Akt1 encodes RAC-alpha serine/threonine-protein kinase (protein kinase B alpha, PKBalpha), an AGC-family kinase with an N-terminal pleckstrin homology (PH) domain, a central catalytic domain and a C-terminal regulatory tail. Downstream of growth factor and insulin receptors, PI3K-generated PI(3,4,5)P3 binds the PH domain and recruits Akt1 to the plasma membrane, where phosphorylation at Thr-308 by PDK1 and Ser-473 by mTORC2 activates it. Active Akt1 phosphorylates serine/threonine residues on many substrates, including GSK3, FOXO transcription factors, TSC2, PDE3B and BAD, thereby mediating insulin effects on glucose uptake, glycogen and protein synthesis, and promoting cell survival, growth and proliferation. It is mainly cytoplasmic and can also translocate to the nucleus and mitochondria. In rat cells and tissues it is activated by insulin in adipocytes and skeletal muscle, by NGF in PC12 cells and by IGF-1 in neurons.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA (PAINT) cytoplasm, is_active_in, placed on the AKT ancestral node. AKT1 is predominantly cytoplasmic in unstimulated cells, and rat Akt1 sits within that clade with no evidence of divergence. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 Cytoplasm {ECO:0000250|UniProtKB:P31750} |
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PAINT) protein serine/threonine kinase activity placed on the AGC kinase ancestral node; rat Akt1 retains the conserved catalytic domain, and the activity is directly supported by rat IDA rows. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: UniProtKB:P47196 AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis file:rat/Akt1/Akt1-deep-research-falcon.md AKT1 catalyzes **ATP-dependent phosphorylation of serine/threonine residues** in protein substrates (EC **2.7.11.1**, protein-serine/threonine kinase). |
| GO:0035556 intracellular signal transduction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA (PAINT) intracellular signal transduction inherited across the AGC kinase family. Correct but very broad for AKT1, whose specific pathway roles are captured by the PI3K/PKB and insulin signaling terms. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) |
| GO:0043066 negative regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA (PAINT) negative regulation of apoptotic process placed on the AKT node. Pro-survival signaling via phosphorylation of apoptotic regulators is a conserved AKT output. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 AKT also regulates cell survival via the phosphorylation of MAP3K5 file:rat/Akt1/Akt1-deep-research-falcon.md Activated AKT1 phosphorylates substrates including **GSK3** and **FOXO1/3a**, thereby promoting cell survival, proliferation, metabolism, and anabolic growth programs. |
| GO:0008286 insulin receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PAINT) insulin receptor signaling pathway placed on the AKT node. Rat Akt1 is inside the clade and rat IMP/IDA rows support the role directly. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: UniProtKB:P47196 Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) file:rat/Akt1/Akt1-deep-research-falcon.md central signaling node downstream of growth factor/insulin pathways, regulating survival, growth, metabolism |
| GO:0043536 positive regulation of blood vessel endothelial cell migration | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA (PAINT) positive regulation of blood vessel endothelial cell migration placed on the AKT node; AKT signaling promotes endothelial migration in angiogenesis contexts. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: IEA (InterPro2GO) protein kinase activity from the protein kinase domain signature. Correct but less precise than protein serine/threonine kinase activity. Reason: InterPro2GO maps the protein kinase domain signature to the generic parent term; the catalytic activity of AKT1 is serine/threonine-specific, so the more precise child term GO:0004674 should be used. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: UniProtKB:P47196 This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA (ARBA/InterPro/EC mapping) protein serine/threonine kinase activity. Consistent with the conserved AGC kinase domain and with rat experimental data. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: UniProtKB:P47196 Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) |
| GO:0005080 protein kinase C binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Rat and mammalian evidence supports a physical association with specific protein kinase C family members, but this is a context-dependent interaction rather than a core defining function of AKT1. Reason: Keep as a real but non-core interaction annotation. Supporting Evidence: UniProtKB:P47196 GO; GO:0005080; F:protein kinase C binding; IPI:RGD. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: IEA ATP binding from the kinase domain; ATP is the phosphate donor for AKT1 catalysis. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. GOA no longer carries this row (retired at the 2026 refresh). Supporting Evidence: UniProtKB:P47196 GO; GO:0005524; F:ATP binding; IDA:RGD. file:rat/Akt1/Akt1-deep-research-falcon.md transfers phosphate from ATP to **Ser/Thr residues on protein substrates** |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA nucleus from the UniProt subcellular location mapping. The activated kinase translocates to the nucleus; rat IDA support exists (PMID:20605787). Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 the activated form translocates to the nucleus file:rat/Akt1/Akt1-deep-research-falcon.md AKT1 is largely **cytosolic (and can be nuclear) in quiescent cells**, but active signaling is concentrated at **membrane-associated compartments**, especially the **plasma membrane** |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA cytoplasm from the UniProt subcellular location mapping. AKT1 is predominantly cytoplasmic in unstimulated cells. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 Cytoplasm {ECO:0000250|UniProtKB:P31750} |
| GO:0005758 mitochondrial intermembrane space | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA mitochondrial intermembrane space from the UniProt subcellular location mapping, based on mouse Akt1 localization after rapamycin treatment. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 Also localizes to mitochondrial intermembrane space in response to rapamycin treatment |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA plasma membrane from the UniProt subcellular location mapping (cell membrane, PubMed:9228007). AKT1 is recruited to the plasma membrane via PH-domain binding of PI(3,4,5)P3. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 Cell membrane {ECO:0000269|PubMed:9228007} file:rat/Akt1/Akt1-deep-research-falcon.md growth factor stimulation triggers **PH-domain-dependent recruitment to membranes** enriched for PIP3/PI(3,4)P2 |
| GO:0010765 positive regulation of sodium ion transport | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA (ARBA) positive regulation of sodium ion transport. Rat IMP evidence (PMID:17715136) shows Akt mediates insulin effects on epithelial sodium channels via Nedd4-2. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0010765; P:positive regulation of sodium ion transport; IMP:MGI. |
| GO:0032869 cellular response to insulin stimulus | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA (ARBA) cellular response to insulin stimulus. AKT1 is a central effector of insulin action; rat IDA/IMP rows support this. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: IEA (Rhea mapping) protein serine kinase activity, from the UniProt catalytic activity annotation (Rhea:17989). Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: UniProtKB:P47196 Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) file:rat/Akt1/Akt1-deep-research-falcon.md increased phosphorylation activity toward substrates such as **GSK3** and **FOXO1/3a** |
| GO:0005515 protein binding | IPI PMID:16362038 Novel roles of Akt and mTOR in suppressing TGF-beta/ALK5-med... | REMOVE | Summary: IPI protein binding with Smad2 (O70436) from a study of Akt suppression of TGF-beta/Smad3 signaling. The abstract shows Akt acts on Smad3 (not Smad2) through its kinase activity and mTOR rather than by physical sequestration. Reason: Generic protein binding is uninformative and the paper does not support a more specific molecular function for an Akt1-Smad2 interaction; the functional effect is captured by kinase activity terms. Removal does not mean the reported interaction is false. Supporting Evidence: PMID:16362038 Wild-type and myristoylated Akts (Akt(WT) and Akt(Myr)) suppress TGF-beta-induced phospho-activation of S3 but not Smad2 (S2) |
| GO:0005515 protein binding | IPI PMID:16642037 Nuclear Akt associates with PKC-phosphorylated Ebp1, prevent... | REMOVE | Summary: IPI protein binding from a PC12 study showing that phosphorylated nuclear Akt binds PKC-phosphorylated Ebp1 and enhances its anti-apoptotic action independently of Akt kinase activity. The WITH partner recorded by GOA is Q63369 (Nfkb1 in the UniProt interaction list), which the abstract does not mention. Reason: Generic protein binding is uninformative, and neither the Ebp1 interaction nor the recorded Nfkb1 partner supports a more specific Akt1 molecular function from the available abstract. Removal does not mean the reported interaction is false. Supporting Evidence: PMID:16642037 phosphorylated nuclear but not cytoplasmic Akt interacts with Ebp1 and enhances its antiapoptotic action independent of Akt kinase activity |
| GO:0005515 protein binding | IPI PMID:20488185 Glyceraldehyde-3-phosphate dehydrogenase interacts with phos... | REMOVE | Summary: IPI protein binding with GAPDH (P04797): insulin induces association of phosphorylated Akt with phosphorylated GAPDH in rat cardiac muscle and H9c2 cells. Reason: Generic protein binding is uninformative; the association is a kinase/substrate-type interaction that does not define a separate Akt1 molecular function. Removal does not mean the reported interaction is false. Supporting Evidence: PMID:20488185 increase in Akt and GAPDH phosporylation and induction of their association were both observed after insulin stimulation |
| GO:0042802 identical protein binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0042802; F:identical protein binding; ISO:RGD. |
| GO:0042307 positive regulation of protein import into nucleus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis (PubMed:9228007, PubMed:11882383, PubMed:21432781, PubMed:21620960). |
| GO:0005654 nucleoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0005654; C:nucleoplasm; ISO:RGD. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-RNO-198601 | ACCEPT | Summary: Reactome TAS protein serine/threonine kinase activity from the rat-inferred AKT phosphorylation reactions. Consistent with rat and mammalian experimental data. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: UniProtKB:P47196 This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates |
| GO:0005886 plasma membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1 and human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 Cell membrane {ECO:0000269|PubMed:9228007} |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term carries direct experimental support (IDA PMID:40285646). The biology is real, but AKT1 is itself the effector kinase of the PI3K/AKT cascade, so a 'positive regulation of' term for its own pathway labels the executing component as an upstream regulator. Reason: The donor evidence is experimental, so source weakness is not the issue. The scoping is: annotating the pathway's central effector kinase as a positive regulator of PI3K/AKT signal transduction conflates effector with regulator, and as a rat gene-level transfer the self-referential pathway-regulation claim adds over-annotation rather than an informative function. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IDA PMID:40285646. The experiment supports the human annotation; the transfer concern is term scoping (AKT1 is the pathway's own effector kinase), not source weakness. Supporting Evidence: UniProtKB:P47196 AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis (PubMed:9228007, PubMed:11882383, PubMed:21432781, PubMed:21620960). |
| GO:0106310 protein serine kinase activity | ISO GO_REF:0000121 | ACCEPT | Summary: The rat ISO traces to mouse Akt1 and human AKT1. The donor annotation has experimental support and represents a conserved core kinase or PI3K/insulin-signaling function. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: UniProtKB:P47196 Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0007224 smoothened signaling pathway | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IMP (PMID:31305241). The donor evidence is experimental, but it records a Hedgehog/Smoothened-pathway readout from an ARHGAP36 study, in which AKT is a signalling input rather than core Smoothened-pathway machinery. Reason: Re-reviewed 2026-10-17: A Hedgehog/Smoothened-pathway readout from an ARHGAP36 study, in which AKT is a signalling input rather than core Smoothened-pathway machinery (IMP, PMID:31305241). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IMP from PMID:31305241, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis (PubMed:9228007, PubMed:11882383, PubMed:21432781, PubMed:21620960). |
| GO:0021525 lateral motor column neuron differentiation | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IMP (PMID:31305241). The donor evidence is experimental, but it records a neuronal-subtype (lateral motor column) differentiation outcome from the same ARHGAP36/Shh study. Reason: Re-reviewed 2026-10-17: A neuronal-subtype (lateral motor column) differentiation outcome from the same ARHGAP36/Shh study (IMP, PMID:31305241). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IMP from PMID:31305241, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis (PubMed:9228007, PubMed:11882383, PubMed:21432781, PubMed:21620960). |
| GO:0050821 protein stabilization | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, whose term rests on IMP (PMID:31305241): AKT stimulates Shh activity in developing motor neurons by stabilising the ARHGAP36 protein. Reason: Re-reviewed 2026-10-17: protein stabilization is not a tissue context, so CONTEXT_OR_TISSUE_MISMATCH was the wrong label. The donor evidence is experimental and nothing argues against it in rat. But the term records the downstream effect of AKT1 on a single substrate's stability; the activity is the phosphorylation. Flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IMP from PMID:31305241, so the donor annotation is experimentally grounded. No reason to think rat differs; the term is a single-substrate downstream effect. Supporting Evidence: PMID:31305241 AKT stimulates the Shh activity to induce LMC MNs through the stabilization of ARHGAP36 proteins |
| GO:0010467 gene expression | ISO GO_REF:0000121 | REMOVE | Summary: The rat ISO traces to mouse Akt1 IMP (PMID:12851395, PMID:31272455), phenotype studies in which loss of Akt signalling changed expression readouts. Reason: Re-reviewed 2026-10-17: the objection is participation, not context. Gene expression is executed by the transcription and translation machinery; AKT1 regulates it from outside by phosphorylating transcription factors such as the FOXO family. A kinase does not perform any step of gene expression, and the defensible regulatory claims are carried by the positive and negative regulation of gene expression rows on this gene, which are kept, although flagged as over-annotation for granularity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS SOURCE BUT NOT TARGET Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IMP from PMID:12851395, PMID:31272455, so the donor annotation is experimentally grounded. The experiments are sound; the objection is that the bare process term casts a regulator as a participant. Supporting Evidence: UniProtKB:P47196 AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization |
| GO:0008286 insulin receptor signaling pathway | IMP PMID:10454575 Insulin-induced phosphorylation and activation of cyclic nuc... | ACCEPT | Summary: IMP (PMID:10454575): a dominant-negative Akt blocks insulin-induced phosphorylation and activation of PDE3B in 3T3-L1 adipocytes, placing Akt in insulin receptor signaling. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: PMID:10454575 Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt. |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | IDA PMID:10454575 Insulin-induced phosphorylation and activation of cyclic nuc... | ACCEPT | Summary: IDA (PMID:10454575): Akt is required for PI3K-dependent, insulin-induced phosphorylation of PDE3B, supporting the PI3K/PKB pathway role. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: PMID:10454575 Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt. |
| GO:0002430 complement receptor mediated signaling pathway | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has direct experimental support (IDA PMID:19162005, BHF-UCL): AKT1 was engaged downstream of complement receptor signalling in the donor cellular context, one of many receptor systems that converge on PI3K/AKT. Reason: The donor experiment is genuine, but per-receptor pathway-membership terms over-annotate a hub kinase that is recruited downstream of dozens of receptor classes; complement-receptor signalling is a donor cell-context observation, not a distinguishing conserved function of rat Akt1. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IDA PMID:19162005. The experiment supports the human annotation; the transfer is contextual (receptor-specific pathway membership for a broadly recruited kinase), not weakly sourced. Supporting Evidence: UniProtKB:P47196 GO; GO:0002430; P:complement receptor mediated signaling pathway; ISO:RGD. |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | IDA PMID:8524413 Inhibition of glycogen synthase kinase-3 by insulin mediated... | ACCEPT | Summary: IDA (PMID:8524413): insulin-stimulated PKB inactivates GSK3, and PKB activation is blocked by PI3K inhibitors. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: PMID:8524413 Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. |
| GO:1905786 positive regulation of anaphase-promoting complex-dependent catabolic process | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has direct experimental support (IDA PMID:29343641): a specific cell-cycle mechanism, AKT-dependent promotion of APC/C-mediated degradation, characterized in human cells. Reason: The donor IDA is genuine, but a single-study mechanistic claim about promoting APC/C-dependent catabolism is a narrow cell-cycle context; carrying it to rat at gene level asserts more specificity than the conserved core (a broad-substrate Ser/Thr kinase) guarantees without rat-directed evidence. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IDA PMID:29343641. The experiment supports the human annotation; the transfer concern is the narrow, single-study cell-cycle scope, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:1905786; P:positive regulation of anaphase-promoting complex-dependent catabolic process; ISO:RGD. |
| GO:0019900 kinase binding | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has direct experimental support (IPI PMID:21177249, ParkinsonsUK-UCL): a documented physical interaction between AKT1 and another kinase. Reason: The donor IPI is genuine, but 'kinase binding' is an uninformative interaction-class term of the same kind as 'protein binding', which this project avoids; the interaction is better conveyed by AKT1's kinase-activity and substrate-directed annotations than by a bare binding term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IPI PMID:21177249. The interaction evidence supports the human annotation; the issue is the uninformative binding-class term, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:0019900; F:kinase binding; ISO:RGD. |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | ISO GO_REF:0000121 | ACCEPT | Summary: The rat ISO traces to mouse Akt1 and human AKT1. The donor annotation has experimental support and represents a conserved core kinase or PI3K/insulin-signaling function. Rat experimental annotations also exist for this term (PMID:10454575, PMID:8524413). Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: UniProtKB:P47196 Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) file:rat/Akt1/Akt1-deep-research-falcon.md AKT1 sits in the canonical **PI3K→AKT→mTOR** axis. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1 (IGI, PMID:18762576) and human AKT1 (IDA, PMID:19057511), studies in which AKT signalling raised transcription of specific Pol II targets. Reason: Re-reviewed 2026-10-17: transcription regulation is not a tissue context, so CONTEXT_OR_TISSUE_MISMATCH was the wrong label. The donor evidence is experimental and transfers. The objection is scope: AKT1 affects Pol II transcription only indirectly, by phosphorylating transcription factors such as CREB1 and the FOXO family, so the transcription-level term describes a downstream outcome rather than a direct role. Flagged as over-annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IGI from PMID:18762576, so the donor annotation is experimentally grounded. Transfers to rat; the objection is term scope. UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Traced against the human AKT1 GOA record (UniProtKB/P31749, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:19057511, so the donor annotation is experimentally grounded. Transfers to rat; the objection is term scope. Supporting Evidence: UniProtKB:P47196 AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 |
| GO:1900087 positive regulation of G1/S transition of mitotic cell cycle | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:18483258). AKT1 promotion of G1/S progression - via inhibitory phosphorylation of cell-cycle brakes such as p21/p27 and GSK3-dependent cyclin D control - is well-established, conserved mammalian biology. Reason: The donor IMP is experimental and the underlying mechanism is a canonical, conserved output of AKT signalling, so the transfer to rat is safe. Kept as non-core: cell-cycle promotion is one downstream programme of the core PI3K effector-kinase function rather than the core activity itself. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:18483258. The loss-of-function experiment supports the term and the mechanism is conserved; the transfer to rat is sound for a non-core annotation. Supporting Evidence: UniProtKB:P47196 GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; ISO:RGD. |
