AKT2 (protein kinase B beta) is a cytosolic AGC-family serine/threonine protein kinase with an N-terminal pleckstrin homology (PH) domain, a central kinase domain and a C-terminal regulatory tail. When growth factors or insulin activate PI3K, the PH domain binds PtdIns(3,4,5)P3/PtdIns(3,4)P2 and recruits AKT2 to the inner leaflet of the plasma membrane, where PDPK1 (Thr-309) and mTORC2 (Ser-474) phosphorylate and activate it. Active AKT2 phosphorylates many substrates in the cytosol and nucleus, including GSK3, TSC2, FOXO factors, TBC1D4/AS160, PDE3B and PKP1. Among the AKT isoforms it has a particularly important role in insulin action in muscle, fat and liver: it promotes GLUT4 translocation, glucose uptake, glycogen synthesis and suppression of hepatic glucose output. It also supports myoblast differentiation and cell survival, proliferation and migration. Inactivating mutations cause insulin resistance and diabetes, an activating E17K variant causes hypoinsulinemic hypoglycemia, and AKT2 is amplified in ovarian and other cancers.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004672 protein kinase activity | IEA GO_REF:0000120 | MODIFY | Summary: Protein kinase activity. Correct but too general. Reason: AKT2 is an established serine/threonine kinase. The specific term, already carried with IDA support, should be used. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:16540465 AKT/PKB is a phosphoinositide-dependent serine/threonine protein kinase |
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Serine/threonine protein kinase activity. This is the core catalytic function of AKT2. Reason: Kinetic studies of purified AKT2, phosphorylation of specific substrates (PKP1, TSC2, CBY1), and the conserved AGC kinase domain all establish this activity. The IBA and the Rhea-based protein serine kinase IEA agree with it. Supporting Evidence: PMID:16540465 Initial velocity studies revealed that all AKT isozymes follow the sequential kinetic mechanism PMID:23444369 Phosphorylation was mediated by Akt2 at four motifs within the plakophilin 1 N-terminal domain. Reactome:R-HSA-165162 All three isoforms of AKT, AKT1 (Inoki et al. 2002), AKT2 (Kearny et al. 2019), and AKT3 (Wainstein et al. 2022) phosphorylate TSC2. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:10983986 The protooncogene TCL1 is an Akt kinase coactivator. | ACCEPT | Summary: Serine/threonine protein kinase activity. This is the core catalytic function of AKT2. Reason: Kinetic studies of purified AKT2, phosphorylation of specific substrates (PKP1, TSC2, CBY1), and the conserved AGC kinase domain all establish this activity. The IBA and the Rhea-based protein serine kinase IEA agree with it. Supporting Evidence: PMID:16540465 Initial velocity studies revealed that all AKT isozymes follow the sequential kinetic mechanism PMID:23444369 Phosphorylation was mediated by Akt2 at four motifs within the plakophilin 1 N-terminal domain. Reactome:R-HSA-165162 All three isoforms of AKT, AKT1 (Inoki et al. 2002), AKT2 (Kearny et al. 2019), and AKT3 (Wainstein et al. 2022) phosphorylate TSC2. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:16540465 Kinetic mechanism of AKT/PKB enzyme family. | ACCEPT | Summary: Serine/threonine protein kinase activity. This is the core catalytic function of AKT2. Reason: Kinetic studies of purified AKT2, phosphorylation of specific substrates (PKP1, TSC2, CBY1), and the conserved AGC kinase domain all establish this activity. The IBA and the Rhea-based protein serine kinase IEA agree with it. Supporting Evidence: PMID:16540465 Initial velocity studies revealed that all AKT isozymes follow the sequential kinetic mechanism PMID:23444369 Phosphorylation was mediated by Akt2 at four motifs within the plakophilin 1 N-terminal domain. Reactome:R-HSA-165162 All three isoforms of AKT, AKT1 (Inoki et al. 2002), AKT2 (Kearny et al. 2019), and AKT3 (Wainstein et al. 2022) phosphorylate TSC2. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:23444369 Insulin signaling via Akt2 switches plakophilin 1 function f... | ACCEPT | Summary: Serine/threonine protein kinase activity. This is the core catalytic function of AKT2. Reason: Kinetic studies of purified AKT2, phosphorylation of specific substrates (PKP1, TSC2, CBY1), and the conserved AGC kinase domain all establish this activity. The IBA and the Rhea-based protein serine kinase IEA agree with it. Supporting Evidence: PMID:16540465 Initial velocity studies revealed that all AKT isozymes follow the sequential kinetic mechanism PMID:23444369 Phosphorylation was mediated by Akt2 at four motifs within the plakophilin 1 N-terminal domain. Reactome:R-HSA-165162 All three isoforms of AKT, AKT1 (Inoki et al. 2002), AKT2 (Kearny et al. 2019), and AKT3 (Wainstein et al. 2022) phosphorylate TSC2. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Serine/threonine protein kinase activity. This is the core catalytic function of AKT2. Reason: Kinetic studies of purified AKT2, phosphorylation of specific substrates (PKP1, TSC2, CBY1), and the conserved AGC kinase domain all establish this activity. The IBA and the Rhea-based protein serine kinase IEA agree with it. Supporting Evidence: PMID:16540465 Initial velocity studies revealed that all AKT isozymes follow the sequential kinetic mechanism PMID:23444369 Phosphorylation was mediated by Akt2 at four motifs within the plakophilin 1 N-terminal domain. Reactome:R-HSA-165162 All three isoforms of AKT, AKT1 (Inoki et al. 2002), AKT2 (Kearny et al. 2019), and AKT3 (Wainstein et al. 2022) phosphorylate TSC2. |
