Akt1

UniProt ID: P47196
Organism: Rattus norvegicus
Review Status: COMPLETE
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Gene Description

Akt1 encodes the rat RAC-alpha/PKB alpha serine/threonine kinase downstream of PI3K. Rat experiments support kinase activity and roles in insulin-responsive signaling, substrate phosphorylation, glucose transport/metabolism, cell survival, and growth-factor responses. The current ISO set is propagated mainly from human AKT1 and mouse Akt1, and conserved kinase and canonical PI3K/insulin signaling functions are the strongest gene-level biology. Many donor-derived developmental, neuronal, immune, stress-response, and highly context-specific terms are less central and may reflect ISO over-annotation.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005737 cytoplasm
IBA
GO_REF:0000033
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:0005737; C:cytoplasm; ISO:RGD.
GO:0004674 protein serine/threonine kinase activity
IBA
GO_REF:0000033
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). Falcon deep research confirms this as the defining core molecular function of AKT1.
Reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
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: 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:0043066 negative regulation of apoptotic process
IBA
GO_REF:0000033
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. Falcon notes pro-survival output is a downstream consequence of AKT1 substrate phosphorylation rather than a defining molecular function, consistent with non-core status.
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.
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: 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
GO; GO:0008286; P:insulin receptor signaling pathway; IDA:BHF-UCL.
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: 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:0004672 protein kinase activity
IEA
GO_REF:0000002
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.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0004672; F:protein kinase activity; IDA:RGD.
GO:0004674 protein serine/threonine kinase activity
IEA
GO_REF:0000120
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
GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
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: 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
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: 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.
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: 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:0005737; C:cytoplasm; ISO:RGD.
GO:0005758 mitochondrial intermembrane space
IEA
GO_REF:0000044
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:0005886 plasma membrane
IEA
GO_REF:0000044
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:0005886; C:plasma membrane; ISS:UniProtKB.
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: 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:0032869 cellular response to insulin stimulus
IEA
GO_REF:0000117
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:0106310 protein serine kinase activity
IEA
GO_REF:0000116
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
GO; GO:0106310; F:protein serine kinase activity; ISO:RGD.
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: The cited studies report individual interactions, but the generic term protein binding is too uninformative to retain in the review.
Reason: Protein binding is not sufficiently specific or useful as a curated AKT1 function term.
Supporting Evidence:
PMID:16362038
Novel roles of Akt and mTOR in suppressing TGF-beta/ALK5-mediated Smad3 activation.
GO:0005515 protein binding
IPI
PMID:16642037
Nuclear Akt associates with PKC-phosphorylated Ebp1, prevent...
REMOVE
Summary: The cited studies report individual interactions, but the generic term protein binding is too uninformative to retain in the review.
Reason: Protein binding is not sufficiently specific or useful as a curated AKT1 function term.
Supporting Evidence:
PMID:16642037
Nuclear Akt associates with PKC-phosphorylated Ebp1, preventing DNA fragmentation by inhibition of caspase-activated DNase.
GO:0005515 protein binding
IPI
PMID:20488185
Glyceraldehyde-3-phosphate dehydrogenase interacts with phos...
REMOVE
Summary: The cited studies report individual interactions, but the generic term protein binding is too uninformative to retain in the review.
Reason: Protein binding is not sufficiently specific or useful as a curated AKT1 function term.
Supporting Evidence:
PMID:20488185
Glyceraldehyde-3-phosphate dehydrogenase interacts with phosphorylated Akt resulting from increased blood glucose in rat cardiac muscle.
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: 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
GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
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
GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
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
GO; GO:0106310; F:protein serine kinase activity; ISO:RGD.
GO:0007224 smoothened signaling pathway
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IMP from PMID:31305241, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IMP from PMID:31305241, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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. Donor experiments support some involvement, but the annotation captures a downstream phenotype or narrow context that is broader than the evidence safely supports for cross-species transfer.
Reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH GRANULARITY MISMATCH
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). The donor's support for this term is IMP from PMID:31305241, so the donor annotation is experimentally grounded. The transferred term is contextual and over-specific to retain as a general rat annotation.
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:0010467 gene expression
