsci.4c00530, doi:10.1021/acsptsci.4c00530. This article has 21 citations and is from a peer-reviewed journal.

  20. (NCT02093598 chunk 1): POEM STUDY: A Phase IIa Trial in Endometrial Carcinoma With Temsirolimus. MedSIR. 2012. ClinicalTrials.gov Identifier: NCT02093598

  21. (NCT06658093 chunk 2): Ellen Kraig. RESTOR: PK/PD mTORi Inhibition in Older Adults. The University of Texas Health Science Center at San Antonio. 2025. ClinicalTrials.gov Identifier: NCT06658093

  22. (NCT05414292 chunk 1): Philip Atherton. Impacts of Mechanistic Target of Rapamycin (mTOR) Inhibition on Aged Human Muscle (Rapamune). University of Nottingham. 2021. ClinicalTrials.gov Identifier: NCT05414292

  23. (mehta2024unveilingtherole pages 8-10): Devashish Mehta, Kajal Rajput, Dolly Jain, Avinash Bajaj, and Ujjaini Dasgupta. Unveiling the role of mechanistic target of rapamycin kinase (mtor) signaling in cancer progression and the emergence of mtor inhibitors as therapeutic strategies. ACS pharmacology & translational science, 7 12:3758-3779, Nov 2024. URL: https://doi.org/10.1021/acsptsci.4c00530, doi:10.1021/acsptsci.4c00530. This article has 21 citations and is from a peer-reviewed journal.

Citations

  1. cui2024structuralbasisfor pages 4-7
  2. cui2024structuralbasisfor pages 23-28
  3. li2023hierarchicalinhibitionof pages 12-13
  4. chen2024targetingthemtorautophagy pages 2-4
  5. subbiah2024phaseistudy pages 1-2
  6. marafie2024mtoritscritical pages 1-3
  7. basnet2024mammaliantargetof pages 7-8
  8. basnet2024mammaliantargetof pages 2-4
  9. cui2024structuralbasisfor pages 7-10
  10. marafie2024mtoritscritical pages 8-9
  11. mehta2024unveilingtherole pages 1-2
  12. mehta2024unveilingtherole pages 8-10
  13. https://doi.org/10.1101/2024.11.15.623810
  14. https://doi.org/10.1093/lifemeta/load005
  15. https://doi.org/10.1158/2767-9764.crc-22-0260
  16. https://doi.org/10.1172/jci167861
  17. https://clinicaltrials.gov/study/NCT05835999.
  18. https://clinicaltrials.gov/study/NCT06658093.
  19. https://clinicaltrials.gov/NCT07166354.
  20. https://doi.org/10.3390/ijms25116141;
  21. https://doi.org/10.2174/1874467217666230331081959
  22. https://doi.org/10.1101/2024.11.15.623810;
  23. https://doi.org/10.2174/1874467217666230331081959;
  24. https://doi.org/10.3390/biom14111452
  25. https://doi.org/10.1172/jci167861;
  26. https://doi.org/10.1021/acsptsci.4c00530
  27. https://doi.org/10.1158/2767-9764.crc-22-0260;
  28. https://doi.org/10.3390/ijms25116141
  29. https://clinicaltrials.gov/study/NCT02093598
  30. https://clinicaltrials.gov/study/NCT05835999
  31. https://clinicaltrials.gov/study/NCT06658093
  32. https://clinicaltrials.gov/study/NCT05414292
  33. https://clinicaltrials.gov/NCT07166354
  34. https://doi.org/10.3390/ijms25116141,
  35. https://doi.org/10.2174/1874467217666230331081959,
  36. https://doi.org/10.3390/biom14111452,
  37. https://doi.org/10.1101/2024.11.15.623810,
  38. https://doi.org/10.1158/2767-9764.crc-22-0260,
  39. https://doi.org/10.1093/lifemeta/load005,
  40. https://doi.org/10.1172/jci167861,
  41. https://doi.org/10.1021/acsptsci.4c00530,

📄 View Raw YAML

id: Q9JLN9
gene_symbol: Mtor
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
description: 'Mtor encodes mechanistic target of rapamycin, a large PI3K-related serine/threonine protein kinase. mTOR is the catalytic subunit of mTORC1 and mTORC2 complexes, integrating nutrient, growth-factor, energy, and stress inputs to regulate proximal outputs including translation, cell growth, autophagy, and AKT/PKC-family kinase signaling. Because mTOR is highly pleiotropic, tissue phenotypes and distal metabolic or developmental consequences are treated as non-core unless they directly describe TORC kinase signaling.'
alternative_products:
- name: '1'
  id: Q9JLN9-1
- name: '2'
  id: Q9JLN9-2
  sequence_note: VSP_011909, VSP_011910
existing_annotations:
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0038203
    label: TORC2 signaling
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0031932
    label: TORC2 complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
    action: ACCEPT
    reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0031931
    label: TORC1 complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: mTOR is the catalytic core of mTORC1 (with RPTOR and MLST8), the nutrient/growth-factor-responsive complex that drives anabolic growth at the lysosomal surface.
    action: ACCEPT
    reason: Core complex; mTOR is an obligate subunit of mTORC1 (IDA/ComplexPortal CPX-4473).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0038202
    label: TORC1 signaling
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: mTORC1 signaling—phosphorylation of S6K1, 4E-BP1 and ULK1 to drive translation/growth and suppress autophagy—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC1 signaling.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0016242
    label: negative regulation of macroautophagy
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: mTORC1 directly restrains macroautophagy by phosphorylating ULK1 and inhibiting the autophagy-initiation machinery when nutrients are abundant.
    action: ACCEPT
    reason: Core; ULK1-mediated suppression of macroautophagy by mTORC1 (IMP/IBA).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: mTOR associates peripherally with the cytoplasmic face of Golgi membranes; a minor location versus lysosomal/plasma-membrane sites.
    action: KEEP_AS_NON_CORE
    reason: Secondary peripheral-membrane localization.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0004715
    label: non-membrane spanning protein tyrosine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  review:
    summary: Mislabels mTOR as a soluble tyrosine kinase; mTOR is a PIKK-family Ser/Thr kinase and any tyrosine activity is by-similarity speculation only.
    action: REMOVE
    reason: IEA electronic mis-mapping inconsistent with mTOR's Ser/Thr kinase identity.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: mTOR shuttles to the nucleus and accumulates there under hypoxia; a regulated secondary localization beyond its cytoplasmic membrane sites.
    action: KEEP_AS_NON_CORE
    reason: Regulated nuclear pool (EXP/IDA); secondary location.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: mTOR is a cytoplasmic kinase that shuttles among lysosomal, ER and plasma-membrane surfaces and the cytosol/nucleus; cytoplasmic localization is experimentally established.
    action: ACCEPT
    reason: Supported localization (EXP/ISS); mTOR carries out its kinase function in the cytoplasm.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0005741
    label: mitochondrial outer membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: mTOR has been localized to the mitochondrial outer membrane and senses osmotic stress via mitochondrial dysfunction; a peripheral secondary location.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization (EXP) linked to stress sensing.
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: mTORC1 is recruited to and activated on the cytosolic face of the lysosomal membrane by Rag-Ragulator and Rheb, the principal site where mTOR integrates nutrient and growth-factor signals.
    action: ACCEPT
    reason: 'Core localization for mTORC1 activation (UniProt: lysosome membrane, peripheral, cytoplasmic side).'
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: mTORC2 signals at the cytoplasmic face of the ER membrane; a real secondary location for mTOR complexes.
    action: KEEP_AS_NON_CORE
    reason: Secondary membrane site for mTORC2.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: mTORC2 is active at the plasma membrane where it phosphorylates AKT/PKC; a genuine secondary location for mTOR.
    action: KEEP_AS_NON_CORE
    reason: mTORC2 plasma-membrane site; secondary to lysosomal mTORC1.
- term:
    id: GO:0016301
    label: kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: Uninformative top-level kinase term; mTOR's activity is precisely captured by protein serine/threonine kinase activity (GO:0004674).
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-general MF superseded by the specific Ser/Thr kinase annotation.
- term:
    id: GO:0016605
    label: PML body
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: PML sequesters mTOR in nuclear PML bodies to repress mTORC1 (HIF1α translation control); a regulatory localization documented by IDA.
    action: KEEP_AS_NON_CORE
    reason: Regulatory nuclear-body localization (IDA).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Nucleus, PML body
- term:
    id: GO:0019216
    label: regulation of lipid metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: mTOR regulates lipid metabolism via SREBP1/LPIN1 and mTORC2 lipogenic outputs; a broad metabolic regulatory role downstream of the kinase.
    action: KEEP_AS_NON_CORE
    reason: Downstream metabolic regulation.
- term:
    id: GO:0031346
    label: positive regulation of cell projection organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: mTORC2 cytoskeletal control and mTORC1 translational control promote cell-projection/process formation; a downstream morphological output.
    action: KEEP_AS_NON_CORE
    reason: Downstream cytoskeletal/translational output.
- term:
    id: GO:0044877
    label: protein-containing complex binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: Non-specific complex-binding term that does not describe mTOR's defined role within mTORC1/mTORC2.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding term; superseded by complex annotations.
- term:
    id: GO:0045335
    label: phagocytic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: mTOR localizes to phagosomes, relevant to phagosome maturation and innate-immune signaling; a peripheral compartment.
    action: KEEP_AS_NON_CORE
    reason: Secondary vesicular localization.
- term:
    id: GO:0045792
    label: negative regulation of cell size
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Captures contexts where mTOR loss/inhibition reduces cell size or where mTOR feedback limits growth; the directionality opposite to its dominant pro-growth role.
    action: KEEP_AS_NON_CORE
    reason: Context/loss-of-function readout of mTOR growth control.
- term:
    id: GO:0048714
    label: positive regulation of oligodendrocyte differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: mTOR signaling promotes oligodendrocyte differentiation and myelination programs; a downstream CNS differentiation role.
    action: KEEP_AS_NON_CORE
    reason: Downstream CNS differentiation effect (IMP).
- term:
    id: GO:0050795
    label: regulation of behavior
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Broad behavioral regulation arising from mTOR's neuronal translation/plasticity roles; a pleiotropic downstream phenotype.
    action: KEEP_AS_NON_CORE
    reason: Downstream pleiotropic behavioral role.
- term:
    id: GO:0051155
    label: positive regulation of striated muscle cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: mTOR supports striated-muscle differentiation via growth and translational programs; a downstream developmental output.
    action: KEEP_AS_NON_CORE
    reason: Downstream muscle differentiation effect.
- term:
    id: GO:0051896
    label: regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: mTOR regulates PI3K-AKT signaling both as the mTORC2 AKT-kinase and via mTORC1 feedback (GRB10/IRS), placing it as a direct regulator of this pathway.
    action: ACCEPT
    reason: Core; mTOR directly sets AKT activity through mTORC2 and mTORC1 feedback.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  review:
    summary: Captures mTOR phosphorylation of serine residues (e.g. AKT Ser473, 4E-BP1 serines), a component of its EC 2.7.11.1 serine/threonine kinase activity.
    action: ACCEPT
    reason: Core MF consistent with experimental serine-phosphorylation of mTOR substrates.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0120035
    label: regulation of plasma membrane bounded cell projection organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: mTOR signaling shapes cell projections (neurites, protrusions) via cytoskeletal and translational outputs; a downstream morphogenetic role.
    action: KEEP_AS_NON_CORE
    reason: Downstream morphogenetic effect of mTOR.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12150926
  review:
    summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding term per curation guidelines; not informative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16541103
  review:
    summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding term per curation guidelines; not informative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18046414
  review:
    summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding term per curation guidelines; not informative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18566586
  review:
    summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding term per curation guidelines; not informative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18664580
  review:
    summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding term per curation guidelines; not informative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20801936
  review:
    summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding term per curation guidelines; not informative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21045808
  review:
    summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding term per curation guidelines; not informative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22307628
  review:
    summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding term per curation guidelines; not informative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23966835
  review:
    summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding term per curation guidelines; not informative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24036451
  review:
    summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding term per curation guidelines; not informative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25686248
  review:
    summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding term per curation guidelines; not informative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25980607
  review:
    summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding term per curation guidelines; not informative.
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR associates peripherally with the cytoplasmic face of Golgi membranes; a minor location versus lysosomal/plasma-membrane sites.
    action: KEEP_AS_NON_CORE
    reason: Secondary peripheral-membrane localization.
- term:
    id: GO:0000822
    label: inositol hexakisphosphate binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: InsP6 is a structural cofactor reported to stabilize the mTOR kinase domain; a structural-ligand feature rather than the catalytic activity.
    action: KEEP_AS_NON_CORE
    reason: Structural cofactor binding; non-core.
- term:
    id: GO:0001002
    label: RNA polymerase III type 1 promoter sequence-specific DNA binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR is a cytoplasmic Ser/Thr kinase, not a sequence-specific DNA-binding protein; it regulates Pol III indirectly via MAF1, so direct promoter DNA binding is an erroneous electronic inference.
    action: REMOVE
    reason: IEA/ISO electronic mis-assignment; mTOR does not directly bind promoter DNA.
- term:
    id: GO:0001003
    label: RNA polymerase III type 2 promoter sequence-specific DNA binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR does not bind Pol III promoter DNA directly; its effect on Pol III is via MAF1 phosphorylation, making this DNA-binding MF an electronic error.
    action: REMOVE
    reason: IEA/ISO electronic mis-assignment inconsistent with a kinase.
- term:
    id: GO:0001006
    label: RNA polymerase III type 3 promoter sequence-specific DNA binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Sequence-specific promoter DNA binding is not a function of the mTOR kinase; Pol III control is indirect via MAF1, so this is an erroneous propagation.
    action: REMOVE
    reason: IEA/ISO electronic mis-assignment inconsistent with a kinase.
- term:
    id: GO:0001156
    label: TFIIIC-class transcription factor complex binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Reflects mTOR's engagement with the Pol III transcription machinery to control tRNA gene transcription; an interaction supporting ribosome biogenesis.
    action: KEEP_AS_NON_CORE
    reason: Interaction supporting Pol III/ribosome biogenesis output.
