APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) is a cytosolic multidomain adaptor and RAB5 effector. It has an N-terminal BAR-PH module that dimerizes and binds Rab5 and phosphoinositides, a C-terminal PTB domain, and a C-terminal PDZ-binding motif. APPL1 is a peripheral membrane protein on the cytoplasmic face of a distinct subpopulation of early endosomes ("APPL endosomes") near the plasma membrane. On these endosomes it scaffolds signaling between internalized receptors and downstream effectors. It binds AKT2 and PI3K, adiponectin receptors (ADIPOR1/2), TGFBR1, GIPC1, OCRL and DCC, and it promotes insulin- and adiponectin-stimulated AKT activation, GLUT4 translocation and glucose uptake. When stimulated (e.g. by EGF or oxidative stress) it can move to the nucleus, where it interacts with the NuRD complex and the beta-catenin/Reptin machinery. Loss-of-function mutations cause a form of familial diabetes (MODY14).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001726 ruffle | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Ruffle, early phagosome, macropinosome and phagocytic vesicle locations, mostly transferred from mouse macrophage studies. Reason: In mouse macrophages APPL1 is recruited to ruffles, macropinosomes and early phagosomes, all of which are Rab5-positive, peripheral, membrane-proximal compartments. These are context-specific sites of the same endosomal adaptor function. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Cell projection, ruffle |
| GO:0001726 ruffle | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ruffle, early phagosome, macropinosome and phagocytic vesicle locations, mostly transferred from mouse macrophage studies. Reason: In mouse macrophages APPL1 is recruited to ruffles, macropinosomes and early phagosomes, all of which are Rab5-positive, peripheral, membrane-proximal compartments. These are context-specific sites of the same endosomal adaptor function. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Cell projection, ruffle |
| GO:0001786 phosphatidylserine binding | IDA PMID:18034774 Membrane targeting by APPL1 and APPL2: dynamic scaffolds tha... | KEEP AS NON CORE | Summary: Phosphatidylserine binding by APPL BAR/PH/PTB domains in lipid overlay assays. Reason: APPL1 domains bind several phospholipids in vitro. This contributes to membrane association but is secondary to Rab5 and phosphoinositide-dependent targeting. Supporting Evidence: PMID:17502098 Lipid binding assays show that the BAR, PH, and PTB domains can bind phospholipids. |
| GO:0001786 phosphatidylserine binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Phosphatidylserine binding by APPL BAR/PH/PTB domains in lipid overlay assays. Reason: APPL1 domains bind several phospholipids in vitro. This contributes to membrane association but is secondary to Rab5 and phosphoinositide-dependent targeting. Supporting Evidence: PMID:17502098 Lipid binding assays show that the BAR, PH, and PTB domains can bind phospholipids. |
| GO:0005515 protein binding | IPI PMID:10490823 Identification of a chromosome 3p14.3-21.1 gene, APPL, encod... | MODIFY | Summary: APPL1 binds AKT2, specifically the inactive form, through its PTB domain. Reason: The interaction is the basis of APPL1's adaptor role in AKT signaling. The informative term is protein kinase B binding, which the gene already carries. Proposed replacements: protein kinase B binding Supporting Evidence: PMID:10490823 APPL interacts with the inactive form of AKT2 |
| GO:0005515 protein binding | IPI PMID:10490823 Identification of a chromosome 3p14.3-21.1 gene, APPL, encod... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:12011067 Mediation of the DCC apoptotic signal by DIP13 alpha. | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:15016378 APPL proteins link Rab5 to nuclear signal transduction via a... | MODIFY | Summary: APPL1 binds RAB5A as a Rab5 effector, through two binding sites on the BAR-PH dimer. Reason: APPL1 binds active Rab5, and this is essential for its endosomal recruitment and its function in proliferation. Small GTPase binding is the informative term. Proposed replacements: small GTPase binding Supporting Evidence: PMID:15016378 This pathway operates via APPL1 and APPL2, two Rab5 effectors, which reside on a subpopulation of endosomes. PMID:17581628 APPL1 is an effector of the small GTPase Rab5. |
| GO:0005515 protein binding | IPI PMID:15016378 APPL proteins link Rab5 to nuclear signal transduction via a... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:16273093 A quantitative protein interaction network for the ErbB rece... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:16622416 APPL1 binds to adiponectin receptors and mediates adiponecti... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:17030088 APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potent... | MODIFY | Summary: APPL1 binds AKT2, specifically the inactive form, through its PTB domain. Reason: The interaction is the basis of APPL1's adaptor role in AKT signaling. The informative term is protein kinase B binding, which the gene already carries. Proposed replacements: protein kinase B binding Supporting Evidence: PMID:10490823 APPL interacts with the inactive form of AKT2 |
| GO:0005515 protein binding | IPI PMID:17030088 APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potent... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:17581628 Structure of the APPL1 BAR-PH domain and characterization of... | MODIFY | Summary: APPL1 binds RAB5A as a Rab5 effector, through two binding sites on the BAR-PH dimer. Reason: APPL1 binds active Rab5, and this is essential for its endosomal recruitment and its function in proliferation. Small GTPase binding is the informative term. Proposed replacements: small GTPase binding Supporting Evidence: PMID:15016378 This pathway operates via APPL1 and APPL2, two Rab5 effectors, which reside on a subpopulation of endosomes. PMID:17581628 APPL1 is an effector of the small GTPase Rab5. |