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IMP from PMID:12851395, PMID:31272455, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0010467; P:gene expression; ISO:RGD.
GO:0008286 insulin receptor signaling pathway
IMP
PMID:10454575
Insulin-induced phosphorylation and activation of cyclic nuc...
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:
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: 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:
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: 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:
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
GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:BHF-UCL.
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 and human AKT1. Donor experiments support some involvement, but the annotation captures a downstream phenotype or narrow context that is broader than the evidence safely supports for cross-species transfer.
Reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH GRANULARITY MISMATCH
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). The donor's support for this term is IGI from PMID:18762576, so the donor annotation is experimentally grounded. The transferred term is contextual and over-specific to retain as a general rat annotation.
UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET
Traced against the human AKT1 GOA record (UniProtKB/P31749, QuickGO retrieved 2026-09-01). The donor's support for this term is IDA from PMID:19057511, so the donor annotation is experimentally grounded. The transferred term is contextual and over-specific to retain as a general rat annotation.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
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: 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.
Supporting Evidence:
PMID:9112399
Potential role of protein kinase B in glucose transporter 4 translocation in adipocytes.
GO:0005829 cytosol
IDA
PMID:9112399
Potential role of protein kinase B in glucose transporter 4 ...
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:
PMID:9112399
Potential role of protein kinase B in glucose transporter 4 translocation in adipocytes.
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: 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:
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: 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.
Supporting Evidence:
PMID:7774014
The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase.
GO:0032869 cellular response to insulin stimulus
IDA
PMID:9005851
Regulation of neuronal survival by the serine-threonine prot...
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:
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.
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: The rat ISO traces to mouse Akt1. Donor experiments support some involvement, but the annotation captures a downstream phenotype or narrow context that is broader than the evidence safely supports for cross-species transfer. Rat experimental annotations also exist for this term (PMID:18772167).
Reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
Supporting Evidence:
PMID:18772167
Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: involvement of the cholinergic pathway.
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
GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
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
MARK AS OVER ANNOTATED
Summary: The rat ISO traces to mouse Akt1. Donor experiments support some involvement, but the annotation captures a downstream phenotype or narrow context that is broader than the evidence safely supports for cross-species transfer.
Reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH GRANULARITY MISMATCH
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). The donor's support for this term is IMP from PMID:23684622, PMID:26235620, so the donor annotation is experimentally grounded. The transferred term is contextual and over-specific to retain as a general rat annotation.
Supporting Evidence:
UniProtKB:P47196
GO; GO:1904515; P:positive regulation of TORC2 signaling; ISO:RGD.
GO:1903898 negative regulation of PERK-mediated unfolded protein response
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:21954288, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
Supporting Evidence:
UniProtKB:P47196
GO; GO:1903898; P:negative regulation of PERK-mediated unfolded protein response; ISO:RGD.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:9065430
Regulation of protein kinase B and glycogen synthase kinase-...
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:
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: 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:
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 and human AKT1. Donor experiments support some involvement, but the annotation captures a downstream phenotype or narrow context that is broader than the evidence safely supports for cross-species transfer.
Reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH GRANULARITY MISMATCH
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). The donor's support for this term is IGI from PMID:19208758, so the donor annotation is experimentally grounded. The transferred term is contextual and over-specific to retain as a general rat annotation.
UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET
Traced against the human AKT1 GOA record (UniProtKB/P31749, QuickGO retrieved 2026-09-01). The donor's support for this term is IDA from PMID:22869525, so the donor annotation is experimentally grounded. The transferred term is contextual and over-specific to retain as a general rat annotation.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0001649; P:osteoblast differentiation; ISO:RGD.
GO:0030425 dendrite
IDA
PMID:31071414
Sex Differences in Neuroplasticity- and Stress-Related Gene ...
REMOVE