- term:
    id: GO:0001558
    label: regulation of cell growth
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR sets cell-growth rate by gating protein/lipid/nucleotide synthesis through mTORC1, making it a central regulator of cell growth.
    action: ACCEPT
    reason: Core mTORC1 output.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0001933
    label: negative regulation of protein phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR can lower phosphorylation of some targets (e.g. via GRB10/IRS feedback dampening insulin signaling); a downstream regulatory effect.
    action: KEEP_AS_NON_CORE
    reason: Indirect feedback effect downstream of core mTOR signaling.
- term:
    id: GO:0001938
    label: positive regulation of endothelial cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR promotes endothelial proliferation in angiogenesis through growth/translation; a downstream vascular phenotype.
    action: KEEP_AS_NON_CORE
    reason: Downstream proliferative effect (vascular).
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR is specifically a serine/threonine protein kinase; the generic 'protein kinase activity' parent should be replaced by the specific Ser/Thr child term.
    action: MODIFY
    reason: Generic parent where the specific Ser/Thr kinase child (GO:0004674) is the correct MF.
    proposed_replacement_terms: &id001
    - id: GO:0004674
      label: protein serine/threonine kinase activity
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: contributes_to
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR is a Ser/Thr (PIKK-family) kinase; the tyrosine-kinase EC 2.7.10.2 activity is only an unproven by-similarity inference and is not an established function of mouse mTOR.
    action: REMOVE
    reason: IEA/ISO/ISS by-similarity only; contradicted by mTOR's Ser/Thr (PIKK) catalytic identity.
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Nuclear-envelope association (e.g. via PLPP7/NET39) consistent with mTOR's nucleocytoplasmic shuttling.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization tied to nuclear interactions.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR is a cytoplasmic kinase that shuttles among lysosomal, ER and plasma-membrane surfaces and the cytosol/nucleus; cytoplasmic localization is experimentally established.
    action: ACCEPT
    reason: Supported localization (EXP/ISS); mTOR carries out its kinase function in the cytoplasm.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0005741
    label: mitochondrial outer membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR has been localized to the mitochondrial outer membrane and senses osmotic stress via mitochondrial dysfunction; a peripheral secondary location.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization (EXP) linked to stress sensing.
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR acts at the lysosomal membrane (cytoplasmic face), not in the lysosomal lumen; the membrane component is the precise localization.
    action: MODIFY
    reason: Over-general; lysosomal membrane (GO:0005765) is the specific compartment for mTORC1.
    proposed_replacement_terms: &id002
    - id: GO:0005765
      label: lysosomal membrane
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Lysosome membrane; Peripheral membrane protein; Cytoplasmic side
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC1 is recruited to and activated on the cytosolic face of the lysosomal membrane by Rag-Ragulator and Rheb, the principal site where mTOR integrates nutrient and growth-factor signals.
    action: ACCEPT
    reason: 'Core localization for mTORC1 activation (UniProt: lysosome membrane, peripheral, cytoplasmic side).'
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC2 is active at the ER membrane; ER localization is a genuine but secondary site relative to the lysosomal mTORC1 hub.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization (mTORC2 at ER).
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC2 signals at the cytoplasmic face of the ER membrane; a real secondary location for mTOR complexes.
    action: KEEP_AS_NON_CORE
    reason: Secondary membrane site for mTORC2.
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Reported Golgi-membrane pool of mTOR (peripheral, cytoplasmic side); a secondary location relative to the lysosomal site of mTORC1 activation.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization by similarity.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Soluble cytosolic pool of mTOR/mTOR complexes consistent with its peripheral-membrane association and shuttling behavior.
    action: ACCEPT
    reason: Supported localization (IDA) for cytoplasmic mTOR.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC2 is active at the plasma membrane where it phosphorylates AKT/PKC; a genuine secondary location for mTOR.
    action: KEEP_AS_NON_CORE
    reason: mTORC2 plasma-membrane site; secondary to lysosomal mTORC1.
- term:
    id: GO:0005979
    label: regulation of glycogen biosynthetic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Via AKT/GSK3 downstream of mTORC2, mTOR signaling modulates glycogen synthesis; an indirect metabolic effect.
    action: KEEP_AS_NON_CORE
    reason: Indirect downstream metabolic regulation.
- term:
    id: GO:0006109
    label: regulation of carbohydrate metabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR shapes carbohydrate handling through AKT-dependent glucose metabolism and glycolytic gene programs; a broad downstream metabolic role.
    action: KEEP_AS_NON_CORE
    reason: Downstream metabolic regulation via AKT/mTORC1.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR catalyzes transfer of phosphate to its protein substrates within mTORC1 and mTORC2, the molecular event underlying all of its signaling outputs.
    action: ACCEPT
    reason: Core catalytic process for a protein kinase; ISO but biologically definitive for mTOR.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0007616
    label: long-term memory
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTORC1-dependent protein synthesis is required for long-term memory consolidation; a downstream cognitive phenotype.
    action: KEEP_AS_NON_CORE
    reason: Downstream cognitive output of mTOR translation control.
- term:
    id: GO:0008361
    label: regulation of cell size
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Through mTORC1-driven biosynthesis, mTOR controls attainment of cell size; loss of mTOR reduces cell size.
    action: ACCEPT
    reason: Core; cell size is a direct readout of mTORC1 anabolic activity.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0008542
    label: visual learning
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR-dependent synaptic plasticity underlies visual learning; a downstream behavioral phenotype.
    action: KEEP_AS_NON_CORE
    reason: Downstream behavioral output of mTOR.
- term:
    id: GO:0009267
    label: cellular response to starvation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Starvation suppresses mTORC1, de-repressing autophagy; mTOR is the switch responding to nutrient deprivation.
    action: KEEP_AS_NON_CORE
    reason: Upstream starvation input gating mTORC1.
- term:
    id: GO:0010507
    label: negative regulation of autophagy
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Under nutrient sufficiency mTORC1 phosphorylates ULK1 (Ser758) and other autophagy regulators to suppress autophagy; this inhibition is a core proximal mTOR output.
    action: ACCEPT
    reason: Core; direct ULK1 phosphorylation by mTORC1 (IMP-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0010507
    label: negative regulation of autophagy
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Under nutrient sufficiency mTORC1 phosphorylates ULK1 (Ser758) and other autophagy regulators to suppress autophagy; this inhibition is a core proximal mTOR output.
    action: ACCEPT
    reason: Core; direct ULK1 phosphorylation by mTORC1 (IMP-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0010718
    label: positive regulation of epithelial to mesenchymal transition
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR signaling (notably mTORC2) can promote EMT during development and cancer; a downstream cell-fate/motility effect.
    action: KEEP_AS_NON_CORE
    reason: Downstream EMT-promoting effect of mTOR.
- term:
    id: GO:0010976
    label: positive regulation of neuron projection development
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTORC1/mTORC2 promote axon/dendrite outgrowth through translation and cytoskeletal regulation; a downstream neuronal output.
    action: KEEP_AS_NON_CORE
    reason: Downstream neurite-growth effect of mTOR.
- term:
    id: GO:0012505
    label: endomembrane system
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Broad endomembrane localization reflecting mTOR's peripheral association with lysosomal/ER/Golgi membranes.
    action: KEEP_AS_NON_CORE
    reason: General localization subsumed by specific membrane terms.
- term:
    id: GO:0014042
    label: positive regulation of neuron maturation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR signaling promotes neuronal maturation via translational and growth control; a downstream developmental role.
    action: KEEP_AS_NON_CORE
    reason: Downstream neurodevelopmental effect of mTOR.
- term:
    id: GO:0014736
    label: negative regulation of muscle atrophy
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Active mTORC1 opposes muscle atrophy by sustaining protein synthesis and suppressing autophagy/proteolysis.
    action: KEEP_AS_NON_CORE
    reason: Downstream anti-atrophy effect of mTORC1.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic membrane association consistent with mTOR being a peripheral membrane protein on several organelles.
    action: KEEP_AS_NON_CORE
    reason: Generic CC subsumed by specific membrane terms.
- term:
    id: GO:0019901
    label: protein kinase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR binds kinase substrates/regulators (e.g. AKT, S6K, ULK1); informative as interaction context but secondary to its own kinase activity.
    action: KEEP_AS_NON_CORE
    reason: Partner-binding adjunct to mTOR's catalytic role.
- term:
    id: GO:0019904
    label: protein domain specific binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR engages partner domains (e.g. FRB-FKBP12/rapamycin, RICTOR/RAPTOR interfaces); contextually useful but not the core function.
    action: KEEP_AS_NON_CORE
    reason: Interaction detail secondary to core kinase/scaffold role.
- term:
    id: GO:0021510
    label: spinal cord development
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR-dependent growth and patterning contribute to spinal cord development; a downstream developmental phenotype.
    action: KEEP_AS_NON_CORE
    reason: Downstream developmental role of mTOR.
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Dendritic localization of mTOR supports local translation underlying synaptic plasticity; a neuron-specific secondary site.
    action: KEEP_AS_NON_CORE
    reason: Neuronal localization linked to local translation.
- term:
    id: GO:0031397
    label: negative regulation of protein ubiquitination
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR phosphorylation can shield substrates from ubiquitination (e.g. AMBRA1-ULK1 axis); a downstream regulatory effect.
    action: KEEP_AS_NON_CORE
    reason: Downstream effect on substrate ubiquitination.
- term:
    id: GO:0031667
    label: response to nutrient levels
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR responds to organismal/cellular nutrient levels to coordinate growth and metabolism via mTORC1.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient input to mTORC1.
- term:
    id: GO:0031669
    label: cellular response to nutrient levels
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Nutrient abundance dictates mTORC1 lysosomal recruitment and activity; mTOR is the effector translating nutrient state into growth decisions.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient input to mTORC1.
- term:
    id: GO:0031670
    label: cellular response to nutrient
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC1 integrates general nutrient availability to switch between anabolism and catabolism; mTOR is the central responder.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient input gating mTORC1.
- term:
    id: GO:0031929
    label: TOR signaling
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR is the namesake kinase of TOR signaling, transducing nutrient/growth-factor inputs into control of growth, translation and autophagy via mTORC1 and mTORC2.
    action: ACCEPT
    reason: Core pathway directly executed by mTOR (IMP/IGI).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0031931
    label: TORC1 complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR is the catalytic core of mTORC1 (with RPTOR and MLST8), the nutrient/growth-factor-responsive complex that drives anabolic growth at the lysosomal surface.
    action: ACCEPT
    reason: Core complex; mTOR is an obligate subunit of mTORC1 (IDA/ComplexPortal CPX-4473).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0031931
    label: TORC1 complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR is the catalytic core of mTORC1 (with RPTOR and MLST8), the nutrient/growth-factor-responsive complex that drives anabolic growth at the lysosomal surface.
    action: ACCEPT
    reason: Core complex; mTOR is an obligate subunit of mTORC1 (IDA/ComplexPortal CPX-4473).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0031932
    label: TORC2 complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
    action: ACCEPT
    reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0031998
    label: regulation of fatty acid beta-oxidation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTORC1 suppresses fatty-acid oxidation when promoting anabolism (e.g. via PPAR/PGC-1 control); a downstream metabolic switch.
    action: KEEP_AS_NON_CORE
    reason: Downstream metabolic regulation of mTORC1.
- term:
    id: GO:0032095
    label: regulation of response to food
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Hypothalamic mTOR signaling links nutrient/energy status to feeding responses; a downstream physiological role.
    action: KEEP_AS_NON_CORE
    reason: Downstream physiological response of nutrient-sensing mTOR.
- term:
    id: GO:0032869
    label: cellular response to insulin stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Insulin activates mTORC1/mTORC2 through PI3K-AKT-TSC-Rheb; mTOR is the central effector of the insulin growth-factor response.
    action: KEEP_AS_NON_CORE
    reason: Upstream growth-factor input to mTOR.
- term:
    id: GO:0032956
    label: regulation of actin cytoskeleton organization
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC2 regulates the actin cytoskeleton through PKC and Rho/Rac GTPases; a characteristic downstream output of mTOR's mTORC2 activity.
    action: KEEP_AS_NON_CORE
    reason: Downstream mTORC2 cytoskeletal output.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Generic 'part of a protein complex' statement; mTOR's specific TORC1/TORC2 complex memberships are the informative annotations.
    action: KEEP_AS_NON_CORE
    reason: Generic CC subsumed by TORC1/TORC2 complex terms.
- term:
    id: GO:0034198
    label: cellular response to amino acid starvation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC1 is inactivated upon amino-acid withdrawal (loss of Rag-Ragulator lysosomal recruitment); mTOR is the sensor-effector responding to this input.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient input gating core mTORC1 activity.
- term:
    id: GO:0035176
    label: social behavior
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR pathway dysregulation alters social behavior (relevant to autism-spectrum models); a downstream behavioral phenotype.
    action: KEEP_AS_NON_CORE
    reason: Downstream behavioral phenotype of mTOR.
- term:
    id: GO:0038202
    label: TORC1 signaling
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC1 signaling—phosphorylation of S6K1, 4E-BP1 and ULK1 to drive translation/growth and suppress autophagy—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC1 signaling.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0038203
    label: TORC2 signaling
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0042220
    label: response to cocaine
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR-dependent synaptic plasticity mediates neuronal responses to cocaine; a downstream pharmacological/behavioral phenotype.
    action: KEEP_AS_NON_CORE
    reason: Downstream behavioral response via mTOR plasticity.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic self-association term; mTOR's functional dimerization is better captured by the TORC1/TORC2 complex annotations.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative generic MF.
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC2 associates with ribosomes to cotranslationally phosphorylate nascent AKT, and mTORC1 couples to translation; a functionally relevant but ancillary interaction.
    action: KEEP_AS_NON_CORE
    reason: Supports cotranslational substrate phosphorylation; secondary to core kinase role.
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Somatic localization of mTOR in neurons consistent with its role in neuronal growth and translation.
    action: KEEP_AS_NON_CORE
    reason: Neuron-specific secondary localization.
- term:
    id: GO:0043200
    label: response to amino acid
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Amino-acid availability is a principal cue activating mTORC1; mTOR senses this through the lysosomal Rag machinery.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient cue for mTORC1.
