Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: cytoplasm localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0004674 protein serine/threonine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: Core AKT1 serine/threonine kinase activity Reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation of serine/threonine residues on downstream substrates. Supporting Evidence: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology module to dock onto phosphoinositide-enriched membranes file:mouse/Akt1/Akt1-deep-research-falcon.md Falcon synthesis supports Akt1 as a PH-domain AGC serine/threonine kinase activated downstream of PI3K by membrane recruitment and phosphorylation.
GO:0035556 intracellular signal transduction	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: intracellular signal transduction pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0043066 negative regulation of apoptotic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: negative regulation of apoptotic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0008286 insulin receptor signaling pathway	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: insulin receptor signaling pathway pathway context Reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than the gene product core molecular activity.
GO:0043536 positive regulation of blood vessel endothelial cell migration	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: positive regulation of blood vessel endothelial cell migration pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0004672 protein kinase activity	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: protein kinase activity is less specific than AKT1 serine/threonine kinase activity Reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity terms are present and better capture the function.
GO:0004674 protein serine/threonine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Core AKT1 serine/threonine kinase activity Reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation of serine/threonine residues on downstream substrates. Supporting Evidence: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology module to dock onto phosphoinositide-enriched membranes
GO:0005524 ATP binding	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: ATP binding supports AKT1 activation or recruitment Reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory to the core serine/threonine kinase activity.
GO:0005634 nucleus	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: nucleus pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005737 cytoplasm	IEA GO_REF:0000120	ACCEPT	Summary: cytoplasm localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0005758 mitochondrial intermembrane space	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: mitochondrial intermembrane space pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005783 endoplasmic reticulum	IEA GO_REF:0000108	KEEP AS NON CORE	Summary: endoplasmic reticulum pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005886 plasma membrane	IEA GO_REF:0000120	ACCEPT	Summary: plasma membrane localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:1903898 negative regulation of PERK-mediated unfolded protein response	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: negative regulation of PERK-mediated unfolded protein response pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0005515 protein binding	IPI PMID:12791994 TRB3: a tribbles homolog that inhibits Akt/PKB activation by...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0005515 protein binding	IPI PMID:16051150 An Akt/beta-arrestin 2/PP2A signaling complex mediates dopam...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0005515 protein binding	IPI PMID:18566586 The mammalian target of rapamycin complex 2 controls folding...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0005515 protein binding	IPI PMID:19122674 Deficiency of a beta-arrestin-2 signal complex contributes t...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0005515 protein binding	IPI PMID:19698782 Evidence for the involvement of FAM110C protein in cell spre...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0005515 protein binding	IPI PMID:21339740 Selective activation of Akt1 by mammalian target of rapamyci...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0005515 protein binding	IPI PMID:22309289 Akt augments the oncogenic potential of the HBx protein of h...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0005515 protein binding	IPI PMID:24955524 Akt1 mediates the posterior Hoxc gene expression through epi...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0001649 osteoblast differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: osteoblast differentiation pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0001938 positive regulation of endothelial cell proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of endothelial cell proliferation pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0002042 cell migration involved in sprouting angiogenesis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cell migration involved in sprouting angiogenesis pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0002430 complement receptor mediated signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: complement receptor mediated signaling pathway pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0003376 sphingosine-1-phosphate receptor signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: sphingosine-1-phosphate receptor signaling pathway pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0004712 protein serine/threonine/tyrosine kinase activity	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: protein serine/threonine/tyrosine kinase activity is less specific than AKT1 serine/threonine kinase activity Reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity terms are present and better capture the function.
GO:0005516 calmodulin binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: calmodulin binding pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005547 phosphatidylinositol-3,4,5-trisphosphate binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: phosphatidylinositol-3,4,5-trisphosphate binding supports AKT1 activation or recruitment Reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory to the core serine/threonine kinase activity.
GO:0005654 nucleoplasm	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: nucleoplasm pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005829 cytosol	IEA GO_REF:0000107	ACCEPT	Summary: cytosol localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0005979 regulation of glycogen biosynthetic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: regulation of glycogen biosynthetic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0007173 epidermal growth factor receptor signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: epidermal growth factor receptor signaling pathway pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0008286 insulin receptor signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: insulin receptor signaling pathway pathway context Reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than the gene product core molecular activity.
GO:0010507 negative regulation of autophagy	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of autophagy pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0010595 positive regulation of endothelial cell migration	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of endothelial cell migration pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0010628 positive regulation of gene expression	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of gene expression pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0010748 negative regulation of long-chain fatty acid import across plasma membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of long-chain fatty acid import across plasma membrane pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0010907 positive regulation of glucose metabolic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of glucose metabolic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0016020 membrane	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Generic membrane annotation Reason: The term is too broad to add useful functional information for AKT1 relative to the more specific kinase, localization, and pathway annotations.
GO:0016301 kinase activity	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: kinase activity is less specific than AKT1 serine/threonine kinase activity Reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity terms are present and better capture the function.
GO:0019900 kinase binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Generic kinase binding annotation Reason: The term is too broad to add useful functional information for AKT1 relative to the more specific kinase, localization, and pathway annotations.
GO:0030235 nitric-oxide synthase regulator activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: nitric-oxide synthase regulator activity pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0030307 positive regulation of cell growth	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of cell growth pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0030334 regulation of cell migration	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: regulation of cell migration pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0030335 positive regulation of cell migration	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of cell migration pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0031397 negative regulation of protein ubiquitination	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of protein ubiquitination pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0031982 vesicle	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: vesicle pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0031999 negative regulation of fatty acid beta-oxidation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of fatty acid beta-oxidation pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of proteasomal ubiquitin-dependent protein catabolic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0032869 cellular response to insulin stimulus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cellular response to insulin stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0032991 protein-containing complex	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Generic protein-containing complex annotation Reason: The term is too broad to add useful functional information for AKT1 relative to the more specific kinase, localization, and pathway annotations.
GO:0034405 response to fluid shear stress	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: response to fluid shear stress pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0035655 interleukin-18-mediated signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: interleukin-18-mediated signaling pathway pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0042307 positive regulation of protein import into nucleus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of protein import into nucleus pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0042802 identical protein binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Generic identical protein binding annotation Reason: The term is too broad to add useful functional information for AKT1 relative to the more specific kinase, localization, and pathway annotations.
GO:0042803 protein homodimerization activity	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Generic protein homodimerization activity annotation Reason: The term is too broad to add useful functional information for AKT1 relative to the more specific kinase, localization, and pathway annotations.
GO:0043066 negative regulation of apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of apoptotic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0043325 phosphatidylinositol-3,4-bisphosphate binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: phosphatidylinositol-3,4-bisphosphate binding supports AKT1 activation or recruitment Reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory to the core serine/threonine kinase activity.
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: phosphatidylinositol 3-kinase/protein kinase B signal transduction pathway context Reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than the gene product core molecular activity.
GO:0043536 positive regulation of blood vessel endothelial cell migration	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of blood vessel endothelial cell migration pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0045429 positive regulation of nitric oxide biosynthetic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of nitric oxide biosynthetic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0045600 positive regulation of fat cell differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of fat cell differentiation pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0045725 positive regulation of glycogen biosynthetic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of glycogen biosynthetic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0045861 negative regulation of proteolysis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of proteolysis pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0045944 positive regulation of transcription by RNA polymerase II	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of transcription by RNA polymerase II pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0046326 positive regulation of D-glucose import across plasma membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of D-glucose import across plasma membrane pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0046889 positive regulation of lipid biosynthetic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of lipid biosynthetic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0048009 insulin-like growth factor receptor signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: insulin-like growth factor receptor signaling pathway pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0048661 positive regulation of smooth muscle cell proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of smooth muscle cell proliferation pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0070141 response to UV-A	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: response to UV-A pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0070585 protein localization to mitochondrion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: protein localization to mitochondrion pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0070848 response to growth factor	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: response to growth factor pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0071364 cellular response to epidermal growth factor stimulus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cellular response to epidermal growth factor stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0071889 14-3-3 protein binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: 14-3-3 protein binding pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0072656 maintenance of protein location in mitochondrion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: maintenance of protein location in mitochondrion pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0099104 potassium channel activator activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: potassium channel activator activity pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0106310 protein serine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Direct AKT1 phosphorylation activity Reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
GO:0110002 regulation of tRNA methylation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: regulation of tRNA methylation pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0140052 cellular response to oxidised low-density lipoprotein particle stimulus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cellular response to oxidised low-density lipoprotein particle stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0150033 negative regulation of protein localization to lysosome	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of protein localization to lysosome pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0160049 negative regulation of cGAS/STING signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of cGAS/STING signaling pathway pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1900182 positive regulation of protein localization to nucleus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of protein localization to nucleus pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1902018 negative regulation of cilium assembly	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of cilium assembly pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1903038 negative regulation of leukocyte cell-cell adhesion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of leukocyte cell-cell adhesion pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1903078 positive regulation of protein localization to plasma membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of protein localization to plasma membrane pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1903384 negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1904263 positive regulation of TORC1 signaling	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of TORC1 signaling pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1904841 TORC2 complex binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: TORC2 complex binding supports AKT1 activation or recruitment Reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory to the core serine/threonine kinase activity.
GO:1905552 positive regulation of protein localization to endoplasmic reticulum	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of protein localization to endoplasmic reticulum pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1905786 positive regulation of anaphase-promoting complex-dependent catabolic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of anaphase-promoting complex-dependent catabolic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1990090 cellular response to nerve growth factor stimulus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cellular response to nerve growth factor stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:2000402 negative regulation of lymphocyte migration	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of lymphocyte migration pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0042307 positive regulation of protein import into nucleus	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of protein import into nucleus pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0005886 plasma membrane	ISO GO_REF:0000119	ACCEPT	Summary: plasma membrane localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0106310 protein serine kinase activity	ISO GO_REF:0000119	ACCEPT	Summary: Direct AKT1 phosphorylation activity Reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
GO:0004674 protein serine/threonine kinase activity	EXP PMID:10454575 Insulin-induced phosphorylation and activation of cyclic nuc...	ACCEPT	Summary: Core AKT1 serine/threonine kinase activity Reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation of serine/threonine residues on downstream substrates. Supporting Evidence: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology module to dock onto phosphoinositide-enriched membranes
GO:0004674 protein serine/threonine kinase activity	TAS Reactome:R-MMU-1445150	ACCEPT	Summary: Core AKT1 serine/threonine kinase activity Reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation of serine/threonine residues on downstream substrates. Supporting Evidence: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology module to dock onto phosphoinositide-enriched membranes
GO:0004674 protein serine/threonine kinase activity	TAS Reactome:R-MMU-9857656	ACCEPT	Summary: Core AKT1 serine/threonine kinase activity Reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation of serine/threonine residues on downstream substrates. Supporting Evidence: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology module to dock onto phosphoinositide-enriched membranes
GO:0004674 protein serine/threonine kinase activity	TAS Reactome:R-MMU-9857664	ACCEPT	Summary: Core AKT1 serine/threonine kinase activity Reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation of serine/threonine residues on downstream substrates. Supporting Evidence: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology module to dock onto phosphoinositide-enriched membranes
GO:0005634 nucleus	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: nucleus pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005829 cytosol	ISO GO_REF:0000119	ACCEPT	Summary: cytosol localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0006468 protein phosphorylation	ISO GO_REF:0000096	ACCEPT	Summary: Direct AKT1 phosphorylation activity Reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
GO:0006468 protein phosphorylation	ISO GO_REF:0000119	ACCEPT	Summary: Direct AKT1 phosphorylation activity Reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
GO:0016310 phosphorylation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: phosphorylation pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0018105 peptidyl-serine phosphorylation	ISO GO_REF:0000119	ACCEPT	Summary: Direct AKT1 phosphorylation activity Reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
GO:0018107 peptidyl-threonine phosphorylation	ISO GO_REF:0000119	ACCEPT	Summary: Direct AKT1 phosphorylation activity Reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
GO:0032079 positive regulation of endodeoxyribonuclease activity	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of endodeoxyribonuclease activity pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0033011 perinuclear theca	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: perinuclear theca pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0033138 positive regulation of peptidyl-serine phosphorylation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of peptidyl-serine phosphorylation pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0046777 protein autophosphorylation	ISO GO_REF:0000096	ACCEPT	Summary: Direct AKT1 phosphorylation activity Reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
GO:0097228 sperm principal piece	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: sperm principal piece pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0097229 sperm end piece	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: sperm end piece pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0120238 sperm glycocalyx	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: sperm glycocalyx pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0001649 osteoblast differentiation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: osteoblast differentiation pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0001938 positive regulation of endothelial cell proliferation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of endothelial cell proliferation pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0002042 cell migration involved in sprouting angiogenesis	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cell migration involved in sprouting angiogenesis pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0002181 cytoplasmic translation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cytoplasmic translation pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0002430 complement receptor mediated signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: complement receptor mediated signaling pathway pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0003376 sphingosine-1-phosphate receptor signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: sphingosine-1-phosphate receptor signaling pathway pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0004672 protein kinase activity	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: protein kinase activity is less specific than AKT1 serine/threonine kinase activity Reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity terms are present and better capture the function.
GO:0004672 protein kinase activity	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: protein kinase activity is less specific than AKT1 serine/threonine kinase activity Reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity terms are present and better capture the function.
GO:0004674 protein serine/threonine kinase activity	ISO GO_REF:0000096	ACCEPT	Summary: Core AKT1 serine/threonine kinase activity Reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation of serine/threonine residues on downstream substrates. Supporting Evidence: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology module to dock onto phosphoinositide-enriched membranes
GO:0004674 protein serine/threonine kinase activity	ISO GO_REF:0000119	ACCEPT	Summary: Core AKT1 serine/threonine kinase activity Reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation of serine/threonine residues on downstream substrates. Supporting Evidence: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology module to dock onto phosphoinositide-enriched membranes
GO:0004712 protein serine/threonine/tyrosine kinase activity	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: protein serine/threonine/tyrosine kinase activity is less specific than AKT1 serine/threonine kinase activity Reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity terms are present and better capture the function.
GO:0005080 protein kinase C binding	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: protein kinase C binding pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005516 calmodulin binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: calmodulin binding pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005524 ATP binding	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: ATP binding supports AKT1 activation or recruitment Reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory to the core serine/threonine kinase activity.
GO:0005524 ATP binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: ATP binding supports AKT1 activation or recruitment Reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory to the core serine/threonine kinase activity.
GO:0005547 phosphatidylinositol-3,4,5-trisphosphate binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: phosphatidylinositol-3,4,5-trisphosphate binding supports AKT1 activation or recruitment Reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory to the core serine/threonine kinase activity.
GO:0005634 nucleus	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: nucleus pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005654 nucleoplasm	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: nucleoplasm pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005737 cytoplasm	ISO GO_REF:0000119	ACCEPT	Summary: cytoplasm localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0005739 mitochondrion	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: mitochondrion pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005829 cytosol	ISO GO_REF:0000096	ACCEPT	Summary: cytosol localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0005929 cilium	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cilium pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005978 glycogen biosynthetic process	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: glycogen biosynthetic process pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005979 regulation of glycogen biosynthetic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: regulation of glycogen biosynthetic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0006094 gluconeogenesis	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: gluconeogenesis pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0006412 translation	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: translation pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0006413 translational initiation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: translational initiation pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0006511 ubiquitin-dependent protein catabolic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: ubiquitin-dependent protein catabolic process pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0006606 protein import into nucleus	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: protein import into nucleus pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0006607 NLS-bearing protein import into nucleus	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: NLS-bearing protein import into nucleus pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: endoplasmic reticulum to Golgi vesicle-mediated transport pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0006893 Golgi to plasma membrane transport	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Golgi to plasma membrane transport pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0006974 DNA damage response	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: DNA damage response pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0007173 epidermal growth factor receptor signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: epidermal growth factor receptor signaling pathway pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0008286 insulin receptor signaling pathway	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: insulin receptor signaling pathway pathway context Reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than the gene product core molecular activity.
GO:0008286 insulin receptor signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: insulin receptor signaling pathway pathway context Reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than the gene product core molecular activity.
GO:0009267 cellular response to starvation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cellular response to starvation pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0010507 negative regulation of autophagy	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of autophagy pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0010595 positive regulation of endothelial cell migration	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of endothelial cell migration pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0010628 positive regulation of gene expression	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of gene expression pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0010748 negative regulation of long-chain fatty acid import across plasma membrane	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of long-chain fatty acid import across plasma membrane pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0010907 positive regulation of glucose metabolic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of glucose metabolic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0010918 positive regulation of mitochondrial membrane potential	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of mitochondrial membrane potential pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0014850 response to muscle activity	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: response to muscle activity pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0015630 microtubule cytoskeleton	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: microtubule cytoskeleton pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0016020 membrane	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Generic membrane annotation Reason: The term is too broad to add useful functional information for AKT1 relative to the more specific kinase, localization, and pathway annotations.
GO:0016477 cell migration	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cell migration pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0019899 enzyme binding	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: Generic enzyme binding annotation Reason: The term is too broad to add useful functional information for AKT1 relative to the more specific kinase, localization, and pathway annotations.
GO:0019900 kinase binding	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Generic kinase binding annotation Reason: The term is too broad to add useful functional information for AKT1 relative to the more specific kinase, localization, and pathway annotations.
GO:0019901 protein kinase binding	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: Generic protein kinase binding annotation Reason: The term is too broad to add useful functional information for AKT1 relative to the more specific kinase, localization, and pathway annotations.
GO:0021510 spinal cord development	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: spinal cord development pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0030235 nitric-oxide synthase regulator activity	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: nitric-oxide synthase regulator activity pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0030291 protein serine/threonine kinase inhibitor activity	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: protein serine/threonine kinase inhibitor activity pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0030307 positive regulation of cell growth	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of cell growth pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0030307 positive regulation of cell growth	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of cell growth pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0030334 regulation of cell migration	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: regulation of cell migration pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0030334 regulation of cell migration	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: regulation of cell migration pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0030335 positive regulation of cell migration	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of cell migration pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0030336 negative regulation of cell migration	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of cell migration pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0030425 dendrite	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: dendrite pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0031145 anaphase-promoting complex-dependent catabolic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: anaphase-promoting complex-dependent catabolic process pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0031397 negative regulation of protein ubiquitination	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of protein ubiquitination pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0031667 response to nutrient levels	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: response to nutrient levels pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0031669 cellular response to nutrient levels	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cellular response to nutrient levels pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0031982 vesicle	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: vesicle pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0031999 negative regulation of fatty acid beta-oxidation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of fatty acid beta-oxidation pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of proteasomal ubiquitin-dependent protein catabolic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0032794 GTPase activating protein binding	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: GTPase activating protein binding pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0032869 cellular response to insulin stimulus	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: cellular response to insulin stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0032869 cellular response to insulin stimulus	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cellular response to insulin stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0032929 negative regulation of superoxide anion generation	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: negative regulation of superoxide anion generation pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0032991 protein-containing complex	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Generic protein-containing complex annotation Reason: The term is too broad to add useful functional information for AKT1 relative to the more specific kinase, localization, and pathway annotations.
GO:0034122 negative regulation of toll-like receptor signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of toll-like receptor signaling pathway pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0034123 positive regulation of toll-like receptor signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of toll-like receptor signaling pathway pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0034142 toll-like receptor 4 signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: toll-like receptor 4 signaling pathway pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0034198 cellular response to amino acid starvation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cellular response to amino acid starvation pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0034405 response to fluid shear stress	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: response to fluid shear stress pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0034605 cellular response to heat	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: cellular response to heat pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0035519 protein K29-linked ubiquitination	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: protein K29-linked ubiquitination pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0035655 interleukin-18-mediated signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: interleukin-18-mediated signaling pathway pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0036064 ciliary basal body	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: ciliary basal body pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0036120 cellular response to platelet-derived growth factor stimulus	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: cellular response to platelet-derived growth factor stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0036316 SREBP-SCAP complex retention in endoplasmic reticulum	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: SREBP-SCAP complex retention in endoplasmic reticulum pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0036416 tRNA stabilization	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: tRNA stabilization pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0036444 calcium import into the mitochondrion	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: calcium import into the mitochondrion pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0036499 PERK-mediated unfolded protein response	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: PERK-mediated unfolded protein response pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0038202 TORC1 signaling	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: TORC1 signaling pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0042802 identical protein binding	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Generic identical protein binding annotation Reason: The term is too broad to add useful functional information for AKT1 relative to the more specific kinase, localization, and pathway annotations.
GO:0042803 protein homodimerization activity	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Generic protein homodimerization activity annotation Reason: The term is too broad to add useful functional information for AKT1 relative to the more specific kinase, localization, and pathway annotations.
GO:0043001 Golgi to plasma membrane protein transport	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Golgi to plasma membrane protein transport pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0043065 positive regulation of apoptotic process	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of apoptotic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0043066 negative regulation of apoptotic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of apoptotic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: proteasome-mediated ubiquitin-dependent protein catabolic process pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0043325 phosphatidylinositol-3,4-bisphosphate binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: phosphatidylinositol-3,4-bisphosphate binding supports AKT1 activation or recruitment Reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory to the core serine/threonine kinase activity.
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: phosphatidylinositol 3-kinase/protein kinase B signal transduction pathway context Reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than the gene product core molecular activity.
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: phosphatidylinositol 3-kinase/protein kinase B signal transduction pathway context Reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than the gene product core molecular activity.
GO:0043536 positive regulation of blood vessel endothelial cell migration	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of blood vessel endothelial cell migration pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0045429 positive regulation of nitric oxide biosynthetic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of nitric oxide biosynthetic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0045542 positive regulation of cholesterol biosynthetic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of cholesterol biosynthetic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0045600 positive regulation of fat cell differentiation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of fat cell differentiation pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0045724 positive regulation of cilium assembly	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of cilium assembly pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0045725 positive regulation of glycogen biosynthetic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of glycogen biosynthetic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0045861 negative regulation of proteolysis	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of proteolysis pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0045907 positive regulation of vasoconstriction	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of vasoconstriction pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0045944 positive regulation of transcription by RNA polymerase II	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of transcription by RNA polymerase II pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0045947 negative regulation of translational initiation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of translational initiation pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0045948 positive regulation of translational initiation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of translational initiation pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0046326 positive regulation of D-glucose import across plasma membrane	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of D-glucose import across plasma membrane pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0046329 negative regulation of JNK cascade	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: negative regulation of JNK cascade pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0046889 positive regulation of lipid biosynthetic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of lipid biosynthetic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0048009 insulin-like growth factor receptor signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: insulin-like growth factor receptor signaling pathway pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0048661 positive regulation of smooth muscle cell proliferation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of smooth muscle cell proliferation pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0051247 positive regulation of protein metabolic process	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of protein metabolic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0051604 protein maturation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: protein maturation pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0051721 protein phosphatase 2A binding	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: protein phosphatase 2A binding pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0060627 regulation of vesicle-mediated transport	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: regulation of vesicle-mediated transport pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0061512 protein localization to cilium	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: protein localization to cilium pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0070141 response to UV-A	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: response to UV-A pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0070848 response to growth factor	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: response to growth factor pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0070972 protein localization to endoplasmic reticulum	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: protein localization to endoplasmic reticulum pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0070979 protein K11-linked ubiquitination	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: protein K11-linked ubiquitination pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0071260 cellular response to mechanical stimulus	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: cellular response to mechanical stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0071277 cellular response to calcium ion	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cellular response to calcium ion pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0071364 cellular response to epidermal growth factor stimulus	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: cellular response to epidermal growth factor stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0071364 cellular response to epidermal growth factor stimulus	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cellular response to epidermal growth factor stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0071456 cellular response to hypoxia	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: cellular response to hypoxia pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0071475 cellular hyperosmotic salinity response	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: cellular hyperosmotic salinity response pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0071889 14-3-3 protein binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: 14-3-3 protein binding pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0072350 tricarboxylic acid metabolic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: tricarboxylic acid metabolic process pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0072656 maintenance of protein location in mitochondrion	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: maintenance of protein location in mitochondrion pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0072709 cellular response to sorbitol	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: cellular response to sorbitol pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0085020 protein K6-linked ubiquitination	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: protein K6-linked ubiquitination pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0099104 potassium channel activator activity	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: potassium channel activator activity pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0106004 tRNA (guanine-N7)-methylation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: tRNA (guanine-N7)-methylation pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0110002 regulation of tRNA methylation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: regulation of tRNA methylation pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0110099 negative regulation of calcium import into the mitochondrion	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: negative regulation of calcium import into the mitochondrion pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0120283 protein serine/threonine kinase binding	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: protein serine/threonine kinase binding pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0140052 cellular response to oxidised low-density lipoprotein particle stimulus	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cellular response to oxidised low-density lipoprotein particle stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0140896 cGAS/STING signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cGAS/STING signaling pathway pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0150033 negative regulation of protein localization to lysosome	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of protein localization to lysosome pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0160049 negative regulation of cGAS/STING signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of cGAS/STING signaling pathway pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1900087 positive regulation of G1/S transition of mitotic cell cycle	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of G1/S transition of mitotic cell cycle pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1900182 positive regulation of protein localization to nucleus	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of protein localization to nucleus pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1902018 negative regulation of cilium assembly	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of cilium assembly pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1903038 negative regulation of leukocyte cell-cell adhesion	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of leukocyte cell-cell adhesion pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1903078 positive regulation of protein localization to plasma membrane	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of protein localization to plasma membrane pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1903384 negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1903715 regulation of aerobic respiration	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: regulation of aerobic respiration pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1904262 negative regulation of TORC1 signaling	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of TORC1 signaling pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1904263 positive regulation of TORC1 signaling	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of TORC1 signaling pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1904841 TORC2 complex binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: TORC2 complex binding supports AKT1 activation or recruitment Reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory to the core serine/threonine kinase activity.
GO:1905552 positive regulation of protein localization to endoplasmic reticulum	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of protein localization to endoplasmic reticulum pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1905786 positive regulation of anaphase-promoting complex-dependent catabolic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of anaphase-promoting complex-dependent catabolic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1990090 cellular response to nerve growth factor stimulus	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: cellular response to nerve growth factor stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:1990090 cellular response to nerve growth factor stimulus	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cellular response to nerve growth factor stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:2000402 negative regulation of lymphocyte migration	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of lymphocyte migration pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0007224 smoothened signaling pathway	IMP PMID:31305241 Critical roles of ARHGAP36 as a signal transduction mediator...	KEEP AS NON CORE	Summary: smoothened signaling pathway pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0021525 lateral motor column neuron differentiation	IMP PMID:31305241 Critical roles of ARHGAP36 as a signal transduction mediator...	KEEP AS NON CORE	Summary: lateral motor column neuron differentiation pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0050821 protein stabilization	IMP PMID:31305241 Critical roles of ARHGAP36 as a signal transduction mediator...	KEEP AS NON CORE	Summary: protein stabilization pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0010467 gene expression	IMP PMID:12851395 Akt signaling regulates side population cell phenotype via B...	KEEP AS NON CORE	Summary: gene expression pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0004674 protein serine/threonine kinase activity	IMP PMID:23684622 Dynamic adipocyte phosphoproteome reveals that Akt directly ...	ACCEPT	Summary: Core AKT1 serine/threonine kinase activity Reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation of serine/threonine residues on downstream substrates. Supporting Evidence: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology module to dock onto phosphoinositide-enriched membranes
GO:0004674 protein serine/threonine kinase activity	IMP PMID:26235620 A Positive Feedback Loop between Akt and mTORC2 via SIN1 Pho...	ACCEPT	Summary: Core AKT1 serine/threonine kinase activity Reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation of serine/threonine residues on downstream substrates. Supporting Evidence: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology module to dock onto phosphoinositide-enriched membranes
GO:0071363 cellular response to growth factor stimulus	IMP PMID:23684622 Dynamic adipocyte phosphoproteome reveals that Akt directly ...	KEEP AS NON CORE	Summary: cellular response to growth factor stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0071363 cellular response to growth factor stimulus	IMP PMID:26235620 A Positive Feedback Loop between Akt and mTORC2 via SIN1 Pho...	KEEP AS NON CORE	Summary: cellular response to growth factor stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:1904515 positive regulation of TORC2 signaling	IMP PMID:23684622 Dynamic adipocyte phosphoproteome reveals that Akt directly ...	KEEP AS NON CORE	Summary: positive regulation of TORC2 signaling pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1904515 positive regulation of TORC2 signaling	IMP PMID:26235620 A Positive Feedback Loop between Akt and mTORC2 via SIN1 Pho...	KEEP AS NON CORE	Summary: positive regulation of TORC2 signaling pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:21954288 Akt determines cell fate through inhibition of the PERK-eIF2...	ACCEPT	Summary: Core AKT1 serine/threonine kinase activity Reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation of serine/threonine residues on downstream substrates. Supporting Evidence: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology module to dock onto phosphoinositide-enriched membranes
GO:1903898 negative regulation of PERK-mediated unfolded protein response	IDA PMID:21954288 Akt determines cell fate through inhibition of the PERK-eIF2...	KEEP AS NON CORE	Summary: negative regulation of PERK-mediated unfolded protein response pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0032991 protein-containing complex	ISO PMID:23223530 Protein kinase N1, a cell inhibitor of Akt kinase, has a cen...	MARK AS OVER ANNOTATED	Summary: Generic protein-containing complex annotation Reason: The term is too broad to add useful functional information for AKT1 relative to the more specific kinase, localization, and pathway annotations.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:30504268 Akt-mediated phosphorylation of MICU1 regulates mitochondria...	ACCEPT	Summary: Core AKT1 serine/threonine kinase activity Reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation of serine/threonine residues on downstream substrates. Supporting Evidence: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology module to dock onto phosphoinositide-enriched membranes
GO:0005758 mitochondrial intermembrane space	IDA PMID:30504268 Akt-mediated phosphorylation of MICU1 regulates mitochondria...	KEEP AS NON CORE	Summary: mitochondrial intermembrane space pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0098978 glutamatergic synapse	IDA PMID:26844834 Bidirectional Synaptic Structural Plasticity after Chronic C...	KEEP AS NON CORE	Summary: glutamatergic synapse pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0098978 glutamatergic synapse	IMP PMID:26844834 Bidirectional Synaptic Structural Plasticity after Chronic C...	KEEP AS NON CORE	Summary: glutamatergic synapse pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0099175 regulation of postsynapse organization	IDA PMID:26844834 Bidirectional Synaptic Structural Plasticity after Chronic C...	KEEP AS NON CORE	Summary: regulation of postsynapse organization pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0099175 regulation of postsynapse organization	IMP PMID:26844834 Bidirectional Synaptic Structural Plasticity after Chronic C...	KEEP AS NON CORE	Summary: regulation of postsynapse organization pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1902018 negative regulation of cilium assembly	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: negative regulation of cilium assembly pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0150033 negative regulation of protein localization to lysosome	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: negative regulation of protein localization to lysosome pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:1904263 positive regulation of TORC1 signaling	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: positive regulation of TORC1 signaling pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0005515 protein binding	IPI PMID:34635817 Gm364 coordinates MIB2/DLL3/Notch2 to regulate female fertil...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0022605 mammalian oogenesis stage	IMP PMID:34635817 Gm364 coordinates MIB2/DLL3/Notch2 to regulate female fertil...	KEEP AS NON CORE	Summary: mammalian oogenesis stage pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0048009 insulin-like growth factor receptor signaling pathway	IDA PMID:11784871 Molecular balance between the regulatory and catalytic subun...	KEEP AS NON CORE	Summary: insulin-like growth factor receptor signaling pathway pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0106310 protein serine kinase activity	IDA PMID:11784871 Molecular balance between the regulatory and catalytic subun...	ACCEPT	Summary: Direct AKT1 phosphorylation activity Reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
GO:0048009 insulin-like growth factor receptor signaling pathway	IGI PMID:32439763 Vessel-derived angiocrine IGF1 promotes Meckel's cartilage p...	KEEP AS NON CORE	Summary: insulin-like growth factor receptor signaling pathway pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0016301 kinase activity	IDA PMID:23886629 The Akt substrate Girdin is a regulator of insulin signaling...	MARK AS OVER ANNOTATED	Summary: kinase activity is less specific than AKT1 serine/threonine kinase activity Reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity terms are present and better capture the function.
GO:0008286 insulin receptor signaling pathway	IDA PMID:20889126 Insulin signaling to the glomerular podocyte is critical for...	KEEP AS NON CORE	Summary: insulin receptor signaling pathway pathway context Reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than the gene product core molecular activity.
GO:0004672 protein kinase activity	IDA PMID:31915252 The GATOR2-mTORC2 axis mediates Sestrin2-induced AKT Ser/Thr...	MARK AS OVER ANNOTATED	Summary: protein kinase activity is less specific than AKT1 serine/threonine kinase activity Reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity terms are present and better capture the function.
GO:0005886 plasma membrane	IDA PMID:31915252 The GATOR2-mTORC2 axis mediates Sestrin2-induced AKT Ser/Thr...	ACCEPT	Summary: plasma membrane localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0006468 protein phosphorylation	IDA PMID:31915252 The GATOR2-mTORC2 axis mediates Sestrin2-induced AKT Ser/Thr...	ACCEPT	Summary: Direct AKT1 phosphorylation activity Reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
GO:0006954 inflammatory response	IGI PMID:31874168 Hyperactive Akt-mTOR pathway as a therapeutic target for pai...	KEEP AS NON CORE	Summary: inflammatory response pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0009408 response to heat	IGI PMID:31874168 Hyperactive Akt-mTOR pathway as a therapeutic target for pai...	KEEP AS NON CORE	Summary: response to heat pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0048266 behavioral response to pain	IGI PMID:31874168 Hyperactive Akt-mTOR pathway as a therapeutic target for pai...	KEEP AS NON CORE	Summary: behavioral response to pain pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0010629 negative regulation of gene expression	IDA PMID:19933931 Reciprocal regulation of microRNA-1 and insulin-like growth ...	KEEP AS NON CORE	Summary: negative regulation of gene expression pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0099104 potassium channel activator activity	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: potassium channel activator activity pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005829 cytosol	IDA PMID:28930673 PexRAP Inhibits PRDM16-Mediated Thermogenic Gene Expression.	UNDECIDED	Summary: cytosol localization lacks direct support in the cached PMID:28930673 record Reason: AKT1 cytosolic localization is plausible, but the cached PexRAP/PRDM16 source does not directly support this evidence-specific annotation.
GO:0046889 positive regulation of lipid biosynthetic process	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: positive regulation of lipid biosynthetic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0010467 gene expression	IMP PMID:31272455 Matrix metalloproteinase activity in the lung is increased i...	KEEP AS NON CORE	Summary: gene expression pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:2001243 negative regulation of intrinsic apoptotic signaling pathway	IMP PMID:19911006 AATF mediates an antiapoptotic effect of the unfolded protei...	KEEP AS NON CORE	Summary: negative regulation of intrinsic apoptotic signaling pathway pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0005516 calmodulin binding	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: calmodulin binding pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005515 protein binding	IPI PMID:19028694 Identification and characterization of a novel gene, dapr, i...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0032880 regulation of protein localization	IMP PMID:9415393 Physiological role of Akt in insulin-stimulated translocatio...	KEEP AS NON CORE	Summary: regulation of protein localization pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:2000010 positive regulation of protein localization to cell surface	IMP PMID:9415393 Physiological role of Akt in insulin-stimulated translocatio...	KEEP AS NON CORE	Summary: positive regulation of protein localization to cell surface pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0010628 positive regulation of gene expression	IMP PMID:18292230 Akt and CHIP coregulate tau degradation through coordinated ...	KEEP AS NON CORE	Summary: positive regulation of gene expression pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0005515 protein binding	IPI PMID:23300339 BSTA promotes mTORC2-mediated phosphorylation of Akt1 to sup...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0071356 cellular response to tumor necrosis factor	IDA PMID:24349514 MicroRNA-494, upregulated by tumor necrosis factor-α, desens...	KEEP AS NON CORE	Summary: cellular response to tumor necrosis factor pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0004674 protein serine/threonine kinase activity	IMP PMID:10983986 The protooncogene TCL1 is an Akt kinase coactivator.	ACCEPT	Summary: Core AKT1 serine/threonine kinase activity Reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation of serine/threonine residues on downstream substrates. Supporting Evidence: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology module to dock onto phosphoinositide-enriched membranes
GO:0042981 regulation of apoptotic process	IDA PMID:18977203 Akt activation prevents Apop-1-induced death of cells.	KEEP AS NON CORE	Summary: regulation of apoptotic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0005886 plasma membrane	ISO PMID:17202487 Nonredundant role of Akt2 for neuroprotection of rod photore...	ACCEPT	Summary: plasma membrane localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0046622 positive regulation of organ growth	IMP PMID:15713641 Role for Akt3/protein kinase Bgamma in attainment of normal ...	KEEP AS NON CORE	Summary: positive regulation of organ growth pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0005829 cytosol	TAS Reactome:R-MMU-9863573	ACCEPT	Summary: cytosol localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0005829 cytosol	TAS Reactome:R-MMU-9906595	ACCEPT	Summary: cytosol localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0005634 nucleus	IDA PMID:23786676 Id4 deficiency attenuates prostate development and promotes ...	KEEP AS NON CORE	Summary: nucleus pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005737 cytoplasm	IDA PMID:23786676 Id4 deficiency attenuates prostate development and promotes ...	ACCEPT	Summary: cytoplasm localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain. Supporting Evidence: PMID:23786676 Id4 deficiency attenuates prostate development and promotes PIN-like lesions by regulating androgen receptor activity and expression of NKX3.1 and PTEN.
GO:0005515 protein binding	IPI PMID:16792529 A WD-FYVE protein binds to the kinases Akt and PKCzeta/lambd...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0005634 nucleus	IDA PMID:18388859 Akt- and Foxo1-interacting WD-repeat-FYVE protein promotes a...	KEEP AS NON CORE	Summary: nucleus pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005737 cytoplasm	IDA PMID:18388859 Akt- and Foxo1-interacting WD-repeat-FYVE protein promotes a...	ACCEPT	Summary: cytoplasm localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0010763 positive regulation of fibroblast migration	IMP PMID:23871832 The small GTPase N-Ras regulates extracellular matrix synthe...	KEEP AS NON CORE	Summary: positive regulation of fibroblast migration pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0035924 cellular response to vascular endothelial growth factor stimulus	IDA PMID:25139353 Phosphoinositide 3-kinase β mediates microvascular endotheli...	KEEP AS NON CORE	Summary: cellular response to vascular endothelial growth factor stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0005886 plasma membrane	IDA PMID:25217619 Phosphoinositide 3-kinase p85beta regulates invadopodium for...	UNDECIDED	Summary: plasma membrane localization lacks direct support in the cached PMID:25217619 record Reason: AKT1 plasma membrane recruitment is plausible in PI3K signaling, but the cached PI3K p85beta/invadopodia source does not directly support this evidence-specific localization annotation.
GO:0036294 cellular response to decreased oxygen levels	IDA PMID:24875179 PTEN degradation after ischemic stroke: a double-edged sword...	KEEP AS NON CORE	Summary: cellular response to decreased oxygen levels pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0060416 response to growth hormone	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: response to growth hormone pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:1990418 response to insulin-like growth factor stimulus	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: response to insulin-like growth factor stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0031663 lipopolysaccharide-mediated signaling pathway	IDA PMID:24740015 Myeloid-specific Rictor deletion induces M1 macrophage polar...	KEEP AS NON CORE	Summary: lipopolysaccharide-mediated signaling pathway pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0071380 cellular response to prostaglandin E stimulus	IDA PMID:23479225 Selective impairment of P2Y signaling by prostaglandin E2 in...	KEEP AS NON CORE	Summary: cellular response to prostaglandin E stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0005829 cytosol	TAS Reactome:R-MMU-162352	ACCEPT	Summary: cytosol localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0005829 cytosol	TAS Reactome:R-MMU-9857656	ACCEPT	Summary: cytosol localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0005829 cytosol	TAS Reactome:R-MMU-9857664	ACCEPT	Summary: cytosol localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0005886 plasma membrane	TAS Reactome:R-MMU-1445150	ACCEPT	Summary: plasma membrane localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0010975 regulation of neuron projection development	IDA PMID:21976490 Leukocyte common antigen-related phosphatase is a functional...	KEEP AS NON CORE	Summary: regulation of neuron projection development pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0005515 protein binding	IPI PMID:23223530 Protein kinase N1, a cell inhibitor of Akt kinase, has a cen...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0005515 protein binding	IPI PMID:18160256 A novel Akt/PKB-interacting protein promotes cell adhesion a...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0005515 protein binding	IPI PMID:24156551 KCTD20, a relative of BTBD10, is a positive regulator of Akt...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:23495099 Oct4 interaction with Hmgb2 regulates Akt signaling and plur...	ACCEPT	Summary: Core AKT1 serine/threonine kinase activity Reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation of serine/threonine residues on downstream substrates. Supporting Evidence: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology module to dock onto phosphoinositide-enriched membranes
GO:0006979 response to oxidative stress	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: response to oxidative stress pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0031641 regulation of myelination	IMP PMID:24101522 MicroRNA-23a promotes myelination in the central nervous sys...	KEEP AS NON CORE	Summary: regulation of myelination pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0005886 plasma membrane	IDA PMID:22750946 External push and internal pull forces recruit curvature-sen...	UNDECIDED	Summary: plasma membrane localization lacks direct support in the cached PMID:22750946 record Reason: The cached N-BAR/plasma-membrane-curvature source does not directly support an AKT1-specific plasma membrane localization annotation.
GO:0004712 protein serine/threonine/tyrosine kinase activity	ISO PMID:22797923 ZNRF2 is released from membranes by growth factors and, toge...	MARK AS OVER ANNOTATED	Summary: protein serine/threonine/tyrosine kinase activity is less specific than AKT1 serine/threonine kinase activity Reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity terms are present and better capture the function.
GO:0005737 cytoplasm	IDA PMID:19596798 Growth arrest induces primary-cilium formation and sensitize...	ACCEPT	Summary: cytoplasm localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0036064 ciliary basal body	IDA PMID:19596798 Growth arrest induces primary-cilium formation and sensitize...	KEEP AS NON CORE	Summary: ciliary basal body pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005911 cell-cell junction	IDA PMID:23793062 The lymphoid lineage-specific actin-uncapping protein Rltpr ...	KEEP AS NON CORE	Summary: cell-cell junction pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:1901653 cellular response to peptide	IDA PMID:23793062 The lymphoid lineage-specific actin-uncapping protein Rltpr ...	KEEP AS NON CORE	Summary: cellular response to peptide pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0097011 cellular response to granulocyte macrophage colony-stimulating factor stimulus	IDA PMID:23610142 Critical role of AZI2 in GM-CSF-induced dendritic cell diffe...	KEEP AS NON CORE	Summary: cellular response to granulocyte macrophage colony-stimulating factor stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0001938 positive regulation of endothelial cell proliferation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: positive regulation of endothelial cell proliferation pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0005515 protein binding	IPI PMID:16116448 Bag1 is essential for differentiation and survival of hemato...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0005739 mitochondrion	IDA PMID:16116448 Bag1 is essential for differentiation and survival of hemato...	KEEP AS NON CORE	Summary: mitochondrion pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0097194 execution phase of apoptosis	IDA PMID:12124386 The role of Asp-462 in regulating Akt activity.	KEEP AS NON CORE	Summary: execution phase of apoptosis pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0010765 positive regulation of sodium ion transport	ISO GO_REF:0000008	KEEP AS NON CORE	Summary: positive regulation of sodium ion transport pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0032869 cellular response to insulin stimulus	ISO GO_REF:0000008	KEEP AS NON CORE	Summary: cellular response to insulin stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0032880 regulation of protein localization	ISO GO_REF:0000008	KEEP AS NON CORE	Summary: regulation of protein localization pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0032287 peripheral nervous system myelin maintenance	IMP PMID:20448149 Dlg1-PTEN interaction regulates myelin thickness to prevent ...	KEEP AS NON CORE	Summary: peripheral nervous system myelin maintenance pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:22057101 ZNRF1 promotes Wallerian degeneration by degrading AKT to in...	ACCEPT	Summary: Core AKT1 serine/threonine kinase activity Reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation of serine/threonine residues on downstream substrates. Supporting Evidence: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology module to dock onto phosphoinositide-enriched membranes
GO:0005515 protein binding	IPI PMID:22057101 ZNRF1 promotes Wallerian degeneration by degrading AKT to in...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0007010 cytoskeleton organization	TAS PMID:22057101 ZNRF1 promotes Wallerian degeneration by degrading AKT to in...	KEEP AS NON CORE	Summary: cytoskeleton organization pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0019901 protein kinase binding	IPI PMID:22057101 ZNRF1 promotes Wallerian degeneration by degrading AKT to in...	MARK AS OVER ANNOTATED	Summary: Generic protein kinase binding annotation Reason: The term is too broad to add useful functional information for AKT1 relative to the more specific kinase, localization, and pathway annotations.
GO:0071364 cellular response to epidermal growth factor stimulus	IDA PMID:21712384 Silencer of death domains (SODD) inhibits skeletal muscle an...	KEEP AS NON CORE	Summary: cellular response to epidermal growth factor stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0090201 negative regulation of release of cytochrome c from mitochondria	IDA PMID:18977203 Akt activation prevents Apop-1-induced death of cells.	KEEP AS NON CORE	Summary: negative regulation of release of cytochrome c from mitochondria pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0030334 regulation of cell migration	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: regulation of cell migration pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0005515 protein binding	IPI PMID:20333297 Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0005634 nucleus	IDA PMID:20333297 Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates...	KEEP AS NON CORE	Summary: nucleus pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005886 plasma membrane	IDA PMID:20333297 Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates...	ACCEPT	Summary: plasma membrane localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain. Supporting Evidence: PMID:20333297 Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation.
GO:0006468 protein phosphorylation	IDA PMID:20333297 Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates...	ACCEPT	Summary: Direct AKT1 phosphorylation activity Reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase. Supporting Evidence: PMID:20333297 Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation.
GO:0005515 protein binding	IPI PMID:21030605 PML regulates apoptosis at endoplasmic reticulum by modulati...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0001649 osteoblast differentiation	IGI PMID:19208758 Akt promotes BMP2-mediated osteoblast differentiation and bo...	KEEP AS NON CORE	Summary: osteoblast differentiation pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0006006 glucose metabolic process	IMP PMID:19897600 Role of insulin-like growth factor-binding protein 5 (IGFBP5...	KEEP AS NON CORE	Summary: glucose metabolic process pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0042593 glucose homeostasis	IMP PMID:19897600 Role of insulin-like growth factor-binding protein 5 (IGFBP5...	KEEP AS NON CORE	Summary: glucose homeostasis pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0045944 positive regulation of transcription by RNA polymerase II	IGI PMID:18762576 IGFBP-5 regulates muscle cell differentiation by binding to ...	KEEP AS NON CORE	Summary: positive regulation of transcription by RNA polymerase II pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0051146 striated muscle cell differentiation	IGI PMID:18762576 IGFBP-5 regulates muscle cell differentiation by binding to ...	KEEP AS NON CORE	Summary: striated muscle cell differentiation pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005886 plasma membrane	IDA PMID:15775979 E-cadherin is essential for in vivo epidermal barrier functi...	UNDECIDED	Summary: plasma membrane localization lacks direct support in the cached PMID:15775979 record Reason: The cached E-cadherin/tight-junction source does not directly support an AKT1-specific plasma membrane localization annotation.
GO:0071363 cellular response to growth factor stimulus	IDA PMID:19744960 GIGYF2 gene disruption in mice results in neurodegeneration ...	KEEP AS NON CORE	Summary: cellular response to growth factor stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0032869 cellular response to insulin stimulus	IDA PMID:19139280 ClipR-59 interacts with Akt and regulates Akt cellular compa...	KEEP AS NON CORE	Summary: cellular response to insulin stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0005515 protein binding	IPI PMID:19139280 ClipR-59 interacts with Akt and regulates Akt cellular compa...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0005515 protein binding	IPI PMID:15722337 Phosphorylation of grb10 regulates its interaction with 14-3...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0010975 regulation of neuron projection development	IDA PMID:19778506 DISC1 regulates new neuron development in the adult brain vi...	KEEP AS NON CORE	Summary: regulation of neuron projection development pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0001893 maternal placenta development	IMP PMID:12783884 Protein kinase B alpha/Akt1 regulates placental development ...	KEEP AS NON CORE	Summary: maternal placenta development pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0060709 glycogen cell differentiation involved in embryonic placenta development	IMP PMID:12783884 Protein kinase B alpha/Akt1 regulates placental development ...	KEEP AS NON CORE	Summary: glycogen cell differentiation involved in embryonic placenta development pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0060716 labyrinthine layer blood vessel development	IMP PMID:12783884 Protein kinase B alpha/Akt1 regulates placental development ...	KEEP AS NON CORE	Summary: labyrinthine layer blood vessel development pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005515 protein binding	IPI PMID:16357133 Akt phosphorylates and regulates Pdcd4 tumor suppressor prot...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0010765 positive regulation of sodium ion transport	IDA PMID:17715136 Akt mediates the effect of insulin on epithelial sodium chan...	KEEP AS NON CORE	Summary: positive regulation of sodium ion transport pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0010765 positive regulation of sodium ion transport	IMP PMID:17715136 Akt mediates the effect of insulin on epithelial sodium chan...	KEEP AS NON CORE	Summary: positive regulation of sodium ion transport pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0032869 cellular response to insulin stimulus	IDA PMID:17715136 Akt mediates the effect of insulin on epithelial sodium chan...	KEEP AS NON CORE	Summary: cellular response to insulin stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0032869 cellular response to insulin stimulus	IMP PMID:17715136 Akt mediates the effect of insulin on epithelial sodium chan...	KEEP AS NON CORE	Summary: cellular response to insulin stimulus pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0032880 regulation of protein localization	IDA PMID:17715136 Akt mediates the effect of insulin on epithelial sodium chan...	KEEP AS NON CORE	Summary: regulation of protein localization pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0006468 protein phosphorylation	IDA PMID:15937334 A role for mitogen-activated protein kinase(Erk1/2) activati...	ACCEPT	Summary: Direct AKT1 phosphorylation activity Reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IMP PMID:15937334 A role for mitogen-activated protein kinase(Erk1/2) activati...	KEEP AS NON CORE	Summary: positive regulation of proteasomal ubiquitin-dependent protein catabolic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0018105 peptidyl-serine phosphorylation	IDA PMID:16513828 Impact of obesity on the growth hormone axis: evidence for a...	ACCEPT	Summary: Direct AKT1 phosphorylation activity Reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
GO:0032094 response to food	IDA PMID:16513828 Impact of obesity on the growth hormone axis: evidence for a...	KEEP AS NON CORE	Summary: response to food pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0045792 negative regulation of cell size	ISO PMID:16286931 Regulation of neuronal morphology and function by the tumor ...	KEEP AS NON CORE	Summary: negative regulation of cell size pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0005886 plasma membrane	ISO PMID:14749367 Regulation of apoptosis by the Ft1 protein, a new modulator ...	ACCEPT	Summary: plasma membrane localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.
GO:0006468 protein phosphorylation	ISO PMID:14749367 Regulation of apoptosis by the Ft1 protein, a new modulator ...	ACCEPT	Summary: Direct AKT1 phosphorylation activity Reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
GO:0006924 activation-induced cell death of T cells	ISO PMID:14749367 Regulation of apoptosis by the Ft1 protein, a new modulator ...	KEEP AS NON CORE	Summary: activation-induced cell death of T cells pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0016301 kinase activity	ISO PMID:14749367 Regulation of apoptosis by the Ft1 protein, a new modulator ...	MARK AS OVER ANNOTATED	Summary: kinase activity is less specific than AKT1 serine/threonine kinase activity Reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity terms are present and better capture the function.
GO:0035556 intracellular signal transduction	ISO PMID:14749367 Regulation of apoptosis by the Ft1 protein, a new modulator ...	KEEP AS NON CORE	Summary: intracellular signal transduction pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005515 protein binding	IPI PMID:15753085 A novel protein kinase B (PKB)/AKT-binding protein enhances ...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and should not be treated as informative core function.
GO:0005977 glycogen metabolic process	IMP PMID:12783884 Protein kinase B alpha/Akt1 regulates placental development ...	KEEP AS NON CORE	Summary: glycogen metabolic process pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction	IGI PMID:15249583 The TSC1-2 tumor suppressor controls insulin-PI3K signaling ...	KEEP AS NON CORE	Summary: phosphatidylinositol 3-kinase/protein kinase B signal transduction pathway context Reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than the gene product core molecular activity.
GO:0004672 protein kinase activity	IDA PMID:16357133 Akt phosphorylates and regulates Pdcd4 tumor suppressor prot...	MARK AS OVER ANNOTATED	Summary: protein kinase activity is less specific than AKT1 serine/threonine kinase activity Reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity terms are present and better capture the function.
GO:0009725 response to hormone	IDA PMID:16357133 Akt phosphorylates and regulates Pdcd4 tumor suppressor prot...	KEEP AS NON CORE	Summary: response to hormone pathway context Reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or downstream cellular response rather than the core molecular function.
GO:0004674 protein serine/threonine kinase activity	ISS GO_REF:0000024	ACCEPT	Summary: Core AKT1 serine/threonine kinase activity Reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation of serine/threonine residues on downstream substrates. Supporting Evidence: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology module to dock onto phosphoinositide-enriched membranes
GO:0008286 insulin receptor signaling pathway	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: insulin receptor signaling pathway pathway context Reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than the gene product core molecular activity.
GO:0008286 insulin receptor signaling pathway	IMP PMID:11282895 Reperfusion-activated Akt kinase prevents apoptosis in trans...	KEEP AS NON CORE	Summary: insulin receptor signaling pathway pathway context Reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than the gene product core molecular activity.
GO:0008286 insulin receptor signaling pathway	IMP PMID:9415393 Physiological role of Akt in insulin-stimulated translocatio...	KEEP AS NON CORE	Summary: insulin receptor signaling pathway pathway context Reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than the gene product core molecular activity.
GO:0043066 negative regulation of apoptotic process	IMP PMID:11282895 Reperfusion-activated Akt kinase prevents apoptosis in trans...	KEEP AS NON CORE	Summary: negative regulation of apoptotic process pathway context Reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core molecular activity itself.
GO:0048009 insulin-like growth factor receptor signaling pathway	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: insulin-like growth factor receptor signaling pathway pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0004672 protein kinase activity	IDA PMID:15010863 IL2-dependent phosphorylation of 40S ribosomal protein S6 is...	MARK AS OVER ANNOTATED	Summary: protein kinase activity is less specific than AKT1 serine/threonine kinase activity Reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity terms are present and better capture the function.
GO:0004672 protein kinase activity	IDA PMID:14730361 The costimulation-regulated duration of PKB activation contr...	MARK AS OVER ANNOTATED	Summary: protein kinase activity is less specific than AKT1 serine/threonine kinase activity Reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity terms are present and better capture the function.
GO:0006468 protein phosphorylation	IDA PMID:14730361 The costimulation-regulated duration of PKB activation contr...	ACCEPT	Summary: Direct AKT1 phosphorylation activity Reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
GO:0006954 inflammatory response	IDA PMID:14730361 The costimulation-regulated duration of PKB activation contr...	KEEP AS NON CORE	Summary: inflammatory response pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005819 spindle	IDA PMID:15509711 Serine-threonine kinases and transcription factors active in...	KEEP AS NON CORE	Summary: spindle pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0004672 protein kinase activity	IDA PMID:15192701 PS1 activates PI3K thus inhibiting GSK-3 activity and tau ov...	MARK AS OVER ANNOTATED	Summary: protein kinase activity is less specific than AKT1 serine/threonine kinase activity Reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity terms are present and better capture the function.
GO:0006468 protein phosphorylation	IDA PMID:15192701 PS1 activates PI3K thus inhibiting GSK-3 activity and tau ov...	ACCEPT	Summary: Direct AKT1 phosphorylation activity Reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
GO:0008637 apoptotic mitochondrial changes	IDA PMID:12869584 The serine/threonine kinase Pim-2 is a transcriptionally reg...	KEEP AS NON CORE	Summary: apoptotic mitochondrial changes pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0006468 protein phosphorylation	IDA PMID:12145204 Phosphorylation-dependent ubiquitylation and degradation of ...	ACCEPT	Summary: Direct AKT1 phosphorylation activity Reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
GO:0016567 protein ubiquitination	IDA PMID:12145204 Phosphorylation-dependent ubiquitylation and degradation of ...	KEEP AS NON CORE	Summary: protein ubiquitination pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0030163 protein catabolic process	IDA PMID:12145204 Phosphorylation-dependent ubiquitylation and degradation of ...	KEEP AS NON CORE	Summary: protein catabolic process pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0007281 germ cell development	IDA PMID:12140361 Dissection of the c-Kit signaling pathway in mouse primordia...	KEEP AS NON CORE	Summary: germ cell development pathway context Reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location, interaction, or phenotype rather than the core catalytic function.
GO:0005737 cytoplasm	IDA PMID:12124386 The role of Asp-462 in regulating Akt activity.	ACCEPT	Summary: cytoplasm localization Reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched plasma membrane signaling sites through its PH domain.

