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.
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.
AKT1 catalyzes **ATP-dependent phosphorylation of serine/threonine residues** in protein substrates (EC **2.7.11.1**, protein-serine/threonine kinase).
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.
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.
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.
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.
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.
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.
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**
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**
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.
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.
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.
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.
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.
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).
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.
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. 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
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).
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.
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
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.
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).
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
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).
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.
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.
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.
Summary: The rat ISO traces to human 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.
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.
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
REMOVE
Summary: The rat ISO traces to human 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:1905786; P:positive regulation of anaphase-promoting complex-dependent catabolic process; ISO:RGD.
Summary: The rat ISO traces to human 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: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 **PI3KβAKTβmTOR** 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.
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
REMOVE
Summary: The rat ISO traces to human 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:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; ISO:RGD.
Summary: The rat ISO traces to human 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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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: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.
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.
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.
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.
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.
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.
Sex Differences in Neuroplasticity- and Stress-Related Gene Expression and Protein Levels in the Rat Hippocampus Following Oxycodone Conditioned Place Preference.
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.
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.
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.
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:0099175; P:regulation of postsynapse organization; ISO:RGD.
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
REMOVE
Summary: The rat ISO traces to human 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:0160049; P:negative regulation of cGAS/STING signaling pathway; ISO:RGD.
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.
Summary: The rat ISO traces to human 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:1902018; P:negative regulation of cilium assembly; ISS:UniProtKB.
Summary: The rat ISO traces to human 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:1902018; P:negative regulation of cilium assembly; ISS:UniProtKB.
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.
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
REMOVE
Summary: The rat ISO traces to human 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:0150033; P:negative regulation of protein localization to lysosome; ISS:UniProtKB.
GO:0150033
negative regulation of protein localization to lysosome
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to human 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:0150033; P:negative regulation of protein localization to lysosome; ISS:UniProtKB.
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.
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.
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.
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.
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.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:RGD.
Summary: The rat ISO traces to human 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:0110002; P:regulation of tRNA methylation; ISO:RGD.
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.
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.
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.
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
REMOVE
Summary: The rat ISO traces to human 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: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.
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
REMOVE
Summary: The rat ISO traces to human 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: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.
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.
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.
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.
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.
GO:1905552
positive regulation of protein localization to endoplasmic reticulum
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to human 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:1905552; P:positive regulation of protein localization to endoplasmic reticulum; ISO:RGD.
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.
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.
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:0048266; P:behavioral response to pain; ISO:RGD.
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:0010629; P:negative regulation of gene expression; ISO:RGD.
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.
Summary: The rat ISO traces to human 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.
Summary: The rat ISO traces to human 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.
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.
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.
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.
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.
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.
Protein kinase B (PKB/AKT1) formed signaling complexes with mitochondrial proteins and prevented glycolytic energy dysfunction in cultured cardiomyocytes during ischemia-reperfusion injury.
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.
Protein kinase B (PKB/AKT1) formed signaling complexes with mitochondrial proteins and prevented glycolytic energy dysfunction in cultured cardiomyocytes during ischemia-reperfusion injury.
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.
Summary: The rat ISO traces to human 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.
GO:0010595
positive regulation of endothelial cell migration
ISO
GO_REF:0000121
MARK AS OVER ANNOTATED
Summary: The rat ISO traces to 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.
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
MARK AS OVER ANNOTATED
Summary: The rat ISO traces to 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.
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.
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.
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.
GO:0002042
cell migration involved in sprouting angiogenesis
ISO
GO_REF:0000121
MARK AS OVER ANNOTATED
Summary: The rat ISO traces to 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.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; ISO:RGD.
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.
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
REMOVE
Summary: The rat ISO traces to human 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.
GO:1903038
negative regulation of leukocyte cell-cell adhesion
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to human 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:1903038; P:negative regulation of leukocyte cell-cell adhesion; ISO:RGD.
GO:2000402
negative regulation of lymphocyte migration
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to human 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:2000402; P:negative regulation of lymphocyte migration; ISO:RGD.
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.
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
REMOVE
Summary: The rat ISO traces to human 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: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.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0071356; P:cellular response to tumor necrosis factor; ISO:RGD.
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.
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.
Summary: The rat ISO traces to 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.
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.
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.
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:0046622; P:positive regulation of organ growth; ISO:RGD.
Summary: The rat ISO traces to human 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.
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. 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:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:RGD.
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.
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
REMOVE
Summary: The rat ISO traces to human 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
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.
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.
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.
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.
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.
Summary: The rat ISO traces to human 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:0031982; C:vesicle; ISO:RGD.
GO:0072656
maintenance of protein location in mitochondrion
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to human 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:0072656; P:maintenance of protein location in mitochondrion; ISO:RGD.
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.
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.
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.
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.
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.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0036294; P:cellular response to decreased oxygen levels; ISO:RGD.
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.
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.
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.
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.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0010975; P:regulation of neuron projection development; ISS:UniProtKB.
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.
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:0031641; P:regulation of myelination; ISO:RGD.
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.
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.
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.
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:
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.
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.
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.
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: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.
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.
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.
Summary: The rat ISO traces to 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.
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.
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.
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.
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.
Supporting Evidence:
UniProtKB:P47196
GO; GO:0032287; P:peripheral nervous system myelin maintenance; ISO:RGD.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
REMOVE
Summary: The rat ISO traces to human 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:0045600; P:positive regulation of fat cell differentiation; ISO:RGD.
GO:0046889
positive regulation of lipid biosynthetic process
ISO
GO_REF:0000121
MARK AS OVER ANNOTATED
Summary: The rat ISO traces to 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.
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.
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.
Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport.
Summary: The rat ISO traces to human 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: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.
Summary: The rat ISO traces to human 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.
Summary: The rat ISO traces to human 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:0034405; P:response to fluid shear stress; ISO:RGD.
GO:0045429
positive regulation of nitric oxide biosynthetic process
ISO
GO_REF:0000121
REMOVE
Summary: The rat ISO traces to human 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:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:RGD.
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.
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.
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).
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.
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.
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.
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.
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.
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
REMOVE
Summary: The rat ISO traces to human 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:0006924; P:activation-induced cell death of T cells; ISO:RGD.
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.
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.
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.
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.
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.
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: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.
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.
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.
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.
Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport.
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.
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.
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.
Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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: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.
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
UniProtKB:P47196
UniProt entry for rat AKT1 (RAC-alpha serine/threonine-protein kinase)
file:rat/Akt1/Akt1-deep-research-falcon.md
Falcon deep research report on rat Akt1 (RAC-alpha Ser/Thr kinase / PKB alpha, UniProt P47196)
AKT1/PKBalpha is an AGC-family serine/threonine protein kinase that acts as a central node downstream of growth factor and insulin signaling, exerting its effects by phosphorylating protein substrates. This is the defining core molecular function.
"AKT1 (Protein kinase B alpha; PKBΞ±) is a **serine/threonine protein kinase** in the **AGC kinase family** that functions as a central signaling node downstream of growth factor/insulin pathways, regulating survival, growth, metabolism, and cytoskeletal programs by **phosphorylating protein substrates**."
AKT1 catalyzes ATP-dependent phosphorylation of Ser/Thr residues on protein substrates (EC 2.7.11.1), with representative substrates including GSK3 and FOXO transcription factors.
"AKT1 catalyzes **ATP-dependent phosphorylation of serine/threonine residues** in protein substrates (EC **2.7.11.1**, protein-serine/threonine kinase)."
AKT1 is recruited to membranes via its PH domain binding PIP3 and PI(3,4)P2 generated by PI3K, then is activated by PDK1 phosphorylation of Thr308 and mTORC2 phosphorylation of Ser473.
"**PDK1 phosphorylates Thr308** in the activation loop for partial activation; **mTORC2 phosphorylates Ser473** in the hydrophobic motif for full activation/substrate tuning. **Thr450** turn-motif phosphorylation contributes to folding/stability."
In unstimulated cells AKT1 is held in an autoinhibited PH-in conformation by an intramolecular PH-kinase domain interface; full activation requires both phosphoinositide binding and regulatory phosphorylation.
"In unstimulated cells, AKT1 adopts a **PH-in autoinhibited conformation** in which a **PHβkinase domain interface** masks the active state and sequesters the lipid-binding site."
AKT1 sits in the canonical PI3K-AKT-mTOR axis; activated AKT1 phosphorylates substrates such as GSK3 and FOXO1/3a to promote survival, proliferation, metabolism, and anabolic growth.
"Activated AKT1 phosphorylates substrates including **GSK3** and **FOXO1/3a**, thereby promoting cell survival, proliferation, metabolism, and anabolic growth programs."
AKT1 is largely cytosolic and can be nuclear in quiescent cells, with active signaling concentrated at membrane compartments, especially the plasma membrane following PH-domain-dependent recruitment.
"AKT1 is largely **cytosolic (and can be nuclear) in quiescent cells**, but active signaling is concentrated at **membrane-associated compartments**, especially the **plasma membrane** and, in some models, **endosomal membranes**."
AKT signaling is terminated by PTEN (which removes the PIP3 membrane recruitment signal) and by phosphatases PP2A and PHLPP that dephosphorylate AKT regulatory residues.
"AKT signaling is terminated at two levels: **PTEN** removes the lipid signal by dephosphorylating **PIP3 to PI(4,5)P2**, preventing membrane recruitment; **PP2A** and **PHLPP** dephosphorylate AKT at key regulatory residues, especially after membrane dissociation."
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.
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.
Suppression of Akt1 phosphorylation by adenoviral transfer of the PTEN gene inhibits hypoxia-induced proliferation of rat pulmonary arterial smooth muscle cells.
Protein kinase B (PKB/AKT1) formed signaling complexes with mitochondrial proteins and prevented glycolytic energy dysfunction in cultured cardiomyocytes during ischemia-reperfusion injury.
Sex Differences in Neuroplasticity- and Stress-Related Gene Expression and Protein Levels in the Rat Hippocampus Following Oxycodone Conditioned Place Preference.
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.
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.
Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport.
Akt kinases and 2-deoxyglucose uptake in rat skeletal muscles in vivo: study with insulin and exercise.
Reactome:R-RNO-198333
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Deep Research
Falcon
(Akt1-deep-research-falcon.md)
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.FalconEdison Scientific Literature31 citations2 artifacts2026-05-31T19:10:46.038172
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Research report: Rat Akt1 (UniProt P47196) β functional annotation and translational context
0) Target verification (mandatory)
The UniProt accession P47196 corresponds to RAC-alpha serine/threonine-protein kinase (Akt-1 / PKBΞ±) in Rattus norvegicus (rat). A rat in vivo study explicitly states that the 3D structure of rat Akt-1 was retrieved from UniProt as βUniProt ID: P47196β, which directly validates the accessionβproteinβorganism mapping for this report. Publication: Alwaili et al., 2024-12 (Frontiers in Molecular Biosciences), https://doi.org/10.3389/fmolb.2024.1507786 (alwaili2024avenanthramidecamelioratedoxorubicininduced pages 2-3).
1) Key concepts, definitions, and current understanding
1.1 What AKT1 is (core definition)
AKT1 (Protein kinase B alpha; PKBΞ±) is a serine/threonine protein kinase in the AGC kinase family that functions as a central signaling node downstream of growth factor/insulin pathways, regulating survival, growth, metabolism, and cytoskeletal programs by phosphorylating protein substrates. (hassan2024aktkinasesas pages 2-3).
1.2 Domain architecture (functional parts)
Canonical AKT proteins (including AKT1) share:
- an N-terminal pleckstrin homology (PH) domain that binds phosphoinositides,
- a central protein kinase catalytic domain, and
- a C-terminal regulatory tail containing a hydrophobic motif (HM) with a key regulatory serine. (chu2018aktkinaseactivation pages 1-3, yudushkin2020controlofakt pages 1-2, hassan2024aktkinasesas pages 2-3).
1.3 Catalytic activity and reaction class
AKT1 catalyzes ATP-dependent phosphorylation of serine/threonine residues in protein substrates (EC 2.7.11.1, protein-serine/threonine kinase). Functional substrate examples frequently used for mechanistic assays include GSK3 and FOXO transcription factors. (chu2018aktkinaseactivation pages 1-3, hassan2024aktkinasesas pages 2-3).
1.4 Activation mechanism (lipid + phosphorylation as dual requirements)
A widely supported mechanistic model is that AKT1 activity is controlled by:
- membrane recruitment via the PH domain binding PI(3,4,5)P3 (PIP3) and/or PI(3,4)P2, generated downstream of PI3K, and
- multisite phosphorylation, especially:
- Thr308 in the activation loop phosphorylated by PDK1, and
- Ser473 in the hydrophobic motif phosphorylated largely by mTORC2.
This dual control produces strong spatiotemporal gating (activity restricted to appropriate lipid membranes) and high pathway specificity. (hassan2024aktkinasesas pages 2-3, chu2018aktkinaseactivation pages 1-3, shaw2025molecularinsighton pages 4-5).
1.5 Autoinhibition (structural basis for βoffβ state)
A key concept for functional annotation is that AKT1 is autoinhibited in unstimulated conditions by an intramolecular PHβkinase domain interface that buries the PH domain lipid-binding site and masks the kinase domain in a way that is incompatible with full activation. Structural work shows that phosphorylation alone does not fully override this autoinhibition; productive activation requires membrane phosphoinositide engagement. (truebestein2021structureofautoinhibited pages 1-2, truebestein2021structureofautoinhibited pages 3-4).
Figure evidence: Cropped figures from the PNAS structural paper illustrate the autoinhibited AKT1 structure and an activation schematic linking lipid binding and phosphorylation events. (truebestein2021structureofautoinhibited media b1c9177b, truebestein2021structureofautoinhibited media 8a846e33).
2) Molecular function in pathways (rat AKT1 in conserved mammalian context)
2.1 Upstream pathway context
AKT1 sits in the canonical PI3KβAKTβmTOR axis. PI3K generates PIP3 from PI(4,5)P2, recruiting AKT to membranes; PDK1 and mTORC2 then phosphorylate AKT at Thr308 and Ser473, respectively, to yield full catalytic competence. (hassan2024aktkinasesas pages 2-3, chu2026structuralandmechanistic pages 6-7).
2.2 Downstream effects (more specific than pleiotropy)
At the biochemical level, activated AKT1 phosphorylates multiple substrates to bias cells toward anabolic/survival states; mechanistic studies specifically cite increased phosphorylation activity toward substrates such as GSK3 and FOXO1/3a upon Thr308/Ser473 phosphorylation and membrane engagement. (chu2018aktkinaseactivation pages 1-3, chu2026structuralandmechanistic pages 3-4).