- term:
    id: GO:0043491
    label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: As the mTORC2 kinase, mTOR phosphorylates AKT (PKB) Ser473, a defining step of PI3K-AKT signal transduction directly executed by mTOR.
    action: ACCEPT
    reason: Core; mTORC2 is the AKT Ser473 kinase linking PI3K to AKT activation.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0043525
    label: positive regulation of neuron apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: In some neuronal contexts mTOR signaling promotes apoptosis; a context-dependent downstream survival effect.
    action: KEEP_AS_NON_CORE
    reason: Context-dependent downstream neuronal effect.
- term:
    id: GO:0043610
    label: regulation of carbohydrate utilization
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR/AKT signaling tunes cellular glucose utilization in response to growth-factor and nutrient state; a downstream metabolic effect.
    action: KEEP_AS_NON_CORE
    reason: Downstream metabolic effect of mTOR signaling.
- term:
    id: GO:0045335
    label: phagocytic vesicle
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR localizes to phagosomes, relevant to phagosome maturation and innate-immune signaling; a peripheral compartment.
    action: KEEP_AS_NON_CORE
    reason: Secondary vesicular localization.
- term:
    id: GO:0045429
    label: positive regulation of nitric oxide biosynthetic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR/AKT signaling can promote eNOS-dependent NO production in endothelium; an indirect downstream metabolic effect.
    action: KEEP_AS_NON_CORE
    reason: Indirect downstream effect of mTOR-AKT signaling.
- term:
    id: GO:0045727
    label: positive regulation of translation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTORC1 promotes cap-dependent translation by phosphorylating 4E-BP1 (releasing eIF4E) and activating S6K1/2, a core anabolic output of mTOR.
    action: ACCEPT
    reason: Core; mTORC1 directly drives translation via 4E-BP1/S6K.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0045727
    label: positive regulation of translation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC1 promotes cap-dependent translation by phosphorylating 4E-BP1 (releasing eIF4E) and activating S6K1/2, a core anabolic output of mTOR.
    action: ACCEPT
    reason: Core; mTORC1 directly drives translation via 4E-BP1/S6K.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0045945
    label: positive regulation of transcription by RNA polymerase III
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC1 activates Pol III transcription by phosphorylating/inhibiting the repressor MAF1, boosting tRNA/5S rRNA synthesis; downstream of mTOR.
    action: KEEP_AS_NON_CORE
    reason: Downstream of mTORC1 (MAF1 phosphorylation).
- term:
    id: GO:0045948
    label: positive regulation of translational initiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: By phosphorylating 4E-BP1 mTORC1 frees eIF4E and stimulates assembly of the cap-binding initiation complex, directly promoting translational initiation.
    action: ACCEPT
    reason: Core; 4E-BP1 phosphorylation by mTORC1 controls initiation.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0046777
    label: protein autophosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR autophosphorylates (e.g. Ser2481) when assembled in mTORC1 or mTORC2, a hallmark of the active kinase used to report complex integrity.
    action: ACCEPT
    reason: Core intrinsic kinase activity; documented mTOR autophosphorylation.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0046889
    label: positive regulation of lipid biosynthetic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR drives lipogenesis through SREBP1 and LPIN1 (mTORC1) and lipid synthesis programs (mTORC2); a major anabolic output downstream of mTOR.
    action: KEEP_AS_NON_CORE
    reason: Downstream lipogenic program of mTOR signaling.
- term:
    id: GO:0048255
    label: mRNA stabilization
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTORC2 phosphorylation of IGF2BP1/IMP1 promotes target mRNA stability/translation; a downstream RNA-regulatory effect of mTOR.
    action: KEEP_AS_NON_CORE
    reason: Downstream effect via mTORC2 substrate phosphorylation.
- term:
    id: GO:0048661
    label: positive regulation of smooth muscle cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR drives smooth-muscle proliferation (e.g. vascular remodeling); a downstream proliferative phenotype.
    action: KEEP_AS_NON_CORE
    reason: Downstream proliferative effect.
- term:
    id: GO:0048714
    label: positive regulation of oligodendrocyte differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR signaling promotes oligodendrocyte differentiation and myelination programs; a downstream CNS differentiation role.
    action: KEEP_AS_NON_CORE
    reason: Downstream CNS differentiation effect (IMP).
- term:
    id: GO:0050769
    label: positive regulation of neurogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR-driven growth/translation supports neural progenitor proliferation and neurogenesis; a downstream developmental output.
    action: KEEP_AS_NON_CORE
    reason: Downstream neurodevelopmental effect of mTOR.
- term:
    id: GO:0051219
    label: phosphoprotein binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR/its complexes recognize phosphorylated regulators (e.g. via SIN1/RPTOR); an interaction feature, not the core activity.
    action: KEEP_AS_NON_CORE
    reason: Partner recognition adjunct to core function.
- term:
    id: GO:0051549
    label: positive regulation of keratinocyte migration
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR signaling promotes keratinocyte migration in wound healing through its cytoskeletal/growth outputs.
    action: KEEP_AS_NON_CORE
    reason: Downstream motility/wound-healing effect.
- 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: mTORC2-mediated AKT hydrophobic-motif phosphorylation positively regulates PI3K-AKT signaling, a direct proximal output of mTOR kinase activity.
    action: ACCEPT
    reason: Core; mTORC2 directly activates AKT via Ser473 phosphorylation.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0060135
    label: maternal process involved in female pregnancy
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR nutrient sensing in maternal/placental tissues supports pregnancy-associated growth processes; a downstream physiological role.
    action: KEEP_AS_NON_CORE
    reason: Downstream physiological role of mTOR sensing.
- term:
    id: GO:0060252
    label: positive regulation of glial cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR's growth/proliferative outputs drive glial cell proliferation; a downstream CNS phenotype.
    action: KEEP_AS_NON_CORE
    reason: Downstream proliferative effect in glia.
- term:
    id: GO:0060999
    label: positive regulation of dendritic spine development
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR-dependent local translation supports dendritic-spine formation/maturation underlying synaptic plasticity.
    action: KEEP_AS_NON_CORE
    reason: Downstream synaptic-plasticity effect of mTOR.
- term:
    id: GO:0061051
    label: positive regulation of cell growth involved in cardiac muscle cell development
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTORC1-driven growth contributes to cardiomyocyte hypertrophic growth during heart development; a tissue-specific instance of mTOR's growth output.
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific instance of mTOR growth control.
- term:
    id: GO:0061431
    label: cellular response to methionine
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Methionine/SAM availability signals to mTORC1 (e.g. via SAMTOR); mTOR responds to set anabolic activity.
    action: KEEP_AS_NON_CORE
    reason: Specific amino-acid input to mTORC1.
- term:
    id: GO:0062027
    label: positive regulation of SCF-dependent proteasomal ubiquitin-dependent catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR phosphorylation can promote SCF-mediated substrate degradation (IRS1 turnover), feeding back on insulin signaling.
    action: KEEP_AS_NON_CORE
    reason: Downstream proteostatic feedback of mTOR signaling.
- term:
    id: GO:0071230
    label: cellular response to amino acid stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Amino acids activate mTORC1 via Rag GTPases/Ragulator and lysosomal recruitment; mTOR responds to this stimulus to drive growth.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient input to mTORC1.
- term:
    id: GO:0071233
    label: cellular response to L-leucine
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Leucine is a key amino acid activating mTORC1 (via Sestrin2/leucyl-tRNA pathways and Rag GTPases); mTOR is the responding effector.
    action: KEEP_AS_NON_CORE
    reason: Specific amino-acid input to mTORC1.
- term:
    id: GO:0090335
    label: regulation of brown fat cell differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR (notably an FLCN-dependent non-canonical mTORC1 axis) regulates adipose browning/brown-fat differentiation; a tissue-level downstream role.
    action: KEEP_AS_NON_CORE
    reason: Downstream tissue differentiation controlled by mTOR.
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Synaptic mTOR pool supports activity-dependent local translation at glutamatergic synapses; a specialized neuronal localization.
    action: KEEP_AS_NON_CORE
    reason: Neuronal-synapse localization.
- term:
    id: GO:0099524
    label: postsynaptic cytosol
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Postsynaptic cytosolic mTOR participates in local translational control of synaptic plasticity.
    action: KEEP_AS_NON_CORE
    reason: Neuronal-synapse localization.
- term:
    id: GO:0099547
    label: regulation of translation at synapse, modulating synaptic transmission
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTORC1-dependent local dendritic translation supports synaptic plasticity; a neuron-specific downstream output of mTOR.
    action: KEEP_AS_NON_CORE
    reason: Downstream neuronal translation control by mTOR.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Captures mTOR phosphorylation of serine residues (e.g. AKT Ser473, 4E-BP1 serines), a component of its EC 2.7.11.1 serine/threonine kinase activity.
    action: ACCEPT
    reason: Core MF consistent with experimental serine-phosphorylation of mTOR substrates.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Captures mTOR phosphorylation of serine residues (e.g. AKT Ser473, 4E-BP1 serines), a component of its EC 2.7.11.1 serine/threonine kinase activity.
    action: ACCEPT
    reason: Core MF consistent with experimental serine-phosphorylation of mTOR substrates.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:1900181
    label: negative regulation of protein localization to nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Active mTORC1 phosphorylates TFEB/TFE3 to retain them in the cytosol, preventing their nuclear entry; a specific mechanistic downstream effect.
    action: KEEP_AS_NON_CORE
    reason: Downstream MiT/TFE cytosolic-retention effect of mTORC1.
- term:
    id: GO:1901838
    label: positive regulation of transcription of nucleolar large rRNA by RNA polymerase I
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC1 promotes rRNA synthesis (Pol I) to support ribosome biogenesis, a downstream anabolic output of mTOR.
    action: KEEP_AS_NON_CORE
    reason: Downstream ribosome-biogenesis output of mTORC1.
- term:
    id: GO:1903691
    label: positive regulation of wound healing, spreading of epidermal cells
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR-dependent migration/proliferation of epidermal cells supports wound re-epithelialization; a downstream tissue process.
    action: KEEP_AS_NON_CORE
    reason: Downstream wound-healing process.
- term:
    id: GO:1904000
    label: positive regulation of eating behavior
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Hypothalamic mTORC1 activity modulates appetite/food intake; a downstream behavioral output of mTOR nutrient sensing.
    action: KEEP_AS_NON_CORE
    reason: Downstream behavioral effect of mTOR signaling.
- term:
    id: GO:1904037
    label: positive regulation of epithelial cell apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: In some contexts mTOR signaling promotes epithelial apoptosis; a context-dependent downstream survival effect.
    action: KEEP_AS_NON_CORE
    reason: Context-dependent downstream apoptotic effect.
- term:
    id: GO:1904056
    label: positive regulation of cholangiocyte proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR signaling promotes cholangiocyte (bile-duct epithelial) proliferation; a downstream hepatic phenotype.
    action: KEEP_AS_NON_CORE
    reason: Downstream proliferative effect (liver).
- term:
    id: GO:1904193
    label: negative regulation of cholangiocyte apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR/AKT survival signaling suppresses cholangiocyte apoptosis; a downstream pro-survival phenotype.
    action: KEEP_AS_NON_CORE
    reason: Downstream pro-survival effect of mTOR.
- term:
    id: GO:1904197
    label: positive regulation of granulosa cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR supports ovarian granulosa-cell proliferation during follicle growth; a downstream tissue phenotype.
    action: KEEP_AS_NON_CORE
    reason: Downstream proliferative effect (ovary).
- term:
    id: GO:1904206
    label: positive regulation of skeletal muscle hypertrophy
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTORC1 drives skeletal-muscle hypertrophy by stimulating protein synthesis; a tissue-specific instance of mTOR's growth output.
    action: KEEP_AS_NON_CORE
    reason: Downstream muscle-growth output of mTORC1.
- term:
    id: GO:1904213
    label: negative regulation of iodide transmembrane transport
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mTOR signaling can suppress thyroid iodide uptake (NIS regulation); a downstream tissue-specific physiological effect.
    action: KEEP_AS_NON_CORE
    reason: Downstream physiological effect of mTOR.
- term:
    id: GO:1905671
    label: regulation of lysosome organization
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Via TFEB/TFE3 phosphorylation mTORC1 regulates lysosomal gene programs and organelle homeostasis.
    action: KEEP_AS_NON_CORE
    reason: Downstream MiT/TFE-mediated effect of mTORC1.
- term:
    id: GO:1905672
    label: negative regulation of lysosome organization
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Active mTORC1 phosphorylates TFEB/TFE3 to keep them cytosolic, suppressing lysosomal/autophagy gene expression and biogenesis.
    action: KEEP_AS_NON_CORE
    reason: Downstream MiT/TFE inhibition by mTORC1.
- term:
    id: GO:1990253
    label: cellular response to leucine starvation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Leucine withdrawal inactivates mTORC1; mTOR is the kinase whose activity drops in response.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient input to mTORC1.
- term:
    id: GO:2000060
    label: positive regulation of ubiquitin-dependent protein catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR-directed phosphorylation can mark substrates for ubiquitin-dependent degradation; a downstream proteostatic effect.
    action: KEEP_AS_NON_CORE
    reason: Downstream proteostatic effect of mTOR signaling.
- term:
    id: GO:2000774
    label: positive regulation of cellular senescence
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Hyperactive mTOR drives geroconversion/cellular senescence (the basis of rapamycin's anti-aging effect); a downstream phenotype.
    action: KEEP_AS_NON_CORE
    reason: Downstream aging-related effect of mTOR.
- term:
    id: GO:2000785
    label: regulation of autophagosome assembly
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC1 negatively regulates autophagosome assembly via ULK1; a specific facet of its autophagy-suppressive output.
    action: KEEP_AS_NON_CORE
    reason: Downstream autophagy regulation by mTORC1.
- term:
    id: GO:0000822
    label: inositol hexakisphosphate binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: InsP6 is a structural cofactor reported to stabilize the mTOR kinase domain; a structural-ligand feature rather than the catalytic activity.
    action: KEEP_AS_NON_CORE
    reason: Structural cofactor binding; non-core.
- term:
    id: GO:0001002
    label: RNA polymerase III type 1 promoter sequence-specific DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTOR is a cytoplasmic Ser/Thr kinase, not a sequence-specific DNA-binding protein; it regulates Pol III indirectly via MAF1, so direct promoter DNA binding is an erroneous electronic inference.
    action: REMOVE
    reason: IEA/ISO electronic mis-assignment; mTOR does not directly bind promoter DNA.
