AKT1

Summary: The cached PAINT IBD places cytoplasmic localization at PTN000682363.

Reason: The cached PAINT IBD places cytoplasmic localization at PTN000682363. Human AKT1 localization and its reversible recruitment to membranes are compatible with this inherited distribution; no target-specific localization loss is evident.

Summary: The cached PAINT IBD at PTN000683254 transfers conserved protein serine/threonine kinase chemistry.

Reason: The cached PAINT IBD at PTN000683254 transfers conserved protein serine/threonine kinase chemistry. AKT1 directly phosphorylates protein substrates and retains the experimentally tested ATP-dependent catalytic mechanism. Human AKT1 among the descendant evidence is legitimate grounding for the ancestral assertion.

Summary: The IBD at PTN000683254 places intracellular signaling within the inherited kinase function.

Reason: The IBD at PTN000683254 places intracellular signaling within the inherited kinase function. Human AKT1 transduces insulin and growth-factor signals by substrate phosphorylation, supporting rather than contradicting the node placement.

Summary: PTN001219338 carries the experimentally grounded antiapoptotic IBD.

Reason: PTN001219338 carries the experimentally grounded antiapoptotic IBD. AKT phosphorylation of FOXO-family factors supplies a conserved survival-signaling mechanism; retain the inherited process as a contextual output of the kinase.

Summary: PTN001219338 carries the insulin-signaling IBD.

Reason: PTN001219338 carries the insulin-signaling IBD. Direct insulin-dependent activation of PKBalpha and its downstream kinase activity support conservation in human AKT1. The presence of target evidence in PAINT is not circular.

Summary: The endothelial-migration IBD at PTN001219338 is consistent with Akt-dependent migration measured in human endothelial cells.

Reason: The endothelial-migration IBD at PTN001219338 is consistent with Akt-dependent migration measured in human endothelial cells. Retain this vascular signaling context without making migration the defining biochemical activity.

Summary: The InterPro kinase-domain and mouse-ortholog mappings correctly identify a protein kinase.

Reason: The InterPro kinase-domain and mouse-ortholog mappings correctly identify a protein kinase. Human kinetic and substrate assays resolve the catalytic activity to protein serine/threonine kinase activity.

Proposed replacements: protein serine/threonine kinase activity

Summary: The combined domain, EC, rule and mouse-ortholog mappings agree with directly demonstrated human AKT1 serine/threonine phosphotransfer.

Reason: The combined domain, EC, rule and mouse-ortholog mappings agree with directly demonstrated human AKT1 serine/threonine phosphotransfer.

Summary: The kinase-domain and ARBA mappings agree with direct AKT1 kinetics: ATP binds before peptide substrate in the ordered catalytic mechanism.

Reason: The kinase-domain and ARBA mappings agree with direct AKT1 kinetics: ATP binds before peptide substrate in the ordered catalytic mechanism. ATP binding is part of the core enzyme activity.

Summary: The nuclear subcellular-location and mouse-ortholog mappings are compatible with directly observed nuclear AKT distribution during signaling.

Reason: The nuclear subcellular-location and mouse-ortholog mappings are compatible with directly observed nuclear AKT distribution during signaling. Nuclear localization is retained at the source resolution.

Summary: The cytoplasmic rule, subcellular-location and ortholog mappings are compatible with the observed cytoplasmic pool of AKT1.

Reason: The cytoplasmic rule, subcellular-location and ortholog mappings are compatible with the observed cytoplasmic pool of AKT1. The broad compartment is valid alongside separately supported cytosolic and membrane annotations.

Summary: The subcellular-location and mouse-ortholog mappings are supported by the MICU1 study: rapamycin induces mitochondrial Akt, and protease-protection experiments resolve a predominantly intermembrane-space pool in HEK293T cells.

Reason: The subcellular-location and mouse-ortholog mappings are supported by the MICU1 study: rapamycin induces mitochondrial Akt, and protease-protection experiments resolve a predominantly intermembrane-space pool in HEK293T cells. Retain this treatment-associated location as non-core.

Summary: The membrane-location and mouse-ortholog mappings agree with AKT1 recruitment to the plasma membrane for activation.

Reason: The membrane-location and mouse-ortholog mappings agree with AKT1 recruitment to the plasma membrane for activation. Preserve the asserted plasma-membrane location without treating it as a transmembrane protein.

Summary: The ARBA migration assertion is supported by Akt phosphorylation of Girdin and the resulting control of motility.

Reason: The ARBA migration assertion is supported by Akt phosphorylation of Girdin and the resulting control of motility. This is a substrate-dependent signaling role rather than migration machinery supplied by AKT itself.

Summary: This location is inferred from the NAS excitatory-postsynaptic-potential annotation, rather than a directly recovered localization experiment.

Reason: This location is inferred from the NAS excitatory-postsynaptic-potential annotation, rather than a directly recovered localization experiment. The exact Akt1-specific neuronal evidence in the cited neurotransmission review was not recovered; preserve uncertainty in that propagation route.

Summary: Akt phosphorylates FKHRL1/FOXO3 in the survival-factor pathway.

Reason: The original study establishes substrate phosphorylation and resulting FOXO3 sequestration. The generic binding row contributes no additional molecular-function information beyond the separately retained kinase annotation; its removal does not dispute the interaction.

Summary: Akt associates with ASK1 and phosphorylates its inhibitory Ser83 site.

Reason: The primary abstract reports coimmunoprecipitation and phosphorylation-dependent suppression of ASK1. Preserve that substrate mechanism in the evidence record, while removing the uninformative protein-binding assertion; this does not reject the measured association.

Summary: Protein-fragment complementation maps PKB interactions within a translation-control signaling network.

Reason: The externally read primary Methods and Results (PMC35401) include PKB constructs and a DHFR complementation interaction matrix. These interaction measurements establish network associations, but the generic binding term does not describe a distinct AKT1 molecular function. Remove the uninformative assertion without interpreting proximity as a new adaptor activity.

Summary: Akt coprecipitates with PP2A during integrin-dependent regulation of Akt phosphorylation.

Reason: The study places Akt on the substrate side of PP2A-mediated dephosphorylation during collagen adhesion. The association is relevant regulatory evidence; generic protein binding adds no useful functional characterization of AKT1 and is removed without denying that association.

Summary: Akt is an Hsp90/Cdc37 client in an intracellular signaling complex.

Reason: The primary abstract reports an active, PI3K-regulated Akt client complex whose stability depends on Hsp90. This does not make AKT1 a chaperone. Remove the generic binding assertion while retaining the client-complex evidence and its direction of regulation.

Summary: Periplakin binds the Akt PH region and influences its cellular targeting.

Reason: The study maps an interaction with periplakin that does not alter Akt activation and proposes periplakin-dependent targeting. Generic binding is removed for lack of molecular-function information; the evidence does not establish AKT1 itself as a cytolinker or scaffold.

Summary: HPV E7 perturbs the PP2A–Akt interaction and thereby sustains Akt phosphorylation.

Reason: The primary abstract identifies Akt as a PP2A-binding substrate and describes E7 sequestration of PP2A subunits. Retain this regulatory interpretation, while removing the uninformative generic interaction annotation rather than assigning the viral or phosphatase function to AKT1.

Summary: TNF-activated Akt1 phosphorylates Bcl10 before its Bcl3-dependent nuclear entry.

Reason: The MCF7 study identifies Ser218 and Ser231 phosphorylation of Bcl10 by Akt1. The supported role is substrate modification, with the nuclear-import consequence represented by the separate process row. Remove generic protein binding without disputing the reported substrate association.

Summary: Akt phosphorylates BimEL at Ser87 in a cytokine-responsive survival mechanism.

Reason: The primary abstract reports recombinant Akt phosphorylation of GST-BimEL and a Ser87-dependent effect on apoptosis. The generic interaction term is uninformative; preserving that kinase-substrate evidence does not require an additional unspecified binding activity.

Summary: Akt binds the SH3 domain of PLCG1 through its C-terminal proline-rich motifs.

Reason: The original full Results (PMC1446077, Figure 3C and proline-rich-motif mutant experiments) demonstrate direct purified Akt–PLCG1 SH3-domain binding and map the Akt-side motifs. This supports the more informative SH3-domain-binding term, whose live GO definition is binding to the SH3 domain of a protein. The finding concerns an interaction interface used in substrate recruitment, not a new general adaptor activity.

Proposed replacements: SH3 domain binding

Summary: The myxoma-virus host-range protein M-T5 associates with Akt during infection of human cancer cells.

Reason: The primary study reports an M-T5–Akt complex and manipulation of Akt activation during viral permissiveness. This establishes a pathogen-associated interaction context, not a distinct host adaptor activity. Remove generic protein binding while retaining the observed association.

Summary: Akt phosphorylates TopBP1 and promotes TopBP1 oligomerization.

Reason: The study links Akt-catalyzed phosphorylation to oligomerization of its substrate TopBP1 and repression of E2F1. Remove the generic binding assertion; the oligomerization activity belongs to TopBP1 in this mechanism and should not be transferred to Akt from the paper title.

Summary: Akt1 binds nuclear SETDB1 without phosphorylating it in the reported assays.

Reason: The study confirms the interaction in vitro and in vivo and explicitly distinguishes it from a kinase-substrate relationship. It does not resolve a separate AKT1 adaptor or histone-methyltransferase activity. Remove generic binding while retaining this noncatalytic interaction evidence.

Summary: MST1 and MST2 associate with and inhibit Akt1 in prostate cancer cells.

Reason: The source identifies endogenous MST kinases as inhibitors of Akt1 and describes an Akt1 multiprotein complex from raft-enriched fractions. Removing generic binding does not reverse this regulatory direction or deny the complex; it omits a term with no specific molecular-function content.

Summary: Akt participates in a beta-arrestin-2/PP2A signaling complex affected by lithium in mice.

Reason: The reported complex provides a context for regulation of Akt/GSK3 signaling. The source abstract explicitly describes mouse experiments. Remove uninformative generic binding without treating this as proof of an AKT1 scaffold activity or claiming an untested human-specific complex.

Summary: Akt interacts with CHIP-associated protein quality-control machinery and with PAR1/MARK2.

Reason: The source reports Akt as a CHIP substrate and regulator of tau turnover, together with a direct PAR1/MARK2 interaction. Keep these distinct directions of regulation in the source assessment. The unspecified protein-binding term is removed without denying either interaction.

Summary: DNA-PK-dependent Akt activation contributes to p53 stabilization after irradiation.

Reason: The abstract describes an Akt/GSK3/MDM2 signaling cascade; it does not resolve the particular pair underlying this IPI row. The generic binding annotation is removed for its lack of functional information, without asserting that the curated pair is false or assigning DNA-PK activity to Akt.

Summary: Nuclear Akt phosphorylates ALY on Thr219 in an mRNA-export regulatory mechanism.

Reason: The source identifies phosphorylation-dependent Akt–ALY association and downstream export effects. Remove the generic interaction term while retaining this substrate evidence; ALY phosphoinositide binding and nuclear-speckle targeting are not automatically AKT1 functions.

Summary: A Ras-MAPK/PI3K interaction screen contributes the AKT1 protein-binding annotation.