Summary: The cited hippocampal study is a tissue-specific expression context and does not justify a stable dendrite localization annotation for AKT1.
Reason: The term is too context-specific and not a reliable general localization assignment.
Supporting Evidence:
PMID:31071414
Sex Differences in Neuroplasticity- and Stress-Related Gene Expression and Protein Levels in the Rat Hippocampus Following Oxycodone Conditioned Place Preference.
GO:0005758 mitochondrial intermembrane space
ISS
GO_REF:0000024
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: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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:26844834; IMP from PMID:26844834, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
GO:0099175 regulation of postsynapse organization
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:26844834; IMP from PMID:26844834, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0004672; F:protein kinase activity; IDA:RGD.
GO:1902018 negative regulation of cilium assembly
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: The rat ISS transfers from the same human AKT1 record as the ISO row for this term, where the donor has direct experimental support (IDA PMID:31204173) for suppression of cilium assembly in a human cell system.
Reason: As for the ISO row: the donor IDA is genuine, but AKT effects on ciliogenesis are reported with opposite signs in different cellular contexts, so a sign-specific gene-level transfer to rat without rat-directed evidence overstates what is conserved; flagged as over-annotation, consistent with the ISO row for this term.
Supporting Evidence:
UniProtKB:P47196
GO; GO:1902018; P:negative regulation of cilium assembly; ISS:UniProtKB.
GO:1902018 negative regulation of cilium assembly
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:31204173) for suppression of cilium assembly in a human cell system.
Reason: The donor IDA is genuine, but AKT signalling has been reported with opposite signs on ciliogenesis in different cellular contexts (suppressive in some settings, supportive in others), so a sign-specific gene-level transfer to rat without rat-directed evidence overstates what is conserved.
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:31204173. The experiment supports the human annotation; the transfer concern is the context-dependent sign of AKT effects on ciliogenesis, not source weakness.
Supporting Evidence:
UniProtKB:P47196
GO; GO:1902018; P:negative regulation of cilium assembly; ISS:UniProtKB.
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
GO; GO:0008286; P:insulin receptor signaling pathway; IDA:BHF-UCL.
GO:0071364 cellular response to epidermal growth factor stimulus
ISS
GO_REF:0000024
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: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
MARK AS OVER ANNOTATED
Summary: The rat ISS transfers from the same human AKT1 record as the ISO row for this term, where the donor has direct experimental support (IDA PMID:24529379): an AKT-dependent block of a substrate's trafficking to the lysosome.
Reason: As for the ISO row: the donor IDA is real but reflects a single-substrate trafficking readout in one human context; a rat gene-level claim about controlling protein localization to the lysosome is more granular than the conserved evidence supports; flagged as over-annotation, consistent with the ISO row for this term.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0150033; P:negative regulation of protein localization to lysosome; ISS:UniProtKB.
GO:0150033 negative regulation of protein localization to lysosome
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:24529379): an AKT-dependent block of a substrate's trafficking to the lysosome observed in human cells.
Reason: The donor IDA is real, but it reflects a single-substrate trafficking readout in one human cellular context; elevating that to a rat gene-level claim about controlling protein localization to the lysosome is more granular and more context-bound than the conserved evidence supports.
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:24529379. The experiment supports the human annotation; the transfer concern is the single-substrate trafficking scope, not source weakness.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0150033; P:negative regulation of protein localization to lysosome; ISS:UniProtKB.
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: 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: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: 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:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
ISO
GO_REF:0000121
MARK AS OVER ANNOTATED
Summary: The rat ISO traces to mouse Akt1 and human AKT1. Donor experiments support some involvement, but the annotation captures a downstream phenotype or narrow context that is broader than the evidence safely supports for cross-species transfer.
Reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH GRANULARITY MISMATCH
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). The donor's support for this term is IMP from PMID:15937334, so the donor annotation is experimentally grounded. The transferred term is contextual and over-specific to retain as a general rat annotation.
UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET
Traced against the human AKT1 GOA record (UniProtKB/P31749, QuickGO retrieved 2026-09-01). The donor's support for this term is IDA from PMID:23512198, so the donor annotation is experimentally grounded. The transferred term is contextual and over-specific to retain as a general rat annotation.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:RGD.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IMP from PMID:34635817, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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: 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:
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: 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:
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 other kinases by phosphorylating them in signaling cascades; that does not make AKT1 itself a kinase inhibitor in the molecular-function sense.
Reason: The term misstates AKT1's biochemistry and should not be retained.
Supporting Evidence:
PMID:8524413
Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B.
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
GO; GO:0046326; P:positive regulation of D-glucose import; ISO:RGD.
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 SOURCE STALE OR MISSING
The current mouse Akt1 record carries no generic kinase activity annotation (QuickGO, checked 2026-08); its evidence is for protein serine/threonine kinase activity.
UniProtKB:P31749 · human AKT1 SOURCE STALE OR MISSING
The current human AKT1 record likewise carries no generic kinase activity annotation (QuickGO, checked 2026-08); its evidence is for 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
GO; GO:0005737; C:cytoplasm; ISO:RGD.
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.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:14730361; IGI from PMID:31874168, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0006954; P:inflammatory response; ISO:RGD.
GO:0009408 response to heat
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IGI from PMID:31874168, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0009408; P:response to heat; ISO:RGD.
GO:0048266 behavioral response to pain
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IGI from PMID:31874168, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:19933931, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
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
MARK AS OVER ANNOTATED
Summary: The rat ISS transfers from the same human AKT1 record as the ISO row for this term, where the donor has direct experimental support (IDA PMID:33505021) for AKT-dependent activation of a potassium channel.
Reason: As for the ISO row: the donor IDA is real, but the MF recasts a kinase-substrate event as a dedicated channel-activator activity, while AKT1's molecular function is protein serine/threonine kinase activity; flagged as over-annotation, consistent with the ISO row for this term.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0099104; F:potassium channel activator activity; ISS:UniProtKB.
GO:0099104 potassium channel activator 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:33505021): AKT-dependent activation of a potassium channel in a human system.
Reason: The donor IDA is real, but the MF 'potassium channel activator activity' recasts a kinase-substrate event (phosphorylation-dependent modulation of one channel) as a dedicated channel-activator molecular function; AKT1's molecular function is protein serine/threonine kinase activity, and the channel effect is one substrate outcome, so the MF transfer over-annotates rat Akt1.
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:33505021. The experiment supports the human annotation; the transfer concern is casting a substrate-level kinase effect as a dedicated activator MF, not source weakness.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0099104; F:potassium channel activator activity; ISS:UniProtKB.
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: 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:
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 ...
REMOVE
Summary: This highly specific mitochondrial calcium-import term is too narrow for the cited cardiomyocyte injury experiment and is not an established general AKT1 function.
Reason: Remove as an over-specific pathway inference.
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: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: 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: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 and human AKT1. Donor experiments support some involvement, but the annotation captures a downstream phenotype or narrow context that is broader than the evidence safely supports for cross-species transfer.
Reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH GRANULARITY MISMATCH
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). The donor's support for this term is IMP from PMID:18292230, so the donor annotation is experimentally grounded. The transferred term is contextual and over-specific to retain as a general rat annotation.
UniProtKB:P31749 · human AKT1 SUPPORTS SOURCE BUT NOT TARGET
Traced against the human AKT1 GOA record (UniProtKB/P31749, QuickGO retrieved 2026-09-01). The donor's support for this term is IMP from PMID:28341552, so the donor annotation is experimentally grounded. The transferred term is contextual and over-specific to retain as a general rat annotation.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IMP from PMID:9415393, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
Supporting Evidence:
UniProtKB:P47196
GO; GO:2000010; P:positive regulation of protein localization to cell surface; ISO:RGD.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:24349514, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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
MARK AS OVER ANNOTATED
Summary: The rat ISO traces to mouse Akt1. Donor experiments support some involvement, but the annotation captures a downstream phenotype or narrow context that is broader than the evidence safely supports for cross-species transfer.
Reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
GO:0042981 regulation of apoptotic process
ISO
GO_REF:0000121
MARK AS OVER ANNOTATED
Summary: The rat ISO traces to mouse Akt1. Donor experiments support some involvement, but the annotation captures a downstream phenotype or narrow context that is broader than the evidence safely supports for cross-species transfer.
Reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH GRANULARITY MISMATCH