- term:
    id: GO:0001003
    label: RNA polymerase III type 2 promoter sequence-specific DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTOR does not bind Pol III promoter DNA directly; its effect on Pol III is via MAF1 phosphorylation, making this DNA-binding MF an electronic error.
    action: REMOVE
    reason: IEA/ISO electronic mis-assignment inconsistent with a kinase.
- term:
    id: GO:0001006
    label: RNA polymerase III type 3 promoter sequence-specific DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Sequence-specific promoter DNA binding is not a function of the mTOR kinase; Pol III control is indirect via MAF1, so this is an erroneous propagation.
    action: REMOVE
    reason: IEA/ISO electronic mis-assignment inconsistent with a kinase.
- term:
    id: GO:0001156
    label: TFIIIC-class transcription factor complex binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Reflects mTOR's engagement with the Pol III transcription machinery to control tRNA gene transcription; an interaction supporting ribosome biogenesis.
    action: KEEP_AS_NON_CORE
    reason: Interaction supporting Pol III/ribosome biogenesis output.
- term:
    id: GO:0001558
    label: regulation of cell growth
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTOR sets cell-growth rate by gating protein/lipid/nucleotide synthesis through mTORC1, making it a central regulator of cell growth.
    action: ACCEPT
    reason: Core mTORC1 output.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTOR is specifically a serine/threonine protein kinase; the generic 'protein kinase activity' parent should be replaced by the specific Ser/Thr child term.
    action: MODIFY
    reason: Generic parent where the specific Ser/Thr kinase child (GO:0004674) is the correct MF.
    proposed_replacement_terms: *id001
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: mTOR is a Ser/Thr (PIKK-family) kinase; the tyrosine-kinase EC 2.7.10.2 activity is only an unproven by-similarity inference and is not an established function of mouse mTOR.
    action: REMOVE
    reason: IEA/ISO/ISS by-similarity only; contradicted by mTOR's Ser/Thr (PIKK) catalytic identity.
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Nuclear-envelope association (e.g. via PLPP7/NET39) consistent with mTOR's nucleocytoplasmic shuttling.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization tied to nuclear interactions.
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTOR acts at the lysosomal membrane (cytoplasmic face), not in the lysosomal lumen; the membrane component is the precise localization.
    action: MODIFY
    reason: Over-general; lysosomal membrane (GO:0005765) is the specific compartment for mTORC1.
    proposed_replacement_terms: *id002
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Lysosome membrane; Peripheral membrane protein; Cytoplasmic side
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTORC2 is active at the ER membrane; ER localization is a genuine but secondary site relative to the lysosomal mTORC1 hub.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization (mTORC2 at ER).
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Reported Golgi-membrane pool of mTOR (peripheral, cytoplasmic side); a secondary location relative to the lysosomal site of mTORC1 activation.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization by similarity.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Soluble cytosolic pool of mTOR/mTOR complexes consistent with its peripheral-membrane association and shuttling behavior.
    action: ACCEPT
    reason: Supported localization (IDA) for cytoplasmic mTOR.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0008361
    label: regulation of cell size
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Through mTORC1-driven biosynthesis, mTOR controls attainment of cell size; loss of mTOR reduces cell size.
    action: ACCEPT
    reason: Core; cell size is a direct readout of mTORC1 anabolic activity.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0009267
    label: cellular response to starvation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Starvation suppresses mTORC1, de-repressing autophagy; mTOR is the switch responding to nutrient deprivation.
    action: KEEP_AS_NON_CORE
    reason: Upstream starvation input gating mTORC1.
- term:
    id: GO:0010507
    label: negative regulation of autophagy
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Under nutrient sufficiency mTORC1 phosphorylates ULK1 (Ser758) and other autophagy regulators to suppress autophagy; this inhibition is a core proximal mTOR output.
    action: ACCEPT
    reason: Core; direct ULK1 phosphorylation by mTORC1 (IMP-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0010718
    label: positive regulation of epithelial to mesenchymal transition
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTOR signaling (notably mTORC2) can promote EMT during development and cancer; a downstream cell-fate/motility effect.
    action: KEEP_AS_NON_CORE
    reason: Downstream EMT-promoting effect of mTOR.
- term:
    id: GO:0012505
    label: endomembrane system
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Broad endomembrane localization reflecting mTOR's peripheral association with lysosomal/ER/Golgi membranes.
    action: KEEP_AS_NON_CORE
    reason: General localization subsumed by specific membrane terms.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Generic membrane association consistent with mTOR being a peripheral membrane protein on several organelles.
    action: KEEP_AS_NON_CORE
    reason: Generic CC subsumed by specific membrane terms.
- term:
    id: GO:0031667
    label: response to nutrient levels
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTOR responds to organismal/cellular nutrient levels to coordinate growth and metabolism via mTORC1.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient input to mTORC1.
- term:
    id: GO:0031669
    label: cellular response to nutrient levels
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Nutrient abundance dictates mTORC1 lysosomal recruitment and activity; mTOR is the effector translating nutrient state into growth decisions.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient input to mTORC1.
- term:
    id: GO:0031670
    label: cellular response to nutrient
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTORC1 integrates general nutrient availability to switch between anabolism and catabolism; mTOR is the central responder.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient input gating mTORC1.
- term:
    id: GO:0031929
    label: TOR signaling
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTOR is the namesake kinase of TOR signaling, transducing nutrient/growth-factor inputs into control of growth, translation and autophagy via mTORC1 and mTORC2.
    action: ACCEPT
    reason: Core pathway directly executed by mTOR (IMP/IGI).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0031931
    label: TORC1 complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: mTOR is the catalytic core of mTORC1 (with RPTOR and MLST8), the nutrient/growth-factor-responsive complex that drives anabolic growth at the lysosomal surface.
    action: ACCEPT
    reason: Core complex; mTOR is an obligate subunit of mTORC1 (IDA/ComplexPortal CPX-4473).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0031932
    label: TORC2 complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
    action: ACCEPT
    reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0032869
    label: cellular response to insulin stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Insulin activates mTORC1/mTORC2 through PI3K-AKT-TSC-Rheb; mTOR is the central effector of the insulin growth-factor response.
    action: KEEP_AS_NON_CORE
    reason: Upstream growth-factor input to mTOR.
- term:
    id: GO:0032956
    label: regulation of actin cytoskeleton organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTORC2 regulates the actin cytoskeleton through PKC and Rho/Rac GTPases; a characteristic downstream output of mTOR's mTORC2 activity.
    action: KEEP_AS_NON_CORE
    reason: Downstream mTORC2 cytoskeletal output.
- term:
    id: GO:0034198
    label: cellular response to amino acid starvation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTORC1 is inactivated upon amino-acid withdrawal (loss of Rag-Ragulator lysosomal recruitment); mTOR is the sensor-effector responding to this input.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient input gating core mTORC1 activity.
- term:
    id: GO:0038202
    label: TORC1 signaling
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTORC1 signaling—phosphorylation of S6K1, 4E-BP1 and ULK1 to drive translation/growth and suppress autophagy—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC1 signaling.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0038203
    label: TORC2 signaling
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Generic self-association term; mTOR's functional dimerization is better captured by the TORC1/TORC2 complex annotations.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative generic MF.
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTORC2 associates with ribosomes to cotranslationally phosphorylate nascent AKT, and mTORC1 couples to translation; a functionally relevant but ancillary interaction.
    action: KEEP_AS_NON_CORE
    reason: Supports cotranslational substrate phosphorylation; secondary to core kinase role.
- term:
    id: GO:0043200
    label: response to amino acid
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Amino-acid availability is a principal cue activating mTORC1; mTOR senses this through the lysosomal Rag machinery.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient cue for mTORC1.
- term:
    id: GO:0043491
    label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: As the mTORC2 kinase, mTOR phosphorylates AKT (PKB) Ser473, a defining step of PI3K-AKT signal transduction directly executed by mTOR.
    action: ACCEPT
    reason: Core; mTORC2 is the AKT Ser473 kinase linking PI3K to AKT activation.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0045727
    label: positive regulation of translation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTORC1 promotes cap-dependent translation by phosphorylating 4E-BP1 (releasing eIF4E) and activating S6K1/2, a core anabolic output of mTOR.
    action: ACCEPT
    reason: Core; mTORC1 directly drives translation via 4E-BP1/S6K.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0045945
    label: positive regulation of transcription by RNA polymerase III
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTORC1 activates Pol III transcription by phosphorylating/inhibiting the repressor MAF1, boosting tRNA/5S rRNA synthesis; downstream of mTOR.
    action: KEEP_AS_NON_CORE
    reason: Downstream of mTORC1 (MAF1 phosphorylation).
- term:
    id: GO:0045948
    label: positive regulation of translational initiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: By phosphorylating 4E-BP1 mTORC1 frees eIF4E and stimulates assembly of the cap-binding initiation complex, directly promoting translational initiation.
    action: ACCEPT
    reason: Core; 4E-BP1 phosphorylation by mTORC1 controls initiation.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0046889
    label: positive regulation of lipid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTOR drives lipogenesis through SREBP1 and LPIN1 (mTORC1) and lipid synthesis programs (mTORC2); a major anabolic output downstream of mTOR.
    action: KEEP_AS_NON_CORE
    reason: Downstream lipogenic program of mTOR signaling.
- term:
    id: GO:0051219
    label: phosphoprotein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTOR/its complexes recognize phosphorylated regulators (e.g. via SIN1/RPTOR); an interaction feature, not the core activity.
    action: KEEP_AS_NON_CORE
    reason: Partner recognition adjunct to core function.
- term:
    id: GO:0051549
    label: positive regulation of keratinocyte migration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTOR signaling promotes keratinocyte migration in wound healing through its cytoskeletal/growth outputs.
    action: KEEP_AS_NON_CORE
    reason: Downstream motility/wound-healing effect.
- term:
    id: GO:0061431
    label: cellular response to methionine
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Methionine/SAM availability signals to mTORC1 (e.g. via SAMTOR); mTOR responds to set anabolic activity.
    action: KEEP_AS_NON_CORE
    reason: Specific amino-acid input to mTORC1.
- term:
    id: GO:0062027
    label: positive regulation of SCF-dependent proteasomal ubiquitin-dependent catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTOR phosphorylation can promote SCF-mediated substrate degradation (IRS1 turnover), feeding back on insulin signaling.
    action: KEEP_AS_NON_CORE
    reason: Downstream proteostatic feedback of mTOR signaling.
- term:
    id: GO:0071230
    label: cellular response to amino acid stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Amino acids activate mTORC1 via Rag GTPases/Ragulator and lysosomal recruitment; mTOR responds to this stimulus to drive growth.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient input to mTORC1.
- term:
    id: GO:0071233
    label: cellular response to L-leucine
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Leucine is a key amino acid activating mTORC1 (via Sestrin2/leucyl-tRNA pathways and Rag GTPases); mTOR is the responding effector.
    action: KEEP_AS_NON_CORE
    reason: Specific amino-acid input to mTORC1.
- term:
    id: GO:1900181
    label: negative regulation of protein localization to nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Active mTORC1 phosphorylates TFEB/TFE3 to retain them in the cytosol, preventing their nuclear entry; a specific mechanistic downstream effect.
    action: KEEP_AS_NON_CORE
    reason: Downstream MiT/TFE cytosolic-retention effect of mTORC1.
- term:
    id: GO:1901838
    label: positive regulation of transcription of nucleolar large rRNA by RNA polymerase I
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTORC1 promotes rRNA synthesis (Pol I) to support ribosome biogenesis, a downstream anabolic output of mTOR.
    action: KEEP_AS_NON_CORE
    reason: Downstream ribosome-biogenesis output of mTORC1.
- term:
    id: GO:1903691
    label: positive regulation of wound healing, spreading of epidermal cells
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTOR-dependent migration/proliferation of epidermal cells supports wound re-epithelialization; a downstream tissue process.
    action: KEEP_AS_NON_CORE
    reason: Downstream wound-healing process.
- term:
    id: GO:1905671
    label: regulation of lysosome organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Via TFEB/TFE3 phosphorylation mTORC1 regulates lysosomal gene programs and organelle homeostasis.
    action: KEEP_AS_NON_CORE
    reason: Downstream MiT/TFE-mediated effect of mTORC1.
- term:
    id: GO:1905672
    label: negative regulation of lysosome organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Active mTORC1 phosphorylates TFEB/TFE3 to keep them cytosolic, suppressing lysosomal/autophagy gene expression and biogenesis.
    action: KEEP_AS_NON_CORE
    reason: Downstream MiT/TFE inhibition by mTORC1.
- term:
    id: GO:1990253
    label: cellular response to leucine starvation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Leucine withdrawal inactivates mTORC1; mTOR is the kinase whose activity drops in response.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient input to mTORC1.
- term:
    id: GO:2000785
    label: regulation of autophagosome assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mTORC1 negatively regulates autophagosome assembly via ULK1; a specific facet of its autophagy-suppressive output.
    action: KEEP_AS_NON_CORE
    reason: Downstream autophagy regulation by mTORC1.
- term:
    id: GO:0031648
    label: protein destabilization
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC2 phosphorylation can target substrates (e.g. AKT, IRS1 via Fbw8) for turnover; a downstream proteostatic consequence of mTOR signaling.
    action: KEEP_AS_NON_CORE
    reason: Downstream effect of mTOR-directed phosphorylation.
- term:
    id: GO:0000045
    label: autophagosome assembly
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC1 gates autophagosome formation by controlling ULK1/the initiation machinery; the process it regulates rather than a structure it builds.
    action: KEEP_AS_NON_CORE
    reason: Downstream autophagy process regulated by mTORC1.
- term:
    id: GO:0002181
    label: cytoplasmic translation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC1 stimulates the cytoplasmic translation apparatus (eIF4F assembly, S6K) as a downstream anabolic output; mTOR is a regulator, not a ribosomal component.
    action: KEEP_AS_NON_CORE
    reason: Downstream translation output of mTORC1.
- term:
    id: GO:0006446
    label: regulation of translational initiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC1 controls initiation through 4E-BP1/eIF4E and S6K; specific positive-initiation terms capture the core direction.
    action: KEEP_AS_NON_CORE
    reason: Generic regulation covered by specific positive-initiation terms.