| GO:1903384 negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:21177249, ParkinsonsUK-UCL) in a hydrogen-peroxide/neuronal apoptosis paradigm. Reason: The donor IMP is genuine and pro-survival signalling is core AKT1 biology, but this composite term pins the claim to one stimulus (hydrogen peroxide) and one cell type (neuron); the conserved function is anti-apoptotic signalling generally, so the hyper-specific stimulus-plus-cell-type transfer over-annotates rat Akt1. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:21177249. The experiment supports the human annotation; the transfer concern is the stimulus- and cell-type-composite term scope, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:1903384; P:negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway; ISO:RGD. |
| GO:1904841 TORC2 complex binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:1904841; F:TORC2 complex binding; ISO:RGD. file:rat/Akt1/Akt1-deep-research-falcon.md **mTORC2 phosphorylates Ser473** in the hydrophobic motif |
| GO:0005080 protein kinase C binding | IPI PMID:8755528 Activation of RAC-protein kinase by heat shock and hyperosmo... | KEEP AS NON CORE | Summary: Rat and mammalian evidence supports a physical association with specific protein kinase C family members, but this is a context-dependent interaction rather than a core defining function of AKT1. Reason: Keep as a real but non-core interaction annotation. Supporting Evidence: PMID:8755528 Activation of RAC-protein kinase by heat shock and hyperosmolarity stress through a pathway independent of phosphatidylinositol 3-kinase. |
| GO:0034605 cellular response to heat | IDA PMID:8755528 Activation of RAC-protein kinase by heat shock and hyperosmo... | KEEP AS NON CORE | Summary: Rat experiments support AKT activation during heat stress, but this is a conditional stress-response context rather than a core AKT1 function. Reason: Keep as a valid but non-core stress-response annotation. Supporting Evidence: PMID:8755528 Activation of RAC-protein kinase by heat shock and hyperosmolarity stress through a pathway independent of phosphatidylinositol 3-kinase. |
| GO:0071475 cellular hyperosmotic salinity response | IDA PMID:8755528 Activation of RAC-protein kinase by heat shock and hyperosmo... | KEEP AS NON CORE | Summary: Rat experiments support AKT activation during hyperosmotic stress, but the term describes a conditional response rather than a core conserved function. Reason: Keep as a valid but non-core stress-response annotation. Supporting Evidence: PMID:8755528 Activation of RAC-protein kinase by heat shock and hyperosmolarity stress through a pathway independent of phosphatidylinositol 3-kinase. |
| GO:0072709 cellular response to sorbitol | IDA PMID:8755528 Activation of RAC-protein kinase by heat shock and hyperosmo... | MARK AS OVER ANNOTATED | Summary: The supporting experiment used sorbitol as a hyperosmotic stimulus; keeping a sorbitol-specific response term overstates a broader stress-signaling observation. Reason: The annotation is too stimulus-specific for a stable AKT1 gene-level assignment. Supporting Evidence: PMID:8755528 Activation of RAC-protein kinase by heat shock and hyperosmolarity stress through a pathway independent of phosphatidylinositol 3-kinase. |
| GO:0004672 protein kinase activity | IDA PMID:9112399 Potential role of protein kinase B in glucose transporter 4 ... | MODIFY | Summary: IDA (PMID:9112399) protein kinase activity: PKB is activated by insulin in adipocytes in parallel with GLUT4 translocation. Correct but less precise than serine/threonine kinase activity. Reason: The rat assay measured activation of PKB, a serine/threonine kinase, in isolated adipocytes; the generic parent protein kinase activity undersells that, so GO:0004674 is the precise term. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:9112399 protein kinase B, a serine/threonine kinase stimulated by PI 3-kinase, is activated by both insulin and okadaic acid in isolated adipocytes |
| GO:0005829 cytosol | IDA PMID:9112399 Potential role of protein kinase B in glucose transporter 4 ... | KEEP AS NON CORE | Summary: IDA (PMID:9112399) cytosol: endogenous PKB fractionation in adipocytes; AKT1 is largely cytosolic. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: PMID:9112399 Gag-PKB was associated with all membrane fractions, whereas the endogenous PKB was mostly cytosolic |
| GO:0071364 cellular response to epidermal growth factor stimulus | IDA PMID:15701816 EGF stimulates mesangial cell mitogenesis via PI3-kinase-med... | KEEP AS NON CORE | Summary: IDA (PMID:15701816): EGF stimulates PI3K-dependent Akt kinase activity in mesangial cells, although EGF-induced DNA synthesis was Akt-independent. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: PMID:15701816 EGF stimulates mesangial cell mitogenesis via PI3-kinase-mediated MAPK-dependent and AKT kinase-independent manner: involvement of c-fos and p27Kip1. |
| GO:0014850 response to muscle activity | IDA PMID:19574345 Lipid-induced mTOR activation in rat skeletal muscle reverse... | KEEP AS NON CORE | Summary: Rat skeletal-muscle experiments implicate AKT1 signaling in adaptation to exercise or muscle activity, but this is a physiological context-specific role rather than the core molecular function. Reason: Keep as a valid but non-core physiology annotation. Supporting Evidence: PMID:19574345 Lipid-induced mTOR activation in rat skeletal muscle reversed by exercise and 5'-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside. |
| GO:0031667 response to nutrient levels | IDA PMID:19574345 Lipid-induced mTOR activation in rat skeletal muscle reverse... | KEEP AS NON CORE | Summary: Rat experiments connect AKT1 signaling to nutrient-sensitive mTOR responses, but this reflects a contextual anabolic program rather than a core stand-alone function term. Reason: Keep as a valid but non-core physiology annotation. Supporting Evidence: PMID:19574345 Lipid-induced mTOR activation in rat skeletal muscle reversed by exercise and 5'-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside. |
| GO:0004672 protein kinase activity | IDA PMID:7774014 The protein kinase encoded by the Akt proto-oncogene is a ta... | MODIFY | Summary: IDA (PMID:7774014) protein kinase activity: Akt is a target of PDGF-activated PI3K. Correct but less precise than serine/threonine kinase activity. Reason: The direct assay measured activity of the serine/threonine protein kinase encoded by Akt; the generic parent protein kinase activity undersells that, so GO:0004674 is the precise term. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:7774014 The serine/threonine protein kinase encoded by the Akt proto-oncogene is catalytically inactive in serum-starved primary and immortalized fibroblasts |
| GO:0032869 cellular response to insulin stimulus | IDA PMID:9005851 Regulation of neuronal survival by the serine-threonine prot... | KEEP AS NON CORE | Summary: IDA (PMID:9005851): IGF-1 activates Akt through PI3K in cerebellar neurons, and Akt mediates PI3K-dependent survival; the abstract describes IGF-1, so the insulin-stimulus framing presumably reflects assays reported in the full text. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: PMID:9005851 Regulation of neuronal survival by the serine-threonine protein kinase Akt. |
| GO:0036120 cellular response to platelet-derived growth factor stimulus | IDA PMID:7774014 The protein kinase encoded by the Akt proto-oncogene is a ta... | KEEP AS NON CORE | Summary: PDGF-dependent activation of AKT is well supported, but this growth-factor response context is narrower than AKT1's core biochemistry. Reason: Keep as a valid but non-core pathway-context annotation. Supporting Evidence: PMID:7774014 The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. |
| GO:0046777 protein autophosphorylation | IDA PMID:7774014 The protein kinase encoded by the Akt proto-oncogene is a ta... | REMOVE | Summary: The early PDGF paper supports AKT activation downstream of PI3K, but protein autophosphorylation is not a stable or well-supported defining activity for AKT1. Reason: Current AKT1 biology supports activation by upstream kinases rather than retaining autophosphorylation as a curated core annotation. GOA no longer carries this row (retired at the 2026 refresh). Supporting Evidence: PMID:7774014 The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. |
| GO:1901653 cellular response to peptide | IEP PMID:18772167 Islet neogenesis-associated protein signaling in neonatal pa... | MARK AS OVER ANNOTATED | Summary: Rat IEP (PMID:18772167): in neonatal rat islets, the INGAP pentadecapeptide INGAP-PP rapidly increased Akt1 Ser-473 phosphorylation, and longer culture raised Akt1 mRNA. Reason: Re-reviewed 2026-10-17: this is rat-direct expression-pattern evidence, with no transfer involved. It shows Akt1 activation in response to one peptide in one tissue, and AKT1 is activated downstream of many receptors, so the generic stimulus class "cellular response to peptide" records a signalling readout rather than a function of the gene. Flagged as over-annotation. Supporting Evidence: PMID:18772167 Short-term exposure of neonatal islets to INGAP-PP (90 s, 5, 15, and 30 min) significantly increased Akt1(-Ser473) and MAPK3/1(-Thr202/Tyr204) phosphorylation |
| GO:0004674 protein serine/threonine kinase activity | ISO GO_REF:0000121 | ACCEPT | Summary: The rat ISO traces to mouse Akt1 and human AKT1. The donor annotation has experimental support and represents a conserved core kinase or PI3K/insulin-signaling function. Rat experimental annotations also exist for this term (PMID:10454575, PMID:12089343, PMID:8524413). Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: UniProtKB:P47196 Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) |
| GO:0071363 cellular response to growth factor stimulus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0071363; P:cellular response to growth factor stimulus; ISO:RGD. |
| GO:1904515 positive regulation of TORC2 signaling | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1, whose term rests on IMP (PMID:23684622, PMID:26235620). UniProt records for rat AKT1, by similarity, a positive feedback loop in which AKT phosphorylates MAPKAP1/SIN1 and promotes mTORC2 activation. Reason: Re-reviewed 2026-10-17: on re-grounding the term describes a defined mechanism, phosphorylation of the mTORC2 subunit MAPKAP1/SIN1, and not a context. The donor evidence is experimental and transfers. Kept as a valid non-core regulatory role. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IMP from PMID:23684622, PMID:26235620, so the donor annotation is experimentally grounded. Substrate-defined feedback mechanism; transfers to the rat ortholog. Supporting Evidence: UniProtKB:P47196 Part of a positive feedback loop of mTORC2 signaling by mediating phosphorylation of MAPKAP1/SIN1, promoting mTORC2 activation |
| GO:1903898 negative regulation of PERK-mediated unfolded protein response | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1 IDA (PMID:21954288): AKT phosphorylates the ER-stress kinase PERK on Thr-799 and inhibits it, lowering eIF2-alpha phosphorylation. Reason: Re-reviewed 2026-10-17: the previous context-mismatch removal does not survive re-grounding. The donor evidence is a defined kinase-substrate mechanism (inhibitory phosphorylation of PERK), the regulation term describes exactly that, and nothing argues against it in rat. Kept as a valid non-core regulatory role. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:21954288, so the donor annotation is experimentally grounded. Mechanistic, substrate-defined evidence; transfers to the rat ortholog. Supporting Evidence: PMID:21954288 PERK, which was inhibited by Akt-dependent phosphorylation at threonine-799 |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:9065430 Regulation of protein kinase B and glycogen synthase kinase-... | ACCEPT | Summary: Rat IDA (PMID:9065430): PKB activity measured in rat epididymal fat cells stimulated by insulin and beta-adrenergic agonists. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: PMID:9065430 Regulation of protein kinase B and glycogen synthase kinase-3 by insulin and beta-adrenergic agonists in rat epididymal fat cells. Activation of protein kinase B by wortmannin-sensitive and -insensitive mechanisms. |
| GO:0032869 cellular response to insulin stimulus | IDA PMID:9065430 Regulation of protein kinase B and glycogen synthase kinase-... | KEEP AS NON CORE | Summary: Rat IDA (PMID:9065430): PKB activation by insulin in rat epididymal fat cells. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: PMID:9065430 Regulation of protein kinase B and glycogen synthase kinase-3 by insulin and beta-adrenergic agonists in rat epididymal fat cells. Activation of protein kinase B by wortmannin-sensitive and -insensitive mechanisms. |
| GO:0001649 osteoblast differentiation | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1 (IGI, PMID:19208758) and human AKT1 (IDA, PMID:22869525): blocking Akt prevents BMP2-driven osteoblast differentiation. Reason: Re-reviewed 2026-10-17: osteoblast differentiation is a genuine cell-type developmental context, so CONTEXT_OR_TISSUE_MISMATCH is kept; GRANULARITY_MISMATCH and PROPAGATION_BAD were dropped. The donor evidence is experimental and no rat divergence is argued, so the source is recorded as supporting transfer. The term is one cell-type outcome of PI3K/AKT signalling, so it stays flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IGI from PMID:19208758, so the donor annotation is experimentally grounded. Cell-type developmental outcome; no reason to think rat differs. UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Traced against the human AKT1 GOA record (UniProtKB/P31749, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:22869525, so the donor annotation is experimentally grounded. Cell-type developmental outcome; no reason to think rat differs. Supporting Evidence: PMID:19208758 an inhibitor of PI3-kinase or a dominant-negative Akt were as potent in preventing osteoblast differentiation as the IGF binding protein IGFBP5 |
| GO:0030425 dendrite | IDA PMID:31071414 Sex Differences in Neuroplasticity- and Stress-Related Gene ... | KEEP AS NON CORE | Summary: Rat IDA (PMID:31071414): in rat hippocampus, phospho-AKT immunoreactivity is found mainly in CA1 pyramidal cell bodies and to a lesser extent in dendrites of stratum oriens and radiatum. Reason: The full text directly reports phospho-AKT immunolabelling in dendrites, so the localization is experimentally supported; it is a neuron-specific location of a broadly cytoplasmic kinase and not a defining one. The previous REMOVE called the term context-specific, which is not grounds for removing an experimental localization. The antibody detects phospho-AKT and may not be isoform-specific. Supporting Evidence: PMID:31071414 pAKT-ir is found primarily in CA1 pyramidal cells and, to a lesser extent, in dendrites within SO and SR |
| GO:0005758 mitochondrial intermembrane space | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: UniProt ISS (is_active_in) mitochondrial intermembrane space from mouse Akt1 (P31750), which localizes there after rapamycin treatment. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 Also localizes to mitochondrial intermembrane space in response to rapamycin treatment |
| GO:0005758 mitochondrial intermembrane space | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0005758; C:mitochondrial intermembrane space; ISS:UniProtKB. |
| GO:0098978 glutamatergic synapse | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1 IDA (PMID:26844834), from a study of synaptic structural plasticity in nucleus accumbens medium spiny neurons after chronic cocaine. Reason: Re-reviewed 2026-10-17: the donor evidence is experimental and no rat divergence is argued, so this is not a removal. Glutamatergic synapse is a neuron-restricted compartment, and the observation comes from one drug-plasticity paradigm; AKT1 acts at many membranes, so this is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:26844834, so the donor annotation is experimentally grounded. Neuron-restricted compartment from one paradigm; no reason to think rat differs. Supporting Evidence: UniProtKB:P47196 GO; GO:0098978; C:glutamatergic synapse; ISO:RGD. |
| GO:0099175 regulation of postsynapse organization | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IDA (PMID:26844834). The donor evidence is experimental, but it records a dendritic-spine plasticity readout in nucleus accumbens neurons after chronic cocaine. Reason: Re-reviewed 2026-10-17: A dendritic-spine plasticity readout in nucleus accumbens neurons after chronic cocaine (IDA, PMID:26844834). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:26844834, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0099175; P:regulation of postsynapse organization; ISO:RGD. |
| GO:0030335 positive regulation of cell migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD. |
| GO:0160049 negative regulation of cGAS/STING signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1, where this term carries two direct experimental annotations (IDA PMID:12172553; IDA PMID:26440888). Akt-mediated inhibitory phosphorylation of cGAS is a described direct kinase-substrate mechanism for damping cGAS/STING signalling. Reason: The donor evidence is direct and mechanistic - an inhibitory phosphorylation event on a defined substrate - and kinase-substrate relationships of this kind transfer well between human and rat orthologs. Kept as non-core: innate-immune damping is one of AKT1's many substrate axes, not its defining function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IDA PMID:12172553 and IDA PMID:26440888. Two direct experiments support the term on the donor and the mechanism is a conserved kinase-substrate event; the transfer to rat is sound for a non-core annotation. Supporting Evidence: UniProtKB:P47196 GO; GO:0160049; P:negative regulation of cGAS/STING signaling pathway; ISO:RGD. |
| GO:0004672 protein kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: The rat ISO traces to mouse Akt1 and human AKT1, and donor experiments support kinase function, but this GO term is either overly broad or chemically inaccurate for AKT1. AKT1 is a serine/threonine kinase, not a generic or tyrosine kinase. Rat experimental annotations also exist for this term (PMID:12084817, PMID:7774014, PMID:9112399). Reason: Replace the transferred ISO term with the specific serine/threonine kinase activity term used for AKT-family biochemistry. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS SOURCE BUT NOT TARGET Mouse Akt1 donor evidence for this term is Ser/Thr-kinase specific (multiple IDAs, e.g. PMID:14730361); the generic parent term loses that precision. UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Human AKT1 carries the term (IDA, PMID:31204173; TAS), but its characterised activity is protein serine/threonine kinase activity, which is the term to use for rat Akt1. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: UniProtKB:P47196 GO; GO:0004672; F:protein kinase activity; IDA:RGD. |
| GO:1902018 negative regulation of cilium assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The rat ISS transfers from human AKT1, where the term rests on IDA (PMID:31204173): serum LPA/LPAR1 signalling through PI3K/Akt inhibits ciliogenesis via the Rab11 effector WDR44. Reason: Re-reviewed 2026-10-17 on re-grounding: the donor paper defines a mechanism (AKT phosphorylation of WDR44 switches Rab11 from preciliary trafficking to endocytic recycling and blocks ciliogenesis initiation), which UniProt records for rat AKT1 by similarity. The earlier over-annotation call rested on an uncited claim that AKT acts with opposite signs on ciliogenesis in other contexts; with no cited support it was dropped. Kept as a valid non-core regulatory role. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries the term by IDA (PMID:31204173), a substrate-defined mechanism (WDR44 phosphorylation) that transfers to the rat ortholog. Supporting Evidence: PMID:31204173 a WDR44-pAkt-phosphomimetic mutant blocks ciliogenesis UniProtKB:P47196 phosphorylates WDR44 which induces WDR44 binding to Rab11, thereby switching Rab11 vesicular function from preciliary trafficking to endocytic recycling |
| GO:1902018 negative regulation of cilium assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO transfers from human AKT1, where the term rests on IDA (PMID:31204173): serum LPA/LPAR1 signalling through PI3K/Akt inhibits ciliogenesis via the Rab11 effector WDR44. Reason: Re-reviewed 2026-10-17 on re-grounding: the donor paper defines a mechanism (AKT phosphorylation of WDR44 switches Rab11 from preciliary trafficking to endocytic recycling and blocks ciliogenesis initiation), which UniProt records for rat AKT1 by similarity. The earlier over-annotation call rested on an uncited claim that AKT acts with opposite signs on ciliogenesis in other contexts; with no cited support it was dropped. Kept as a valid non-core regulatory role. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries the term by IDA (PMID:31204173), a substrate-defined mechanism (WDR44 phosphorylation) that transfers to the rat ortholog. Supporting Evidence: PMID:31204173 a WDR44-pAkt-phosphomimetic mutant blocks ciliogenesis UniProtKB:P47196 phosphorylates WDR44 which induces WDR44 binding to Rab11, thereby switching Rab11 vesicular function from preciliary trafficking to endocytic recycling |
| GO:0008286 insulin receptor signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: The rat ISO traces to mouse Akt1 and human AKT1. The donor annotation has experimental support and represents a conserved core kinase or PI3K/insulin-signaling function. Rat experimental annotations also exist for this term (PMID:10454575, PMID:8524413, PMID:9632753). Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: UniProtKB:P47196 Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) |
| GO:0071364 cellular response to epidermal growth factor stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: UniProt ISS cellular response to EGF from human AKT1 (P31749). AKT1 is activated downstream of EGF receptor/PI3K. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) |
| GO:0071364 cellular response to epidermal growth factor stimulus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1 and human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Rat experimental annotations also exist for this term (PMID:15701816). Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IDA:RGD. |