| GO:0005515 protein binding | IPI PMID:17581628 Structure of the APPL1 BAR-PH domain and characterization of... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:18034774 Membrane targeting by APPL1 and APPL2: dynamic scaffolds tha... | MODIFY | Summary: APPL1 binds RAB5A as a Rab5 effector, through two binding sites on the BAR-PH dimer. Reason: APPL1 binds active Rab5, and this is essential for its endosomal recruitment and its function in proliferation. Small GTPase binding is the informative term. Proposed replacements: small GTPase binding Supporting Evidence: PMID:15016378 This pathway operates via APPL1 and APPL2, two Rab5 effectors, which reside on a subpopulation of endosomes. PMID:17581628 APPL1 is an effector of the small GTPase Rab5. |
| GO:0005515 protein binding | IPI PMID:18034774 Membrane targeting by APPL1 and APPL2: dynamic scaffolds tha... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:19433865 Endosomal adaptor proteins APPL1 and APPL2 are novel activat... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:19433865 Endosomal adaptor proteins APPL1 and APPL2 are novel activat... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:19661063 Yin-Yang regulation of adiponectin signaling by APPL isoform... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:21233288 The PH domain proteins IPIP27A and B link OCRL1 to receptor ... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:21291857 Interactions between GIPC-APPL and GIPC-TRP1 regulate melano... | MODIFY | Summary: APPL1 binds the PDZ protein GIPC1 through its C-terminal PDZ-binding motif. Reason: The interaction is mediated by the GIPC PDZ domain, so PDZ domain binding is the informative term. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:21291857 Since both TRP1 and APPL bind to GIPC thorough its PDZ-binding motif |
| GO:0005515 protein binding | IPI PMID:21291857 Interactions between GIPC-APPL and GIPC-TRP1 regulate melano... | MODIFY | Summary: APPL1 in a complex with GIPC1 and phospho-AKT in melanocytes. Reason: This row records APPL1 association with GIPC1 and AKT. GIPC1 binds the APPL1 C-terminal PDZ-binding motif, and AKT binds the PTB domain. Both interactions can be described with informative terms. Proposed replacements: protein kinase B binding PDZ domain binding Supporting Evidence: PMID:21291857 In melanocytes, APPL exists in a complex with GIPC and phospho-AKT. |
| GO:0005515 protein binding | IPI PMID:21291857 Interactions between GIPC-APPL and GIPC-TRP1 regulate melano... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:21645192 Biochemical characterization of APPL endosomes: the role of ... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:23414517 A human skeletal muscle interactome centered on proteins inv... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:23414517 A human skeletal muscle interactome centered on proteins inv... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:23414517 A human skeletal muscle interactome centered on proteins inv... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:23752268 The functional interactome landscape of the human histone de... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:24879834 The adaptor protein APPL2 inhibits insulin-stimulated glucos... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:25814554 Phospho-tyrosine dependent protein-protein interaction netwo... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:26583432 APPL proteins promote TGFΞ²-induced nuclear transport of the ... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:26583432 APPL proteins promote TGFΞ²-induced nuclear transport of the ... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:29568061 An AP-MS- and BioID-compatible MAC-tag enables comprehensive... | MODIFY | Summary: APPL1 binds RAB5A as a Rab5 effector, through two binding sites on the BAR-PH dimer. Reason: APPL1 binds active Rab5, and this is essential for its endosomal recruitment and its function in proliferation. Small GTPase binding is the informative term. Proposed replacements: small GTPase binding Supporting Evidence: PMID:15016378 This pathway operates via APPL1 and APPL2, two Rab5 effectors, which reside on a subpopulation of endosomes. PMID:17581628 APPL1 is an effector of the small GTPase Rab5. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: APPL1 binds RAB5A as a Rab5 effector, through two binding sites on the BAR-PH dimer. Reason: APPL1 binds active Rab5, and this is essential for its endosomal recruitment and its function in proliferation. Small GTPase binding is the informative term. Proposed replacements: small GTPase binding Supporting Evidence: PMID:15016378 This pathway operates via APPL1 and APPL2, two Rab5 effectors, which reside on a subpopulation of endosomes. PMID:17581628 APPL1 is an effector of the small GTPase Rab5. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:35384245 Physical and functional interactome atlas of human receptor ... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Quantitative fragmentomics measurement of APPL1 PDZ-binding motif affinities for many PDZ domain proteins. Reason: The study measures PDZ domain binding to PDZ-binding motifs. APPL1's C-terminal motif is the interacting element, so PDZ domain binding is the informative replacement for generic protein binding. The physiological relevance of individual low-affinity partners is not established. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Generic protein binding with diverse partners (APPL2, PIK3CA, DCC, EGFR, Reptin, TGFBR1, TRAF6, ANXA2, OCRL, adiponectin receptor, high-throughput screen hits). Reason: The protein-binding policy treats bare GO:0005515 as uninformative. These interactions reflect APPL1's scaffolding role, which is captured by signaling adaptor activity, protein kinase B binding and small GTPase binding elsewhere in this review. Removing the rows does not dispute that the interactions happen. Supporting Evidence: PMID:10490823 APPL binds to the PI3K catalytic subunit, p110alpha PMID:21645192 we identified Annexin A2 as an interacting partner of both APPL1 and APPL2 |