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). The donor's support for this term is IDA from PMID:18977203, so the donor annotation is experimentally grounded. The transferred term is contextual and over-specific to retain as a general rat annotation.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
GO:0046622 positive regulation of organ growth
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IMP from PMID:15713641, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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: 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:
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.
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: The cited studies report individual interactions, but the generic term protein binding is too uninformative to retain in the review.
Reason: Protein binding is not sufficiently specific or useful as a curated AKT1 function term.
Supporting Evidence:
PMID:20605787
Ribosomal protein S3, a new substrate of Akt, serves as a signal mediator between neuronal apoptosis and DNA repair.
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.
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: 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:
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: 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: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: The rat ISO traces to mouse Akt1. Donor experiments support some involvement, but the annotation captures a downstream phenotype or narrow context that is broader than the evidence safely supports for cross-species transfer. Rat experimental annotations also exist for this term (PMID:24583056).
Reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
Supporting Evidence:
PMID:24583056
PRAS40 plays a pivotal role in protecting against stroke by linking the Akt and mTOR pathways.
GO:0021510 spinal cord development
IDA
PMID:23681769
The mechanisms of EGFR in the regulation of axon regeneratio...
REMOVE
Summary: The cited study concerns axon regeneration signaling and does not justify a stable spinal cord development annotation for rat AKT1.
Reason: The term is too developmental and indirect for the supporting evidence.
Supporting Evidence:
PMID:23681769
The mechanisms of EGFR in the regulation of axon regeneration.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IMP from PMID:23871832, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:25139353, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:24875179, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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: Growth-hormone response may occur through conserved signaling context, but the evidence here is indirect and too specific to keep as a strong general AKT1 annotation.
Reason: The term is plausible but over-annotated for the available support.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0060416; P:response to growth hormone; ISS:AgBase.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:24740015, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:23479225, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:19778506, PMID:21976490, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0010975; P:regulation of neuron projection development; ISS:UniProtKB.
GO:0005515 protein binding
IPI
PMID:16832058
Ebp1 isoforms distinctively regulate cell survival and diffe...
REMOVE
Summary: The cited studies report individual interactions, but the generic term protein binding is too uninformative to retain in the review.
Reason: Protein binding is not sufficiently specific or useful as a curated AKT1 function term.
Supporting Evidence:
PMID:16832058
Ebp1 isoforms distinctively regulate cell survival and differentiation.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IMP from PMID:24101522, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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...
REMOVE
Summary: The cited PP2A/Shc paper does not provide a clear, stable basis for retaining protein phosphatase 2A binding as a curated AKT1 function.
Reason: The evidence is indirect and the partner-specific binding call is not well supported for rat AKT1.
Supporting Evidence:
PMID:11884620
Protein phosphatase 2A forms a molecular complex with Shc and regulates Shc tyrosine phosphorylation and downstream mitogenic signaling.
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.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:19596798, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0036064; C:ciliary basal body; ISO:RGD.
GO:0005911 cell-cell junction
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:23793062, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0005911; C:cell-cell junction; ISO:RGD.
GO:1901653 cellular response to peptide
ISO
GO_REF:0000121
MARK AS OVER ANNOTATED
Summary: The rat ISO traces to mouse Akt1. Donor experiments support some involvement, but the annotation captures a downstream phenotype or narrow context that is broader than the evidence safely supports for cross-species transfer. Rat experimental annotations also exist for this term (PMID:18772167).
Reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH GRANULARITY MISMATCH
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). The donor's support for this term is IDA from PMID:23793062, so the donor annotation is experimentally grounded. The transferred term is contextual and over-specific to retain as a general rat annotation.
Supporting Evidence:
UniProtKB:P47196
GO; GO:1901653; P:cellular response to peptide; IEP:RGD.
GO:0097011 cellular response to granulocyte macrophage colony-stimulating factor stimulus
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:23610142, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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: 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: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: The cited studies report individual interactions, but the generic term protein binding is too uninformative to retain in the review.