| GO:0150033 negative regulation of protein localization to lysosome | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The rat ISS transfers from human AKT1, where the term rests on IDA (PMID:24529379): insulin drives dissociation of the TSC complex from the lysosomal surface, and this requires Akt-mediated TSC2 phosphorylation. Reason: Re-reviewed 2026-10-17 on re-grounding: the "single-substrate trafficking readout" framing undersold the donor evidence. The substrate is TSC2, AKT1's central route to mTORC1 activation (recorded for rat AKT1 in UniProt), and the term describes the mechanism by which that phosphorylation acts. Kept as a valid non-core regulatory role; the core claim stays with protein serine/threonine kinase activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries the term by IDA (PMID:24529379); TSC2 phosphorylation by AKT is conserved and transfers to the rat ortholog. Supporting Evidence: PMID:24529379 its dissociation in response to insulin requires Akt-mediated TSC2 phosphorylation UniProtKB:P47196 AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462' |
| GO:0150033 negative regulation of protein localization to lysosome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO transfers from human AKT1, where the term rests on IDA (PMID:24529379): insulin drives dissociation of the TSC complex from the lysosomal surface, and this requires Akt-mediated TSC2 phosphorylation. Reason: Re-reviewed 2026-10-17 on re-grounding: the "single-substrate trafficking readout" framing undersold the donor evidence. The substrate is TSC2, AKT1's central route to mTORC1 activation (recorded for rat AKT1 in UniProt), and the term describes the mechanism by which that phosphorylation acts. Kept as a valid non-core regulatory role; the core claim stays with protein serine/threonine kinase activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries the term by IDA (PMID:24529379); TSC2 phosphorylation by AKT is conserved and transfers to the rat ortholog. Supporting Evidence: PMID:24529379 its dissociation in response to insulin requires Akt-mediated TSC2 phosphorylation UniProtKB:P47196 AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462' |
| GO:0016020 membrane | ISO GO_REF:0000121 | MODIFY | Summary: The rat ISO traces to human AKT1, where donor experiments support membrane recruitment of AKT1, but the transferable location is the plasma membrane rather than the unspecific parent term 'membrane'. Reason: The donor evidence concerns regulated plasma-membrane recruitment/activation, so the parent term membrane is too broad. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET The human AKT1 membrane annotation (IDA, PMID:24529379) reflects regulated recruitment to the plasma membrane; the parent term is broader than the donor evidence. Proposed replacements: plasma membrane Supporting Evidence: UniProtKB:P47196 GO; GO:0016020; C:membrane; ISO:RGD. |
| GO:0032869 cellular response to insulin stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: UniProt ISS cellular response to insulin stimulus from human AKT1 (P31749); rat IDA/IMP rows also support this. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface |
| GO:0032869 cellular response to insulin stimulus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1 and human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Rat experimental annotations also exist for this term (PMID:17715136, PMID:9005851, PMID:9065430). Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0032869; P:cellular response to insulin stimulus; IDA:RGD. |
| GO:1904263 positive regulation of TORC1 signaling | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:1904263; P:positive regulation of TORC1 signaling; ISS:UniProtKB. |
| GO:1904263 positive regulation of TORC1 signaling | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: UniProt ISS positive regulation of TORC1 signaling from human AKT1 (P31749). AKT1 phosphorylates TSC2 and PRAS40 to activate mTORC1. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 thereby activating the mTORC1 signaling pathway |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1 (IMP, PMID:15937334) and human AKT1 (IDA, PMID:23512198). AKT promotes proteasomal degradation of specific substrates; for example, Akt phosphorylation of Mdm2 is required for Mdm2-dependent ubiquitylation and degradation of the androgen receptor. Reason: Re-reviewed 2026-10-17: a regulation term is the right way to record the effect of AKT1 on E3-ligase-dependent degradation. AKT1 regulates the ubiquitin machinery (e.g. by phosphorylating Mdm2) without performing ubiquitination itself, which is why the protein ubiquitination and protein catabolic process rows are removed and this row is kept. CONTEXT_OR_TISSUE_MISMATCH did not describe the term. Kept as a valid non-core regulatory role. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IMP from PMID:15937334, so the donor annotation is experimentally grounded. Transfers to rat as a regulatory role. UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Traced against the human AKT1 GOA record (UniProtKB/P31749, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:23512198, so the donor annotation is experimentally grounded. Transfers to rat as a regulatory role. Supporting Evidence: PMID:12145204 the E3 ligase activity of Mdm2 and phosphorylation of Mdm2 by Akt are essential for Mdm2 to affect AR ubiquitylation and degradation |
| GO:0110002 regulation of tRNA methylation | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has direct experimental support (IDA PMID:15861136) from a single human study linking AKT activity to control of tRNA methylation. Reason: The donor IDA is genuine, but 'regulation of tRNA methylation' generalizes one human study into a process-level regulatory claim in a niche far from AKT1's characterized signalling outputs; without rat-directed or corroborating evidence this term over-annotates rat Akt1. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IDA PMID:15861136. The experiment supports the human annotation; the transfer concern is elevating a single-study readout to a niche process-regulation claim, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:0110002; P:regulation of tRNA methylation; ISO:RGD. |
| GO:0022605 mammalian oogenesis stage | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IMP (PMID:34635817). The donor evidence is experimental, but it records a female-fertility phenotype from a Gm364/MIB2/DLL3/Notch2 study in which AKT is a downstream pathway node. Reason: Re-reviewed 2026-10-17: A female-fertility phenotype from a Gm364/MIB2/DLL3/Notch2 study in which AKT is a downstream pathway node (IMP, PMID:34635817). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IMP from PMID:34635817, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0022605; P:mammalian oogenesis stage; ISO:RGD. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:8524413 Inhibition of glycogen synthase kinase-3 by insulin mediated... | ACCEPT | Summary: IDA (PMID:8524413): PKB phosphorylates and inactivates GSK3 in response to insulin. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: PMID:8524413 Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. |
| GO:0008286 insulin receptor signaling pathway | IDA PMID:8524413 Inhibition of glycogen synthase kinase-3 by insulin mediated... | ACCEPT | Summary: IDA (PMID:8524413): insulin-stimulated PKB mediates GSK3 inhibition, placing Akt1 in insulin receptor signaling. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: PMID:8524413 Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. |
| GO:0010748 negative regulation of long-chain fatty acid import across plasma membrane | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:16814735, BHF-UCL) from metabolic phenotyping in a specific human cellular context. Reason: The donor IMP is genuine, but this transport-phenotype term derives from loss-of-function readouts in one cellular setting; control of long-chain fatty-acid import across the plasma membrane is an indirect metabolic consequence of AKT signalling, too narrow to carry to rat at gene level without rat-directed evidence. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:16814735. The experiment supports the human annotation; the transfer concern is the narrow, indirect transport-phenotype scope, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:0010748; P:negative regulation of long-chain fatty acid import across plasma membrane; ISO:RGD. |
| GO:0010907 positive regulation of glucose metabolic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0010907; P:positive regulation of glucose metabolic process; ISO:RGD. |
| GO:0030291 protein serine/threonine kinase inhibitor activity | IPI PMID:8524413 Inhibition of glycogen synthase kinase-3 by insulin mediated... | REMOVE | Summary: AKT1 inhibits GSK3 by phosphorylating it on inhibitory serines; the downstream decrease in GSK3 activity is a catalytic signaling consequence of AKT1's serine/threonine kinase activity, not a stoichiometric kinase-inhibitor molecular function. Reason: GO:0030291 is defined for gene products that bind to and inhibit a protein serine/threonine kinase. The PMID:8524413 evidence behind this row instead shows that active Akt/PKB catalyzes inhibitory phosphorylation of GSK3, so the row mis-types a downstream regulatory outcome as a binding-based molecular function. Supporting Evidence: PMID:8524413 Another insulin-stimulated protein kinase inactivates GSK3 under these conditions, and we demonstrate that it is the product of the proto-oncogene protein kinase B file:rat/Akt1/Akt1-hypotheses/prediction-kinase-inhibitor-activity/openscientist.md Akt1 reduces GSK3 activity enzymatically, by phosphorylation. |
| GO:0031999 negative regulation of fatty acid beta-oxidation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:16814735, BHF-UCL). Suppression of fatty-acid beta-oxidation is a coherent output of insulin-PI3K-AKT anabolic signalling, which reciprocally promotes lipogenesis and restrains catabolic fat use. Reason: The donor IMP is experimental and the direction of the claim matches the conserved anabolic logic of insulin-AKT signalling across mammals, so the transfer to rat is defensible. Kept as non-core: a downstream metabolic output of the core effector-kinase function, not the core function itself. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:16814735. The loss-of-function experiment supports the term and the metabolic logic is conserved; the transfer to rat is sound for a non-core annotation. Supporting Evidence: UniProtKB:P47196 GO; GO:0031999; P:negative regulation of fatty acid beta-oxidation; ISO:RGD. |
| GO:0045725 positive regulation of glycogen biosynthetic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; ISO:RGD. |
| GO:0046326 positive regulation of D-glucose import across plasma membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface |
| GO:0120283 protein serine/threonine kinase binding | IPI PMID:8524413 Inhibition of glycogen synthase kinase-3 by insulin mediated... | KEEP AS NON CORE | Summary: The supporting study shows physical association with another serine/threonine kinase, but this is a partner-specific interaction rather than a core defining AKT1 function. Reason: Keep as a valid but non-core binding annotation. Supporting Evidence: PMID:8524413 Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. |
| GO:0048009 insulin-like growth factor receptor signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1 and human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISS:UniProtKB. |
| GO:0016301 kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: The rat ISO traces to mouse Akt1 and human AKT1, and donor experiments support kinase function, but this GO term is either overly broad or chemically inaccurate for AKT1. AKT1 is a serine/threonine kinase, not a generic or tyrosine kinase. Reason: Replace the transferred ISO term with the specific serine/threonine kinase activity term used for AKT-family biochemistry. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS SOURCE BUT NOT TARGET Mouse Akt1 carries kinase activity by IDA (PMID:23886629) (QuickGO, checked 2026-10-10); its characterised activity is protein serine/threonine kinase activity. UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Human AKT1 carries kinase activity by IDA (PMID:14749367) (QuickGO, checked 2026-10-10); its characterised activity is protein serine/threonine kinase activity. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: UniProtKB:P47196 GO; GO:0016301; F:kinase activity; ISO:RGD. |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1 and human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 Cytoplasm {ECO:0000250|UniProtKB:P31750} |
| GO:0006468 protein phosphorylation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1 and human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Rat experimental annotations also exist for this term (PMID:12084817, PMID:9887206). Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. GOA no longer carries this row (retired at the 2026 refresh). Supporting Evidence: UniProtKB:P47196 This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates |
| GO:1905552 positive regulation of protein localization to endoplasmic reticulum | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has direct experimental support (IDA PMID:32322062, listed twice on the donor record): an AKT-dependent increase in a substrate's localization to the endoplasmic reticulum. Reason: The donor IDA is genuine, but it is a substrate-specific trafficking readout; casting it as gene-level positive regulation of protein localization to the ER overstates granularity for a cross-species transfer without rat-directed evidence. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IDA PMID:32322062. The experiment supports the human annotation; the transfer concern is the substrate-specific trafficking scope, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:1905552; P:positive regulation of protein localization to endoplasmic reticulum; ISO:RGD. |
| GO:0006954 inflammatory response | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IDA (PMID:14730361). The donor evidence is experimental, but it records an organismal immune process inferred from a T-cell costimulation and survival study. Reason: Re-reviewed 2026-10-17: An organismal immune process inferred from a T-cell costimulation and survival study (IDA, PMID:14730361). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:14730361, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0006954; P:inflammatory response; ISO:RGD. |
| GO:0009408 response to heat | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IGI (PMID:31874168). The donor evidence is experimental, but it records a thermal-sensitivity readout from an Akt-mTOR pain-hypersensitivity study. Reason: Re-reviewed 2026-10-17: A thermal-sensitivity readout from an Akt-mTOR pain-hypersensitivity study (IGI, PMID:31874168). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IGI from PMID:31874168, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0009408; P:response to heat; ISO:RGD. |
| GO:0048266 behavioral response to pain | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IGI (PMID:31874168). The donor evidence is experimental, but it records a behavioural pain phenotype from an Akt-mTOR pain-hypersensitivity study. Reason: Re-reviewed 2026-10-17: A behavioural pain phenotype from an Akt-mTOR pain-hypersensitivity study (IGI, PMID:31874168). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IGI from PMID:31874168, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0048266; P:behavioral response to pain; ISO:RGD. |
| GO:0010629 negative regulation of gene expression | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1 IDA (PMID:19933931), from a study of reciprocal regulation of microRNA-1 and IGF-1 signalling. The term is a generic regulation-of-expression readout. Reason: Re-reviewed 2026-10-17: the donor IDA is genuine and no rat divergence is argued, so this is not a removal. The problem is granularity, not context: negative regulation of gene expression is an uninformative readout for a kinase whose effect on expression is mediated by phosphorylation of transcriptional regulators such as the FOXO factors. Flagged as over-annotation, consistent with the positive regulation of gene expression row. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:19933931, so the donor annotation is experimentally grounded. The objection is the generic term, not the transfer. Supporting Evidence: UniProtKB:P47196 AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization |
| GO:0070848 response to growth factor | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0070848; P:response to growth factor; ISO:RGD. |
| GO:0099104 potassium channel activator activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The rat ISS transfers from human AKT1, where the term rests on IDA (PMID:33505021): AKT and the pore protein TMEM175 form the growth-factor-activated lysosomal K+ channel complex lysoK(GF), and AKT opens the channel. Reason: Re-reviewed 2026-10-17 on re-grounding: the earlier over-annotation call said the term recasts a kinase-substrate event as an activator activity, but the donor paper shows the opposite: TMEM175 is opened by conformational changes in AKT, not by its catalytic activity, and UniProt records this for rat AKT1 by similarity. Potassium channel activator activity is therefore the accurate MF for this non-catalytic role. Kept as non-core, because AKT1's defining activity is protein serine/threonine kinase activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries the term by IDA (PMID:33505021); the paper also measured native lysosomal K+ currents in mouse neurons, so the role is not human-specific. Supporting Evidence: PMID:33505021 TMEM175 is opened by conformational changes in, but not the catalytic activity of, AKT UniProtKB:P47196 acts by promoting TMEM175 channel activation, independently of its protein kinase activity |
| GO:0099104 potassium channel activator activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO transfers from human AKT1, where the term rests on IDA (PMID:33505021): AKT and the pore protein TMEM175 form the growth-factor-activated lysosomal K+ channel complex lysoK(GF), and AKT opens the channel. Reason: Re-reviewed 2026-10-17 on re-grounding: the earlier over-annotation call said the term recasts a kinase-substrate event as an activator activity, but the donor paper shows the opposite: TMEM175 is opened by conformational changes in AKT, not by its catalytic activity, and UniProt records this for rat AKT1 by similarity. Potassium channel activator activity is therefore the accurate MF for this non-catalytic role. Kept as non-core, because AKT1's defining activity is protein serine/threonine kinase activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries the term by IDA (PMID:33505021); the paper also measured native lysosomal K+ currents in mouse neurons, so the role is not human-specific. Supporting Evidence: PMID:33505021 TMEM175 is opened by conformational changes in, but not the catalytic activity of, AKT UniProtKB:P47196 acts by promoting TMEM175 channel activation, independently of its protein kinase activity |
| GO:1990090 cellular response to nerve growth factor stimulus | IEP PMID:9492284 Nerve growth factor promotes activation of the alpha, beta a... | KEEP AS NON CORE | Summary: Rat IEP (PMID:9492284): NGF activates PKB alpha, beta and gamma in PC12 cells. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: PMID:9492284 Nerve growth factor promotes activation of the alpha, beta and gamma isoforms of protein kinase B in PC12 pheochromocytoma cells. |
| GO:0002931 response to ischemia | IEP PMID:24601882 Protein kinase B (PKB/AKT1) formed signaling complexes with ... | KEEP AS NON CORE | Summary: Cardiomyocyte experiments support AKT1 involvement in ischemia response, but the annotation captures a disease or tissue context rather than AKT1's core evolved role. Reason: Keep as a valid but non-core physiology annotation. Supporting Evidence: PMID:24601882 Protein kinase B (PKB/AKT1) formed signaling complexes with mitochondrial proteins and prevented glycolytic energy dysfunction in cultured cardiomyocytes during ischemia-reperfusion injury. |
| GO:0010918 positive regulation of mitochondrial membrane potential | IMP PMID:24601882 Protein kinase B (PKB/AKT1) formed signaling complexes with ... | MARK AS OVER ANNOTATED | Summary: The evidence comes from cardiomyocyte ischemia-reperfusion experiments and supports a protective mitochondrial context, but the term is too specific for a stable general AKT1 annotation. Reason: Retains some signal of a real observation while flagging the term as over-specific. Supporting Evidence: PMID:24601882 Protein kinase B (PKB/AKT1) formed signaling complexes with mitochondrial proteins and prevented glycolytic energy dysfunction in cultured cardiomyocytes during ischemia-reperfusion injury. |
| GO:0032929 negative regulation of superoxide anion generation | IMP PMID:24601882 Protein kinase B (PKB/AKT1) formed signaling complexes with ... | MARK AS OVER ANNOTATED | Summary: The cardiomyocyte evidence suggests reduced oxidative damage in a specific injury model, but the term is too narrow and context-bound to retain broadly. Reason: The annotation is too context-specific for a general AKT1 function statement. Supporting Evidence: PMID:24601882 Protein kinase B (PKB/AKT1) formed signaling complexes with mitochondrial proteins and prevented glycolytic energy dysfunction in cultured cardiomyocytes during ischemia-reperfusion injury. |
| GO:0110099 negative regulation of calcium import into the mitochondrion | IMP PMID:24601882 Protein kinase B (PKB/AKT1) formed signaling complexes with ... | MARK AS OVER ANNOTATED | Summary: Rat IMP (PMID:24601882): in cardiomyocytes under ischemia-reperfusion, mitochondria-targeted AKT1 signaling suppressed mitochondrial calcium overload. Reason: The abstract supports the term in this stress model, so REMOVE is not justified. It is a downstream consequence of mitochondrial AKT1 signaling observed with targeted constructs during injury, and generalizing it to a regulatory role in mitochondrial calcium import overshoots the evidence. UniProt describes AKT1 phosphorylation of MICU1 as regulating mitochondrial calcium uptake in another context, so the direction may depend on context. Treated like the sibling rows from this paper. Supporting Evidence: PMID:24601882 Mitochondrial AKT1 signaling played a protective role against apoptosis and necrosis during ischemia-reperfusion stress, suppressed mitochondrial calcium overload, and alleviated mitochondrial membrane depolarization. UniProtKB:P47196 Acts as a regulator of mitochondrial calcium uptake by mediating phosphorylation of MICU1 in the mitochondrial intermembrane space |