| GO:0005634 nucleus | IDA PMID:15016378 APPL proteins link Rab5 to nuclear signal transduction via a... | KEEP AS NON CORE | Summary: Nuclear pool. APPL1 moves to the nucleus after EGF or oxidative stress and interacts with NuRD/MeCP1 and Reptin. Reason: Nucleocytoplasmic shuttling of APPL1 is well documented. It is a regulated secondary location; at steady state APPL1 is mainly on early endosomes and in the cytosol. Supporting Evidence: PMID:15016378 APPL1 translocates from the membranes to the nucleus where it interacts with the nucleosome remodeling and histone deacetylase multiprotein complex NuRD/MeCP1 |
| GO:0005634 nucleus | IDA PMID:18034774 Membrane targeting by APPL1 and APPL2: dynamic scaffolds tha... | KEEP AS NON CORE | Summary: Nuclear pool. APPL1 moves to the nucleus after EGF or oxidative stress and interacts with NuRD/MeCP1 and Reptin. Reason: Nucleocytoplasmic shuttling of APPL1 is well documented. It is a regulated secondary location; at steady state APPL1 is mainly on early endosomes and in the cytosol. Supporting Evidence: PMID:15016378 APPL1 translocates from the membranes to the nucleus where it interacts with the nucleosome remodeling and histone deacetylase multiprotein complex NuRD/MeCP1 |
| GO:0005634 nucleus | IDA PMID:19433865 Endosomal adaptor proteins APPL1 and APPL2 are novel activat... | KEEP AS NON CORE | Summary: Nuclear pool. APPL1 moves to the nucleus after EGF or oxidative stress and interacts with NuRD/MeCP1 and Reptin. Reason: Nucleocytoplasmic shuttling of APPL1 is well documented. It is a regulated secondary location; at steady state APPL1 is mainly on early endosomes and in the cytosol. Supporting Evidence: PMID:15016378 APPL1 translocates from the membranes to the nucleus where it interacts with the nucleosome remodeling and histone deacetylase multiprotein complex NuRD/MeCP1 |
| GO:0005634 nucleus | IDA PMID:26583432 APPL proteins promote TGFΞ²-induced nuclear transport of the ... | KEEP AS NON CORE | Summary: Nuclear pool. APPL1 moves to the nucleus after EGF or oxidative stress and interacts with NuRD/MeCP1 and Reptin. Reason: Nucleocytoplasmic shuttling of APPL1 is well documented. It is a regulated secondary location; at steady state APPL1 is mainly on early endosomes and in the cytosol. Supporting Evidence: PMID:15016378 APPL1 translocates from the membranes to the nucleus where it interacts with the nucleosome remodeling and histone deacetylase multiprotein complex NuRD/MeCP1 |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear pool. APPL1 moves to the nucleus after EGF or oxidative stress and interacts with NuRD/MeCP1 and Reptin. Reason: Nucleocytoplasmic shuttling of APPL1 is well documented. It is a regulated secondary location; at steady state APPL1 is mainly on early endosomes and in the cytosol. Supporting Evidence: PMID:15016378 APPL1 translocates from the membranes to the nucleus where it interacts with the nucleosome remodeling and histone deacetylase multiprotein complex NuRD/MeCP1 |
| GO:0005737 cytoplasm | IDA PMID:19433865 Endosomal adaptor proteins APPL1 and APPL2 are novel activat... | MODIFY | Summary: Cytoplasm. Correct but general. Reason: APPL1 is a soluble cytosolic adaptor that associates peripherally with early endosome membranes. The specific locations (cytosol, early endosome membrane) are already annotated. Proposed replacements: early endosome membrane cytosol Supporting Evidence: PMID:15016378 two Rab5 effectors, which reside on a subpopulation of endosomes |
| GO:0005737 cytoplasm | IDA PMID:19661063 Yin-Yang regulation of adiponectin signaling by APPL isoform... | MODIFY | Summary: Cytoplasm. Correct but general. Reason: APPL1 is a soluble cytosolic adaptor that associates peripherally with early endosome membranes. The specific locations (cytosol, early endosome membrane) are already annotated. Proposed replacements: early endosome membrane cytosol Supporting Evidence: PMID:15016378 two Rab5 effectors, which reside on a subpopulation of endosomes |
| GO:0005737 cytoplasm | IDA PMID:21291857 Interactions between GIPC-APPL and GIPC-TRP1 regulate melano... | MODIFY | Summary: Cytoplasm. Correct but general. Reason: APPL1 is a soluble cytosolic adaptor that associates peripherally with early endosome membranes. The specific locations (cytosol, early endosome membrane) are already annotated. Proposed replacements: early endosome membrane cytosol Supporting Evidence: PMID:15016378 two Rab5 effectors, which reside on a subpopulation of endosomes |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | MODIFY | Summary: Cytoplasm. Correct but general. Reason: APPL1 is a soluble cytosolic adaptor that associates peripherally with early endosome membranes. The specific locations (cytosol, early endosome membrane) are already annotated. Proposed replacements: early endosome membrane cytosol Supporting Evidence: PMID:15016378 two Rab5 effectors, which reside on a subpopulation of endosomes |