Core Functions

AKT1 phosphorylates serine and threonine residues on downstream protein substrates after PI3K-dependent membrane recruitment and activation by upstream kinases.

Molecular Function:

protein serine/threonine kinase activity

Directly Involved In:

protein phosphorylation

Cellular Locations:

cytosol plasma membrane

Supporting Evidence:

file:mouse/Akt1/Akt1-notes.md
AKT1 is a PH-domain AGC serine/threonine protein kinase activated downstream of PI3K and growth factor/insulin signaling.
file:mouse/Akt1/Akt1-deep-research-falcon.md
Falcon synthesis supports Akt1 as an ATP-dependent serine/threonine kinase that phosphorylates downstream substrates after PI3K-dependent activation.

References

GO_REF:0000008

Gene Ontology annotation by the MGI curatorial staff, curated orthology

GO_REF:0000024

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

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000096

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

GO_REF:0000107

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

GO_REF:0000108

Automatic assignment of GO terms using logical inference, based on on inter-ontology links

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000119

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

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10454575

Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt.

PMID:10983986

The protooncogene TCL1 is an Akt kinase coactivator.

PMID:11282895

Reperfusion-activated Akt kinase prevents apoptosis in transgenic mouse hearts overexpressing insulin-like growth factor-1.

PMID:11784871

Molecular balance between the regulatory and catalytic subunits of phosphoinositide 3-kinase regulates cell signaling and survival.

PMID:12124386

The role of Asp-462 in regulating Akt activity.

PMID:12140361

Dissection of the c-Kit signaling pathway in mouse primordial germ cells by retroviral-mediated gene transfer.

PMID:12145204

Phosphorylation-dependent ubiquitylation and degradation of androgen receptor by Akt require Mdm2 E3 ligase.

PMID:12783884

Protein kinase B alpha/Akt1 regulates placental development and fetal growth.

PMID:12791994

TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver.

PMID:12851395

Akt signaling regulates side population cell phenotype via Bcrp1 translocation.

PMID:12869584

The serine/threonine kinase Pim-2 is a transcriptionally regulated apoptotic inhibitor.

PMID:14730361

The costimulation-regulated duration of PKB activation controls T cell longevity.

PMID:14749367

Regulation of apoptosis by the Ft1 protein, a new modulator of protein kinase B/Akt.

PMID:15010863

IL2-dependent phosphorylation of 40S ribosomal protein S6 is controlled by PI-3K/mTOR signalling in CTLL2 cells.

PMID:15192701

PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations.

PMID:15249583

The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins.

PMID:15509711

Serine-threonine kinases and transcription factors active in signal transduction are detected at high levels of phosphorylation during mitosis in preimplantation embryos and trophoblast stem cells.

PMID:15713641

Role for Akt3/protein kinase Bgamma in attainment of normal brain size.

PMID:15722337

Phosphorylation of grb10 regulates its interaction with 14-3-3.

PMID:15753085

A novel protein kinase B (PKB)/AKT-binding protein enhances PKB kinase activity and regulates DNA synthesis.

PMID:15775979

E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions.

PMID:15937334

A role for mitogen-activated protein kinase(Erk1/2) activation and non-selective pore formation in P2X7 receptor-mediated thymocyte death.

PMID:16051150

An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior.

PMID:16116448

Bag1 is essential for differentiation and survival of hematopoietic and neuronal cells.

PMID:16286931

Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2.

PMID:16357133

Akt phosphorylates and regulates Pdcd4 tumor suppressor protein.

PMID:16513828

Impact of obesity on the growth hormone axis: evidence for a direct inhibitory effect of hyperinsulinemia on pituitary function.

PMID:16792529

A WD-FYVE protein binds to the kinases Akt and PKCzeta/lambda.

PMID:17202487

Nonredundant role of Akt2 for neuroprotection of rod photoreceptor cells from light-induced cell death.

PMID:17715136

Akt mediates the effect of insulin on epithelial sodium channels by inhibiting Nedd4-2.

PMID:18160256

A novel Akt/PKB-interacting protein promotes cell adhesion and inhibits familial amyotrophic lateral sclerosis-linked mutant SOD1-induced neuronal death via inhibition of PP2A-mediated dephosphorylation of Akt/PKB.

PMID:18292230

Akt and CHIP coregulate tau degradation through coordinated interactions.

PMID:18388859

Akt- and Foxo1-interacting WD-repeat-FYVE protein promotes adipogenesis.

PMID:18566586

The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C.

PMID:18762576

IGFBP-5 regulates muscle cell differentiation by binding to IGF-II and switching on the IGF-II auto-regulation loop.

PMID:18977203

Akt activation prevents Apop-1-induced death of cells.

PMID:19028694

Identification and characterization of a novel gene, dapr, involved in skeletal muscle differentiation and protein kinase B signaling.

PMID:19122674

Deficiency of a beta-arrestin-2 signal complex contributes to insulin resistance.

PMID:19139280

ClipR-59 interacts with Akt and regulates Akt cellular compartmentalization.

PMID:19208758

Akt promotes BMP2-mediated osteoblast differentiation and bone development.

PMID:19596798

Growth arrest induces primary-cilium formation and sensitizes IGF-1-receptor signaling during differentiation induction of 3T3-L1 preadipocytes.

PMID:19698782

Evidence for the involvement of FAM110C protein in cell spreading and migration.

PMID:19744960

GIGYF2 gene disruption in mice results in neurodegeneration and altered insulin-like growth factor signaling.

PMID:19778506

DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212.

PMID:19897600

Role of insulin-like growth factor-binding protein 5 (IGFBP5) in organismal and pancreatic beta-cell growth.

PMID:19911006

AATF mediates an antiapoptotic effect of the unfolded protein response through transcriptional regulation of AKT1.

PMID:19933931

Reciprocal regulation of microRNA-1 and insulin-like growth factor-1 signal transduction cascade in cardiac and skeletal muscle in physiological and pathological conditions.

PMID:20333297

Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation.

PMID:20448149

Dlg1-PTEN interaction regulates myelin thickness to prevent damaging peripheral nerve overmyelination.

PMID:20889126

Insulin signaling to the glomerular podocyte is critical for normal kidney function.

PMID:21030605

PML regulates apoptosis at endoplasmic reticulum by modulating calcium release.

PMID:21339740

Selective activation of Akt1 by mammalian target of rapamycin complex 2 regulates cancer cell migration, invasion, and metastasis.

PMID:21712384

Silencer of death domains (SODD) inhibits skeletal muscle and kidney enriched inositol 5-phosphatase (SKIP) and regulates phosphoinositide 3-kinase (PI3K)/Akt signaling to the actin cytoskeleton.

PMID:21954288

Akt determines cell fate through inhibition of the PERK-eIF2α phosphorylation pathway.

PMID:21976490

Leukocyte common antigen-related phosphatase is a functional receptor for chondroitin sulfate proteoglycan axon growth inhibitors.

PMID:22057101

ZNRF1 promotes Wallerian degeneration by degrading AKT to induce GSK3B-dependent CRMP2 phosphorylation.

PMID:22309289

Akt augments the oncogenic potential of the HBx protein of hepatitis B virus by phosphorylation.

PMID:22750946

External push and internal pull forces recruit curvature-sensing N-BAR domain proteins to the plasma membrane.

PMID:22797923

ZNRF2 is released from membranes by growth factors and, together with ZNRF1, regulates the Na+/K+ATPase.

PMID:23223530

Protein kinase N1, a cell inhibitor of Akt kinase, has a central role in quality control of germinal center formation.

PMID:23300339

BSTA promotes mTORC2-mediated phosphorylation of Akt1 to suppress expression of FoxC2 and stimulate adipocyte differentiation.

PMID:23479225

Selective impairment of P2Y signaling by prostaglandin E2 in macrophages: implications for Ca2+-dependent responses.

PMID:23495099

Oct4 interaction with Hmgb2 regulates Akt signaling and pluripotency.

PMID:23610142

Critical role of AZI2 in GM-CSF-induced dendritic cell differentiation.

PMID:23684622

Dynamic adipocyte phosphoproteome reveals that Akt directly regulates mTORC2.

PMID:23786676

Id4 deficiency attenuates prostate development and promotes PIN-like lesions by regulating androgen receptor activity and expression of NKX3.1 and PTEN.

PMID:23793062

The lymphoid lineage-specific actin-uncapping protein Rltpr is essential for costimulation via CD28 and the development of regulatory T cells.

PMID:23871832

The small GTPase N-Ras regulates extracellular matrix synthesis, proliferation and migration in fibroblasts.

PMID:23886629

The Akt substrate Girdin is a regulator of insulin signaling in myoblast cells.

PMID:24101522

MicroRNA-23a promotes myelination in the central nervous system.

PMID:24156551

KCTD20, a relative of BTBD10, is a positive regulator of Akt.

PMID:24349514

MicroRNA-494, upregulated by tumor necrosis factor-α, desensitizes insulin effect in C2C12 muscle cells.

PMID:24740015

Myeloid-specific Rictor deletion induces M1 macrophage polarization and potentiates in vivo pro-inflammatory response to lipopolysaccharide.

PMID:24875179

PTEN degradation after ischemic stroke: a double-edged sword.

PMID:24955524

Akt1 mediates the posterior Hoxc gene expression through epigenetic modifications in mouse embryonic fibroblasts.

PMID:25139353

Phosphoinositide 3-kinase β mediates microvascular endothelial repair of thrombotic microangiopathy.

PMID:25217619

Phosphoinositide 3-kinase p85beta regulates invadopodium formation.

PMID:26235620

A Positive Feedback Loop between Akt and mTORC2 via SIN1 Phosphorylation.

PMID:26844834

Bidirectional Synaptic Structural Plasticity after Chronic Cocaine Administration Occurs through Rap1 Small GTPase Signaling.

PMID:28930673

PexRAP Inhibits PRDM16-Mediated Thermogenic Gene Expression.

PMID:30504268

Akt-mediated phosphorylation of MICU1 regulates mitochondrial Ca(2+) levels and tumor growth.

PMID:31272455

Matrix metalloproteinase activity in the lung is increased in Hermansky-Pudlak syndrome.

PMID:31305241

Critical roles of ARHGAP36 as a signal transduction mediator of Shh pathway in lateral motor columnar specification.

PMID:31874168

Hyperactive Akt-mTOR pathway as a therapeutic target for pain hypersensitivity in Cntnap2-deficient mice.

PMID:31915252

The GATOR2-mTORC2 axis mediates Sestrin2-induced AKT Ser/Thr kinase activation.

PMID:32439763

Vessel-derived angiocrine IGF1 promotes Meckel's cartilage proliferation to drive jaw growth during embryogenesis.

PMID:34635817

Gm364 coordinates MIB2/DLL3/Notch2 to regulate female fertility through AKT activation.

PMID:9415393

Physiological role of Akt in insulin-stimulated translocation of GLUT4 in transfected rat adipose cells.

Reactome:R-MMU-1445150

Akt Phosphorylates As160 (Tbc1d4)

Reactome:R-MMU-162352

Phosphorylation of PDE3B by AKT-1

Reactome:R-MMU-9857656

Phosphorylated Akt1 phosphorylates Connexin-43 (Gja1)

Reactome:R-MMU-9857664

p-T308,S473-Akt1 phosphorylates Itga5 (Integrin alpha5) in Itga5:Itgb1 (Integrin alpha5:Integrin beta1)

Reactome:R-MMU-9863573

Akt1 binds phosphoinositol-3,4,5-trisphosphate

Reactome:R-MMU-9906595

Activation of Akt1 by shear stress in osteocytes

file:mouse/Akt1/Akt1-bioreason-rl-predictions.md

BioReason deep research report on Akt1

file:mouse/Akt1/Akt1-deep-research-falcon.md

Falcon deep research summary for mouse Akt1

Akt1 is a broadly expressed PH-domain AGC serine/threonine kinase activated downstream of PI3K signaling.
Falcon synthesis supports Akt substrate phosphorylation in cytoplasmic, membrane-recruited, and nuclear signaling contexts.

file:mouse/Akt1/Akt1-notes.md

AIGR curator notes for Akt1

Deep Research

Falcon

(Akt1-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 23 citations 2026-05-04T00:04:09.247875

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

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

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

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

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

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

Research Report: Mouse Akt1 (UniProt P31750) — Functional Annotation and Current Understanding

0) Target verification (critical identity check)

The requested target is mouse Akt1 (Mus musculus), UniProt P31750, described as RAC‑alpha serine/threonine‑protein kinase (AKT1/PKBα). The retrieved literature used here addresses the AKT/PKB family, consistently describing AKT proteins as AGC-family Ser/Thr kinases with an N‑terminal PH domain, central kinase domain, and C‑terminal hydrophobic motif/tail, and uses canonical activation residues Thr308 and Ser473 that match the expected AKT1 architecture/function for mouse Akt1. Where sources address isoforms, AKT1 is treated explicitly as the broadly expressed isoform distinct from AKT2 and AKT3, and interpretations are restricted to AKT1 unless otherwise stated. (chu2026structuralandmechanistic pages 2-3, modi2023theroleof pages 1-2)

1) Key concepts and definitions (current consensus)

1.1 What Akt1 is

Akt1 is a protein kinase (EC 2.7.11.1) in the AGC Ser/Thr kinase family. Canonically, AKT kinases phosphorylate Ser/Thr residues in substrates containing a basophilic consensus motif approximated as R‑X‑R‑X‑X‑S/T‑φ (φ = hydrophobic residue). (chu2026structuralandmechanistic pages 2-3)

1.2 Catalyzed reaction and substrate specificity

Functionally, Akt1 catalyzes ATP-dependent phosphorylation of protein substrates on Ser/Thr. Its substrate repertoire is broad (>100 substrates are commonly reported for AKT family members), but repeatedly emphasized “well-established” targets include GSK3, FOXO transcription factors, and TSC2, with additional frequent mention of PRAS40 as an mTORC1-regulatory substrate in pathway schematics. (chu2026structuralandmechanistic pages 2-3, leiphrakpam2024pi3kaktmtorsignalingpathway pages 2-4)

1.3 Canonical activation mechanism (PI3K → PIP3 → Akt)

A central defining concept is that Akt activation is membrane-coupled:

1) PI3K produces PIP3 at the plasma membrane.
2) PIP3 binds PH domains in Akt and PDK1, recruiting both to the plasma membrane.
3) PDK1 phosphorylates Akt at Thr308 (activation loop) to yield partial activation.
4) mTORC2 phosphorylates Akt at Ser473 (C-terminal hydrophobic motif) to yield full activation.