| GO:0004674 protein serine/threonine kinase activity | TAS PMID:1409633 AKT2, a putative oncogene encoding a member of a subfamily o... | ACCEPT | Summary: Serine/threonine protein kinase activity. This is the core catalytic function of AKT2. Reason: Kinetic studies of purified AKT2, phosphorylation of specific substrates (PKP1, TSC2, CBY1), and the conserved AGC kinase domain all establish this activity. The IBA and the Rhea-based protein serine kinase IEA agree with it. Supporting Evidence: PMID:16540465 Initial velocity studies revealed that all AKT isozymes follow the sequential kinetic mechanism PMID:23444369 Phosphorylation was mediated by Akt2 at four motifs within the plakophilin 1 N-terminal domain. Reactome:R-HSA-165162 All three isoforms of AKT, AKT1 (Inoki et al. 2002), AKT2 (Kearny et al. 2019), and AKT3 (Wainstein et al. 2022) phosphorylate TSC2. |
| GO:0004674 protein serine/threonine kinase activity | TAS PMID:21432781 Akt1 and Akt2: differentiating the aktion. | ACCEPT | Summary: Serine/threonine protein kinase activity. This is the core catalytic function of AKT2. Reason: Kinetic studies of purified AKT2, phosphorylation of specific substrates (PKP1, TSC2, CBY1), and the conserved AGC kinase domain all establish this activity. The IBA and the Rhea-based protein serine kinase IEA agree with it. Supporting Evidence: PMID:16540465 Initial velocity studies revealed that all AKT isozymes follow the sequential kinetic mechanism PMID:23444369 Phosphorylation was mediated by Akt2 at four motifs within the plakophilin 1 N-terminal domain. Reactome:R-HSA-165162 All three isoforms of AKT, AKT1 (Inoki et al. 2002), AKT2 (Kearny et al. 2019), and AKT3 (Wainstein et al. 2022) phosphorylate TSC2. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-165162 | ACCEPT | Summary: Serine/threonine protein kinase activity. This is the core catalytic function of AKT2. Reason: Kinetic studies of purified AKT2, phosphorylation of specific substrates (PKP1, TSC2, CBY1), and the conserved AGC kinase domain all establish this activity. The IBA and the Rhea-based protein serine kinase IEA agree with it. Supporting Evidence: PMID:16540465 Initial velocity studies revealed that all AKT isozymes follow the sequential kinetic mechanism PMID:23444369 Phosphorylation was mediated by Akt2 at four motifs within the plakophilin 1 N-terminal domain. Reactome:R-HSA-165162 All three isoforms of AKT, AKT1 (Inoki et al. 2002), AKT2 (Kearny et al. 2019), and AKT3 (Wainstein et al. 2022) phosphorylate TSC2. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-165182 | ACCEPT | Summary: Serine/threonine protein kinase activity. This is the core catalytic function of AKT2. Reason: Kinetic studies of purified AKT2, phosphorylation of specific substrates (PKP1, TSC2, CBY1), and the conserved AGC kinase domain all establish this activity. The IBA and the Rhea-based protein serine kinase IEA agree with it. Supporting Evidence: PMID:16540465 Initial velocity studies revealed that all AKT isozymes follow the sequential kinetic mechanism PMID:23444369 Phosphorylation was mediated by Akt2 at four motifs within the plakophilin 1 N-terminal domain. Reactome:R-HSA-165162 All three isoforms of AKT, AKT1 (Inoki et al. 2002), AKT2 (Kearny et al. 2019), and AKT3 (Wainstein et al. 2022) phosphorylate TSC2. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-3769394 | ACCEPT | Summary: Serine/threonine protein kinase activity. This is the core catalytic function of AKT2. Reason: Kinetic studies of purified AKT2, phosphorylation of specific substrates (PKP1, TSC2, CBY1), and the conserved AGC kinase domain all establish this activity. The IBA and the Rhea-based protein serine kinase IEA agree with it. Supporting Evidence: PMID:16540465 Initial velocity studies revealed that all AKT isozymes follow the sequential kinetic mechanism PMID:23444369 Phosphorylation was mediated by Akt2 at four motifs within the plakophilin 1 N-terminal domain. Reactome:R-HSA-165162 All three isoforms of AKT, AKT1 (Inoki et al. 2002), AKT2 (Kearny et al. 2019), and AKT3 (Wainstein et al. 2022) phosphorylate TSC2. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-377186 | ACCEPT | Summary: Serine/threonine protein kinase activity. This is the core catalytic function of AKT2. Reason: Kinetic studies of purified AKT2, phosphorylation of specific substrates (PKP1, TSC2, CBY1), and the conserved AGC kinase domain all establish this activity. The IBA and the Rhea-based protein serine kinase IEA agree with it. Supporting Evidence: PMID:16540465 Initial velocity studies revealed that all AKT isozymes follow the sequential kinetic mechanism PMID:23444369 Phosphorylation was mediated by Akt2 at four motifs within the plakophilin 1 N-terminal domain. Reactome:R-HSA-165162 All three isoforms of AKT, AKT1 (Inoki et al. 2002), AKT2 (Kearny et al. 2019), and AKT3 (Wainstein et al. 2022) phosphorylate TSC2. |
| GO:0005515 protein binding | IPI PMID:10490823 Identification of a chromosome 3p14.3-21.1 gene, APPL, encod... | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:10983986 The protooncogene TCL1 is an Akt kinase coactivator. | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:10983986 The protooncogene TCL1 is an Akt kinase coactivator. | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:10983986 The protooncogene TCL1 is an Akt kinase coactivator. | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:12434148 Crystal structure of an activated Akt/protein kinase B terna... | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:16417406 Hem-1 complexes are essential for Rac activation, actin poly... | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:16792529 A WD-FYVE protein binds to the kinases Akt and PKCzeta/lambd... | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:17030088 APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potent... | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:19713527 The E3 ligase TRAF6 regulates Akt ubiquitination and activat... | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:20059950 