2.3 Negative regulation and signal termination
AKT signaling is terminated by:
- PTEN, which removes the membrane recruitment signal by converting PIP3 back to PI(4,5)P2, preventing AKT membrane recruitment; and
- protein phosphatases such as PP2A and PHLPP, which dephosphorylate AKT regulatory sites. Because phosphorylation state is stabilized by membrane association, AKT membrane dissociation is tightly coupled to dephosphorylation and inactivation. (chu2026structuralandmechanistic pages 3-4, yudushkin2020controlofakt pages 5-7, chu2026structuralandmechanistic pages 4-5).
3) Subcellular localization and where AKT1 acts
3.1 Basal vs activated localization
In quiescent cells, AKT is described as present in cytosol and nucleus, while growth factor stimulation triggers PH-domain-dependent recruitment to membranes enriched for PIP3/PI(3,4)P2. A key modern view is an βallosteric lipid switchβ in which catalysis in cells is strongly constrained to phosphoinositide-containing membranes, even when phosphorylation is present. (yudushkin2020controlofakt pages 5-7, yudushkin2020controlofakt pages 2-4).
3.2 Compartmentalized signaling logic
Compartmental signaling can be shaped by lipid identity and lifetime:
- PIP3 is associated with acute recruitment of Akt1/3 to plasma membrane,
- PI(3,4)P2 can support sustained signaling at plasma membrane and early endosomes in some models.
Additionally, phosphatase access and membrane dissociation kinetics govern how long AKT remains active. (yudushkin2020controlofakt pages 5-7).
4) Recent developments and latest research (prioritizing 2023β2024)
4.1 2024 authoritative synthesis: therapeutic targeting and isoform-/allele-selectivity
A 2024 expert review emphasizes that AKT inhibitors fall into multiple mechanistic classes (ATP-competitive, allosteric/PH-domain, PIP3 analogues, covalent-allosteric concepts), and highlights increasing interest in isoform-centric and allele-selective strategies (e.g., AKT1 E17K and other activating variants) to improve therapeutic index compared with pan-AKT blockade. Publication: Hassan et al., 2024-11, https://doi.org/10.1186/s13046-024-03207-4 (hassan2024aktkinasesas pages 13-14, hassan2024aktkinasesas pages 14-16).
4.2 2024: resistance/toxicity framing for clinical implementation
A 2024 resistance-focused review underscores that many AKT inhibitors faced limitations from dose-limiting toxicity and adaptive resistance, reinforcing biomarker selection and combination regimens as key design features in current practice. Publication: Browne & Okines, 2024-06, https://doi.org/10.3390/cancers16122259 (browne2024resistancetotargeted pages 4-6).
4.3 2023: AKT1 isoform-specific biology can be non-intuitive
In a 2023 TNBC brain-metastasis model, CRISPR AKT1 knockout produced mixed phenotypes (reduced viability in one clone, but increased migration/clonogenic survival and decreased radiosensitivity in both KO clones), illustrating that AKT1βs role can be context-specific and that isoform-specific perturbation does not necessarily phenocopy pharmacologic pan-AKT inhibition. Publication: Kempska et al., 2023-07, https://doi.org/10.3389/fonc.2023.1129682 (kempska2023impactofakt1 pages 1-2).
5) Current applications and real-world implementations (with statistics)
Clinical translation of AKT inhibition is exemplified by capivasertib (ATP-competitive pan-AKT inhibitor) combined with endocrine therapy.
In CAPItello-291, capivasertib + fulvestrant improved median progression-free survival (PFS) from 3.6 to 7.2 months overall (HR 0.60, 95% CI 0.51β0.71; p<0.001), with larger effect in patients with pathway alterations (PFS 3.1 to 7.3 months, HR 0.50). (browne2024resistancetotargeted pages 4-6).
Supporting earlier trial evidence (FAKTION) reported PFS 10.3 vs 4.8 months and OS 29.3 vs 23.4 months, with larger biomarker-subgroup effects. (browne2024resistancetotargeted pages 4-6).
These outcomes are widely cited as pivotal for the clinical role of AKT inhibitors in biomarker-defined HR+/HER2β breast cancer. (browne2024resistancetotargeted pages 4-6, alves2023druggingthepi3kaktmtor pages 1-2).
CAPItello-291 registry record:
- Trial: NCT04305496 (AstraZeneca), phase 3, randomized, double-blind capivasertib + fulvestrant vs placebo + fulvestrant; enrollment 818.
- Dosing in the registry: capivasertib 400 mg BID on intermittent schedule (Days 1β4 weekly in 28-day cycle) + fulvestrant 500 mg IM with loading then q28 days.
- Primary endpoint includes PFS (RECIST 1.1) in overall and βAltered Populationβ.
URL: https://clinicaltrials.gov/study/NCT04305496 (NCT04305496 chunk 1).
Implementation-oriented phase III study using historical control:
- Trial: NCT07281833 (CAPIcorn, West German Study Group), phase 3, open-label; plans to screen ~600 and enroll 250 enriched for PIK3CA/AKT1/PTEN alterations.
- Includes patient-reported outcome (PRO) adherence endpoints (digital monitoring) in addition to clinical outcomes.
URL: https://clinicaltrials.gov/study/NCT07281833 (NCT07281833 chunk 1).
5.3 Disease-model application in rats (rat AKT1 structure used operationally)
A 2024 rat hepatotoxicity study used the rat AKT1 (P47196) structure as an explicit computational target for docking analyses in a therapeutic modulation context (doxorubicin hepatotoxicity; AKT/GSK-3Ξ² axis). While not definitive mechanistic biology for AKT1 function per se, it is a concrete example of real-world use of the specific rat protein identifier in applied research workflows. (alwaili2024avenanthramidecamelioratedoxorubicininduced pages 2-3).
6) Expert opinions and authoritative analysis (selected viewpoints)
Lipid dependence as a mechanistic constraint: Structural and cellular analyses emphasize that AKT1βs maximal activity in cells is constrained to membranes containing PIP3/PI(3,4)P2, because the autoinhibited cytosolic conformation sequesters the lipid-binding site and phosphorylation alone is insufficient to fully unlock activity. (truebestein2021structureofautoinhibited pages 1-2, yudushkin2020controlofakt pages 5-7).
Biomarker-driven clinical strategy: Reviews emphasize that pan-AKT toxicity and pathway feedback loops make biomarker selection and combination therapies central to clinical success of AKT inhibition. (browne2024resistancetotargeted pages 4-6, hassan2024aktkinasesas pages 13-14).
7) Evidence summary table
The following table provides a compact functional-annotation summary for rat AKT1 (P47196) with citations.
Annotation topic
Summary for rat AKT1 (UniProt P47196)
Key evidence
Identity verification
The target matches Rattus norvegicus Akt1, encoding RAC-alpha serine/threonine-protein kinase / PKBΞ±. A 2024 rat study explicitly states that the Rattus norvegicus Akt-1 structure used for docking was retrieved from UniProt as P47196, confirming the accession-gene-organism mapping. Core AKT1 architecture and regulation are consistent with canonical mammalian AKT1/PKBΞ± literature.
AKT1 has the canonical AKT layout: N-terminal PH domain, central bilobal kinase domain, and C-terminal hydrophobic/regulatory tail (hydrophobic motif). This organization underlies phosphoinositide sensing, catalytic phosphorylation, and C-tail-dependent regulation.
AKT1 is an AGC-family serine/threonine protein kinase that transfers phosphate from ATP to Ser/Thr residues on protein substrates. Its kinase activity is central to growth, survival, metabolism, and anabolic signaling. Representative downstream substrates include GSK3 and FOXO proteins.
Activation is membrane- and phosphorylation-coupled. The PH domain binds PI(3,4,5)P3 (PIP3) and PI(3,4)P2, recruiting AKT1 to phosphoinositide-enriched membranes. PDK1 phosphorylates Thr308 in the activation loop for partial activation; mTORC2 phosphorylates Ser473 in the hydrophobic motif for full activation/substrate tuning. Thr450 turn-motif phosphorylation contributes to folding/stability.
In unstimulated cells, AKT1 adopts a PH-in autoinhibited conformation in which a PHβkinase domain interface masks the active state and sequesters the lipid-binding site. Structural work showed that phosphorylation alone does not fully relieve this state; productive activation requires both phosphoinositide binding and regulatory phosphorylation.
AKT1 is largely cytosolic (and can be nuclear) in quiescent cells, but active signaling is concentrated at membrane-associated compartments, especially the plasma membrane and, in some models, endosomal membranes. Lipid identity helps specify compartmental signaling, and dissociation from membranes promotes rapid inactivation.
AKT signaling is terminated at two levels: PTEN removes the lipid signal by dephosphorylating PIP3 to PI(4,5)P2, preventing membrane recruitment; PP2A and PHLPP dephosphorylate AKT at key regulatory residues, especially after membrane dissociation. This couples localization, phosphorylation state, and signaling duration.
Activated AKT1 phosphorylates substrates including GSK3 and FOXO1/3a, thereby promoting cell survival, proliferation, metabolism, and anabolic growth programs. Phosphorylation state, especially the Thr308/Ser473 balance, can influence substrate preference and signaling output.
A major recent milestone was capivasertib clinical translation. In CAPItello-291, capivasertib + fulvestrant improved median PFS from 3.6 to 7.2 months overall (HR 0.60) and from 3.1 to 7.3 months in pathway-altered tumors; reviews note FDA approval in HR+/HER2β advanced breast cancer with PIK3CA/AKT/PTEN alterations. Earlier supportive phase II data (FAKTION) showed PFS 10.3 vs 4.8 months and OS 29.3 vs 23.4 months.
NCT04305496 (CAPItello-291): phase III, randomized, double-blind capivasertib + fulvestrant vs placebo + fulvestrant; enrollment 818; capivasertib 400 mg BID, 4 days on/3 days off; primary endpoint PFS in overall and altered populations. NCT07281833 (CAPIcorn): phase III implementation-oriented study; plans to screen ~600 and enroll 250, enriching for PIK3CA/AKT1/PTEN alterations; evaluates treatment plus patient-reported-outcome adherence metrics.
In a 2023 TNBC brain-metastasis model, ipatasertib reduced viability and radiosensitized MDA-MB-231BR cells, but AKT1 knockout showed mixed/complex isoform-specific biology: reduced viability in one clone yet increased migration and clonogenic survival in both KO clones with decreased radiosensitivity, highlighting that AKT1 loss is not functionally equivalent to pan-AKT inhibition. The paper notes PI3K/AKT pathway activation in 43β70% of breast cancers.
(kempska2023impactofakt1 pages 1-2)
Table: This table summarizes verified identity, molecular function, regulation, localization, and recent translational evidence for rat AKT1/PKBΞ± (UniProt P47196). It is designed as a compact functional-annotation reference with citations to the available evidence contexts.
Limitations of this report
Much mechanistic AKT1 regulation literature is derived from human/mouse systems, but core activation/autoinhibition mechanisms are highly conserved and align with rat AKT1βs domain architecture and UniProt identity validation here. (hassan2024aktkinasesas pages 2-3, alwaili2024avenanthramidecamelioratedoxorubicininduced pages 2-3).
Clinical outcomes (capivasertib) pertain to human oncology; they are included as βapplications/implementationsβ relevant to AKT1 biology and translational targeting. (browne2024resistancetotargeted pages 4-6, NCT04305496 chunk 1).
References
(alwaili2024avenanthramidecamelioratedoxorubicininduced pages 2-3): Maha Abdullah Alwaili, Amal S. Abu-Almakarem, Salwa Aljohani, Sahar Abdulrahman Alkhodair, Maha M. Al-Bazi, Thamir M. Eid, Jehan Alamri, Maysa A. Mobasher, Norah K. Algarza, Arwa Ishaq A. Khayyat, Luluah Saleh Alshaygy, and Karim Samy El-Said. Avenanthramide-c ameliorate doxorubicin-induced hepatotoxicity via modulating akt/gsk-3Ξ² and wnt-4/Ξ²-catenin pathways in male rats. Frontiers in Molecular Biosciences, Dec 2024. URL: https://doi.org/10.3389/fmolb.2024.1507786, doi:10.3389/fmolb.2024.1507786. This article has 9 citations.
(hassan2024aktkinasesas pages 2-3): Dalal Hassan, Craig W. Menges, Joseph R Testa, and Alfonso Bellacosa. Akt kinases as therapeutic targets. Journal of Experimental & Clinical Cancer Research : CR, Nov 2024. URL: https://doi.org/10.1186/s13046-024-03207-4, doi:10.1186/s13046-024-03207-4. This article has 62 citations.
(chu2018aktkinaseactivation pages 1-3): Nam Chu, Nam Chu, Nam Chu, Antonieta L. Salguero, Antonieta L. Salguero, Antonieta L. Salguero, Albert Z. Liu, Zan Chen, Daniel R. Dempsey, Daniel R. Dempsey, Daniel R. Dempsey, S. Ficarro, William M. Alexander, J. Marto, J. Marto, Yana Li, L. Amzel, S. Gabelli, and P. Cole. Akt kinase activation mechanisms revealed using protein semisynthesis. Cell, 174:897-907.e14, Aug 2018. URL: https://doi.org/10.1016/j.cell.2018.07.003, doi:10.1016/j.cell.2018.07.003. This article has 173 citations and is from a highest quality peer-reviewed journal.
(yudushkin2020controlofakt pages 1-2): Ivan Yudushkin. Control of akt activity and substrate phosphorylation in cells. Iubmb Life, 72:1115-1125, Mar 2020. URL: https://doi.org/10.1002/iub.2264, doi:10.1002/iub.2264. This article has 64 citations and is from a peer-reviewed journal.
(shaw2025molecularinsighton pages 4-5): Alexandria L. Shaw and John E. Burke. Molecular insight on the role of the phosphoinositide pip3 in regulating the protein kinases akt, pdk1, and btk. Biochemical Society Transactions, Jul 2025. URL: https://doi.org/10.1042/bst20253059, doi:10.1042/bst20253059. This article has 17 citations and is from a peer-reviewed journal.