Reason: The primary abstract describes yeast two-hybrid screening and targeted validation of a subset of interactions. The exact AKT1 pair and its individual validation remain unresolved in the available abstract. Remove the generic term for lack of functional information, without claiming the interaction was invalid or deriving a specific AKT1 function from network membership.

Summary: Par-4 and PKCzeta regulate Akt activation in a tumor-suppression mechanism.

Reason: The source describes Akt regulation by Par-4 through PKCzeta in biochemical, cellular and mouse experiments. Remove unspecified protein binding without reversing regulator and target roles; the exact IPI pair is not independently resolved from the abstract.

Summary: Purified Akt1 phosphorylates the FOXO1 DNA-binding domain at Ser256.

Reason: The externally inspected full primary study (PMC2597217, Akt Phosphorylation Methods and Fig. 5) explicitly uses purchased Akt1/PKBalpha and verifies phosphorylation. This is useful substrate evidence, although generic protein binding adds no distinct function and is removed. The paper does not show that this phosphorylation directly reduces FOXO1 DNA affinity.

Summary: The primary abstract describes insulin-induced recruitment of Akt and Src to an insulin-receptor complex scaffolded by beta-arrestin-2. The scaffold activity is assigned to beta-arrestin-2, while Akt is its recruited kinase.

Reason: The primary abstract describes insulin-induced recruitment of Akt and Src to an insulin-receptor complex scaffolded by beta-arrestin-2. The scaffold activity is assigned to beta-arrestin-2, while Akt is its recruited kinase. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The abstract distinguishes Pim-phosphorylated MDM2 binding to 14-3-3 from Akt-phosphorylated MDM2. It supports an Akt substrate context but does not resolve every curated physical pair in the accessible text.

Reason: The abstract distinguishes Pim-phosphorylated MDM2 binding to 14-3-3 from Akt-phosphorylated MDM2. It supports an Akt substrate context but does not resolve every curated physical pair in the accessible text. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: PEBP4 associates with Akt in differentiating human myoblasts.

Reason: The externally recovered full primary Results (PMC2658556, PEBP does not mediate AKT inhibition of ERK signalling; supplementary Fig. S8) reports coimmunoprecipitation with transfected and endogenous Akt. The authors distinguish this from their proposed adaptor model. Remove the generic binding assertion while retaining the observed association and the source-specific mechanistic limits.

Summary: The abstract describes CTMP-dependent suppression of Akt phosphorylation in macrophages from obese mice. The precise human AKT1 interaction assay is not resolved by that abstract; no claim of a false interaction or species misattribution is made.

Reason: The abstract describes CTMP-dependent suppression of Akt phosphorylation in macrophages from obese mice. The precise human AKT1 interaction assay is not resolved by that abstract; no claim of a false interaction or species misattribution is made. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The primary abstract reports transient interaction or complex membership between FAM110C and Akt1 by coimmunoprecipitation and colocalization in HepG2 cells. This is an upstream regulatory association, not evidence that Akt1 supplies the FAM110C cytoskeletal role.

Reason: The primary abstract reports transient interaction or complex membership between FAM110C and Akt1 by coimmunoprecipitation and colocalization in HepG2 cells. This is an upstream regulatory association, not evidence that Akt1 supplies the FAM110C cytoskeletal role. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: TTC3 binds phosphorylated Akt and promotes its ubiquitination and nuclear degradation. Akt is the ubiquitin-ligase substrate in this interaction.

Reason: TTC3 binds phosphorylated Akt and promotes its ubiquitination and nuclear degradation. Akt is the ubiquitin-ligase substrate in this interaction. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The study reports PP1–Akt association and direct Akt dephosphorylation by purified PP1. Akt is the phosphatase substrate, not the phosphatase or its adaptor.

Reason: The study reports PP1–Akt association and direct Akt dephosphorylation by purified PP1. Akt is the phosphatase substrate, not the phosphatase or its adaptor. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The abstract describes ANT2 depletion, HSP90-dependent HER2 stability and consequent Akt signaling changes in SK-BR3 cells. The exact curated AKT1 physical pair is unresolved from that abstract, so the interaction itself is not rejected.

Reason: The abstract describes ANT2 depletion, HSP90-dependent HER2 stability and consequent Akt signaling changes in SK-BR3 cells. The exact curated AKT1 physical pair is unresolved from that abstract, so the interaction itself is not rejected. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: AKT1 binds vimentin through the AKT tail and vimentin head regions, then phosphorylates vimentin Ser39 in the reported sarcoma-cell mechanism. This supports a kinase–substrate interaction rather than an additional unspecified binding function.

Reason: AKT1 binds vimentin through the AKT tail and vimentin head regions, then phosphorylates vimentin Ser39 in the reported sarcoma-cell mechanism. This supports a kinase–substrate interaction rather than an additional unspecified binding function. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The YFP-complementation study maps candidate interactions of telomeric proteins in human cells. The accessible study-level evidence establishes the screening design; the exact AKT1 pair is not independently resolved here.

Reason: The YFP-complementation study maps candidate interactions of telomeric proteins in human cells. The accessible study-level evidence establishes the screening design; the exact AKT1 pair is not independently resolved here. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: AKT1 directly associates with DNMT1 and phosphorylates Ser143, antagonizing adjacent Lys142 methylation and DNMT1 turnover. The methyltransferase activity belongs to DNMT1/SET7, while AKT1 supplies phosphorylation.

Reason: AKT1 directly associates with DNMT1 and phosphorylates Ser143, antagonizing adjacent Lys142 methylation and DNMT1 turnover. The methyltransferase activity belongs to DNMT1/SET7, while AKT1 supplies phosphorylation. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The source distinguishes Akt docking to FOXO3 from its phosphorylation-recognition motifs and from subsequent FOXO3 binding to 14-3-3. The observed docking supports substrate regulation without an unspecified additional AKT1 binding activity.

Reason: The source distinguishes Akt docking to FOXO3 from its phosphorylation-recognition motifs and from subsequent FOXO3 binding to 14-3-3. The observed docking supports substrate regulation without an unspecified additional AKT1 binding activity. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The abstract reports recombinant LRRK2 phosphorylation of Akt1 at Ser473 and cellular knockdown evidence. Akt1 is the substrate of the interacting upstream kinase in this experiment.

Reason: The abstract reports recombinant LRRK2 phosphorylation of Akt1 at Ser473 and cellular knockdown evidence. Akt1 is the substrate of the interacting upstream kinase in this experiment. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: SIRT1-mediated deacetylation of the Akt PH domain promotes PIP3 binding and membrane recruitment. Akt is a deacetylase substrate here; its separate phosphoinositide-binding function is independently represented.

Reason: SIRT1-mediated deacetylation of the Akt PH domain promotes PIP3 binding and membrane recruitment. Akt is a deacetylase substrate here; its separate phosphoinositide-binding function is independently represented. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The primary abstract reports HBx–Akt1 coimmunoprecipitation and Akt-dependent HBx Ser31 phosphorylation. Retain this viral-substrate interaction context; the linked correction requires its own bounded source assessment.

Reason: The primary abstract reports HBx–Akt1 coimmunoprecipitation and Akt-dependent HBx Ser31 phosphorylation. Retain this viral-substrate interaction context; the linked correction requires its own bounded source assessment. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: Akt phosphorylates Niban/FAM129A at Ser602 during the reported UV-response mechanism, changing Niban interactions with nucleophosmin and MDM2. The evidence supports kinase-substrate regulation; it does not make Akt the downstream ubiquitin ligase.

Reason: Akt phosphorylates Niban/FAM129A at Ser602 during the reported UV-response mechanism, changing Niban interactions with nucleophosmin and MDM2. The evidence supports kinase-substrate regulation; it does not make Akt the downstream ubiquitin ligase. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The abstract reports complexes containing STYK1/NOK, Akt and GSK3beta, with Akt activation coupled to GSK3beta Ser9 phosphorylation. The molecular activity supplied by Akt is substrate phosphorylation.

Reason: The abstract reports complexes containing STYK1/NOK, Akt and GSK3beta, with Akt activation coupled to GSK3beta Ser9 phosphorylation. The molecular activity supplied by Akt is substrate phosphorylation. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The study measures endogenous interaction proximity across hepatocellular-carcinoma signaling networks by in-situ proximity ligation. Its accessible abstract does not independently resolve the individual curated AKT1 pair or a distinct AKT1 adaptor function.

Reason: The study measures endogenous interaction proximity across hepatocellular-carcinoma signaling networks by in-situ proximity ligation. Its accessible abstract does not independently resolve the individual curated AKT1 pair or a distinct AKT1 adaptor function. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: Akt phosphorylates CBP at Thr1871, reducing CBP association with histone H3 and H3 Lys18 acetylation. AKT1 is the regulatory kinase, not the acetyltransferase.

Reason: Akt phosphorylates CBP at Thr1871, reducing CBP association with histone H3 and H3 Lys18 acetylation. AKT1 is the regulatory kinase, not the acetyltransferase. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The A549 study reports ATRA-dependent RARalpha–Akt association, colocalization at the plasma membrane and Akt-pathway activation. This is a receptor-associated signaling context rather than an additional unspecified binding activity.

Reason: The A549 study reports ATRA-dependent RARalpha–Akt association, colocalization at the plasma membrane and Akt-pathway activation. This is a receptor-associated signaling context rather than an additional unspecified binding activity. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: AKT1 directly phosphorylates NR3C1 at Ser134 and limits glucocorticoid-induced nuclear translocation in T-ALL. The physical association is consistent with kinase-substrate regulation.

Reason: AKT1 directly phosphorylates NR3C1 at Ser134 and limits glucocorticoid-induced nuclear translocation in T-ALL. The physical association is consistent with kinase-substrate regulation. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The study maps interactions between colorectal-cancer driver and susceptibility proteins. The accessible abstract establishes the network-assay scope but not the individual AKT1 pair or a mechanistically specific AKT1 molecular function.

Reason: The study maps interactions between colorectal-cancer driver and susceptibility proteins. The accessible abstract establishes the network-assay scope but not the individual AKT1 pair or a mechanistically specific AKT1 molecular function. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: MaMTH detects membrane-protein interactions by split-ubiquitin complementation in human cells. The accessible study summary does not establish which specific AKT1 binding interface or independent molecular activity the curated pair represents.

Reason: MaMTH detects membrane-protein interactions by split-ubiquitin complementation in human cells. The accessible study summary does not establish which specific AKT1 binding interface or independent molecular activity the curated pair represents. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: Cyclin-A/CDK2 or mTORC2 phosphorylates the Akt C terminus at Ser477/Thr479 under distinct conditions. Akt is an upstream-kinase substrate in this activation mechanism.

Reason: Cyclin-A/CDK2 or mTORC2 phosphorylates the Akt C terminus at Ser477/Thr479 under distinct conditions. Akt is an upstream-kinase substrate in this activation mechanism. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The HeLa proximity-ligation screen identifies AKT1 as a network hub among tested endogenous protein pairs. Proximity evidence is retained as interaction context without inferring a new AKT1 scaffold activity.

Reason: The HeLa proximity-ligation screen identifies AKT1 as a network hub among tested endogenous protein pairs. Proximity evidence is retained as interaction context without inferring a new AKT1 scaffold activity. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: This study profiles variant-dependent perturbations of protein interactions. The accessible study-level evidence does not resolve the exact AKT1 pair or establish a separate mechanistic binding function for AKT1.