The E3 ligase TTC3 facilitates ubiquitination and degradatio... | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:20856200 Vimentin is a novel AKT1 target mediating motility and invas... | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:21291857 Interactions between GIPC-APPL and GIPC-TRP1 regulate melano... | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:21737686 Ankrd2/ARPP is a novel Akt2 specific substrate and regulates... | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:22939624 Quantitative analysis of HSP90-client interactions reveals p... | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:23444369 Insulin signaling via Akt2 switches plakophilin 1 function f... | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:23823123 Systematic Analysis Reveals Elongation Factor 2 and Ξ±-Enolas... | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding. Partners include APPL1, TCL1 family coactivators, GSK3B, TTC3, WDFY2, HSP90AB1, PKP1, AKT1, UBE2O and others. Reason: The protein-binding policy treats bare GO:0005515 as uninformative. Many partners are kinase substrates (GSK3B, PKP1, ANKRD2), whose relevance is already captured by the serine/threonine kinase activity. Others are regulators of AKT (TCL1 coactivators, TTC3/UBE2O E3 ligases, APPL1/WDFY2 adaptors). No partner supports a more informative AKT2 molecular-function term. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10983986 All TCL1 isoforms bind to the Akt pleckstrin homology domain. PMID:20059950 TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. |
| GO:0005524 ATP binding | IDA PMID:16540465 Kinetic mechanism of AKT/PKB enzyme family. | ACCEPT | Summary: ATP binding by the kinase domain. Reason: The kinetic study shows ordered binding of ATP before the peptide substrate. Supporting Evidence: PMID:16540465 consistent with an ordered substrate addition mechanism with ATP binding to the enzymes prior to the peptide substrate |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding by the kinase domain. Reason: The kinetic study shows ordered binding of ATP before the peptide substrate. Supporting Evidence: PMID:16540465 consistent with an ordered substrate addition mechanism with ATP binding to the enzymes prior to the peptide substrate |
| GO:0005634 nucleus | EXP PMID:17565718 Akt2 is implicated in skeletal muscle differentiation and sp... | KEEP AS NON CORE | Summary: Nuclear pool of AKT2, seen in differentiating myoblasts and as the site of TTC3-mediated degradation of phospho-AKT. Reason: AKT2 shuttles into the nucleus, where it phosphorylates nuclear substrates (e.g. FOXO, CBY1) and is degraded via TTC3. In differentiated myoblasts it is mostly nuclear. This is a genuine but secondary location; the main site of activation is the cytosol and the plasma membrane inner leaflet. Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt Localizes within both nucleus and cytoplasm in proliferative primary myoblasts and mostly within the nucleus of differentiated primary myoblasts PMID:20059950 facilitates its ubiquitination and degradation within the nucleus |
| GO:0005634 nucleus | IDA PMID:20059950 The E3 ligase TTC3 facilitates ubiquitination and degradatio... | KEEP AS NON CORE | Summary: Nuclear pool of AKT2, seen in differentiating myoblasts and as the site of TTC3-mediated degradation of phospho-AKT. Reason: AKT2 shuttles into the nucleus, where it phosphorylates nuclear substrates (e.g. FOXO, CBY1) and is degraded via TTC3. In differentiated myoblasts it is mostly nuclear. This is a genuine but secondary location; the main site of activation is the cytosol and the plasma membrane inner leaflet. Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt Localizes within both nucleus and cytoplasm in proliferative primary myoblasts and mostly within the nucleus of differentiated primary myoblasts PMID:20059950 facilitates its ubiquitination and degradation within the nucleus |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear pool of AKT2, seen in differentiating myoblasts and as the site of TTC3-mediated degradation of phospho-AKT. Reason: AKT2 shuttles into the nucleus, where it phosphorylates nuclear substrates (e.g. FOXO, CBY1) and is degraded via TTC3. In differentiated myoblasts it is mostly nuclear. This is a genuine but secondary location; the main site of activation is the cytosol and the plasma membrane inner leaflet. Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt Localizes within both nucleus and cytoplasm in proliferative primary myoblasts and mostly within the nucleus of differentiated primary myoblasts PMID:20059950 facilitates its ubiquitination and degradation within the nucleus |
| GO:0005634 nucleus | TAS PMID:21432781 Akt1 and Akt2: differentiating the aktion. | KEEP AS NON CORE | Summary: Nuclear pool of AKT2, seen in differentiating myoblasts and as the site of TTC3-mediated degradation of phospho-AKT. Reason: AKT2 shuttles into the nucleus, where it phosphorylates nuclear substrates (e.g. FOXO, CBY1) and is degraded via TTC3. In differentiated myoblasts it is mostly nuclear. This is a genuine but secondary location; the main site of activation is the cytosol and the plasma membrane inner leaflet. Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt Localizes within both nucleus and cytoplasm in proliferative primary myoblasts and mostly within the nucleus of differentiated primary myoblasts PMID:20059950 facilitates its ubiquitination and degradation within the nucleus |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nuclear pool of AKT2, seen in differentiating myoblasts and as the site of TTC3-mediated degradation of phospho-AKT. Reason: AKT2 shuttles into the nucleus, where it phosphorylates nuclear substrates (e.g. FOXO, CBY1) and is degraded via TTC3. In differentiated myoblasts it is mostly nuclear. This is a genuine but secondary location; the main site of activation is the cytosol and the plasma membrane inner leaflet. Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt Localizes within both nucleus and cytoplasm in proliferative primary myoblasts and mostly within the nucleus of differentiated primary myoblasts PMID:20059950 facilitates its ubiquitination and degradation within the nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3769394 | KEEP AS NON CORE | Summary: Nuclear pool of AKT2, seen in differentiating myoblasts and as the site of TTC3-mediated degradation of phospho-AKT. Reason: AKT2 shuttles into the nucleus, where it phosphorylates nuclear substrates (e.g. FOXO, CBY1) and is degraded via TTC3. In differentiated myoblasts it is mostly nuclear. This is a genuine but secondary location; the main site of activation is the cytosol and the plasma membrane inner leaflet. Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt Localizes within both nucleus and cytoplasm in proliferative primary myoblasts and mostly within the nucleus of differentiated primary myoblasts PMID:20059950 facilitates its ubiquitination and degradation within the nucleus |
| GO:0005737 cytoplasm | EXP PMID:17565718 Akt2 is implicated in skeletal muscle differentiation and sp... | MODIFY | Summary: Cytoplasm. Correct but less specific than the cytosol, where soluble AKT2 resides. Reason: AKT2 is a soluble kinase that is not bound to any organelle lumen. The cytosol (GO:0005829), already annotated from HPA and Reactome, is the specific supported term. Membrane-recruited pools are captured separately by plasma membrane. Proposed replacements: cytosol Supporting Evidence: PMID:23444369 accumulated in the cytoplasm, where it increased translation and proliferation rates |
| GO:0005737 cytoplasm | IDA PMID:23444369 Insulin signaling via Akt2 switches plakophilin 1 function f... | MODIFY | Summary: Cytoplasm. Correct but less specific than the cytosol, where soluble AKT2 resides. Reason: AKT2 is a soluble kinase that is not bound to any organelle lumen. The cytosol (GO:0005829), already annotated from HPA and Reactome, is the specific supported term. Membrane-recruited pools are captured separately by plasma membrane. Proposed replacements: cytosol Supporting Evidence: PMID:23444369 accumulated in the cytoplasm, where it increased translation and proliferation rates |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | MODIFY | Summary: Cytoplasm. Correct but less specific than the cytosol, where soluble AKT2 resides. Reason: AKT2 is a soluble kinase that is not bound to any organelle lumen. The cytosol (GO:0005829), already annotated from HPA and Reactome, is the specific supported term. Membrane-recruited pools are captured separately by plasma membrane. Proposed replacements: cytosol Supporting Evidence: PMID:23444369 accumulated in the cytoplasm, where it increased translation and proliferation rates |
| GO:0005769 early endosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Early endosome localization, transferred from mouse Akt2 colocalization with WDFY2. Reason: Endosomal AKT2 pools (with WDFY2/APPL1) are reported by similarity. This is a minor signaling location. Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt Colocalizes with WDFY2 in early endosomes (By similarity). |
| GO:0005769 early endosome | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Early endosome localization, transferred from mouse Akt2 colocalization with WDFY2. Reason: Endosomal AKT2 pools (with WDFY2/APPL1) are reported by similarity. This is a minor signaling location. Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt Colocalizes with WDFY2 in early endosomes (By similarity). |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosol is the resting location of inactive AKT2 and the site of many substrate phosphorylations. Reason: Consistent with HPA imaging and Reactome reactions, AKT2 is a soluble cytosolic kinase that is recruited to membranes when PI3K is activated. Supporting Evidence: Reactome:R-HSA-165162 AKT (PKB) phosphorylates TSC2 decreasing its activity |
| GO:0005829 cytosol | TAS Reactome:R-HSA-109700 | ACCEPT | Summary: Cytosol is the resting location of inactive AKT2 and the site of many substrate phosphorylations. Reason: Consistent with HPA imaging and Reactome reactions, AKT2 is a soluble cytosolic kinase that is recruited to membranes when PI3K is activated. Supporting Evidence: Reactome:R-HSA-165162 AKT (PKB) phosphorylates TSC2 decreasing its activity |
| GO:0005829 cytosol | TAS Reactome:R-HSA-109702 | ACCEPT | Summary: Cytosol is the resting location of inactive AKT2 and the site of many substrate phosphorylations. Reason: Consistent with HPA imaging and Reactome reactions, AKT2 is a soluble cytosolic kinase that is recruited to membranes when PI3K is activated. Supporting Evidence: Reactome:R-HSA-165162 AKT (PKB) phosphorylates TSC2 decreasing its activity |
| GO:0005829 cytosol | TAS Reactome:R-HSA-165162 | ACCEPT | Summary: Cytosol is the resting location of inactive AKT2 and the site of many substrate phosphorylations. Reason: Consistent with HPA imaging and Reactome reactions, AKT2 is a soluble cytosolic kinase that is recruited to membranes when PI3K is activated. Supporting Evidence: Reactome:R-HSA-165162 AKT (PKB) phosphorylates TSC2 decreasing its activity |
| GO:0005829 cytosol | TAS Reactome:R-HSA-165182 | ACCEPT | Summary: Cytosol is the resting location of inactive AKT2 and the site of many substrate phosphorylations. Reason: Consistent with HPA imaging and Reactome reactions, AKT2 is a soluble cytosolic kinase that is recruited to membranes when PI3K is activated. Supporting Evidence: Reactome:R-HSA-165162 AKT (PKB) phosphorylates TSC2 decreasing its activity |