Reason: Protein binding is not sufficiently specific or useful as a curated AKT1 function term.
Supporting Evidence:
PMID:22218591
PKB/Akt partners with Dab2 in albumin endocytosis.
GO:0097194 execution phase of apoptosis
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:12124386, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0097194; P:execution phase of apoptosis; ISO:RGD.
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: 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:
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: 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:
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: 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:
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IMP from PMID:20448149, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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. Donor experiments support some involvement, but the annotation captures a downstream phenotype or narrow context that is broader than the evidence safely supports for cross-species transfer. Rat experimental annotations also exist for this term (PMID:24583056).
Reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH GRANULARITY MISMATCH
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). The donor's support for this term is IPI from PMID:22057101, so the donor annotation is experimentally grounded. The transferred term is contextual and over-specific to retain as a general rat annotation.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0019901; F:protein kinase binding; IPI:RGD.
GO:0045907 positive regulation of vasoconstriction
IMP
PMID:21532183
Acute modulation of vasoconstrictor responses by pravastatin...
REMOVE
Summary: The pravastatin vascular study is too context-specific and indirect to retain positive regulation of vasoconstriction as a stable AKT1 annotation.
Reason: The term overstates a narrow vascular physiology context.
Supporting Evidence:
PMID:21532183
Acute modulation of vasoconstrictor responses by pravastatin in small vessels.
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: 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: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
GO; GO:0005524; F:ATP binding; IDA:RGD.
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.
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: 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:0005886; C:plasma membrane; ISS:UniProtKB.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IGI from PMID:18762576, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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
Molecular cloning and characterization of a new member of the RAC protein kinase family: association of the pleckstrin homology domain of three types of RAC protein kinase with 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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0010975; P:regulation of neuron projection development; ISS:UniProtKB.
GO:0005829 cytosol
TAS
Reactome:R-RNO-437185
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:0005829 cytosol
TAS
Reactome:R-RNO-437189
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: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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IMP from PMID:12783884, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IMP from PMID:12783884, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IMP from PMID:12783884, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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: 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:
PMID:9887206
Akt kinases and 2-deoxyglucose uptake in rat skeletal muscles in vivo: study with insulin and exercise.
GO:0005524 ATP binding
IDA
PMID:9887206
Akt kinases and 2-deoxyglucose uptake in rat skeletal muscle...
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:
PMID:9887206
Akt kinases and 2-deoxyglucose uptake in rat skeletal muscles in vivo: study with insulin and exercise.
GO:0006468 protein phosphorylation
IDA
PMID:9887206
Akt kinases and 2-deoxyglucose uptake in rat skeletal muscle...
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.
Supporting Evidence:
PMID:9887206
Akt kinases and 2-deoxyglucose uptake in rat skeletal muscles in vivo: study with insulin and exercise.
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
GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; ISO:RGD.
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: 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:
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...
REMOVE
Summary: The PDE3B study supports substrate phosphorylation by AKT rather than retaining the broad and uninformative term enzyme binding.
Reason: The term is too generic to be useful as a curated AKT1 annotation.
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.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:16513828, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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 ...
REMOVE
Summary: This term conflicts with the broader body of AKT biology linking AKT activity to growth promotion rather than negative regulation of cell size.
Reason: Remove as biologically inconsistent with established AKT1 function.
Supporting Evidence:
PMID:16286931
Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2.
GO:0005654 nucleoplasm
TAS
Reactome:R-RNO-198333
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:0005829 cytosol
TAS
Reactome:R-RNO-198333
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:0005829 cytosol
TAS
Reactome:R-RNO-198601
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: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: 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:
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: The cited studies report individual interactions, but the generic term protein binding is too uninformative to retain in the review.
Reason: Protein binding is not sufficiently specific or useful as a curated AKT1 function term.