Reason: This study profiles variant-dependent perturbations of protein interactions. The accessible study-level evidence does not resolve the exact AKT1 pair or establish a separate mechanistic binding function for AKT1. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The study combines Akt1 simulations with mutagenesis and recruitment assays for PDK1/PP2A to test ATP-dependent protection of Akt phosphorylation. ATP binding is separately represented; recruitment of its kinase/phosphatase does not establish a new generic molecular function.

Reason: The study combines Akt1 simulations with mutagenesis and recruitment assays for PDK1/PP2A to test ATP-dependent protection of Akt phosphorylation. ATP binding is separately represented; recruitment of its kinase/phosphatase does not establish a new generic molecular function. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The study compares interaction profiles of alternatively spliced protein isoforms. The particular AKT1 interaction and isoform context are not independently resolved from the accessible study summary.

Reason: The study compares interaction profiles of alternatively spliced protein isoforms. The particular AKT1 interaction and isoform context are not independently resolved from the accessible study summary. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: BioPlex 2.0 maps affinity-purification/mass-spectrometry co-complex associations. Such evidence supports a physical context without by itself specifying a direct AKT1 binding interface or adaptor mechanism.

Reason: BioPlex 2.0 maps affinity-purification/mass-spectrometry co-complex associations. Such evidence supports a physical context without by itself specifying a direct AKT1 binding interface or adaptor mechanism. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: LuTHy measures BRET and luminescence coprecipitation in the same interaction-screening workflow. The accessible source does not independently resolve the particular AKT1 pair or a distinct AKT1 molecular activity.

Reason: LuTHy measures BRET and luminescence coprecipitation in the same interaction-screening workflow. The accessible source does not independently resolve the particular AKT1 pair or a distinct AKT1 molecular activity. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The study profiles how human missense variants perturb protein interactions. It supports an interaction-testing context, while the individual AKT1 partner and variant dependence remain unresolved here.

Reason: The study profiles how human missense variants perturb protein interactions. It supports an interaction-testing context, while the individual AKT1 partner and variant dependence remain unresolved here. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The study measures rewiring of EGFR interaction networks in colorectal-cancer cells expressing KRAS G13D. The accessible source establishes the network context but does not resolve a separate AKT1 adaptor activity.

Reason: The study measures rewiring of EGFR interaction networks in colorectal-cancer cells expressing KRAS G13D. The accessible source establishes the network context but does not resolve a separate AKT1 adaptor activity. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: HuRI is a systematic human binary-interaction map. The curated pair is retained as interaction evidence without claiming that the accessible study summary independently identifies a mechanistic AKT1 binding function.

Reason: HuRI is a systematic human binary-interaction map. The curated pair is retained as interaction evidence without claiming that the accessible study summary independently identifies a mechanistic AKT1 binding function. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The neurodegeneration interactome combines systematic yeast-two-hybrid screening with literature interactions. The exact AKT1 pair and assay provenance remain unresolved from the accessible abstract.

Reason: The neurodegeneration interactome combines systematic yeast-two-hybrid screening with literature interactions. The exact AKT1 pair and assay provenance remain unresolved from the accessible abstract. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: BioPlex 3.0 maps cell-line-dependent affinity-purification/mass-spectrometry associations in 293T and HCT116 cells. These co-complex measurements do not by themselves define a new AKT1 adaptor mechanism.

Reason: BioPlex 3.0 maps cell-line-dependent affinity-purification/mass-spectrometry associations in 293T and HCT116 cells. These co-complex measurements do not by themselves define a new AKT1 adaptor mechanism. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The breast-cancer interactome profiles wild-type and mutant cancer-protein complexes across three human cell lines. The individual AKT1 pair and its allele dependence are not independently established by the accessible abstract.

Reason: The breast-cancer interactome profiles wild-type and mutant cancer-protein complexes across three human cell lines. The individual AKT1 pair and its allele dependence are not independently established by the accessible abstract. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: OpenCell combines endogenous tagging, imaging and mass spectrometry to map protein locations and associations. The exact AKT1 pair is not resolved here, and the annotation does not specify a mechanistic molecular activity.

Reason: OpenCell combines endogenous tagging, imaging and mass spectrometry to map protein locations and associations. The exact AKT1 pair is not resolved here, and the annotation does not specify a mechanistic molecular activity. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: The externally inspected primary Results and Methods compare wild-type and oncogenic-variant interaction profiles, including AKT1 E17K. This assay design does not justify treating every variant-enabled pair as a constitutive wild-type function.

Reason: The externally inspected primary Results and Methods compare wild-type and oncogenic-variant interaction profiles, including AKT1 E17K. This assay design does not justify treating every variant-enabled pair as a constitutive wild-type function. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: MPST associates with AKT in transfected HEK293T cells and in recombinant-protein assays; generic protein binding does not identify a specific AKT1 molecular function.

Reason: The recovered primary Methods 2.13 and Results/Figure 9 report tagged-protein co-immunoprecipitation, AKT deletion mapping and recombinant MPST-AKT association. These experiments support the interaction, while the assay descriptions use AKT without a sequence accession resolving every endogenous isoform. The generic protein-binding term remains uninformative and is removed without denying the interaction. The Results describe MPST sustaining AKT phosphorylation in this context, despite opposite wording in the abstract; this discrepancy is recorded in the reference assessment rather than converted into a separate function.

Summary: The accessible abstract establishes Akt2-dependent PGC-1alpha regulation in hepatic metabolism but does not resolve the curated AKT1 self-interaction assay. The full source was not recovered. This is an evidence-access limit, not proof of a wrong-paralog annotation.

Reason: The accessible abstract establishes Akt2-dependent PGC-1alpha regulation in hepatic metabolism but does not resolve the curated AKT1 self-interaction assay. The full source was not recovered. This is an evidence-access limit, not proof of a wrong-paralog annotation.

Summary: The primary Results establish a wild-type-versus-mutant BRET interaction screen including AKT1 E17K, but the exact AKT1 self-pair, construct combination and variant dependence were not recovered. Retain uncertainty rather than treating the screen title as direct wild-type self-association evidence.

Reason: The primary Results establish a wild-type-versus-mutant BRET interaction screen including AKT1 E17K, but the exact AKT1 self-pair, construct combination and variant dependence were not recovered. Retain uncertainty rather than treating the screen title as direct wild-type self-association evidence.

Summary: The primary abstract directly reports specific AH/PH-domain-mediated Akt self-association, including deletion tests and failure to bind Akt2. Retain this activation-associated molecular interaction as non-core without inferring obligate dimer stoichiometry for native Akt.

Reason: The primary abstract directly reports specific AH/PH-domain-mediated Akt self-association, including deletion tests and failure to bind Akt2. Retain this activation-associated molecular interaction as non-core without inferring obligate dimer stoichiometry for native Akt.

Summary: The mouse donor carries experimental mitochondrial localization, and the independent MICU1 work recovers a rapamycin-responsive mitochondrial Akt pool in human cells.

Reason: The mouse donor carries experimental mitochondrial localization, and the independent MICU1 work recovers a rapamycin-responsive mitochondrial Akt pool in human cells. Retain the broad organelle annotation without upgrading this source row to a submitochondrial compartment.

Summary: Mouse Akt1 carries an IDA spindle annotation from the mitotic-phosphoprotein study.

Reason: Mouse Akt1 carries an IDA spindle annotation from the mitotic-phosphoprotein study. Its accessible abstract describes spindle-associated phosphoproteins, but the exact Akt1 reagent and localization panel were not recovered; transfer of this precise location remains unresolved.

Summary: Mouse-to-human transfer of cytosolic localization agrees with direct cytosolic AKT1 interactions observed in human endothelial cells.

Reason: Mouse-to-human transfer of cytosolic localization agrees with direct cytosolic AKT1 interactions observed in human endothelial cells. The source location has no demonstrated compartment mismatch.

Summary: The mouse donor carries a junction-localization IDA from the Rltpr/CD28 study.

Reason: The mouse donor carries a junction-localization IDA from the Rltpr/CD28 study. The accessible abstract describes the immunological synapse but does not resolve the Akt1-specific location assay; this transfer remains uncertain rather than disproven.

Summary: The mouse ortholog participates in insulin signaling, and direct PKBalpha activation by insulin independently establishes the corresponding human signaling role.

Reason: The mouse ortholog participates in insulin signaling, and direct PKBalpha activation by insulin independently establishes the corresponding human signaling role.

Summary: The mouse donor includes the Cntnap2 pain/thermal-response experiment, while human fibroblast experiments independently show heat-induced Akt activation and increased heat sensitivity after Akt suppression.

Reason: The mouse donor includes the Cntnap2 pain/thermal-response experiment, while human fibroblast experiments independently show heat-induced Akt activation and increased heat sensitivity after Akt suppression. Retain the broad heat-response function without equating cellular heat stress with all aspects of mouse nociception.

Summary: The mouse hormone-response assertion is compatible with conserved Akt activation by insulin and IGF-1.

Reason: The mouse hormone-response assertion is compatible with conserved Akt activation by insulin and IGF-1. Retain the broad stimulus-response context while the kinase chemistry and receptor pathways provide the specific functional account.

Summary: The mouse donor is linked to Akt/CHIP regulation: suppressing Akt lowers CHIP expression, and mouse Akt1 knockout also changes tau phosphorylation.

Reason: The mouse donor is linked to Akt/CHIP regulation: suppressing Akt lowers CHIP expression, and mouse Akt1 knockout also changes tau phosphorylation. Retain contextual control of gene expression without assigning DNA-binding or transcription-factor activity.

Summary: The mouse donor study tests active and dominant-negative Akt in the IGF-1/FOXO3/miR-1 circuit and reports reduced miR-1 expression with active Akt.

Reason: The mouse donor study tests active and dominant-negative Akt in the IGF-1/FOXO3/miR-1 circuit and reports reduced miR-1 expression with active Akt. This supports a conserved signaling-mediated negative effect on gene expression, not direct DNA binding.

Summary: The mouse source studies place Akt-mTOR signaling in adult-born neuronal development and CSPG/LAR-dependent growth restriction.

Reason: The mouse source studies place Akt-mTOR signaling in adult-born neuronal development and CSPG/LAR-dependent growth restriction. The kinase supplies signaling within neurite regulation; retain this neuronal context without claiming Akt builds neurites structurally.

Summary: The ortholog-based kinase assignment is correct but its substrate class is directly resolved in human AKT1 kinetic experiments.

Reason: The ortholog-based kinase assignment is correct but its substrate class is directly resolved in human AKT1 kinetic experiments. Refine to protein serine/threonine kinase activity.

Proposed replacements: protein serine/threonine kinase activity

Summary: The mouse donor interaction is curated against a GSK3 kinase partner in the ZNRF1/AKT/GSK3B axonal pathway.

Reason: The mouse donor interaction is curated against a GSK3 kinase partner in the ZNRF1/AKT/GSK3B axonal pathway. Its phosphorylation-dependent inhibition provides a meaningful kinase-substrate binding context, retained as non-core.

Summary: The donor experiment explicitly locates activated Akt-1 at the basal body of growth-arrested 3T3-L1 preadipocytes during IGF-1 signaling.