| GO:0005829 cytosol | TAS Reactome:R-HSA-377186 | ACCEPT | Summary: Cytosol is the resting location of inactive AKT2 and the site of many substrate phosphorylations. Reason: Consistent with HPA imaging and Reactome reactions, AKT2 is a soluble cytosolic kinase that is recruited to membranes when PI3K is activated. Supporting Evidence: Reactome:R-HSA-165162 AKT (PKB) phosphorylates TSC2 decreasing its activity |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | MODIFY | Summary: Plasma membrane. AKT2 is a peripheral protein of the cytoplasmic face, recruited when its PH domain binds PIP3. Reason: AKT2 has no transmembrane segment or extracellular exposure. When PI3K is activated, its PH domain binds PtdIns(3,4,5)P3 at the inner leaflet of the plasma membrane, where PDPK1 and mTORC2 phosphorylate it. Plasma membrane is a correct location for this activation step, but only for an intracellular, membrane-associated pool. The specific supported term is cytoplasmic side of plasma membrane (GO:0009898, part_of plasma membrane); AKT2 has no transmembrane segment and faces the cytosol, and this term is not yet a separate GOA row. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt Through binding of the N-terminal PH domain to phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) or phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)P2), recruited to the plasma membrane. Reactome:R-HSA-109700 The phosphorylation of membrane-recruited AKT at threonine and serine can be inhibited |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | MODIFY | Summary: Plasma membrane. AKT2 is a peripheral protein of the cytoplasmic face, recruited when its PH domain binds PIP3. Reason: AKT2 has no transmembrane segment or extracellular exposure. When PI3K is activated, its PH domain binds PtdIns(3,4,5)P3 at the inner leaflet of the plasma membrane, where PDPK1 and mTORC2 phosphorylate it. Plasma membrane is a correct location for this activation step, but only for an intracellular, membrane-associated pool. The specific supported term is cytoplasmic side of plasma membrane (GO:0009898, part_of plasma membrane); AKT2 has no transmembrane segment and faces the cytosol, and this term is not yet a separate GOA row. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt Through binding of the N-terminal PH domain to phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) or phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)P2), recruited to the plasma membrane. Reactome:R-HSA-109700 The phosphorylation of membrane-recruited AKT at threonine and serine can be inhibited |
| GO:0005886 plasma membrane | TAS PMID:21432781 Akt1 and Akt2: differentiating the aktion. | MODIFY | Summary: Plasma membrane. AKT2 is a peripheral protein of the cytoplasmic face, recruited when its PH domain binds PIP3. Reason: AKT2 has no transmembrane segment or extracellular exposure. When PI3K is activated, its PH domain binds PtdIns(3,4,5)P3 at the inner leaflet of the plasma membrane, where PDPK1 and mTORC2 phosphorylate it. Plasma membrane is a correct location for this activation step, but only for an intracellular, membrane-associated pool. The specific supported term is cytoplasmic side of plasma membrane (GO:0009898, part_of plasma membrane); AKT2 has no transmembrane segment and faces the cytosol, and this term is not yet a separate GOA row. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt Through binding of the N-terminal PH domain to phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) or phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)P2), recruited to the plasma membrane. Reactome:R-HSA-109700 The phosphorylation of membrane-recruited AKT at threonine and serine can be inhibited |
| GO:0005938 cell cortex | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cell cortex and ruffle membrane, from mouse Akt2 recruitment to cortical actin and to ruffles in insulin-stimulated cells. Reason: These are sub-regions of the plasma membrane's cytoplasmic face where PIP3 accumulates and AKT2 is recruited. The evidence is by similarity and the locations are peripheral. Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt recruited to the plasma membrane |
| GO:0005938 cell cortex | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cell cortex and ruffle membrane, from mouse Akt2 recruitment to cortical actin and to ruffles in insulin-stimulated cells. Reason: These are sub-regions of the plasma membrane's cytoplasmic face where PIP3 accumulates and AKT2 is recruited. The evidence is by similarity and the locations are peripheral. Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt recruited to the plasma membrane |
| GO:0007165 signal transduction | TAS PMID:21432781 Akt1 and Akt2: differentiating the aktion. | MODIFY | Summary: Signal transduction. Correct but too general. Reason: AKT2 is the effector kinase of the PI3K-AKT pathway. Proposed replacements: phosphatidylinositol 3-kinase/protein kinase B signal transduction Supporting Evidence: PMID:21432781 Kinases of the Akt family are integral and essential components in growth factor signaling pathways activated downstream of the membrane bound phospho-inositol-3 kinase. |
| GO:0008286 insulin receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Insulin receptor signaling and cellular response to insulin. This is AKT2's principal physiological role. Reason: siRNA silencing in human skeletal muscle shows that AKT2, unlike AKT1, is required for insulin-stimulated glucose metabolism. AKT2 is the main AKT isoform relaying insulin signaling to metabolic endpoints. The IBA agrees. Supporting Evidence: PMID:16814735 IRS-1 and Akt2 were required for myoblast differentiation and glucose metabolism, whereas IRS-2 and Akt1 were dispensable. |