Supporting Evidence:
PMID:15120593
Altered Bad localization and interaction between Bad and Bcl-xL in the hippocampus after transient global ischemia.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:12089343
The phosphatidylinositol 3-kinase/Akt signaling pathway modu...
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:
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: 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.
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:16357133, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
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: 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
GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
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: 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.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
GO:0008286 insulin receptor signaling pathway
ISS
GO_REF:0000024
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
GO; GO:0008286; P:insulin receptor signaling pathway; IDA:BHF-UCL.
GO:0008286 insulin receptor signaling pathway
IMP
PMID:9632753
Requirement for activation of the serine-threonine kinase Ak...
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:
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: 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:0004672 protein kinase activity
IDA
PMID:12084817
A protein kinase B-dependent and rapamycin-sensitive pathway...
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.
Supporting Evidence:
PMID:12084817
A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification.
GO:0004674 protein serine/threonine kinase activity
TAS
PMID:12084817
A protein kinase B-dependent and rapamycin-sensitive pathway...
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:
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: The cited studies report individual interactions, but the generic term protein binding is too uninformative to retain in the review.
Reason: Protein binding is not sufficiently specific or useful as a curated AKT1 function term.
Supporting Evidence:
PMID:12194869
Akt1 regulates a JNK scaffold during excitotoxic apoptosis.
GO:0030307 positive regulation of cell growth
IDA
PMID:12084817
A protein kinase B-dependent and rapamycin-sensitive pathway...
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:
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 ...
REMOVE
Summary: The cited myocardial-injury study describes a narrow pathological context and does not justify retaining positive regulation of apoptotic process as a stable AKT1 annotation.
Reason: Remove as a context-specific and biologically atypical apoptosis annotation for AKT1.
Supporting Evidence:
PMID:20403980
Selective blockade of protein kinase B protects the rat and human myocardium against ischaemic injury.
GO:0043066 negative regulation of apoptotic process
TAS
PMID:12084817
A protein kinase B-dependent and rapamycin-sensitive pathway...
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:
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
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:15509711, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0005819; C:spindle; ISO:RGD.
GO:0008637 apoptotic mitochondrial changes
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:12869584, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0008637; P:apoptotic mitochondrial changes; ISO:RGD.
GO:0016567 protein ubiquitination
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:12145204, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0016567; P:protein ubiquitination; ISO:RGD.
GO:0030163 protein catabolic process
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:12145204, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0030163; P:protein catabolic process; ISO:RGD.
GO:0007281 germ cell development
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to mouse Akt1. Although donor experiments support the term in the source species, it reflects a highly specific tissue, developmental, neuronal, immune, or stimulus context with no direct rat-directed confirmation for this exact claim.
Reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
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). The donor's support for this term is IDA from PMID:12140361, so the donor annotation is experimentally grounded. The donor context is too narrow to transfer to rat without rat-directed evidence.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0007281; P:germ cell development; ISO:RGD.

Core Functions

AKT1 is the rat RAC-alpha/PKB alpha serine/threonine kinase that transduces phosphatidylinositol 3-kinase signals to regulate insulin-responsive metabolism, growth, and survival programs through phosphorylation of downstream substrates.

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).
  • 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).

References

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Deep Research

Falcon

(Akt1-deep-research-falcon.md)

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OpenScientist

(Akt1-hypotheses/prediction-kinase-inhibitor-activity/openscientist.md)

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📚 Additional Documentation

Notes

(Akt1-notes.md)

Akt1 review notes

Description cleanup note

The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.

  • Moved out of the YAML description: this review keeps conserved kinase and canonical PI3K/insulin signaling functions, while removing or downranking many donor-derived developmental, neuronal, immune, stress-response, and context-specific terms as ISO over-annotation.

Bioreason Rl Predictions

(Akt1-bioreason-rl-predictions.md)

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Bioreason Rl Review

(Akt1-bioreason-rl-review.md)

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📄 View Raw YAML

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