| GO:1903715 regulation of aerobic respiration | IMP PMID:24601882 Protein kinase B (PKB/AKT1) formed signaling complexes with ... | MARK AS OVER ANNOTATED | Summary: The ischemia-reperfusion study links AKT1 to protection of cellular energetics, but regulation of aerobic respiration is too system-level and context-dependent to retain as a stable gene function. Reason: The term overgeneralizes a specific injury-model phenotype. Supporting Evidence: PMID:24601882 Protein kinase B (PKB/AKT1) formed signaling complexes with mitochondrial proteins and prevented glycolytic energy dysfunction in cultured cardiomyocytes during ischemia-reperfusion injury. |
| GO:0005829 cytosol | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1 and human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Rat experimental annotations also exist for this term (PMID:9112399). Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0005829; C:cytosol; IDA:RGD. |
| GO:0003376 sphingosine-1-phosphate receptor signaling pathway | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:18558630, BHF-UCL) placing AKT1 downstream of sphingosine-1-phosphate receptor signalling in donor vascular-type cells. Reason: The donor IMP is genuine, but per-receptor pathway-membership terms over-annotate a kinase engaged downstream of many GPCRs and RTKs; S1P-receptor pathway membership is a donor cell-context observation rather than a distinguishing conserved rat Akt1 function. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:18558630. The experiment supports the human annotation; the transfer is contextual (receptor-specific pathway membership), not weakly sourced. Supporting Evidence: UniProtKB:P47196 GO; GO:0003376; P:sphingosine-1-phosphate receptor signaling pathway; ISO:RGD. |
| GO:0010595 positive regulation of endothelial cell migration | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:18558630, BHF-UCL). AKT1's pro-migratory role in endothelium is well described. Reason: The donor IMP is genuine, but the term is a cell-type-restricted migration phenotype; as a rat gene-level annotation, endothelial-cell-specific migration promotion is contextual over-annotation rather than a distinguishing conserved function. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:18558630. The experiment supports the human annotation; the transfer concern is the cell-type-restricted phenotype scope, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:RGD. |
| GO:0046889 positive regulation of lipid biosynthetic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The rat ISS transfers from the same human AKT1 record as the ISO row for this term, where the donor carries two experimental annotations (IDA PMID:32322062; IMP PMID:8940145) for promotion of lipid biosynthesis, a canonical output of insulin-AKT signalling. Reason: As for the ISO row: two independent donor experiments support the term and the lipogenic axis of insulin-AKT signalling is conserved across mammals, so the transfer to rat is safe as a non-core metabolic-output annotation, consistent with the ISO row for this term. Supporting Evidence: UniProtKB:P47196 GO; GO:0046889; P:positive regulation of lipid biosynthetic process; ISS:UniProtKB. |
| GO:2001243 negative regulation of intrinsic apoptotic signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; ISO:RGD. |
| GO:0005516 calmodulin binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: UniProt ISS calmodulin binding from human AKT1 (P31749). Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB. |
| GO:0005516 calmodulin binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB. |
| GO:0002042 cell migration involved in sprouting angiogenesis | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:28341552, BHF-UCL) in an angiogenesis model; AKT1 contributes to angiogenic signalling. Reason: The donor IMP is genuine, but the term names a highly specific cellular behaviour within one vascular developmental programme (migration during sprouting angiogenesis); for rat, without rat-directed evidence, this remains contextual over-annotation of a broadly acting kinase. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:28341552. The experiment supports the human annotation; the transfer concern is the narrow angiogenic-programme scope, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; ISO:RGD. |
| GO:0010628 positive regulation of gene expression | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1 (IMP, PMID:18292230) and human AKT1 (IMP, PMID:28341552), perturbation studies in which AKT signalling changed expression readouts. Reason: Re-reviewed 2026-10-17: aligned with the negative regulation of gene expression row and the human donor-split row. The donor evidence is experimental and transfers, so this is not a removal. The problem is granularity: positive regulation of gene expression is an uninformative readout for a kinase that acts on expression indirectly, by phosphorylating transcriptional regulators such as CREB1. Flagged as over-annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IMP from PMID:18292230, so the donor annotation is experimentally grounded. The objection is the generic term, not the transfer. UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Traced against the human AKT1 GOA record (UniProtKB/P31749, QuickGO retrieved 2026-09-01): donor support is IMP from PMID:28341552, so the donor annotation is experimentally grounded. The objection is the generic term, not the transfer. Supporting Evidence: UniProtKB:P47196 AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 |
| GO:0140052 cellular response to oxidised low-density lipoprotein particle stimulus | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:28341552, BHF-UCL) from vascular-cell experiments using oxidised LDL as stimulus. Reason: The donor IMP is real, but 'cellular response to oxidised low-density lipoprotein particle stimulus' is a disease-context stimulus term; stimulus-response membership of a kinase activated downstream of many stimuli is contextual over-annotation for the rat gene-level record. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:28341552. The experiment supports the human annotation; the transfer concern is the disease-context stimulus scope, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:0140052; P:cellular response to oxidised low-density lipoprotein particle stimulus; ISO:RGD. |
| GO:1903038 negative regulation of leukocyte cell-cell adhesion | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:28341552, BHF-UCL): reduced AKT1 function increased leukocyte adhesion in a vascular-inflammation setting. Reason: The donor IMP is genuine, and regulation terms tolerate indirect action, but the adhesion effect arises through AKT1-dependent endothelial signalling in one vascular-inflammation model; the claim is context-bound and not rat-verified, so it is flagged as over-annotation rather than removed. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:28341552. The experiment supports the human annotation; the transfer concern is the indirect, model-bound adhesion phenotype, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:1903038; P:negative regulation of leukocyte cell-cell adhesion; ISO:RGD. |
| GO:2000402 negative regulation of lymphocyte migration | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:28341552, BHF-UCL): altered lymphocyte migration downstream of AKT1 perturbation in a vascular-inflammation model. Reason: The donor IMP is genuine, but the lymphocyte-migration effect is an indirect, model-bound consequence of AKT1-dependent endothelial signalling; for the rat gene-level record this immune-trafficking claim is contextual over-annotation rather than grounds for outright removal. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:28341552. The experiment supports the human annotation; the transfer concern is the indirect immune-trafficking phenotype scope, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:2000402; P:negative regulation of lymphocyte migration; ISO:RGD. |
| GO:0032880 regulation of protein localization | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Rat experimental annotations also exist for this term (PMID:17715136). Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0032880; P:regulation of protein localization; IMP:MGI. |
| GO:2000010 positive regulation of protein localization to cell surface | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1 IMP (PMID:9415393), a study of Akt in insulin-stimulated GLUT4 translocation to the cell surface in transfected rat adipose cells. Reason: Re-reviewed 2026-10-17: the previous context-mismatch removal was wrong. Insulin-stimulated GLUT4 translocation to the cell surface is one of the best-established AKT functions and is recorded for rat AKT1 in UniProt; the term is a valid annotation. Kept as non-core because the more specific glucose-uptake and insulin-signalling terms carry the core claim. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IMP from PMID:9415393, so the donor annotation is experimentally grounded. The experiment was done in rat adipose cells, so this transfer is well grounded for rat. Supporting Evidence: UniProtKB:P47196 AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface PMID:9415393 we have overexpressed a dominant inhibitory mutant of Akt in rat adipose cells to investigate the effects of inhibiting endogenous Akt in a physiologically relevant insulin target cell |
| GO:0031397 negative regulation of protein ubiquitination | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:18292230, ARUK-UCL): AKT-dependent protection of a substrate from ubiquitination. Reason: The donor IMP is real, but it reflects AKT phosphorylation shielding particular substrates from ubiquitination; generalizing that to a gene-level 'negative regulation of protein ubiquitination' claim is broader than the substrate-specific evidence, so the transfer over-annotates rat Akt1. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:18292230. The experiment supports the human annotation; the transfer concern is generalizing a substrate-specific effect to a process-level claim, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:0031397; P:negative regulation of protein ubiquitination; ISO:RGD. |
| GO:0071356 cellular response to tumor necrosis factor | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IDA (PMID:24349514). The donor evidence is experimental, but it records a TNF stimulus-response readout in which TNF-induced microRNA-494 desensitises insulin signalling and AKT is the signalling readout. Reason: Re-reviewed 2026-10-17: A TNF stimulus-response readout in which TNF-induced microRNA-494 desensitises insulin signalling and AKT is the signalling readout (IDA, PMID:24349514). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:24349514, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0071356; P:cellular response to tumor necrosis factor; ISO:RGD. |
| GO:0042803 protein homodimerization activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0042803; F:protein homodimerization activity; ISO:RGD. |
| GO:0007173 epidermal growth factor receptor signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISO:RGD. |
| GO:0032991 protein-containing complex | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term carries two direct experimental annotations (IDA PMID:23223530; IDA PMID:20878056): human AKT1 was found in protein complexes. Reason: The donor IDA evidence is genuine, but 'protein-containing complex' is the root cellular-component term and conveys nothing about which complex; it is true but uninformative at gene level, so it is retained only as flagged over-annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IDA PMID:23223530 and IDA PMID:20878056. The experiments support the human annotation; the transfer concern is the uninformative root-term granularity, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:0032991; C:protein-containing complex; ISO:RGD. |
| GO:0042981 regulation of apoptotic process | ISS GO_REF:0000024 | MODIFY | Summary: UniProt ISS regulation of apoptotic process from mouse Akt1 (P31750). The term is correct but less informative than the negative regulation of apoptotic process rows, because AKT1 regulates apoptosis in one direction. Reason: Re-reviewed 2026-10-17: the previous reason called this term too specific, which contradicted the summary. The real problem is that it is too general. The ISS row's own support is anti-apoptotic (AKT mediates the antiapoptotic effects of IGF1), so it supports the more specific child GO:0043066 negative regulation of apoptotic process. MODIFY to that term, which this gene already carries on its IBA, ISO and TAS rows. Proposed replacements: negative regulation of apoptotic process Supporting Evidence: UniProtKB:P47196 AKT mediates the antiapoptotic effects of IGF1 |
| GO:0042981 regulation of apoptotic process | ISO GO_REF:0000121 | MODIFY | Summary: The rat ISO traces to mouse Akt1, whose term rests on IDA (PMID:18977203): Akt activation mediates IGF-1 protection of vascular smooth muscle cells against Apop-1-induced death. The term is correct but less informative than negative regulation of apoptotic process. Reason: Re-reviewed 2026-10-17: moved with the sibling ISS row. The donor experiment is anti-apoptotic, so it supports the more specific child GO:0043066 negative regulation of apoptotic process rather than the bidirectional parent. The previous "too specific" reason pointed the wrong way. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:18977203, so the donor annotation is experimentally grounded. The donor result transfers to rat; it supports the negative-regulation child, so the objection is term scope only. Proposed replacements: negative regulation of apoptotic process Supporting Evidence: PMID:18977203 the inhibition of Apop-1-induced death by IGF-1 is mediated by the activation of the PI3K/Akt signaling pathway UniProtKB:P47196 AKT mediates the antiapoptotic effects of IGF1 |
| GO:0046622 positive regulation of organ growth | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IMP (PMID:15713641). The donor evidence is experimental, but it records an organ-size phenotype from a knockout study of brain size. Reason: Re-reviewed 2026-10-17: An organ-size phenotype from a knockout study of brain size (IMP, PMID:15713641). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IMP from PMID:15713641, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0046622; P:positive regulation of organ growth; ISO:RGD. |
| GO:0035655 interleukin-18-mediated signaling pathway | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has direct experimental support (IDA PMID:21321938, BHF-UCL): AKT1 engagement downstream of interleukin-18 in the donor cellular context. Reason: The donor IDA is genuine, but per-cytokine pathway-membership terms for a kinase engaged downstream of many cytokine receptors are context observations; IL-18 pathway membership is not a distinguishing conserved rat Akt1 function, so the transfer is flagged as over-annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IDA PMID:21321938. The experiment supports the human annotation; the transfer is contextual (cytokine-specific pathway membership), not weakly sourced. Supporting Evidence: UniProtKB:P47196 GO; GO:0035655; P:interleukin-18-mediated signaling pathway; ISO:RGD. |
| GO:0048661 positive regulation of smooth muscle cell proliferation | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has direct experimental support (IDA PMID:21321938, BHF-UCL). AKT1 signalling drives proliferation, here read out in smooth muscle cells. Reason: The donor IDA is genuine and pro-proliferative signalling is core AKT biology, but the term restricts the claim to smooth muscle cells - the donor experimental context - rather than a conserved cell-type-specific rat function, so it is flagged as over-annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IDA PMID:21321938. The experiment supports the human annotation; the transfer concern is the cell-type-restricted phenotype scope, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:RGD. |
| GO:0005634 nucleus | IDA PMID:20605787 Ribosomal protein S3, a new substrate of Akt, serves as a si... | KEEP AS NON CORE | Summary: IDA (PMID:20605787): nuclear Akt in NGF-stimulated neuronal cells phosphorylates RPS3, which then accumulates in the nucleus. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: PMID:20605787 Ribosomal protein S3, a new substrate of Akt, serves as a signal mediator between neuronal apoptosis and DNA repair. |
| GO:1900182 positive regulation of protein localization to nucleus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISO:RGD. |
| GO:0032079 positive regulation of endodeoxyribonuclease activity | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has direct experimental support (IDA PMID:20605787): AKT-dependent activation of an endodeoxyribonuclease in one human study. Reason: The donor IDA is real, but it reflects activation of a specific nuclease in a single study; a gene-level claim of positively regulating endodeoxyribonuclease activity overstates the single-substrate evidence for the rat record. GOA no longer carries this row (retired at the 2026 refresh). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IDA PMID:20605787. The experiment supports the human annotation; the transfer concern is elevating a single-substrate readout to a process-level claim, not source weakness. Supporting Evidence: UniProtKB:P47196 AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis (PubMed:9228007, PubMed:11882383, PubMed:21432781, PubMed:21620960). |
| GO:1990090 cellular response to nerve growth factor stimulus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Rat experimental annotations also exist for this term (PMID:20605787, PMID:9492284). Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IDA:UniProtKB. |
| GO:0005515 protein binding | IPI PMID:20605787 Ribosomal protein S3, a new substrate of Akt, serves as a si... | REMOVE | Summary: IPI protein binding with RPS3 (P62909): NGF-stimulated Akt phosphorylates RPS3 at Thr70, and this phosphorylation is required for Akt binding to RPS3. Reason: This is a kinase-substrate interaction already captured by protein serine/threonine kinase activity; generic protein binding adds no information. Removal does not mean the reported interaction is false. Supporting Evidence: PMID:20605787 this phosphorylation was required for Akt binding to RPS3 |
| GO:0006974 DNA damage response | IDA PMID:20605787 Ribosomal protein S3, a new substrate of Akt, serves as a si... | KEEP AS NON CORE | Summary: Rat evidence supports AKT1 participation in DNA damage-associated signaling, but this is a context-dependent response program rather than a core canonical AKT1 term. Reason: Keep as a valid but non-core stress-response annotation. Supporting Evidence: PMID:20605787 Ribosomal protein S3, a new substrate of Akt, serves as a signal mediator between neuronal apoptosis and DNA repair. |
| GO:0018107 peptidyl-threonine phosphorylation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. GOA no longer carries this row (retired at the 2026 refresh). Supporting Evidence: UniProtKB:P47196 AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis (PubMed:9228007, PubMed:11882383, PubMed:21432781, PubMed:21620960). |
| GO:1990090 cellular response to nerve growth factor stimulus | IDA PMID:20605787 Ribosomal protein S3, a new substrate of Akt, serves as a si... | KEEP AS NON CORE | Summary: IDA (PMID:20605787): NGF stimulation leads to Akt-mediated phosphorylation of RPS3 in neuronal cells. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: PMID:20605787 Ribosomal protein S3, a new substrate of Akt, serves as a signal mediator between neuronal apoptosis and DNA repair. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: UniProt ISS nucleus from human AKT1 (P31749). The activated kinase translocates to the nucleus; rat IDA support exists (PMID:20605787). Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 Nucleus {ECO:0000250|UniProtKB:P31749} |
| GO:0005634 nucleus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1 and human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Rat experimental annotations also exist for this term (PMID:20605787). Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0005634; C:nucleus; IDA:UniProtKB. |
| GO:0031982 vesicle | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has direct experimental support (IDA PMID:16792529): AKT1 detected on vesicular structures, consistent with its membrane recruitment during PI3K signalling. Reason: The donor IDA is genuine, but 'vesicle' is a near-root cellular-component term that adds no information beyond the existing membrane and cytoplasm annotations on this record; true but uninformative, so flagged as over-annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IDA PMID:16792529. The experiment supports the human annotation; the transfer concern is the uninformative near-root CC granularity, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:0031982; C:vesicle; ISO:RGD. |
| GO:0072656 maintenance of protein location in mitochondrion | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:23962723, ParkinsonsUK-UCL): an AKT-dependent mitochondrial retention readout for a specific protein in a neurodegeneration-focused study. Reason: The donor IMP is genuine, but it captures a substrate-specific mitochondrial retention readout from one disease-focused context; the trafficking-maintenance claim is too narrow and context-bound to carry to rat at gene level, so it is flagged as over-annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:23962723. The experiment supports the human annotation; the transfer concern is the substrate- and context-specific retention readout, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:0072656; P:maintenance of protein location in mitochondrion; ISO:RGD. |