| GO:0008286 insulin receptor signaling pathway | IMP PMID:16814735 siRNA-based gene silencing reveals specialized roles of IRS-... | ACCEPT | Summary: Insulin receptor signaling and cellular response to insulin. This is AKT2's principal physiological role. Reason: siRNA silencing in human skeletal muscle shows that AKT2, unlike AKT1, is required for insulin-stimulated glucose metabolism. AKT2 is the main AKT isoform relaying insulin signaling to metabolic endpoints. The IBA agrees. Supporting Evidence: PMID:16814735 IRS-1 and Akt2 were required for myoblast differentiation and glucose metabolism, whereas IRS-2 and Akt1 were dispensable. |
| GO:0008286 insulin receptor signaling pathway | TAS PMID:21432781 Akt1 and Akt2: differentiating the aktion. | ACCEPT | Summary: Insulin receptor signaling and cellular response to insulin. This is AKT2's principal physiological role. Reason: siRNA silencing in human skeletal muscle shows that AKT2, unlike AKT1, is required for insulin-stimulated glucose metabolism. AKT2 is the main AKT isoform relaying insulin signaling to metabolic endpoints. The IBA agrees. Supporting Evidence: PMID:16814735 IRS-1 and Akt2 were required for myoblast differentiation and glucose metabolism, whereas IRS-2 and Akt1 were dispensable. |
| GO:0010748 negative regulation of long-chain fatty acid import across plasma membrane | IMP PMID:16814735 siRNA-based gene silencing reveals specialized roles of IRS-... | UNDECIDED | Summary: Lipid-metabolism phenotypes (fatty acid uptake, beta-oxidation) from the human muscle siRNA study. Reason: The abstract assigns the key role in lipid metabolism to IRS-2/AKT1 rather than AKT2. The full text, which may contain AKT2-specific lipid data, was not available. Following the rule not to overrule curators, these rows are left undecided. Supporting Evidence: PMID:16814735 A key role of IRS-2 and Akt1 in lipid metabolism was revealed |
| GO:0010907 positive regulation of glucose metabolic process | IMP PMID:16814735 siRNA-based gene silencing reveals specialized roles of IRS-... | KEEP AS NON CORE | Summary: Positive regulation of glucose metabolism and glycogen synthesis downstream of insulin. Reason: AKT2 promotes glycogen synthesis by inhibitory phosphorylation of GSK3. The siRNA study supports its requirement. These are metabolic outputs of the core insulin-signaling kinase role. Supporting Evidence: PMID:16814735 IRS-1 and Akt2 were required for myoblast differentiation and glucose metabolism |
| GO:0030334 regulation of cell migration | TAS PMID:21432781 Akt1 and Akt2: differentiating the aktion. | KEEP AS NON CORE | Summary: Regulation of cell migration and motility in cancer cells (gastric cancer miR-29/siRNA; Twist-induced AKT2 in breast cancer). Reason: Knockdown and overexpression in cancer cell lines link AKT2 to migration and invasion. These are downstream, context-dependent outcomes of AKT2 signaling. Supporting Evidence: PMID:25428377 Introduction of miR-29s into GC cells resulted in decreased AKT2 expression and decreased the ability of cancer cells invasion, so did the siRNA-AKT2. |
| GO:0030335 positive regulation of cell migration | IDA PMID:25428377 MicroRNA-29s could target AKT2 to inhibit gastric cancer cel... | KEEP AS NON CORE | Summary: Regulation of cell migration and motility in cancer cells (gastric cancer miR-29/siRNA; Twist-induced AKT2 in breast cancer). Reason: Knockdown and overexpression in cancer cell lines link AKT2 to migration and invasion. These are downstream, context-dependent outcomes of AKT2 signaling. Supporting Evidence: PMID:25428377 Introduction of miR-29s into GC cells resulted in decreased AKT2 expression and decreased the ability of cancer cells invasion, so did the siRNA-AKT2. |
| GO:0030335 positive regulation of cell migration | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Regulation of cell migration and motility in cancer cells (gastric cancer miR-29/siRNA; Twist-induced AKT2 in breast cancer). Reason: Knockdown and overexpression in cancer cell lines link AKT2 to migration and invasion. These are downstream, context-dependent outcomes of AKT2 signaling. Supporting Evidence: PMID:25428377 Introduction of miR-29s into GC cells resulted in decreased AKT2 expression and decreased the ability of cancer cells invasion, so did the siRNA-AKT2. |
| GO:0032000 positive regulation of fatty acid beta-oxidation | IMP PMID:16814735 siRNA-based gene silencing reveals specialized roles of IRS-... | UNDECIDED | Summary: Lipid-metabolism phenotypes (fatty acid uptake, beta-oxidation) from the human muscle siRNA study. Reason: The abstract assigns the key role in lipid metabolism to IRS-2/AKT1 rather than AKT2. The full text, which may contain AKT2-specific lipid data, was not available. Following the rule not to overrule curators, these rows are left undecided. Supporting Evidence: PMID:16814735 A key role of IRS-2 and Akt1 in lipid metabolism was revealed |
| GO:0032555 purine ribonucleotide binding | IEA GO_REF:0000117 | TOO GENERAL | Summary: Purine ribonucleotide binding and anion binding, from automated mappings. Reason: These terms are true but uninformative. ATP binding, which is accepted here, entails both of them. Supporting Evidence: PMID:16540465 ATP binding to the enzymes prior to the peptide substrate |
| GO:0032587 ruffle membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cell cortex and ruffle membrane, from mouse Akt2 recruitment to cortical actin and to ruffles in insulin-stimulated cells. Reason: These are sub-regions of the plasma membrane's cytoplasmic face where PIP3 accumulates and AKT2 is recruited. The evidence is by similarity and the locations are peripheral. Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt recruited to the plasma membrane |