- term:
    id: GO:0006511
    label: ubiquitin-dependent protein catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR signaling influences proteasomal turnover of substrates (e.g. IRS1 via Fbw8, AKT); a downstream proteostatic consequence.
    action: KEEP_AS_NON_CORE
    reason: Downstream effect of mTOR-directed phosphorylation on turnover.
- term:
    id: GO:0007040
    label: lysosome organization
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC1 controls lysosome biogenesis/organization through TFEB/TFE3 phosphorylation and cytosolic retention; a downstream organelle-level output.
    action: KEEP_AS_NON_CORE
    reason: Downstream TFEB/TFE3-mediated effect of mTORC1.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: By promoting growth and survival, mTOR signaling supports cell proliferation; a downstream proliferative output.
    action: KEEP_AS_NON_CORE
    reason: Downstream proliferative effect of mTOR.
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR operates downstream of the insulin receptor and exerts feedback (GRB10/IRS1) on it; an integral but downstream node of insulin signaling.
    action: KEEP_AS_NON_CORE
    reason: Downstream/feedback node of insulin signaling.
- term:
    id: GO:0010508
    label: positive regulation of autophagy
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Atypical positive autophagy contexts (e.g. selective/non-canonical autophagy) attributed to mTOR signaling; minor relative to its dominant suppressive role.
    action: KEEP_AS_NON_CORE
    reason: Context-specific downstream effect opposite to mTOR's main autophagy role.
- term:
    id: GO:0031146
    label: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC2-driven phosphorylation routes substrates (e.g. IRS1) to SCF/Fbw8-mediated degradation; a downstream proteostatic output.
    action: KEEP_AS_NON_CORE
    reason: Downstream proteostasis via mTORC2 phosphorylation.
- term:
    id: GO:0045824
    label: negative regulation of innate immune response
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR can dampen innate immune output (e.g. via metabolic/translational control); a downstream immune-regulatory effect.
    action: KEEP_AS_NON_CORE
    reason: Downstream immune-regulatory effect.
- term:
    id: GO:0045947
    label: negative regulation of translational initiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: In some contexts mTOR-linked feedback restrains initiation (e.g. when mTORC1 is inhibited); a context-dependent downstream effect.
    action: KEEP_AS_NON_CORE
    reason: Context-dependent downstream effect on initiation.
- term:
    id: GO:0046627
    label: negative regulation of insulin receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTORC1 phosphorylates GRB10 and promotes IRS1 turnover, providing negative feedback on insulin-receptor signaling.
    action: KEEP_AS_NON_CORE
    reason: Downstream feedback inhibition by mTORC1.
- 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: mTORC2-mediated AKT hydrophobic-motif phosphorylation positively regulates PI3K-AKT signaling, a direct proximal output of mTOR kinase activity.
    action: ACCEPT
    reason: Core; mTORC2 directly activates AKT via Ser473 phosphorylation.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0140367
    label: antibacterial innate immune response
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mTOR shapes innate antibacterial responses (autophagy/translation control in immune cells); a downstream immune role.
    action: KEEP_AS_NON_CORE
    reason: Downstream innate-immune role of mTOR.
- term:
    id: GO:1902554
    label: serine/threonine protein kinase complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic parent of the mTORC1/mTORC2 kinase complexes; the specific TORC1/TORC2 complex terms are the informative annotations for mTOR.
    action: KEEP_AS_NON_CORE
    reason: Subsumed by the specific TORC1/TORC2 complex annotations.
- term:
    id: GO:1903940
    label: negative regulation of TORC2 signaling
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Negative feedback on mTORC2 signaling; a regulatory nuance secondary to mTOR's core mTORC2 kinase role.
    action: KEEP_AS_NON_CORE
    reason: Feedback aspect of mTORC2 signaling, not the core function.
- term:
    id: GO:1904262
    label: negative regulation of TORC1 signaling
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Captures contexts where mTOR activity (e.g. RPTOR phosphorylation) feeds back to dampen mTORC1; a regulatory facet of, rather than the core driving role of, mTOR.
    action: KEEP_AS_NON_CORE
    reason: Feedback regulation downstream of core mTORC1 kinase activity.
- term:
    id: GO:1904263
    label: positive regulation of TORC1 signaling
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Reflects mTOR autophosphorylation/assembly events that enhance mTORC1 output; ancillary to the core catalytic signaling annotation.
    action: KEEP_AS_NON_CORE
    reason: Positive autoregulation downstream of core mTORC1 activity.
- term:
    id: GO:2000059
    label: negative regulation of ubiquitin-dependent protein catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: In other contexts mTOR signaling stabilizes substrates by limiting their ubiquitin-dependent turnover; a context-dependent proteostatic effect.
    action: KEEP_AS_NON_CORE
    reason: Context-dependent downstream proteostatic effect.
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: NAS
  original_reference_id: PMID:17041623
  review:
    summary: mTOR (a PIKK-family kinase) intersects DNA-damage/stress signaling; a contextual role secondary to its growth-control function.
    action: KEEP_AS_NON_CORE
    reason: Contextual PIKK-family stress role (NAS).
- term:
    id: GO:0007010
    label: cytoskeleton organization
  evidence_type: NAS
  original_reference_id: PMID:15268862
  review:
    summary: mTORC2 controls cytoskeletal organization via PKCα/Rho-Rac signaling; a broad downstream effect of mTOR.
    action: KEEP_AS_NON_CORE
    reason: Downstream mTORC2 cytoskeletal output (NAS).
- term:
    id: GO:0010507
    label: negative regulation of autophagy
  evidence_type: NAS
  original_reference_id: PMID:28283069
  review:
    summary: Under nutrient sufficiency mTORC1 phosphorylates ULK1 (Ser758) and other autophagy regulators to suppress autophagy; this inhibition is a core proximal mTOR output.
    action: ACCEPT
    reason: Core; direct ULK1 phosphorylation by mTORC1 (IMP-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0030307
    label: positive regulation of cell growth
  evidence_type: NAS
  original_reference_id: PMID:22500797
  review:
    summary: Integrating its translational and anabolic outputs, mTORC1 promotes increases in cell mass/size; cell growth is the canonical phenotype of mTOR activity.
    action: ACCEPT
    reason: Core; growth promotion is the defining mTORC1 output.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0030307
    label: positive regulation of cell growth
  evidence_type: NAS
  original_reference_id: PMID:25906254
  review:
    summary: Integrating its translational and anabolic outputs, mTORC1 promotes increases in cell mass/size; cell growth is the canonical phenotype of mTOR activity.
    action: ACCEPT
    reason: Core; growth promotion is the defining mTORC1 output.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0031669
    label: cellular response to nutrient levels
  evidence_type: NAS
  original_reference_id: PMID:19299511
  review:
    summary: Nutrient abundance dictates mTORC1 lysosomal recruitment and activity; mTOR is the effector translating nutrient state into growth decisions.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient input to mTORC1.
- term:
    id: GO:0031669
    label: cellular response to nutrient levels
  evidence_type: NAS
  original_reference_id: PMID:22500797
  review:
    summary: Nutrient abundance dictates mTORC1 lysosomal recruitment and activity; mTOR is the effector translating nutrient state into growth decisions.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient input to mTORC1.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: NAS
  original_reference_id: PMID:22500797
  review:
    summary: Through mTORC2-AKT survival signaling mTOR generally suppresses apoptosis; a downstream pro-survival output.
    action: KEEP_AS_NON_CORE
    reason: Downstream pro-survival effect (mTORC2-AKT).
- term:
    id: GO:0045821
    label: positive regulation of glycolytic process
  evidence_type: NAS
  original_reference_id: PMID:20670887
  review:
    summary: mTORC1 boosts glycolysis (via HIF1/MYC programs) to fuel anabolic growth; a metabolic consequence of mTORC1 activity.
    action: KEEP_AS_NON_CORE
    reason: Downstream metabolic output of mTORC1.
- term:
    id: GO:0046889
    label: positive regulation of lipid biosynthetic process
  evidence_type: NAS
  original_reference_id: PMID:20670887
  review:
    summary: mTOR drives lipogenesis through SREBP1 and LPIN1 (mTORC1) and lipid synthesis programs (mTORC2); a major anabolic output downstream of mTOR.
    action: KEEP_AS_NON_CORE
    reason: Downstream lipogenic program of mTOR signaling.
- term:
    id: GO:0071456
    label: cellular response to hypoxia
  evidence_type: NAS
  original_reference_id: PMID:17041623
  review:
    summary: Hypoxia inhibits mTORC1 (REDD1/TSC-dependent) and triggers mTOR nuclear accumulation; mTOR is the responding effector.
    action: KEEP_AS_NON_CORE
    reason: Upstream stress input gating mTORC1 (IDA/NAS).
- term:
    id: GO:0071470
    label: cellular response to osmotic stress
  evidence_type: NAS
  original_reference_id: PMID:17041623
  review:
    summary: mTOR senses osmotic stress via mitochondrial dysfunction, altering its activity; an upstream stress input.
    action: KEEP_AS_NON_CORE
    reason: Upstream stress response of mTOR.
- term:
    id: GO:1905857
    label: positive regulation of pentose-phosphate shunt
  evidence_type: NAS
  original_reference_id: PMID:20670887
  review:
    summary: mTORC1 promotes flux through the pentose phosphate pathway to supply nucleotide precursors, a delayed metabolic output of mTORC1.
    action: KEEP_AS_NON_CORE
    reason: Downstream metabolic effect of mTORC1.
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mTOR associates peripherally with the cytoplasmic face of Golgi membranes; a minor location versus lysosomal/plasma-membrane sites.
    action: KEEP_AS_NON_CORE
    reason: Secondary peripheral-membrane localization.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mTOR is a Ser/Thr (PIKK-family) kinase; the tyrosine-kinase EC 2.7.10.2 activity is only an unproven by-similarity inference and is not an established function of mouse mTOR.
    action: REMOVE
    reason: IEA/ISO/ISS by-similarity only; contradicted by mTOR's Ser/Thr (PIKK) catalytic identity.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:16915281
  review:
    summary: mTOR shuttles to the nucleus and accumulates there under hypoxia; a regulated secondary localization beyond its cytoplasmic membrane sites.
    action: KEEP_AS_NON_CORE
    reason: Regulated nuclear pool (EXP/IDA); secondary location.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:11930000
  review:
    summary: mTOR is a cytoplasmic kinase that shuttles among lysosomal, ER and plasma-membrane surfaces and the cytosol/nucleus; cytoplasmic localization is experimentally established.
    action: ACCEPT
    reason: Supported localization (EXP/ISS); mTOR carries out its kinase function in the cytoplasm.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:16915281
  review:
    summary: mTOR is a cytoplasmic kinase that shuttles among lysosomal, ER and plasma-membrane surfaces and the cytosol/nucleus; cytoplasmic localization is experimentally established.
    action: ACCEPT
    reason: Supported localization (EXP/ISS); mTOR carries out its kinase function in the cytoplasm.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0005741
    label: mitochondrial outer membrane
  evidence_type: EXP
  original_reference_id: PMID:11930000
  review:
    summary: mTOR has been localized to the mitochondrial outer membrane and senses osmotic stress via mitochondrial dysfunction; a peripheral secondary location.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization (EXP) linked to stress sensing.
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mTORC1 is recruited to and activated on the cytosolic face of the lysosomal membrane by Rag-Ragulator and Rheb, the principal site where mTOR integrates nutrient and growth-factor signals.
    action: ACCEPT
    reason: 'Core localization for mTORC1 activation (UniProt: lysosome membrane, peripheral, cytoplasmic side).'
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mTORC2 signals at the cytoplasmic face of the ER membrane; a real secondary location for mTOR complexes.
    action: KEEP_AS_NON_CORE
    reason: Secondary membrane site for mTORC2.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mTORC2 is active at the plasma membrane where it phosphorylates AKT/PKC; a genuine secondary location for mTOR.
    action: KEEP_AS_NON_CORE
    reason: mTORC2 plasma-membrane site; secondary to lysosomal mTORC1.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:11792863
  review:
    summary: Captures mTOR phosphorylation of serine residues (e.g. AKT Ser473, 4E-BP1 serines), a component of its EC 2.7.11.1 serine/threonine kinase activity.
    action: ACCEPT
    reason: Core MF consistent with experimental serine-phosphorylation of mTOR substrates.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:18566587
  review:
    summary: Captures mTOR phosphorylation of serine residues (e.g. AKT Ser473, 4E-BP1 serines), a component of its EC 2.7.11.1 serine/threonine kinase activity.
    action: ACCEPT
    reason: Core MF consistent with experimental serine-phosphorylation of mTOR substrates.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:21321111
  review:
    summary: Captures mTOR phosphorylation of serine residues (e.g. AKT Ser473, 4E-BP1 serines), a component of its EC 2.7.11.1 serine/threonine kinase activity.
    action: ACCEPT
    reason: Core MF consistent with experimental serine-phosphorylation of mTOR substrates.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:27913603
  review:
    summary: Captures mTOR phosphorylation of serine residues (e.g. AKT Ser473, 4E-BP1 serines), a component of its EC 2.7.11.1 serine/threonine kinase activity.
    action: ACCEPT
    reason: Core MF consistent with experimental serine-phosphorylation of mTOR substrates.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:31548312
  review:
    summary: Captures mTOR phosphorylation of serine residues (e.g. AKT Ser473, 4E-BP1 serines), a component of its EC 2.7.11.1 serine/threonine kinase activity.
    action: ACCEPT
    reason: Core MF consistent with experimental serine-phosphorylation of mTOR substrates.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0044325
    label: transmembrane transporter binding
  evidence_type: IPI
  original_reference_id: PMID:27782176
  review:
    summary: mTOR interacts with lysosomal transporters/channels (e.g. TPCN1/2, SLC38A9-type recruiters) relevant to nutrient sensing and recruitment.
    action: KEEP_AS_NON_CORE
    reason: IPI interaction linked to lysosomal recruitment; non-core.
- term:
    id: GO:0009615
    label: response to virus
  evidence_type: IDA
  original_reference_id: PMID:36735752
  review:
    summary: mTOR signaling is engaged during antiviral responses (translational control, innate immunity); a downstream physiological role.
    action: KEEP_AS_NON_CORE
    reason: Downstream innate-immune/translational role.