| GO:0005768 endosome | IDA PMID:26583432 APPL proteins promote TGFΞ²-induced nuclear transport of the ... | MODIFY | Summary: Endosome, early endosome, vesicle membrane, membrane and cytoplasmic vesicle. Correct but general. Reason: APPL1 is a peripheral protein on the cytosolic face of APPL-positive early endosomes, which are Rab5-positive and largely EEA1-negative. Early endosome membrane (GO:0031901), which the gene already carries by EXP, is the supported specific term. Proposed replacements: early endosome membrane Supporting Evidence: PMID:21645192 APPL endosomes are a recently identified subpopulation of early endosomes characterized by the presence of two homologous Rab5 effector proteins APPL1 and APPL2. |
| GO:0005768 endosome | IEA GO_REF:0000120 | MODIFY | Summary: Endosome, early endosome, vesicle membrane, membrane and cytoplasmic vesicle. Correct but general. Reason: APPL1 is a peripheral protein on the cytosolic face of APPL-positive early endosomes, which are Rab5-positive and largely EEA1-negative. Early endosome membrane (GO:0031901), which the gene already carries by EXP, is the supported specific term. Proposed replacements: early endosome membrane Supporting Evidence: PMID:21645192 APPL endosomes are a recently identified subpopulation of early endosomes characterized by the presence of two homologous Rab5 effector proteins APPL1 and APPL2. |
| GO:0005769 early endosome | IDA PMID:21645192 Biochemical characterization of APPL endosomes: the role of ... | MODIFY | Summary: Endosome, early endosome, vesicle membrane, membrane and cytoplasmic vesicle. Correct but general. Reason: APPL1 is a peripheral protein on the cytosolic face of APPL-positive early endosomes, which are Rab5-positive and largely EEA1-negative. Early endosome membrane (GO:0031901), which the gene already carries by EXP, is the supported specific term. Proposed replacements: early endosome membrane Supporting Evidence: PMID:21645192 APPL endosomes are a recently identified subpopulation of early endosomes characterized by the presence of two homologous Rab5 effector proteins APPL1 and APPL2. |
| GO:0005769 early endosome | IEA GO_REF:0000107 | MODIFY | Summary: Endosome, early endosome, vesicle membrane, membrane and cytoplasmic vesicle. Correct but general. Reason: APPL1 is a peripheral protein on the cytosolic face of APPL-positive early endosomes, which are Rab5-positive and largely EEA1-negative. Early endosome membrane (GO:0031901), which the gene already carries by EXP, is the supported specific term. Proposed replacements: early endosome membrane Supporting Evidence: PMID:21645192 APPL endosomes are a recently identified subpopulation of early endosomes characterized by the presence of two homologous Rab5 effector proteins APPL1 and APPL2. |
| GO:0005769 early endosome | ISS GO_REF:0000024 | MODIFY | Summary: Endosome, early endosome, vesicle membrane, membrane and cytoplasmic vesicle. Correct but general. Reason: APPL1 is a peripheral protein on the cytosolic face of APPL-positive early endosomes, which are Rab5-positive and largely EEA1-negative. Early endosome membrane (GO:0031901), which the gene already carries by EXP, is the supported specific term. Proposed replacements: early endosome membrane Supporting Evidence: PMID:21645192 APPL endosomes are a recently identified subpopulation of early endosomes characterized by the presence of two homologous Rab5 effector proteins APPL1 and APPL2. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Cytosolic pool of APPL1. Reason: APPL1 is a soluble adaptor with a cytosolic pool, for example the APPL1-AKT2 complex in adipocytes that dissociates on insulin stimulation. The functional site is the endosome surface. Supporting Evidence: PMID:18034774 full-length APPL-yellow fluorescent protein (YFP) fusion proteins associated with cytosolic membrane structures |
| GO:0005829 cytosol | IDA PMID:17848569 The interaction of Akt with APPL1 is required for insulin-st... | KEEP AS NON CORE | Summary: Cytosolic pool of APPL1. Reason: APPL1 is a soluble adaptor with a cytosolic pool, for example the APPL1-AKT2 complex in adipocytes that dissociates on insulin stimulation. The functional site is the endosome surface. Supporting Evidence: PMID:18034774 full-length APPL-yellow fluorescent protein (YFP) fusion proteins associated with cytosolic membrane structures |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Plasma membrane. APPL1 structures cluster at the inner surface of the plasma membrane, and isolated PH domains target the plasma membrane. Reason: APPL1 is a cytosolic peripheral protein with no transmembrane or extracellular segment. It is found on APPL endosomes concentrated beneath the plasma membrane, and isolated PH domains associate with the PM inner leaflet. Any plasma membrane association is intracellular-face and transient, so this location is non-core and APPL1 is not a cell-surface-exposed protein. Supporting Evidence: PMID:18034774 APPL1 and APPL2 colocalize with each other and with activated RAB5 on punctate cytosolic structures often concentrated at the inner surface of the plasma membrane |
| GO:0005886 plasma membrane | IDA PMID:18034774 Membrane targeting by APPL1 and APPL2: dynamic scaffolds tha... | KEEP AS NON CORE | Summary: Plasma membrane. APPL1 structures cluster at the inner surface of the plasma membrane, and isolated PH domains target the plasma membrane. Reason: APPL1 is a cytosolic peripheral protein with no transmembrane or extracellular segment. It is found on APPL endosomes concentrated beneath the plasma membrane, and isolated PH domains associate with the PM inner leaflet. Any plasma membrane association is intracellular-face and transient, so this location is non-core and APPL1 is not a cell-surface-exposed protein. Supporting Evidence: PMID:18034774 APPL1 and APPL2 colocalize with each other and with activated RAB5 on punctate cytosolic structures often concentrated at the inner surface of the plasma membrane |