This sequence is summarized explicitly in multiple 2023–2024 reviews and in a 2023 primary mechanistic study, and is also captured visually in a PI3K/Akt/mTOR pathway diagram in a 2024 review (Figure 1). (leiphrakpam2024pi3kaktmtorsignalingpathway pages 2-4, palma2023nuak1coordinatesgrowth pages 1-2, leiphrakpam2024pi3kaktmtorsignalingpathway media b35ad198)

1.4 Negative regulation/termination

A key negative regulator is PTEN, which opposes Akt activation by converting PIP3 to PIP2, thereby reducing Akt membrane recruitment and pathway activation. (modi2023theroleof pages 1-2, chu2026structuralandmechanistic pages 3-4)

2) Functional roles, biological processes, and pathway placement

2.1 Primary pathway role: central PI3K–Akt–mTOR signaling node

Across reviews, Akt is positioned as a central node coupling growth factor/RTK signaling to cellular programs of growth, survival, metabolism, and protein synthesis, with prominent functional coupling to mTORC1 through phosphorylation of upstream regulators including TSC2 and PRAS40. (chu2026structuralandmechanistic pages 1-2, leiphrakpam2024pi3kaktmtorsignalingpathway pages 2-4)

2.2 Representative downstream processes (mechanistic examples)

Cell survival / anti-apoptosis: Reviews emphasize Akt-mediated survival signaling through phosphorylation of multiple downstream targets and modulation of apoptotic regulators. (modi2023theroleof pages 2-3, caturano2024insulin–heartaxisbridging pages 2-3)
Metabolism (insulin signaling): In insulin-responsive contexts, Akt phosphorylates regulators including TSC2, PRAS40, and GSK3, linking insulin signaling to metabolism and mTORC1-regulated growth programs; cardiovascular-focused reviews highlight NO production through NOS3/eNOS as a downstream consequence. (caturano2024insulin–heartaxisbridging pages 2-3)
Transcriptional control via FOXO: FOXO family members are repeatedly listed as Akt substrates; phosphorylation of FOXO can alter FOXO localization and transcriptional outputs (e.g., cytoplasmic sequestration in pathway summaries). (beker2026bmal1pi3kaktcrosstalkin pages 5-7, palma2023nuak1coordinatesgrowth pages 2-4)

3) Subcellular localization: where Akt1 acts

3.1 Membrane recruitment as a localization-dependent activation step

A consensus concept is that Akt activation requires recruitment to the plasma membrane via PH-domain binding to PIP3, which positions Akt for phosphorylation by PDK1 and mTORC2. (leiphrakpam2024pi3kaktmtorsignalingpathway pages 2-4, palma2023nuak1coordinatesgrowth pages 1-2)

3.2 Cytoplasmic and nuclear action

Reviews describe Akt as mediating substrate phosphorylation in both cytoplasm and nucleus, consistent with signaling outputs ranging from metabolic enzymes to transcription factors. (leiphrakpam2024pi3kaktmtorsignalingpathway pages 2-4)

3.3 Compartmentalization and substrate selectivity (recent mechanistic evidence)

A 2023 primary study adds an important refinement: subcellular compartmentalization can bias which Akt substrates are phosphorylated.

Palma et al., 2023 (Cell & Bioscience; Dec 2023; https://doi.org/10.1186/s13578-023-01185-2) report that NUAK1 is a regulator of growth factor–dependent Akt activation and is associated with Rab5+ early endosomes (not late endosomes/lysosomes in their assays). Pharmacologic inhibition or loss of NUAK1 reduces Akt Ser473 phosphorylation and preferentially reduces FOXO1/3a phosphorylation (Thr24/Thr32) while leaving TSC2 Thr1462 phosphorylation largely unaffected, supporting a model where endosomal organization and mTORC2 localization influence Akt substrate routing. (palma2023nuak1coordinatesgrowth pages 2-4, palma2023nuak1coordinatesgrowth pages 4-7, palma2023nuak1coordinatesgrowth pages 1-2)

Note (limitation): mitochondria-specific localization of Akt1 was not supported by the retrieved excerpts and is therefore not asserted here.

4) Isoform specificity (Akt1 vs Akt2 vs Akt3) — why it matters for annotation

A recurring expert consensus in 2023–2024 reviews is that AKT isoforms are not redundant:
* Akt1 is broadly expressed and is commonly linked to cell proliferation and survival programs.
* Akt2 is enriched in insulin-sensitive tissues and is closely tied to glucose homeostasis/metabolic control.
* Akt3 is often emphasized in brain contexts (e.g., brain size/development and certain brain tumor contexts).

This isoform framing is important for functional annotation because many studies report “Akt” phosphorylation or activity readouts that may reflect a mixture of isoforms. (modi2023theroleof pages 1-2, chu2026structuralandmechanistic pages 2-3)

5) Recent developments (prioritizing 2023–2024)

5.1 New regulators and location-specific Akt signaling (Dec 2023)

NUAK1→mTORC2→Akt Ser473 regulation is proposed as a mechanism tuning growth-factor responses and substrate selection (FOXO-biased vs TSC2). This is a concrete 2023 addition to mechanistic understanding that intersects directly with “where in the cell” Akt signaling is executed. (palma2023nuak1coordinatesgrowth pages 2-4, palma2023nuak1coordinatesgrowth pages 4-7)

5.2 Mutation/alteration statistics informing pathway targeting (Mar 2024)

In colorectal cancer, a 2024 review summarizes clinically relevant pathway alteration frequencies upstream of Akt:
* PIK3CA somatic missense mutations occur in ~1/3 of CRC cases during the adenoma–carcinoma transition.
* Hotspot mutations (E542K, E545K, H1047R) comprise ~80% of PIK3CA mutations.

These statistics motivate PI3K–Akt–mTOR axis targeting strategies and indicate how often Akt lies downstream of genetically activated signaling. (leiphrakpam2024pi3kaktmtorsignalingpathway pages 2-4)

5.3 Isoform-selective therapeutic logic supported by 2024 primary evidence (Oct 2024)

Miller et al., Oncogene (Oct 2024; https://doi.org/10.1038/s41388-023-02875-4) provide primary evidence that PTEN status rewires PI3K/AKT isoform dependence in prostate cancer models. They report that PTEN-deficient cells preferentially depend on AKT2 (and sometimes AKT3), whereas PTEN re-expression shifts functional dependence toward AKT1; they operationalize this with isoform-selective inhibitors and specific concentrations (e.g., AKT1 inhibitor A‑674563 100 nM; AKT2 inhibitor CCT‑128930 300 nM; PI3Kα inhibitor BYL‑719 5 nM; PI3Kβ inhibitor GSK‑2636771 25 nM). This is a pragmatic 2024 result supporting isoform-aware targeting rather than assuming pan-AKT inhibition is optimal. (miller2024ptenregulatedpi3kp110and pages 2-3)

5.4 Microbiome–metabolite modulation of insulin signaling that intersects Akt–mTOR wiring (Aug 2024)

Du et al., PNAS (Aug 2024; https://doi.org/10.1073/pnas.2400385121) report that a microbiota-derived tryptophan metabolite (5‑HIAA) is depleted in diet-induced insulin resistance and that administering 5‑HIAA improves glucose intolerance and preserves hepatic insulin sensitivity in mice, mechanistically via AhR activation → increased TSC2 transcription → inhibition of mTORC1, which intersects canonical insulin/PI3K/Akt pathway control of mTORC1 signaling. (du2024themicrobiotadependenttryptophan pages 1-2)

6) Current applications and real-world implementations

6.1 Preclinical/experimental implementations in mouse and mammalian systems

Mouse models and PTEN context are used to test isoform dependencies and therapeutic combinations in oncology; PTEN-dependent shifts in AKT isoform reliance have been demonstrated in transgenic mouse-derived prostate cancer lines and human prostate cancer cell models. (miller2024ptenregulatedpi3kp110and pages 2-3)

In metabolism, HFD mouse models are used to test interventions (e.g., microbiota-linked metabolite supplementation) that converge on the insulin→Akt→mTOR axis. (du2024themicrobiotadependenttryptophan pages 1-2)

6.2 Therapeutic modulation in neurological/cardiovascular injury contexts

A 2023 review synthesizes translational evidence that Akt signaling changes rapidly after TBI (on the order of minutes to days) and summarizes multiple interventions reported to modulate Akt/PI3K/mTOR signaling, including valproic acid, simvastatin (14-day regimen cited), stachydrine, and sevoflurane, discussed as approaches that may influence apoptosis, inflammation, and autophagy via Akt-linked mechanisms. (modi2023theroleof pages 2-3)

7) Expert opinions / analysis (from authoritative sources)

Akt is repeatedly described as a central hub downstream of RTKs/PI3K and upstream of mTOR-driven programs; as a result, dysregulation is presented as mechanistically linked to diverse diseases (cancer, insulin resistance, neurological injury, cardiovascular disorders). (leiphrakpam2024pi3kaktmtorsignalingpathway pages 2-4, caturano2024insulin–heartaxisbridging pages 2-3, modi2023theroleof pages 1-2)
Reviews emphasize that activation is multi-step and localization-dependent (PIP3-dependent recruitment; PDK1/mTORC2 phosphorylation), which has direct implications for interpreting phospho-Akt biomarkers and for designing inhibitors that act at specific pathway nodes. (leiphrakpam2024pi3kaktmtorsignalingpathway pages 2-4)
A primary-study-driven expert inference emerging in 2023–2024 is that subcellular compartmentalization can drive substrate selectivity, meaning that “Akt activation” may not imply uniform phosphorylation of all substrates; rather, spatial organization (e.g., endosome/lysosome positioning and mTORC2 association) can route outputs toward FOXO-like targets versus TSC2-like targets. (palma2023nuak1coordinatesgrowth pages 4-7)

8) Relevant statistics and quantitative data (from recent sources)

CRC pathway genetics: PIK3CA missense mutations in ~1/3 of CRC; common hotspots comprise ~80% of PIK3CA mutations. (leiphrakpam2024pi3kaktmtorsignalingpathway pages 2-4)
TBI epidemiology and Akt time-course: worldwide annual TBI prevalence 200 per 100,000 and mortality 18 per 100,000; Akt expression time-course post-TBI: ~15 min initiation, ~4 h rise, 4–24 h peak, ~72 h decline. (modi2023theroleof pages 2-3)
Implementation parameters for isoform targeting (preclinical): example inhibitor concentrations for AKT1 vs AKT2 and PI3K isoforms (AKT1i 100 nM, AKT2i 300 nM, p110αi 5 nM, p110βi 25 nM) and functional assay time windows (chemotaxis 16–24 h; invasion 24–48 h; lysates 48–72 h) used to demonstrate PTEN-dependent isoform reliance. (miller2024ptenregulatedpi3kp110and pages 2-3)

9) Summary tables

The following tables provide a compact synthesis of (i) core functional annotation details and (ii) 2023–2024 developments/applications.

Topic	Evidence summary	Key citations
Identity/domains	Mouse Akt1 corresponds to RAC-alpha serine/threonine-protein kinase/PKBα in the AGC kinase family. The collected evidence describes AKT proteins as having an N-terminal PH domain, a central kinase domain, and a C-terminal regulatory tail/hydrophobic motif, which is consistent with the UniProt P31750 architecture.	(chu2026structuralandmechanistic pages 2-3, modi2023theroleof pages 1-2)
Catalytic activity	Akt1 is a serine/threonine protein kinase that recognizes basophilic substrate motifs of the form R-X-R-X-X-S/T-φ. Reported well-established AKT substrates include GSK3, FOXO transcription factors, TSC2, and PRAS40-linked mTORC1 regulation.	(chu2026structuralandmechanistic pages 2-3, chu2026structuralandmechanistic pages 1-2, leiphrakpam2024pi3kaktmtorsignalingpathway pages 2-4)
Activation mechanism	Canonical activation begins when PI3K generates PIP3, which recruits Akt through its PH domain to the plasma membrane together with PDK1. PDK1 phosphorylates Thr308 for partial activation, and mTORC2 phosphorylates Ser473 in the C-terminal hydrophobic region for full activation; the Thr308/Ser473 phosphorylation balance can influence substrate preference.	(chu2026structuralandmechanistic pages 3-4, leiphrakpam2024pi3kaktmtorsignalingpathway pages 2-4, palma2023nuak1coordinatesgrowth pages 1-2)
Key substrates/outputs	Evidence supports phosphorylation of FOXO1/3a, GSK3, TSC2, and PRAS40 as representative downstream events. These outputs connect Akt signaling to cell survival, proliferation, metabolism, and activation of mTORC1 through inhibition of negative regulators such as TSC2 and PRAS40.	(chu2026structuralandmechanistic pages 1-2, leiphrakpam2024pi3kaktmtorsignalingpathway pages 2-4, beker2026bmal1pi3kaktcrosstalkin pages 5-7)
Localization/compartmentalization	Akt activation depends on plasma-membrane recruitment by PIP3, but downstream signaling is not confined to that site. Evidence also indicates substrate-specific signaling in cytoplasm and nucleus, and a 2023 primary study links compartmentalization around early endosomes, lysosomes, and mTORC2 to differential phosphorylation of FOXO1/3a versus TSC2.	(leiphrakpam2024pi3kaktmtorsignalingpathway pages 2-4, palma2023nuak1coordinatesgrowth pages 1-2, palma2023nuak1coordinatesgrowth pages 4-7)
Isoform specificity notes	The evidence identifies Akt1 as the broadly expressed isoform mainly associated with proliferation and survival, whereas Akt2 is more linked to insulin-responsive metabolism and Akt3 to brain/testis functions. A 2024 cancer study further supports isoform-specific wiring by showing PTEN-positive contexts depend more on AKT1, whereas PTEN-deficient metastatic contexts depend more on AKT2.	(chu2026structuralandmechanistic pages 2-3, modi2023theroleof pages 1-2, miller2024ptenregulatedpi3kp110and pages 1-2)
Negative regulation/termination	Negative regulation occurs upstream through PTEN, which dephosphorylates PIP3 and opposes Akt membrane recruitment/activation. Termination is also reported through phosphatases such as PP2A and PHLPP that reverse activating phosphorylations.	(chu2026structuralandmechanistic pages 3-4, modi2023theroleof pages 1-2)

Table: This table summarizes the core functional annotation points for mouse Akt1 (UniProt P31750) based strictly on the collected evidence snippets. It is useful as a compact reference for identity, mechanism, substrates, localization, isoform context, and negative regulation.

Source (first author, year)	Type (review/primary)	System/context	Key finding relevant to Akt1 function or targeting	Quantitative/statistical detail	URL/DOI
Modi, 2023	Review	Neurological and cardiovascular pathologies; traumatic brain injury (TBI) emphasized	Summarizes Akt isoform biology, noting Akt1 as ubiquitous and associated with cell formation, apoptosis control, proliferation, angiogenesis, and tumor invasiveness; highlights therapeutic Akt upregulation/modulation as a translational strategy in TBI and related disorders (modi2023theroleof pages 1-2, modi2023theroleof pages 2-3)	TBI burden reported as annual prevalence 200/100,000 and mortality 18/100,000 worldwide; Akt expression starts ~15 min after TBI, rises to 4 h, peaks at 4–24 h, and subsides after ~72 h; Simvastatin regimen noted as 14 days (modi2023theroleof pages 2-3)	https://doi.org/10.26650/eurjbiol.2023.1240220
Palma, 2023	Primary	Growth-factor signaling in cultured cancer/HEK293T cells; mTORC2-Akt regulation	Demonstrates canonical Akt activation (PI3K→PIP3→PH-domain recruitment; PDK1 Thr308; mTORC2 Ser473) and identifies NUAK1 as a regulator of Akt Ser473 phosphorylation and substrate selectivity, preferentially affecting FOXO1/3a over TSC2; supports compartment-specific Akt signaling relevant to functional annotation and drug targeting (palma2023nuak1coordinatesgrowth pages 2-4, palma2023nuak1coordinatesgrowth pages 4-7, palma2023nuak1coordinatesgrowth pages 1-2)	NUAK1 inhibitor pretreatment 10 µM for 90 min; effects tracked over EGF stimulation windows including ~20–60 min; reduced Akt Ser473 and FOXO1/3a phosphorylation but not TSC2 in reported assays (palma2023nuak1coordinatesgrowth pages 2-4, palma2023nuak1coordinatesgrowth pages 4-7)	https://doi.org/10.1186/s13578-023-01185-2
Leiphrakpam, 2024	Review	Colorectal cancer (CRC)	Frames PI3K/Akt/mTOR as a therapeutic target in CRC; details Akt activation steps and downstream targets including PRAS40, TSC2, FOXO, and GSK3, supporting intervention at PI3K, Akt, and mTOR nodes (leiphrakpam2024pi3kaktmtorsignalingpathway pages 2-4)	PIK3CA somatic missense mutations occur in ~1/3 of CRC cases; hotspot mutations E542K, E545K, H1047R account for ~80% of PIK3CA mutations (leiphrakpam2024pi3kaktmtorsignalingpathway pages 2-4)	https://doi.org/10.3390/ijms25063178
Giaccari, 2024	Review	Mammalian ovary; fertility, PCOS, premature ovarian failure, ovarian cancer	Reviews PI3K/Akt as central to oogenesis, folliculogenesis, oocyte maturation, embryo development, and ovarian pathology; explicitly discusses use of inhibitors and activators to rebalance Akt signaling in ovarian disease contexts (giaccari2024anupdateon pages 1-2)	No specific quantitative/statistical values reported in the extracted context (giaccari2024anupdateon pages 1-2)	https://doi.org/10.3390/life14060722
Caturano, 2024	Review	Insulin signaling and cardiac physiology/pathophysiology	Summarizes canonical Akt activation and downstream phosphorylation of TSC2, PRAS40, GSK3, and NOS3/eNOS, linking Akt to cardiac metabolism, growth, survival, angiogenesis, vasorelaxation, and insulin-resistance biology (caturano2024insulin–heartaxisbridging pages 2-3)	No specific mutation-frequency or intervention statistics reported in the extracted context (caturano2024insulin–heartaxisbridging pages 2-3)	https://doi.org/10.3390/ijms25158369
Miller, 2024	Primary	Prostate cancer models, including transgenic mice and human PC cell lines	Shows PTEN status rewires PI3K/AKT isoform dependence: PTEN-deficient settings depend more on AKT2, whereas PTEN re-expression shifts dependency toward AKT1; supports isoform-selective targeting strategies rather than generic pan-AKT inhibition (miller2024ptenregulatedpi3kp110and pages 2-3)	Inhibitor conditions included A-674563 (AKT1i) 100 nM, CCT-128930 (AKT2i) 300 nM, BYL-719 (p110αi) 5 nM, GSK-2636771 (p110βi) 25 nM, Saracatinib 150 nM; sample sizes reported to provide >80% power; coefficient of variation 0.6; chemotaxis 16–24 h, invasion 24–48 h, lysate analysis 48–72 h post-transfection (miller2024ptenregulatedpi3kp110and pages 2-3)	https://doi.org/10.1038/s41388-023-02875-4
Du, 2024	Primary	High-fat-diet mouse model and human T2D-associated metabolite context	Identifies microbiota-derived 5-HIAA as a metabolite that improves glucose intolerance and preserves hepatic insulin sensitivity through AhR→TSC2→mTORC1 signaling, intersecting with insulin/PI3K/Akt pathway biology relevant to Akt-centered metabolic applications (du2024themicrobiotadependenttryptophan pages 1-2)	Qualitative effects reported in extracted context (improved glucose intolerance, obesity, hepatic insulin sensitivity), but no numerical phospho-Akt/pGSK3 statistics are provided in the retrieved excerpt (du2024themicrobiotadependenttryptophan pages 1-2)	https://doi.org/10.1073/pnas.2400385121

Table: This table compiles recent 2023–2024 reviews and primary studies relevant to Akt1/PI3K/Akt/mTOR biology, emphasizing functional findings, translational applications, and quantitative details where available. It is useful for quickly identifying recent evidence on mechanism, disease relevance, and therapeutic targeting.

10) Evidence and coverage limitations

1) The retrieved excerpts include robust support for domain architecture, canonical activation, representative substrates, and compartmentalized signaling, but do not provide sequence-level mapping explicitly to UniProt P31750 within the text itself; identity is therefore anchored to the user-provided UniProt accession and the conserved AKT1 features documented in the sources. (chu2026structuralandmechanistic pages 2-3, modi2023theroleof pages 1-2)
2) Some recent primary studies (e.g., PNAS 2024 on 5‑HIAA) are represented here via abstract/limited excerpt; quantitative phospho-Akt effect sizes (e.g., fold changes, p-values) were not available in the retrieved text snippets and are not reported. (du2024themicrobiotadependenttryptophan pages 1-2)
3) While Akt biology is deeply developed, the current evidence set retrieved for this report does not include a mouse Akt1-specific subcellular localization dataset beyond plasma membrane recruitment and general cytoplasm/nucleus localization and the endosome/lysosome compartmentalization framework; additional targeted retrieval (e.g., Akt1 mitochondrial localization studies) would be required to expand the localization section beyond what is supported here.