| GO:0019901 protein kinase binding | IPI PMID:24583056 PRAS40 plays a pivotal role in protecting against stroke by ... | MARK AS OVER ANNOTATED | Summary: Rat IPI (PMID:24583056) with mTOR (RGD:68371) as the WITH partner: in a stroke model, co-immunoprecipitation showed reduced Akt-mTOR association in PRAS40-knockout brain. Reason: Re-reviewed 2026-10-17: this is rat-direct physical-interaction evidence, with no transfer involved. The co-IP is genuine, but it is a pathway-level association measured in an ischaemia model, and the informative relationship (AKT1 phosphorylating PRAS40 to relieve mTORC1 inhibition) is a kinase-substrate one that protein serine/threonine kinase activity already captures. A generic kinase-binding MF adds little, so it is flagged as over-annotation. Supporting Evidence: PMID:24583056 co-immunoprecipitation suggests that there were less interactive effects between Akt and mTOR in the PRAS40 KO |
| GO:0021510 spinal cord development | IDA PMID:23681769 The mechanisms of EGFR in the regulation of axon regeneratio... | MARK AS OVER ANNOTATED | Summary: Rat IDA (PMID:23681769): Akt Ser473 phosphorylation is high in fetal and newborn rat neural tissue and declines in adults; EGFR overexpression raises p-Akt in cultured neurons. Reason: The evidence is a developmental change in Akt phosphorylation level (an expression-type observation) plus an EGFR-driven regeneration assay. It does not show that AKT1 carries out a step of spinal cord development, so the developmental process term overshoots. Not removed, because the curator had the full text. Supporting Evidence: PMID:23681769 Ser473 phosphorylation of Akt and Ser2448 phosphorylation of mTOR were highly expressed in foetal and newborn rats but decreased obviously in adult rats |
| GO:0032794 GTPase activating protein binding | IPI PMID:14707121 Ras GTPase-activating protein binds to Akt and is required f... | KEEP AS NON CORE | Summary: Direct interaction with Ras GTPase-activating protein is supported, but this is a partner-specific interaction rather than a core defining AKT1 function. Reason: Keep as a valid but non-core binding annotation. Supporting Evidence: PMID:14707121 Ras GTPase-activating protein binds to Akt and is required for its activation. |
| GO:0010763 positive regulation of fibroblast migration | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IMP (PMID:23871832). The donor evidence is experimental, but it records a fibroblast-migration readout from an N-Ras study. Reason: Re-reviewed 2026-10-17: A fibroblast-migration readout from an N-Ras study (IMP, PMID:23871832). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IMP from PMID:23871832, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0010763; P:positive regulation of fibroblast migration; ISO:RGD. |
| GO:0035924 cellular response to vascular endothelial growth factor stimulus | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IDA (PMID:25139353). The donor evidence is experimental, but it records a VEGF stimulus-response readout from a PI3K-beta endothelial-repair study. Reason: Re-reviewed 2026-10-17: A VEGF stimulus-response readout from a PI3K-beta endothelial-repair study (IDA, PMID:25139353). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:25139353, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; ISO:RGD. |
| GO:0036294 cellular response to decreased oxygen levels | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IDA (PMID:24875179). The donor evidence is experimental, but it records a hypoxia stimulus-response readout from an ischaemic-stroke PTEN-degradation study. Reason: Re-reviewed 2026-10-17: A hypoxia stimulus-response readout from an ischaemic-stroke PTEN-degradation study (IDA, PMID:24875179). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:24875179, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0036294; P:cellular response to decreased oxygen levels; ISO:RGD. |
| GO:0060416 response to growth hormone | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: UniProt ISS from bovine AKT1 (UniProtKB:Q01314), whose term rests on AgBase IDA PMID:16698222: in bovine mammary epithelial cells, growth hormone enhanced IGF-I-induced Akt phosphorylation by suppressing IGFBP-5. Reason: Re-grounded 2026-10-17: in the donor study growth hormone acts indirectly, by lowering IGFBP-5 and so enhancing IGF-I signalling, and AKT phosphorylation is the readout. The term is defensible in that loose sense, but it records a stimulus whose effect on AKT1 is indirect and was measured in one bovine cell system, so it remains flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:Q01314 · bovine AKT1 SUPPORTS TRANSFER Bovine AKT1 carries the term by IDA (PMID:16698222, AgBase; QuickGO checked 2026-10-17). AKT phosphorylation is the readout of an indirect, IGFBP-5-mediated GH effect in mammary epithelial cells. Supporting Evidence: PMID:16698222 GH along with IGF-I enhanced the phosphorylation of Akt through the reduction of IGF binding protein (IGFBP)-5 |
| GO:1990418 response to insulin-like growth factor stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: AKT1 is a canonical downstream effector of insulin-like growth factor signaling, but this stimulus-response term is still contextual rather than a core molecular function. Reason: Keep as a valid but non-core pathway-context annotation. Supporting Evidence: UniProtKB:P47196 GO; GO:1990418; P:response to insulin-like growth factor stimulus; ISS:AgBase. |
| GO:0031663 lipopolysaccharide-mediated signaling pathway | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IDA (PMID:24740015). The donor evidence is experimental, but it records an LPS stimulus-response readout from a myeloid Rictor-deletion macrophage study. Reason: Re-reviewed 2026-10-17: An LPS stimulus-response readout from a myeloid Rictor-deletion macrophage study (IDA, PMID:24740015). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:24740015, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISO:RGD. |
| GO:0071380 cellular response to prostaglandin E stimulus | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IDA (PMID:23479225). The donor evidence is experimental, but it records a prostaglandin E2 stimulus-response readout in macrophages. Reason: Re-reviewed 2026-10-17: A prostaglandin E2 stimulus-response readout in macrophages (IDA, PMID:23479225). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:23479225, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0071380; P:cellular response to prostaglandin E stimulus; ISO:RGD. |
| GO:0010975 regulation of neuron projection development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1 IDA (PMID:19778506, PMID:21976490): AKT-mTOR signalling controls neuronal development of adult-born neurons and axonal growth responses. Reason: Re-reviewed 2026-10-17 on re-grounding: the previous removal cited only the self-referential UniProt GO line. The donor evidence is experimental (mouse IDA, PMID:19778506 and PMID:21976490) and UniProt records an AKT-mTOR role in dendritic development of newborn neurons for rat AKT1 by similarity. A regulation term tolerates this kinase-signalling role, and nothing argues against it in rat. Kept as non-core: neuron projection development is one cell-type outcome of PI3K/AKT signalling, not a defining AKT1 function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:19778506, PMID:21976490, so the donor annotation is experimentally grounded. Experimental neuronal evidence; transfers to the rat ortholog. Supporting Evidence: UniProtKB:P47196 AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation PMID:19778506 multiple genetic manipulations to enhance AKT signaling in adult-born neurons in vivo exhibit similar defects as DISC1 suppression in neuronal development |
| GO:0005515 protein binding | IPI PMID:16832058 Ebp1 isoforms distinctively regulate cell survival and diffe... | REMOVE | Summary: IPI protein binding with Ebp1/PA2G4 (Q6AYD3), consistent with the UniProt SUBUNIT note that rat Akt1 interacts with PA2G4 (PubMed:16832058). The paper characterises Ebp1 isoforms; Akt is a binding partner of nuclear Ebp1 p48. Reason: Generic protein binding is uninformative and the paper defines no specific Akt1 molecular function for this interaction. Removal does not mean the reported interaction is false. Supporting Evidence: PMID:16832058 Ebp1 binds nuclear Akt and prevents DNA fragmentation by inhibiting caspase-activated DNase |
| GO:0006979 response to oxidative stress | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Oxidative-stress signaling through AKT1 is biologically plausible and supported in mammalian systems, but it is not the core defining function of AKT1. Reason: Keep as a valid but non-core stress-response annotation. Supporting Evidence: UniProtKB:P47196 GO; GO:0006979; P:response to oxidative stress; ISS:ParkinsonsUK-UCL. |
| GO:0031641 regulation of myelination | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IMP (PMID:24101522). The donor evidence is experimental, but it records a CNS myelination phenotype from a microRNA-23a study. Reason: Re-reviewed 2026-10-17: A CNS myelination phenotype from a microRNA-23a study (IMP, PMID:24101522). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IMP from PMID:24101522, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0031641; P:regulation of myelination; ISO:RGD. |
| GO:0051721 protein phosphatase 2A binding | IPI PMID:11884620 Protein phosphatase 2A forms a molecular complex with Shc an... | KEEP AS NON CORE | Summary: Rat IPI (PMID:11884620) protein phosphatase 2A binding with the PP2A catalytic subunit (WITH RGD:3380, Ppp2ca). The cached abstract concerns PP2A-Shc association in Rat-1 fibroblasts and does not mention Akt; the full text is not available. Reason: Association of AKT1 with PP2A, which dephosphorylates and inactivates it, is well established, and UniProt records AKT1 interaction with the PP2A regulatory subunit PPP2R5B. The previous REMOVE second-guessed an IPI whose full text we have not read; defer to the curator and keep it as a non-core regulatory interaction. Supporting Evidence: UniProtKB:P47196 Interacts with BAD, PPP2R5B, STK3 and STK4 file:rat/Akt1/Akt1-deep-research-falcon.md protein phosphatases such as **PP2A** and **PHLPP**, which dephosphorylate AKT regulatory sites |
| GO:0071889 14-3-3 protein binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0071889; F:14-3-3 protein binding; ISO:RGD. |
| GO:0004712 protein serine/threonine/tyrosine kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: The rat ISO traces to human AKT1, and donor experiments support kinase function, but this GO term is either overly broad or chemically inaccurate for AKT1. AKT1 is a serine/threonine kinase, not a generic or tyrosine kinase. Reason: Replace the transferred ISO term with the specific serine/threonine kinase activity term used for AKT-family biochemistry. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Human AKT1 carries this term by IDA (PMID:19162005, PMID:22797923), but for rat Akt1 the serine/threonine-specific term is the accurate description. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: UniProtKB:P47196 GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; ISO:RGD. |
| GO:0036064 ciliary basal body | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1 IDA (PMID:19596798): in growth-arrested 3T3-L1 preadipocytes, activated Akt-1 was detected at the ciliary basal body as part of ciliary IGF-1-receptor signalling. Reason: Re-reviewed 2026-10-17: this is a subcellular location, not a tissue or stimulus context, and the previous CONTEXT_OR_TISSUE_MISMATCH removal did not describe the objection. The donor observation is direct and fits the ciliary roles UniProt records for AKT1 (Rab11-effector switch in preciliary trafficking), and nothing argues against it in rat. Kept as a valid non-core location for a kinase that acts at several membranes. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:19596798, so the donor annotation is experimentally grounded. Direct localisation of activated Akt-1 at the basal body; transfers to the rat ortholog. Supporting Evidence: PMID:19596798 Akt-1, an important signal molecule of the IGF-1 receptor in adipocyte differentiation, was also activated at the basal body |
| GO:0005911 cell-cell junction | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1 IDA (PMID:23793062), a T-cell study of Rltpr in CD28 costimulation at the immunological synapse. Reason: Re-reviewed 2026-10-17: a subcellular location, not a tissue or stimulus context, so CONTEXT_OR_TISSUE_MISMATCH was the wrong label and REMOVE is not argued. The donor observation is an experimental localisation, but it captures a transient signalling pool at the T-cell/APC contact in one study, and AKT1 is not a junctional protein in general; flagged as over-annotation rather than removed. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:23793062, so the donor annotation is experimentally grounded. Single-study localisation at a T-cell contact; no reason to think rat differs. Supporting Evidence: PMID:23793062 Engagement of TCR-CD28 at the immunological synapse resulted in the colocalization of CD28 with both wild-type and mutant Rltpr proteins |
| GO:1901653 cellular response to peptide | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1 IDA (PMID:23793062), a T-cell CD28 costimulation study. Rat expression-pattern evidence also exists for this term (IEP, PMID:18772167). Reason: Re-reviewed 2026-10-17: a stimulus class is not a tissue context, so CONTEXT_OR_TISSUE_MISMATCH was the wrong label. The donor evidence is experimental and transfers. The objection, as for the rat IEP row, is that "cellular response to peptide" is a generic stimulus class: AKT1 is activated downstream of many receptors, so the term records a signalling readout. Flagged as over-annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:23793062, so the donor annotation is experimentally grounded. The objection is the generic stimulus term, not the transfer. Supporting Evidence: PMID:18772167 Short-term exposure of neonatal islets to INGAP-PP (90 s, 5, 15, and 30 min) significantly increased Akt1(-Ser473) and MAPK3/1(-Thr202/Tyr204) phosphorylation |
| GO:0097011 cellular response to granulocyte macrophage colony-stimulating factor stimulus | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IDA (PMID:23610142). The donor evidence is experimental, but it records a GM-CSF stimulus-response readout from a dendritic-cell differentiation study. Reason: Re-reviewed 2026-10-17: A GM-CSF stimulus-response readout from a dendritic-cell differentiation study (IDA, PMID:23610142). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:23610142, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; ISO:RGD. |
| GO:0001938 positive regulation of endothelial cell proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: UniProt ISS positive regulation of endothelial cell proliferation from human AKT1 (P31749); AKT signaling promotes endothelial proliferation in angiogenesis. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis |
| GO:0001938 positive regulation of endothelial cell proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:UniProtKB. |
| GO:0005739 mitochondrion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0005739; C:mitochondrion; ISO:RGD. |
| GO:0005515 protein binding | IPI PMID:22218591 PKB/Akt partners with Dab2 in albumin endocytosis. | REMOVE | Summary: IPI protein binding with Dab2 shown by co-immunoprecipitation and GST pull-down in proximal tubule cells. Reason: Generic protein binding is uninformative; the paper does not establish a specific Akt1 molecular function for the Dab2 interaction. Removal does not mean the reported interaction is false. GOA no longer carries this row (retired at the 2026 refresh). Supporting Evidence: PMID:22218591 We showed a novel interaction between prosurvival protein, protein kinase B (PKB/Akt), and adaptor protein, disabled 2 (Dab2), with coimmunoprecipitation. |
| GO:0097194 execution phase of apoptosis | ISO GO_REF:0000121 | REMOVE | Summary: The rat ISO traces to mouse Akt1 IDA (PMID:12124386): during cytokine withdrawal Akt1 is cleaved by caspases at Asp-462, and the cleavage product loses kinase activity. Reason: Re-reviewed 2026-10-17: the objection is role conflation, not context. In the donor study AKT1 is the substrate of the executioner caspases: its cleavage at Asp-462 switches off a survival signal. A substrate destroyed during the execution phase does none of the work of that phase, and AKT1's own activity opposes apoptosis. UniProt records the caspase-3 cleavage for rat AKT1 as a PTM. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS SOURCE BUT NOT TARGET Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:12124386, so the donor annotation is experimentally grounded. The experiment is sound; it shows AKT1 as a caspase substrate, which is not participation in apoptotic execution. Supporting Evidence: PMID:12124386 we demonstrated residue Asp-462 of Akt1 which is just upstream of the hydrophobic motif to be the primary cleavage site UniProtKB:P47196 Cleaved at the caspase-3 consensus site Asp-462 during apoptosis |
| GO:0071260 cellular response to mechanical stimulus | IDA PMID:20042609 Mechano-transduction in osteoblastic cells involves strain-r... | KEEP AS NON CORE | Summary: Mechanical-stimulus signaling can engage AKT-dependent pathways in rat cells, but the term reflects a specific physiological context rather than the core AKT1 function. Reason: Keep as a valid but non-core physiology annotation. Supporting Evidence: PMID:20042609 Mechano-transduction in osteoblastic cells involves strain-regulated estrogen receptor alpha-mediated control of insulin-like growth factor (IGF) I receptor sensitivity to Ambient IGF, leading to phosphatidylinositol 3-kinase/AKT-dependent Wnt/LRP5 receptor-independent activation of beta-catenin signaling. |
| GO:0010507 negative regulation of autophagy | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0010507; P:negative regulation of autophagy; ISO:RGD. |
| GO:0045861 negative regulation of proteolysis | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:18387192, BHF-UCL): AKT-dependent protection of a substrate from proteolysis. Reason: The donor IMP is genuine, but 'negative regulation of proteolysis' is a broad parent term generalized from protection of particular substrates; at gene level it is true but uninformative, so it is kept only as flagged over-annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:18387192. The experiment supports the human annotation; the transfer concern is the broad, uninformative parent-term granularity, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:0045861; P:negative regulation of proteolysis; ISO:RGD. |
| GO:0010765 positive regulation of sodium ion transport | IMP PMID:17715136 Akt mediates the effect of insulin on epithelial sodium chan... | KEEP AS NON CORE | Summary: IMP (PMID:17715136): Akt mediates insulin stimulation of epithelial sodium channels by inhibiting Nedd4-2. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: PMID:17715136 Akt mediates the effect of insulin on epithelial sodium channels by inhibiting Nedd4-2. |
| GO:0032869 cellular response to insulin stimulus | IMP PMID:17715136 Akt mediates the effect of insulin on epithelial sodium chan... | KEEP AS NON CORE | Summary: IMP (PMID:17715136): Akt is required for the insulin effect on epithelial sodium channels. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: PMID:17715136 Akt mediates the effect of insulin on epithelial sodium channels by inhibiting Nedd4-2. |
| GO:0032880 regulation of protein localization | IMP PMID:17715136 Akt mediates the effect of insulin on epithelial sodium chan... | KEEP AS NON CORE | Summary: IMP (PMID:17715136): Akt-mediated inhibition of Nedd4-2 regulates ENaC surface abundance. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: PMID:17715136 Akt mediates the effect of insulin on epithelial sodium channels by inhibiting Nedd4-2. |
| GO:0032287 peripheral nervous system myelin maintenance | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IMP (PMID:20448149). The donor evidence is experimental, but it records a peripheral-nerve myelin phenotype from a Dlg1-PTEN study. Reason: Re-reviewed 2026-10-17: A peripheral-nerve myelin phenotype from a Dlg1-PTEN study (IMP, PMID:20448149). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IMP from PMID:20448149, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0032287; P:peripheral nervous system myelin maintenance; ISO:RGD. |
| GO:0019901 protein kinase binding | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1 IPI (PMID:22057101), from a ZNRF1/AKT/GSK3B axonal-degeneration study. Rat IPI evidence also exists for this term (PMID:24583056). Reason: Re-reviewed 2026-10-17: protein kinase binding is not a tissue context, so CONTEXT_OR_TISSUE_MISMATCH was the wrong label. The donor evidence is experimental and transfers. The objection is granularity: AKT1's interactions with other kinases (GSK3B, mTOR) are kinase-substrate or pathway associations, which protein serine/threonine kinase activity captures more informatively. Flagged as over-annotation, consistent with the rat IPI row. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IPI from PMID:22057101, so the donor annotation is experimentally grounded. The objection is the generic binding term, not the transfer. Supporting Evidence: PMID:22057101 AKT phosphorylates glycogen synthase kinase-3β (GSK3B), and thereby inactivates it in axons |
| GO:0045907 positive regulation of vasoconstriction | IMP PMID:21532183 Acute modulation of vasoconstrictor responses by pravastatin... | MODIFY | Summary: Rat IMP (PMID:21532183): in isolated rat mesenteric small vessels, an Akt1/2 inhibitor abolished the ability of pravastatin to reduce vasoconstrictor responses; the authors conclude that pravastatin inhibits constriction by increasing endothelial NO via the Akt pathway. Reason: The abstract's finding runs opposite to the annotated direction: Akt mediates the statin-induced, NO-dependent reduction of vasoconstrictor responses. That affirmatively supports negative regulation of vasoconstriction, so the row is modified to GO:0045906 rather than removed. The pan-Akt1/2 inhibitor caveat applies either way; a curator should confirm against the full text. Proposed replacements: negative regulation of vasoconstriction Supporting Evidence: PMID:21532183 In small vessels, pravastatin inhibits constrictor responses by increasing endothelial NO bioavailability via the Akt pathway. |
| GO:0071456 cellular response to hypoxia | IDA PMID:20515660 Suppression of Akt1 phosphorylation by adenoviral transfer o... | KEEP AS NON CORE | Summary: Rat pulmonary arterial smooth-muscle data support AKT1 involvement in hypoxia-responsive signaling, but the term remains a context-specific response annotation. Reason: Keep as a valid but non-core stimulus-response annotation. Supporting Evidence: PMID:20515660 Suppression of Akt1 phosphorylation by adenoviral transfer of the PTEN gene inhibits hypoxia-induced proliferation of rat pulmonary arterial smooth muscle cells. |