| GO:0006606 protein import into nucleus | IDA PMID:26583432 APPL proteins promote TGFΞ²-induced nuclear transport of the ... | KEEP AS NON CORE | Summary: TGF-beta-induced nuclear transport of the TGFBR1 intracellular domain along microtubules, which depends on APPL1. Reason: In prostate and breast cancer cells, APPL proteins are needed for nuclear translocation of TbetaRI-ICD and associate with beta-tubulin. This is a specialized, context-dependent signaling role. Supporting Evidence: PMID:26583432 APPL1 and APPL2 are required for TGFΞ²-induced nuclear translocation of TΞ²RI-ICD PMID:26583432 we found that APPL1 associates with microtubules and that this interaction is promoted by TRAF6 |
| GO:0006606 protein import into nucleus | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: TGF-beta-induced nuclear transport of the TGFBR1 intracellular domain along microtubules, which depends on APPL1. Reason: In prostate and breast cancer cells, APPL proteins are needed for nuclear translocation of TbetaRI-ICD and associate with beta-tubulin. This is a specialized, context-dependent signaling role. Supporting Evidence: PMID:26583432 APPL1 and APPL2 are required for TGFΞ²-induced nuclear translocation of TΞ²RI-ICD PMID:26583432 we found that APPL1 associates with microtubules and that this interaction is promoted by TRAF6 |
| GO:0007165 signal transduction | TAS PMID:10490823 Identification of a chromosome 3p14.3-21.1 gene, APPL, encod... | MODIFY | Summary: Signal transduction. Correct but general. Reason: APPL1's best-supported signaling roles are adaptor functions in insulin and adiponectin signaling. Proposed replacements: insulin receptor signaling pathway adiponectin-activated signaling pathway Supporting Evidence: PMID:26073777 APPL1 binds to AKT2, a key molecule in the insulin signaling pathway, thereby enhancing insulin-induced AKT2 activation and downstream signaling |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: TGF-beta-induced nuclear transport of the TGFBR1 intracellular domain along microtubules, which depends on APPL1. Reason: In prostate and breast cancer cells, APPL proteins are needed for nuclear translocation of TbetaRI-ICD and associate with beta-tubulin. This is a specialized, context-dependent signaling role. Supporting Evidence: PMID:26583432 APPL1 and APPL2 are required for TGFΞ²-induced nuclear translocation of TΞ²RI-ICD PMID:26583432 we found that APPL1 associates with microtubules and that this interaction is promoted by TRAF6 |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IMP PMID:26583432 APPL proteins promote TGFΞ²-induced nuclear transport of the ... | KEEP AS NON CORE | Summary: TGF-beta-induced nuclear transport of the TGFBR1 intracellular domain along microtubules, which depends on APPL1. Reason: In prostate and breast cancer cells, APPL proteins are needed for nuclear translocation of TbetaRI-ICD and associate with beta-tubulin. This is a specialized, context-dependent signaling role. Supporting Evidence: PMID:26583432 APPL1 and APPL2 are required for TGFΞ²-induced nuclear translocation of TΞ²RI-ICD PMID:26583432 we found that APPL1 associates with microtubules and that this interaction is promoted by TRAF6 |
| GO:0008286 insulin receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Insulin receptor signaling pathway. APPL1 is a positive adaptor for insulin-stimulated AKT2 activation. Reason: Familial diabetes loss-of-function mutations reduce insulin-stimulated AKT2/GSK3B phosphorylation. APPL1 knockdown suppresses insulin-stimulated AKT phosphorylation and GLUT4 translocation. The IBA agrees. Supporting Evidence: PMID:26073777 the p.Asp94Asn alteration causes significant reduction in the enhancement of the insulin-stimulated AKT2 and GSK3Ξ² phosphorylation that is observed after wild-type APPL1 transfection PMID:17848569 APPL1 knockdown suppressed Akt phosphorylation, glucose uptake, and Glut4 translocation |
| GO:0008286 insulin receptor signaling pathway | IMP PMID:26073777 Loss-of-Function Mutations in APPL1 in Familial Diabetes Mel... | ACCEPT | Summary: Insulin receptor signaling pathway. APPL1 is a positive adaptor for insulin-stimulated AKT2 activation. Reason: Familial diabetes loss-of-function mutations reduce insulin-stimulated AKT2/GSK3B phosphorylation. APPL1 knockdown suppresses insulin-stimulated AKT phosphorylation and GLUT4 translocation. The IBA agrees. Supporting Evidence: PMID:26073777 the p.Asp94Asn alteration causes significant reduction in the enhancement of the insulin-stimulated AKT2 and GSK3Ξ² phosphorylation that is observed after wild-type APPL1 transfection PMID:17848569 APPL1 knockdown suppressed Akt phosphorylation, glucose uptake, and Glut4 translocation |
| GO:0008286 insulin receptor signaling pathway | TAS PMID:17848569 The interaction of Akt with APPL1 is required for insulin-st... | ACCEPT | Summary: Insulin receptor signaling pathway. APPL1 is a positive adaptor for insulin-stimulated AKT2 activation. Reason: Familial diabetes loss-of-function mutations reduce insulin-stimulated AKT2/GSK3B phosphorylation. APPL1 knockdown suppresses insulin-stimulated AKT phosphorylation and GLUT4 translocation. The IBA agrees. Supporting Evidence: PMID:26073777 the p.Asp94Asn alteration causes significant reduction in the enhancement of the insulin-stimulated AKT2 and GSK3Ξ² phosphorylation that is observed after wild-type APPL1 transfection PMID:17848569 APPL1 knockdown suppressed Akt phosphorylation, glucose uptake, and Glut4 translocation |