Reason: The donor experiment explicitly locates activated Akt-1 at the basal body of growth-arrested 3T3-L1 preadipocytes during IGF-1 signaling. Retain the ortholog-based, cell-state-specific location without treating AKT1 as a constitutive basal-body component.

Summary: The mouse Apop-1 study places PI3K/Akt signaling in protection of vascular smooth-muscle cells from death.

Reason: The mouse Apop-1 study places PI3K/Akt signaling in protection of vascular smooth-muscle cells from death. Human AKT-dependent survival mechanisms independently support this broad apoptotic-regulation transfer.

Summary: The conserved antiapoptotic signaling role is directly supported by Akt-mediated phosphorylation and inhibition of FOXO-family death-promoting transcription factors.

Reason: The conserved antiapoptotic signaling role is directly supported by Akt-mediated phosphorylation and inhibition of FOXO-family death-promoting transcription factors. Retain this survival output as non-core.

Summary: The mouse IGF-receptor signaling transfer is independently supported by direct activation of human PKBalpha in IGF-1-stimulated 293 cells.

Reason: The mouse IGF-receptor signaling transfer is independently supported by direct activation of human PKBalpha in IGF-1-stimulated 293 cells.

Summary: The donor is an IGI assertion from Cntnap2-deficient mouse pain experiments.

Reason: The donor is an IGI assertion from Cntnap2-deficient mouse pain experiments. The accessible abstract reports pathway inhibitors and pain behavior; the exact Akt1 genetic interaction and its transfer to human behavioral response were not independently recovered.

Summary: The donor study reports reduced EGF-induced Akt phosphorylation in SODD-null fibroblasts and rescue of cytoskeletal responses by active Akt1.

Reason: The donor study reports reduced EGF-induced Akt phosphorylation in SODD-null fibroblasts and rescue of cytoskeletal responses by active Akt1. This supports a contextual EGF-response signaling function.

Summary: The mouse donor carries an IDA cytochrome-c-release annotation from the Apop-1 survival study.

Reason: The mouse donor carries an IDA cytochrome-c-release annotation from the Apop-1 survival study. The accessible abstract establishes antiapoptotic Akt signaling but not the specific cytochrome-c assay, so the narrower transfer remains unresolved.

Summary: The full mouse study detects Akt signaling in nucleus-accumbens synaptoneurosomes during cocaine-dependent plasticity.

Reason: The full mouse study detects Akt signaling in nucleus-accumbens synaptoneurosomes during cocaine-dependent plasticity. Retain the donor-supported glutamatergic-synapse context, without equating the biochemical fraction with a universal residence of all AKT1.

Summary: In the mouse donor study, dominant-negative Akt changes spine morphology and blocks Rap1b-dependent thin-spine formation.

Reason: In the mouse donor study, dominant-negative Akt changes spine morphology and blocks Rap1b-dependent thin-spine formation. This is positive signaling participation in synaptic organization, retained as a contextual neuronal role.

Summary: The Rhea reaction and mouse-ortholog mappings specify transfer to protein serine.

Reason: The Rhea reaction and mouse-ortholog mappings specify transfer to protein serine. Direct human AKT substrate assays establish this chemistry; retain the true serine activity alongside its broader serine/threonine activity.

Summary: The mouse donor study directly tests active Akt1/2 phosphorylation of PERK Thr799 and the enhanced PERK activity of a nonphosphorylatable mutant.

Reason: The mouse donor study directly tests active Akt1/2 phosphorylation of PERK Thr799 and the enhanced PERK activity of a nonphosphorylatable mutant. Retain conserved negative PERK regulation as an ER-stress signaling context.

Summary: The donor phosphoproteomic study follows SIN1 Thr86 with direct Akt kinase assays and SIN1 mutant rescue of mTORC2 activity.

Reason: The donor phosphoproteomic study follows SIN1 Thr86 with direct Akt kinase assays and SIN1 mutant rescue of mTORC2 activity. This establishes positive feedback within the central Akt-mTOR signaling network, rather than merely Akt being an mTORC2 substrate.

Summary: The source experiment tests wild-type, active and dominant-inhibitory Akt constructs in adipose cells and measures GLUT4 surface translocation.

Reason: The source experiment tests wild-type, active and dominant-inhibitory Akt constructs in adipose cells and measures GLUT4 surface translocation. Retain the signaling-mediated protein-trafficking outcome with its assay context.

Summary: The mouse donor study reports protection from ER-stress death by active AKT1 and sensitization after AKT1 knockdown.

Reason: The mouse donor study reports protection from ER-stress death by active AKT1 and sensitization after AKT1 knockdown. Retain this intracellular stress-survival context; AKT1 provides the signaling activity rather than the execution machinery of apoptosis.

Summary: Akt1 phosphorylates Bcl10 at Ser218/Ser231 in TNFalpha-treated MCF7 cells, enabling Bcl3-dependent nuclear entry.

Reason: Akt1 phosphorylates Bcl10 at Ser218/Ser231 in TNFalpha-treated MCF7 cells, enabling Bcl3-dependent nuclear entry. Retain this substrate-specific nuclear-import regulation.

Summary: The current Human Protein Atlas AKT1 page reports supported nucleoplasmic localization, with HPA002891 staining in A-431, U-251MG and U2OS cells.

Reason: The current Human Protein Atlas AKT1 page reports supported nucleoplasmic localization, with HPA002891 staining in A-431, U-251MG and U2OS cells. Retain the directly observed compartment at the source resolution.

Summary: FLT3-ligand signaling activates the PI3K–AKT pathway, with AKT-catalyzed FOXO3 phosphorylation represented as a downstream step.

Reason: FLT3-ligand signaling activates the PI3K–AKT pathway, with AKT-catalyzed FOXO3 phosphorylation represented as a downstream step. Retain this defined signaling or regulatory context as non-core alongside the integrated kinase function.

Summary: CD28 costimulation engages the PI3K–AKT signaling branch in T cells; the constituent event models AKT phosphorylation of MAP3K8/Cot.

Reason: CD28 costimulation engages the PI3K–AKT signaling branch in T cells; the constituent event models AKT phosphorylation of MAP3K8/Cot. Retain this defined signaling or regulatory context as non-core alongside the integrated kinase function.

Summary: The stress-response pathway includes an AKT–ESR1 signaling branch responding to mitochondrial protein-folding stress, alongside other stress pathways.

Reason: The stress-response pathway includes an AKT–ESR1 signaling branch responding to mitochondrial protein-folding stress, alongside other stress pathways. Retain this defined signaling or regulatory context as non-core alongside the integrated kinase function.

Summary: AKT1 phosphorylates ZFP36L1/BRF1, permitting its sequestration by 14-3-3 and inhibiting its mRNA-destabilizing activity.

Reason: AKT1 phosphorylates ZFP36L1/BRF1, permitting its sequestration by 14-3-3 and inhibiting its mRNA-destabilizing activity. Retain this defined signaling or regulatory context as non-core alongside the integrated kinase function.

Summary: AKT phosphorylation of KHSRP at Ser193 inhibits its mRNA-destabilizing activity and promotes 14-3-3-dependent nuclear retention.

Reason: AKT phosphorylation of KHSRP at Ser193 inhibits its mRNA-destabilizing activity and promotes 14-3-3-dependent nuclear retention. Retain this defined signaling or regulatory context as non-core alongside the integrated kinase function.

Summary: AKT phosphorylates MDM2 at Ser166 and Ser188 in the cytosol, regulating MDM2 stability and subsequent signaling.

Reason: AKT phosphorylates MDM2 at Ser166 and Ser188 in the cytosol, regulating MDM2 stability and subsequent signaling. AKT performs the phosphorylation step in this signaling process.

Summary: AKT phosphorylates TSC2 at Ser939 and Thr1462 in the cytosol, inhibiting the TSC regulatory branch upstream of mTORC1.

Reason: AKT phosphorylates TSC2 at Ser939 and Thr1462 in the cytosol, inhibiting the TSC regulatory branch upstream of mTORC1. AKT performs the phosphorylation step in this signaling process.

Summary: AKT phosphorylates the IKK subunit CHUK at Thr23 in the cytosol.

Reason: AKT phosphorylates the IKK subunit CHUK at Thr23 in the cytosol. AKT performs the phosphorylation step in this signaling process.

Summary: AKT phosphorylates the cell-cycle inhibitors CDKN1A and CDKN1B in the cytosol.

Reason: AKT phosphorylates the cell-cycle inhibitors CDKN1A and CDKN1B in the cytosol. AKT performs the phosphorylation step in this signaling process.

Summary: AKT phosphorylates caspase-9 at Ser196 in the cytosol, inhibiting this apoptotic protease.

Reason: AKT phosphorylates caspase-9 at Ser196 in the cytosol, inhibiting this apoptotic protease. AKT performs the phosphorylation step in this signaling process.

Summary: AKT phosphorylates CREB1 at Ser133 in the nucleoplasm, linking PI3K signaling to CREB-dependent transcription.

Reason: AKT phosphorylates CREB1 at Ser133 in the nucleoplasm, linking PI3K signaling to CREB-dependent transcription. AKT performs the phosphorylation step in this signaling process.

Summary: Nuclear AKT phosphorylates FOXO1, FOXO3 and FOXO4 at defined serine/threonine sites; the event explicitly distinguishes the less certain FOXO6 inference.

Reason: Nuclear AKT phosphorylates FOXO1, FOXO3 and FOXO4 at defined serine/threonine sites; the event explicitly distinguishes the less certain FOXO6 inference. AKT performs the phosphorylation step in this signaling process.

Summary: The event models AKT phosphorylation of RPS6KB2 in the nucleoplasm; this is the nuclear S6 kinase substrate, not a transfer of its activity to AKT.

Reason: The event models AKT phosphorylation of RPS6KB2 in the nucleoplasm; this is the nuclear S6 kinase substrate, not a transfer of its activity to AKT. AKT performs the phosphorylation step in this signaling process.

Summary: The event models nuclear AKT phosphorylation of NR4A1 but explicitly notes subsequent work favoring RSK/MSK as the physiological NR4A1 kinase.

Reason: The event models nuclear AKT phosphorylation of NR4A1 but explicitly notes subsequent work favoring RSK/MSK as the physiological NR4A1 kinase. AKT performs the phosphorylation step in this signaling process.

Summary: AKT phosphorylates AKT1S1/PRAS40 in the cytosol, relieving its inhibition of mTORC1.

Reason: AKT phosphorylates AKT1S1/PRAS40 in the cytosol, relieving its inhibition of mTORC1. AKT performs the phosphorylation step in this signaling process.

Summary: AKT1 phosphorylates cytosolic MKRN1 at Ser109, stabilizing this ubiquitin ligase in an EGF-responsive regulatory circuit.

Reason: AKT1 phosphorylates cytosolic MKRN1 at Ser109, stabilizing this ubiquitin ligase in an EGF-responsive regulatory circuit. AKT performs the phosphorylation step in this signaling process.

Summary: Recombinant human AKT1 phosphorylates human NOTCH4 intracellular domain at four serines; the model places this inhibitory Notch-regulatory step in the cytosol.