- term:
    id: GO:2000060
    label: positive regulation of ubiquitin-dependent protein catabolic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mTOR-directed phosphorylation can mark substrates for ubiquitin-dependent degradation; a downstream proteostatic effect.
    action: KEEP_AS_NON_CORE
    reason: Downstream proteostatic effect of mTOR signaling.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: ISO
  original_reference_id: PMID:15185396
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:1905671
    label: regulation of lysosome organization
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Via TFEB/TFE3 phosphorylation mTORC1 regulates lysosomal gene programs and organelle homeostasis.
    action: KEEP_AS_NON_CORE
    reason: Downstream MiT/TFE-mediated effect of mTORC1.
- term:
    id: GO:0046889
    label: positive regulation of lipid biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:29232555
  review:
    summary: mTOR drives lipogenesis through SREBP1 and LPIN1 (mTORC1) and lipid synthesis programs (mTORC2); a major anabolic output downstream of mTOR.
    action: KEEP_AS_NON_CORE
    reason: Downstream lipogenic program of mTOR signaling.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:34245780
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0038203
    label: TORC2 signaling
  evidence_type: IDA
  original_reference_id: PMID:34245780
  review:
    summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:23142081
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:23388827
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0031932
    label: TORC2 complex
  evidence_type: IDA
  original_reference_id: PMID:23142081
  review:
    summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
    action: ACCEPT
    reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0031932
    label: TORC2 complex
  evidence_type: IDA
  original_reference_id: PMID:23388827
  review:
    summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
    action: ACCEPT
    reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0032869
    label: cellular response to insulin stimulus
  evidence_type: IDA
  original_reference_id: PMID:23142081
  review:
    summary: Insulin activates mTORC1/mTORC2 through PI3K-AKT-TSC-Rheb; mTOR is the central effector of the insulin growth-factor response.
    action: KEEP_AS_NON_CORE
    reason: Upstream growth-factor input to mTOR.
- term:
    id: GO:0038203
    label: TORC2 signaling
  evidence_type: IDA
  original_reference_id: PMID:23142081
  review:
    summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0038203
    label: TORC2 signaling
  evidence_type: IDA
  original_reference_id: PMID:23388827
  review:
    summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0038203
    label: TORC2 signaling
  evidence_type: IDA
  original_reference_id: PMID:29232555
  review:
    summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mTORC2 is active at the ER membrane; ER localization is a genuine but secondary site relative to the lysosomal mTORC1 hub.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization (mTORC2 at ER).
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:18566586
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:18566587
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:21321111
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:24670654
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:31548312
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:33850054
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0031932
    label: TORC2 complex
  evidence_type: IDA
  original_reference_id: PMID:24670654
  review:
    summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
    action: ACCEPT
    reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0031932
    label: TORC2 complex
  evidence_type: IDA
  original_reference_id: PMID:33850054
  review:
    summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
    action: ACCEPT
    reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0038203
    label: TORC2 signaling
  evidence_type: IDA
  original_reference_id: PMID:18566586
  review:
    summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0038203
    label: TORC2 signaling
  evidence_type: IDA
  original_reference_id: PMID:18566587
  review:
    summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0038203
    label: TORC2 signaling
  evidence_type: IDA
  original_reference_id: PMID:21321111
  review:
    summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0038203
    label: TORC2 signaling
  evidence_type: IDA
  original_reference_id: PMID:24670654
  review:
    summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0038203
    label: TORC2 signaling
  evidence_type: IDA
  original_reference_id: PMID:31548312
  review:
    summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0038203
    label: TORC2 signaling
  evidence_type: IDA
  original_reference_id: PMID:33850054
  review:
    summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0051896
    label: regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IDA
  original_reference_id: PMID:18566586
  review:
    summary: mTOR regulates PI3K-AKT signaling both as the mTORC2 AKT-kinase and via mTORC1 feedback (GRB10/IRS), placing it as a direct regulator of this pathway.
    action: ACCEPT
    reason: Core; mTOR directly sets AKT activity through mTORC2 and mTORC1 feedback.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0051896
    label: regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IDA
  original_reference_id: PMID:21321111
  review:
    summary: mTOR regulates PI3K-AKT signaling both as the mTORC2 AKT-kinase and via mTORC1 feedback (GRB10/IRS), placing it as a direct regulator of this pathway.
    action: ACCEPT
    reason: Core; mTOR directly sets AKT activity through mTORC2 and mTORC1 feedback.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0051896
    label: regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IDA
  original_reference_id: PMID:31548312
  review:
    summary: mTOR regulates PI3K-AKT signaling both as the mTORC2 AKT-kinase and via mTORC1 feedback (GRB10/IRS), placing it as a direct regulator of this pathway.
    action: ACCEPT
    reason: Core; mTOR directly sets AKT activity through mTORC2 and mTORC1 feedback.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0000822
    label: inositol hexakisphosphate binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: InsP6 is a structural cofactor reported to stabilize the mTOR kinase domain; a structural-ligand feature rather than the catalytic activity.
    action: KEEP_AS_NON_CORE
    reason: Structural cofactor binding; non-core.
- term:
    id: GO:0031932
    label: TORC2 complex
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
    action: ACCEPT
    reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0038203
    label: TORC2 signaling
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0038202
    label: TORC1 signaling
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mTORC1 signaling—phosphorylation of S6K1, 4E-BP1 and ULK1 to drive translation/growth and suppress autophagy—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC1 signaling.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:1900181
    label: negative regulation of protein localization to nucleus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Active mTORC1 phosphorylates TFEB/TFE3 to retain them in the cytosol, preventing their nuclear entry; a specific mechanistic downstream effect.
    action: KEEP_AS_NON_CORE
    reason: Downstream MiT/TFE cytosolic-retention effect of mTORC1.
- term:
    id: GO:1905672
    label: negative regulation of lysosome organization
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Active mTORC1 phosphorylates TFEB/TFE3 to keep them cytosolic, suppressing lysosomal/autophagy gene expression and biogenesis.
    action: KEEP_AS_NON_CORE
    reason: Downstream MiT/TFE inhibition by mTORC1.
- term:
    id: GO:0031929
    label: TOR signaling
  evidence_type: IMP
  original_reference_id: PMID:15485918
  review:
    summary: mTOR is the namesake kinase of TOR signaling, transducing nutrient/growth-factor inputs into control of growth, translation and autophagy via mTORC1 and mTORC2.
    action: ACCEPT
    reason: Core pathway directly executed by mTOR (IMP/IGI).
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: ISO
  original_reference_id: PMID:31915252
  review:
    summary: mTOR catalyzes transfer of phosphate to its protein substrates within mTORC1 and mTORC2, the molecular event underlying all of its signaling outputs.
    action: ACCEPT
    reason: Core catalytic process for a protein kinase; ISO but biologically definitive for mTOR.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0038202
    label: TORC1 signaling
  evidence_type: ISO
  original_reference_id: PMID:31915252
  review:
    summary: mTORC1 signaling—phosphorylation of S6K1, 4E-BP1 and ULK1 to drive translation/growth and suppress autophagy—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC1 signaling.
- term:
    id: GO:0038203
    label: TORC2 signaling
  evidence_type: ISO
  original_reference_id: PMID:31915252
  review:
    summary: mTORC2 signaling—phosphorylation of AKT, PKC and SGK1 hydrophobic/turn motifs controlling survival, cytoskeleton and metabolism—is a core output mTOR directly mediates.
    action: ACCEPT
    reason: Core pathway; mTOR is the catalytic effector of mTORC2 signaling (IDA-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0045860
    label: positive regulation of protein kinase activity
  evidence_type: ISO
  original_reference_id: PMID:31915252
  review:
    summary: By phosphorylating AGC kinases (AKT, PKC, SGK1) mTORC2 increases their activity; a downstream consequence of mTOR's core kinase function.
    action: KEEP_AS_NON_CORE
    reason: Downstream activation of substrate kinases.
- term:
    id: GO:0006954
    label: inflammatory response
  evidence_type: IGI
  original_reference_id: PMID:31874168
  review:
    summary: mTOR modulates inflammatory programs in immune cells through metabolic and translational control; a downstream immune phenotype (IGI).
    action: KEEP_AS_NON_CORE
    reason: Downstream inflammatory role of mTOR.
- term:
    id: GO:0009408
    label: response to heat
  evidence_type: IGI
  original_reference_id: PMID:31874168
  review:
    summary: mTOR signaling responds to heat/proteotoxic stress as part of cellular stress adaptation; a downstream phenotype (IGI).
    action: KEEP_AS_NON_CORE
    reason: Stress-response context downstream of mTOR.
- term:
    id: GO:0019228
    label: neuronal action potential
  evidence_type: IGI
  original_reference_id: PMID:31874168
  review:
    summary: mTOR signaling influences neuronal excitability/action-potential properties (e.g. via channel/translation control); a downstream neuronal phenotype (IGI).
    action: KEEP_AS_NON_CORE
    reason: Downstream neurophysiological effect of mTOR.
- term:
    id: GO:0048266
    label: behavioral response to pain
  evidence_type: IGI
  original_reference_id: PMID:31874168
  review:
    summary: mTOR-dependent translation in sensory neurons modulates nociceptive/pain behavior; a downstream behavioral phenotype (IGI).
    action: KEEP_AS_NON_CORE
    reason: Downstream nociceptive behavioral effect.
- term:
    id: GO:0045335
    label: phagocytic vesicle
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mTOR localizes to phagosomes, relevant to phagosome maturation and innate-immune signaling; a peripheral compartment.
    action: KEEP_AS_NON_CORE
    reason: Secondary vesicular localization.
- term:
    id: GO:0034198
    label: cellular response to amino acid starvation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mTORC1 is inactivated upon amino-acid withdrawal (loss of Rag-Ragulator lysosomal recruitment); mTOR is the sensor-effector responding to this input.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient input gating core mTORC1 activity.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:24011591
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0010506
    label: regulation of autophagy
  evidence_type: IDA
  original_reference_id: PMID:24011591
  review:
    summary: Generic regulation-of-autophagy; mTOR's core, well-defined role is the negative regulation captured by the specific ULK1-linked terms.
    action: KEEP_AS_NON_CORE
    reason: Generic; specific negative-regulation terms are the informative ones.
- term:
    id: GO:0010507
    label: negative regulation of autophagy
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Under nutrient sufficiency mTORC1 phosphorylates ULK1 (Ser758) and other autophagy regulators to suppress autophagy; this inhibition is a core proximal mTOR output.
    action: ACCEPT
    reason: Core; direct ULK1 phosphorylation by mTORC1 (IMP-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0042752
    label: regulation of circadian rhythm
  evidence_type: IMP
  original_reference_id: PMID:29750810
  review:
    summary: mTOR signaling regulates circadian period and amplitude in the SCN and liver clocks; a downstream physiological role (IMP).
    action: KEEP_AS_NON_CORE
    reason: Downstream circadian role of mTOR.
- term:
    id: GO:1904059
    label: regulation of locomotor rhythm
  evidence_type: IMP
  original_reference_id: PMID:29750810
  review:
    summary: mTOR modulates circadian control of locomotor activity rhythms; a downstream behavioral-physiological phenotype (IMP).
    action: KEEP_AS_NON_CORE
    reason: Downstream circadian-behavioral effect of mTOR.
- term:
    id: GO:0031929
    label: TOR signaling
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mTOR is the namesake kinase of TOR signaling, transducing nutrient/growth-factor inputs into control of growth, translation and autophagy via mTORC1 and mTORC2.
    action: ACCEPT
    reason: Core pathway directly executed by mTOR (IMP/IGI).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0070885
    label: negative regulation of calcineurin-NFAT signaling cascade
  evidence_type: IMP
  original_reference_id: PMID:18347059
  review:
    summary: mTOR signaling can antagonize calcineurin-NFAT signaling in immune/cardiac contexts; a downstream cross-talk effect (IMP).
    action: KEEP_AS_NON_CORE
    reason: Downstream signaling cross-talk effect.
- term:
    id: GO:0002296
    label: T-helper 1 cell lineage commitment
  evidence_type: IMP
  original_reference_id: PMID:26410627
  review:
    summary: mTOR signaling directs Th1 lineage commitment in CD4+ T cells; a downstream immune-differentiation phenotype (IMP).
    action: KEEP_AS_NON_CORE
    reason: Downstream immune differentiation role.
- term:
    id: GO:0031929
    label: TOR signaling
  evidence_type: IGI
  original_reference_id: PMID:26160071
  review:
    summary: mTOR is the namesake kinase of TOR signaling, transducing nutrient/growth-factor inputs into control of growth, translation and autophagy via mTORC1 and mTORC2.
    action: ACCEPT
    reason: Core pathway directly executed by mTOR (IMP/IGI).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0016242
    label: negative regulation of macroautophagy
  evidence_type: ISO
  original_reference_id: PMID:25327288
  review:
    summary: mTORC1 directly restrains macroautophagy by phosphorylating ULK1 and inhibiting the autophagy-initiation machinery when nutrients are abundant.
    action: ACCEPT
    reason: Core; ULK1-mediated suppression of macroautophagy by mTORC1 (IMP/IBA).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0031931
    label: TORC1 complex
  evidence_type: IDA
  original_reference_id: PMID:12718876
  review:
    summary: mTOR is the catalytic core of mTORC1 (with RPTOR and MLST8), the nutrient/growth-factor-responsive complex that drives anabolic growth at the lysosomal surface.
    action: ACCEPT
    reason: Core complex; mTOR is an obligate subunit of mTORC1 (IDA/ComplexPortal CPX-4473).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0001932
    label: regulation of protein phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:17556672
  review:
    summary: Generic regulation-of-phosphorylation reflecting mTOR's kinase outputs; less informative than its direct Ser/Thr kinase annotations.
    action: KEEP_AS_NON_CORE
    reason: Generic; covered by specific phosphorylation/kinase terms.
- term:
    id: GO:0016242
    label: negative regulation of macroautophagy
  evidence_type: IMP
  original_reference_id: PMID:23274896
  review:
    summary: mTORC1 directly restrains macroautophagy by phosphorylating ULK1 and inhibiting the autophagy-initiation machinery when nutrients are abundant.
    action: ACCEPT
    reason: Core; ULK1-mediated suppression of macroautophagy by mTORC1 (IMP/IBA).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0001934
    label: positive regulation of protein phosphorylation
  evidence_type: IMP
  original_reference_id: PMID:25139234
  review:
    summary: Generic statement of mTOR increasing substrate phosphorylation (e.g. AKT, S6K); the specific kinase-activity terms convey the mechanism.
    action: KEEP_AS_NON_CORE
    reason: Generic regulatory term subsumed by mTOR's specific kinase MF.