| GO:0010008 endosome membrane | IBA GO_REF:0000033 | MODIFY | Summary: Endosome membrane. Correct, but early endosome membrane is more specific. Reason: APPL1 sits on an early-endosome subpopulation. The child term early endosome membrane is already annotated by EXP. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000572460 SUPPORTS TRANSFER APPL clade node carrying endosome membrane; correct for APPL1, refined to early endosome membrane. Proposed replacements: early endosome membrane Supporting Evidence: PMID:21645192 APPL endosomes are a recently identified subpopulation of early endosomes |
| GO:0010008 endosome membrane | IDA PMID:15016378 APPL proteins link Rab5 to nuclear signal transduction via a... | MODIFY | Summary: Endosome membrane. Correct, but early endosome membrane is more specific. Reason: APPL1 sits on an early-endosome subpopulation. The child term early endosome membrane is already annotated by EXP. Proposed replacements: early endosome membrane Supporting Evidence: PMID:21645192 APPL endosomes are a recently identified subpopulation of early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-373700 | MODIFY | Summary: Endosome membrane. Correct, but early endosome membrane is more specific. Reason: APPL1 sits on an early-endosome subpopulation. The child term early endosome membrane is already annotated by EXP. Proposed replacements: early endosome membrane Supporting Evidence: PMID:21645192 APPL endosomes are a recently identified subpopulation of early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-373717 | MODIFY | Summary: Endosome membrane. Correct, but early endosome membrane is more specific. Reason: APPL1 sits on an early-endosome subpopulation. The child term early endosome membrane is already annotated by EXP. Proposed replacements: early endosome membrane Supporting Evidence: PMID:21645192 APPL endosomes are a recently identified subpopulation of early endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-418845 | MODIFY | Summary: Endosome membrane. Correct, but early endosome membrane is more specific. Reason: APPL1 sits on an early-endosome subpopulation. The child term early endosome membrane is already annotated by EXP. Proposed replacements: early endosome membrane Supporting Evidence: PMID:21645192 APPL endosomes are a recently identified subpopulation of early endosomes |
| GO:0010762 regulation of fibroblast migration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Immune and motility roles transferred from mouse APPL1 (TLR4 and Fc-gamma receptor signaling in macrophages, macropinocytosis, cytokine production, HGF-driven fibroblast migration). Reason: These are by-similarity, cell-type-specific outcomes of APPL1 adaptor function at Rab5-positive membranes in mouse cells. They are plausible but peripheral to the core endosomal adaptor role. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). |
| GO:0010762 regulation of fibroblast migration | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Immune and motility roles transferred from mouse APPL1 (TLR4 and Fc-gamma receptor signaling in macrophages, macropinocytosis, cytokine production, HGF-driven fibroblast migration). Reason: These are by-similarity, cell-type-specific outcomes of APPL1 adaptor function at Rab5-positive membranes in mouse cells. They are plausible but peripheral to the core endosomal adaptor role. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). |
| GO:0012506 vesicle membrane | IDA PMID:17848569 The interaction of Akt with APPL1 is required for insulin-st... | MODIFY | Summary: Endosome, early endosome, vesicle membrane, membrane and cytoplasmic vesicle. Correct but general. Reason: APPL1 is a peripheral protein on the cytosolic face of APPL-positive early endosomes, which are Rab5-positive and largely EEA1-negative. Early endosome membrane (GO:0031901), which the gene already carries by EXP, is the supported specific term. Proposed replacements: early endosome membrane Supporting Evidence: PMID:21645192 APPL endosomes are a recently identified subpopulation of early endosomes characterized by the presence of two homologous Rab5 effector proteins APPL1 and APPL2. |
| GO:0016020 membrane | IDA PMID:18034774 Membrane targeting by APPL1 and APPL2: dynamic scaffolds tha... | MODIFY | Summary: Endosome, early endosome, vesicle membrane, membrane and cytoplasmic vesicle. Correct but general. Reason: APPL1 is a peripheral protein on the cytosolic face of APPL-positive early endosomes, which are Rab5-positive and largely EEA1-negative. Early endosome membrane (GO:0031901), which the gene already carries by EXP, is the supported specific term. Proposed replacements: early endosome membrane Supporting Evidence: PMID:21645192 APPL endosomes are a recently identified subpopulation of early endosomes characterized by the presence of two homologous Rab5 effector proteins APPL1 and APPL2. |
| GO:0023052 signaling | IBA GO_REF:0000033 | MODIFY | Summary: Signaling. Correct but very general. Reason: The specific pathways in which APPL1 acts as an adaptor are already annotated. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000572460 SUPPORTS TRANSFER APPL clade node carrying generic signaling; correct but refined to insulin/adiponectin pathways. Proposed replacements: insulin receptor signaling pathway adiponectin-activated signaling pathway Supporting Evidence: PMID:19661063 APPL1 is a newly identified adiponectin receptor-binding protein that positively mediates adiponectin signaling in cells. |
| GO:0031410 cytoplasmic vesicle | IDA PMID:18034774 Membrane targeting by APPL1 and APPL2: dynamic scaffolds tha... | MODIFY | Summary: Endosome, early endosome, vesicle membrane, membrane and cytoplasmic vesicle. Correct but general. Reason: APPL1 is a peripheral protein on the cytosolic face of APPL-positive early endosomes, which are Rab5-positive and largely EEA1-negative. Early endosome membrane (GO:0031901), which the gene already carries by EXP, is the supported specific term. Proposed replacements: early endosome membrane Supporting Evidence: PMID:21645192 APPL endosomes are a recently identified subpopulation of early endosomes characterized by the presence of two homologous Rab5 effector proteins APPL1 and APPL2. |