(truebestein2021structureofautoinhibited pages 1-2): Linda Truebestein, Harald Hornegger, Dorothea Anrather, Markus Hartl, Kaelin D. Fleming, Jordan T. B. Stariha, Els Pardon, Jan Steyaert, John E. Burke, and Thomas A. Leonard. Structure of autoinhibited akt1 reveals mechanism of pip3-mediated activation. Proceedings of the National Academy of Sciences of the United States of America, Aug 2021. URL: https://doi.org/10.1073/pnas.2101496118, doi:10.1073/pnas.2101496118. This article has 106 citations and is from a highest quality peer-reviewed journal.
(truebestein2021structureofautoinhibited pages 3-4): Linda Truebestein, Harald Hornegger, Dorothea Anrather, Markus Hartl, Kaelin D. Fleming, Jordan T. B. Stariha, Els Pardon, Jan Steyaert, John E. Burke, and Thomas A. Leonard. Structure of autoinhibited akt1 reveals mechanism of pip3-mediated activation. Proceedings of the National Academy of Sciences of the United States of America, Aug 2021. URL: https://doi.org/10.1073/pnas.2101496118, doi:10.1073/pnas.2101496118. This article has 106 citations and is from a highest quality peer-reviewed journal.
(truebestein2021structureofautoinhibited media b1c9177b): Linda Truebestein, Harald Hornegger, Dorothea Anrather, Markus Hartl, Kaelin D. Fleming, Jordan T. B. Stariha, Els Pardon, Jan Steyaert, John E. Burke, and Thomas A. Leonard. Structure of autoinhibited akt1 reveals mechanism of pip3-mediated activation. Proceedings of the National Academy of Sciences of the United States of America, Aug 2021. URL: https://doi.org/10.1073/pnas.2101496118, doi:10.1073/pnas.2101496118. This article has 106 citations and is from a highest quality peer-reviewed journal.
(truebestein2021structureofautoinhibited media 8a846e33): Linda Truebestein, Harald Hornegger, Dorothea Anrather, Markus Hartl, Kaelin D. Fleming, Jordan T. B. Stariha, Els Pardon, Jan Steyaert, John E. Burke, and Thomas A. Leonard. Structure of autoinhibited akt1 reveals mechanism of pip3-mediated activation. Proceedings of the National Academy of Sciences of the United States of America, Aug 2021. URL: https://doi.org/10.1073/pnas.2101496118, doi:10.1073/pnas.2101496118. This article has 106 citations and is from a highest quality peer-reviewed journal.
(chu2026structuralandmechanistic pages 6-7): Nam Chu, Nhat Le, Ouada Nebie, and Sammi Yang. Structural and mechanistic basis of mtorc2 activation of protein kinase akt/pkb. Biochemical Journal, 483:375-389, Mar 2026. URL: https://doi.org/10.1042/bcj20253108, doi:10.1042/bcj20253108. This article has 1 citations and is from a domain leading peer-reviewed journal.
(chu2026structuralandmechanistic pages 3-4): Nam Chu, Nhat Le, Ouada Nebie, and Sammi Yang. Structural and mechanistic basis of mtorc2 activation of protein kinase akt/pkb. Biochemical Journal, 483:375-389, Mar 2026. URL: https://doi.org/10.1042/bcj20253108, doi:10.1042/bcj20253108. This article has 1 citations and is from a domain leading peer-reviewed journal.
(yudushkin2020controlofakt pages 5-7): Ivan Yudushkin. Control of akt activity and substrate phosphorylation in cells. Iubmb Life, 72:1115-1125, Mar 2020. URL: https://doi.org/10.1002/iub.2264, doi:10.1002/iub.2264. This article has 64 citations and is from a peer-reviewed journal.
(chu2026structuralandmechanistic pages 4-5): Nam Chu, Nhat Le, Ouada Nebie, and Sammi Yang. Structural and mechanistic basis of mtorc2 activation of protein kinase akt/pkb. Biochemical Journal, 483:375-389, Mar 2026. URL: https://doi.org/10.1042/bcj20253108, doi:10.1042/bcj20253108. This article has 1 citations and is from a domain leading peer-reviewed journal.
(yudushkin2020controlofakt pages 2-4): Ivan Yudushkin. Control of akt activity and substrate phosphorylation in cells. Iubmb Life, 72:1115-1125, Mar 2020. URL: https://doi.org/10.1002/iub.2264, doi:10.1002/iub.2264. This article has 64 citations and is from a peer-reviewed journal.
(hassan2024aktkinasesas pages 13-14): Dalal Hassan, Craig W. Menges, Joseph R Testa, and Alfonso Bellacosa. Akt kinases as therapeutic targets. Journal of Experimental & Clinical Cancer Research : CR, Nov 2024. URL: https://doi.org/10.1186/s13046-024-03207-4, doi:10.1186/s13046-024-03207-4. This article has 62 citations.
(hassan2024aktkinasesas pages 14-16): Dalal Hassan, Craig W. Menges, Joseph R Testa, and Alfonso Bellacosa. Akt kinases as therapeutic targets. Journal of Experimental & Clinical Cancer Research : CR, Nov 2024. URL: https://doi.org/10.1186/s13046-024-03207-4, doi:10.1186/s13046-024-03207-4. This article has 62 citations.
(browne2024resistancetotargeted pages 4-6): Iseult M. Browne and Alicia F. C. Okines. Resistance to targeted inhibitors of the pi3k/akt/mtor pathway in advanced oestrogen-receptor-positive breast cancer. Cancers, 16:2259, Jun 2024. URL: https://doi.org/10.3390/cancers16122259, doi:10.3390/cancers16122259. This article has 44 citations.
(kempska2023impactofakt1 pages 1-2): Joanna Kempska, Leticia Oliveira-Ferrer, Astrid Grottke, Minyue Qi, Malik Alawi, Felix Meyer, Kerstin Borgmann, Fabienne Hamester, Kathrin Eylmann, Maila Rossberg, Daniel J. Smit, Manfred JΓΌcker, Elena Laakmann, Isabell Witzel, Barbara Schmalfeldt, Volkmar MΓΌller, and Karen Legler. Impact of akt1 on cell invasion and radiosensitivity in a triple negative breast cancer cell line developing brain metastasis. Frontiers in Oncology, Jul 2023. URL: https://doi.org/10.3389/fonc.2023.1129682, doi:10.3389/fonc.2023.1129682. This article has 13 citations.
(alves2023druggingthepi3kaktmtor pages 1-2): Carla L. Alves and Henrik J. Ditzel. Drugging the pi3k/akt/mtor pathway in er+ breast cancer. International Journal of Molecular Sciences, 24:4522, Feb 2023. URL: https://doi.org/10.3390/ijms24054522, doi:10.3390/ijms24054522. This article has 127 citations.
(NCT04305496 chunk 1): Capivasertib+Fulvestrant vs Placebo+Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic HR+/HER2- Breast Cancer. AstraZeneca. 2020. ClinicalTrials.gov Identifier: NCT04305496
(NCT07281833 chunk 1): Phase III Study to Evaluate the Safety, Efficacy, and Impact on Quality of Life of Capivasertib Alongside Standard-of-care Endocrine Treatment in Patients With HR+/HER2- Advanced Breast Cancer and Progression on Prior Endocrine-based Treatment. West German Study Group. 2025. ClinicalTrials.gov Identifier: NCT07281833
(NCT04305496 chunk 6): Capivasertib+Fulvestrant vs Placebo+Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic HR+/HER2- Breast Cancer. AstraZeneca. 2020. ClinicalTrials.gov Identifier: NCT04305496
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.
I begin with the domain architecture. The N-terminus (residues 1β123) carries IPR011993 (PH-like domain superfamily), with a refined PH-module core annotated by IPR039026 (Protein Kinase B, pleckstrin homology domain, residues 4β111) and IPR001849 (Pleckstrin homology domain, residues 5β110). This tandem PH/PH-like annotation establishes a lipid-sensing module that binds phosphoinositides and thereby controls subcellular targeting and activation gating. Immediately downstream, the polypeptide transitions into a canonical AGC kinase scaffold: IPR034676 (Protein kinase B alpha, catalytic domain, residues 124β479) encompasses the central kinase engine, reinforced by IPR011009 (Protein kinase-like domain superfamily, residues 145β459) and the core IPR000719 (Protein kinase domain, residues 150β408). Within this engine, IPR017441 marks the ATP-binding pocket (residues 156β189), and IPR008271 annotates the catalytic HRD/DLG motif region (active site, residues 270β282), defining serine/threonine phosphorylation chemistry. The C-terminal regulatory tail is characteristic of AGC kinases: IPR000961 (AGC-kinase, C-terminal, residues 409β480) and IPR017892 (Protein kinase, C-terminal, residues 429β474) encode hydrophobic/turn motifs that dock upstream signals and stabilize the active conformation. This ordered layoutβPH domain followed by a bilobal kinase core and an AGC regulatory tailβcausally dictates a phosphoinositide-gated serine/threonine kinase that shuttles between inactive and active states.
From these features, the molecular function follows directly. The PH domain concentrates the enzyme at membranes enriched in specific phosphoinositides, positioning the IPR000719 catalytic core to transfer the Ξ³-phosphate of ATP via the IPR017441 nucleotide-binding site and the IPR008271 catalytic center. This architecture enforces GO:0004674 protein serine/threonine kinase activity and necessitates GO:0005524 ATP binding. The AGC-tail modules (IPR000961, IPR017892) couple activation to upstream cues, ensuring substrate selection and timing are tightly coordinated.
These activities drive higher-order biology through phosphorylation cascades. A PH-gated AGC kinase at this position of the pathway is a canonical signal transducer, so it naturally executes GO:0006468 protein phosphorylation and propagates intracellular signaling cascades. Because its activation is tightly tied to PI3K-generated phosphoinositides and it modulates downstream survival and metabolic circuits, it contributes to signal transduction that regulates growth and metabolism. Thus, the kinaseβs chemistry and regulatory logic place it squarely in GO:0007165 signal transduction.
Cellular location emerges from the PH-mediated targeting and soluble kinase architecture. The absence of transmembrane segments and the soluble AGC fold argue for a cytosolic pool, consistent with cytoplasmic residence (GO:0005737). The PH domain nonetheless drives transient membrane association, but the steady-state operating environment is cytoplasm where substrates and adaptors accumulate.
This mechanistic picture suggests how the protein interacts. The PH domain recruits it to PI3K-active zones, where it likely engages scaffold/adaptor assemblies that present substrates. It plausibly forms complexes with PDPK1 (PDK1) that primes the activation loop, and with mTORC2 that modifies the C-terminal hydrophobic motifβboth events are encoded by the AGC-tail architecture. Substrates and pathway neighbors are expected to include GSK3 isoforms and FOXO transcription factors, whose phosphorylation status reflects its central position in growth and survival signaling. Together, lipid-gated membrane proximity, ATP-fueled catalysis, and AGC-tail control define a cytoplasmic serine/threonine kinase that orchestrates phosphorylation-driven signal transduction.
Functional Summary
A cytoplasmic serine/threonine kinase that uses an N-terminal lipid-binding module to dock onto phosphoinositide-enriched membranes and become spatially primed for catalysis. Its central kinase engine, stabilized by an AGC-family regulatory tail, transfers phosphate from ATP to diverse substrates, thereby propagating intracellular signaling that governs growth and metabolic control. By coupling membrane-proximal targeting to precise activation-loop regulation, it executes phosphorylation cascades that coordinate survival and biosynthetic pathways within the cytoplasm.
UniProt Summary
Acts redundantly with PRKCB in T-cell activation and is involved in the regulation of growth and metabolism.