- term:
    id: GO:0003007
    label: heart morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:25139234
  review:
    summary: mTOR-dependent cardiomyocyte growth contributes to heart morphogenesis; a downstream developmental phenotype (IMP).
    action: KEEP_AS_NON_CORE
    reason: Downstream cardiac morphogenesis role.
- term:
    id: GO:0003179
    label: heart valve morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:25139234
  review:
    summary: mTOR signaling participates in valve development via growth/EMT control; a downstream developmental phenotype (IMP).
    action: KEEP_AS_NON_CORE
    reason: Downstream valve morphogenesis role.
- term:
    id: GO:0006112
    label: energy reserve metabolic process
  evidence_type: IMP
  original_reference_id: PMID:25139234
  review:
    summary: mTORC1 influences glycogen/energy-store metabolism as part of anabolic control; a downstream metabolic phenotype (IMP).
    action: KEEP_AS_NON_CORE
    reason: Downstream metabolic role of mTORC1.
- term:
    id: GO:0009791
    label: post-embryonic development
  evidence_type: IMP
  original_reference_id: PMID:25139234
  review:
    summary: mTOR is required for postnatal growth and development as a consequence of its anabolic/growth-control function.
    action: KEEP_AS_NON_CORE
    reason: Developmental phenotype downstream of mTOR growth control.
- term:
    id: GO:0035264
    label: multicellular organism growth
  evidence_type: IMP
  original_reference_id: PMID:25139234
  review:
    summary: Organism-level growth depends on mTORC1-driven cell growth; a whole-animal phenotype downstream of mTOR (IMP).
    action: KEEP_AS_NON_CORE
    reason: Organismal phenotype of core cell-growth role.
- term:
    id: GO:0048738
    label: cardiac muscle tissue development
  evidence_type: IMP
  original_reference_id: PMID:25139234
  review:
    summary: mTOR supports growth and maturation of cardiac muscle tissue; a downstream developmental phenotype (IMP).
    action: KEEP_AS_NON_CORE
    reason: Downstream cardiac tissue development.
- term:
    id: GO:0050882
    label: voluntary musculoskeletal movement
  evidence_type: IMP
  original_reference_id: PMID:25139234
  review:
    summary: mTOR's roles in neuromuscular growth and translation affect voluntary movement; a downstream organismal phenotype (IMP).
    action: KEEP_AS_NON_CORE
    reason: Downstream motor phenotype of mTOR.
- term:
    id: GO:0051896
    label: regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IMP
  original_reference_id: PMID:25139234
  review:
    summary: mTOR regulates PI3K-AKT signaling both as the mTORC2 AKT-kinase and via mTORC1 feedback (GRB10/IRS), placing it as a direct regulator of this pathway.
    action: ACCEPT
    reason: Core; mTOR directly sets AKT activity through mTORC2 and mTORC1 feedback.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0055013
    label: cardiac muscle cell development
  evidence_type: IMP
  original_reference_id: PMID:25139234
  review:
    summary: mTORC1-driven growth contributes to cardiomyocyte development/maturation; a downstream tissue phenotype (IMP).
    action: KEEP_AS_NON_CORE
    reason: Downstream cardiomyocyte developmental role.
- term:
    id: GO:0060048
    label: cardiac muscle contraction
  evidence_type: IMP
  original_reference_id: PMID:25139234
  review:
    summary: mTOR-dependent maintenance of cardiomyocyte growth/metabolism affects cardiac contractile function; a downstream physiological phenotype (IMP).
    action: KEEP_AS_NON_CORE
    reason: Downstream cardiac-function phenotype of mTOR.
- term:
    id: GO:0090559
    label: regulation of membrane permeability
  evidence_type: IMP
  original_reference_id: PMID:25139234
  review:
    summary: mTOR signaling modulates ion-channel/membrane permeability in excitable cells; a downstream physiological effect (IMP).
    action: KEEP_AS_NON_CORE
    reason: Downstream physiological effect of mTOR.
- term:
    id: GO:0048714
    label: positive regulation of oligodendrocyte differentiation
  evidence_type: IMP
  original_reference_id: PMID:25411504
  review:
    summary: mTOR signaling promotes oligodendrocyte differentiation and myelination programs; a downstream CNS differentiation role.
    action: KEEP_AS_NON_CORE
    reason: Downstream CNS differentiation effect (IMP).
- term:
    id: GO:0045670
    label: regulation of osteoclast differentiation
  evidence_type: IDA
  original_reference_id: PMID:19440205
  review:
    summary: mTOR regulates osteoclastogenesis by adjusting CEBPB isoform expression; a downstream cell-differentiation role (IDA).
    action: KEEP_AS_NON_CORE
    reason: Downstream differentiation effect (bone).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23027611
  review:
    summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding term per curation guidelines; not informative.
- term:
    id: GO:0031641
    label: regulation of myelination
  evidence_type: IMP
  original_reference_id: PMID:24101522
  review:
    summary: mTOR controls myelination through oligodendrocyte/Schwann-cell growth and lipid synthesis; a downstream tissue-level role (IMP).
    action: KEEP_AS_NON_CORE
    reason: Downstream myelination phenotype of mTOR.
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: IDA
  original_reference_id: PMID:23836929
  review:
    summary: Dendritic localization of mTOR supports local translation underlying synaptic plasticity; a neuron-specific secondary site.
    action: KEEP_AS_NON_CORE
    reason: Neuronal localization linked to local translation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21413931
  review:
    summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding term per curation guidelines; not informative.
- term:
    id: GO:0006207
    label: '''de novo'' pyrimidine nucleobase biosynthetic process'
  evidence_type: IDA
  original_reference_id: PMID:23429704
  review:
    summary: mTORC1 stimulates pyrimidine synthesis via S6K1-mediated phosphorylation of CAD and pentose-phosphate-fed PRPP; a metabolic output downstream of mTORC1.
    action: KEEP_AS_NON_CORE
    reason: Downstream anabolic process of mTORC1 signaling.
- term:
    id: GO:0055006
    label: cardiac cell development
  evidence_type: IMP
  original_reference_id: PMID:23342106
  review:
    summary: mTOR-dependent growth is required for cardiac cell development; a tissue-specific downstream phenotype (IMP).
    action: KEEP_AS_NON_CORE
    reason: Downstream cardiac developmental role.
- term:
    id: GO:0010831
    label: positive regulation of myotube differentiation
  evidence_type: IGI
  original_reference_id: PMID:19704009
  review:
    summary: mTOR signaling promotes myoblast fusion/myotube differentiation during myogenesis; a downstream developmental role (IGI).
    action: KEEP_AS_NON_CORE
    reason: Downstream myogenic differentiation effect.
- term:
    id: GO:0046889
    label: positive regulation of lipid biosynthetic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mTOR drives lipogenesis through SREBP1 and LPIN1 (mTORC1) and lipid synthesis programs (mTORC2); a major anabolic output downstream of mTOR.
    action: KEEP_AS_NON_CORE
    reason: Downstream lipogenic program of mTOR signaling.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:21258367
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21258367
  review:
    summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding term per curation guidelines; not informative.
- term:
    id: GO:0010507
    label: negative regulation of autophagy
  evidence_type: IMP
  original_reference_id: PMID:21258367
  review:
    summary: Under nutrient sufficiency mTORC1 phosphorylates ULK1 (Ser758) and other autophagy regulators to suppress autophagy; this inhibition is a core proximal mTOR output.
    action: ACCEPT
    reason: Core; direct ULK1 phosphorylation by mTORC1 (IMP-supported).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0031669
    label: cellular response to nutrient levels
  evidence_type: IDA
  original_reference_id: PMID:21258367
  review:
    summary: Nutrient abundance dictates mTORC1 lysosomal recruitment and activity; mTOR is the effector translating nutrient state into growth decisions.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient input to mTORC1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16915281
  review:
    summary: Uninformative IPI 'protein binding' that does not capture mTOR's specific kinase or scaffolding role within its complexes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic binding term per curation guidelines; not informative.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:16915281
  review:
    summary: Soluble cytosolic pool of mTOR/mTOR complexes consistent with its peripheral-membrane association and shuttling behavior.
    action: ACCEPT
    reason: Supported localization (IDA) for cytoplasmic mTOR.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0016605
    label: PML body
  evidence_type: IDA
  original_reference_id: PMID:16915281
  review:
    summary: PML sequesters mTOR in nuclear PML bodies to repress mTORC1 (HIF1α translation control); a regulatory localization documented by IDA.
    action: KEEP_AS_NON_CORE
    reason: Regulatory nuclear-body localization (IDA).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Nucleus, PML body
- term:
    id: GO:0071456
    label: cellular response to hypoxia
  evidence_type: IDA
  original_reference_id: PMID:16915281
  review:
    summary: Hypoxia inhibits mTORC1 (REDD1/TSC-dependent) and triggers mTOR nuclear accumulation; mTOR is the responding effector.
    action: KEEP_AS_NON_CORE
    reason: Upstream stress input gating mTORC1 (IDA/NAS).
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: IDA
  original_reference_id: PMID:21045808
  review:
    summary: mTORC2 associates with ribosomes to cotranslationally phosphorylate nascent AKT, and mTORC1 couples to translation; a functionally relevant but ancillary interaction.
    action: KEEP_AS_NON_CORE
    reason: Supports cotranslational substrate phosphorylation; secondary to core kinase role.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:18347059
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:18347059
  review:
    summary: mTOR shuttles to the nucleus and accumulates there under hypoxia; a regulated secondary localization beyond its cytoplasmic membrane sites.
    action: KEEP_AS_NON_CORE
    reason: Regulated nuclear pool (EXP/IDA); secondary location.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:18347059
  review:
    summary: Soluble cytosolic pool of mTOR/mTOR complexes consistent with its peripheral-membrane association and shuttling behavior.
    action: ACCEPT
    reason: Supported localization (IDA) for cytoplasmic mTOR.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0018105
    label: peptidyl-serine phosphorylation
  evidence_type: IMP
  original_reference_id: PMID:18347059
  review:
    summary: mTOR phosphorylates serine residues of substrate peptides (e.g. AKT Ser473, 4E-BP1, ULK1 Ser758), the residue-level activity of its Ser/Thr kinase function.
    action: ACCEPT
    reason: Core; IMP-supported residue-specific phosphorylation by mTOR.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mTOR is a cytoplasmic kinase that shuttles among lysosomal, ER and plasma-membrane surfaces and the cytosol/nucleus; cytoplasmic localization is experimentally established.
    action: ACCEPT
    reason: Supported localization (EXP/ISS); mTOR carries out its kinase function in the cytoplasm.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mTOR acts at the lysosomal membrane (cytoplasmic face), not in the lysosomal lumen; the membrane component is the precise localization.
    action: MODIFY
    reason: Over-general; lysosomal membrane (GO:0005765) is the specific compartment for mTORC1.
    proposed_replacement_terms: *id002
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Lysosome membrane; Peripheral membrane protein; Cytoplasmic side
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:18381428
  review:
    summary: mTOR shuttles to the nucleus and accumulates there under hypoxia; a regulated secondary localization beyond its cytoplasmic membrane sites.
    action: KEEP_AS_NON_CORE
    reason: Regulated nuclear pool (EXP/IDA); secondary location.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: ISO
  original_reference_id: PMID:15467718
  review:
    summary: mTOR catalyzes transfer of phosphate to its protein substrates within mTORC1 and mTORC2, the molecular event underlying all of its signaling outputs.
    action: ACCEPT
    reason: Core catalytic process for a protein kinase; ISO but biologically definitive for mTOR.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0031931
    label: TORC1 complex
  evidence_type: ISO
  original_reference_id: PMID:15467718
  review:
    summary: mTOR is the catalytic core of mTORC1 (with RPTOR and MLST8), the nutrient/growth-factor-responsive complex that drives anabolic growth at the lysosomal surface.
    action: ACCEPT
    reason: Core complex; mTOR is an obligate subunit of mTORC1 (IDA/ComplexPortal CPX-4473).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0031932
    label: TORC2 complex
  evidence_type: ISO
  original_reference_id: PMID:15467718
  review:
    summary: mTOR is the catalytic core of mTORC2 (with RICTOR, MAPKAP1/SIN1 and MLST8), the growth-factor-responsive complex that phosphorylates AKT/PKC/SGK hydrophobic motifs.
    action: ACCEPT
    reason: Core complex; mTOR is an obligate subunit of mTORC2 (IDA/ComplexPortal CPX-4472).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0046777
    label: protein autophosphorylation
  evidence_type: ISO
  original_reference_id: PMID:15467718
  review:
    summary: mTOR autophosphorylates (e.g. Ser2481) when assembled in mTORC1 or mTORC2, a hallmark of the active kinase used to report complex integrity.
    action: ACCEPT
    reason: Core intrinsic kinase activity; documented mTOR autophosphorylation.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0010592
    label: positive regulation of lamellipodium assembly
  evidence_type: IDA
  original_reference_id: PMID:15467718
  review:
    summary: mTORC2-Rac1 signaling promotes lamellipodia formation during cell migration; a downstream motility output.
    action: KEEP_AS_NON_CORE
    reason: Downstream mTORC2 motility effect (IDA).
- term:
    id: GO:0030838
    label: positive regulation of actin filament polymerization
  evidence_type: IDA
  original_reference_id: PMID:15467718
  review:
    summary: mTORC2 promotes actin polymerization through Rac/Rho and PKC, driving cell shape and motility changes.
    action: KEEP_AS_NON_CORE
    reason: Downstream mTORC2 cytoskeletal effect (IDA/IMP).
- term:
    id: GO:0030838
    label: positive regulation of actin filament polymerization
  evidence_type: IMP
  original_reference_id: PMID:15467718
  review:
    summary: mTORC2 promotes actin polymerization through Rac/Rho and PKC, driving cell shape and motility changes.
    action: KEEP_AS_NON_CORE
    reason: Downstream mTORC2 cytoskeletal effect (IDA/IMP).
- term:
    id: GO:0032868
    label: response to insulin
  evidence_type: IDA
  original_reference_id: PMID:15467718
  review:
    summary: mTOR transduces insulin signaling into anabolic and metabolic outputs; an upstream stimulus for its complexes.
    action: KEEP_AS_NON_CORE
    reason: Upstream growth-factor input to mTOR.