References

(chu2026structuralandmechanistic pages 2-3): Nam Chu, Nhat Le, Ouada Nebie, and Sammi Yang. Structural and mechanistic basis of mtorc2 activation of protein kinase akt/pkb. Biochemical Journal, 483:375-389, Mar 2026. URL: https://doi.org/10.1042/bcj20253108, doi:10.1042/bcj20253108. This article has 1 citations and is from a domain leading peer-reviewed journal.
(modi2023theroleof pages 1-2): Akshat D. Modi, Aahmad Mahoon, and Dharmeshkumar M Modi. The role of akt signalling pathway in neurological and cardiovascular pathologies. European Journal of Biology, 82:95-108, Jun 2023. URL: https://doi.org/10.26650/eurjbiol.2023.1240220, doi:10.26650/eurjbiol.2023.1240220. This article has 3 citations.
(leiphrakpam2024pi3kaktmtorsignalingpathway pages 2-4): Premila Leiphrakpam and Chandrakanth Are. Pi3k/akt/mtor signaling pathway as a target for colorectal cancer treatment. International Journal of Molecular Sciences, 25:3178, Mar 2024. URL: https://doi.org/10.3390/ijms25063178, doi:10.3390/ijms25063178. This article has 179 citations.
(palma2023nuak1coordinatesgrowth pages 1-2): Mario Palma, Elizabeth Riffo, Alejandro Farias, Viviana Coliboro-Dannich, Luis Espinoza-Francine, Emilia Escalona, Roberto Amigo, José L. Gutiérrez, Roxana Pincheira, and Ariel F. Castro. Nuak1 coordinates growth factor-dependent activation of mtorc2 and akt signaling. Cell & Bioscience, Dec 2023. URL: https://doi.org/10.1186/s13578-023-01185-2, doi:10.1186/s13578-023-01185-2. This article has 9 citations and is from a peer-reviewed journal.
(leiphrakpam2024pi3kaktmtorsignalingpathway media b35ad198): Premila Leiphrakpam and Chandrakanth Are. Pi3k/akt/mtor signaling pathway as a target for colorectal cancer treatment. International Journal of Molecular Sciences, 25:3178, Mar 2024. URL: https://doi.org/10.3390/ijms25063178, doi:10.3390/ijms25063178. This article has 179 citations.
(chu2026structuralandmechanistic pages 3-4): Nam Chu, Nhat Le, Ouada Nebie, and Sammi Yang. Structural and mechanistic basis of mtorc2 activation of protein kinase akt/pkb. Biochemical Journal, 483:375-389, Mar 2026. URL: https://doi.org/10.1042/bcj20253108, doi:10.1042/bcj20253108. This article has 1 citations and is from a domain leading peer-reviewed journal.
(chu2026structuralandmechanistic pages 1-2): Nam Chu, Nhat Le, Ouada Nebie, and Sammi Yang. Structural and mechanistic basis of mtorc2 activation of protein kinase akt/pkb. Biochemical Journal, 483:375-389, Mar 2026. URL: https://doi.org/10.1042/bcj20253108, doi:10.1042/bcj20253108. This article has 1 citations and is from a domain leading peer-reviewed journal.
(modi2023theroleof pages 2-3): Akshat D. Modi, Aahmad Mahoon, and Dharmeshkumar M Modi. The role of akt signalling pathway in neurological and cardiovascular pathologies. European Journal of Biology, 82:95-108, Jun 2023. URL: https://doi.org/10.26650/eurjbiol.2023.1240220, doi:10.26650/eurjbiol.2023.1240220. This article has 3 citations.
(caturano2024insulin–heartaxisbridging pages 2-3): Alfredo Caturano, Raffaele Galiero, Erica Vetrano, Celestino Sardu, Luca Rinaldi, Vincenzo Russo, Marcellino Monda, Raffaele Marfella, and Ferdinando Carlo Sasso. Insulin–heart axis: bridging physiology to insulin resistance. International Journal of Molecular Sciences, 25:8369, Jul 2024. URL: https://doi.org/10.3390/ijms25158369, doi:10.3390/ijms25158369. This article has 44 citations.
(beker2026bmal1pi3kaktcrosstalkin pages 5-7): Mustafa C. Beker, Dirk M. Hermann, and Ertugrul Kilic. Bmal1-pi3k/akt crosstalk in ischemic injury and vascular repair: a circadian framework for neurovascular resilience. Exploration of Neuroscience, Mar 2026. URL: https://doi.org/10.37349/en.2026.1006127, doi:10.37349/en.2026.1006127. This article has 0 citations.
(palma2023nuak1coordinatesgrowth pages 2-4): Mario Palma, Elizabeth Riffo, Alejandro Farias, Viviana Coliboro-Dannich, Luis Espinoza-Francine, Emilia Escalona, Roberto Amigo, José L. Gutiérrez, Roxana Pincheira, and Ariel F. Castro. Nuak1 coordinates growth factor-dependent activation of mtorc2 and akt signaling. Cell & Bioscience, Dec 2023. URL: https://doi.org/10.1186/s13578-023-01185-2, doi:10.1186/s13578-023-01185-2. This article has 9 citations and is from a peer-reviewed journal.
(palma2023nuak1coordinatesgrowth pages 4-7): Mario Palma, Elizabeth Riffo, Alejandro Farias, Viviana Coliboro-Dannich, Luis Espinoza-Francine, Emilia Escalona, Roberto Amigo, José L. Gutiérrez, Roxana Pincheira, and Ariel F. Castro. Nuak1 coordinates growth factor-dependent activation of mtorc2 and akt signaling. Cell & Bioscience, Dec 2023. URL: https://doi.org/10.1186/s13578-023-01185-2, doi:10.1186/s13578-023-01185-2. This article has 9 citations and is from a peer-reviewed journal.
(miller2024ptenregulatedpi3kp110and pages 2-3): Karina A. Miller, Seamus Degan, Yanqing Wang, Joseph Cohen, Sheng Yu Ku, David W. Goodrich, and Irwin H. Gelman. Pten-regulated pi3k-p110 and akt isoform plasticity controls metastatic prostate cancer progression. Oncogene, 43:22-34, Oct 2024. URL: https://doi.org/10.1038/s41388-023-02875-4, doi:10.1038/s41388-023-02875-4. This article has 26 citations and is from a domain leading peer-reviewed journal.
(du2024themicrobiotadependenttryptophan pages 1-2): Wei Du, Shanshan Jiang, Shengxiang Yin, Rongjiang Wang, Chunling Zhang, Bin-Cheng Yin, Jialin Li, Li Li, Nan Qi, Ying Zhou, and Bang-Ce Ye. The microbiota-dependent tryptophan metabolite alleviates high-fat diet–induced insulin resistance through the hepatic ahr/tsc2/mtorc1 axis. Proceedings of the National Academy of Sciences of the United States of America, Aug 2024. URL: https://doi.org/10.1073/pnas.2400385121, doi:10.1073/pnas.2400385121. This article has 59 citations and is from a highest quality peer-reviewed journal.
(miller2024ptenregulatedpi3kp110and pages 1-2): Karina A. Miller, Seamus Degan, Yanqing Wang, Joseph Cohen, Sheng Yu Ku, David W. Goodrich, and Irwin H. Gelman. Pten-regulated pi3k-p110 and akt isoform plasticity controls metastatic prostate cancer progression. Oncogene, 43:22-34, Oct 2024. URL: https://doi.org/10.1038/s41388-023-02875-4, doi:10.1038/s41388-023-02875-4. This article has 26 citations and is from a domain leading peer-reviewed journal.
(giaccari2024anupdateon pages 1-2): Carlo Giaccari, Sevastiani Antonouli, George Anifandis, Sandra Cecconi, and Valentina Di Nisio. An update on physiopathological roles of akt in the reprodaktive mammalian ovary. Life, 14:722, Jun 2024. URL: https://doi.org/10.3390/life14060722, doi:10.3390/life14060722. This article has 26 citations.

Citations

chu2026structuralandmechanistic pages 2-3
du2024themicrobiotadependenttryptophan pages 1-2
modi2023theroleof pages 2-3
giaccari2024anupdateon pages 1-2
modi2023theroleof pages 1-2
chu2026structuralandmechanistic pages 3-4
chu2026structuralandmechanistic pages 1-2
https://doi.org/10.1186/s13578-023-01185-2
https://doi.org/10.1038/s41388-023-02875-4
https://doi.org/10.1073/pnas.2400385121
https://doi.org/10.26650/eurjbiol.2023.1240220
https://doi.org/10.3390/ijms25063178
https://doi.org/10.3390/life14060722
https://doi.org/10.3390/ijms25158369
https://doi.org/10.1042/bcj20253108,
https://doi.org/10.26650/eurjbiol.2023.1240220,
https://doi.org/10.3390/ijms25063178,
https://doi.org/10.1186/s13578-023-01185-2,
https://doi.org/10.3390/ijms25158369,
https://doi.org/10.37349/en.2026.1006127,
https://doi.org/10.1038/s41388-023-02875-4,
https://doi.org/10.1073/pnas.2400385121,
https://doi.org/10.3390/life14060722,

📚 Additional Documentation

Notes

(Akt1-notes.md)

Akt1 review notes

Falcon deep research attempt timed out on 2026-05-04 while running
just deep-research-falcon mouse Akt1; no Akt1-deep-research-falcon.md file
was produced. Review decisions used the cached UniProt record, cached
publications, and BioReason research.

Core function judgment: AKT1 is a PH-domain AGC serine/threonine protein kinase
activated downstream of PI3K and growth factor/insulin signaling. UniProt
describes AKT1 as one of three closely related AKT serine/threonine kinases that
regulate metabolism, proliferation, survival, growth, and angiogenesis through
serine/threonine phosphorylation of downstream substrates [UniProt:P31750
"This is mediated through serine and/or threonine phosphorylation"]. The
BioReason report supports the same architecture-based conclusion:
PH-domain membrane recruitment plus an AGC kinase domain explains
ATP-dependent serine/threonine kinase activity
[file:mouse/Akt1/Akt1-bioreason-rl-predictions.md "A cytoplasmic AGC-type
serine/threonine kinase"].

Key local evidence for process calls includes insulin-stimulated GLUT4
translocation PMID:9415393, GSK3/CRMP2 signaling PMID:22057101, direct regulation of mTORC2
[PMID:23684622 "Akt directly regulates mTORC2"; PMID:26235620 "positive
feedback loop between Akt and mTORC2"], and MICU1/mitochondrial calcium control
PMID:30504268.

Curation stance: protein serine/threonine kinase activity and protein
phosphorylation are core. PI3K/AKT, insulin, mTORC1/2, growth factor, survival,
metabolic, migration, and development terms are valid pathway contexts but are
kept as non-core unless the term directly describes AKT1 catalytic activity.
Generic protein binding, broad kinase/transferase labels, and very broad
cellular responses are marked as over-annotated when a more informative term is
already present.

Bioreason Rl Predictions

(Akt1-bioreason-rl-predictions.md)

BioReason Chat Export

Exported on March 22, 2026 at 03:11 AM

Organism: Mus musculus

Sequence:

MNDVAIVKEGWLHKRGEYIKTWRPRYFLLKNDGTFIGYKERPQDVDQRESPLNNFSVAQCQLMKTERPRPNTFIIRCLQWTTVIERTFHVETPEEREEWATAIQTVADGLKRQEEETMDFRSGSPSDNSGAEEMEVSLAKPKHRVTMNEFEYLKLLGKGTFGKVILVKEKATGRYYAMKILKKEVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHLSRERVFSEDRARFYGAEIVSALDYLHSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGIKDGATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPRTLGPEAKSLLSGLLKKDPTQRLGGGSEDAKEIMQHRFFANIVWQDVYEKKLSPPFKPQVTSETDTRYFDEEFTAQMITITPPDQDDSMECVDSERRPHFPQFSYSASGTA

Thinking Trace

I begin with the InterPro architecture. The N-terminus (residues 1–123) carries IPR011993 (PH-like domain superfamily), within which three pleckstrin-homology annotations converge: IPR039026 (Protein Kinase B, pleckstrin homology domain, residues 4–111), IPR001849 (Pleckstrin homology domain, residues 5–110), and the AKT/kinase B PH signature IPR034676 (Protein kinase B alpha, catalytic domain, residues 124–479). This tandem clearly establishes a canonical PH module that binds phosphoinositide headgroups and thereby recruits the kinase to membrane-proximal signaling sites. Immediately downstream lies the bilobal catalytic core: IPR034676 overlaps and transitions into the kinase region marked by IPR011009 (Protein kinase-like domain superfamily, residues 145–459) and IPR000719 (Protein kinase domain, residues 150–408). The active chemistry is specified by IPR017441 (Protein kinase, ATP binding site, residues 156–189) and IPR008271 (Serine/threonine-protein kinase, active site, residues 270–282), which together define an ATP-dependent serine/threonine phosphotransferase mechanism. The C-terminus is characteristic of AGC kinases: IPR000961 (AGC-kinase, C-terminal, residues 409–480) and IPR017892 (Protein kinase, C-terminal, residues 429–474) encode the regulatory tail that stabilizes the active conformation and integrates activation-loop and hydrophobic motif phosphorylation.

This ordered layout—membrane-targeting PH domain followed by an AGC-type catalytic core and regulatory tail—causes ATP-dependent serine/threonine kinase activity. The PH domain dictates lipid-dependent localization and substrate selection, while the kinase core and AGC tail execute phosphorylation of protein substrates; together these features support GO:0004674 protein serine/threonine kinase activity and the broader GO:0004672 protein kinase activity. The presence of a high-affinity ATP-binding pocket (residues 156–189) and an AGC activation segment (residues 270–282) ensures robust catalytic function.

From this molecular function, the biological process follows. PH-directed recruitment to phosphoinositide-enriched membranes positions the enzyme downstream of PI3K signaling. There, it phosphorylates targets that regulate metabolism, growth, and survival. This places the protein squarely in phosphatidylinositol-mediated signaling and explains its role in broader intracellular signaling cascades. Thus, the kinase architecture and membrane targeting logically drive GO:0006468 protein phosphorylation and implicate processes such as PI3K signaling and its downstream pathways.

The cellular component is inferred from the soluble kinase fold and membrane-targeting PH domain. The absence of transmembrane segments and the soluble AGC architecture indicate a cytosolic enzyme that transiently associates with membranes. Therefore, a cytoplasmic localization is expected, aligning with GO:0005737 cytoplasm and the observed soluble nature of the architecture.

Mechanistically, the PH module first concentrates the kinase at PI(3,4,5)P3/PI(3,4)P2-rich membrane microdomains. There, activation-loop and hydrophobic-motif phosphorylation switch the AGC tail into an active state, enabling phosphorylation of cytosolic and peripheral-membrane substrates that govern metabolism and survival. Likely interaction partners follow from this model: upstream activators and adaptors that dock via PH or scaffolds; 14-3-3 proteins that stabilize phosphorylated states; and membrane-proximal substrates that relay PI3K signals. Together these interactions coordinate cytoplasmic signaling assemblies that couple lipid cues to phosphorylation cascades.

Functional Summary

A cytoplasmic AGC-type serine/threonine kinase that uses an N‑terminal pleckstrin‑homology module to dock onto phosphoinositide-enriched membranes and become activated. Once recruited and switched into its active conformation through its regulatory C‑terminal tail, it phosphorylates downstream targets to propagate phosphatidylinositol-driven signaling, thereby coordinating intracellular signaling, cell growth and survival programs from a soluble cytoplasmic hub.

UniProt Summary

May play an important role in cellular processes involving the cytoplasmic action of the second messenger ins phosphatidylinositol 3,4,5-trisphosphate.

InterPro Domains

PH-like domain superfamily (IPR011993, homologous_superfamily) — residues 1-123
Protein Kinase B, pleckstrin homology domain (IPR039026, domain) — residues 4-111
Pleckstrin homology domain (IPR001849, domain) — residues 5-110
Protein kinase B alpha, catalytic domain (IPR034676, domain) — residues 124-479
Protein kinase-like domain superfamily (IPR011009, homologous_superfamily) — residues 145-459
Protein kinase domain (IPR000719, domain) — residues 150-408
Protein kinase, ATP binding site (IPR017441, binding_site) — residues 156-189
Serine/threonine-protein kinase, active site (IPR008271, active_site) — residues 270-282
AGC-kinase, C-terminal (IPR000961, domain) — residues 409-480
Protein kinase, C-terminal (IPR017892, domain) — residues 429-474

GO Terms

Molecular Function: molecular_function (GO:0003674), binding (GO:0005488), catalytic activity (GO:0003824), transferase activity (GO:0016740), catalytic activity, acting on a protein (GO:0140096), protein binding (GO:0005515), transferase activity, transferring phosphorus-containing groups (GO:0016772), protein kinase activity (GO:0004672), enzyme binding (GO:0019899), protein serine/threonine kinase activity (GO:0004674), kinase activity (GO:0016301), phosphotransferase activity, alcohol group as acceptor (GO:0016773), kinase binding (GO:0019900), protein kinase binding (GO:0019901)

Biological Process: biological_process (GO:0008150), signaling (GO:0023052), biological regulation (GO:0065007), response to stimulus (GO:0050896), biological process involved in interspecies interaction between organisms (GO:0044419), reproductive process (GO:0022414), negative regulation of biological process (GO:0048519), positive regulation of biological process (GO:0048518), regulation of biological process (GO:0050789), reproduction (GO:0000003), multicellular organismal process (GO:0032501), developmental process (GO:0032502), cellular process (GO:0009987), metabolic process (GO:0008152), homeostatic process (GO:0042592), sexual reproduction (GO:0019953), anatomical structure development (GO:0048856), negative regulation of signaling (GO:0023057), positive regulation of multicellular organismal process (GO:0051240), cellular component organization or biogenesis (GO:0071840), regulation of multicellular organismal process (GO:0051239), ensheathment of neurons (GO:0007272), developmental process involved in reproduction (GO:0003006), positive regulation of transport (GO:0051050), negative regulation of metabolic process (GO:0009892), regulation of biological quality (GO:0065008), cellular process involved in reproduction in multicellular organism (GO:0022412), multicellular organismal response to stress (GO:0033555), regulation of cellular process (GO:0050794), multi-organism reproductive process (GO:0044703), regulation of response to stimulus (GO:0048583), cellular response to stimulus (GO:0051716), negative regulation of cellular process (GO:0048523), regulation of locomotion (GO:0040012), response to abiotic stimulus (GO:0009628), cellular developmental process (GO:0048869), regulation of metabolic process (GO:0019222), catabolic process (GO:0009056), ossification (GO:0001503), regulation of molecular function (GO:0065009), cell communication (GO:0007154), positive regulation of cellular process (GO:0048522), response to external stimulus (GO:0009605), response to chemical (GO:0042221), execution phase of apoptosis (GO:0097194), nitrogen compound metabolic process (GO:0006807), multicellular organism reproduction (GO:0032504), positive regulation of growth (GO:0045927), regulation of developmental process (GO:0050793), multi-multicellular organism process (GO:0044706), response to biotic stimulus (GO:0009607), response to endogenous stimulus (GO:0009719), cell death (GO:0008219), positive regulation of locomotion (GO:0040017), regulation of signaling (GO:0023051), response to other organism (GO:0051707), signal transduction (GO:0007165), multicellular organism development (GO:0007275), regulation of localization (GO:0032879), organic substance metabolic process (GO:0071704), chemical homeostasis (GO:0048878), cellular metabolic process (GO:0044237), small molecule metabolic process (GO:0044281), positive regulation of metabolic process (GO:0009893), response to stress (GO:0006950), positive regulation of developmental process (GO:0051094), multicellular organismal reproductive process (GO:0048609), negative regulation of response to stimulus (GO:0048585), regulation of growth (GO:0040008), primary metabolic process (GO:0044238), behavior (GO:0007610), negative regulation of cellular component organization (GO:0051129), response to external biotic stimulus (GO:0043207), regulation of cell motility (GO:2000145), animal organ development (GO:0048513), regulation of signal transduction (GO:0009966), regulation of macromolecule metabolic process (GO:0060255), carbohydrate metabolic process (GO:0005975), maternal process involved in female pregnancy (GO:0060135), response to hormone (GO:0009725), negative regulation of macromolecule metabolic process (GO:0010605), embryo development (GO:0009790), cellular macromolecule metabolic process (GO:0044260), positive regulation of nitrogen compound metabolic process (GO:0051173), germ cell development (GO:0007281), regulation of catalytic activity (GO:0050790), negative regulation of nitrogen compound metabolic process (GO:0051172), positive regulation of protein localization (GO:1903829), axon ensheathment (GO:0008366), positive regulation of macromolecule metabolic process (GO:0010604), blood vessel development (GO:0001568), negative regulation of molecular function (GO:0044092), regulation of cellular localization (GO:0060341), protein metabolic process (GO:0019538), carbohydrate homeostasis (GO:0033500), monosaccharide metabolic process (GO:0005996), response to oxygen-containing compound (GO:1901700), behavioral response to pain (GO:0048266), macromolecule metabolic process (GO:0043170), cellular response to biotic stimulus (GO:0071216), positive regulation of cell motility (GO:2000147), positive regulation of biosynthetic process (GO:0009891), muscle structure development (GO:0061061), regulation of multicellular organismal development (GO:2000026), regulation of cell death (GO:0010941), response to nitrogen compound (GO:1901698), positive regulation of cellular metabolic process (GO:0031325), response to pain (GO:0048265), regulation of cellular metabolic process (GO:0031323), regulation of primary metabolic process (GO:0080090), generation of precursor metabolites and energy (GO:0006091), response to temperature stimulus (GO:0009266), negative regulation of signal transduction (GO:0009968), programmed cell death (GO:0012501), negative regulation of cell death (GO:0060548), cell development (GO:0048468), cell differentiation (GO:0030154), cellular catabolic process (GO:0044248), system development (GO:0048731), response to oxygen levels (GO:0070482), response to growth factor (GO:0070848), cellular response to endogenous stimulus (GO:0071495), regulation of organ growth (GO:0046620), regulation of synapse structure or activity (GO:0050803), phosphorus metabolic process (GO:0006793), response to heat (GO:0009408), regulation of catabolic process (GO:0009894), regulation of myelination (GO:0031641), positive regulation of monoatomic ion transport (GO:0043270), regulation of nitrogen compound metabolic process (GO:0051171), maternal placenta development (GO:0001893), cellular component organization (GO:0016043), cell surface receptor signaling pathway (GO:0007166), regulation of cellular component organization (GO:0051128), organic substance catabolic process (GO:1901575), regulation of developmental growth (GO:0048638), cellular carbohydrate metabolic process (GO:0044262), positive regulation of developmental growth (GO:0048639), gamete generation (GO:0007276), negative regulation of cell communication (GO:0010648), regulation of transport (GO:0051049), organonitrogen compound metabolic process (GO:1901564), response to food (GO:0032094), intracellular signal transduction (GO:0035556), osteoblast differentiation (GO:0001649), cell differentiation involved in embryonic placenta development (GO:0060706), defense response (GO:0006952), positive regulation of organ growth (GO:0046622), response to organic substance (GO:0010033), response to extracellular stimulus (GO:0009991), female pregnancy (GO:0007565), tissue development (GO:0009888), regulation of cell communication (GO:0010646), cellular response to chemical stimulus (GO:0070887), response to bacterium (GO:0009617), regulation of biosynthetic process (GO:0009889), labyrinthine layer development (GO:0060711), positive regulation of catabolic process (GO:0009896), response to alcohol (GO:0097305), response to ketone (GO:1901654), regulation of synapse organization (GO:0050807), regulation of macromolecule biosynthetic process (GO:0010556), cellular response to oxygen levels (GO:0071453), regulation of protein metabolic process (GO:0051246), vasculature development (GO:0001944), peripheral nervous system axon ensheathment (GO:0032292), lipopolysaccharide-mediated signaling pathway (GO:0031663), glial cell differentiation (GO:0010001), positive regulation of protein localization to cell surface (GO:2000010), regulation of gene expression (GO:0010468), macromolecule modification (GO:0043412), muscle cell differentiation (GO:0042692), circulatory system development (GO:0072359), response to decreased oxygen levels (GO:0036293), polysaccharide metabolic process (GO:0005976), positive regulation of cell migration (GO:0030335), energy derivation by oxidation of organic compounds (GO:0015980), cellular response to oxygen-containing compound (GO:1901701), negative regulation of gene expression (GO:0010629), cellular response to organonitrogen compound (GO:0071417), protein kinase B signaling (GO:0043491), hexose metabolic process (GO:0019318), response to lipopolysaccharide (GO:0032496), response to epidermal growth factor (GO:0070849), enzyme-linked receptor protein signaling pathway (GO:0007167), organonitrogen compound catabolic process (GO:1901565), proteolysis (GO:0006508), regulation of cell projection organization (GO:0031344), cellular response to organic substance (GO:0071310), negative regulation of protein metabolic process (GO:0051248), cellular response to nitrogen compound (GO:1901699), negative regulation of apoptotic signaling pathway (GO:2001234), regulation of protein localization (GO:0032880), placenta development (GO:0001890), protein modification process (GO:0036211), response to peptide hormone (GO:0043434), positive regulation of macromolecule biosynthetic process (GO:0010557), neurogenesis (GO:0022008), negative regulation of organelle organization (GO:0010639), positive regulation of RNA metabolic process (GO:0051254), cellular response to hormone stimulus (GO:0032870), inflammatory response (GO:0006954), cellular macromolecule catabolic process (GO:0044265), response to lipid (GO:0033993), glucose homeostasis (GO:0042593), regulation of cellular biosynthetic process (GO:0031326), apoptotic process (GO:0006915), regulation of nucleobase-containing compound metabolic process (GO:0019219), regulation of organelle organization (GO:0033043), positive regulation of protein catabolic process (GO:0045732), cellular response to growth factor stimulus (GO:0071363), positive regulation of cellular biosynthetic process (GO:0031328), embryo development ending in birth or egg hatching (GO:0009792), response to peptide (GO:1901652), positive regulation of sodium ion transport (GO:0010765), negative regulation of programmed cell death (GO:0043069), regulation of programmed cell death (GO:0043067), protein catabolic process (GO:0030163), response to prostaglandin (GO:0034694), response to molecule of bacterial origin (GO:0002237), regulation of cell migration (GO:0030334), macromolecule catabolic process (GO:0009057), embryonic organ development (GO:0048568), nervous system development (GO:0007399), response to nutrient levels (GO:0031667), placenta blood vessel development (GO:0060674), labyrinthine layer blood vessel development (GO:0060716), regulation of RNA metabolic process (GO:0051252), gene expression (GO:0010467), membrane organization (GO:0061024), negative regulation of catalytic activity (GO:0043086), response to cytokine (GO:0034097), cellular response to molecule of bacterial origin (GO:0071219), regulation of protein catabolic process (GO:0042176), myelination (GO:0042552), endomembrane system organization (GO:0010256), regulation of hydrolase activity (GO:0051336), glial cell development (GO:0021782), positive regulation of gene expression (GO:0010628), phosphate-containing compound metabolic process (GO:0006796), negative regulation of intracellular signal transduction (GO:1902532), regulation of nervous system development (GO:0051960), regulation of apoptotic signaling pathway (GO:2001233), cellular polysaccharide metabolic process (GO:0044264), positive regulation of nucleobase-containing compound metabolic process (GO:0045935), response to organonitrogen compound (GO:0010243), peripheral nervous system development (GO:0007422), positive regulation of protein metabolic process (GO:0051247), positive regulation of cellular catabolic process (GO:0031331), regulation of monoatomic ion transport (GO:0043269), regulation of cellular catabolic process (GO:0031329), organelle organization (GO:0006996), regulation of intracellular signal transduction (GO:1902531), glucose metabolic process (GO:0006006), mitochondrion organization (GO:0007005), regulation of apoptotic process (GO:0042981), embryonic placenta development (GO:0001892), regulation of RNA biosynthetic process (GO:2001141), peptidyl-amino acid modification (GO:0018193), cellular response to cytokine stimulus (GO:0071345), phosphorylation (GO:0016310), positive regulation of RNA biosynthetic process (GO:1902680), cellular response to alcohol (GO:0097306), positive regulation of fibroblast migration (GO:0010763), cellular response to ketone (GO:1901655), regulation of intrinsic apoptotic signaling pathway (GO:2001242), regulation of plasma membrane bounded cell projection organization (GO:0120035), response to prostaglandin E (GO:0034695), energy reserve metabolic process (GO:0006112), response to insulin (GO:0032868), protein modification by small protein conjugation or removal (GO:0070647), modification-dependent macromolecule catabolic process (GO:0043632), cellular response to prostaglandin stimulus (GO:0071379), gliogenesis (GO:0042063), cellular response to peptide (GO:1901653), positive regulation of proteasomal protein catabolic process (GO:1901800), response to tumor necrosis factor (GO:0034612), regulation of fibroblast migration (GO:0010762), negative regulation of proteolysis (GO:0045861), negative regulation of release of cytochrome c from mitochondria (GO:0090201), regulation of release of cytochrome c from mitochondria (GO:0090199), negative regulation of mitochondrion organization (GO:0010823), cellular response to lipopolysaccharide (GO:0071222), negative regulation of hydrolase activity (GO:0051346), regulation of proteolysis (GO:0030162), regulation of mitochondrion organization (GO:0010821), regulation of peptidase activity (GO:0052547), apoptotic mitochondrial changes (GO:0008637), negative regulation of intrinsic apoptotic signaling pathway (GO:2001243), regulation of metal ion transport (GO:0010959), cytoskeleton organization (GO:0007010), transmembrane receptor protein tyrosine kinase signaling pathway (GO:0007169), Schwann cell differentiation (GO:0014037), regulation of ubiquitin-dependent protein catabolic process (GO:2000058), proteasomal protein catabolic process (GO:0010498), cellular response to epidermal growth factor stimulus (GO:0071364), chordate embryonic development (GO:0043009), regulation of postsynapse organization (GO:0099175), glucan metabolic process (GO:0044042), cellular response to peptide hormone stimulus (GO:0071375), negative regulation of apoptotic process (GO:0043066), myelination in peripheral nervous system (GO:0022011), protein phosphorylation (GO:0006468), Schwann cell development (GO:0014044), regulation of DNA-templated transcription (GO:0006355), proteolysis involved in protein catabolic process (GO:0051603), cellular glucan metabolic process (GO:0006073), cellular response to lipid (GO:0071396), cellular response to decreased oxygen levels (GO:0036294), positive regulation of proteolysis (GO:0045862), striated muscle cell differentiation (GO:0051146), positive regulation of ubiquitin-dependent protein catabolic process (GO:2000060), plasma membrane organization (GO:0007009), regulation of proteasomal protein catabolic process (GO:0061136), regulation of protein localization to cell surface (GO:2000008), cellular response to vascular endothelial growth factor stimulus (GO:0035924), in utero embryonic development (GO:0001701), cellular response to insulin stimulus (GO:0032869), regulation of endopeptidase activity (GO:0052548), negative regulation of cysteine-type endopeptidase activity involved in apoptotic process (GO:0043154), positive regulation of nucleic acid-templated transcription (GO:1903508), modification-dependent protein catabolic process (GO:0019941), regulation of neuron projection development (GO:0010975), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of DNA-templated transcription (GO:0045893), cellular response to prostaglandin E stimulus (GO:0071380), regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032434), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), insulin-like growth factor receptor signaling pathway (GO:0048009), regulation of proteolysis involved in protein catabolic process (GO:1903050), negative regulation of peptidase activity (GO:0010466), regulation of nucleic acid-templated transcription (GO:1903506), peptidyl-serine phosphorylation (GO:0018105), protein modification by small protein conjugation (GO:0032446), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), peptidyl-serine modification (GO:0018209), insulin receptor signaling pathway (GO:0008286), glycogen metabolic process (GO:0005977), positive regulation of proteolysis involved in protein catabolic process (GO:1903052), regulation of sodium ion transport (GO:0002028), cellular response to tumor necrosis factor (GO:0071356), ubiquitin-dependent protein catabolic process (GO:0006511), regulation of cysteine-type endopeptidase activity (GO:2000116), protein ubiquitination (GO:0016567), negative regulation of endopeptidase activity (GO:0010951), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of cysteine-type endopeptidase activity (GO:2000117), regulation of cysteine-type endopeptidase activity involved in apoptotic process (GO:0043281)