Reason: Recombinant human AKT1 phosphorylates human NOTCH4 intracellular domain at four serines; the model places this inhibitory Notch-regulatory step in the cytosol. Retain this defined signaling or regulatory context as non-core alongside the integrated kinase function.

Summary: The eNOS-activation pathway includes AKT1-catalyzed NOS3 phosphorylation as a concrete regulatory step in nitric-oxide production.

Reason: The eNOS-activation pathway includes AKT1-catalyzed NOS3 phosphorylation as a concrete regulatory step in nitric-oxide production. Retain this defined signaling or regulatory context as non-core alongside the integrated kinase function.

Summary: Laminar shear stress activates endothelial AKT1, which phosphorylates NOS3 as a defined downstream signaling step.

Reason: Laminar shear stress activates endothelial AKT1, which phosphorylates NOS3 as a defined downstream signaling step. Retain this defined signaling or regulatory context as non-core alongside the integrated kinase function.

Summary: AKT phosphorylates KAT6A at Thr369 within the pathway controlling TP53 acetylation; KAT6A, not AKT, performs the acetylation.

Reason: AKT phosphorylates KAT6A at Thr369 within the pathway controlling TP53 acetylation; KAT6A, not AKT, performs the acetylation. Retain this defined signaling or regulatory context as non-core alongside the integrated kinase function.

Summary: AKT phosphorylation of PHF20 at Ser291 regulates its effect on TP53 stability, providing a defined step in the cofactor-regulation pathway.

Reason: AKT phosphorylation of PHF20 at Ser291 regulates its effect on TP53 stability, providing a defined step in the cofactor-regulation pathway. Retain this defined signaling or regulatory context as non-core alongside the integrated kinase function.

Summary: AKT-mediated FOXO1 phosphorylation and nuclear exclusion are modeled within regulation of pancreatic beta-cell gene expression and development.

Reason: AKT-mediated FOXO1 phosphorylation and nuclear exclusion are modeled within regulation of pancreatic beta-cell gene expression and development. Retain this defined signaling or regulatory context as non-core alongside the integrated kinase function.

Summary: Akt-dependent eNOS Ser1177 phosphorylation and the phosphorylation-site mutant establish protein serine kinase chemistry within the accepted serine/threonine activity.

Reason: Akt-dependent eNOS Ser1177 phosphorylation and the phosphorylation-site mutant establish protein serine kinase chemistry within the accepted serine/threonine activity.

Summary: PKB phosphorylates BRF1 at Ser92 and Ser203; kinase labeling and site mutants resolve substrate phosphorylation that controls BRF1 stability and RNA-decay activity.

Reason: PKB phosphorylates BRF1 at Ser92 and Ser203; kinase labeling and site mutants resolve substrate phosphorylation that controls BRF1 stability and RNA-decay activity.

Summary: AKT phosphorylates USP8 at Thr945 in the cytosol, stabilizing the USP8–NRDP1 regulatory pathway.

Reason: AKT phosphorylates USP8 at Thr945 in the cytosol, stabilizing the USP8–NRDP1 regulatory pathway. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT phosphorylates MDM2 at Ser166 and Ser188 in the cytosol, regulating MDM2 stability and subsequent signaling.

Reason: AKT phosphorylates MDM2 at Ser166 and Ser188 in the cytosol, regulating MDM2 stability and subsequent signaling. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT phosphorylates TSC2 at Ser939 and Thr1462 in the cytosol, inhibiting the TSC regulatory branch upstream of mTORC1.

Reason: AKT phosphorylates TSC2 at Ser939 and Thr1462 in the cytosol, inhibiting the TSC regulatory branch upstream of mTORC1. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT phosphorylates the IKK subunit CHUK at Thr23 in the cytosol.

Reason: AKT phosphorylates the IKK subunit CHUK at Thr23 in the cytosol. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT phosphorylates the cell-cycle inhibitors CDKN1A and CDKN1B in the cytosol.

Reason: AKT phosphorylates the cell-cycle inhibitors CDKN1A and CDKN1B in the cytosol. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT phosphorylates caspase-9 at Ser196 in the cytosol, inhibiting this apoptotic protease.

Reason: AKT phosphorylates caspase-9 at Ser196 in the cytosol, inhibiting this apoptotic protease. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT phosphorylates CREB1 at Ser133 in the nucleoplasm, linking PI3K signaling to CREB-dependent transcription.

Reason: AKT phosphorylates CREB1 at Ser133 in the nucleoplasm, linking PI3K signaling to CREB-dependent transcription. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: Nuclear AKT phosphorylates FOXO1, FOXO3 and FOXO4 at defined serine/threonine sites; the event explicitly distinguishes the less certain FOXO6 inference.

Reason: Nuclear AKT phosphorylates FOXO1, FOXO3 and FOXO4 at defined serine/threonine sites; the event explicitly distinguishes the less certain FOXO6 inference. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: The event models AKT phosphorylation of RPS6KB2 in the nucleoplasm; this is the nuclear S6 kinase substrate, not a transfer of its activity to AKT.

Reason: The event models AKT phosphorylation of RPS6KB2 in the nucleoplasm; this is the nuclear S6 kinase substrate, not a transfer of its activity to AKT. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: The event models nuclear AKT phosphorylation of NR4A1 but explicitly notes subsequent work favoring RSK/MSK as the physiological NR4A1 kinase.

Reason: The event models nuclear AKT phosphorylation of NR4A1 but explicitly notes subsequent work favoring RSK/MSK as the physiological NR4A1 kinase. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT phosphorylates AKT1S1/PRAS40 in the cytosol, relieving its inhibition of mTORC1.

Reason: AKT phosphorylates AKT1S1/PRAS40 in the cytosol, relieving its inhibition of mTORC1. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT catalyzes FOXO1 phosphorylation at Thr24, Ser256 and Ser319 in the nucleoplasm.

Reason: AKT catalyzes FOXO1 phosphorylation at Thr24, Ser256 and Ser319 in the nucleoplasm. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: The cancer event models cytosolic AKT1 E17K phosphorylation of BAD, retaining the normal AKT serine/threonine kinase chemistry.

Reason: The cancer event models cytosolic AKT1 E17K phosphorylation of BAD, retaining the normal AKT serine/threonine kinase chemistry. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT1 E17K retains cytosolic phosphorylation of GSK3, an inhibitory modification of that substrate.

Reason: AKT1 E17K retains cytosolic phosphorylation of GSK3, an inhibitory modification of that substrate. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT1 E17K phosphorylates CDKN1B; extension to CDKN1A is explicitly predicted rather than experimentally tested in this event.

Reason: AKT1 E17K phosphorylates CDKN1B; extension to CDKN1A is explicitly predicted rather than experimentally tested in this event. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: The event predicts cytosolic AKT1 E17K phosphorylation of PRAS40 from the established wild-type reaction; mutant-specific testing is not claimed.

Reason: The event predicts cytosolic AKT1 E17K phosphorylation of PRAS40 from the established wild-type reaction; mutant-specific testing is not claimed. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: The event predicts cytosolic AKT1 E17K phosphorylation of MDM2 from the established wild-type reaction; mutant-specific testing is not claimed.

Reason: The event predicts cytosolic AKT1 E17K phosphorylation of MDM2 from the established wild-type reaction; mutant-specific testing is not claimed. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: The event predicts cytosolic AKT1 E17K phosphorylation and inhibition of TSC2 from the established wild-type reaction.

Reason: The event predicts cytosolic AKT1 E17K phosphorylation and inhibition of TSC2 from the established wild-type reaction. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: The event predicts cytosolic AKT1 E17K phosphorylation of caspase-9 from the established wild-type reaction.

Reason: The event predicts cytosolic AKT1 E17K phosphorylation of caspase-9 from the established wild-type reaction. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: The event predicts nuclear AKT1 E17K phosphorylation of NR4A1; its wild-type counterpart also records uncertainty about the physiological NR4A1 kinase.

Reason: The event predicts nuclear AKT1 E17K phosphorylation of NR4A1; its wild-type counterpart also records uncertainty about the physiological NR4A1 kinase. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT1 E17K phosphorylates FOXO3; the model extends this to other FOXO proteins with explicit experimental limitations.

Reason: AKT1 E17K phosphorylates FOXO3; the model extends this to other FOXO proteins with explicit experimental limitations. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: The event predicts nuclear AKT1 E17K phosphorylation of CREB1 from the established wild-type reaction.

Reason: The event predicts nuclear AKT1 E17K phosphorylation of CREB1 from the established wild-type reaction. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: The event predicts nuclear AKT1 E17K phosphorylation of RPS6KB2 from the wild-type reaction.

Reason: The event predicts nuclear AKT1 E17K phosphorylation of RPS6KB2 from the wild-type reaction. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: The event predicts cytosolic AKT1 E17K phosphorylation of CHUK from the wild-type reaction.

Reason: The event predicts cytosolic AKT1 E17K phosphorylation of CHUK from the wild-type reaction. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT1/AKT2 phosphorylates CBY1 at Ser20 in a nuclear beta-catenin complex, enabling subsequent 14-3-3-dependent export.

Reason: AKT1/AKT2 phosphorylates CBY1 at Ser20 in a nuclear beta-catenin complex, enabling subsequent 14-3-3-dependent export. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT phosphorylates AKT1S1/PRAS40 at Thr246; the current model explicitly places the AKT catalyst in the cytosol and the mTORC1 substrate complex at the lysosomal membrane.

Reason: AKT phosphorylates AKT1S1/PRAS40 at Thr246; the current model explicitly places the AKT catalyst in the cytosol and the mTORC1 substrate complex at the lysosomal membrane. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT interacts with MAP3K8/Cot and phosphorylates Ser400 in cytosolic assays; Reactome explicitly limits the evidence to in-vitro and overexpression conditions.

Reason: AKT interacts with MAP3K8/Cot and phosphorylates Ser400 in cytosolic assays; Reactome explicitly limits the evidence to in-vitro and overexpression conditions. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT1 can phosphorylate the integrin beta3 cytoplasmic tail at Thr779; the modeled kinase entity is at the plasma membrane.

Reason: AKT1 can phosphorylate the integrin beta3 cytoplasmic tail at Thr779; the modeled kinase entity is at the plasma membrane. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT phosphorylates nuclear KAT6A at Thr369, preventing association with PML and reducing KAT6A-mediated TP53 acetylation.

Reason: AKT phosphorylates nuclear KAT6A at Thr369, preventing association with PML and reducing KAT6A-mediated TP53 acetylation. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT phosphorylates PHF20 at Ser291 in the nucleoplasm, regulating damage-induced TP53 stabilization.

Reason: AKT phosphorylates PHF20 at Ser291 in the nucleoplasm, regulating damage-induced TP53 stabilization. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT phosphorylates DENND1A/DENND1B in the cytosol, relieving their autoinhibition and promoting RAB35 activation.

Reason: AKT phosphorylates DENND1A/DENND1B in the cytosol, relieving their autoinhibition and promoting RAB35 activation. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT1 phosphorylates cytosolic MKRN1 at Ser109, stabilizing this ubiquitin ligase in an EGF-responsive regulatory circuit.

Reason: AKT1 phosphorylates cytosolic MKRN1 at Ser109, stabilizing this ubiquitin ligase in an EGF-responsive regulatory circuit. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT phosphorylates FOXO3 in the nucleoplasm downstream of estrogen/EGFR signaling, promoting FOXO3 nuclear export.