Protein kinase, C-terminal (IPR017892, domain) β residues 429-474
GO Terms
Molecular Function: molecular_function (GO:0003674), catalytic activity (GO:0003824), protein serine/threonine kinase inhibitor activity (GO:0030291), binding (GO:0005488), carbohydrate derivative binding (GO:0097367), small molecule binding (GO:0036094), organic cyclic compound binding (GO:0097159), transferase activity (GO:0016740), heterocyclic compound binding (GO:1901363), ion binding (GO:0043167), catalytic activity, acting on a protein (GO:0140096), protein binding (GO:0005515), nucleoside phosphate binding (GO:1901265), protein kinase activity (GO:0004672), anion binding (GO:0043168), GTPase activating protein binding (GO:0032794), transferase activity, transferring phosphorus-containing groups (GO:0016772), nucleotide binding (GO:0000166), enzyme binding (GO:0019899), ribonucleotide binding (GO:0032553), protein serine/threonine kinase activity (GO:0004674), kinase activity (GO:0016301), phosphotransferase activity, alcohol group as acceptor (GO:0016773), kinase binding (GO:0019900), phosphatase binding (GO:0019902), purine nucleotide binding (GO:0017076), purine ribonucleoside triphosphate binding (GO:0035639), purine ribonucleotide binding (GO:0032555), ATP binding (GO:0005524), adenyl ribonucleotide binding (GO:0032559), adenyl nucleotide binding (GO:0030554), protein kinase binding (GO:0019901), protein phosphatase binding (GO:0019903), protein phosphatase 2A binding (GO:0051721), protein kinase C binding (GO:0005080)
Biological Process: biological_process (GO:0008150), positive regulation of biological process (GO:0048518), regulation of biological process (GO:0050789), signaling (GO:0023052), multicellular organismal process (GO:0032501), biological regulation (GO:0065007), response to stimulus (GO:0050896), developmental process (GO:0032502), cellular process (GO:0009987), metabolic process (GO:0008152), negative regulation of biological process (GO:0048519), response to external stimulus (GO:0009605), anatomical structure development (GO:0048856), negative regulation of signaling (GO:0023057), response to chemical (GO:0042221), positive regulation of multicellular organismal process (GO:0051240), nitrogen compound metabolic process (GO:0006807), cellular component organization or biogenesis (GO:0071840), regulation of multicellular organismal process (GO:0051239), positive regulation of growth (GO:0045927), positive regulation of transport (GO:0051050), negative regulation of metabolic process (GO:0009892), regulation of biological quality (GO:0065008), response to endogenous stimulus (GO:0009719), cell death (GO:0008219), regulation of cellular process (GO:0050794), regulation of response to stimulus (GO:0048583), cellular response to stimulus (GO:0051716), regulation of signaling (GO:0023051), aging (GO:0007568), negative regulation of cellular process (GO:0048523), signal transduction (GO:0007165), regulation of locomotion (GO:0040012), response to abiotic stimulus (GO:0009628), multicellular organism development (GO:0007275), biosynthetic process (GO:0009058), negative regulation of transport (GO:0051051), regulation of metabolic process (GO:0019222), regulation of localization (GO:0032879), organic substance metabolic process (GO:0071704), system process (GO:0003008), cellular metabolic process (GO:0044237), positive regulation of metabolic process (GO:0009893), regulation of molecular function (GO:0065009), response to stress (GO:0006950), negative regulation of response to stimulus (GO:0048585), cell communication (GO:0007154), regulation of growth (GO:0040008), primary metabolic process (GO:0044238), positive regulation of cellular process (GO:0048522), response to hypoxia (GO:0001666), positive regulation of cell death (GO:0010942), negative regulation of signal transduction (GO:0009968), programmed cell death (GO:0012501), regulation of cell motility (GO:2000145), negative regulation of cell death (GO:0060548), regulation of response to stress (GO:0080134), system development (GO:0048731), response to oxygen levels (GO:0070482), regulation of system process (GO:0044057), animal organ development (GO:0048513), response to growth factor (GO:0070848), regulation of signal transduction (GO:0009966), cellular response to endogenous stimulus (GO:0071495), regulation of macromolecule metabolic process (GO:0060255), carbohydrate metabolic process (GO:0005975), circulatory system process (GO:0003013), response to hormone (GO:0009725), negative regulation of transmembrane transport (GO:0034763), phosphorus metabolic process (GO:0006793), negative regulation of macromolecule metabolic process (GO:0010605), positive regulation of monoatomic ion transport (GO:0043270), regulation of membrane potential (GO:0042391), cellular response to abiotic stimulus (GO:0071214), regulation of nitrogen compound metabolic process (GO:0051171), cellular component organization (GO:0016043), cell surface receptor signaling pathway (GO:0007166), amide metabolic process (GO:0043603), regulation of cellular component organization (GO:0051128), cellular macromolecule metabolic process (GO:0044260), cellular response to external stimulus (GO:0071496), regulation of anatomical structure size (GO:0090066), cellular carbohydrate metabolic process (GO:0044262), positive regulation of nitrogen compound metabolic process (GO:0051173), regulation of catalytic activity (GO:0050790), negative regulation of cell communication (GO:0010648), negative regulation of nitrogen compound metabolic process (GO:0051172), regulation of transport (GO:0051049), organonitrogen compound metabolic process (GO:1901564), organic substance biosynthetic process (GO:1901576), positive regulation of macromolecule metabolic process (GO:0010604), regulation of cellular localization (GO:0060341), protein metabolic process (GO:0019538), regulation of cell growth (GO:0001558), negative regulation of molecular function (GO:0044092), regulation of cellular response to stress (GO:0080135), regulation of transmembrane transport (GO:0034762), cellular biosynthetic process (GO:0044249), response to oxygen-containing compound (GO:1901700), cellular nitrogen compound metabolic process (GO:0034641), positive regulation of cell growth (GO:0030307), negative regulation of cellular metabolic process (GO:0031324), macromolecule metabolic process (GO:0043170), response to organic substance (GO:0010033), cellular response to environmental stimulus (GO:0104004), regulation of cell death (GO:0010941), response to nitrogen compound (GO:1901698), regulation of cell communication (GO:0010646), cellular response to chemical stimulus (GO:0070887), cellular response to stress (GO:0033554), negative regulation of monoatomic ion transport (GO:0043271), positive regulation of vasoconstriction (GO:0045907), regulation of cellular metabolic process (GO:0031323), regulation of primary metabolic process (GO:0080090), response to mechanical stimulus (GO:0009612), response to ischemia (GO:0002931), generation of precursor metabolites and energy (GO:0006091), response to peptide (GO:1901652), regulation of cellular component size (GO:0032535), positive regulation of sodium ion transport (GO:0010765), spinal cord development (GO:0021510), macromolecule biosynthetic process (GO:0009059), cell projection organization (GO:0030030), cellular response to oxygen levels (GO:0071453), blood circulation (GO:0008015), regulation of protein metabolic process (GO:0051246), negative regulation of programmed cell death (GO:0043069), regulation of programmed cell death (GO:0043067), negative regulation of reactive oxygen species metabolic process (GO:2000378), regulation of stress-activated protein kinase signaling cascade (GO:0070302), regulation of cell migration (GO:0030334), regulation of mitochondrial membrane potential (GO:0051881), regulation of blood circulation (GO:1903522), organonitrogen compound biosynthetic process (GO:1901566), translation (GO:0006412), macromolecule modification (GO:0043412), negative regulation of monoatomic ion transmembrane transport (GO:0034766), nervous system development (GO:0007399), response to decreased oxygen levels (GO:0036293), polysaccharide metabolic process (GO:0005976), negative regulation of phosphorus metabolic process (GO:0010563), central nervous system development (GO:0007417), energy derivation by oxidation of organic compounds (GO:0015980), cellular response to oxygen-containing compound (GO:1901701), gene expression (GO:0010467), cellular response to hypoxia (GO:0071456), cellular response to organonitrogen compound (GO:0071417), vascular process in circulatory system (GO:0003018), negative regulation of catalytic activity (GO:0043086), enzyme-linked receptor protein signaling pathway (GO:0007167), peptide metabolic process (GO:0006518), regulation of reactive oxygen species metabolic process (GO:2000377), cellular response to DNA damage stimulus (GO:0006974), cellular response to organic substance (GO:0071310), positive regulation of programmed cell death (GO:0043068), response to nerve growth factor (GO:1990089), regulation of monoatomic ion transmembrane transport (GO:0034765), carbohydrate biosynthetic process (GO:0016051), negative regulation of protein metabolic process (GO:0051248), cellular carbohydrate biosynthetic process (GO:0034637), cellular response to nitrogen compound (GO:1901699), amide biosynthetic process (GO:0043604), phosphate-containing compound metabolic process (GO:0006796), regulation of protein localization (GO:0032880), negative regulation of intracellular signal transduction (GO:1902532), cellular polysaccharide metabolic process (GO:0044264), regulation of tube size (GO:0035150), protein modification process (GO:0036211), response to peptide hormone (GO:0043434), regulation of generation of precursor metabolites and energy (GO:0043467), cellular response to hormone stimulus (GO:0032870), response to organonitrogen compound (GO:0010243), positive regulation of membrane potential (GO:0045838), apoptotic process (GO:0006915), positive regulation of protein metabolic process (GO:0051247), cellular nitrogen compound biosynthetic process (GO:0044271), negative regulation of calcium ion transport (GO:0051926), cellular response to mechanical stimulus (GO:0071260), cellular macromolecule biosynthetic process (GO:0034645), response to organic cyclic compound (GO:0014070), regulation of transferase activity (GO:0051338), regulation of monoatomic ion transport (GO:0043269), cellular response to growth factor stimulus (GO:0071363), regulation of intracellular signal transduction (GO:1902531), regulation of phosphorus metabolic process (GO:0051174), regulation of apoptotic process (GO:0042981), negative regulation of protein modification process (GO:0031400), regulation of metal ion transport (GO:0010959), peptidyl-amino acid modification (GO:0018193), phosphorylation (GO:0016310), blood vessel diameter maintenance (GO:0097746), regulation of kinase activity (GO:0043549), negative regulation of transferase activity (GO:0051348), regulation of tube diameter (GO:0035296), transmembrane receptor protein tyrosine kinase signaling pathway (GO:0007169), regulation of cellular respiration (GO:0043457), negative regulation of calcium ion transmembrane transport (GO:1903170), negative regulation of stress-activated protein kinase signaling cascade (GO:0070303), regulation of monoatomic cation transmembrane transport (GO:1904062), regulation of stress-activated MAPK cascade (GO:0032872), negative regulation of MAPK cascade (GO:0043409), regulation of MAPK cascade (GO:0043408), positive regulation of apoptotic process (GO:0043065), peptide biosynthetic process (GO:0043043), cellular polysaccharide biosynthetic process (GO:0033692), glucan metabolic process (GO:0044042), regulation of superoxide metabolic process (GO:0090322), regulation of protein modification process (GO:0031399), cellular response to peptide hormone stimulus (GO:0071375), regulation of vasoconstriction (GO:0019229), positive regulation of mitochondrial membrane potential (GO:0010918), energy reserve metabolic process (GO:0006112), response to insulin (GO:0032868), polysaccharide biosynthetic process (GO:0000271), negative regulation of apoptotic process (GO:0043066), protein phosphorylation (GO:0006468), negative regulation of cation transmembrane transport (GO:1904063), regulation of cell size (GO:0008361), cellular response to organic cyclic compound (GO:0071407), cellular glucan metabolic process (GO:0006073), regulation of phosphate metabolic process (GO:0019220), cellular response to peptide (GO:1901653), cellular response to decreased oxygen levels (GO:0036294), cellular response to nerve growth factor stimulus (GO:1990090), negative regulation of phosphate metabolic process (GO:0045936), regulation of superoxide anion generation (GO:0032928), regulation of protein phosphorylation (GO:0001932), cellular response to insulin stimulus (GO:0032869), negative regulation of phosphorylation (GO:0042326), regulation of protein kinase activity (GO:0045859), glucan biosynthetic process (GO:0009250), regulation of calcium ion transport (GO:0051924), peptidyl-serine phosphorylation (GO:0018105), regulation of aerobic respiration (GO:1903715), peptidyl-serine modification (GO:0018209), negative regulation of stress-activated MAPK cascade (GO:0032873), regulation of phosphorylation (GO:0042325), negative regulation of protein phosphorylation (GO:0001933), regulation of JNK cascade (GO:0046328), insulin receptor signaling pathway (GO:0008286), glycogen metabolic process (GO:0005977), negative regulation of kinase activity (GO:0033673), negative regulation of cell size (GO:0045792), regulation of sodium ion transport (GO:0002028), regulation of calcium ion transmembrane transport (GO:1903169), negative regulation of JNK cascade (GO:0046329), glycogen biosynthetic process (GO:0005978), negative regulation of protein kinase activity (GO:0006469)
The functional summary accurately captures Akt1 as:
A cytoplasmic serine/threonine kinase that uses an N-terminal lipid-binding module to dock onto phosphoinositide-enriched membranes and become spatially primed for catalysis. Its central kinase engine, stabilized by an AGC-family regulatory tail, transfers phosphate from ATP to diverse substrates, thereby propagating intracellular signaling that governs growth and metabolic control.
This is well-supported. The PH domain-mediated membrane recruitment, AGC kinase architecture, and role in PI3K/Akt signaling are all accurately described. The curated review confirms protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), intracellular signal transduction (GO:0035556), cytoplasm (GO:0005737), insulin receptor signaling pathway (GO:0008286), and negative regulation of apoptotic process (GO:0043066) -- all consistent with BioReason's narrative.
The summary correctly emphasizes cytoplasmic localization and membrane-proximal activation. The mention of "survival and biosynthetic pathways" aligns with the curated anti-apoptotic and insulin signaling annotations.
One minor gap: the summary does not explicitly mention the anti-apoptotic role (GO:0043066) or insulin signaling (GO:0008286), both of which are IBA-annotated core functions. The summary speaks generically of "growth and metabolic control" which is accurate but less specific than the curated annotations warrant.
Comparison with interpro2go:
The interpro2go (GO_REF:0000002) annotations for Akt1 are protein kinase activity (GO:0004672) and ATP binding (GO:0005524). BioReason's summary directly recapitulates these -- describing the ATP-binding pocket and phosphotransfer chemistry. BioReason goes beyond interpro2go by correctly inferring the PH domain-mediated membrane recruitment, AGC-family regulatory mechanism, and downstream signaling context. No interpro2go errors are recapitulated.
Notes on thinking trace
The trace methodically walks through domain architecture (PH domain, kinase core, AGC tail) and logically derives function from structure. The reasoning about PDPK1-mediated activation loop phosphorylation and mTORC2 hydrophobic motif modification is accurate. The mention of GSK3 and FOXO as substrates is correct. The trace is thorough and well-organized.
π View Raw YAML
id: P47196
gene_symbol: Akt1
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:10116
label: Rattus norvegicus
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:
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005737; C:cytoplasm; ISO:RGD.
- term:
id: GO:0004674
label: protein serine/threonine kinase activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
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.'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
- reference_id: file:rat/Akt1/Akt1-deep-research-falcon.md
supporting_text: AKT1 catalyzes **ATP-dependent phosphorylation of serine/threonine residues** in protein substrates (EC **2.7.11.1**, protein-serine/threonine kinase).
- term:
id: GO:0035556
label: intracellular signal transduction
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0035556; P:intracellular signal transduction; ISO:RGD.
- term:
id: GO:0043066
label: negative regulation of apoptotic process
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
- reference_id: file:rat/Akt1/Akt1-deep-research-falcon.md
supporting_text: Activated AKT1 phosphorylates substrates including **GSK3** and **FOXO1/3a**, thereby promoting cell survival, proliferation, metabolism, and anabolic growth programs.
- term:
id: GO:0008286
label: insulin receptor signaling pathway
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0008286; P:insulin receptor signaling pathway; IDA:BHF-UCL.
- reference_id: file:rat/Akt1/Akt1-deep-research-falcon.md
supporting_text: central signaling node downstream of growth factor/insulin pathways, regulating survival, growth, metabolism
- term:
id: GO:0043536
label: positive regulation of blood vessel endothelial cell migration
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:RGD.
- term:
id: GO:0004672
label: protein kinase activity
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
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).'
action: MODIFY
reason: Replace the transferred ISO term with the specific serine/threonine kinase activity term used for AKT-family biochemistry.
proposed_replacement_terms: &id001
- id: GO:0004674
label: protein serine/threonine kinase activity
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0004672; F:protein kinase activity; IDA:RGD.
- term:
id: GO:0004674
label: protein serine/threonine kinase activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
- term:
id: GO:0005080
label: protein kinase C binding
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a real but non-core interaction annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005080; F:protein kinase C binding; IPI:RGD.
- term:
id: GO:0005524
label: ATP binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005524; F:ATP binding; IDA:RGD.
- reference_id: file:rat/Akt1/Akt1-deep-research-falcon.md
supporting_text: transfers phosphate from ATP to **Ser/Thr residues on protein substrates**
- term:
id: GO:0005634
label: nucleus
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005634; C:nucleus; IDA:UniProtKB.
- reference_id: file:rat/Akt1/Akt1-deep-research-falcon.md
supporting_text: AKT1 is largely **cytosolic (and can be nuclear) in quiescent cells**, but active signaling is concentrated at **membrane-associated compartments**, especially the **plasma membrane**
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005737; C:cytoplasm; ISO:RGD.