| GO:0032587 ruffle membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cell cortex and ruffle membrane, from mouse Akt2 recruitment to cortical actin and to ruffles in insulin-stimulated cells. Reason: These are sub-regions of the plasma membrane's cytoplasmic face where PIP3 accumulates and AKT2 is recruited. The evidence is by similarity and the locations are peripheral. Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt recruited to the plasma membrane |
| GO:0032869 cellular response to insulin stimulus | IMP PMID:16814735 siRNA-based gene silencing reveals specialized roles of IRS-... | ACCEPT | Summary: Insulin receptor signaling and cellular response to insulin. This is AKT2's principal physiological role. Reason: siRNA silencing in human skeletal muscle shows that AKT2, unlike AKT1, is required for insulin-stimulated glucose metabolism. AKT2 is the main AKT isoform relaying insulin signaling to metabolic endpoints. The IBA agrees. Supporting Evidence: PMID:16814735 IRS-1 and Akt2 were required for myoblast differentiation and glucose metabolism, whereas IRS-2 and Akt1 were dispensable. |
| GO:0035556 intracellular signal transduction | IBA GO_REF:0000033 | MODIFY | Summary: Intracellular signal transduction. Correct but general. Reason: The more specific PI3K/PKB signal transduction term describes the AKT2 role. The IBA ancestral node is sound. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000683254 SUPPORTS TRANSFER Ancestral node carrying generic intracellular signal transduction; correct for AKT2 but less specific than PI3K/PKB signal transduction. Proposed replacements: phosphatidylinositol 3-kinase/protein kinase B signal transduction Supporting Evidence: PMID:21432781 Kinases of the Akt family are integral and essential components in growth factor signaling pathways activated downstream of the membrane bound phospho-inositol-3 kinase. |
| GO:0036211 protein modification process | TAS PMID:1409633 AKT2, a putative oncogene encoding a member of a subfamily o... | MODIFY | Summary: Protein modification process. Correct but too general. Reason: AKT2 modifies proteins by phosphorylating them. Proposed replacements: protein phosphorylation Supporting Evidence: PMID:1409633 AKT2 encodes a 56-kDa protein with homology to serine/threonine kinases |
| GO:0043066 negative regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Negative regulation of apoptosis, inherited from the AKT clade. Reason: AKT kinases promote survival by phosphorylating BAD, MAP3K5 and FOXO. This is a well-established family function, but it is downstream of the kinase activity and context-dependent. Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt AKT also regulates cell survival via the phosphorylation of MAP3K5 |
| GO:0043168 anion binding | IEA GO_REF:0000117 | TOO GENERAL | Summary: Purine ribonucleotide binding and anion binding, from automated mappings. Reason: These terms are true but uninformative. ATP binding, which is accepted here, entails both of them. Supporting Evidence: PMID:16540465 ATP binding to the enzymes prior to the peptide substrate |
| GO:0043536 positive regulation of blood vessel endothelial cell migration | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Positive regulation of blood vessel endothelial cell migration, inherited from AKT1/AKT3 evidence. Reason: The IBA is plausible for the AKT clade, but endothelial migration is mainly AKT1-dependent. For AKT2 it is at most a peripheral role. Supporting Evidence: PMID:21432781 the two isoforms frequently act in a complementary opposing manner |
| GO:0045444 fat cell differentiation | TAS PMID:21432781 Akt1 and Akt2: differentiating the aktion. | KEEP AS NON CORE | Summary: Fat cell differentiation, cell cycle regulation and mammary epithelial differentiation, cited to a review of AKT1 versus AKT2. Reason: The review discusses isoform-specific AKT2 roles in differentiation and proliferation. These are downstream developmental and cellular outcomes, not core activities. Supporting Evidence: PMID:21432781 pointed to isoform specific functions in different cellular events and diseases |
| GO:0045725 positive regulation of glycogen biosynthetic process | IMP PMID:16814735 siRNA-based gene silencing reveals specialized roles of IRS-... | KEEP AS NON CORE | Summary: Positive regulation of glucose metabolism and glycogen synthesis downstream of insulin. Reason: AKT2 promotes glycogen synthesis by inhibitory phosphorylation of GSK3. The siRNA study supports its requirement. These are metabolic outputs of the core insulin-signaling kinase role. Supporting Evidence: PMID:16814735 IRS-1 and Akt2 were required for myoblast differentiation and glucose metabolism |
| GO:0046326 positive regulation of D-glucose import across plasma membrane | IMP PMID:16814735 siRNA-based gene silencing reveals specialized roles of IRS-... | ACCEPT | Summary: Positive regulation of insulin-stimulated glucose uptake. Reason: AKT2 is required for insulin-stimulated glucose metabolism in human muscle and promotes GLUT4 translocation (by phosphorylating TBC1D4 and C2CD5). Supporting Evidence: PMID:16814735 IRS-1 and Akt2 were required for myoblast differentiation and glucose metabolism file:human/AKT2/AKT2-uniprot.txt Regulates insulin-stimulated glucose transport by the increase of glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane. |
| GO:0050821 protein stabilization | IMP PMID:23444369 Insulin signaling via Akt2 switches plakophilin 1 function f... | KEEP AS NON CORE | Summary: Protein stabilization. AKT2 phosphorylation of plakophilin 1 increases PKP1 half-life. Reason: The stabilization is a consequence of substrate phosphorylation, a downstream regulatory outcome for one substrate. Supporting Evidence: PMID:23444369 The cytoplasmic accumulation was mediated by the stabilization of phosphorylated plakophilin 1, which displayed a considerably increased half-life |