Cellular Component: cellular_component (GO:0005575), protein-containing complex (GO:0032991), cellular anatomical entity (GO:0110165), microtubule organizing center (GO:0005815), intracellular anatomical structure (GO:0005622), organelle (GO:0043226), cell projection (GO:0042995), membrane (GO:0016020), cell junction (GO:0030054), cytosol (GO:0005829), cytoplasm (GO:0005737), cell periphery (GO:0071944), ciliary basal body (GO:0036064), mitochondrion (GO:0005739), plasma membrane bounded cell projection (GO:0120025), intracellular organelle (GO:0043229), anchoring junction (GO:0070161), synapse (GO:0045202), membrane-bounded organelle (GO:0043227), plasma membrane (GO:0005886), non-membrane-bounded organelle (GO:0043228), intracellular membrane-bounded organelle (GO:0043231), cilium (GO:0005929), cell-cell junction (GO:0005911), intracellular non-membrane-bounded organelle (GO:0043232), glutamatergic synapse (GO:0098978), cytoskeleton (GO:0005856), spindle (GO:0005819), nucleus (GO:0005634), microtubule cytoskeleton (GO:0015630)

Generated by BioReason

Bioreason Rl Review

(Akt1-bioreason-rl-review.md)

BioReason-Pro RL Review: Akt1 (mouse)

Source: Akt1-bioreason-rl-predictions.md

Correctness: 5/5
Completeness: 4/5

Functional Summary Review

The BioReason functional summary is accurate and well-constructed:

A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology module to dock onto phosphoinositide-enriched membranes and become activated. Once recruited and switched into its active conformation through its regulatory C-terminal tail, it phosphorylates downstream targets to propagate phosphatidylinositol-driven signaling, thereby coordinating intracellular signaling, cell growth and survival programs from a soluble cytoplasmic hub.

This correctly identifies all major features: (1) the AGC-type serine/threonine kinase identity, (2) the PH domain-mediated membrane recruitment by PI(3,4,5)P3/PI(3,4)P2, (3) the C-terminal regulatory tail characteristic of AGC kinases, and (4) the downstream roles in growth and survival. The description aligns well with GO:0004674 (protein serine/threonine kinase activity), GO:0005737 (cytoplasm), GO:0006468 (protein phosphorylation), and GO:0035556 (intracellular signal transduction) -- all core curated annotations for Akt1.

The summary accurately places Akt1 downstream of PI3K signaling and describes the PH-domain-driven membrane translocation mechanism, which is the canonical activation mode. The mention of "cell growth and survival programs" is appropriate and well-supported.

The only minor gap is that specific well-established downstream targets and pathways (e.g., mTOR signaling, GSK3 phosphorylation, glucose homeostasis, anti-apoptotic signaling via BAD phosphorylation) are not mentioned, though this is understandable for a domain-architecture-driven summary.

Comparison with interpro2go:

No GO_REF:0000002 annotations exist for mouse Akt1 in the curated review; IEA annotations come from UniRule (GO_REF:0000120) instead. The BioReason predictions include the same core terms (GO:0004674, GO:0004672, GO:0006468, GO:0005737) that UniRule and IBA annotations provide. BioReason adds narrative value by explaining the mechanistic logic connecting the PH domain to membrane recruitment and kinase activation, which goes beyond what interpro2go-style mappings provide. The functional summary is not merely recapitulating automated annotations but synthesizing them into a coherent mechanistic narrative.

Notes on thinking trace

The thinking trace methodically walks through the InterPro domain architecture from N-terminus to C-terminus, correctly interpreting the PH domain, kinase core, and AGC tail. The reasoning from domain architecture to molecular function to biological process to cellular component is logical and well-ordered. The trace appropriately identifies the lipid-binding specificity of the PH domain and the AGC-family activation mechanism.