Reason: AKT phosphorylates FOXO3 in the nucleoplasm downstream of estrogen/EGFR signaling, promoting FOXO3 nuclear export. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: AKT phosphorylates FOXO3 in the nucleoplasm downstream of FLT3 signaling, promoting FOXO3 nuclear export.

Reason: AKT phosphorylates FOXO3 in the nucleoplasm downstream of FLT3 signaling, promoting FOXO3 nuclear export. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: This mixed-species reaction uses recombinant human AKT to phosphorylate recombinant mouse Bad at Ser136; the catalyst is human and the modeled location is cytosol.

Reason: This mixed-species reaction uses recombinant human AKT to phosphorylate recombinant mouse Bad at Ser136; the catalyst is human and the modeled location is cytosol. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: This mixed-species reaction uses recombinant human AKT1 to phosphorylate mouse Runx2-5 at Ser203, Thr205 and Thr207; the model places the catalyst in nucleoplasm.

Reason: This mixed-species reaction uses recombinant human AKT1 to phosphorylate mouse Runx2-5 at Ser203, Thr205 and Thr207; the model places the catalyst in nucleoplasm. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: The original TMCO3 study uses membrane fractionation and microscopy in HCC cells to show growth-factor-dependent AKT membrane recruitment (Figure 5).

Reason: The original TMCO3 study uses membrane fractionation and microscopy in HCC cells to show growth-factor-dependent AKT membrane recruitment (Figure 5). Retain plasma-membrane localization.

Summary: The TMCO3 study measures PI3K-dependent AKT activation and downstream signaling in HCC cells.

Reason: The TMCO3 study measures PI3K-dependent AKT activation and downstream signaling in HCC cells. AKT supplies the pathway kinase activity.

Summary: The recovered TMCO3 Results establish TMCO3-dependent AKT recruitment and activation.

Reason: The recovered TMCO3 Results establish TMCO3-dependent AKT recruitment and activation. The exact evidence that AKT1 itself positively regulates this pathway beyond serving as its activated effector remains unresolved; retain the separate pathway-participation annotation.

Summary: The original MOZ Results and Figure 3 test phosphorylation at Thr369, including T369A and recombinant Akt assays.

Reason: The original MOZ Results and Figure 3 test phosphorylation at Thr369, including T369A and recombinant Akt assays. Replace the serine-only activity with protein serine/threonine kinase activity to represent the demonstrated threonine chemistry. Live AmiGO lists GO:0106311 as an alternate ID of GO:0004674, so the canonical replacement already covers this threonine activity.

Proposed replacements: protein serine/threonine kinase activity

Summary: SIRT7-dependent FKBP51 deacetylation changes FKBP51–Akt–PHLPP interactions and Akt dephosphorylation.

Reason: SIRT7-dependent FKBP51 deacetylation changes FKBP51–Akt–PHLPP interactions and Akt dephosphorylation. This directly situates Akt as the regulated kinase in PI3K/Akt signaling.

Summary: The rat donor carries insulin-responsive Akt kinase and metabolic-signaling experiments.

Reason: The rat donor carries insulin-responsive Akt kinase and metabolic-signaling experiments. Human PKBalpha activation by insulin corroborates transfer of the receptor-signaling function.

Summary: The neurotransmission review explicitly describes PI3K-dependent activation of AKT isoforms and the AKT1 Thr308/Ser473 activation sites.

Reason: The neurotransmission review explicitly describes PI3K-dependent activation of AKT isoforms and the AKT1 Thr308/Ser473 activation sites. Retain central pathway participation, corroborated by primary PKBalpha activation experiments.

Summary: The recovered review describes a dopamine-D2-induced Akt–beta-arrestin-2–PP2A complex that decreases Akt activity and releases GSK3 from inhibition.

Reason: The recovered review describes a dopamine-D2-induced Akt–beta-arrestin-2–PP2A complex that decreases Akt activity and releases GSK3 from inhibition. Retain this neuronal receptor-signaling context; the scaffold is beta-arrestin-2.

Summary: The full source stimulates aortic endothelial cells by assembling sublytic C5b-9 from purified complement components.

Reason: The full source stimulates aortic endothelial cells by assembling sublytic C5b-9 from purified complement components. GO:0002430 specifically requires a complement component binding a complement receptor. The recovered mechanism supports complement-triggered Akt signaling but does not establish that receptor-mediated subtype.

Summary: Purified Akt phosphorylates human RGC-32 and the S45A/S47A mutant loses labeling.

Reason: Purified Akt phosphorylates human RGC-32 and the S45A/S47A mutant loses labeling. GO:0004712 requires serine/threonine AND tyrosine kinase chemistry, whereas these assays establish serine phosphorylation. Use GO:0004674 without claiming that all possible AKT tyrosine chemistry is excluded.

Proposed replacements: protein serine/threonine kinase activity

Summary: The RGC-32 study measures C5b-9-dependent Akt activation and direct Akt phosphorylation of RGC-32.

Reason: The RGC-32 study measures C5b-9-dependent Akt activation and direct Akt phosphorylation of RGC-32. Retain the PI3K/Akt signaling role.

Summary: Akt phosphorylates FBXO31 Ser33, which is required for recognition and degradation by APC/C.

Reason: Akt phosphorylates FBXO31 Ser33, which is required for recognition and degradation by APC/C. This is direct protein-serine phosphotransfer.

Summary: Akt-catalyzed FBXO31 Ser33 phosphorylation permits APC/C-dependent ubiquitination and degradation.

Reason: Akt-catalyzed FBXO31 Ser33 phosphorylation permits APC/C-dependent ubiquitination and degradation. Retain this regulatory step without assigning APC/C ligase activity to AKT1.

Summary: The review correctly identifies Akt as a serine/threonine kinase; independent primary substrate and kinetic experiments establish that core chemistry.

Reason: The review correctly identifies Akt as a serine/threonine kinase; independent primary substrate and kinetic experiments establish that core chemistry.

Summary: In UVA-exposed HaCaT keratinocytes, EGFR inhibition attenuates Akt/cyclin-D1 signaling and cell-cycle progression.

Reason: In UVA-exposed HaCaT keratinocytes, EGFR inhibition attenuates Akt/cyclin-D1 signaling and cell-cycle progression. Retain AKT as a downstream kinase in this receptor context.

Summary: The recovered PINK1 study shows mTORC2-dependent phosphorylation of Akt, while its coprecipitation experiments prominently concern PINK1 with rictor/SIN1.

Reason: The recovered PINK1 study shows mTORC2-dependent phosphorylation of Akt, while its coprecipitation experiments prominently concern PINK1 with rictor/SIN1. The particular physical kinase-binding pair underlying this Akt1 IPI row was not independently resolved.

Summary: The full PINK1 study reports reduced SH-SY5Y migration after Akt inhibitor treatment (Figure 6).

Reason: The full PINK1 study reports reduced SH-SY5Y migration after Akt inhibitor treatment (Figure 6). Retain the signaling contribution to cell motility in this assay context.

Summary: The UVA keratinocyte study uses PI3K/Akt inhibition and dominant-negative Akt to place AKT within the EGFR-driven signaling cascade.

Reason: The UVA keratinocyte study uses PI3K/Akt inhibition and dominant-negative Akt to place AKT within the EGFR-driven signaling cascade.

Summary: PKBalpha expression and insulin/IGF-1 stimulation regulate GSK3beta Ser9 phosphorylation in 293 cells.

Reason: PKBalpha expression and insulin/IGF-1 stimulation regulate GSK3beta Ser9 phosphorylation in 293 cells. This is a direct downstream step of the PI3K/Akt pathway.

Summary: Akt phosphorylation of EGR1 at S350/T309 promotes EGR1 sumoylation and PTEN transcription.

Reason: Akt phosphorylation of EGR1 at S350/T309 promotes EGR1 sumoylation and PTEN transcription. AKT performs the regulatory phosphorylation, while EGR1 supplies the DNA-binding transcriptional function.

Summary: Dominant-negative Akt or PI3K/Akt inhibition blocks UVA-induced cyclin-D1 accumulation and G1/S progression in HaCaT cells.

Reason: Dominant-negative Akt or PI3K/Akt inhibition blocks UVA-induced cyclin-D1 accumulation and G1/S progression in HaCaT cells. Retain this cell-cycle signaling context.

Summary: The PINK1 study connects Akt activation to protection of SH-SY5Y cells from apoptotic stress, including hydrogen peroxide.

Reason: The PINK1 study connects Akt activation to protection of SH-SY5Y cells from apoptotic stress, including hydrogen peroxide. Retain the neuronal stress-survival context with the source cell-line and inhibitor limitations.

Summary: The recovered Figure 5 uses immunoprecipitated mTORC2 to phosphorylate recombinant Akt and establishes functional enzyme-substrate engagement.

Reason: The recovered Figure 5 uses immunoprecipitated mTORC2 to phosphorylate recombinant Akt and establishes functional enzyme-substrate engagement. Retain contextual TORC2 binding with curator deference, without treating Akt as a constitutive mTORC2 subunit.

Summary: The GO-CAM attaches this cGAS process edge to PMID:12172553, while its cGAS substrate and inhibitory causal edges cite PMID:26440888.

Reason: The GO-CAM attaches this cGAS process edge to PMID:12172553, while its cGAS substrate and inhibitory causal edges cite PMID:26440888. The accessible 2002 source establishes TSC2/mTOR signaling, and its full text was not recovered. Preserve source-specific uncertainty rather than substituting the later cGAS evidence into the original identifier.

Summary: The MGI Akt1 donor is linked to direct PERK Thr799 phosphorylation and inhibition.

Reason: The MGI Akt1 donor is linked to direct PERK Thr799 phosphorylation and inhibition. The cached GO-CAM preserves this Akt-to-PERK regulatory step, supporting contextual transfer to human AKT1.

Summary: The recovered source includes MC3T3 preosteoblast Akt/PTEN signaling, so its vascular-smooth-muscle title does not exclude bone-cell experiments.

Reason: The recovered source includes MC3T3 preosteoblast Akt/PTEN signaling, so its vascular-smooth-muscle title does not exclude bone-cell experiments. However, the exact AKT1 osteoblast-differentiation endpoint underlying the IDA row was not recovered; signaling in preosteoblasts alone does not resolve differentiation.

Summary: The source reports a PKN1–Akt1 interaction that inhibits Akt signaling during B-cell regulation.

Reason: The source reports a PKN1–Akt1 interaction that inhibits Akt signaling during B-cell regulation. Retain the broad protein-complex location as contextual membership, without assigning a more specific unverified complex.

Summary: The study identifies Akt-dependent EphA2 Ser897 phosphorylation and loss of the ligand-independent motility effect with S897A.

Reason: The study identifies Akt-dependent EphA2 Ser897 phosphorylation and loss of the ligand-independent motility effect with S897A. Retain the demonstrated serine/threonine kinase chemistry.

Summary: The MICU1 study identifies Akt-dependent MICU1 Ser124 phosphorylation using phosphosite mutants and mitochondrial experiments.

Reason: The MICU1 study identifies Akt-dependent MICU1 Ser124 phosphorylation using phosphosite mutants and mitochondrial experiments. Retain kinase activity; its processing and calcium effects are substrate-dependent consequences.