- term:
id: GO:0005758
label: mitochondrial intermembrane space
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005758; C:mitochondrial intermembrane space; ISS:UniProtKB.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
- reference_id: file:rat/Akt1/Akt1-deep-research-falcon.md
supporting_text: growth factor stimulation triggers **PH-domain-dependent recruitment to membranes** enriched for PIP3/PI(3,4)P2
- term:
id: GO:0010765
label: positive regulation of sodium ion transport
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0010765; P:positive regulation of sodium ion transport; IMP:MGI.
- term:
id: GO:0032869
label: cellular response to insulin stimulus
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0032869; P:cellular response to insulin stimulus; IDA:RGD.
- term:
id: GO:0106310
label: protein serine kinase activity
evidence_type: IEA
original_reference_id: GO_REF:0000116
review:
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.'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0106310; F:protein serine kinase activity; ISO:RGD.
- reference_id: file:rat/Akt1/Akt1-deep-research-falcon.md
supporting_text: increased phosphorylation activity toward substrates such as **GSK3** and **FOXO1/3a**
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:16362038
review:
summary: 'The cited studies report individual interactions, but the generic term protein binding is too uninformative to retain in the review.'
action: REMOVE
reason: Protein binding is not sufficiently specific or useful as a curated AKT1 function term.
supported_by:
- reference_id: PMID:16362038
supporting_text: Novel roles of Akt and mTOR in suppressing TGF-beta/ALK5-mediated Smad3 activation.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:16642037
review:
summary: 'The cited studies report individual interactions, but the generic term protein binding is too uninformative to retain in the review.'
action: REMOVE
reason: Protein binding is not sufficiently specific or useful as a curated AKT1 function term.
supported_by:
- reference_id: PMID:16642037
supporting_text: Nuclear Akt associates with PKC-phosphorylated Ebp1, preventing DNA fragmentation by inhibition of caspase-activated DNase.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:20488185
review:
summary: 'The cited studies report individual interactions, but the generic term protein binding is too uninformative to retain in the review.'
action: REMOVE
reason: Protein binding is not sufficiently specific or useful as a curated AKT1 function term.
supported_by:
- reference_id: PMID:20488185
supporting_text: Glyceraldehyde-3-phosphate dehydrogenase interacts with phosphorylated Akt resulting from increased blood glucose in rat cardiac muscle.
- term:
id: GO:0042802
label: identical protein binding
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0042802; F:identical protein binding; ISO:RGD.
- term:
id: GO:0042307
label: positive regulation of protein import into nucleus
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: 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).
- term:
id: GO:0005654
label: nucleoplasm
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005654; C:nucleoplasm; ISO:RGD.
- term:
id: GO:0004674
label: protein serine/threonine kinase activity
evidence_type: TAS
original_reference_id: Reactome:R-RNO-198601
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
- term:
id: GO:0051897
label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to 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.
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: 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).
- term:
id: GO:0106310
label: protein serine kinase activity
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0106310; F:protein serine kinase activity; ISO:RGD.
- term:
id: GO:0007224
label: smoothened signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: 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).
- term:
id: GO:0021525
label: lateral motor column neuron differentiation
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: 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).
- term:
id: GO:0050821
label: protein stabilization
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: 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).
- term:
id: GO:0010467
label: gene expression
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0010467; P:gene expression; ISO:RGD.
- term:
id: GO:0008286
label: insulin receptor signaling pathway
evidence_type: IMP
original_reference_id: PMID:10454575
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: PMID:10454575
supporting_text: Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt.
- term:
id: GO:0043491
label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
evidence_type: IDA
original_reference_id: PMID:10454575
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: PMID:10454575
supporting_text: Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt.
- term:
id: GO:0002430
label: complement receptor mediated signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0002430; P:complement receptor mediated signaling pathway; ISO:RGD.
- term:
id: GO:0043491
label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
evidence_type: IDA
original_reference_id: PMID:8524413
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: PMID:8524413
supporting_text: Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B.
- term:
id: GO:1905786
label: positive regulation of anaphase-promoting complex-dependent catabolic process
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:1905786; P:positive regulation of anaphase-promoting complex-dependent catabolic process; ISO:RGD.
- term:
id: GO:0019900
label: kinase binding
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0019900; F:kinase binding; ISO:RGD.
- term:
id: GO:0043491
label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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).
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:BHF-UCL.
- reference_id: file:rat/Akt1/Akt1-deep-research-falcon.md
supporting_text: AKT1 sits in the canonical **PI3KβAKTβmTOR** axis.
- term:
id: GO:0045944
label: positive regulation of transcription by RNA polymerase II
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
- term:
id: GO:1900087
label: positive regulation of G1/S transition of mitotic cell cycle
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; ISO:RGD.
- term:
id: GO:1903384
label: negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:1903384; P:negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway; ISO:RGD.
- term:
id: GO:1904841
label: TORC2 complex binding
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:1904841; F:TORC2 complex binding; ISO:RGD.
- reference_id: file:rat/Akt1/Akt1-deep-research-falcon.md
supporting_text: '**mTORC2 phosphorylates Ser473** in the hydrophobic motif'
- term:
id: GO:0005080
label: protein kinase C binding
evidence_type: IPI
original_reference_id: PMID:8755528
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a real but non-core interaction annotation.
supported_by:
- reference_id: PMID:8755528
supporting_text: Activation of RAC-protein kinase by heat shock and hyperosmolarity stress through a pathway independent of phosphatidylinositol 3-kinase.
- term:
id: GO:0034605
label: cellular response to heat
evidence_type: IDA
original_reference_id: PMID:8755528
review:
summary: 'Rat experiments support AKT activation during heat stress, but this is a conditional stress-response context rather than a core AKT1 function.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core stress-response annotation.
supported_by:
- reference_id: PMID:8755528
supporting_text: Activation of RAC-protein kinase by heat shock and hyperosmolarity stress through a pathway independent of phosphatidylinositol 3-kinase.
- term:
id: GO:0071475
label: cellular hyperosmotic salinity response
evidence_type: IDA
original_reference_id: PMID:8755528
review:
summary: 'Rat experiments support AKT activation during hyperosmotic stress, but the term describes a conditional response rather than a core conserved function.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core stress-response annotation.
supported_by:
- reference_id: PMID:8755528
supporting_text: Activation of RAC-protein kinase by heat shock and hyperosmolarity stress through a pathway independent of phosphatidylinositol 3-kinase.
- term:
id: GO:0072709
label: cellular response to sorbitol
evidence_type: IDA
original_reference_id: PMID:8755528
review:
summary: 'The supporting experiment used sorbitol as a hyperosmotic stimulus; keeping a sorbitol-specific response term overstates a broader stress-signaling observation.'
action: MARK_AS_OVER_ANNOTATED
reason: The annotation is too stimulus-specific for a stable AKT1 gene-level assignment.
supported_by:
- reference_id: PMID:8755528
supporting_text: Activation of RAC-protein kinase by heat shock and hyperosmolarity stress through a pathway independent of phosphatidylinositol 3-kinase.
- term:
id: GO:0004672
label: protein kinase activity
evidence_type: IDA
original_reference_id: PMID:9112399
review:
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).'
action: MODIFY
reason: Replace the transferred ISO term with the specific serine/threonine kinase activity term used for AKT-family biochemistry.
proposed_replacement_terms: *id001
supported_by:
- reference_id: PMID:9112399
supporting_text: Potential role of protein kinase B in glucose transporter 4 translocation in adipocytes.
- term:
id: GO:0005829
label: cytosol
evidence_type: IDA
original_reference_id: PMID:9112399
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: PMID:9112399
supporting_text: Potential role of protein kinase B in glucose transporter 4 translocation in adipocytes.
- term:
id: GO:0071364
label: cellular response to epidermal growth factor stimulus
evidence_type: IDA
original_reference_id: PMID:15701816
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: PMID:15701816
supporting_text: 'EGF stimulates mesangial cell mitogenesis via PI3-kinase-mediated MAPK-dependent and AKT kinase-independent manner: involvement of c-fos and p27Kip1.'
- term:
id: GO:0014850
label: response to muscle activity
evidence_type: IDA
original_reference_id: PMID:19574345
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core physiology annotation.
supported_by:
- reference_id: PMID:19574345
supporting_text: Lipid-induced mTOR activation in rat skeletal muscle reversed by exercise and 5'-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside.
- term:
id: GO:0031667
label: response to nutrient levels
evidence_type: IDA
original_reference_id: PMID:19574345
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core physiology annotation.
supported_by:
- reference_id: PMID:19574345
supporting_text: Lipid-induced mTOR activation in rat skeletal muscle reversed by exercise and 5'-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside.
- term:
id: GO:0004672
label: protein kinase activity
evidence_type: IDA
original_reference_id: PMID:7774014
review:
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).'
action: MODIFY
reason: Replace the transferred ISO term with the specific serine/threonine kinase activity term used for AKT-family biochemistry.
proposed_replacement_terms: *id001
supported_by:
- reference_id: PMID:7774014
supporting_text: The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase.
- term:
id: GO:0032869
label: cellular response to insulin stimulus
evidence_type: IDA
original_reference_id: PMID:9005851
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: PMID:9005851
supporting_text: Regulation of neuronal survival by the serine-threonine protein kinase Akt.
- term:
id: GO:0036120
label: cellular response to platelet-derived growth factor stimulus
evidence_type: IDA
original_reference_id: PMID:7774014
review:
summary: 'PDGF-dependent activation of AKT is well supported, but this growth-factor response context is narrower than AKT1''s core biochemistry.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core pathway-context annotation.
supported_by:
- reference_id: PMID:7774014
supporting_text: The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase.
- term:
id: GO:0046777
label: protein autophosphorylation
evidence_type: IDA
original_reference_id: PMID:7774014
review:
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.'
action: REMOVE
reason: Current AKT1 biology supports activation by upstream kinases rather than retaining autophosphorylation as a curated core annotation.
supported_by:
- reference_id: PMID:7774014
supporting_text: The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase.
- term:
id: GO:1901653
label: cellular response to peptide
evidence_type: IEP
original_reference_id: PMID:18772167
review:
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).'
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: PMID:18772167
supporting_text: 'Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: involvement of the cholinergic pathway.'
- term:
id: GO:0004674
label: protein serine/threonine kinase activity
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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).
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
- term:
id: GO:0071363
label: cellular response to growth factor stimulus
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0071363; P:cellular response to growth factor stimulus; ISO:RGD.
- term:
id: GO:1904515
label: positive regulation of TORC2 signaling
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:1904515; P:positive regulation of TORC2 signaling; ISO:RGD.
- term:
id: GO:1903898
label: negative regulation of PERK-mediated unfolded protein response
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:1903898; P:negative regulation of PERK-mediated unfolded protein response; ISO:RGD.
- term:
id: GO:0004674
label: protein serine/threonine kinase activity
evidence_type: IDA
original_reference_id: PMID:9065430
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: PMID:9065430
supporting_text: 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.
- term:
id: GO:0032869
label: cellular response to insulin stimulus
evidence_type: IDA
original_reference_id: PMID:9065430
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: PMID:9065430
supporting_text: 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.
- term:
id: GO:0001649
label: osteoblast differentiation
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0001649; P:osteoblast differentiation; ISO:RGD.
- term:
id: GO:0030425
label: dendrite
evidence_type: IDA
original_reference_id: PMID:31071414
review:
summary: 'The cited hippocampal study is a tissue-specific expression context and does not justify a stable dendrite localization annotation for AKT1.'
action: REMOVE
reason: The term is too context-specific and not a reliable general localization assignment.
supported_by:
- reference_id: PMID:31071414
supporting_text: Sex Differences in Neuroplasticity- and Stress-Related Gene Expression and Protein Levels in the Rat Hippocampus Following Oxycodone Conditioned Place Preference.
- term:
id: GO:0005758
label: mitochondrial intermembrane space
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005758; C:mitochondrial intermembrane space; ISS:UniProtKB.
- term:
id: GO:0005758
label: mitochondrial intermembrane space
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005758; C:mitochondrial intermembrane space; ISS:UniProtKB.
- term:
id: GO:0098978
label: glutamatergic synapse
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
- term:
id: GO:0099175
label: regulation of postsynapse organization
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0099175; P:regulation of postsynapse organization; ISO:RGD.
- term:
id: GO:0030335
label: positive regulation of cell migration
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
- term:
id: GO:0160049
label: negative regulation of cGAS/STING signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0160049; P:negative regulation of cGAS/STING signaling pathway; ISO:RGD.
- term:
id: GO:0004672
label: protein kinase activity
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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).
action: MODIFY
reason: Replace the transferred ISO term with the specific serine/threonine kinase activity term used for AKT-family biochemistry.
proposed_replacement_terms: *id001
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0004672; F:protein kinase activity; IDA:RGD.
- term:
id: GO:1902018
label: negative regulation of cilium assembly
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: 'The rat ISO traces to human 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.'
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:1902018; P:negative regulation of cilium assembly; ISS:UniProtKB.
- term:
id: GO:1902018
label: negative regulation of cilium assembly
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:1902018; P:negative regulation of cilium assembly; ISS:UniProtKB.
- term:
id: GO:0008286
label: insulin receptor signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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).
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0008286; P:insulin receptor signaling pathway; IDA:BHF-UCL.
- term:
id: GO:0071364
label: cellular response to epidermal growth factor stimulus
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IDA:RGD.
- term:
id: GO:0071364
label: cellular response to epidermal growth factor stimulus
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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).
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IDA:RGD.
- term:
id: GO:0150033
label: negative regulation of protein localization to lysosome
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: 'The rat ISO traces to human 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.'
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0150033; P:negative regulation of protein localization to lysosome; ISS:UniProtKB.
- term:
id: GO:0150033
label: negative regulation of protein localization to lysosome
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0150033; P:negative regulation of protein localization to lysosome; ISS:UniProtKB.
- term:
id: GO:0016020
label: membrane
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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'.
action: MODIFY
reason: The donor evidence concerns regulated plasma-membrane recruitment/activation, so the parent term membrane is too broad.
proposed_replacement_terms:
- id: GO:0005886
label: plasma membrane
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0016020; C:membrane; ISO:RGD.
- term:
id: GO:0032869
label: cellular response to insulin stimulus
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0032869; P:cellular response to insulin stimulus; IDA:RGD.
- term:
id: GO:0032869
label: cellular response to insulin stimulus
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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).
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0032869; P:cellular response to insulin stimulus; IDA:RGD.