📄 View Raw YAML

id: P31750
gene_symbol: Akt1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
description: RAC-alpha serine/threonine-protein kinase AKT1, a PH-domain AGC kinase that is recruited
  to phosphoinositide-rich membranes downstream of PI3K and phosphorylates protein substrates controlling
  insulin/growth-factor signaling, metabolism, survival, growth, migration, and mTOR pathway feedback.
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: cytoplasm localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Core AKT1 serine/threonine kinase activity
    action: ACCEPT
    reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation
      of serine/threonine residues on downstream substrates.
    supported_by:
    - reference_id: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md
      supporting_text: A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology
        module to dock onto phosphoinositide-enriched membranes
    - reference_id: file:mouse/Akt1/Akt1-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Akt1 as a PH-domain AGC serine/threonine
        kinase activated downstream of PI3K by membrane recruitment and phosphorylation.
- term:
    id: GO:0035556
    label: intracellular signal transduction
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: intracellular signal transduction pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: negative regulation of apoptotic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: insulin receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than
      the gene product core molecular activity.
- term:
    id: GO:0043536
    label: positive regulation of blood vessel endothelial cell migration
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: positive regulation of blood vessel endothelial cell migration pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: protein kinase activity is less specific than AKT1 serine/threonine kinase activity
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity
      terms are present and better capture the function.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Core AKT1 serine/threonine kinase activity
    action: ACCEPT
    reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation
      of serine/threonine residues on downstream substrates.
    supported_by:
    - reference_id: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md
      supporting_text: A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology
        module to dock onto phosphoinositide-enriched membranes
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ATP binding supports AKT1 activation or recruitment
    action: KEEP_AS_NON_CORE
    reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory
      to the core serine/threonine kinase activity.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: nucleus pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: cytoplasm localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:0005758
    label: mitochondrial intermembrane space
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: mitochondrial intermembrane space pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  review:
    summary: endoplasmic reticulum pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: plasma membrane localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:1903898
    label: negative regulation of PERK-mediated unfolded protein response
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: negative regulation of PERK-mediated unfolded protein response pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12791994
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16051150
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18566586
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19122674
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19698782
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21339740
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22309289
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24955524
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0001649
    label: osteoblast differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: osteoblast differentiation pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0001938
    label: positive regulation of endothelial cell proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of endothelial cell proliferation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0002042
    label: cell migration involved in sprouting angiogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cell migration involved in sprouting angiogenesis pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0002430
    label: complement receptor mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: complement receptor mediated signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0003376
    label: sphingosine-1-phosphate receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: sphingosine-1-phosphate receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0004712
    label: protein serine/threonine/tyrosine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: protein serine/threonine/tyrosine kinase activity is less specific than AKT1 serine/threonine
      kinase activity
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity
      terms are present and better capture the function.
- term:
    id: GO:0005516
    label: calmodulin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: calmodulin binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005547
    label: phosphatidylinositol-3,4,5-trisphosphate binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: phosphatidylinositol-3,4,5-trisphosphate binding supports AKT1 activation or recruitment
    action: KEEP_AS_NON_CORE
    reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory
      to the core serine/threonine kinase activity.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: nucleoplasm pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:0005979
    label: regulation of glycogen biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: regulation of glycogen biosynthetic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: epidermal growth factor receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: insulin receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than
      the gene product core molecular activity.
- term:
    id: GO:0010507
    label: negative regulation of autophagy
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of autophagy pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0010595
    label: positive regulation of endothelial cell migration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of endothelial cell migration pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of gene expression pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0010748
    label: negative regulation of long-chain fatty acid import across plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of long-chain fatty acid import across plasma membrane pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0010907
    label: positive regulation of glucose metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of glucose metabolic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Generic membrane annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful functional information for AKT1 relative to the more specific
      kinase, localization, and pathway annotations.
- term:
    id: GO:0016301
    label: kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: kinase activity is less specific than AKT1 serine/threonine kinase activity
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity
      terms are present and better capture the function.
- term:
    id: GO:0019900
    label: kinase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Generic kinase binding annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful functional information for AKT1 relative to the more specific
      kinase, localization, and pathway annotations.
- term:
    id: GO:0030235
    label: nitric-oxide synthase regulator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: nitric-oxide synthase regulator activity pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0030307
    label: positive regulation of cell growth
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of cell growth pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0030334
    label: regulation of cell migration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: regulation of cell migration pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0030335
    label: positive regulation of cell migration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of cell migration pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0031397
    label: negative regulation of protein ubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of protein ubiquitination pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0031982
    label: vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: vesicle pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0031999
    label: negative regulation of fatty acid beta-oxidation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of fatty acid beta-oxidation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0032436
    label: positive regulation of proteasomal ubiquitin-dependent protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of proteasomal ubiquitin-dependent protein catabolic process pathway
      context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0032869
    label: cellular response to insulin stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to insulin stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Generic protein-containing complex annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful functional information for AKT1 relative to the more specific
      kinase, localization, and pathway annotations.
- term:
    id: GO:0034405
    label: response to fluid shear stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to fluid shear stress pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0035655
    label: interleukin-18-mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: interleukin-18-mediated signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0042307
    label: positive regulation of protein import into nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of protein import into nucleus pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Generic identical protein binding annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful functional information for AKT1 relative to the more specific
      kinase, localization, and pathway annotations.
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Generic protein homodimerization activity annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful functional information for AKT1 relative to the more specific
      kinase, localization, and pathway annotations.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of apoptotic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0043325
    label: phosphatidylinositol-3,4-bisphosphate binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: phosphatidylinositol-3,4-bisphosphate binding supports AKT1 activation or recruitment
    action: KEEP_AS_NON_CORE
    reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory
      to the core serine/threonine kinase activity.
- term:
    id: GO:0043491
    label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: phosphatidylinositol 3-kinase/protein kinase B signal transduction pathway context
    action: KEEP_AS_NON_CORE
    reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than
      the gene product core molecular activity.
- term:
    id: GO:0043536
    label: positive regulation of blood vessel endothelial cell migration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of blood vessel endothelial cell migration pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0045429
    label: positive regulation of nitric oxide biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of nitric oxide biosynthetic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0045600
    label: positive regulation of fat cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of fat cell differentiation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0045725
    label: positive regulation of glycogen biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of glycogen biosynthetic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0045861
    label: negative regulation of proteolysis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of proteolysis pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of transcription by RNA polymerase II pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0046326
    label: positive regulation of D-glucose import across plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of D-glucose import across plasma membrane pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0046889
    label: positive regulation of lipid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of lipid biosynthetic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0048009
    label: insulin-like growth factor receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: insulin-like growth factor receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0048661
    label: positive regulation of smooth muscle cell proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of smooth muscle cell proliferation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
      pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0070141
    label: response to UV-A
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to UV-A pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0070585
    label: protein localization to mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: protein localization to mitochondrion pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0070848
    label: response to growth factor
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to growth factor pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0071364
    label: cellular response to epidermal growth factor stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to epidermal growth factor stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0071889
    label: 14-3-3 protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 14-3-3 protein binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0072656
    label: maintenance of protein location in mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: maintenance of protein location in mitochondrion pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0099104
    label: potassium channel activator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: potassium channel activator activity pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Direct AKT1 phosphorylation activity
    action: ACCEPT
    reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
- term:
    id: GO:0110002
    label: regulation of tRNA methylation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: regulation of tRNA methylation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0140052
    label: cellular response to oxidised low-density lipoprotein particle stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to oxidised low-density lipoprotein particle stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0150033
    label: negative regulation of protein localization to lysosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of protein localization to lysosome pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0160049
    label: negative regulation of cGAS/STING signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of cGAS/STING signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1900182
    label: positive regulation of protein localization to nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of protein localization to nucleus pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1902018
    label: negative regulation of cilium assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of cilium assembly pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1903038
    label: negative regulation of leukocyte cell-cell adhesion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of leukocyte cell-cell adhesion pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1903078
    label: positive regulation of protein localization to plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of protein localization to plasma membrane pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1903384
    label: negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway
      pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1904263
    label: positive regulation of TORC1 signaling
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of TORC1 signaling pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1904841
    label: TORC2 complex binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: TORC2 complex binding supports AKT1 activation or recruitment
    action: KEEP_AS_NON_CORE
    reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory
      to the core serine/threonine kinase activity.
- term:
    id: GO:1905552
    label: positive regulation of protein localization to endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of protein localization to endoplasmic reticulum pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1905786
    label: positive regulation of anaphase-promoting complex-dependent catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of anaphase-promoting complex-dependent catabolic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1990090
    label: cellular response to nerve growth factor stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to nerve growth factor stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:2000402
    label: negative regulation of lymphocyte migration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of lymphocyte migration pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0042307
    label: positive regulation of protein import into nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of protein import into nucleus pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: plasma membrane localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- 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: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
      pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Direct AKT1 phosphorylation activity
    action: ACCEPT
    reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:10454575
  review:
    summary: Core AKT1 serine/threonine kinase activity
    action: ACCEPT
    reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation
      of serine/threonine residues on downstream substrates.
    supported_by:
    - reference_id: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md
      supporting_text: A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology
        module to dock onto phosphoinositide-enriched membranes
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-1445150
  review:
    summary: Core AKT1 serine/threonine kinase activity
    action: ACCEPT
    reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation
      of serine/threonine residues on downstream substrates.
    supported_by:
    - reference_id: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md
      supporting_text: A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology
        module to dock onto phosphoinositide-enriched membranes
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9857656
  review:
    summary: Core AKT1 serine/threonine kinase activity
    action: ACCEPT
    reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation
      of serine/threonine residues on downstream substrates.
    supported_by:
    - reference_id: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md
      supporting_text: A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology
        module to dock onto phosphoinositide-enriched membranes
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9857664
  review:
    summary: Core AKT1 serine/threonine kinase activity
    action: ACCEPT
    reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation
      of serine/threonine residues on downstream substrates.
    supported_by:
    - reference_id: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md
      supporting_text: A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology
        module to dock onto phosphoinositide-enriched membranes
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: nucleus pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Direct AKT1 phosphorylation activity
    action: ACCEPT
    reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Direct AKT1 phosphorylation activity
    action: ACCEPT
    reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
- term:
    id: GO:0016310
    label: phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: phosphorylation pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0018105
    label: peptidyl-serine phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Direct AKT1 phosphorylation activity
    action: ACCEPT
    reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
- term:
    id: GO:0018107
    label: peptidyl-threonine phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Direct AKT1 phosphorylation activity
    action: ACCEPT
    reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
- term:
    id: GO:0032079
    label: positive regulation of endodeoxyribonuclease activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of endodeoxyribonuclease activity pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0033011
    label: perinuclear theca
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: perinuclear theca pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0033138
    label: positive regulation of peptidyl-serine phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of peptidyl-serine phosphorylation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0046777
    label: protein autophosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Direct AKT1 phosphorylation activity
    action: ACCEPT
    reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
- term:
    id: GO:0097228
    label: sperm principal piece
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: sperm principal piece pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0097229
    label: sperm end piece
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: sperm end piece pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0120238
    label: sperm glycocalyx
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: sperm glycocalyx pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0001649
    label: osteoblast differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: osteoblast differentiation pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0001938
    label: positive regulation of endothelial cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of endothelial cell proliferation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0002042
    label: cell migration involved in sprouting angiogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cell migration involved in sprouting angiogenesis pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0002181
    label: cytoplasmic translation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cytoplasmic translation pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0002430
    label: complement receptor mediated signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: complement receptor mediated signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0003376
    label: sphingosine-1-phosphate receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: sphingosine-1-phosphate receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: protein kinase activity is less specific than AKT1 serine/threonine kinase activity
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity
      terms are present and better capture the function.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein kinase activity is less specific than AKT1 serine/threonine kinase activity
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity
      terms are present and better capture the function.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Core AKT1 serine/threonine kinase activity
    action: ACCEPT
    reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation
      of serine/threonine residues on downstream substrates.
    supported_by:
    - reference_id: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md
      supporting_text: A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology
        module to dock onto phosphoinositide-enriched membranes
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Core AKT1 serine/threonine kinase activity
    action: ACCEPT
    reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation
      of serine/threonine residues on downstream substrates.
    supported_by:
    - reference_id: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md
      supporting_text: A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology
        module to dock onto phosphoinositide-enriched membranes
- term:
    id: GO:0004712
    label: protein serine/threonine/tyrosine kinase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein serine/threonine/tyrosine kinase activity is less specific than AKT1 serine/threonine
      kinase activity
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity
      terms are present and better capture the function.
- term:
    id: GO:0005080
    label: protein kinase C binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: protein kinase C binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005516
    label: calmodulin binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: calmodulin binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: ATP binding supports AKT1 activation or recruitment
    action: KEEP_AS_NON_CORE
    reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory
      to the core serine/threonine kinase activity.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: ATP binding supports AKT1 activation or recruitment
    action: KEEP_AS_NON_CORE
    reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory
      to the core serine/threonine kinase activity.
- term:
    id: GO:0005547
    label: phosphatidylinositol-3,4,5-trisphosphate binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: phosphatidylinositol-3,4,5-trisphosphate binding supports AKT1 activation or recruitment
    action: KEEP_AS_NON_CORE
    reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory
      to the core serine/threonine kinase activity.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: nucleus pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: nucleoplasm pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cytoplasm localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mitochondrion pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:0005929
    label: cilium
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cilium pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005978
    label: glycogen biosynthetic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: glycogen biosynthetic process pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005979
    label: regulation of glycogen biosynthetic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: regulation of glycogen biosynthetic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0006094
    label: gluconeogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: gluconeogenesis pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0006412
    label: translation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: translation pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0006413
    label: translational initiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: translational initiation pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0006511
    label: ubiquitin-dependent protein catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: ubiquitin-dependent protein catabolic process pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0006606
    label: protein import into nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein import into nucleus pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0006607
    label: NLS-bearing protein import into nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: NLS-bearing protein import into nucleus pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0006888
    label: endoplasmic reticulum to Golgi vesicle-mediated transport
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: endoplasmic reticulum to Golgi vesicle-mediated transport pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0006893
    label: Golgi to plasma membrane transport
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Golgi to plasma membrane transport pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: DNA damage response pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: epidermal growth factor receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: insulin receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than
      the gene product core molecular activity.
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: insulin receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than
      the gene product core molecular activity.
- term:
    id: GO:0009267
    label: cellular response to starvation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cellular response to starvation pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0010507
    label: negative regulation of autophagy
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of autophagy pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0010595
    label: positive regulation of endothelial cell migration
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of endothelial cell migration pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of gene expression pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0010748
    label: negative regulation of long-chain fatty acid import across plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of long-chain fatty acid import across plasma membrane pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0010907
    label: positive regulation of glucose metabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of glucose metabolic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0010918
    label: positive regulation of mitochondrial membrane potential
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of mitochondrial membrane potential pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0014850
    label: response to muscle activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: response to muscle activity pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0015630
    label: microtubule cytoskeleton
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: microtubule cytoskeleton pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic membrane annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful functional information for AKT1 relative to the more specific
      kinase, localization, and pathway annotations.
- term:
    id: GO:0016477
    label: cell migration
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cell migration pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Generic enzyme binding annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful functional information for AKT1 relative to the more specific
      kinase, localization, and pathway annotations.
- term:
    id: GO:0019900
    label: kinase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic kinase binding annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful functional information for AKT1 relative to the more specific
      kinase, localization, and pathway annotations.
- term:
    id: GO:0019901
    label: protein kinase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Generic protein kinase binding annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful functional information for AKT1 relative to the more specific
      kinase, localization, and pathway annotations.
- term:
    id: GO:0021510
    label: spinal cord development
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: spinal cord development pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0030235
    label: nitric-oxide synthase regulator activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: nitric-oxide synthase regulator activity pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0030291
    label: protein serine/threonine kinase inhibitor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: protein serine/threonine kinase inhibitor activity pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0030307
    label: positive regulation of cell growth
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of cell growth pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0030307
    label: positive regulation of cell growth
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of cell growth pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0030334
    label: regulation of cell migration
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: regulation of cell migration pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0030334
    label: regulation of cell migration
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: regulation of cell migration pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0030335
    label: positive regulation of cell migration
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of cell migration pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0030336
    label: negative regulation of cell migration
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of cell migration pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: dendrite pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0031145
    label: anaphase-promoting complex-dependent catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: anaphase-promoting complex-dependent catabolic process pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0031146
    label: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0031397
    label: negative regulation of protein ubiquitination
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of protein ubiquitination pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0031667
    label: response to nutrient levels
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: response to nutrient levels pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0031669
    label: cellular response to nutrient levels
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cellular response to nutrient levels pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0031982
    label: vesicle
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: vesicle pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0031999
    label: negative regulation of fatty acid beta-oxidation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of fatty acid beta-oxidation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0032436
    label: positive regulation of proteasomal ubiquitin-dependent protein catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of proteasomal ubiquitin-dependent protein catabolic process pathway
      context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0032794
    label: GTPase activating protein binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: GTPase activating protein binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0032869
    label: cellular response to insulin stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: cellular response to insulin stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0032869
    label: cellular response to insulin stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cellular response to insulin stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0032929
    label: negative regulation of superoxide anion generation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: negative regulation of superoxide anion generation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic protein-containing complex annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful functional information for AKT1 relative to the more specific
      kinase, localization, and pathway annotations.
- term:
    id: GO:0034122
    label: negative regulation of toll-like receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of toll-like receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0034123
    label: positive regulation of toll-like receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of toll-like receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0034142
    label: toll-like receptor 4 signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: toll-like receptor 4 signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0034198
    label: cellular response to amino acid starvation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cellular response to amino acid starvation pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0034405
    label: response to fluid shear stress
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: response to fluid shear stress pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0034605
    label: cellular response to heat
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: cellular response to heat pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0035519
    label: protein K29-linked ubiquitination
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein K29-linked ubiquitination pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0035655
    label: interleukin-18-mediated signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: interleukin-18-mediated signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: ciliary basal body pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0036120
    label: cellular response to platelet-derived growth factor stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: cellular response to platelet-derived growth factor stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0036316
    label: SREBP-SCAP complex retention in endoplasmic reticulum
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: SREBP-SCAP complex retention in endoplasmic reticulum pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0036416
    label: tRNA stabilization
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: tRNA stabilization pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0036444
    label: calcium import into the mitochondrion
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: calcium import into the mitochondrion pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0036499
    label: PERK-mediated unfolded protein response
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: PERK-mediated unfolded protein response pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0038202
    label: TORC1 signaling
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: TORC1 signaling pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic identical protein binding annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful functional information for AKT1 relative to the more specific
      kinase, localization, and pathway annotations.
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic protein homodimerization activity annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful functional information for AKT1 relative to the more specific
      kinase, localization, and pathway annotations.
- term:
    id: GO:0043001
    label: Golgi to plasma membrane protein transport
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Golgi to plasma membrane protein transport pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of apoptotic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of apoptotic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: proteasome-mediated ubiquitin-dependent protein catabolic process pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0043325
    label: phosphatidylinositol-3,4-bisphosphate binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: phosphatidylinositol-3,4-bisphosphate binding supports AKT1 activation or recruitment
    action: KEEP_AS_NON_CORE
    reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory
      to the core serine/threonine kinase activity.
- term:
    id: GO:0043491
    label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: phosphatidylinositol 3-kinase/protein kinase B signal transduction pathway context
    action: KEEP_AS_NON_CORE
    reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than
      the gene product core molecular activity.
- term:
    id: GO:0043491
    label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: phosphatidylinositol 3-kinase/protein kinase B signal transduction pathway context
    action: KEEP_AS_NON_CORE
    reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than
      the gene product core molecular activity.
- term:
    id: GO:0043536
    label: positive regulation of blood vessel endothelial cell migration
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of blood vessel endothelial cell migration pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0045429
    label: positive regulation of nitric oxide biosynthetic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of nitric oxide biosynthetic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0045542
    label: positive regulation of cholesterol biosynthetic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of cholesterol biosynthetic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0045600
    label: positive regulation of fat cell differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of fat cell differentiation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0045724
    label: positive regulation of cilium assembly
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of cilium assembly pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0045725
    label: positive regulation of glycogen biosynthetic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of glycogen biosynthetic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0045861
    label: negative regulation of proteolysis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of proteolysis pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0045907
    label: positive regulation of vasoconstriction
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of vasoconstriction pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of transcription by RNA polymerase II pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0045947
    label: negative regulation of translational initiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of translational initiation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0045948
    label: positive regulation of translational initiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of translational initiation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0046326
    label: positive regulation of D-glucose import across plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of D-glucose import across plasma membrane pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0046329
    label: negative regulation of JNK cascade
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: negative regulation of JNK cascade pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0046889
    label: positive regulation of lipid biosynthetic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of lipid biosynthetic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0048009
    label: insulin-like growth factor receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: insulin-like growth factor receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0048661
    label: positive regulation of smooth muscle cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of smooth muscle cell proliferation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0051247
    label: positive regulation of protein metabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of protein metabolic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0051604
    label: protein maturation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein maturation pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0051721
    label: protein phosphatase 2A binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: protein phosphatase 2A binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0060627
    label: regulation of vesicle-mediated transport
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: regulation of vesicle-mediated transport pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0061512
    label: protein localization to cilium
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein localization to cilium pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0070141
    label: response to UV-A
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: response to UV-A pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0070848
    label: response to growth factor
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: response to growth factor pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0070972
    label: protein localization to endoplasmic reticulum
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein localization to endoplasmic reticulum pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0070979
    label: protein K11-linked ubiquitination
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein K11-linked ubiquitination pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0071260
    label: cellular response to mechanical stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: cellular response to mechanical stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0071277
    label: cellular response to calcium ion
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cellular response to calcium ion pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0071364
    label: cellular response to epidermal growth factor stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: cellular response to epidermal growth factor stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0071364
    label: cellular response to epidermal growth factor stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cellular response to epidermal growth factor stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0071456
    label: cellular response to hypoxia
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: cellular response to hypoxia pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0071475
    label: cellular hyperosmotic salinity response
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: cellular hyperosmotic salinity response pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0071889
    label: 14-3-3 protein binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 14-3-3 protein binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0072350
    label: tricarboxylic acid metabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: tricarboxylic acid metabolic process pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0072656
    label: maintenance of protein location in mitochondrion
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: maintenance of protein location in mitochondrion pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0072709
    label: cellular response to sorbitol
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: cellular response to sorbitol pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0085020
    label: protein K6-linked ubiquitination
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein K6-linked ubiquitination pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0099104
    label: potassium channel activator activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: potassium channel activator activity pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0106004
    label: tRNA (guanine-N7)-methylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: tRNA (guanine-N7)-methylation pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0110002
    label: regulation of tRNA methylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: regulation of tRNA methylation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0110099
    label: negative regulation of calcium import into the mitochondrion
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: negative regulation of calcium import into the mitochondrion pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0120283
    label: protein serine/threonine kinase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: protein serine/threonine kinase binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0140052
    label: cellular response to oxidised low-density lipoprotein particle stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cellular response to oxidised low-density lipoprotein particle stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0140896
    label: cGAS/STING signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cGAS/STING signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0150033
    label: negative regulation of protein localization to lysosome
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of protein localization to lysosome pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0160049
    label: negative regulation of cGAS/STING signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of cGAS/STING signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1900087
    label: positive regulation of G1/S transition of mitotic cell cycle
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of G1/S transition of mitotic cell cycle pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1900182
    label: positive regulation of protein localization to nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of protein localization to nucleus pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1902018
    label: negative regulation of cilium assembly
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of cilium assembly pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1903038
    label: negative regulation of leukocyte cell-cell adhesion
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of leukocyte cell-cell adhesion pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1903078
    label: positive regulation of protein localization to plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of protein localization to plasma membrane pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1903384
    label: negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway
      pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1903715
    label: regulation of aerobic respiration