| GO:0090201 negative regulation of release of cytochrome c from mitochondria | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: UniProt ISS negative regulation of release of cytochrome c from mitochondria from mouse Akt1 (P31750); AKT1 suppresses intrinsic apoptosis. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 AKT also regulates cell survival via the phosphorylation of MAP3K5 |
| GO:0090201 negative regulation of release of cytochrome c from mitochondria | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISS:UniProtKB. |
| GO:0005524 ATP binding | ISO GO_REF:0000121 | ACCEPT | Summary: The rat ISO traces to human AKT1. The donor annotation has experimental support and represents a conserved core kinase or PI3K/insulin-signaling function. Rat experimental annotations also exist for this term (PMID:9887206). Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: UniProtKB:P47196 Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) |
| GO:0030334 regulation of cell migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Rat experimental annotations also exist for this term (PMID:17109063). Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0030334; P:regulation of cell migration; IMP:RGD. |
| GO:0033138 positive regulation of peptidyl-serine phosphorylation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. GOA no longer carries this row (retired at the 2026 refresh). Supporting Evidence: UniProtKB:P47196 AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface (PubMed:10400692, PubMed:9632753). |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: UniProt ISS plasma membrane from human AKT1 (P31749). AKT1 is recruited to the plasma membrane via PH-domain binding of PI(3,4,5)P3. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 Cell membrane {ECO:0000269|PubMed:9228007} |
| GO:0006006 glucose metabolic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0006006; P:glucose metabolic process; ISO:RGD. |
| GO:0042593 glucose homeostasis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0042593; P:glucose homeostasis; ISO:RGD. |
| GO:0051146 striated muscle cell differentiation | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IGI (PMID:18762576). The donor evidence is experimental, but it records a muscle-cell differentiation outcome from an IGFBP-5/IGF-II study. Reason: Re-reviewed 2026-10-17: A muscle-cell differentiation outcome from an IGFBP-5/IGF-II study (IGI, PMID:18762576). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IGI from PMID:18762576, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0051146; P:striated muscle cell differentiation; ISO:RGD. |
| GO:0005080 protein kinase C binding | IPI PMID:7488143 Molecular cloning and characterization of a new member of th... | KEEP AS NON CORE | Summary: Rat and mammalian evidence supports a physical association with specific protein kinase C family members, but this is a context-dependent interaction rather than a core defining function of AKT1. Reason: Keep as a real but non-core interaction annotation. Supporting Evidence: PMID:7488143 the pleckstrin homology domain of the three subtypes of RAC-PK associate with both protein kinase C subspecies and beta gamma subunits of G proteins |
| GO:0043536 positive regulation of blood vessel endothelial cell migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:RGD. |
| GO:0010975 regulation of neuron projection development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: UniProt ISS regulation of neuron projection development from mouse Akt1 (P31750), based on mouse neuronal studies. Reason: Re-reviewed 2026-10-17: this ISS (GO_REF:0000024) row is reviewed consistently with the ISO rows for the same term. UniProt transfers it from mouse Akt1, whose support is experimental (IDA, PMID:19778506), and the rat UniProt FUNCTION text records the AKT-mTOR role in dendritic development of newborn neurons by similarity. Kept as non-core rather than removed. Supporting Evidence: UniProtKB:P47196 AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation PMID:19778506 multiple genetic manipulations to enhance AKT signaling in adult-born neurons in vivo exhibit similar defects as DISC1 suppression in neuronal development |
| GO:0005829 cytosol | TAS Reactome:R-RNO-437185 | KEEP AS NON CORE | Summary: Reactome TAS cytosol from a rat-inferred AKT reaction (R-RNO-437185). AKT1 is largely cytosolic. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: file:rat/Akt1/Akt1-deep-research-falcon.md AKT1 is largely **cytosolic (and can be nuclear) in quiescent cells** |
| GO:0005829 cytosol | TAS Reactome:R-RNO-437189 | KEEP AS NON CORE | Summary: Reactome TAS cytosol from a rat-inferred AKT reaction (R-RNO-437189). AKT1 is largely cytosolic. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: file:rat/Akt1/Akt1-deep-research-falcon.md AKT1 is largely **cytosolic (and can be nuclear) in quiescent cells** |
| GO:1903078 positive regulation of protein localization to plasma membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISO:RGD. |
| GO:0001893 maternal placenta development | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IMP (PMID:12783884). The donor evidence is experimental, but it records a knockout placental phenotype (Akt1-null placentas); the phenotype establishes necessity for normal placental development, a pleiotropic downstream outcome. Reason: Re-reviewed 2026-10-17: A knockout placental phenotype (Akt1-null placentas); the phenotype establishes necessity for normal placental development, a pleiotropic downstream outcome (IMP, PMID:12783884). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IMP from PMID:12783884, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0001893; P:maternal placenta development; ISO:RGD. |
| GO:0060709 glycogen cell differentiation involved in embryonic placenta development | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IMP (PMID:12783884). The donor evidence is experimental, but it records a knockout placental phenotype (glycogen cells of Akt1-null placentas), a pleiotropic downstream outcome. Reason: Re-reviewed 2026-10-17: A knockout placental phenotype (glycogen cells of Akt1-null placentas), a pleiotropic downstream outcome (IMP, PMID:12783884). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IMP from PMID:12783884, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0060709; P:glycogen cell differentiation involved in embryonic placenta development; ISO:RGD. |
| GO:0060716 labyrinthine layer blood vessel development | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IMP (PMID:12783884). The donor evidence is experimental, but it records a knockout placental phenotype (labyrinth vasculature of Akt1-null placentas), a pleiotropic downstream outcome. Reason: Re-reviewed 2026-10-17: A knockout placental phenotype (labyrinth vasculature of Akt1-null placentas), a pleiotropic downstream outcome (IMP, PMID:12783884). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IMP from PMID:12783884, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0060716; P:labyrinthine layer blood vessel development; ISO:RGD. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:9887206 Akt kinases and 2-deoxyglucose uptake in rat skeletal muscle... | ACCEPT | Summary: Rat IDA (PMID:9887206): Akt kinase activity measured in rat skeletal muscle in vivo after insulin and exercise. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: PMID:9887206 Administration of insulin resulted in rapid activation of Akt1 kinase, with peak activity observed 5 min after insulin injection |
| GO:0005524 ATP binding | IDA PMID:9887206 Akt kinases and 2-deoxyglucose uptake in rat skeletal muscle... | ACCEPT | Summary: Rat IDA (PMID:9887206) ATP binding inferred from in vitro Akt kinase assays in rat skeletal muscle. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: PMID:9887206 Administration of insulin resulted in rapid activation of Akt1 kinase, with peak activity observed 5 min after insulin injection |
| GO:0006468 protein phosphorylation | IDA PMID:9887206 Akt kinases and 2-deoxyglucose uptake in rat skeletal muscle... | KEEP AS NON CORE | Summary: Rat IDA (PMID:9887206) protein phosphorylation from in vitro Akt kinase assays in rat skeletal muscle. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. GOA no longer carries this row (retired at the 2026 refresh). Supporting Evidence: PMID:9887206 Administration of insulin resulted in rapid activation of Akt1 kinase, with peak activity observed 5 min after insulin injection |
| GO:0005547 phosphatidylinositol-3,4,5-trisphosphate binding | ISO GO_REF:0000121 | ACCEPT | Summary: The rat ISO traces to human AKT1. The donor annotation has experimental support and represents a conserved core kinase or PI3K/insulin-signaling function. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: UniProtKB:P47196 PI(3,4,5)P3 is also required for phosphorylation at Thr-308 and subsequent activation file:rat/Akt1/Akt1-deep-research-falcon.md The PH domain binds **PI(3,4,5)P3 (PIP3)** |
| GO:0030307 positive regulation of cell growth | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Rat experimental annotations also exist for this term (PMID:12084817). Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0030307; P:positive regulation of cell growth; IDA:RGD. |
| GO:0043066 negative regulation of apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1 and human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD. |
| GO:0043325 phosphatidylinositol-3,4-bisphosphate binding | ISO GO_REF:0000121 | ACCEPT | Summary: The rat ISO traces to human AKT1. The donor annotation has experimental support and represents a conserved core kinase or PI3K/insulin-signaling function. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: UniProtKB:P47196 GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; ISO:RGD. file:rat/Akt1/Akt1-deep-research-falcon.md binds **PI(3,4,5)P3 (PIP3)** and **PI(3,4)P2**, recruiting AKT1 to phosphoinositide-enriched membranes |
| GO:0005979 regulation of glycogen biosynthetic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0005979; P:regulation of glycogen biosynthetic process; ISO:RGD. |
| GO:0045600 positive regulation of fat cell differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:8940145, BHF-UCL). The requirement for AKT signalling in adipocyte differentiation is classical, conserved mammalian biology, with Akt-deficient rodent models showing severely impaired adipogenesis. Reason: The donor IMP is experimental and the adipogenic role of AKT is conserved across mammals, so the transfer to rat is defensible. Kept as non-core: adipogenic differentiation is a downstream developmental programme of the core insulin-PI3K effector-kinase function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:8940145. The loss-of-function experiment supports the term and the adipogenic role is conserved; the transfer to rat is sound for a non-core annotation. Supporting Evidence: UniProtKB:P47196 GO; GO:0045600; P:positive regulation of fat cell differentiation; ISO:RGD. |
| GO:0046889 positive regulation of lipid biosynthetic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1, where this term carries two experimental annotations (IDA PMID:32322062; IMP PMID:8940145). Promotion of lipogenesis is a canonical output of insulin-AKT signalling, e.g. through SREBP-dependent lipogenic gene programmes. Reason: Two independent donor experiments support the term and promotion of lipid biosynthesis is a conserved output of insulin-AKT anabolic signalling across mammals, so the transfer to rat is safe. Kept as non-core: a downstream metabolic output of the core effector-kinase function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IDA PMID:32322062 and IMP PMID:8940145. Two experiments support the term on the donor and the lipogenic axis is conserved; the transfer to rat is sound for a non-core annotation. Supporting Evidence: UniProtKB:P47196 GO; GO:0046889; P:positive regulation of lipid biosynthetic process; ISS:UniProtKB. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:10454575 Insulin-induced phosphorylation and activation of cyclic nuc... | ACCEPT | Summary: IDA (PMID:10454575): Akt phosphorylates PDE3B within an RXRXXS motif downstream of insulin/PI3K. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: PMID:10454575 Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt. |
| GO:0019899 enzyme binding | IPI PMID:10454575 Insulin-induced phosphorylation and activation of cyclic nuc... | TOO GENERAL | Summary: IPI enzyme binding with PDE3B (WITH UniProtKB:Q61409, mouse PDE3B): Akt phosphorylates PDE3B at an RXRXXS motif in insulin-stimulated adipocytes. Reason: Enzyme binding is as uninformative as generic protein binding; the interaction is a kinase-substrate relationship already captured by protein serine/threonine kinase activity (IDA from the same paper). Removal does not mean the reported interaction is false. TOO_GENERAL rather than REMOVE: protein kinase C binding, protein phosphatase 2A binding and protein serine/threonine kinase binding, kept in this review, entail this term, so the claim is true but less informative. Supporting Evidence: PMID:10454575 Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt. |
| GO:0051247 positive regulation of protein metabolic process | IMP PMID:9632753 Requirement for activation of the serine-threonine kinase Ak... | MARK AS OVER ANNOTATED | Summary: AKT contributes to anabolic signaling and protein synthesis, but positive regulation of protein metabolic process is too broad and downstream to retain as a precise AKT1 function term. Reason: The annotation captures a real phenotype but is too broad for stable curation. Supporting Evidence: PMID:9632753 Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport. |
| GO:0070141 response to UV-A | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has direct experimental support (IDA PMID:18483258, BHF-UCL): AKT1 engagement observed under UV-A exposure in human cells. Reason: The donor IDA is genuine, but 'response to UV-A' records the stimulus of one experimental paradigm rather than an AKT1 function; carrying it to rat would over-annotate Akt1 as a UV-response gene on the strength of a single stimulus-context observation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IDA PMID:18483258. The experiment supports the human annotation; the transfer concern is the stimulus-context term scope, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:0070141; P:response to UV-A; ISO:RGD. |
| GO:0010765 positive regulation of sodium ion transport | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Rat experimental annotations also exist for this term (PMID:17715136). Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0010765; P:positive regulation of sodium ion transport; IMP:MGI. |
| GO:0030235 nitric-oxide synthase regulator activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:10376603, BHF-UCL) from the classical demonstration that Akt directly phosphorylates and activates endothelial nitric-oxide synthase. Reason: The donor IMP reflects a direct kinase-substrate regulatory relationship - activating phosphorylation of eNOS - that is conserved across mammals and well documented in rodent vascular biology, so the MF transfer to rat is sound. Kept as non-core relative to the general protein serine/threonine kinase activity that is AKT1's core molecular function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:10376603. The experiment supports the term via a direct, conserved kinase-substrate mechanism; the transfer to rat is sound for a non-core annotation. Supporting Evidence: UniProtKB:P47196 GO; GO:0030235; F:nitric-oxide synthase regulator activity; ISO:RGD. |
| GO:0034405 response to fluid shear stress | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:10376603, BHF-UCL): fluid shear stress was the stimulus of the donor endothelial experiments on Akt-dependent eNOS activation. Reason: The donor IMP is genuine, but shear stress is the experimental stimulus of the donor endothelial system rather than an AKT1 function; the mechanistic content is better carried by the NOS-regulator and NO-biosynthesis annotations, leaving this stimulus-response term as contextual over-annotation for rat. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:10376603. The experiment supports the human annotation; the transfer concern is the stimulus-context term scope, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:0034405; P:response to fluid shear stress; ISO:RGD. |
| GO:0045429 positive regulation of nitric oxide biosynthetic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:10376603, BHF-UCL): Akt-mediated activating phosphorylation of eNOS increases nitric-oxide production. Reason: The donor IMP is experimental and the mechanism - direct activating phosphorylation of eNOS driving NO synthesis - is conserved endothelial biology across mammals, so the transfer to rat is defensible. Kept as non-core: one substrate axis downstream of the core kinase function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:10376603. The experiment supports the term via a direct, conserved kinase-substrate mechanism; the transfer to rat is sound for a non-core annotation. Supporting Evidence: UniProtKB:P47196 GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:RGD. |
| GO:0046329 negative regulation of JNK cascade | IDA PMID:17064355 Inhibition of MLK3-MKK4/7-JNK1/2 pathway by Akt1 in exogenou... | KEEP AS NON CORE | Summary: Rat ischemia studies support AKT1-dependent suppression of JNK signaling in a specific neuroprotective context, but this is not the core evolved function of AKT1. Reason: Keep as a valid but non-core pathway-regulation annotation. Supporting Evidence: PMID:17064355 Inhibition of MLK3-MKK4/7-JNK1/2 pathway by Akt1 in exogenous estrogen-induced neuroprotection against transient global cerebral ischemia by a non-genomic mechanism in male rats. |
| GO:0018105 peptidyl-serine phosphorylation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1 and human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. GOA no longer carries this row (retired at the 2026 refresh). Supporting Evidence: UniProtKB:P47196 AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis (PubMed:9228007, PubMed:11882383, PubMed:21432781, PubMed:21620960). |
| GO:0032094 response to food | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IDA (PMID:16513828). The donor evidence is experimental, but it records a pituitary Akt-phosphorylation readout from a diet-induced obesity study of the growth-hormone axis. Reason: Re-reviewed 2026-10-17: A pituitary Akt-phosphorylation readout from a diet-induced obesity study of the growth-hormone axis (IDA, PMID:16513828). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:16513828, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0032094; P:response to food; ISO:RGD. |
| GO:0030030 cell projection organization | IDA PMID:16286931 Regulation of neuronal morphology and function by the tumor ... | MARK AS OVER ANNOTATED | Summary: Neuronal morphology data suggest AKT-pathway involvement in projection organization, but the term is too phenotype-level and context-dependent to retain strongly. Reason: The annotation is plausible but over-annotated for a general AKT1 review. Supporting Evidence: PMID:16286931 Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2. |
| GO:0045792 negative regulation of cell size | IDA PMID:16286931 Regulation of neuronal morphology and function by the tumor ... | UNDECIDED | Summary: Rat IDA (PMID:16286931) negative regulation of cell size from a study of Tsc1/Tsc2 in hippocampal neurons, where loss of Tsc1 or Tsc2 enlarged somas and dendritic spines. The cached abstract does not mention Akt, and the full text is not available. Reason: AKT1 promotes cell growth, partly by inhibiting TSC2, so a negative regulation of cell size annotation looks inconsistent with established AKT1 biology. However, the evidence behind this IDA is in the unavailable full text, so it cannot be adjudicated here. The previous REMOVE is downgraded to UNDECIDED pending curator review. Supporting Evidence: PMID:16286931 loss of Tsc1 or Tsc2 triggered enlargement of somas and dendritic spines and altered the properties of glutamatergic synapses |
| GO:0005654 nucleoplasm | TAS Reactome:R-RNO-198333 | KEEP AS NON CORE | Summary: Reactome TAS nucleoplasm from a rat-inferred AKT reaction (R-RNO-198333), reflecting nuclear AKT activity toward substrates such as FOXO. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 the activated form translocates to the nucleus |
| GO:0005829 cytosol | TAS Reactome:R-RNO-198333 | KEEP AS NON CORE | Summary: Reactome TAS cytosol from a rat-inferred AKT reaction (R-RNO-198333). AKT1 is largely cytosolic. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: file:rat/Akt1/Akt1-deep-research-falcon.md AKT1 is largely **cytosolic (and can be nuclear) in quiescent cells** |
| GO:0005829 cytosol | TAS Reactome:R-RNO-198601 | KEEP AS NON CORE | Summary: Reactome TAS cytosol from a rat-inferred AKT reaction (R-RNO-198601). AKT1 is largely cytosolic. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: file:rat/Akt1/Akt1-deep-research-falcon.md AKT1 is largely **cytosolic (and can be nuclear) in quiescent cells** |
| GO:0006924 activation-induced cell death of T cells | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to human AKT1, where this term has genuine loss-of-function support (IMP PMID:14749367, assigned by MGI, qualifier acts_upstream_of_or_within on the donor record). Reason: The donor IMP is genuine, but the term names a T-cell-lineage-specific organismal immune process read out from loss-of-function phenotypes; for the rat gene-level record this lineage- and context-restricted phenotype is better flagged as over-annotation than carried as a function claim. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Traced against the human AKT1 GOA record (UniProtKB:P31749, genes/human/AKT1/AKT1-goa.tsv), the sole donor named in the rat GOA WITH/FROM. Donor support for this term is experimental: IMP PMID:14749367. The experiment supports the human annotation; the transfer concern is the lineage-restricted immune-phenotype scope, not source weakness. Supporting Evidence: UniProtKB:P47196 GO; GO:0006924; P:activation-induced cell death of T cells; ISO:RGD. |
| GO:0035556 intracellular signal transduction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to human AKT1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0035556; P:intracellular signal transduction; ISO:RGD. |