- term:
id: GO:1904263
label: positive regulation of TORC1 signaling
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:1904263; P:positive regulation of TORC1 signaling; ISS:UniProtKB.
- term:
id: GO:1904263
label: positive regulation of TORC1 signaling
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:1904263; P:positive regulation of TORC1 signaling; ISS:UniProtKB.
- term:
id: GO:0032436
label: positive regulation of proteasomal ubiquitin-dependent protein catabolic process
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:RGD.
- term:
id: GO:0110002
label: regulation of tRNA methylation
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0110002; P:regulation of tRNA methylation; ISO:RGD.
- term:
id: GO:0022605
label: mammalian oogenesis stage
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0022605; P:mammalian oogenesis stage; ISO:RGD.
- term:
id: GO:0004674
label: protein serine/threonine kinase activity
evidence_type: IDA
original_reference_id: PMID:8524413
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: PMID:8524413
supporting_text: Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B.
- term:
id: GO:0008286
label: insulin receptor signaling pathway
evidence_type: IDA
original_reference_id: PMID:8524413
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: PMID:8524413
supporting_text: Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B.
- term:
id: GO:0010748
label: negative regulation of long-chain fatty acid import across plasma membrane
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0010748; P:negative regulation of long-chain fatty acid import across plasma membrane; ISO:RGD.
- term:
id: GO:0010907
label: positive regulation of glucose metabolic process
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0010907; P:positive regulation of glucose metabolic process; ISO:RGD.
- term:
id: GO:0030291
label: protein serine/threonine kinase inhibitor activity
evidence_type: IPI
original_reference_id: PMID:8524413
review:
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.'
action: REMOVE
reason: The term misstates AKT1's biochemistry and should not be retained.
supported_by:
- reference_id: PMID:8524413
supporting_text: Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B.
- term:
id: GO:0031999
label: negative regulation of fatty acid beta-oxidation
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0031999; P:negative regulation of fatty acid beta-oxidation; ISO:RGD.
- term:
id: GO:0045725
label: positive regulation of glycogen biosynthetic process
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; ISO:RGD.
- term:
id: GO:0046326
label: positive regulation of D-glucose import across plasma membrane
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0046326; P:positive regulation of D-glucose import; ISO:RGD.
- term:
id: GO:0120283
label: protein serine/threonine kinase binding
evidence_type: IPI
original_reference_id: PMID:8524413
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core binding annotation.
supported_by:
- reference_id: PMID:8524413
supporting_text: Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B.
- term:
id: GO:0048009
label: insulin-like growth factor receptor signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISS:UniProtKB.
- term:
id: GO:0016301
label: kinase activity
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: MODIFY
reason: Replace the transferred ISO term with the specific serine/threonine kinase activity term used for AKT-family biochemistry.
proposed_replacement_terms:
- id: GO:0004674
label: protein serine/threonine kinase activity
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0016301; F:kinase activity; ISO:RGD.
- term:
id: GO:0005737
label: cytoplasm
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005737; C:cytoplasm; ISO:RGD.
- term:
id: GO:0006468
label: protein phosphorylation
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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).
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
- term:
id: GO:1905552
label: positive regulation of protein localization to endoplasmic reticulum
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:1905552; P:positive regulation of protein localization to endoplasmic reticulum; ISO:RGD.
- term:
id: GO:0006954
label: inflammatory response
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0006954; P:inflammatory response; ISO:RGD.
- term:
id: GO:0009408
label: response to heat
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0009408; P:response to heat; ISO:RGD.
- term:
id: GO:0048266
label: behavioral response to pain
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0048266; P:behavioral response to pain; ISO:RGD.
- term:
id: GO:0010629
label: negative regulation of gene expression
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
- term:
id: GO:0070848
label: response to growth factor
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0070848; P:response to growth factor; ISO:RGD.
- term:
id: GO:0099104
label: potassium channel activator activity
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: 'The rat ISO traces to human 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.'
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0099104; F:potassium channel activator activity; ISS:UniProtKB.
- term:
id: GO:0099104
label: potassium channel activator activity
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0099104; F:potassium channel activator activity; ISS:UniProtKB.
- term:
id: GO:1990090
label: cellular response to nerve growth factor stimulus
evidence_type: IEP
original_reference_id: PMID:9492284
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: PMID:9492284
supporting_text: Nerve growth factor promotes activation of the alpha, beta and gamma isoforms of protein kinase B in PC12 pheochromocytoma cells.
- term:
id: GO:0002931
label: response to ischemia
evidence_type: IEP
original_reference_id: PMID:24601882
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core physiology annotation.
supported_by:
- reference_id: PMID:24601882
supporting_text: Protein kinase B (PKB/AKT1) formed signaling complexes with mitochondrial proteins and prevented glycolytic energy dysfunction in cultured cardiomyocytes during ischemia-reperfusion injury.
- term:
id: GO:0010918
label: positive regulation of mitochondrial membrane potential
evidence_type: IMP
original_reference_id: PMID:24601882
review:
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.'
action: MARK_AS_OVER_ANNOTATED
reason: Retains some signal of a real observation while flagging the term as over-specific.
supported_by:
- reference_id: PMID:24601882
supporting_text: Protein kinase B (PKB/AKT1) formed signaling complexes with mitochondrial proteins and prevented glycolytic energy dysfunction in cultured cardiomyocytes during ischemia-reperfusion injury.
- term:
id: GO:0032929
label: negative regulation of superoxide anion generation
evidence_type: IMP
original_reference_id: PMID:24601882
review:
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.'
action: MARK_AS_OVER_ANNOTATED
reason: The annotation is too context-specific for a general AKT1 function statement.
supported_by:
- reference_id: PMID:24601882
supporting_text: Protein kinase B (PKB/AKT1) formed signaling complexes with mitochondrial proteins and prevented glycolytic energy dysfunction in cultured cardiomyocytes during ischemia-reperfusion injury.
- term:
id: GO:0110099
label: negative regulation of calcium import into the mitochondrion
evidence_type: IMP
original_reference_id: PMID:24601882
review:
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.'
action: REMOVE
reason: Remove as an over-specific pathway inference.
supported_by:
- reference_id: PMID:24601882
supporting_text: Protein kinase B (PKB/AKT1) formed signaling complexes with mitochondrial proteins and prevented glycolytic energy dysfunction in cultured cardiomyocytes during ischemia-reperfusion injury.
- term:
id: GO:1903715
label: regulation of aerobic respiration
evidence_type: IMP
original_reference_id: PMID:24601882
review:
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.'
action: MARK_AS_OVER_ANNOTATED
reason: The term overgeneralizes a specific injury-model phenotype.
supported_by:
- reference_id: PMID:24601882
supporting_text: Protein kinase B (PKB/AKT1) formed signaling complexes with mitochondrial proteins and prevented glycolytic energy dysfunction in cultured cardiomyocytes during ischemia-reperfusion injury.
- term:
id: GO:0005829
label: cytosol
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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).
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005829; C:cytosol; IDA:RGD.
- term:
id: GO:0003376
label: sphingosine-1-phosphate receptor signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0003376; P:sphingosine-1-phosphate receptor signaling pathway; ISO:RGD.
- term:
id: GO:0010595
label: positive regulation of endothelial cell migration
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to 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.
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:RGD.
- term:
id: GO:0046889
label: positive regulation of lipid biosynthetic process
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: 'The rat ISO traces to 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.'
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0046889; P:positive regulation of lipid biosynthetic process; ISS:UniProtKB.
- term:
id: GO:2001243
label: negative regulation of intrinsic apoptotic signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; ISO:RGD.
- term:
id: GO:0005516
label: calmodulin binding
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB.
- term:
id: GO:0005516
label: calmodulin binding
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB.
- term:
id: GO:0002042
label: cell migration involved in sprouting angiogenesis
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to 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.
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; ISO:RGD.
- term:
id: GO:0010628
label: positive regulation of gene expression
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
- term:
id: GO:0140052
label: cellular response to oxidised low-density lipoprotein particle stimulus
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0140052; P:cellular response to oxidised low-density lipoprotein particle stimulus; ISO:RGD.
- term:
id: GO:1903038
label: negative regulation of leukocyte cell-cell adhesion
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:1903038; P:negative regulation of leukocyte cell-cell adhesion; ISO:RGD.
- term:
id: GO:2000402
label: negative regulation of lymphocyte migration
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:2000402; P:negative regulation of lymphocyte migration; ISO:RGD.
- term:
id: GO:0032880
label: regulation of protein localization
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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).
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0032880; P:regulation of protein localization; IMP:MGI.
- term:
id: GO:2000010
label: positive regulation of protein localization to cell surface
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:2000010; P:positive regulation of protein localization to cell surface; ISO:RGD.
- term:
id: GO:0031397
label: negative regulation of protein ubiquitination
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0031397; P:negative regulation of protein ubiquitination; ISO:RGD.
- term:
id: GO:0071356
label: cellular response to tumor necrosis factor
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0071356; P:cellular response to tumor necrosis factor; ISO:RGD.
- term:
id: GO:0042803
label: protein homodimerization activity
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
- term:
id: GO:0007173
label: epidermal growth factor receptor signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISO:RGD.
- term:
id: GO:0032991
label: protein-containing complex
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to 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.
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0032991; C:protein-containing complex; ISO:RGD.
- term:
id: GO:0042981
label: regulation of apoptotic process
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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.'
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
- term:
id: GO:0042981
label: regulation of apoptotic process
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
- term:
id: GO:0046622
label: positive regulation of organ growth
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0046622; P:positive regulation of organ growth; ISO:RGD.
- term:
id: GO:0035655
label: interleukin-18-mediated signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0035655; P:interleukin-18-mediated signaling pathway; ISO:RGD.
- term:
id: GO:0048661
label: positive regulation of smooth muscle cell proliferation
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to 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.
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:RGD.
- term:
id: GO:0005634
label: nucleus
evidence_type: IDA
original_reference_id: PMID:20605787
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: PMID:20605787
supporting_text: Ribosomal protein S3, a new substrate of Akt, serves as a signal mediator between neuronal apoptosis and DNA repair.
- term:
id: GO:1900182
label: positive regulation of protein localization to nucleus
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISO:RGD.
- term:
id: GO:0032079
label: positive regulation of endodeoxyribonuclease activity
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: 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).
- term:
id: GO:1990090
label: cellular response to nerve growth factor stimulus
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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).
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IDA:UniProtKB.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:20605787
review:
summary: 'The cited studies report individual interactions, but the generic term protein binding is too uninformative to retain in the review.'
action: REMOVE
reason: Protein binding is not sufficiently specific or useful as a curated AKT1 function term.
supported_by:
- reference_id: PMID:20605787
supporting_text: Ribosomal protein S3, a new substrate of Akt, serves as a signal mediator between neuronal apoptosis and DNA repair.
- term:
id: GO:0006974
label: DNA damage response
evidence_type: IDA
original_reference_id: PMID:20605787
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core stress-response annotation.
supported_by:
- reference_id: PMID:20605787
supporting_text: Ribosomal protein S3, a new substrate of Akt, serves as a signal mediator between neuronal apoptosis and DNA repair.
- term:
id: GO:0018107
label: peptidyl-threonine phosphorylation
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: 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).
- term:
id: GO:1990090
label: cellular response to nerve growth factor stimulus
evidence_type: IDA
original_reference_id: PMID:20605787
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: PMID:20605787
supporting_text: Ribosomal protein S3, a new substrate of Akt, serves as a signal mediator between neuronal apoptosis and DNA repair.
- term:
id: GO:0005634
label: nucleus
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005634; C:nucleus; IDA:UniProtKB.
- term:
id: GO:0005634
label: nucleus
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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).
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005634; C:nucleus; IDA:UniProtKB.
- term:
id: GO:0031982
label: vesicle
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0031982; C:vesicle; ISO:RGD.
- term:
id: GO:0072656
label: maintenance of protein location in mitochondrion
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0072656; P:maintenance of protein location in mitochondrion; ISO:RGD.
- term:
id: GO:0019901
label: protein kinase binding
evidence_type: IPI
original_reference_id: PMID:24583056
review:
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).'
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: PMID:24583056
supporting_text: PRAS40 plays a pivotal role in protecting against stroke by linking the Akt and mTOR pathways.
- term:
id: GO:0021510
label: spinal cord development
evidence_type: IDA
original_reference_id: PMID:23681769
review:
summary: 'The cited study concerns axon regeneration signaling and does not justify a stable spinal cord development annotation for rat AKT1.'
action: REMOVE
reason: The term is too developmental and indirect for the supporting evidence.
supported_by:
- reference_id: PMID:23681769
supporting_text: The mechanisms of EGFR in the regulation of axon regeneration.
- term:
id: GO:0032794
label: GTPase activating protein binding
evidence_type: IPI
original_reference_id: PMID:14707121
review:
summary: 'Direct interaction with Ras GTPase-activating protein is supported, but this is a partner-specific interaction rather than a core defining AKT1 function.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core binding annotation.
supported_by:
- reference_id: PMID:14707121
supporting_text: Ras GTPase-activating protein binds to Akt and is required for its activation.
- term:
id: GO:0010763
label: positive regulation of fibroblast migration
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0010763; P:positive regulation of fibroblast migration; ISO:RGD.
- term:
id: GO:0035924
label: cellular response to vascular endothelial growth factor stimulus
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; ISO:RGD.
- term:
id: GO:0036294
label: cellular response to decreased oxygen levels
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0036294; P:cellular response to decreased oxygen levels; ISO:RGD.
- term:
id: GO:0060416
label: response to growth hormone
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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.'
action: MARK_AS_OVER_ANNOTATED
reason: The term is plausible but over-annotated for the available support.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0060416; P:response to growth hormone; ISS:AgBase.
- term:
id: GO:1990418
label: response to insulin-like growth factor stimulus
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core pathway-context annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:1990418; P:response to insulin-like growth factor stimulus; ISS:AgBase.
- term:
id: GO:0031663
label: lipopolysaccharide-mediated signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISO:RGD.
- term:
id: GO:0071380
label: cellular response to prostaglandin E stimulus
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0071380; P:cellular response to prostaglandin E stimulus; ISO:RGD.
- term:
id: GO:0010975
label: regulation of neuron projection development
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0010975; P:regulation of neuron projection development; ISS:UniProtKB.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:16832058
review:
summary: 'The cited studies report individual interactions, but the generic term protein binding is too uninformative to retain in the review.'
action: REMOVE
reason: Protein binding is not sufficiently specific or useful as a curated AKT1 function term.
supported_by:
- reference_id: PMID:16832058
supporting_text: Ebp1 isoforms distinctively regulate cell survival and differentiation.