Summary: The donor and MICU1 GO-CAM identify a rapamycin-responsive mitochondrial Akt pool.

Reason: The donor and MICU1 GO-CAM identify a rapamycin-responsive mitochondrial Akt pool. The original full study independently resolves predominantly intermembrane-space Akt in human-cell mitochondria by protease protection. Retain the treatment-associated compartment.

Summary: The donor-linked MICU1 study measures rapamycin-induced mitochondrial Akt accumulation and phosphorylation-dependent effects on MICU1.

Reason: The donor-linked MICU1 study measures rapamycin-induced mitochondrial Akt accumulation and phosphorylation-dependent effects on MICU1. This supports a cellular drug-response context, not a new intrinsic drug-binding activity.

Summary: The donor-linked MICU1 study reports phosphorylation-dependent impairment of MICU1 processing.

Reason: The donor-linked MICU1 study reports phosphorylation-dependent impairment of MICU1 processing. Akt performs the regulatory phosphorylation step; it is not the protease responsible for protein maturation. Retain this substrate-specific negative regulation.

Summary: AKT1 phosphorylates NOS3 Ser1177 at the plasma membrane during endothelial flow signaling.

Reason: AKT1 phosphorylates NOS3 Ser1177 at the plasma membrane during endothelial flow signaling. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: The original study identifies PKB as the insulin-stimulated kinase that phosphorylates and inactivates GSK3.

Reason: The original study identifies PKB as the insulin-stimulated kinase that phosphorylates and inactivates GSK3. This establishes protein serine/threonine kinase activity.

Summary: PKB phosphorylates HIF-3alpha1 Ser524, and mutation of that site alters insulin-dependent migration.

Reason: PKB phosphorylates HIF-3alpha1 Ser524, and mutation of that site alters insulin-dependent migration. Retain this substrate-mediated motility response.

Summary: Mitochondrial folding stress causes phosphorylation of cytosolic AKT1 at Ser473; the model does not place AKT1 inside the mitochondrial intermembrane space.

Reason: Mitochondrial folding stress causes phosphorylation of cytosolic AKT1 at Ser473; the model does not place AKT1 inside the mitochondrial intermembrane space. Retain the compartment assigned to the AKT-containing participant; this does not imply exclusive localization.

Summary: Activated cytosolic AKT1 phosphorylates ESR1 at Ser167 in a mitochondrial stress-response signaling branch.

Reason: Activated cytosolic AKT1 phosphorylates ESR1 at Ser167 in a mitochondrial stress-response signaling branch. Retain the compartment assigned to the AKT-containing participant; this does not imply exclusive localization.

Summary: Activated cytosolic AKT1 phosphorylates ESR1 at Ser167 in a mitochondrial stress-response signaling branch.

Reason: Activated cytosolic AKT1 phosphorylates ESR1 at Ser167 in a mitochondrial stress-response signaling branch. Retain the supported catalytic activity; the modeled substrate context does not imply a separate activity of the substrate or its other partners.

Summary: Akt directly phosphorylates human cGAS Ser305 and mouse cGAS Ser291, suppressing cGAMP production.

Reason: Akt directly phosphorylates human cGAS Ser305 and mouse cGAS Ser291, suppressing cGAMP production. Retain negative cGAS/STING signaling as a substrate-specific immune-regulatory role.

Summary: IL-18 activates PI3K/Akt-dependent signaling in human saphenous-vein smooth-muscle cells, including regulation of GSK3beta and WISP1.

Reason: IL-18 activates PI3K/Akt-dependent signaling in human saphenous-vein smooth-muscle cells, including regulation of GSK3beta and WISP1. Retain pathway kinase participation.

Summary: The ciliogenesis study places Akt phosphorylation of WDR44 in the Rab11-effector switch.

Reason: The ciliogenesis study places Akt phosphorylation of WDR44 in the Rab11-effector switch. Protein serine/threonine kinase activity expresses the resolved chemistry more precisely than generic protein kinase activity.

Proposed replacements: protein serine/threonine kinase activity

Summary: Akt-dependent WDR44 phosphorylation stabilizes Rab11–WDR44 association, and the phosphomimetic inhibits ciliogenesis.

Reason: Akt-dependent WDR44 phosphorylation stabilizes Rab11–WDR44 association, and the phosphomimetic inhibits ciliogenesis. AKT supplies a regulatory phosphorylation step rather than the structural cilium machinery.

Summary: AKT-dependent USP4 phosphorylation links EGF stimulation to Rheb deubiquitination.

Reason: AKT-dependent USP4 phosphorylation links EGF stimulation to Rheb deubiquitination. Retain the demonstrated kinase activity, distinct from USP4 deubiquitinase activity.

Summary: The Rheb study traces EGF stimulation through AKT-dependent USP4 phosphorylation.

Reason: The Rheb study traces EGF stimulation through AKT-dependent USP4 phosphorylation. Retain this stimulus-response context.

Summary: AKT phosphorylation of USP4 promotes Rheb deubiquitination and release from the TSC complex, activating mTORC1.

Reason: AKT phosphorylation of USP4 promotes Rheb deubiquitination and release from the TSC complex, activating mTORC1. This is a mechanistic branch of the core growth-factor/Akt/mTOR network.

Summary: Akt phosphorylates TSC2 to change the TSC complex association with lysosomes.

Reason: Akt phosphorylates TSC2 to change the TSC complex association with lysosomes. Retain the catalytic serine/threonine activity.

Summary: Insulin-induced TSC-complex dissociation requires Akt-mediated TSC2 phosphorylation.

Reason: Insulin-induced TSC-complex dissociation requires Akt-mediated TSC2 phosphorylation. Retain this hormone-response signaling context.

Summary: Akt-dependent TSC2 phosphorylation displaces the inhibitory TSC complex from the lysosomal surface.

Reason: Akt-dependent TSC2 phosphorylation displaces the inhibitory TSC complex from the lysosomal surface. This supports negative regulation of that substrate-complex localization.

Summary: The study links Akt phosphorylation of TSC2 to lysosomal TSC-complex dissociation and Rheb-dependent mTORC1 activation.

Reason: The study links Akt phosphorylation of TSC2 to lysosomal TSC-complex dissociation and Rheb-dependent mTORC1 activation. Retain this central signaling output.

Summary: The source directly reports Akt phosphorylation and inhibition of TSC2.

Reason: The source directly reports Akt phosphorylation and inhibition of TSC2. This supports the core protein serine/threonine kinase activity.

Summary: Membrane-associated Akt participates in the spatial TSC/mTOR signaling mechanism.

Reason: Membrane-associated Akt participates in the spatial TSC/mTOR signaling mechanism. Retain the broad experimentally curated membrane compartment; the broad location does not become an overannotation merely because other rows resolve plasma membrane.

Summary: Akt-dependent TSC2 phosphorylation is stimulated in the insulin-signaling mechanism described by the source.

Reason: Akt-dependent TSC2 phosphorylation is stimulated in the insulin-signaling mechanism described by the source. Retain this cellular response without inferring all metabolic endpoints.

Summary: Phosphorylation of TSC2 by Akt relieves TSC-mediated suppression of mTOR signaling.

Reason: Phosphorylation of TSC2 by Akt relieves TSC-mediated suppression of mTOR signaling. AKT supplies the regulatory catalytic step in this central growth-control branch.

Summary: Akt/PKB phosphorylates PRAS40 after insulin stimulation and relieves its inhibition of mTORC1.

Reason: Akt/PKB phosphorylates PRAS40 after insulin stimulation and relieves its inhibition of mTORC1. Retain the protein serine/threonine kinase activity.

Summary: Insulin induces Akt-dependent PRAS40 phosphorylation.

Reason: Insulin induces Akt-dependent PRAS40 phosphorylation. Retain this ligand-response context.

Summary: Akt-catalyzed PRAS40 phosphorylation prevents PRAS40-mediated inhibition of mTORC1.

Reason: Akt-catalyzed PRAS40 phosphorylation prevents PRAS40-mediated inhibition of mTORC1. The kinase therefore directly performs a regulatory step in mTORC1 activation.

Summary: The DEPDC5 study tests AKT-sensitive phosphosites and phospho-inactive mutants.

Reason: The DEPDC5 study tests AKT-sensitive phosphosites and phospho-inactive mutants. Retain kinase chemistry while distinguishing AKT from the separately assayed Pim kinases.

Summary: AKT-dependent DEPDC5 phosphorylation relieves GATOR1-mediated suppression of mTORC1.

Reason: AKT-dependent DEPDC5 phosphorylation relieves GATOR1-mediated suppression of mTORC1. Retain this substrate-specific route within central growth signaling.

Summary: Akt phosphorylates Rac1 Ser71 in the source mechanism; the S71A mutant resists FBXL19-mediated disposal.

Reason: Akt phosphorylates Rac1 Ser71 in the source mechanism; the S71A mutant resists FBXL19-mediated disposal. Retain protein-serine phosphotransfer.

Summary: Rac1 Ser71 phosphorylation by Akt permits FBXL19-dependent ubiquitination and proteasomal degradation.

Reason: Rac1 Ser71 phosphorylation by Akt permits FBXL19-dependent ubiquitination and proteasomal degradation. Retain the regulatory step; FBXL19 supplies substrate recognition for the ubiquitin ligase.

Summary: PKBalpha directly phosphorylates METTL1 Ser27 in vitro and during IGF-1 signaling.

Reason: PKBalpha directly phosphorylates METTL1 Ser27 in vitro and during IGF-1 signaling. Retain the established serine/threonine kinase chemistry.

Summary: METTL1 Ser27 phosphorylation inhibits its methyltransferase function.

Reason: METTL1 Ser27 phosphorylation inhibits its methyltransferase function. Akt thus regulates tRNA modification through phosphorylation; it does not itself methylate tRNA.

Summary: The recovered primary imaging experiment uses EGFP-AktPH in NIH3T3 cells as a phosphoinositide reporter.

Reason: The recovered primary imaging experiment uses EGFP-AktPH in NIH3T3 cells as a phosphoinositide reporter. It does not independently resolve this cell-cortex assignment to full-length human AKT1; retain uncertainty in the NAS inference.

Summary: The rat donor directly phosphorylates protein substrates, including GSK3, and human AKT1 kinetics independently establish the same ATP-dependent serine/threonine chemistry.

Reason: The rat donor directly phosphorylates protein substrates, including GSK3, and human AKT1 kinetics independently establish the same ATP-dependent serine/threonine chemistry.

Summary: The source abstract positively identifies IRS-2/Akt1 control of lipid metabolism in human skeletal muscle.

Reason: The source abstract positively identifies IRS-2/Akt1 control of lipid metabolism in human skeletal muscle. The full palmitate-import assay and exact negative direction were not recovered, so retain uncertainty at this precise endpoint.

Summary: The source distinguishes Akt2-dependent glucose metabolism from Akt1-dependent lipid metabolism in human skeletal muscle.

Reason: The source distinguishes Akt2-dependent glucose metabolism from Akt1-dependent lipid metabolism in human skeletal muscle. Without the full assay data, the particular positive AKT1 glucose-metabolism annotation remains unresolved; this is not a blanket denial of AKT1 metabolic signaling.