| GO:0030334 regulation of cell migration | IMP PMID:17109063 Akt-mediated GSK-3beta inhibition prevents migration of poly... | KEEP AS NON CORE | Summary: Rat IMP (PMID:17109063): Akt-mediated GSK-3beta inhibition affects migration of polyamine-depleted intestinal epithelial cells. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: PMID:17109063 Akt-mediated GSK-3beta inhibition prevents migration of polyamine-depleted intestinal epithelial cells via Rac1. |
| GO:0005977 glycogen metabolic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: The rat ISO traces to mouse Akt1. Donor experiments support the term, and the transfer is plausible in rat, but it reflects a contextual localization or process rather than the core evolved AKT1 function. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 GO; GO:0005977; P:glycogen metabolic process; ISO:RGD. |
| GO:0005515 protein binding | IPI PMID:15120593 Altered Bad localization and interaction between Bad and Bcl... | REMOVE | Summary: IPI protein binding with Bad from co-immunoprecipitation in hippocampus after transient global ischemia. Reason: Generic protein binding is uninformative; Akt-Bad association reflects kinase-substrate regulation captured by the kinase activity terms. Removal does not mean the reported interaction is false. GOA no longer carries this row (retired at the 2026 refresh). Supporting Evidence: PMID:15120593 Co-immunoprecipitation studies showed decreased interactions of Bad with Akt and calcineurin in the cytosol |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:12089343 The phosphatidylinositol 3-kinase/Akt signaling pathway modu... | ACCEPT | Summary: IDA (PMID:12089343): Akt shows differentiation-dependent activation downstream of PI3K in trophoblast cells. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: PMID:12089343 The phosphatidylinositol 3-kinase/Akt signaling pathway modulates the endocrine differentiation of trophoblast cells. |
| GO:0006468 protein phosphorylation | IDA PMID:12084817 A protein kinase B-dependent and rapamycin-sensitive pathway... | KEEP AS NON CORE | Summary: Rat IDA (PMID:12084817) protein phosphorylation from a study showing a PKB-dependent, rapamycin-sensitive pathway controls skeletal muscle growth. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. GOA no longer carries this row (retired at the 2026 refresh). Supporting Evidence: PMID:12084817 A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification. |
| GO:0009725 response to hormone | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IDA (PMID:16357133). The donor evidence is experimental, but it records a generic hormone-response term from a study of AKT phosphorylation of the Pdcd4 tumour suppressor. Reason: Re-reviewed 2026-10-17: A generic hormone-response term from a study of AKT phosphorylation of the Pdcd4 tumour suppressor (IDA, PMID:16357133). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:16357133, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0009725; P:response to hormone; ISO:RGD. |
| GO:0004674 protein serine/threonine kinase activity | ISS GO_REF:0000024 | ACCEPT | Summary: UniProt ISS protein serine/threonine kinase activity from human AKT1 (P31749). The defining catalytic activity, also supported by rat IDA rows. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: UniProtKB:P47196 Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) |
| GO:0005978 glycogen biosynthetic process | IMP PMID:10400692 Requirement for Akt (protein kinase B) in insulin-induced ac... | KEEP AS NON CORE | Summary: Rat insulin-signaling experiments support AKT1 contribution to glycogen synthesis control, but this is a downstream physiological program rather than the core molecular function. Reason: Keep as a valid but non-core metabolic-process annotation. Supporting Evidence: PMID:10400692 Requirement for Akt (protein kinase B) in insulin-induced activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1). |
| GO:0006412 translation | IMP PMID:10400692 Requirement for Akt (protein kinase B) in insulin-induced ac... | KEEP AS NON CORE | Summary: AKT1 promotes translation and protein synthesis in insulin-responsive contexts, but translation is a downstream anabolic program rather than AKT1's core direct function. Reason: Keep as a valid but non-core process annotation. Supporting Evidence: PMID:10400692 Requirement for Akt (protein kinase B) in insulin-induced activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1). |
| GO:0006412 translation | IMP PMID:9632753 Requirement for activation of the serine-threonine kinase Ak... | KEEP AS NON CORE | Summary: AKT1 promotes translation and protein synthesis in insulin-responsive contexts, but translation is a downstream anabolic program rather than AKT1's core direct function. Reason: Keep as a valid but non-core process annotation. Supporting Evidence: PMID:9632753 Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport. |
| GO:0006468 protein phosphorylation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: UniProt ISS protein phosphorylation from human AKT1 (P31749). Correct process framing of the core kinase activity. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates |
| GO:0008286 insulin receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: UniProt ISS insulin receptor signaling pathway from human AKT1 (P31749); rat IMP/IDA rows support this directly. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: UniProtKB:P47196 Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) |
| GO:0008286 insulin receptor signaling pathway | IMP PMID:9632753 Requirement for activation of the serine-threonine kinase Ak... | ACCEPT | Summary: IMP (PMID:9632753): a dominant-negative Akt (Akt-AA) blocks insulin stimulation of protein synthesis but not glucose transport in CHO cells and 3T3-L1 adipocytes. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: PMID:9632753 Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport. |
| GO:0048009 insulin-like growth factor receptor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: UniProt ISS IGF receptor signaling pathway from human AKT1 (P31749). AKT mediates IGF1 signaling downstream of PI3K. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: UniProtKB:P47196 AKT mediates the antiapoptotic effects of IGF1 |
| GO:0004672 protein kinase activity | IDA PMID:12084817 A protein kinase B-dependent and rapamycin-sensitive pathway... | MODIFY | Summary: Rat IDA (PMID:12084817) protein kinase activity from a skeletal muscle growth study. Correct but less precise than serine/threonine kinase activity. Reason: The rat assay measured PKB kinase activity in regenerating muscle, and PKB is a serine/threonine kinase; the generic parent protein kinase activity undersells that, so GO:0004674 is the precise term. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:12084817 PKB kinase activity and phosphorylation status are significantly increased in innervated compared with denervated regenerating muscles |
| GO:0004674 protein serine/threonine kinase activity | TAS PMID:12084817 A protein kinase B-dependent and rapamycin-sensitive pathway... | ACCEPT | Summary: TAS (PMID:12084817) protein serine/threonine kinase activity from a PKB skeletal muscle growth study; consistent with rat IDA rows. Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals. Supporting Evidence: PMID:12084817 A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification. |
| GO:0005515 protein binding | IPI PMID:12194869 Akt1 regulates a JNK scaffold during excitotoxic apoptosis. | REMOVE | Summary: IPI protein binding with the JNK scaffold JIP1; Akt1-JIP1 association in neurons limits JIP1-mediated JNK activation. Reason: Generic protein binding is uninformative. The row has been withdrawn from GOA, so no replacement term is proposed here; the regulatory effect is represented by negative regulation of JNK cascade. Removal does not mean the reported interaction is false. GOA no longer carries this row (retired at the 2026 refresh). Supporting Evidence: PMID:12194869 Direct association between Akt1 and JIP1 was observed in primary neurons. |
| GO:0030307 positive regulation of cell growth | IDA PMID:12084817 A protein kinase B-dependent and rapamycin-sensitive pathway... | KEEP AS NON CORE | Summary: Rat IDA (PMID:12084817): a PKB-dependent, rapamycin-sensitive pathway controls skeletal muscle growth (fiber size) in regenerating muscle. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: PMID:12084817 A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification. |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:20403980 Selective blockade of protein kinase B protects the rat and ... | MARK AS OVER ANNOTATED | Summary: Rat IMP (PMID:20403980): in rat and human myocardial slices subjected to ischaemia/reoxygenation, PKB inhibitors reduced creatine kinase release, necrosis and apoptosis. Reason: The abstract supports a pro-death role of PKB in this ischaemia model, so REMOVE is not justified. However, the inhibitors are not AKT1-specific, the effect is confined to ischaemic myocardium, and it runs against the well-established anti-apoptotic role of AKT1. Retaining positive regulation of apoptotic process as a general rat Akt1 annotation overshoots the evidence. Supporting Evidence: PMID:20403980 blockade of PKB activity caused significant reduction of CK release and cell death |
| GO:0043066 negative regulation of apoptotic process | TAS PMID:12084817 A protein kinase B-dependent and rapamycin-sensitive pathway... | KEEP AS NON CORE | Summary: TAS (PMID:12084817) negative regulation of apoptotic process, author statement from a PKB skeletal muscle growth study; pro-survival signaling is a well-established AKT output. Reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function. Supporting Evidence: PMID:12084817 A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification. |
| GO:0005819 spindle | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1 IDA (PMID:15509711), an immunocytochemical survey of phosphorylated kinases and transcription factors in mitotic trophoblast stem cells and preimplantation embryos. Reason: Re-reviewed 2026-10-17: a subcellular location, not a tissue or stimulus context, so CONTEXT_OR_TISSUE_MISMATCH was the wrong label and REMOVE is not argued. The donor evidence is a phospho-epitope survey in which most of the surveyed phosphoproteins associated with the spindle during M phase, so it says little that is specific to AKT1; flagged as over-annotation rather than removed. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:15509711, so the donor annotation is experimentally grounded. Survey-level localisation; no reason to think rat differs. Supporting Evidence: PMID:15509711 Most phosphoproteins appeared to associate with the spindle complex during M phase |
| GO:0008637 apoptotic mitochondrial changes | ISO GO_REF:0000121 | REMOVE | Summary: The rat ISO traces to mouse Akt1 IDA (PMID:12869584), a study of the survival kinase Pim-2 in which survival kinases maintain mitochondrial potential after growth-factor withdrawal. Reason: Re-reviewed 2026-10-17: the objection is role conflation, not context. AKT1 is a survival kinase that suppresses the mitochondrial events of apoptosis, for example through inhibitory phosphorylation of MAP3K5 and of BAD. Involved_in apoptotic mitochondrial changes names it as a participant in a process its activity opposes; a correct claim would be a negative-regulation term, which the anti-apoptotic rows on this gene already cover. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS SOURCE BUT NOT TARGET Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:12869584, so the donor annotation is experimentally grounded. The experiment is sound; the objection is that the term names an inhibitor of the process as a participant. Supporting Evidence: UniProtKB:P47196 Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis PMID:12869584 Pim-2 expression maintained cell size and mitochondrial potential independently of the PI3K/Akt/TOR pathway |
| GO:0016567 protein ubiquitination | ISO GO_REF:0000121 | REMOVE | Summary: The rat ISO traces to mouse Akt1 IDA (PMID:12145204): Akt and Mdm2 form a complex with the androgen receptor, and Akt phosphorylation of Mdm2 promotes Mdm2-dependent AR ubiquitylation. Reason: Re-reviewed 2026-10-17: the objection is participation, not context. The ubiquitination is catalysed by the Mdm2 E3 ligase; AKT1 phosphorylates Mdm2 and so regulates the ligase, but does not perform the ubiquitin transfer. Involved_in protein ubiquitination names AKT1 as the agent of a step another gene product carries out. The regulatory relationship is what the positive regulation of proteasomal ubiquitin-dependent protein catabolic process row on this gene expresses, so removal loses no biology. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS SOURCE BUT NOT TARGET Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:12145204, so the donor annotation is experimentally grounded. The experiment is sound; the objection is that the term casts the regulating kinase as the ubiquitinating agent. Supporting Evidence: PMID:12145204 the E3 ligase activity of Mdm2 and phosphorylation of Mdm2 by Akt are essential for Mdm2 to affect AR ubiquitylation and degradation |
| GO:0030163 protein catabolic process | ISO GO_REF:0000121 | REMOVE | Summary: The rat ISO traces to mouse Akt1 IDA (PMID:12145204): Akt promotes Mdm2-dependent ubiquitylation and proteasomal degradation of the androgen receptor. Reason: Re-reviewed 2026-10-17: the objection is participation, not context. The degradation is carried out by the Mdm2 E3 ligase and the proteasome; AKT1 phosphorylates Mdm2 and so regulates that machinery without catalysing any step of protein catabolism. The regulatory relationship is captured by the positive regulation of proteasomal ubiquitin-dependent protein catabolic process row on this gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS SOURCE BUT NOT TARGET Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:12145204, so the donor annotation is experimentally grounded. The experiment is sound; the objection is that the term casts the regulating kinase as the degradation machinery. Supporting Evidence: PMID:12145204 the E3 ligase activity of Mdm2 and phosphorylation of Mdm2 by Akt are essential for Mdm2 to affect AR ubiquitylation and degradation |
| GO:0007281 germ cell development | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The rat ISO traces to mouse Akt1, where the term rests on IDA (PMID:12140361). The donor evidence is experimental, but it records a germ-cell development outcome from a c-Kit signalling study in primordial germ cells. Reason: Re-reviewed 2026-10-17: A germ-cell development outcome from a c-Kit signalling study in primordial germ cells (IDA, PMID:12140361). The donor experiment is genuine and nothing argues for divergence in rat (rat and mouse Akt1 are orthologs with conserved kinase and PH domains), so this is not a removal; but the term records one downstream outcome of AKT1 kinase signalling in that setting rather than a function that characterises the gene, so it is flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Traced against the mouse Akt1 GOA record (UniProtKB/P31750, QuickGO retrieved 2026-09-01): donor support is IDA from PMID:12140361, so the donor annotation is experimentally grounded. Nothing argues that rat Akt1 diverges from mouse Akt1 here; the concern is that the term is a context-bound downstream outcome, not that it fails to transfer. Supporting Evidence: UniProtKB:P47196 GO; GO:0007281; P:germ cell development; ISO:RGD. |
| GO:0001649 osteoblast differentiation | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Donor-split duplicate of the mouse-sourced osteoblast differentiation ISO row, here from human AKT1. The donor annotation is experimental, but osteoblast differentiation is a context-specific downstream outcome of AKT signaling, not an activity AKT1 performs. Reason: Consistent with the mouse-sourced sibling row (re-reviewed 2026-10-17): the human donor IDA (PMID:22869525) is genuine and no rat divergence is argued, but osteoblast differentiation is one cell-type outcome of PI3K/AKT signalling, so it stays flagged as over-annotation. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries involved_in osteoblast differentiation by IDA (PMID:22869525) (QuickGO, checked 2026-10-10); a cell-type-specific outcome. Supporting Evidence: PMID:19208758 an inhibitor of PI3-kinase or a dominant-negative Akt were as potent in preventing osteoblast differentiation as the IGF binding protein IGFBP5 |
| GO:0004672 protein kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: Donor-split duplicate of the protein kinase activity ISO row, here from human AKT1. The term is correct but less precise than the serine/threonine kinase activity established for AKT1. Reason: Human AKT1 donor carries the generic term (IDA, PMID:31204173); AKT1 catalyses Ser/Thr phosphorylation of protein substrates, so the specific child term is the appropriate annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Human AKT1 carries protein kinase activity by IDA (PMID:31204173) (QuickGO, checked 2026-10-10); its characterised activity is protein serine/threonine kinase activity. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: UniProtKB:P47196 This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates UniProtKB:P47196 Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) |
| GO:0004674 protein serine/threonine kinase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split duplicate of the protein serine/threonine kinase activity ISO row, here from human AKT1. This is the defining catalytic activity of AKT1 and is also supported by rat IDA rows (PMID:8524413, PMID:10454575). Reason: Human AKT1 donor has extensive experimental support for this activity; the kinase domain and catalytic mechanism are conserved in rat. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries this term by multiple EXP/IDA annotations (e.g. PMID:10376603, PMID:10102273) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis UniProtKB:P47196 Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) |
| GO:0005080 protein kinase C binding | IPI PMID:7488143 Molecular cloning and characterization of a new member of th... | KEEP AS NON CORE | Summary: Second WITH/FROM split of the PMID:7488143 protein kinase C binding IPI row. The paper shows that the PH domains of all three RAC-PK isoforms, including RAC-PK alpha, associate with PKC subspecies in GST pull-downs. The WITH entity RGD:62390 resolves to rat Akt3 (RAC-PK gamma, the kinase cloned in that paper) rather than a PKC, so the WITH field looks inconsistent with the term. Reason: The pull-down supports a PH-domain interaction with PKC isoforms, but this is an in vitro, partner-specific interaction and not a defining AKT1 function. The WITH oddity is noted for RGD but does not change the paper-level claim. Supporting Evidence: PMID:7488143 the pleckstrin homology domain of the three subtypes of RAC-PK associate with both protein kinase C subspecies and beta gamma subunits of G proteins |
| GO:0005515 protein binding | IPI PMID:16362038 Novel roles of Akt and mTOR in suppressing TGF-beta/ALK5-med... | REMOVE | Summary: IPI protein binding with Smad3 (P84025) from the same study as the Smad2 row. The abstract reports Akt1-Smad3 binding data but concludes that Akt1 suppresses Smad3 activation through its kinase activity via mTOR, not through physical sequestration. Reason: Generic protein binding is uninformative. A more specific binding term (e.g. SMAD binding) is not adopted because the paper argues the interaction is not how Akt1 acts on Smad3; the kinase-dependent mechanism is captured by the kinase activity terms. Removal does not mean the reported interaction is false. Supporting Evidence: PMID:16362038 These and further data on Akt1-S3 binding do not support a recently proposed model that Akt blocks S3 activation through physical interaction and sequestration of S3 from TGF-beta receptors |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic ATP binding annotation from ARBA/InterPro protein kinase domain signatures. ATP is the phosphate donor for AKT1 catalysis; rat IDA support also exists (PMID:9887206). Reason: ATP binding is intrinsic to the conserved kinase domain and the catalysed reaction. Supporting Evidence: UniProtKB:P47196 Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) |
| GO:0005634 nucleus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split duplicate of the nucleus ISO rows, here from pig AKT1. AKT1 is largely cytoplasmic but the activated kinase translocates to the nucleus; rat IDA support exists (PMID:20605787). Reason: Nuclear localization from the pig AKT1 donor is plausible and conserved, but it is a conditional location of the activated kinase rather than its defining site of action. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: RGD:13974772 · pig AKT1 SUPPORTS TRANSFER RGD gene record RGD:13974772 is pig AKT1 (RGD REST lookup, 2026-10-10); the pig annotation behind this transfer was not traced. Nuclear localization of activated AKT1 is independently supported by rat IDA (PMID:20605787) and UniProt. Supporting Evidence: UniProtKB:P47196 Nucleus {ECO:0000250|UniProtKB:P31749} UniProtKB:P47196 the activated form translocates to the nucleus |