| GO:0031901 early endosome membrane | EXP PMID:15016378 APPL proteins link Rab5 to nuclear signal transduction via a... | ACCEPT | Summary: Early endosome membrane. This is the principal location of APPL1, as a peripheral protein on Rab5-positive APPL endosomes. Reason: Fractionation, imaging and Rab5-binding data place APPL1 on the cytosolic face of a distinct early-endosome subpopulation. Annexin A2 helps recruit it to the membrane. Supporting Evidence: PMID:21645192 APPL endosomes are a recently identified subpopulation of early endosomes characterized by the presence of two homologous Rab5 effector proteins APPL1 and APPL2. PMID:15016378 which reside on a subpopulation of endosomes |
| GO:0031901 early endosome membrane | EXP PMID:20133602 Two closely related endocytic proteins that share a common O... | ACCEPT | Summary: Early endosome membrane. This is the principal location of APPL1, as a peripheral protein on Rab5-positive APPL endosomes. Reason: Fractionation, imaging and Rab5-binding data place APPL1 on the cytosolic face of a distinct early-endosome subpopulation. Annexin A2 helps recruit it to the membrane. Supporting Evidence: PMID:21645192 APPL endosomes are a recently identified subpopulation of early endosomes characterized by the presence of two homologous Rab5 effector proteins APPL1 and APPL2. PMID:15016378 which reside on a subpopulation of endosomes |
| GO:0031901 early endosome membrane | EXP PMID:21645192 Biochemical characterization of APPL endosomes: the role of ... | ACCEPT | Summary: Early endosome membrane. This is the principal location of APPL1, as a peripheral protein on Rab5-positive APPL endosomes. Reason: Fractionation, imaging and Rab5-binding data place APPL1 on the cytosolic face of a distinct early-endosome subpopulation. Annexin A2 helps recruit it to the membrane. Supporting Evidence: PMID:21645192 APPL endosomes are a recently identified subpopulation of early endosomes characterized by the presence of two homologous Rab5 effector proteins APPL1 and APPL2. PMID:15016378 which reside on a subpopulation of endosomes |
| GO:0031901 early endosome membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Early endosome membrane. This is the principal location of APPL1, as a peripheral protein on Rab5-positive APPL endosomes. Reason: Fractionation, imaging and Rab5-binding data place APPL1 on the cytosolic face of a distinct early-endosome subpopulation. Annexin A2 helps recruit it to the membrane. Supporting Evidence: PMID:21645192 APPL endosomes are a recently identified subpopulation of early endosomes characterized by the presence of two homologous Rab5 effector proteins APPL1 and APPL2. PMID:15016378 which reside on a subpopulation of endosomes |
| GO:0032009 early phagosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ruffle, early phagosome, macropinosome and phagocytic vesicle locations, mostly transferred from mouse macrophage studies. Reason: In mouse macrophages APPL1 is recruited to ruffles, macropinosomes and early phagosomes, all of which are Rab5-positive, peripheral, membrane-proximal compartments. These are context-specific sites of the same endosomal adaptor function. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Cell projection, ruffle |
| GO:0032009 early phagosome | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ruffle, early phagosome, macropinosome and phagocytic vesicle locations, mostly transferred from mouse macrophage studies. Reason: In mouse macrophages APPL1 is recruited to ruffles, macropinosomes and early phagosomes, all of which are Rab5-positive, peripheral, membrane-proximal compartments. These are context-specific sites of the same endosomal adaptor function. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Cell projection, ruffle |
| GO:0033211 adiponectin-activated signaling pathway | IMP PMID:19661063 Yin-Yang regulation of adiponectin signaling by APPL isoform... | ACCEPT | Summary: Adiponectin-activated signaling pathway. APPL1 binds ADIPOR1/2 and mediates adiponectin signaling. Reason: APPL1 is the adiponectin receptor-binding adaptor that positively mediates adiponectin signaling in muscle cells, and APPL2 opposes it. Supporting Evidence: PMID:19661063 APPL1 is a newly identified adiponectin receptor-binding protein that positively mediates adiponectin signaling in cells. |
| GO:0034143 regulation of toll-like receptor 4 signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Immune and motility roles transferred from mouse APPL1 (TLR4 and Fc-gamma receptor signaling in macrophages, macropinocytosis, cytokine production, HGF-driven fibroblast migration). Reason: These are by-similarity, cell-type-specific outcomes of APPL1 adaptor function at Rab5-positive membranes in mouse cells. They are plausible but peripheral to the core endosomal adaptor role. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). |
| GO:0034143 regulation of toll-like receptor 4 signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Immune and motility roles transferred from mouse APPL1 (TLR4 and Fc-gamma receptor signaling in macrophages, macropinocytosis, cytokine production, HGF-driven fibroblast migration). Reason: These are by-similarity, cell-type-specific outcomes of APPL1 adaptor function at Rab5-positive membranes in mouse cells. They are plausible but peripheral to the core endosomal adaptor role. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). |