Summary: Rat Akt1 carries IPI annotations from PMID:8524413 with GSK3alpha/beta.

Reason: Rat Akt1 P47196 carries the traced PMID:8524413 IPI assertion with GSK3alpha/beta. The conserved positive evidence is GSK3 inactivation by phosphorylation, independently corroborated by PKBalpha-dependent GSK3beta Ser9 phosphorylation in PMID:9373175. GO:0030291 inherits GO:0140678 and GO:0098772, whose definitions restrict regulation to non-covalent target binding without covalent modification. Replace this MF with the established kinase activity. The inhibitory outcome belongs to a regulation BP, such as GO:0006469, rather than this non-covalent inhibitor MF; no additional NEW annotation is needed to repeat existing kinase coverage.

Proposed replacements: protein serine/threonine kinase activity

Summary: The review describes Akt-mediated inhibitory phosphorylation of GSK3, corroborated by primary PKBalpha/GSK3beta Ser9 experiments.

Reason: This review provides Akt/GSK3 signaling context; primary PMID:9373175 demonstrates PKBalpha-dependent GSK3beta Ser9 phosphorylation and inactivation. That is covalent kinase regulation. GO:0030291 inherits the non-covalent mechanism restriction of GO:0140678 and GO:0098772, so replace it with protein serine/threonine kinase activity. Negative regulation of protein kinase activity (GO:0006469) describes the biological outcome separately; retain the existing kinase coverage without adding redundant NEW assertions.

Proposed replacements: protein serine/threonine kinase activity

Summary: The accessible study supports Akt1-dependent lipid regulation but does not expose the complete beta-oxidation measurements.

Reason: The accessible study supports Akt1-dependent lipid regulation but does not expose the complete beta-oxidation measurements. The precise negative oxidation effect remains source-limited rather than rejected from an abstract.

Summary: The siRNA study directly tests Akt1 within insulin signaling in human skeletal muscle and identifies its lipid-metabolic role.

Reason: The siRNA study directly tests Akt1 within insulin signaling in human skeletal muscle and identifies its lipid-metabolic role. Retain cellular response to insulin without asserting Akt1 controls every glucose endpoint in that system.

Summary: The full glycogen-synthesis data were not recovered from the human skeletal-muscle isoform study.

Reason: The full glycogen-synthesis data were not recovered from the human skeletal-muscle isoform study. Its abstract emphasizes Akt2 dependence of glucose metabolism, so the exact AKT1 glycogen claim needs source-level resolution.

Summary: The full glucose-uptake assay was not recovered.

Reason: The full glucose-uptake assay was not recovered. The study distinguishes Akt isoforms in human muscle; retain uncertainty for this AKT1-specific positive import annotation rather than inferring it from pan-Akt signaling.

Summary: The Ft1 study measures regulation of PKB catalytic activity and downstream GSK3/NFAT signaling.

Reason: The Ft1 study measures regulation of PKB catalytic activity and downstream GSK3/NFAT signaling. Retain the serine/threonine kinase activity.

Summary: Akt phosphorylates the cytoplasmic DNA-sensing enzyme cGAS; retain the experimentally curated cytoplasmic location in that source context.

Reason: Akt phosphorylates the cytoplasmic DNA-sensing enzyme cGAS; retain the experimentally curated cytoplasmic location in that source context.

Summary: Sestrin2 binds the Akt PH domain and promotes membrane recruitment while GATOR2 connects the Sestrin2 pathway to mTORC2. Akt is the recruited kinase; the bridging function is not assigned to Akt from this association.

Reason: Sestrin2 binds the Akt PH domain and promotes membrane recruitment while GATOR2 connects the Sestrin2 pathway to mTORC2. Akt is the recruited kinase; the bridging function is not assigned to Akt from this association. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: AKT phosphorylates CASTOR1 Ser14, altering its binding to RNF167 and MIOS.

Reason: AKT phosphorylates CASTOR1 Ser14, altering its binding to RNF167 and MIOS. This is direct protein-serine kinase chemistry.

Summary: AKT phosphorylation promotes CASTOR1 turnover and releases inhibition of mTORC1.

Reason: AKT phosphorylation promotes CASTOR1 turnover and releases inhibition of mTORC1. This is an experimentally defined kinase-mediated growth-signaling mechanism.

Summary: AKT phosphorylation of PCK1 Ser90 promotes PCK1 relocation from cytosol to ER in HCC cells.

Reason: AKT phosphorylation of PCK1 Ser90 promotes PCK1 relocation from cytosol to ER in HCC cells. Retain regulation of the substrate location, not an inferred ER location for all AKT1.

Summary: Akt directly phosphorylates the cGAS enzymatic domain at Ser291/Ser305 in mouse/human proteins.

Reason: Akt directly phosphorylates the cGAS enzymatic domain at Ser291/Ser305 in mouse/human proteins. Retain the catalytic activity separately from its immune consequence.

Summary: The source identifies a TMEM175–Akt channel complex and kinase-independent channel opening by Akt conformational changes. That informative channel-activator function already has a separate annotation from this same source.

Reason: The source identifies a TMEM175–Akt channel complex and kinase-independent channel opening by Akt conformational changes. That informative channel-activator function already has a separate annotation from this same source. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.

Summary: Growth factors activate the AKT–TMEM175 lysosomal channel complex.

Reason: Growth factors activate the AKT–TMEM175 lysosomal channel complex. Retain this organelle response, distinguishing conformational channel gating from the canonical Akt substrate-phosphorylation mechanism.

Summary: The full study tests human AKT1 with TMEM175 by patch clamp, catalytic mutants and recombinant protein.

Reason: The full study tests human AKT1 with TMEM175 by patch clamp, catalytic mutants and recombinant protein. Kinase-inactive AKT1 can support channel current, establishing a noncatalytic potassium-channel-activator function in this lysosomal complex.

Summary: The source places Akt downstream of the PI3Kbeta branch of S1P-induced endothelial migration.

Reason: The source places Akt downstream of the PI3Kbeta branch of S1P-induced endothelial migration. Retain this receptor-signaling context without making AKT the S1P receptor.

Summary: Human and mouse endothelial experiments identify an Akt-sensitive migratory branch downstream of S1P/PI3Kbeta, distinct from the Rac1 and eNOS branches.

Reason: Human and mouse endothelial experiments identify an Akt-sensitive migratory branch downstream of S1P/PI3Kbeta, distinct from the Rac1 and eNOS branches. Retain the specific vascular motility role.

Summary: The full imaging source visualizes an isolated Akt PH-domain lipid reporter at protrusions.

Reason: The full imaging source visualizes an isolated Akt PH-domain lipid reporter at protrusions. The exact inference to full-length human AKT1 in lamellipodia remains unresolved.

Summary: The fibroblast study inhibits PI3K and tracks an Akt PH-domain reporter.

Reason: The fibroblast study inhibits PI3K and tracks an Akt PH-domain reporter. The recovered source establishes phosphoinositide dynamics and migration but does not independently resolve an AKT1 catalytic contribution to that migration assay.

Summary: AKT directly phosphorylates PCK1 Ser90 in human HCC cells.

Reason: AKT directly phosphorylates PCK1 Ser90 in human HCC cells. PCK1 subsequently supplies the separate INSIG-directed kinase activity; the two enzymes are distinguished.

Summary: AKT phosphorylation triggers the PCK1–INSIG–SREBP lipogenic signaling sequence in HCC cells.

Reason: AKT phosphorylation triggers the PCK1–INSIG–SREBP lipogenic signaling sequence in HCC cells. Retain regulation of lipid synthesis without assigning fatty-acid synthetic chemistry to AKT.

Summary: The full ATP2B1-silencing study measures Akt–calmodulin coprecipitation after insulin stimulation in HUVECs (Figure 3C).

Reason: The full ATP2B1-silencing study measures Akt–calmodulin coprecipitation after insulin stimulation in HUVECs (Figure 3C). Retain the contextual binding activity; W7 inhibition alone is not the sole evidence, and the source does not map a purified binding interface.

Summary: The accessible source reports endothelial migration/proliferation and active-AKT1 rescue in the ADTRP network.

Reason: The accessible source reports endothelial migration/proliferation and active-AKT1 rescue in the ADTRP network. The full sprouting-specific assay was not recovered, so the narrower angiogenic-migration term remains unresolved.

Summary: The ADTRP/PIK3R3 pathway activates AKT and increases MIA3/TANGO1 expression.

Reason: The ADTRP/PIK3R3 pathway activates AKT and increases MIA3/TANGO1 expression. Retain this gene-expression signaling outcome without assigning transcription-factor activity to AKT1.

Summary: Constitutively active AKT1 rescues endothelial phenotypes following ADTRP loss, within the defined PIK3R3/AKT/MIA3 signaling cascade.

Reason: Constitutively active AKT1 rescues endothelial phenotypes following ADTRP loss, within the defined PIK3R3/AKT/MIA3 signaling cascade. Retain central pathway participation.

Summary: The study tests oxidized-LDL-dependent endothelial responses and rescue by active AKT1.

Reason: The study tests oxidized-LDL-dependent endothelial responses and rescue by active AKT1. Retain this lipid-stimulus response in the vascular experimental context.

Summary: Active AKT1 reverses the increased monocyte–endothelial adhesion caused by ADTRP depletion.

Reason: Active AKT1 reverses the increased monocyte–endothelial adhesion caused by ADTRP depletion. Retain signaling-mediated negative regulation of leukocyte adhesion, not a direct adhesion-receptor function.

Summary: The accessible source explicitly describes monocyte transendothelial migration, whereas this term specifies lymphocytes.

Reason: The accessible source explicitly describes monocyte transendothelial migration, whereas this term specifies lymphocytes. The complete cellular assay set was not recovered; preserve uncertainty rather than declaring a cell-type miscitation from the abstract alone.

Summary: The donor-linked Akt/CHIP study shows that lowering Akt reduces CHIP expression and includes Akt1-knockout mouse evidence.

Reason: The donor-linked Akt/CHIP study shows that lowering Akt reduces CHIP expression and includes Akt1-knockout mouse evidence. Retain this feedback effect on gene expression; the precise human transfer remains ortholog-based.

Summary: Akt limits CHIP-dependent tau ubiquitination through chaperone-client competition/regulation and kinase effects.

Reason: Akt limits CHIP-dependent tau ubiquitination through chaperone-client competition/regulation and kinase effects. Retain the measured negative ubiquitination outcome without calling AKT1 a deubiquitinase.

Summary: The tau review places Akt among protein kinases regulating phosphorylation.

Reason: The tau review places Akt among protein kinases regulating phosphorylation. Independently established AKT1 enzyme chemistry supports retaining the NAS serine/threonine kinase annotation; the review is not treated as a new direct assay.

Summary: BSTA association promotes mTORC2-mediated Akt1 Ser473 phosphorylation and subsequent adipogenic signaling. Akt1 is the recruited substrate of the BSTA/mTORC2 activation mechanism.

Reason: BSTA association promotes mTORC2-mediated Akt1 Ser473 phosphorylation and subsequent adipogenic signaling. Akt1 is the recruited substrate of the BSTA/mTORC2 activation mechanism. Remove the uninformative generic protein-binding assertion without denying the reported interaction or resolving an assay limitation by assumption.