| GO:0051726 regulation of cell cycle | TAS PMID:21432781 Akt1 and Akt2: differentiating the aktion. | KEEP AS NON CORE | Summary: Fat cell differentiation, cell cycle regulation and mammary epithelial differentiation, cited to a review of AKT1 versus AKT2. Reason: The review discusses isoform-specific AKT2 roles in differentiation and proliferation. These are downstream developmental and cellular outcomes, not core activities. Supporting Evidence: PMID:21432781 pointed to isoform specific functions in different cellular events and diseases |
| GO:0060644 mammary gland epithelial cell differentiation | TAS PMID:21432781 Akt1 and Akt2: differentiating the aktion. | KEEP AS NON CORE | Summary: Fat cell differentiation, cell cycle regulation and mammary epithelial differentiation, cited to a review of AKT1 versus AKT2. Reason: The review discusses isoform-specific AKT2 roles in differentiation and proliferation. These are downstream developmental and cellular outcomes, not core activities. Supporting Evidence: PMID:21432781 pointed to isoform specific functions in different cellular events and diseases |
| GO:0090314 positive regulation of protein targeting to membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of protein targeting to membrane (GLUT4 translocation), transferred from mouse Akt2. Reason: AKT2 promotes insulin-stimulated GLUT4 translocation to the plasma membrane through substrates such as TBC1D4 and C2CD5. This is consistent with the core insulin role but is a regulatory outcome. Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt Regulates insulin-stimulated glucose transport by the increase of glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane. |
| GO:0090314 positive regulation of protein targeting to membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of protein targeting to membrane (GLUT4 translocation), transferred from mouse Akt2. Reason: AKT2 promotes insulin-stimulated GLUT4 translocation to the plasma membrane through substrates such as TBC1D4 and C2CD5. This is consistent with the core insulin role but is a regulatory outcome. Supporting Evidence: file:human/AKT2/AKT2-uniprot.txt Regulates insulin-stimulated glucose transport by the increase of glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Serine/threonine protein kinase activity. This is the core catalytic function of AKT2. Reason: Kinetic studies of purified AKT2, phosphorylation of specific substrates (PKP1, TSC2, CBY1), and the conserved AGC kinase domain all establish this activity. The IBA and the Rhea-based protein serine kinase IEA agree with it. Supporting Evidence: PMID:16540465 Initial velocity studies revealed that all AKT isozymes follow the sequential kinetic mechanism PMID:23444369 Phosphorylation was mediated by Akt2 at four motifs within the plakophilin 1 N-terminal domain. Reactome:R-HSA-165162 All three isoforms of AKT, AKT1 (Inoki et al. 2002), AKT2 (Kearny et al. 2019), and AKT3 (Wainstein et al. 2022) phosphorylate TSC2. |
| GO:0140677 molecular function activator activity | EXP PMID:12517337 Crystal structure of an inactive Akt2 kinase domain. | UNDECIDED | Summary: Molecular function activator activity, attributed to a crystal structure of the inactive AKT2 kinase domain. Reason: The abstract describes only an inactive, unliganded kinase-domain structure and gives no basis for an activator activity. The curator may have used details from the full text that cannot be checked here. AKT2 activates some substrates (e.g. PDE3B) by phosphorylating them, but that is kinase activity, not binding-mediated activator activity. Supporting Evidence: PMID:12517337 The structure of an inactive and unliganded Akt2 kinase domain reveals several features that distinguish it from other kinases. |
| GO:1903676 positive regulation of cap-dependent translational initiation | IMP PMID:23444369 Insulin signaling via Akt2 switches plakophilin 1 function f... | KEEP AS NON CORE | Summary: Positive regulation of cap-dependent translation initiation, through AKT2 phosphorylation of PKP1. Reason: AKT2-phosphorylated PKP1 accumulates in the cytoplasm and stimulates translation. This is a substrate-mediated downstream effect. Supporting Evidence: PMID:23444369 accumulated in the cytoplasm, where it increased translation and proliferation rates |
| GO:1903898 negative regulation of PERK-mediated unfolded protein response | IEA GO_REF:0000107 | UNDECIDED | Summary: Negative regulation of the PERK-mediated UPR, transferred by orthology. Reason: No human AKT2-specific evidence was examined for this ortholog-derived inference. |
| GO:2000147 positive regulation of cell motility | IMP PMID:17332325 Twist transcriptionally up-regulates AKT2 in breast cancer c... | KEEP AS NON CORE | Summary: Regulation of cell migration and motility in cancer cells (gastric cancer miR-29/siRNA; Twist-induced AKT2 in breast cancer). Reason: Knockdown and overexpression in cancer cell lines link AKT2 to migration and invasion. These are downstream, context-dependent outcomes of AKT2 signaling. Supporting Evidence: PMID:25428377 Introduction of miR-29s into GC cells resulted in decreased AKT2 expression and decreased the ability of cancer cells invasion, so did the siRNA-AKT2. |
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Download this section (compressed HTML)Q: Which substrates are phosphorylated specifically by AKT2 and not by AKT1/AKT3 in human adipocytes and myocytes, and what determines isoform selectivity (localization, partner adaptors)?
Q: What fraction of AKT2 signaling occurs at endosomal versus plasma-membrane PIP3 pools?
Experiment: Isoform-specific chemical-genetic (analog-sensitive) AKT2 phosphoproteomics in human primary adipocytes after insulin stimulation.
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