- term:
id: GO:0006979
label: response to oxidative stress
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: 'Oxidative-stress signaling through AKT1 is biologically plausible and supported in mammalian systems, but it is not the core defining function of AKT1.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core stress-response annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0006979; P:response to oxidative stress; ISS:ParkinsonsUK-UCL.
- term:
id: GO:0031641
label: regulation of myelination
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0031641; P:regulation of myelination; ISO:RGD.
- term:
id: GO:0051721
label: protein phosphatase 2A binding
evidence_type: IPI
original_reference_id: PMID:11884620
review:
summary: 'The cited PP2A/Shc paper does not provide a clear, stable basis for retaining protein phosphatase 2A binding as a curated AKT1 function.'
action: REMOVE
reason: The evidence is indirect and the partner-specific binding call is not well supported for rat AKT1.
supported_by:
- reference_id: PMID:11884620
supporting_text: Protein phosphatase 2A forms a molecular complex with Shc and regulates Shc tyrosine phosphorylation and downstream mitogenic signaling.
- term:
id: GO:0071889
label: 14-3-3 protein binding
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0071889; F:14-3-3 protein binding; ISO:RGD.
- term:
id: GO:0004712
label: protein serine/threonine/tyrosine kinase activity
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: MODIFY
reason: Replace the transferred ISO term with the specific serine/threonine kinase activity term used for AKT-family biochemistry.
proposed_replacement_terms:
- id: GO:0004674
label: protein serine/threonine kinase activity
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; ISO:RGD.
- term:
id: GO:0036064
label: ciliary basal body
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0036064; C:ciliary basal body; ISO:RGD.
- term:
id: GO:0005911
label: cell-cell junction
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005911; C:cell-cell junction; ISO:RGD.
- term:
id: GO:1901653
label: cellular response to peptide
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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).
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:1901653; P:cellular response to peptide; IEP:RGD.
- term:
id: GO:0097011
label: cellular response to granulocyte macrophage colony-stimulating factor stimulus
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; ISO:RGD.
- term:
id: GO:0001938
label: positive regulation of endothelial cell proliferation
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:UniProtKB.
- term:
id: GO:0001938
label: positive regulation of endothelial cell proliferation
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:UniProtKB.
- term:
id: GO:0005739
label: mitochondrion
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005739; C:mitochondrion; ISO:RGD.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22218591
review:
summary: 'The cited studies report individual interactions, but the generic term protein binding is too uninformative to retain in the review.'
action: REMOVE
reason: Protein binding is not sufficiently specific or useful as a curated AKT1 function term.
supported_by:
- reference_id: PMID:22218591
supporting_text: PKB/Akt partners with Dab2 in albumin endocytosis.
- term:
id: GO:0097194
label: execution phase of apoptosis
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0097194; P:execution phase of apoptosis; ISO:RGD.
- term:
id: GO:0071260
label: cellular response to mechanical stimulus
evidence_type: IDA
original_reference_id: PMID:20042609
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core physiology annotation.
supported_by:
- reference_id: PMID:20042609
supporting_text: 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.
- term:
id: GO:0010507
label: negative regulation of autophagy
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0010507; P:negative regulation of autophagy; ISO:RGD.
- term:
id: GO:0045861
label: negative regulation of proteolysis
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to 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.
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0045861; P:negative regulation of proteolysis; ISO:RGD.
- term:
id: GO:0010765
label: positive regulation of sodium ion transport
evidence_type: IMP
original_reference_id: PMID:17715136
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: PMID:17715136
supporting_text: Akt mediates the effect of insulin on epithelial sodium channels by inhibiting Nedd4-2.
- term:
id: GO:0032869
label: cellular response to insulin stimulus
evidence_type: IMP
original_reference_id: PMID:17715136
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: PMID:17715136
supporting_text: Akt mediates the effect of insulin on epithelial sodium channels by inhibiting Nedd4-2.
- term:
id: GO:0032880
label: regulation of protein localization
evidence_type: IMP
original_reference_id: PMID:17715136
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: PMID:17715136
supporting_text: Akt mediates the effect of insulin on epithelial sodium channels by inhibiting Nedd4-2.
- term:
id: GO:0032287
label: peripheral nervous system myelin maintenance
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0032287; P:peripheral nervous system myelin maintenance; ISO:RGD.
- term:
id: GO:0019901
label: protein kinase binding
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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).
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0019901; F:protein kinase binding; IPI:RGD.
- term:
id: GO:0045907
label: positive regulation of vasoconstriction
evidence_type: IMP
original_reference_id: PMID:21532183
review:
summary: 'The pravastatin vascular study is too context-specific and indirect to retain positive regulation of vasoconstriction as a stable AKT1 annotation.'
action: REMOVE
reason: The term overstates a narrow vascular physiology context.
supported_by:
- reference_id: PMID:21532183
supporting_text: Acute modulation of vasoconstrictor responses by pravastatin in small vessels.
- term:
id: GO:0071456
label: cellular response to hypoxia
evidence_type: IDA
original_reference_id: PMID:20515660
review:
summary: 'Rat pulmonary arterial smooth-muscle data support AKT1 involvement in hypoxia-responsive signaling, but the term remains a context-specific response annotation.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core stimulus-response annotation.
supported_by:
- reference_id: PMID:20515660
supporting_text: Suppression of Akt1 phosphorylation by adenoviral transfer of the PTEN gene inhibits hypoxia-induced proliferation of rat pulmonary arterial smooth muscle cells.
- term:
id: GO:0090201
label: negative regulation of release of cytochrome c from mitochondria
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISS:UniProtKB.
- term:
id: GO:0090201
label: negative regulation of release of cytochrome c from mitochondria
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISS:UniProtKB.
- term:
id: GO:0005524
label: ATP binding
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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).
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005524; F:ATP binding; IDA:RGD.
- term:
id: GO:0030334
label: regulation of cell migration
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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).
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0030334; P:regulation of cell migration; IMP:RGD.
- term:
id: GO:0033138
label: positive regulation of peptidyl-serine phosphorylation
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: 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).
- term:
id: GO:0005886
label: plasma membrane
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
- term:
id: GO:0006006
label: glucose metabolic process
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0006006; P:glucose metabolic process; ISO:RGD.
- term:
id: GO:0042593
label: glucose homeostasis
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
- term:
id: GO:0051146
label: striated muscle cell differentiation
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0051146; P:striated muscle cell differentiation; ISO:RGD.
- term:
id: GO:0005080
label: protein kinase C binding
evidence_type: IPI
original_reference_id: PMID:7488143
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a real but non-core interaction annotation.
supported_by:
- reference_id: PMID:7488143
supporting_text: '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.'
- term:
id: GO:0043536
label: positive regulation of blood vessel endothelial cell migration
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:RGD.
- term:
id: GO:0010975
label: regulation of neuron projection development
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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.'
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0010975; P:regulation of neuron projection development; ISS:UniProtKB.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-RNO-437185
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005829; C:cytosol; IDA:RGD.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-RNO-437189
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005829; C:cytosol; IDA:RGD.
- term:
id: GO:1903078
label: positive regulation of protein localization to plasma membrane
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISO:RGD.
- term:
id: GO:0001893
label: maternal placenta development
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0001893; P:maternal placenta development; ISO:RGD.
- term:
id: GO:0060709
label: glycogen cell differentiation involved in embryonic placenta development
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0060709; P:glycogen cell differentiation involved in embryonic placenta development; ISO:RGD.
- term:
id: GO:0060716
label: labyrinthine layer blood vessel development
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0060716; P:labyrinthine layer blood vessel development; ISO:RGD.
- term:
id: GO:0004674
label: protein serine/threonine kinase activity
evidence_type: IDA
original_reference_id: PMID:9887206
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: PMID:9887206
supporting_text: 'Akt kinases and 2-deoxyglucose uptake in rat skeletal muscles in vivo: study with insulin and exercise.'
- term:
id: GO:0005524
label: ATP binding
evidence_type: IDA
original_reference_id: PMID:9887206
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: PMID:9887206
supporting_text: 'Akt kinases and 2-deoxyglucose uptake in rat skeletal muscles in vivo: study with insulin and exercise.'
- term:
id: GO:0006468
label: protein phosphorylation
evidence_type: IDA
original_reference_id: PMID:9887206
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: PMID:9887206
supporting_text: 'Akt kinases and 2-deoxyglucose uptake in rat skeletal muscles in vivo: study with insulin and exercise.'
- term:
id: GO:0005547
label: phosphatidylinositol-3,4,5-trisphosphate binding
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; ISO:RGD.
- reference_id: file:rat/Akt1/Akt1-deep-research-falcon.md
supporting_text: The PH domain binds **PI(3,4,5)P3 (PIP3)**
- term:
id: GO:0030307
label: positive regulation of cell growth
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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).
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0030307; P:positive regulation of cell growth; IDA:RGD.
- term:
id: GO:0043066
label: negative regulation of apoptotic process
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
- term:
id: GO:0043325
label: phosphatidylinositol-3,4-bisphosphate binding
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; ISO:RGD.
- reference_id: file:rat/Akt1/Akt1-deep-research-falcon.md
supporting_text: binds **PI(3,4,5)P3 (PIP3)** and **PI(3,4)P2**, recruiting AKT1 to phosphoinositide-enriched membranes
- term:
id: GO:0005979
label: regulation of glycogen biosynthetic process
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005979; P:regulation of glycogen biosynthetic process; ISO:RGD.
- term:
id: GO:0045600
label: positive regulation of fat cell differentiation
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0045600; P:positive regulation of fat cell differentiation; ISO:RGD.
- term:
id: GO:0046889
label: positive regulation of lipid biosynthetic process
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to 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.
action: MARK_AS_OVER_ANNOTATED
reason: Likely true in some mammalian contexts, but the transferred term is too specific to retain as a general rat ISO annotation.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0046889; P:positive regulation of lipid biosynthetic process; ISS:UniProtKB.
- term:
id: GO:0004674
label: protein serine/threonine kinase activity
evidence_type: IDA
original_reference_id: PMID:10454575
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: PMID:10454575
supporting_text: Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt.
- term:
id: GO:0019899
label: enzyme binding
evidence_type: IPI
original_reference_id: PMID:10454575
review:
summary: 'The PDE3B study supports substrate phosphorylation by AKT rather than retaining the broad and uninformative term enzyme binding.'
action: REMOVE
reason: The term is too generic to be useful as a curated AKT1 annotation.
supported_by:
- reference_id: PMID:10454575
supporting_text: Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt.
- term:
id: GO:0051247
label: positive regulation of protein metabolic process
evidence_type: IMP
original_reference_id: PMID:9632753
review:
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.'
action: MARK_AS_OVER_ANNOTATED
reason: The annotation captures a real phenotype but is too broad for stable curation.
supported_by:
- reference_id: PMID:9632753
supporting_text: Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport.
- term:
id: GO:0070141
label: response to UV-A
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0070141; P:response to UV-A; ISO:RGD.
- term:
id: GO:0010765
label: positive regulation of sodium ion transport
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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).
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0010765; P:positive regulation of sodium ion transport; IMP:MGI.
- term:
id: GO:0030235
label: nitric-oxide synthase regulator activity
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0030235; F:nitric-oxide synthase regulator activity; ISO:RGD.
- term:
id: GO:0034405
label: response to fluid shear stress
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0034405; P:response to fluid shear stress; ISO:RGD.
- term:
id: GO:0045429
label: positive regulation of nitric oxide biosynthetic process
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:RGD.
- term:
id: GO:0046329
label: negative regulation of JNK cascade
evidence_type: IDA
original_reference_id: PMID:17064355
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core pathway-regulation annotation.
supported_by:
- reference_id: PMID:17064355
supporting_text: 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.
- term:
id: GO:0018105
label: peptidyl-serine phosphorylation
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: 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).
- term:
id: GO:0032094
label: response to food
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0032094; P:response to food; ISO:RGD.
- term:
id: GO:0030030
label: cell projection organization
evidence_type: IDA
original_reference_id: PMID:16286931
review:
summary: 'Neuronal morphology data suggest AKT-pathway involvement in projection organization, but the term is too phenotype-level and context-dependent to retain strongly.'
action: MARK_AS_OVER_ANNOTATED
reason: The annotation is plausible but over-annotated for a general AKT1 review.
supported_by:
- reference_id: PMID:16286931
supporting_text: Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2.
- term:
id: GO:0045792
label: negative regulation of cell size
evidence_type: IDA
original_reference_id: PMID:16286931
review:
summary: 'This term conflicts with the broader body of AKT biology linking AKT activity to growth promotion rather than negative regulation of cell size.'
action: REMOVE
reason: Remove as biologically inconsistent with established AKT1 function.
supported_by:
- reference_id: PMID:16286931
supporting_text: Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2.
- term:
id: GO:0005654
label: nucleoplasm
evidence_type: TAS
original_reference_id: Reactome:R-RNO-198333
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005654; C:nucleoplasm; ISO:RGD.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-RNO-198333
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005829; C:cytosol; IDA:RGD.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-RNO-198601
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005829; C:cytosol; IDA:RGD.
- term:
id: GO:0006924
label: activation-induced cell death of T cells
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: The rat ISO traces to human 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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0006924; P:activation-induced cell death of T cells; ISO:RGD.
- term:
id: GO:0035556
label: intracellular signal transduction
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0035556; P:intracellular signal transduction; ISO:RGD.
- term:
id: GO:0030334
label: regulation of cell migration
evidence_type: IMP
original_reference_id: PMID:17109063
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: PMID:17109063
supporting_text: Akt-mediated GSK-3beta inhibition prevents migration of polyamine-depleted intestinal epithelial cells via Rac1.
- term:
id: GO:0005977
label: glycogen metabolic process
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005977; P:glycogen metabolic process; ISO:RGD.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:15120593
review:
summary: 'The cited studies report individual interactions, but the generic term protein binding is too uninformative to retain in the review.'
action: REMOVE
reason: Protein binding is not sufficiently specific or useful as a curated AKT1 function term.
supported_by:
- reference_id: PMID:15120593
supporting_text: Altered Bad localization and interaction between Bad and Bcl-xL in the hippocampus after transient global ischemia.
- term:
id: GO:0004674
label: protein serine/threonine kinase activity
evidence_type: IDA
original_reference_id: PMID:12089343
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: PMID:12089343
supporting_text: The phosphatidylinositol 3-kinase/Akt signaling pathway modulates the endocrine differentiation of trophoblast cells.