| GO:0005634 nucleus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split duplicate of the nucleus ISO rows, here from human AKT1. AKT1 is largely cytoplasmic but the activated kinase translocates to the nucleus; rat IDA support exists (PMID:20605787). Reason: Nuclear localization from the human AKT1 donor is plausible and conserved, but it is a conditional location of the activated kinase rather than its defining site of action. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries nucleus by IDA (PMID:20333297) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 Nucleus {ECO:0000250|UniProtKB:P31749} UniProtKB:P47196 the activated form translocates to the nucleus |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: UniProt ISS nucleus annotation transferred from mouse Akt1 (P31750). The activated kinase translocates to the nucleus; rat IDA support exists (PMID:20605787). Reason: Valid conditional location of activated AKT1, not its defining site of action. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31750 · mouse Akt1 SUPPORTS TRANSFER Mouse Akt1 carries nucleus by EXP/IDA (PMID:20189988, PMID:18388859) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 Nucleus {ECO:0000250|UniProtKB:P31749} UniProtKB:P47196 the activated form translocates to the nucleus |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split duplicate of the cytoplasm rows (ISO, located_in), here from mouse Akt1. AKT1 is predominantly cytoplasmic in unstimulated cells. Reason: Cytoplasmic localization from the mouse Akt1 donor is correct and conserved; it is a broad location annotation rather than a defining function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Mouse Akt1 carries located_in cytoplasm by EXP/IDA (PMID:19028694, PMID:18388859) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 Cytoplasm {ECO:0000250|UniProtKB:P31750} file:rat/Akt1/Akt1-deep-research-falcon.md AKT1 is largely **cytosolic (and can be nuclear) in quiescent cells** |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split duplicate of the cytoplasm rows (ISO, located_in), here from pig AKT1. AKT1 is predominantly cytoplasmic in unstimulated cells. Reason: Cytoplasmic localization from the pig AKT1 donor is correct and conserved; it is a broad location annotation rather than a defining function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: RGD:13974772 · pig AKT1 SUPPORTS TRANSFER RGD gene record RGD:13974772 is pig AKT1 (RGD REST lookup, 2026-10-10); the pig annotation behind this transfer was not traced. Cytoplasmic localization is independently supported by UniProt and rat cytosol IDA (PMID:9112399). Supporting Evidence: UniProtKB:P47196 Cytoplasm {ECO:0000250|UniProtKB:P31750} file:rat/Akt1/Akt1-deep-research-falcon.md AKT1 is largely **cytosolic (and can be nuclear) in quiescent cells** |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split duplicate of the cytoplasm rows (ISO, located_in), here from human AKT1. AKT1 is predominantly cytoplasmic in unstimulated cells. Reason: Cytoplasmic localization from the human AKT1 donor is correct and conserved; it is a broad location annotation rather than a defining function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries cytoplasm by IDA (PMID:19203586, PMID:25190803) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 Cytoplasm {ECO:0000250|UniProtKB:P31750} file:rat/Akt1/Akt1-deep-research-falcon.md AKT1 is largely **cytosolic (and can be nuclear) in quiescent cells** |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Donor-split duplicate of the cytoplasm rows (ISS, located_in), here from mouse Akt1. AKT1 is predominantly cytoplasmic in unstimulated cells. Reason: Cytoplasmic localization from the mouse Akt1 donor is correct and conserved; it is a broad location annotation rather than a defining function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31750 · mouse Akt1 SUPPORTS TRANSFER UniProt ISS from mouse Akt1 (P31750), which carries located_in cytoplasm by EXP/IDA (PMID:19028694, PMID:18388859) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 Cytoplasm {ECO:0000250|UniProtKB:P31750} file:rat/Akt1/Akt1-deep-research-falcon.md AKT1 is largely **cytosolic (and can be nuclear) in quiescent cells** |
| GO:0005758 mitochondrial intermembrane space | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: UniProt ISS (located_in) duplicate of the mitochondrial intermembrane space row from mouse Akt1 (P31750). Mouse Akt1 localizes to the intermembrane space under rapamycin treatment, where it phosphorylates MICU1. Reason: Plausible conditional sub-mitochondrial pool of AKT1; non-core relative to its cytosolic/membrane signaling role. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31750 · mouse Akt1 SUPPORTS TRANSFER Mouse Akt1 carries is_active_in mitochondrial intermembrane space by IDA (PMID:30504268) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 Also localizes to mitochondrial intermembrane space in response to rapamycin treatment |
| GO:0005829 cytosol | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split duplicate of the cytosol ISO row, here from human AKT1. Rat IDA (PMID:9112399) and Reactome also place AKT1 in the cytosol. Reason: Correct, conserved location of inactive and active AKT1 pools; a location rather than a defining function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries cytosol by IDA (PMID:21045808) and Reactome TAS (QuickGO, checked 2026-10-10). Supporting Evidence: file:rat/Akt1/Akt1-deep-research-falcon.md AKT1 is largely **cytosolic (and can be nuclear) in quiescent cells** |
| GO:0005886 plasma membrane | EXP PMID:9228007 Dual role of phosphatidylinositol-3,4,5-trisphosphate in the... | KEEP AS NON CORE | Summary: UniProt EXP plasma membrane annotation based on Stokoe et al. 1997, which showed that PtdIns(3,4,5)P3 binding to the PKB PH domain is required for its activation by the upstream kinase; UniProt records cell-membrane targeting from this work. Reason: PH-domain-mediated recruitment to the plasma membrane is a key, transient step in AKT1 activation; it is kept as a well-supported location consistent with the other plasma membrane rows rather than as the core function itself. Supporting Evidence: UniProtKB:P47196 Cell membrane {ECO:0000269|PubMed:9228007} UniProtKB:P47196 results in its targeting to the plasma membrane (PubMed:9228007) PMID:9228007 Its binding to the pleckstrin homology domain of PKB was required to allow phosphorylation by the upstream kinase |
| GO:0005886 plasma membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split duplicate of the plasma membrane rows (located_in), here from mouse Akt1. AKT1 is recruited to the plasma membrane through PH-domain binding of PI(3,4,5)P3. Reason: Plasma membrane recruitment from the mouse Akt1 donor is conserved and also supported for rat by UniProt (PMID:9228007); kept as a non-core location. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Mouse Akt1 carries located_in plasma membrane by EXP/IDA (PMID:19028694, PMID:15775979) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 Cell membrane {ECO:0000269|PubMed:9228007} UniProtKB:P47196 results in its targeting to the plasma membrane (PubMed:9228007) |
| GO:0005886 plasma membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split duplicate of the plasma membrane rows (located_in), here from human AKT1. AKT1 is recruited to the plasma membrane through PH-domain binding of PI(3,4,5)P3. Reason: Plasma membrane recruitment from the human AKT1 donor is conserved and also supported for rat by UniProt (PMID:9228007); kept as a non-core location. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries plasma membrane by IDA (PMID:14749367, PMID:19203586) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 Cell membrane {ECO:0000269|PubMed:9228007} UniProtKB:P47196 results in its targeting to the plasma membrane (PubMed:9228007) |
| GO:0006954 inflammatory response | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Donor-split duplicate of the inflammatory response ISO row; this split traces to mouse Akt1 IGI (PMID:31874168), an Akt-mTOR pain-hypersensitivity study. Reason: Consistent with the sibling row: the donor evidence is experimental and no rat divergence is argued, but inflammatory response is an organismal outcome inferred from a pain-hypersensitivity study, so it is flagged as over-annotation rather than removed. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Mouse Akt1 carries involved_in inflammatory response by IGI (PMID:31874168) (QuickGO, checked 2026-10-10); context-specific in vivo phenotype. Supporting Evidence: UniProtKB:P47196 AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis |
| GO:0008286 insulin receptor signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split duplicate of the insulin receptor signaling pathway ISO rows, here from pig AKT1. AKT1 is a canonical transducer of insulin signaling; rat experiments support this directly. Reason: Core, conserved pathway role of AKT1 downstream of PI3K in insulin signaling. Propagation Review Root cause: NO FAILURE CORE Sources checked: RGD:13974772 · pig AKT1 SUPPORTS TRANSFER RGD gene record RGD:13974772 is pig AKT1 (RGD REST lookup, 2026-10-10); the pig annotation behind this transfer was not traced. Insulin receptor signaling is independently supported by rat IMP/IDA rows (PMID:10454575, PMID:8524413, PMID:9632753). Supporting Evidence: UniProtKB:P47196 Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) UniProtKB:P47196 AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface |
| GO:0008286 insulin receptor signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split duplicate of the insulin receptor signaling pathway ISO rows, here from human AKT1. AKT1 is a canonical transducer of insulin signaling; rat experiments support this directly. Reason: Core, conserved pathway role of AKT1 downstream of PI3K in insulin signaling. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries this term by IMP (PMID:8978681) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) UniProtKB:P47196 AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface |
| GO:0010467 gene expression | ISO GO_REF:0000121 | REMOVE | Summary: Donor-split (acts_upstream_of_or_within_positive_effect) duplicate of the gene expression ISO row from mouse Akt1 (IMP, PMID:31272455). Reason: Consistent with the sibling row: "gene expression" is a generic readout of knockout phenotypes and conveys no specific AKT1 function. Propagation Review Root cause: PROPAGATION BAD Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS SOURCE BUT NOT TARGET Mouse Akt1 carries acts_upstream_of_or_within_positive_effect gene expression by IMP (PMID:31272455) (QuickGO, checked 2026-10-10); uninformative phenotype readout. Supporting Evidence: UniProtKB:P47196 AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis |
| GO:0010628 positive regulation of gene expression | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Donor-split duplicate of the positive regulation of gene expression ISO row, here from human AKT1 (IMP, PMID:28341552). Reason: Gene-expression changes are indirect consequences of AKT1 substrate phosphorylation (e.g. FOXO, CREB1); the broad term overstates a direct role. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries this term by IMP (PMID:28341552) (QuickGO, checked 2026-10-10); the objection is the generic term, not the transfer. Supporting Evidence: UniProtKB:P47196 AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 |
| GO:0010975 regulation of neuron projection development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (involved_in) duplicate of the regulation of neuron projection development rows from mouse Akt1 (IDA, PMID:19778506). Reason: Consistent with the sibling ISO and ISS rows (re-reviewed 2026-10-17). The previous removal cited only the self-referential UniProt GO line. The donor evidence is experimental (mouse IDA, PMID:19778506 and PMID:21976490) and UniProt records an AKT-mTOR role in dendritic development of newborn neurons for rat AKT1 by similarity. A regulation term tolerates this kinase-signalling role, and nothing argues against it in rat. Kept as non-core: neuron projection development is one cell-type outcome of PI3K/AKT signalling, not a defining AKT1 function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Mouse Akt1 carries involved_in this term by IDA (PMID:19778506) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation PMID:19778506 multiple genetic manipulations to enhance AKT signaling in adult-born neurons in vivo exhibit similar defects as DISC1 suppression in neuronal development |
| GO:0016301 kinase activity | ISO GO_REF:0000121 | MODIFY | Summary: Donor-split duplicate of the kinase activity ISO row, here from human AKT1 (IDA, PMID:14749367). The generic parent term is correct but uninformative for AKT1. Reason: AKT1 is a protein serine/threonine kinase; the specific term should replace generic kinase activity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Human AKT1 carries kinase activity by IDA (PMID:14749367) (QuickGO, checked 2026-10-10); its characterised activity is protein serine/threonine kinase activity. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: UniProtKB:P47196 This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates UniProtKB:P47196 Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) |
| GO:0030291 protein serine/threonine kinase inhibitor activity | IPI PMID:8524413 Inhibition of glycogen synthase kinase-3 by insulin mediated... | REMOVE | Summary: Second WITH/FROM split (GSK3B, P18266) of the PMID:8524413 kinase inhibitor activity row. The paper shows PKB phosphorylates and inactivates GSK3. Reason: AKT1 inactivates GSK3 catalytically by phosphorylation, which is captured by protein serine/threonine kinase activity (rat IDA from the same paper); the inhibitor-activity term describes a non-catalytic inhibitor and misstates the mechanism. Supporting Evidence: PMID:8524413 Another insulin-stimulated protein kinase inactivates GSK3 under these conditions, and we demonstrate that it is the product of the proto-oncogene protein kinase B |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (involved_in) duplicate of the positive regulation of proteasomal ubiquitin-dependent protein catabolic process row, here from human AKT1 (IDA, PMID:23512198). Reason: Consistent with the mouse-sourced sibling row (re-reviewed 2026-10-17): AKT1 regulates E3-ligase-dependent degradation of specific substrates by phosphorylation (e.g. Mdm2), which a regulation term records correctly. Kept as a valid non-core regulatory role. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries this term by IDA (PMID:23512198) (QuickGO, checked 2026-10-10); transfers to rat as a regulatory role. Supporting Evidence: PMID:12145204 the E3 ligase activity of Mdm2 and phosphorylation of Mdm2 by Akt are essential for Mdm2 to affect AR ubiquitylation and degradation |
| GO:0032869 cellular response to insulin stimulus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (involved_in) duplicate of the cellular response to insulin stimulus rows, here from mouse Akt1. Rat IDA/IMP rows support this directly. Reason: Valid and conserved, but broader response-level framing of the core insulin-signaling role already captured by insulin receptor signaling pathway. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Mouse Akt1 carries involved_in this term by IDA (PMID:19139280) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface |
| GO:0032869 cellular response to insulin stimulus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (involved_in) duplicate of the cellular response to insulin stimulus rows, here from human AKT1. Rat IDA/IMP rows support this directly. Reason: Valid and conserved, but broader response-level framing of the core insulin-signaling role already captured by insulin receptor signaling pathway. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries this term by IDA/IMP (e.g. PMID:12172553, PMID:16814735) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface |
| GO:0032880 regulation of protein localization | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (involved_in) duplicate of the regulation of protein localization rows from mouse Akt1 (IMP, PMID:9415393). AKT1 controls the localization of substrates such as FOXO factors and GLUT4 via phosphorylation; rat IMP support exists (PMID:17715136). Reason: Valid indirect consequence of AKT1 substrate phosphorylation; non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Mouse Akt1 carries involved_in by IMP (PMID:9415393) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 leading to binding of 14-3-3 proteins and cytoplasmic localization |
| GO:0043066 negative regulation of apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split duplicate of the negative regulation of apoptotic process ISO row, here from human AKT1 (IDA, PMID:19203586). AKT1 promotes survival by phosphorylating pro-apoptotic substrates. Reason: Well-established conserved pro-survival output of AKT1 kinase activity; kept as non-core relative to the kinase activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries this term by IDA (PMID:19203586) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 AKT mediates the antiapoptotic effects of IGF1 UniProtKB:P47196 AKT also regulates cell survival via the phosphorylation of MAP3K5 |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split (involved_in) duplicate of the PI3K/PKB signal transduction rows, here from pig AKT1. AKT1 is the protein kinase B of this pathway. Reason: Core, conserved pathway role. Propagation Review Root cause: NO FAILURE CORE Sources checked: RGD:13974772 · pig AKT1 SUPPORTS TRANSFER RGD gene record RGD:13974772 is pig AKT1 (RGD REST lookup, 2026-10-10); the pig annotation behind this transfer was not traced. The pathway role is independently supported by rat IDA rows (PMID:10454575, PMID:8524413). Supporting Evidence: UniProtKB:P47196 Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split (involved_in) duplicate of the PI3K/PKB signal transduction rows, here from human AKT1. AKT1 is the protein kinase B of this pathway. Reason: Core, conserved pathway role. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries this term by multiple IDA annotations (e.g. PMID:19162005, PMID:21321938) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Donor-split (involved_in) duplicate of the positive regulation of transcription by RNA polymerase II row, here from human AKT1 (IDA, PMID:19057511, an Akt-EGR1-ARF-PTEN axis study). Reason: AKT1 affects transcription indirectly by phosphorylating transcription factors and regulators; the transcription-regulation term overstates a direct role. Propagation Review Root cause: PROPAGATION BAD Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Human AKT1 carries this term by IDA (PMID:19057511) (QuickGO, checked 2026-10-10); indirect effect. Supporting Evidence: UniProtKB:P47196 AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 |
| GO:0048009 insulin-like growth factor receptor signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split duplicate of the IGF receptor signaling pathway rows, here from human AKT1 (IMP, PMID:8978681). Reason: AKT1 mediates IGF1 signaling downstream of PI3K; valid and conserved but secondary to the insulin/PI3K core annotations. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries this term by IMP (PMID:8978681) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) UniProtKB:P47196 AKT mediates the antiapoptotic effects of IGF1 |
| GO:0070585 protein localization to mitochondrion | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: New ISO row: protein localization to mitochondrion from human AKT1, whose annotation rests on IMP in PMID:23962723. That study found that parkin recruitment to depolarized mitochondria was reduced by pharmacological AKT inhibition, proposing Akt-dependent hexokinase recruitment as a step. Reason: The donor evidence uses a pan-AKT inhibitor in a mitophagy context and places AKT upstream of hexokinase localization; AKT1 does not itself carry out protein localization to mitochondria, and the transfer to rat overstates a narrow indirect effect. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH GRANULARITY MISMATCH Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET Human AKT1 carries this term by IMP (PMID:23962723) (QuickGO, checked 2026-10-10); the experiment used AKT inhibition, not isoform-specific loss. Supporting Evidence: PMID:23962723 Mitochondrial parkin recruitment was attenuated with AKT inhibition |
| GO:0071363 cellular response to growth factor stimulus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (involved_in) duplicate of the cellular response to growth factor stimulus row from mouse Akt1 (IMP, PMID:23684622, PMID:26235620). Reason: AKT1 mediates growth-factor signaling downstream of PI3K; valid but a broad response-level term. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:87986 · mouse Akt1 SUPPORTS TRANSFER Mouse Akt1 carries involved_in this term by IMP (PMID:23684622, PMID:26235620) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) |
| GO:0071364 cellular response to epidermal growth factor stimulus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split duplicate of the cellular response to EGF stimulus rows, here from human AKT1 (IDA, PMID:30514904). Rat IDA support exists (PMID:15701816). Reason: AKT1 is activated downstream of EGF receptor/PI3K; valid but stimulus-specific. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries this term by IDA (PMID:30514904) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) |
| GO:0106310 protein serine kinase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split duplicate of the protein serine kinase activity ISO row, here from human AKT1. AKT1 phosphorylates serine residues of protein substrates (Rhea:17989). Reason: Conserved catalytic activity, experimentally established for human AKT1. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P31749 · human AKT1 SUPPORTS TRANSFER Human AKT1 carries this term by multiple EXP annotations (e.g. PMID:12172553, PMID:15861136) (QuickGO, checked 2026-10-10). Supporting Evidence: UniProtKB:P47196 Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) |
| GO:0120283 protein serine/threonine kinase binding | IPI PMID:8524413 Inhibition of glycogen synthase kinase-3 by insulin mediated... | KEEP AS NON CORE | Summary: Second WITH/FROM split (GSK3B, P18266) of the PMID:8524413 protein serine/threonine kinase binding row. PKB phosphorylates and inactivates GSK3, implying a kinase-substrate interaction. Reason: Consistent with the GSK3A sibling: a real kinase-substrate interaction, but partner-specific and not a defining AKT1 function. Supporting Evidence: PMID:8524413 Another insulin-stimulated protein kinase inactivates GSK3 under these conditions, and we demonstrate that it is the product of the proto-oncogene protein kinase B |
Loading supporting content…
Download this section (compressed HTML)Q: GO:0045907 positive regulation of vasoconstriction (rat IMP, PMID:21532183): the abstract reports that Akt mediates the statin-induced, NO-dependent reduction of constrictor responses. Should RGD replace the term with GO:0045906 negative regulation of vasoconstriction?
Q: PMID:7488143 protein kinase C binding (IPI): the WITH/FROM fields resolve to RGD:62390 (rat Akt3, the kinase cloned in that paper) and RGD:2802 (Hmgb1) rather than to a PKC isoform. Should RGD correct the WITH entities to the PKC subspecies actually pulled down?
Q: GO:0045792 negative regulation of cell size (IDA, PMID:16286931): this conflicts with the growth-promoting role of AKT1. Does the full text support the negative direction, or is the annotation a direction error?
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)