- term:
    id: GO:0043200
    label: response to amino acid
  evidence_type: IDA
  original_reference_id: PMID:15467718
  review:
    summary: Amino-acid availability is a principal cue activating mTORC1; mTOR senses this through the lysosomal Rag machinery.
    action: KEEP_AS_NON_CORE
    reason: Upstream nutrient cue for mTORC1.
- term:
    id: GO:0050731
    label: positive regulation of peptidyl-tyrosine phosphorylation
  evidence_type: IMP
  original_reference_id: PMID:15467718
  review:
    summary: mTOR signaling can raise tyrosine phosphorylation of downstream effectors indirectly; not direct mTOR catalysis on tyrosine.
    action: KEEP_AS_NON_CORE
    reason: Indirect downstream effect, not direct mTOR tyrosine kinase activity.
- term:
    id: GO:0051496
    label: positive regulation of stress fiber assembly
  evidence_type: IDA
  original_reference_id: PMID:15467718
  review:
    summary: mTORC2-RhoA signaling promotes stress-fiber formation; a downstream cytoskeletal output.
    action: KEEP_AS_NON_CORE
    reason: Downstream mTORC2 cytoskeletal effect (IDA).
- term:
    id: GO:1900029
    label: positive regulation of ruffle assembly
  evidence_type: IDA
  original_reference_id: PMID:15467718
  review:
    summary: mTORC2-driven actin remodeling promotes membrane ruffling; a downstream cytoskeletal output.
    action: KEEP_AS_NON_CORE
    reason: Downstream mTORC2 cytoskeletal effect (IDA).
- term:
    id: GO:0045792
    label: negative regulation of cell size
  evidence_type: IGI
  original_reference_id: PMID:15185396
  review:
    summary: Captures contexts where mTOR loss/inhibition reduces cell size or where mTOR feedback limits growth; the directionality opposite to its dominant pro-growth role.
    action: KEEP_AS_NON_CORE
    reason: Context/loss-of-function readout of mTOR growth control.
- term:
    id: GO:0045792
    label: negative regulation of cell size
  evidence_type: ISO
  original_reference_id: PMID:16286931
  review:
    summary: Captures contexts where mTOR loss/inhibition reduces cell size or where mTOR feedback limits growth; the directionality opposite to its dominant pro-growth role.
    action: KEEP_AS_NON_CORE
    reason: Context/loss-of-function readout of mTOR growth control.
- term:
    id: GO:0045792
    label: negative regulation of cell size
  evidence_type: IGI
  original_reference_id: PMID:16286931
  review:
    summary: Captures contexts where mTOR loss/inhibition reduces cell size or where mTOR feedback limits growth; the directionality opposite to its dominant pro-growth role.
    action: KEEP_AS_NON_CORE
    reason: Context/loss-of-function readout of mTOR growth control.
- term:
    id: GO:0045859
    label: regulation of protein kinase activity
  evidence_type: IGI
  original_reference_id: PMID:15185396
  review:
    summary: mTOR modulates activity of downstream kinases through phosphorylation; regulatory consequence of its catalytic role.
    action: KEEP_AS_NON_CORE
    reason: Downstream of core kinase activity.
- term:
    id: GO:0016242
    label: negative regulation of macroautophagy
  evidence_type: IMP
  original_reference_id: PMID:16714284
  review:
    summary: mTORC1 directly restrains macroautophagy by phosphorylating ULK1 and inhibiting the autophagy-initiation machinery when nutrients are abundant.
    action: ACCEPT
    reason: Core; ULK1-mediated suppression of macroautophagy by mTORC1 (IMP/IBA).
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:11707573
  review:
    summary: "mTOR's defining catalytic activity (EC 2.7.11.1): as the kinase subunit of mTORC1/mTORC2 it phosphorylates Ser/Thr residues of 4E-BP1, S6K1, ULK1, AKT, PKC and many other substrates."
    action: ACCEPT
    reason: Core MF; directly supported by experimental catalytic-activity assays and the EC 2.7.11.1 reaction in UniProt.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0018107
    label: peptidyl-threonine phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:11707573
  review:
    summary: mTOR phosphorylates threonine residues of substrates (e.g. AKT Thr450 turn motif), part of its Ser/Thr kinase catalytic repertoire.
    action: ACCEPT
    reason: Core; IDA-supported threonine phosphorylation by mTOR.
    supported_by:
    - reference_id: UniProt:Q9JLN9
      supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
    - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
      supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- term:
    id: GO:0007281
    label: germ cell development
  evidence_type: IDA
  original_reference_id: PMID:12140361
  review:
    summary: mTOR-dependent growth/translation supports germ-cell development; a downstream developmental phenotype (IDA).
    action: KEEP_AS_NON_CORE
    reason: Downstream developmental role of mTOR.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  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:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  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:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  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:11707573
  title: FRAP/mTOR is required for proliferation and patterning during embryonic development in the mouse.
  findings: []
- id: PMID:11792863
  title: Insulin-stimulated phosphorylation of lipin mediated by the mammalian target of rapamycin.
  findings: []
- id: PMID:11930000
  title: FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction.
  findings: []
- id: PMID:12140361
  title: Dissection of the c-Kit signaling pathway in mouse primordial germ cells by retroviral-mediated gene transfer.
  findings: []
- id: PMID:12150926
  title: Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action.
  findings: []
- id: PMID:12718876
  title: GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR.
  findings: []
- id: PMID:15185396
  title: Loss of tuberous sclerosis complex 1 (Tsc1) expression results in increased Rheb/S6K pathway signaling important for astrocyte cell size regulation.
  findings: []
- id: PMID:15268862
  title: Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton.
  findings: []
- id: PMID:15467718
  title: Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive.
  findings: []
- id: PMID:15485918
  title: Disruption of the mouse mTOR gene leads to early postimplantation lethality and prohibits embryonic stem cell development.
  findings: []
- id: PMID:16286931
  title: Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2.
  findings: []
- id: PMID:16541103
  title: mTOR-dependent stimulation of the association of eIF4G and eIF3 by insulin.
  findings: []
- id: PMID:16714284
  title: Autophagy is disrupted in a knock-in mouse model of juvenile neuronal ceroid lipofuscinosis.
  findings: []
- id: PMID:16915281
  title: PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR.
  findings: []
- id: PMID:17041623
  title: Stress and mTORture signaling.
  findings: []
- id: PMID:17556672
  title: Steroid and oxygen effects on eIF4F complex, mTOR, and ENaC translation in fetal lung epithelia.
  findings: []
- id: PMID:18046414
  title: mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex.
  findings: []
- id: PMID:18347059
  title: Integration of protein kinases mTOR and extracellular signal-regulated kinase 5 in regulating nucleocytoplasmic localization of NFATc4.
  findings: []
- id: PMID:18381428
  title: Lkb1 deficiency causes prostate neoplasia in the mouse.
  findings: []
- id: PMID:18566586
  title: The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C.
  findings: []
- id: PMID:18566587
  title: Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling.
  findings: []
- id: PMID:18664580
  title: mTORC1 promotes survival through translational control of Mcl-1.
  findings: []
- id: PMID:19299511
  title: Specific activation of mTORC1 by Rheb G-protein in vitro involves enhanced recruitment of its substrate protein.
  findings: []
- id: PMID:19440205
  title: Transcription factor C/EBPbeta isoform ratio regulates osteoclastogenesis through MafB.
  findings: []
- id: PMID:19704009
  title: Regulation of myoblast differentiation by the nuclear envelope protein NET39.
  findings: []
- id: PMID:20670887
  title: Activation of a metabolic gene regulatory network downstream of mTOR complex 1.
  findings: []
- id: PMID:20801936
  title: Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes.
  findings: []
- id: PMID:21045808
  title: mTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide.
  findings: []
- id: PMID:21258367
  title: AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1.
  findings: []
- id: PMID:21321111
  title: mTOR complex 2 targets Akt for proteasomal degradation via phosphorylation at the hydrophobic motif.
  findings: []
- id: PMID:21413931
  title: Protor-1 is required for efficient mTORC2-mediated activation of SGK1 in the kidney.
  findings: []
- id: PMID:22307628
  title: Glycerolipid signals alter mTOR complex 2 (mTORC2) to diminish insulin signaling.
  findings: []
- id: PMID:22500797
  title: mTOR signaling in growth control and disease.
  findings: []
- id: PMID:23027611
  title: 5-HT(6) receptor recruitment of mTOR as a mechanism for perturbed cognition in schizophrenia.
  findings: []
- id: PMID:23142081
  title: mTOR complex 2 regulates proper turnover of insulin receptor substrate-1 via the ubiquitin ligase subunit Fbw8.
  findings: []
- id: PMID:23274896
  title: Stimulation of autophagy improves endoplasmic reticulum stress-induced diabetes.
  findings: []
- id: PMID:23342106
  title: Mechanistic target of rapamycin (Mtor) is essential for murine embryonic heart development and growth.
  findings: []
- id: PMID:23388827
  title: mTOR complex 2 phosphorylates IMP1 cotranslationally to promote IGF2 production and the proliferation of mouse embryonic fibroblasts.
  findings: []
- id: PMID:23429704
  title: Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis.
  findings: []
- id: PMID:23836929
  title: Degradation of high affinity HuD targets releases Kv1.1 mRNA from miR-129 repression by mTORC1.
  findings: []
- id: PMID:23966835
  title: Reduced juvenile long-term depression in tuberous sclerosis complex is mitigated in adults by compensatory recruitment of mGluR5 and Erk signaling.
  findings: []
- id: PMID:24011591
  title: Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy.
  findings: []
- id: PMID:24036451
  title: PIH1D1 interacts with mTOR complex 1 and enhances ribosome RNA transcription.
  findings: []
- id: PMID:24101522
  title: MicroRNA-23a promotes myelination in the central nervous system.
  findings: []
- id: PMID:24670654
  title: Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus.
  findings: []
- id: PMID:25139234
  title: Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice.
  findings: []
- id: PMID:25327288
  title: Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo.
  findings: []
- id: PMID:25411504
  title: Oligodendrocyte precursor cell-intrinsic effect of Rheb1 controls differentiation and mediates mTORC1-dependent myelination in brain.
  findings: []
- id: PMID:25686248
  title: Huntingtin functions as a scaffold for selective macroautophagy.
  findings: []
- id: PMID:25906254
  title: mLST8 Promotes mTOR-Mediated Tumor Progression.
  findings: []
- id: PMID:25980607
  title: Phosphorylation of ULK1 by AMPK regulates translocation of ULK1 to mitochondria and mitophagy.
  findings: []
- id: PMID:26160071
  title: miR-199a impairs autophagy and induces cardiac hypertrophy through mTOR activation.
  findings: []
- id: PMID:26410627
  title: The Interleukin-2-mTORc1 Kinase Axis Defines the Signaling, Differentiation, and Metabolism of T Helper 1 and Follicular B Helper T Cells.
  findings: []
- id: PMID:27782176
  title: Functional kinomics establishes a critical node of volume-sensitive cation-Cl(-) cotransporter regulation in the mammalian brain.
  findings: []
- id: PMID:27913603
  title: The tumor suppressor FLCN mediates an alternate mTOR pathway to regulate browning of adipose tissue.
  findings: []
- id: PMID:28283069
  title: mTOR Signaling in Growth, Metabolism, and Disease.
  findings: []
- id: PMID:29232555
  title: mTORC2 Promotes Tumorigenesis via Lipid Synthesis.
  findings: []
- id: PMID:29750810
  title: mTOR signaling regulates central and peripheral circadian clock function.
  findings: []
- id: PMID:31548312
  title: Serine 474 phosphorylation is essential for maximal Akt2 kinase activity in adipocytes.
  findings: []
- id: PMID:31874168
  title: Hyperactive Akt-mTOR pathway as a therapeutic target for pain hypersensitivity in Cntnap2-deficient mice.
  findings: []
- id: PMID:31915252
  title: The GATOR2-mTORC2 axis mediates Sestrin2-induced AKT Ser/Thr kinase activation.
  findings: []
- id: PMID:33850054
  title: mTORC2 controls the activity of PKC and Akt by phosphorylating a conserved TOR interaction motif.
  findings: []
- id: PMID:34245780
  title: The innate immune kinase TBK1 directly increases mTORC2 activity and downstream signaling to Akt.
  findings: []
- id: PMID:36735752
  title: Picornavirus infection enhances aspartate by the SLC38A8 transporter to promote viral replication.
  findings: []
- id: UniProt:Q9JLN9
  title: UniProtKB record for mouse Mtor (Q9JLN9)
  findings: []
- id: file:mouse/Mtor/Mtor-deep-research-falcon.md
  title: Falcon deep research synthesis for mouse Mtor
  findings: []
core_functions:
- molecular_function:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  description: Acts as the catalytic kinase of mTORC1, integrating nutrient and growth-factor inputs at lysosomal membranes to regulate translation, cell growth, and autophagy.
  in_complex:
    id: GO:0031931
    label: TORC1 complex
  locations:
  - id: GO:0005765
    label: lysosomal membrane
  - id: GO:0005829
    label: cytosol
  directly_involved_in:
  - id: GO:0038202
    label: TORC1 signaling
  - id: GO:0016242
    label: negative regulation of macroautophagy
  - id: GO:0045948
    label: positive regulation of translational initiation
  supported_by:
  - reference_id: UniProt:Q9JLN9
    supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
  - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
    supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.
- molecular_function:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  description: Acts as the catalytic kinase of mTORC2, phosphorylating AGC-family kinase substrates including AKT and supporting PI3K-AKT pathway output.
  in_complex:
    id: GO:0031932
    label: TORC2 complex
  locations:
  - id: GO:0005737
    label: cytoplasm
  directly_involved_in:
  - id: GO:0038203
    label: TORC2 signaling
  - id: GO:0051896
    label: regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
  supported_by:
  - reference_id: UniProt:Q9JLN9
    supporting_text: Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
  - reference_id: file:mouse/Mtor/Mtor-deep-research-falcon.md
    supporting_text: Mouse **Mtor** encodes **mechanistic/mammalian target of rapamycin (mTOR)**, a PI3K-related **serine/threonine kinase** that nucleates two signaling complexes, **mTORC1** and **mTORC2**.