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: regulation of aerobic respiration pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1904262
    label: negative regulation of TORC1 signaling
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of TORC1 signaling pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1904263
    label: positive regulation of TORC1 signaling
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of TORC1 signaling pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1904841
    label: TORC2 complex binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: TORC2 complex binding supports AKT1 activation or recruitment
    action: KEEP_AS_NON_CORE
    reason: This molecular interaction is mechanistically plausible for AKT1 regulation but is accessory
      to the core serine/threonine kinase activity.
- term:
    id: GO:1905552
    label: positive regulation of protein localization to endoplasmic reticulum
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of protein localization to endoplasmic reticulum pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1905786
    label: positive regulation of anaphase-promoting complex-dependent catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of anaphase-promoting complex-dependent catabolic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1990090
    label: cellular response to nerve growth factor stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: cellular response to nerve growth factor stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:1990090
    label: cellular response to nerve growth factor stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cellular response to nerve growth factor stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:2000402
    label: negative regulation of lymphocyte migration
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of lymphocyte migration pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0007224
    label: smoothened signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:31305241
  review:
    summary: smoothened signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0021525
    label: lateral motor column neuron differentiation
  evidence_type: IMP
  original_reference_id: PMID:31305241
  review:
    summary: lateral motor column neuron differentiation pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IMP
  original_reference_id: PMID:31305241
  review:
    summary: protein stabilization pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0010467
    label: gene expression
  evidence_type: IMP
  original_reference_id: PMID:12851395
  review:
    summary: gene expression pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:23684622
  review:
    summary: Core AKT1 serine/threonine kinase activity
    action: ACCEPT
    reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation
      of serine/threonine residues on downstream substrates.
    supported_by:
    - reference_id: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md
      supporting_text: A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology
        module to dock onto phosphoinositide-enriched membranes
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:26235620
  review:
    summary: Core AKT1 serine/threonine kinase activity
    action: ACCEPT
    reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation
      of serine/threonine residues on downstream substrates.
    supported_by:
    - reference_id: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md
      supporting_text: A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology
        module to dock onto phosphoinositide-enriched membranes
- term:
    id: GO:0071363
    label: cellular response to growth factor stimulus
  evidence_type: IMP
  original_reference_id: PMID:23684622
  review:
    summary: cellular response to growth factor stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0071363
    label: cellular response to growth factor stimulus
  evidence_type: IMP
  original_reference_id: PMID:26235620
  review:
    summary: cellular response to growth factor stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:1904515
    label: positive regulation of TORC2 signaling
  evidence_type: IMP
  original_reference_id: PMID:23684622
  review:
    summary: positive regulation of TORC2 signaling pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1904515
    label: positive regulation of TORC2 signaling
  evidence_type: IMP
  original_reference_id: PMID:26235620
  review:
    summary: positive regulation of TORC2 signaling pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:21954288
  review:
    summary: Core AKT1 serine/threonine kinase activity
    action: ACCEPT
    reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation
      of serine/threonine residues on downstream substrates.
    supported_by:
    - reference_id: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md
      supporting_text: A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology
        module to dock onto phosphoinositide-enriched membranes
- term:
    id: GO:1903898
    label: negative regulation of PERK-mediated unfolded protein response
  evidence_type: IDA
  original_reference_id: PMID:21954288
  review:
    summary: negative regulation of PERK-mediated unfolded protein response pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: ISO
  original_reference_id: PMID:23223530
  review:
    summary: Generic protein-containing complex annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful functional information for AKT1 relative to the more specific
      kinase, localization, and pathway annotations.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:30504268
  review:
    summary: Core AKT1 serine/threonine kinase activity
    action: ACCEPT
    reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation
      of serine/threonine residues on downstream substrates.
    supported_by:
    - reference_id: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md
      supporting_text: A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology
        module to dock onto phosphoinositide-enriched membranes
- term:
    id: GO:0005758
    label: mitochondrial intermembrane space
  evidence_type: IDA
  original_reference_id: PMID:30504268
  review:
    summary: mitochondrial intermembrane space pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: IDA
  original_reference_id: PMID:26844834
  review:
    summary: glutamatergic synapse pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: IMP
  original_reference_id: PMID:26844834
  review:
    summary: glutamatergic synapse pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0099175
    label: regulation of postsynapse organization
  evidence_type: IDA
  original_reference_id: PMID:26844834
  review:
    summary: regulation of postsynapse organization pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0099175
    label: regulation of postsynapse organization
  evidence_type: IMP
  original_reference_id: PMID:26844834
  review:
    summary: regulation of postsynapse organization pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1902018
    label: negative regulation of cilium assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: negative regulation of cilium assembly pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0150033
    label: negative regulation of protein localization to lysosome
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: negative regulation of protein localization to lysosome pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:1904263
    label: positive regulation of TORC1 signaling
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of TORC1 signaling pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34635817
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0022605
    label: mammalian oogenesis stage
  evidence_type: IMP
  original_reference_id: PMID:34635817
  review:
    summary: mammalian oogenesis stage pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0048009
    label: insulin-like growth factor receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:11784871
  review:
    summary: insulin-like growth factor receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:11784871
  review:
    summary: Direct AKT1 phosphorylation activity
    action: ACCEPT
    reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
- term:
    id: GO:0048009
    label: insulin-like growth factor receptor signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:32439763
  review:
    summary: insulin-like growth factor receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0016301
    label: kinase activity
  evidence_type: IDA
  original_reference_id: PMID:23886629
  review:
    summary: kinase activity is less specific than AKT1 serine/threonine kinase activity
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity
      terms are present and better capture the function.
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:20889126
  review:
    summary: insulin receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than
      the gene product core molecular activity.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IDA
  original_reference_id: PMID:31915252
  review:
    summary: protein kinase activity is less specific than AKT1 serine/threonine kinase activity
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity
      terms are present and better capture the function.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:31915252
  review:
    summary: plasma membrane localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:31915252
  review:
    summary: Direct AKT1 phosphorylation activity
    action: ACCEPT
    reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
- term:
    id: GO:0006954
    label: inflammatory response
  evidence_type: IGI
  original_reference_id: PMID:31874168
  review:
    summary: inflammatory response pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0009408
    label: response to heat
  evidence_type: IGI
  original_reference_id: PMID:31874168
  review:
    summary: response to heat pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0048266
    label: behavioral response to pain
  evidence_type: IGI
  original_reference_id: PMID:31874168
  review:
    summary: behavioral response to pain pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: IDA
  original_reference_id: PMID:19933931
  review:
    summary: negative regulation of gene expression pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0099104
    label: potassium channel activator activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: potassium channel activator activity pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:28930673
  review:
    summary: cytosol localization lacks direct support in the cached PMID:28930673 record
    action: UNDECIDED
    reason: AKT1 cytosolic localization is plausible, but the cached PexRAP/PRDM16 source does not
      directly support this evidence-specific annotation.
- term:
    id: GO:0046889
    label: positive regulation of lipid biosynthetic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of lipid biosynthetic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0010467
    label: gene expression
  evidence_type: IMP
  original_reference_id: PMID:31272455
  review:
    summary: gene expression pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:2001243
    label: negative regulation of intrinsic apoptotic signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:19911006
  review:
    summary: negative regulation of intrinsic apoptotic signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0005516
    label: calmodulin binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: calmodulin binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19028694
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0032880
    label: regulation of protein localization
  evidence_type: IMP
  original_reference_id: PMID:9415393
  review:
    summary: regulation of protein localization pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:2000010
    label: positive regulation of protein localization to cell surface
  evidence_type: IMP
  original_reference_id: PMID:9415393
  review:
    summary: positive regulation of protein localization to cell surface pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:18292230
  review:
    summary: positive regulation of gene expression pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23300339
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0071356
    label: cellular response to tumor necrosis factor
  evidence_type: IDA
  original_reference_id: PMID:24349514
  review:
    summary: cellular response to tumor necrosis factor pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:10983986
  review:
    summary: Core AKT1 serine/threonine kinase activity
    action: ACCEPT
    reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation
      of serine/threonine residues on downstream substrates.
    supported_by:
    - reference_id: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md
      supporting_text: A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology
        module to dock onto phosphoinositide-enriched membranes
- term:
    id: GO:0042981
    label: regulation of apoptotic process
  evidence_type: IDA
  original_reference_id: PMID:18977203
  review:
    summary: regulation of apoptotic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: PMID:17202487
  review:
    summary: plasma membrane localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:0046622
    label: positive regulation of organ growth
  evidence_type: IMP
  original_reference_id: PMID:15713641
  review:
    summary: positive regulation of organ growth pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9863573
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9906595
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:23786676
  review:
    summary: nucleus pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:23786676
  review:
    summary: cytoplasm localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
    supported_by:
    - reference_id: PMID:23786676
      supporting_text: Id4 deficiency attenuates prostate development and promotes PIN-like lesions by
        regulating androgen receptor activity and expression of NKX3.1 and PTEN.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16792529
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:18388859
  review:
    summary: nucleus pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:18388859
  review:
    summary: cytoplasm localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:0010763
    label: positive regulation of fibroblast migration
  evidence_type: IMP
  original_reference_id: PMID:23871832
  review:
    summary: positive regulation of fibroblast migration pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0035924
    label: cellular response to vascular endothelial growth factor stimulus
  evidence_type: IDA
  original_reference_id: PMID:25139353
  review:
    summary: cellular response to vascular endothelial growth factor stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:25217619
  review:
    summary: plasma membrane localization lacks direct support in the cached PMID:25217619 record
    action: UNDECIDED
    reason: AKT1 plasma membrane recruitment is plausible in PI3K signaling, but the cached PI3K p85beta/invadopodia
      source does not directly support this evidence-specific localization annotation.
- term:
    id: GO:0036294
    label: cellular response to decreased oxygen levels
  evidence_type: IDA
  original_reference_id: PMID:24875179
  review:
    summary: cellular response to decreased oxygen levels pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0060416
    label: response to growth hormone
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: response to growth hormone pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:1990418
    label: response to insulin-like growth factor stimulus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: response to insulin-like growth factor stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0031663
    label: lipopolysaccharide-mediated signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:24740015
  review:
    summary: lipopolysaccharide-mediated signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0071380
    label: cellular response to prostaglandin E stimulus
  evidence_type: IDA
  original_reference_id: PMID:23479225
  review:
    summary: cellular response to prostaglandin E stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-162352
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9857656
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9857664
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-1445150
  review:
    summary: plasma membrane localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:0010975
    label: regulation of neuron projection development
  evidence_type: IDA
  original_reference_id: PMID:21976490
  review:
    summary: regulation of neuron projection development pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23223530
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18160256
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24156551
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:23495099
  review:
    summary: Core AKT1 serine/threonine kinase activity
    action: ACCEPT
    reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation
      of serine/threonine residues on downstream substrates.
    supported_by:
    - reference_id: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md
      supporting_text: A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology
        module to dock onto phosphoinositide-enriched membranes
- term:
    id: GO:0006979
    label: response to oxidative stress
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: response to oxidative stress pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0031641
    label: regulation of myelination
  evidence_type: IMP
  original_reference_id: PMID:24101522
  review:
    summary: regulation of myelination pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:22750946
  review:
    summary: plasma membrane localization lacks direct support in the cached PMID:22750946 record
    action: UNDECIDED
    reason: The cached N-BAR/plasma-membrane-curvature source does not directly support an AKT1-specific
      plasma membrane localization annotation.
- term:
    id: GO:0004712
    label: protein serine/threonine/tyrosine kinase activity
  evidence_type: ISO
  original_reference_id: PMID:22797923
  review:
    summary: protein serine/threonine/tyrosine kinase activity is less specific than AKT1 serine/threonine
      kinase activity
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity
      terms are present and better capture the function.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:19596798
  review:
    summary: cytoplasm localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: IDA
  original_reference_id: PMID:19596798
  review:
    summary: ciliary basal body pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: IDA
  original_reference_id: PMID:23793062
  review:
    summary: cell-cell junction pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:1901653
    label: cellular response to peptide
  evidence_type: IDA
  original_reference_id: PMID:23793062
  review:
    summary: cellular response to peptide pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0097011
    label: cellular response to granulocyte macrophage colony-stimulating factor stimulus
  evidence_type: IDA
  original_reference_id: PMID:23610142
  review:
    summary: cellular response to granulocyte macrophage colony-stimulating factor stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0001938
    label: positive regulation of endothelial cell proliferation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of endothelial cell proliferation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16116448
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:16116448
  review:
    summary: mitochondrion pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0097194
    label: execution phase of apoptosis
  evidence_type: IDA
  original_reference_id: PMID:12124386
  review:
    summary: execution phase of apoptosis pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0010765
    label: positive regulation of sodium ion transport
  evidence_type: ISO
  original_reference_id: GO_REF:0000008
  review:
    summary: positive regulation of sodium ion transport pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0032869
    label: cellular response to insulin stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000008
  review:
    summary: cellular response to insulin stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0032880
    label: regulation of protein localization
  evidence_type: ISO
  original_reference_id: GO_REF:0000008
  review:
    summary: regulation of protein localization pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0032287
    label: peripheral nervous system myelin maintenance
  evidence_type: IMP
  original_reference_id: PMID:20448149
  review:
    summary: peripheral nervous system myelin maintenance pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:22057101
  review:
    summary: Core AKT1 serine/threonine kinase activity
    action: ACCEPT
    reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation
      of serine/threonine residues on downstream substrates.
    supported_by:
    - reference_id: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md
      supporting_text: A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology
        module to dock onto phosphoinositide-enriched membranes
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22057101
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0007010
    label: cytoskeleton organization
  evidence_type: TAS
  original_reference_id: PMID:22057101
  review:
    summary: cytoskeleton organization pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0019901
    label: protein kinase binding
  evidence_type: IPI
  original_reference_id: PMID:22057101
  review:
    summary: Generic protein kinase binding annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful functional information for AKT1 relative to the more specific
      kinase, localization, and pathway annotations.
- term:
    id: GO:0071364
    label: cellular response to epidermal growth factor stimulus
  evidence_type: IDA
  original_reference_id: PMID:21712384
  review:
    summary: cellular response to epidermal growth factor stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0090201
    label: negative regulation of release of cytochrome c from mitochondria
  evidence_type: IDA
  original_reference_id: PMID:18977203
  review:
    summary: negative regulation of release of cytochrome c from mitochondria pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0030334
    label: regulation of cell migration
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: regulation of cell migration pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20333297
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:20333297
  review:
    summary: nucleus pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:20333297
  review:
    summary: plasma membrane localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
    supported_by:
    - reference_id: PMID:20333297
      supporting_text: Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:20333297
  review:
    summary: Direct AKT1 phosphorylation activity
    action: ACCEPT
    reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
    supported_by:
    - reference_id: PMID:20333297
      supporting_text: Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21030605
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0001649
    label: osteoblast differentiation
  evidence_type: IGI
  original_reference_id: PMID:19208758
  review:
    summary: osteoblast differentiation pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0006006
    label: glucose metabolic process
  evidence_type: IMP
  original_reference_id: PMID:19897600
  review:
    summary: glucose metabolic process pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0042593
    label: glucose homeostasis
  evidence_type: IMP
  original_reference_id: PMID:19897600
  review:
    summary: glucose homeostasis pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IGI
  original_reference_id: PMID:18762576
  review:
    summary: positive regulation of transcription by RNA polymerase II pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0051146
    label: striated muscle cell differentiation
  evidence_type: IGI
  original_reference_id: PMID:18762576
  review:
    summary: striated muscle cell differentiation pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:15775979
  review:
    summary: plasma membrane localization lacks direct support in the cached PMID:15775979 record
    action: UNDECIDED
    reason: The cached E-cadherin/tight-junction source does not directly support an AKT1-specific plasma
      membrane localization annotation.
- term:
    id: GO:0071363
    label: cellular response to growth factor stimulus
  evidence_type: IDA
  original_reference_id: PMID:19744960
  review:
    summary: cellular response to growth factor stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0032869
    label: cellular response to insulin stimulus
  evidence_type: IDA
  original_reference_id: PMID:19139280
  review:
    summary: cellular response to insulin stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19139280
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15722337
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0010975
    label: regulation of neuron projection development
  evidence_type: IDA
  original_reference_id: PMID:19778506
  review:
    summary: regulation of neuron projection development pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0001893
    label: maternal placenta development
  evidence_type: IMP
  original_reference_id: PMID:12783884
  review:
    summary: maternal placenta development pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0060709
    label: glycogen cell differentiation involved in embryonic placenta development
  evidence_type: IMP
  original_reference_id: PMID:12783884
  review:
    summary: glycogen cell differentiation involved in embryonic placenta development pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0060716
    label: labyrinthine layer blood vessel development
  evidence_type: IMP
  original_reference_id: PMID:12783884
  review:
    summary: labyrinthine layer blood vessel development pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16357133
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0010765
    label: positive regulation of sodium ion transport
  evidence_type: IDA
  original_reference_id: PMID:17715136
  review:
    summary: positive regulation of sodium ion transport pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0010765
    label: positive regulation of sodium ion transport
  evidence_type: IMP
  original_reference_id: PMID:17715136
  review:
    summary: positive regulation of sodium ion transport pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0032869
    label: cellular response to insulin stimulus
  evidence_type: IDA
  original_reference_id: PMID:17715136
  review:
    summary: cellular response to insulin stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0032869
    label: cellular response to insulin stimulus
  evidence_type: IMP
  original_reference_id: PMID:17715136
  review:
    summary: cellular response to insulin stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0032880
    label: regulation of protein localization
  evidence_type: IDA
  original_reference_id: PMID:17715136
  review:
    summary: regulation of protein localization pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:15937334
  review:
    summary: Direct AKT1 phosphorylation activity
    action: ACCEPT
    reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
- term:
    id: GO:0032436
    label: positive regulation of proteasomal ubiquitin-dependent protein catabolic process
  evidence_type: IMP
  original_reference_id: PMID:15937334
  review:
    summary: positive regulation of proteasomal ubiquitin-dependent protein catabolic process pathway
      context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0018105
    label: peptidyl-serine phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:16513828
  review:
    summary: Direct AKT1 phosphorylation activity
    action: ACCEPT
    reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
- term:
    id: GO:0032094
    label: response to food
  evidence_type: IDA
  original_reference_id: PMID:16513828
  review:
    summary: response to food pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0045792
    label: negative regulation of cell size
  evidence_type: ISO
  original_reference_id: PMID:16286931
  review:
    summary: negative regulation of cell size pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: PMID:14749367
  review:
    summary: plasma membrane localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: ISO
  original_reference_id: PMID:14749367
  review:
    summary: Direct AKT1 phosphorylation activity
    action: ACCEPT
    reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
- term:
    id: GO:0006924
    label: activation-induced cell death of T cells
  evidence_type: ISO
  original_reference_id: PMID:14749367
  review:
    summary: activation-induced cell death of T cells pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0016301
    label: kinase activity
  evidence_type: ISO
  original_reference_id: PMID:14749367
  review:
    summary: kinase activity is less specific than AKT1 serine/threonine kinase activity
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity
      terms are present and better capture the function.
- term:
    id: GO:0035556
    label: intracellular signal transduction
  evidence_type: ISO
  original_reference_id: PMID:14749367
  review:
    summary: intracellular signal transduction pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15753085
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding does not identify the functional interaction or catalytic role of AKT1 and
      should not be treated as informative core function.
- term:
    id: GO:0005977
    label: glycogen metabolic process
  evidence_type: IMP
  original_reference_id: PMID:12783884
  review:
    summary: glycogen metabolic process pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0043491
    label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IGI
  original_reference_id: PMID:15249583
  review:
    summary: phosphatidylinositol 3-kinase/protein kinase B signal transduction pathway context
    action: KEEP_AS_NON_CORE
    reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than
      the gene product core molecular activity.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IDA
  original_reference_id: PMID:16357133
  review:
    summary: protein kinase activity is less specific than AKT1 serine/threonine kinase activity
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity
      terms are present and better capture the function.
- term:
    id: GO:0009725
    label: response to hormone
  evidence_type: IDA
  original_reference_id: PMID:16357133
  review:
    summary: response to hormone pathway context
    action: KEEP_AS_NON_CORE
    reason: This is a valid stimulus context for AKT1 signaling but represents upstream activation or
      downstream cellular response rather than the core molecular function.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Core AKT1 serine/threonine kinase activity
    action: ACCEPT
    reason: AKT1 is an AGC protein kinase whose main molecular function is ATP-dependent phosphorylation
      of serine/threonine residues on downstream substrates.
    supported_by:
    - reference_id: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md
      supporting_text: A cytoplasmic AGC-type serine/threonine kinase that uses an N-terminal pleckstrin-homology
        module to dock onto phosphoinositide-enriched membranes
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: insulin receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than
      the gene product core molecular activity.
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:11282895
  review:
    summary: insulin receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than
      the gene product core molecular activity.
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:9415393
  review:
    summary: insulin receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: AKT1 is a central downstream kinase in this pathway, but the pathway term is broader than
      the gene product core molecular activity.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:11282895
  review:
    summary: negative regulation of apoptotic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory term reflects downstream consequences of AKT1 signaling and is not the core
      molecular activity itself.
- term:
    id: GO:0048009
    label: insulin-like growth factor receptor signaling pathway
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: insulin-like growth factor receptor signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IDA
  original_reference_id: PMID:15010863
  review:
    summary: protein kinase activity is less specific than AKT1 serine/threonine kinase activity
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity
      terms are present and better capture the function.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IDA
  original_reference_id: PMID:14730361
  review:
    summary: protein kinase activity is less specific than AKT1 serine/threonine kinase activity
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity
      terms are present and better capture the function.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:14730361
  review:
    summary: Direct AKT1 phosphorylation activity
    action: ACCEPT
    reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
- term:
    id: GO:0006954
    label: inflammatory response
  evidence_type: IDA
  original_reference_id: PMID:14730361
  review:
    summary: inflammatory response pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005819
    label: spindle
  evidence_type: IDA
  original_reference_id: PMID:15509711
  review:
    summary: spindle pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IDA
  original_reference_id: PMID:15192701
  review:
    summary: protein kinase activity is less specific than AKT1 serine/threonine kinase activity
    action: MARK_AS_OVER_ANNOTATED
    reason: The annotation is directionally correct but over-broad because more specific AKT1 kinase activity
      terms are present and better capture the function.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:15192701
  review:
    summary: Direct AKT1 phosphorylation activity
    action: ACCEPT
    reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
- term:
    id: GO:0008637
    label: apoptotic mitochondrial changes
  evidence_type: IDA
  original_reference_id: PMID:12869584
  review:
    summary: apoptotic mitochondrial changes pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:12145204
  review:
    summary: Direct AKT1 phosphorylation activity
    action: ACCEPT
    reason: This term directly describes the catalytic output of AKT1 as a serine/threonine protein kinase.
- term:
    id: GO:0016567
    label: protein ubiquitination
  evidence_type: IDA
  original_reference_id: PMID:12145204
  review:
    summary: protein ubiquitination pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0030163
    label: protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:12145204
  review:
    summary: protein catabolic process pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0007281
    label: germ cell development
  evidence_type: IDA
  original_reference_id: PMID:12140361
  review:
    summary: germ cell development pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with known AKT1 signaling biology but represents a pathway, location,
      interaction, or phenotype rather than the core catalytic function.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:12124386
  review:
    summary: cytoplasm localization
    action: ACCEPT
    reason: AKT1 is a soluble kinase that is cytosolic/cytoplasmic and is recruited to phosphoinositide-enriched
      plasma membrane signaling sites through its PH domain.
references:
- id: GO_REF:0000008
  title: Gene Ontology annotation by the MGI curatorial staff, curated orthology
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator
    judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF: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:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links
  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:10454575
  title: Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the
    serine-threonine kinase Akt.
  findings: []
- id: PMID:10983986
  title: The protooncogene TCL1 is an Akt kinase coactivator.
  findings: []
- id: PMID:11282895
  title: Reperfusion-activated Akt kinase prevents apoptosis in transgenic mouse hearts overexpressing
    insulin-like growth factor-1.
  findings: []
- id: PMID:11784871
  title: Molecular balance between the regulatory and catalytic subunits of phosphoinositide 3-kinase
    regulates cell signaling and survival.
  findings: []
- id: PMID:12124386
  title: The role of Asp-462 in regulating Akt activity.
  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:12145204
  title: Phosphorylation-dependent ubiquitylation and degradation of androgen receptor by Akt require
    Mdm2 E3 ligase.
  findings: []
- id: PMID:12783884
  title: Protein kinase B alpha/Akt1 regulates placental development and fetal growth.
  findings: []
- id: PMID:12791994
  title: 'TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver.'
  findings: []
- id: PMID:12851395
  title: Akt signaling regulates side population cell phenotype via Bcrp1 translocation.
  findings: []
- id: PMID:12869584
  title: The serine/threonine kinase Pim-2 is a transcriptionally regulated apoptotic inhibitor.
  findings: []
- id: PMID:14730361
  title: The costimulation-regulated duration of PKB activation controls T cell longevity.
  findings: []
- id: PMID:14749367
  title: Regulation of apoptosis by the Ft1 protein, a new modulator of protein kinase B/Akt.
  findings: []
- id: PMID:15010863
  title: IL2-dependent phosphorylation of 40S ribosomal protein S6 is controlled by PI-3K/mTOR signalling
    in CTLL2 cells.
  findings: []
- id: PMID:15192701
  title: 'PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD
    mutations.'
  findings: []
- id: PMID:15249583
  title: The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins.
  findings: []
- id: PMID:15509711
  title: Serine-threonine kinases and transcription factors active in signal transduction are detected
    at high levels of phosphorylation during mitosis in preimplantation embryos and trophoblast stem cells.
  findings: []
- id: PMID:15713641
  title: Role for Akt3/protein kinase Bgamma in attainment of normal brain size.
  findings: []
- id: PMID:15722337
  title: Phosphorylation of grb10 regulates its interaction with 14-3-3.
  findings: []
- id: PMID:15753085
  title: A novel protein kinase B (PKB)/AKT-binding protein enhances PKB kinase activity and regulates
    DNA synthesis.
  findings: []
- id: PMID:15775979
  title: E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions.
  findings: []
- id: PMID:15937334
  title: A role for mitogen-activated protein kinase(Erk1/2) activation and non-selective pore formation
    in P2X7 receptor-mediated thymocyte death.
  findings: []
- id: PMID:16051150
  title: An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior.
  findings: []
- id: PMID:16116448
  title: Bag1 is essential for differentiation and survival of hematopoietic and neuronal cells.
  findings: []
- id: PMID:16286931
  title: Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2.
  findings: []
- id: PMID:16357133
  title: Akt phosphorylates and regulates Pdcd4 tumor suppressor protein.
  findings: []
- id: PMID:16513828
  title: 'Impact of obesity on the growth hormone axis: evidence for a direct inhibitory effect of hyperinsulinemia
    on pituitary function.'
  findings: []
- id: PMID:16792529
  title: A WD-FYVE protein binds to the kinases Akt and PKCzeta/lambda.
  findings: []
- id: PMID:17202487
  title: Nonredundant role of Akt2 for neuroprotection of rod photoreceptor cells from light-induced cell
    death.
  findings: []
- id: PMID:17715136
  title: Akt mediates the effect of insulin on epithelial sodium channels by inhibiting Nedd4-2.
  findings: []
- id: PMID:18160256
  title: A novel Akt/PKB-interacting protein promotes cell adhesion and inhibits familial amyotrophic
    lateral sclerosis-linked mutant SOD1-induced neuronal death via inhibition of PP2A-mediated dephosphorylation
    of Akt/PKB.
  findings: []
- id: PMID:18292230
  title: Akt and CHIP coregulate tau degradation through coordinated interactions.
  findings: []
- id: PMID:18388859
  title: Akt- and Foxo1-interacting WD-repeat-FYVE protein promotes adipogenesis.
  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:18762576
  title: IGFBP-5 regulates muscle cell differentiation by binding to IGF-II and switching on the IGF-II
    auto-regulation loop.
  findings: []
- id: PMID:18977203
  title: Akt activation prevents Apop-1-induced death of cells.
  findings: []
- id: PMID:19028694
  title: Identification and characterization of a novel gene, dapr, involved in skeletal muscle differentiation
    and protein kinase B signaling.
  findings: []
- id: PMID:19122674
  title: Deficiency of a beta-arrestin-2 signal complex contributes to insulin resistance.
  findings: []
- id: PMID:19139280
  title: ClipR-59 interacts with Akt and regulates Akt cellular compartmentalization.
  findings: []
- id: PMID:19208758
  title: Akt promotes BMP2-mediated osteoblast differentiation and bone development.
  findings: []
- id: PMID:19596798
  title: Growth arrest induces primary-cilium formation and sensitizes IGF-1-receptor signaling during
    differentiation induction of 3T3-L1 preadipocytes.
  findings: []
- id: PMID:19698782
  title: Evidence for the involvement of FAM110C protein in cell spreading and migration.
  findings: []
- id: PMID:19744960
  title: GIGYF2 gene disruption in mice results in neurodegeneration and altered insulin-like growth factor
    signaling.
  findings: []
- id: PMID:19778506
  title: DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling
    through KIAA1212.
  findings: []
- id: PMID:19897600
  title: Role of insulin-like growth factor-binding protein 5 (IGFBP5) in organismal and pancreatic beta-cell
    growth.
  findings: []
- id: PMID:19911006
  title: AATF mediates an antiapoptotic effect of the unfolded protein response through transcriptional
    regulation of AKT1.
  findings: []
- id: PMID:19933931
  title: Reciprocal regulation of microRNA-1 and insulin-like growth factor-1 signal transduction cascade
    in cardiac and skeletal muscle in physiological and pathological conditions.
  findings: []
- id: PMID:20333297
  title: Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation.
  findings: []
- id: PMID:20448149
  title: Dlg1-PTEN interaction regulates myelin thickness to prevent damaging peripheral nerve overmyelination.
  findings: []
- id: PMID:20889126
  title: Insulin signaling to the glomerular podocyte is critical for normal kidney function.
  findings: []
- id: PMID:21030605
  title: PML regulates apoptosis at endoplasmic reticulum by modulating calcium release.
  findings: []
- id: PMID:21339740
  title: Selective activation of Akt1 by mammalian target of rapamycin complex 2 regulates cancer cell
    migration, invasion, and metastasis.
  findings: []
- id: PMID:21712384
  title: Silencer of death domains (SODD) inhibits skeletal muscle and kidney enriched inositol 5-phosphatase
    (SKIP) and regulates phosphoinositide 3-kinase (PI3K)/Akt signaling to the actin cytoskeleton.
  findings: []
- id: PMID:21954288
  title: Akt determines cell fate through inhibition of the PERK-eIF2α phosphorylation pathway.
  findings: []
- id: PMID:21976490
  title: Leukocyte common antigen-related phosphatase is a functional receptor for chondroitin sulfate
    proteoglycan axon growth inhibitors.
  findings: []
- id: PMID:22057101
  title: ZNRF1 promotes Wallerian degeneration by degrading AKT to induce GSK3B-dependent CRMP2 phosphorylation.
  findings: []
- id: PMID:22309289
  title: Akt augments the oncogenic potential of the HBx protein of hepatitis B virus by phosphorylation.
  findings: []
- id: PMID:22750946
  title: External push and internal pull forces recruit curvature-sensing N-BAR domain proteins to the
    plasma membrane.
  findings: []
- id: PMID:22797923
  title: ZNRF2 is released from membranes by growth factors and, together with ZNRF1, regulates the Na+/K+ATPase.
  findings: []
- id: PMID:23223530
  title: Protein kinase N1, a cell inhibitor of Akt kinase, has a central role in quality control of germinal
    center formation.
  findings: []
- id: PMID:23300339
  title: BSTA promotes mTORC2-mediated phosphorylation of Akt1 to suppress expression of FoxC2 and stimulate
    adipocyte differentiation.
  findings: []
- id: PMID:23479225
  title: 'Selective impairment of P2Y signaling by prostaglandin E2 in macrophages: implications for Ca2+-dependent
    responses.'
  findings: []
- id: PMID:23495099
  title: Oct4 interaction with Hmgb2 regulates Akt signaling and pluripotency.
  findings: []
- id: PMID:23610142
  title: Critical role of AZI2 in GM-CSF-induced dendritic cell differentiation.
  findings: []
- id: PMID:23684622
  title: Dynamic adipocyte phosphoproteome reveals that Akt directly regulates mTORC2.
  findings: []
- id: PMID:23786676
  title: Id4 deficiency attenuates prostate development and promotes PIN-like lesions by regulating androgen
    receptor activity and expression of NKX3.1 and PTEN.
  findings: []
- id: PMID:23793062
  title: The lymphoid lineage-specific actin-uncapping protein Rltpr is essential for costimulation via
    CD28 and the development of regulatory T cells.
  findings: []
- id: PMID:23871832
  title: The small GTPase N-Ras regulates extracellular matrix synthesis, proliferation and migration
    in fibroblasts.
  findings: []
- id: PMID:23886629
  title: The Akt substrate Girdin is a regulator of insulin signaling in myoblast cells.
  findings: []
- id: PMID:24101522
  title: MicroRNA-23a promotes myelination in the central nervous system.
  findings: []
- id: PMID:24156551
  title: KCTD20, a relative of BTBD10, is a positive regulator of Akt.
  findings: []
- id: PMID:24349514
  title: MicroRNA-494, upregulated by tumor necrosis factor-α, desensitizes insulin effect in C2C12 muscle
    cells.
  findings: []
- id: PMID:24740015
  title: Myeloid-specific Rictor deletion induces M1 macrophage polarization and potentiates in vivo pro-inflammatory
    response to lipopolysaccharide.
  findings: []
- id: PMID:24875179
  title: 'PTEN degradation after ischemic stroke: a double-edged sword.'
  findings: []
- id: PMID:24955524
  title: Akt1 mediates the posterior Hoxc gene expression through epigenetic modifications in mouse embryonic
    fibroblasts.
  findings: []
- id: PMID:25139353
  title: Phosphoinositide 3-kinase β mediates microvascular endothelial repair of thrombotic microangiopathy.
  findings: []
- id: PMID:25217619
  title: Phosphoinositide 3-kinase p85beta regulates invadopodium formation.
  findings: []
- id: PMID:26235620
  title: A Positive Feedback Loop between Akt and mTORC2 via SIN1 Phosphorylation.
  findings: []
- id: PMID:26844834
  title: Bidirectional Synaptic Structural Plasticity after Chronic Cocaine Administration Occurs through
    Rap1 Small GTPase Signaling.
  findings: []
- id: PMID:28930673
  title: PexRAP Inhibits PRDM16-Mediated Thermogenic Gene Expression.
  findings: []
- id: PMID:30504268
  title: Akt-mediated phosphorylation of MICU1 regulates mitochondrial Ca(2+) levels and tumor growth.
  findings: []
- id: PMID:31272455
  title: Matrix metalloproteinase activity in the lung is increased in Hermansky-Pudlak syndrome.
  findings: []
- id: PMID:31305241
  title: Critical roles of ARHGAP36 as a signal transduction mediator of Shh pathway in lateral motor
    columnar specification.
  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:32439763
  title: Vessel-derived angiocrine IGF1 promotes Meckel's cartilage proliferation to drive jaw growth
    during embryogenesis.
  findings: []
- id: PMID:34635817
  title: Gm364 coordinates MIB2/DLL3/Notch2 to regulate female fertility through AKT activation.
  findings: []
- id: PMID:9415393
  title: Physiological role of Akt in insulin-stimulated translocation of GLUT4 in transfected rat adipose
    cells.
  findings: []
- id: Reactome:R-MMU-1445150
  title: Akt Phosphorylates As160 (Tbc1d4)
  findings: []
- id: Reactome:R-MMU-162352
  title: Phosphorylation of PDE3B by AKT-1
  findings: []
- id: Reactome:R-MMU-9857656
  title: Phosphorylated Akt1 phosphorylates Connexin-43 (Gja1)
  findings: []
- id: Reactome:R-MMU-9857664
  title: p-T308,S473-Akt1 phosphorylates Itga5 (Integrin alpha5) in Itga5:Itgb1 (Integrin alpha5:Integrin
    beta1)
  findings: []
- id: Reactome:R-MMU-9863573
  title: Akt1 binds phosphoinositol-3,4,5-trisphosphate
  findings: []
- id: Reactome:R-MMU-9906595
  title: Activation of Akt1 by shear stress in osteocytes
  findings: []
- id: file:mouse/Akt1/Akt1-bioreason-rl-predictions.md
  title: BioReason deep research report on Akt1
  findings: []
- id: file:mouse/Akt1/Akt1-deep-research-falcon.md
  title: Falcon deep research summary for mouse Akt1
  findings:
  - statement: Akt1 is a broadly expressed PH-domain AGC serine/threonine kinase
      activated downstream of PI3K signaling.
  - statement: Falcon synthesis supports Akt substrate phosphorylation in cytoplasmic,
      membrane-recruited, and nuclear signaling contexts.
- id: file:mouse/Akt1/Akt1-notes.md
  title: AIGR curator notes for Akt1
  findings: []
core_functions:
- molecular_function:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  description: AKT1 phosphorylates serine and threonine residues on downstream protein substrates after
    PI3K-dependent membrane recruitment and activation by upstream kinases.
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005886
    label: plasma membrane
  directly_involved_in:
  - id: GO:0006468
    label: protein phosphorylation
  supported_by:
  - reference_id: file:mouse/Akt1/Akt1-notes.md
    supporting_text: AKT1 is a PH-domain AGC serine/threonine protein kinase activated downstream of PI3K
      and growth factor/insulin signaling.
  - reference_id: file:mouse/Akt1/Akt1-deep-research-falcon.md
    supporting_text: Falcon synthesis supports Akt1 as an ATP-dependent serine/threonine
      kinase that phosphorylates downstream substrates after PI3K-dependent activation.