- term:
id: GO:0006468
label: protein phosphorylation
evidence_type: IDA
original_reference_id: PMID:12084817
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: PMID:12084817
supporting_text: A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification.
- term:
id: GO:0009725
label: response to hormone
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0009725; P:response to hormone; ISO:RGD.
- term:
id: GO:0004674
label: protein serine/threonine kinase activity
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
- term:
id: GO:0005978
label: glycogen biosynthetic process
evidence_type: IMP
original_reference_id: PMID:10400692
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core metabolic-process annotation.
supported_by:
- reference_id: PMID:10400692
supporting_text: Requirement for Akt (protein kinase B) in insulin-induced activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1).
- term:
id: GO:0006412
label: translation
evidence_type: IMP
original_reference_id: PMID:10400692
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core process annotation.
supported_by:
- reference_id: PMID:10400692
supporting_text: Requirement for Akt (protein kinase B) in insulin-induced activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1).
- term:
id: GO:0006412
label: translation
evidence_type: IMP
original_reference_id: PMID:9632753
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core process annotation.
supported_by:
- reference_id: PMID:9632753
supporting_text: Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport.
- term:
id: GO:0006468
label: protein phosphorylation
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
- term:
id: GO:0008286
label: insulin receptor signaling pathway
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0008286; P:insulin receptor signaling pathway; IDA:BHF-UCL.
- term:
id: GO:0008286
label: insulin receptor signaling pathway
evidence_type: IMP
original_reference_id: PMID:9632753
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: PMID:9632753
supporting_text: Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport.
- term:
id: GO:0048009
label: insulin-like growth factor receptor signaling pathway
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISS:UniProtKB.
- term:
id: GO:0004672
label: protein kinase activity
evidence_type: IDA
original_reference_id: PMID:12084817
review:
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).'
action: MODIFY
reason: Replace the transferred ISO term with the specific serine/threonine kinase activity term used for AKT-family biochemistry.
proposed_replacement_terms: *id001
supported_by:
- reference_id: PMID:12084817
supporting_text: A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification.
- term:
id: GO:0004674
label: protein serine/threonine kinase activity
evidence_type: TAS
original_reference_id: PMID:12084817
review:
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).'
action: ACCEPT
reason: Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
supported_by:
- reference_id: PMID:12084817
supporting_text: A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:12194869
review:
summary: 'The cited studies report individual interactions, but the generic term protein binding is too uninformative to retain in the review.'
action: REMOVE
reason: Protein binding is not sufficiently specific or useful as a curated AKT1 function term.
supported_by:
- reference_id: PMID:12194869
supporting_text: Akt1 regulates a JNK scaffold during excitotoxic apoptosis.
- term:
id: GO:0030307
label: positive regulation of cell growth
evidence_type: IDA
original_reference_id: PMID:12084817
review:
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).'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: PMID:12084817
supporting_text: A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification.
- term:
id: GO:0043065
label: positive regulation of apoptotic process
evidence_type: IMP
original_reference_id: PMID:20403980
review:
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.'
action: REMOVE
reason: Remove as a context-specific and biologically atypical apoptosis annotation for AKT1.
supported_by:
- reference_id: PMID:20403980
supporting_text: Selective blockade of protein kinase B protects the rat and human myocardium against ischaemic injury.
- term:
id: GO:0043066
label: negative regulation of apoptotic process
evidence_type: TAS
original_reference_id: PMID:12084817
review:
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.'
action: KEEP_AS_NON_CORE
reason: Keep as a valid but non-core localization or process-level annotation rather than a defining AKT1 function.
supported_by:
- reference_id: PMID:12084817
supporting_text: A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification.
- term:
id: GO:0005819
label: spindle
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0005819; C:spindle; ISO:RGD.
- term:
id: GO:0008637
label: apoptotic mitochondrial changes
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0008637; P:apoptotic mitochondrial changes; ISO:RGD.
- term:
id: GO:0016567
label: protein ubiquitination
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0016567; P:protein ubiquitination; ISO:RGD.
- term:
id: GO:0030163
label: protein catabolic process
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0030163; P:protein catabolic process; ISO:RGD.
- term:
id: GO:0007281
label: germ cell development
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
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.
action: REMOVE
reason: Transferred donor phenotype/context is too narrow, tissue-specific, or stimulus-specific to justify a rat ISO annotation without rat-directed evidence.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: GO; GO:0007281; P:germ cell development; ISO:RGD.
references:
- id: UniProtKB:P47196
title: UniProt entry for rat AKT1 (RAC-alpha serine/threonine-protein kinase)
findings: []
- id: file:rat/Akt1/Akt1-deep-research-falcon.md
title: Falcon deep research report on rat Akt1 (RAC-alpha Ser/Thr kinase / PKB alpha,
UniProt P47196)
findings:
- statement: AKT1/PKBalpha is an AGC-family serine/threonine protein kinase that acts
as a central node downstream of growth factor and insulin signaling, exerting
its effects by phosphorylating protein substrates. This is the defining core
molecular function.
supporting_text: |-
AKT1 (Protein kinase B alpha; PKBΞ±) is a **serine/threonine protein kinase** in the **AGC kinase family** that functions as a central signaling node downstream of growth factor/insulin pathways, regulating survival, growth, metabolism, and cytoskeletal programs by **phosphorylating protein substrates**.
reference_section_type: OTHER
- statement: AKT1 catalyzes ATP-dependent phosphorylation of Ser/Thr residues on
protein substrates (EC 2.7.11.1), with representative substrates including GSK3
and FOXO transcription factors.
supporting_text: |-
AKT1 catalyzes **ATP-dependent phosphorylation of serine/threonine residues** in protein substrates (EC **2.7.11.1**, protein-serine/threonine kinase).
reference_section_type: OTHER
- statement: AKT1 is recruited to membranes via its PH domain binding PIP3 and PI(3,4)P2
generated by PI3K, then is activated by PDK1 phosphorylation of Thr308 and mTORC2
phosphorylation of Ser473.
supporting_text: |-
**PDK1 phosphorylates Thr308** in the activation loop for partial activation; **mTORC2 phosphorylates Ser473** in the hydrophobic motif for full activation/substrate tuning. **Thr450** turn-motif phosphorylation contributes to folding/stability.
reference_section_type: OTHER
- statement: In unstimulated cells AKT1 is held in an autoinhibited PH-in conformation
by an intramolecular PH-kinase domain interface; full activation requires both
phosphoinositide binding and regulatory phosphorylation.
supporting_text: |-
In unstimulated cells, AKT1 adopts a **PH-in autoinhibited conformation** in which a **PHβkinase domain interface** masks the active state and sequesters the lipid-binding site.
reference_section_type: OTHER
- statement: AKT1 sits in the canonical PI3K-AKT-mTOR axis; activated AKT1 phosphorylates
substrates such as GSK3 and FOXO1/3a to promote survival, proliferation, metabolism,
and anabolic growth.
supporting_text: |-
Activated AKT1 phosphorylates substrates including **GSK3** and **FOXO1/3a**, thereby promoting cell survival, proliferation, metabolism, and anabolic growth programs.
reference_section_type: OTHER
- statement: AKT1 is largely cytosolic and can be nuclear in quiescent cells, with
active signaling concentrated at membrane compartments, especially the plasma
membrane following PH-domain-dependent recruitment.
supporting_text: |-
AKT1 is largely **cytosolic (and can be nuclear) in quiescent cells**, but active signaling is concentrated at **membrane-associated compartments**, especially the **plasma membrane** and, in some models, **endosomal membranes**.
reference_section_type: OTHER
- statement: AKT signaling is terminated by PTEN (which removes the PIP3 membrane
recruitment signal) and by phosphatases PP2A and PHLPP that dephosphorylate AKT
regulatory residues.
supporting_text: |-
AKT signaling is terminated at two levels: **PTEN** removes the lipid signal by dephosphorylating **PIP3 to PI(4,5)P2**, preventing membrane recruitment; **PP2A** and **PHLPP** dephosphorylate AKT at key regulatory residues, especially after membrane dissociation.
reference_section_type: OTHER
- id: GO_REF:0000002
title: 'TODO: Fetch title'
findings: []
- id: GO_REF:0000024
title: 'TODO: Fetch title'
findings: []
- id: GO_REF:0000033
title: 'TODO: Fetch title'
findings: []
- id: GO_REF:0000044
title: 'TODO: Fetch title'
findings: []
- id: GO_REF:0000116
title: 'TODO: Fetch title'
findings: []
- id: GO_REF:0000117
title: 'TODO: Fetch title'
findings: []
- id: GO_REF:0000120
title: 'TODO: Fetch title'
findings: []
- id: GO_REF:0000121
title: 'TODO: Fetch title'
findings: []
- id: PMID:10400692
title: Requirement for Akt (protein kinase B) in insulin-induced activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1).
findings: []
- id: PMID:10454575
title: Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt.
findings: []
- id: PMID:11884620
title: Protein phosphatase 2A forms a molecular complex with Shc and regulates Shc tyrosine phosphorylation and downstream mitogenic signaling.
findings: []
- id: PMID:12084817
title: A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification.
findings: []
- id: PMID:12089343
title: The phosphatidylinositol 3-kinase/Akt signaling pathway modulates the endocrine differentiation of trophoblast cells.
findings: []
- id: PMID:12194869
title: Akt1 regulates a JNK scaffold during excitotoxic apoptosis.
findings: []
- id: PMID:14707121
title: Ras GTPase-activating protein binds to Akt and is required for its activation.
findings: []
- id: PMID:15120593
title: Altered Bad localization and interaction between Bad and Bcl-xL in the hippocampus after transient global ischemia.
findings: []
- id: PMID:15701816
title: 'EGF stimulates mesangial cell mitogenesis via PI3-kinase-mediated MAPK-dependent and AKT kinase-independent manner: involvement of c-fos and p27Kip1.'
findings: []
- id: PMID:16286931
title: Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2.
findings: []
- id: PMID:16362038
title: Novel roles of Akt and mTOR in suppressing TGF-beta/ALK5-mediated Smad3 activation.
findings: []
- id: PMID:16642037
title: Nuclear Akt associates with PKC-phosphorylated Ebp1, preventing DNA fragmentation by inhibition of caspase-activated DNase.
findings: []
- id: PMID:16832058
title: Ebp1 isoforms distinctively regulate cell survival and differentiation.
findings: []
- id: PMID:17064355
title: 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.
findings: []
- id: PMID:17109063
title: Akt-mediated GSK-3beta inhibition prevents migration of polyamine-depleted intestinal epithelial cells via Rac1.
findings: []
- id: PMID:17715136
title: Akt mediates the effect of insulin on epithelial sodium channels by inhibiting Nedd4-2.
findings: []
- id: PMID:18772167
title: 'Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: involvement of the cholinergic pathway.'
findings: []
- id: PMID:19574345
title: Lipid-induced mTOR activation in rat skeletal muscle reversed by exercise and 5'-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside.
findings: []
- id: PMID:20042609
title: 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.
findings: []
- id: PMID:20403980
title: Selective blockade of protein kinase B protects the rat and human myocardium against ischaemic injury.
findings: []
- id: PMID:20488185
title: Glyceraldehyde-3-phosphate dehydrogenase interacts with phosphorylated Akt resulting from increased blood glucose in rat cardiac muscle.
findings: []
- id: PMID:20515660
title: Suppression of Akt1 phosphorylation by adenoviral transfer of the PTEN gene inhibits hypoxia-induced proliferation of rat pulmonary arterial smooth muscle cells.
findings: []
- id: PMID:20605787
title: Ribosomal protein S3, a new substrate of Akt, serves as a signal mediator between neuronal apoptosis and DNA repair.
findings: []
- id: PMID:21532183
title: Acute modulation of vasoconstrictor responses by pravastatin in small vessels.
findings: []
- id: PMID:22218591
title: PKB/Akt partners with Dab2 in albumin endocytosis.
findings: []
- id: PMID:23681769
title: The mechanisms of EGFR in the regulation of axon regeneration.
findings: []
- id: PMID:24583056
title: PRAS40 plays a pivotal role in protecting against stroke by linking the Akt and mTOR pathways.
findings: []
- id: PMID:24601882
title: Protein kinase B (PKB/AKT1) formed signaling complexes with mitochondrial proteins and prevented glycolytic energy dysfunction in cultured cardiomyocytes during ischemia-reperfusion injury.
findings: []
- id: PMID:31071414
title: Sex Differences in Neuroplasticity- and Stress-Related Gene Expression and Protein Levels in the Rat Hippocampus Following Oxycodone Conditioned Place Preference.
findings: []
- id: PMID:7488143
title: '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.'
findings: []
- id: PMID:7774014
title: The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase.
findings: []
- id: PMID:8524413
title: Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B.
findings: []
- id: PMID:8755528
title: Activation of RAC-protein kinase by heat shock and hyperosmolarity stress through a pathway independent of phosphatidylinositol 3-kinase.
findings: []
- id: PMID:9005851
title: Regulation of neuronal survival by the serine-threonine protein kinase Akt.
findings: []
- id: PMID:9065430
title: 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.
findings: []
- id: PMID:9112399
title: Potential role of protein kinase B in glucose transporter 4 translocation in adipocytes.
findings: []
- id: PMID:9492284
title: Nerve growth factor promotes activation of the alpha, beta and gamma isoforms of protein kinase B in PC12 pheochromocytoma cells.
findings: []
- id: PMID:9632753
title: Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport.
findings: []
- id: PMID:9887206
title: 'Akt kinases and 2-deoxyglucose uptake in rat skeletal muscles in vivo: study with insulin and exercise.'
findings: []
- id: Reactome:R-RNO-198333
title: 'TODO: Fetch title'
findings: []
- id: Reactome:R-RNO-198601
title: 'TODO: Fetch title'
findings: []
- id: Reactome:R-RNO-437185
title: 'TODO: Fetch title'
findings: []
- id: Reactome:R-RNO-437189
title: 'TODO: Fetch title'
findings: []
core_functions:
- description: 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.
supported_by:
- reference_id: UniProtKB:P47196
supporting_text: 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).
- reference_id: UniProtKB:P47196
supporting_text: 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).
molecular_function:
id: GO:0004674
label: protein serine/threonine kinase activity
directly_involved_in:
- id: GO:0043491
label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
- id: GO:0008286
label: insulin receptor signaling pathway