Akt1

Gene Description

Existing Annotations Review

Core Functions

AKT1 phosphorylates serine and threonine residues on downstream protein substrates after PI3K-dependent membrane recruitment and activation by upstream kinases.

References

Deep Research

Falcon

Research Report: Mouse Akt1 (UniProt P31750) — Functional Annotation and Current Understanding

0) Target verification (critical identity check)

1) Key concepts and definitions (current consensus)

1.1 What Akt1 is

1.2 Catalyzed reaction and substrate specificity

1.3 Canonical activation mechanism (PI3K → PIP3 → Akt)

1.4 Negative regulation/termination

2) Functional roles, biological processes, and pathway placement

2.1 Primary pathway role: central PI3K–Akt–mTOR signaling node

2.2 Representative downstream processes (mechanistic examples)

3) Subcellular localization: where Akt1 acts

3.1 Membrane recruitment as a localization-dependent activation step

3.2 Cytoplasmic and nuclear action

3.3 Compartmentalization and substrate selectivity (recent mechanistic evidence)

4) Isoform specificity (Akt1 vs Akt2 vs Akt3) — why it matters for annotation

5) Recent developments (prioritizing 2023–2024)

5.1 New regulators and location-specific Akt signaling (Dec 2023)

5.2 Mutation/alteration statistics informing pathway targeting (Mar 2024)

5.3 Isoform-selective therapeutic logic supported by 2024 primary evidence (Oct 2024)

5.4 Microbiome–metabolite modulation of insulin signaling that intersects Akt–mTOR wiring (Aug 2024)

6) Current applications and real-world implementations

6.1 Preclinical/experimental implementations in mouse and mammalian systems

6.2 Therapeutic modulation in neurological/cardiovascular injury contexts

7) Expert opinions / analysis (from authoritative sources)

8) Relevant statistics and quantitative data (from recent sources)

9) Summary tables

10) Evidence and coverage limitations

Citations

📚 Additional Documentation

Notes

Akt1 review notes

Bioreason Rl Predictions

BioReason Chat Export

Thinking Trace

Functional Summary

UniProt Summary

InterPro Domains

GO Terms

Bioreason Rl Review

BioReason-Pro RL Review: Akt1 (mouse)

Functional Summary Review

Notes on thinking trace

📄 View Raw YAML