| GO:0035091 phosphatidylinositol binding | IDA PMID:18034774 Membrane targeting by APPL1 and APPL2: dynamic scaffolds tha... | ACCEPT | Summary: Phosphoinositide binding by the BAR-PH and PTB domains. Reason: Full-length APPL1 and its isolated PH/PTB domains bind phosphoinositides in vitro. Together with Rab5 binding, this contributes to endosomal membrane targeting. Supporting Evidence: PMID:18034774 full-length APPL proteins bound to phosphoinositides, and the APPL isolated PH or PTB domains were sufficient for in vitro phosphoinositide binding |
| GO:0035091 phosphatidylinositol binding | IEA GO_REF:0000117 | ACCEPT | Summary: Phosphoinositide binding by the BAR-PH and PTB domains. Reason: Full-length APPL1 and its isolated PH/PTB domains bind phosphoinositides in vitro. Together with Rab5 binding, this contributes to endosomal membrane targeting. Supporting Evidence: PMID:18034774 full-length APPL proteins bound to phosphoinositides, and the APPL isolated PH or PTB domains were sufficient for in vitro phosphoinositide binding |
| GO:0035729 cellular response to hepatocyte growth factor stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Immune and motility roles transferred from mouse APPL1 (TLR4 and Fc-gamma receptor signaling in macrophages, macropinocytosis, cytokine production, HGF-driven fibroblast migration). Reason: These are by-similarity, cell-type-specific outcomes of APPL1 adaptor function at Rab5-positive membranes in mouse cells. They are plausible but peripheral to the core endosomal adaptor role. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). |
| GO:0035729 cellular response to hepatocyte growth factor stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Immune and motility roles transferred from mouse APPL1 (TLR4 and Fc-gamma receptor signaling in macrophages, macropinocytosis, cytokine production, HGF-driven fibroblast migration). Reason: These are by-similarity, cell-type-specific outcomes of APPL1 adaptor function at Rab5-positive membranes in mouse cells. They are plausible but peripheral to the core endosomal adaptor role. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). |
| GO:0042802 identical protein binding | IEA GO_REF:0000002 | MODIFY | Summary: Identical protein binding. APPL1 self-associates through its BAR domain. Reason: The BAR-PH crystal structures and co-IP show a defined homodimer. Protein homodimerization activity, already annotated, is the more specific term. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:17502098 The structures reveal novel features for BAR domain dimerization |
| GO:0042802 identical protein binding | IPI PMID:17502098 Crystal structures of the BAR-PH and PTB domains of human AP... | MODIFY | Summary: Identical protein binding. APPL1 self-associates through its BAR domain. Reason: The BAR-PH crystal structures and co-IP show a defined homodimer. Protein homodimerization activity, already annotated, is the more specific term. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:17502098 The structures reveal novel features for BAR domain dimerization |
| GO:0042802 identical protein binding | IPI PMID:17581628 Structure of the APPL1 BAR-PH domain and characterization of... | MODIFY | Summary: Identical protein binding. APPL1 self-associates through its BAR domain. Reason: The BAR-PH crystal structures and co-IP show a defined homodimer. Protein homodimerization activity, already annotated, is the more specific term. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:17502098 The structures reveal novel features for BAR domain dimerization |
| GO:0042802 identical protein binding | IPI PMID:18034774 Membrane targeting by APPL1 and APPL2: dynamic scaffolds tha... | MODIFY | Summary: Identical protein binding. APPL1 self-associates through its BAR domain. Reason: The BAR-PH crystal structures and co-IP show a defined homodimer. Protein homodimerization activity, already annotated, is the more specific term. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:17502098 The structures reveal novel features for BAR domain dimerization |
| GO:0042802 identical protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Identical protein binding. APPL1 self-associates through its BAR domain. Reason: The BAR-PH crystal structures and co-IP show a defined homodimer. Protein homodimerization activity, already annotated, is the more specific term. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:17502098 The structures reveal novel features for BAR domain dimerization |
| GO:0042802 identical protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MODIFY | Summary: Identical protein binding. APPL1 self-associates through its BAR domain. Reason: The BAR-PH crystal structures and co-IP show a defined homodimer. Protein homodimerization activity, already annotated, is the more specific term. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:17502098 The structures reveal novel features for BAR domain dimerization |
| GO:0042802 identical protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Identical protein binding. APPL1 self-associates through its BAR domain. Reason: The BAR-PH crystal structures and co-IP show a defined homodimer. Protein homodimerization activity, already annotated, is the more specific term. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:17502098 The structures reveal novel features for BAR domain dimerization |
| GO:0042802 identical protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: Identical protein binding. APPL1 self-associates through its BAR domain. Reason: The BAR-PH crystal structures and co-IP show a defined homodimer. Protein homodimerization activity, already annotated, is the more specific term. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:17502098 The structures reveal novel features for BAR domain dimerization |
| GO:0042803 protein homodimerization activity | IDA PMID:18034774 Membrane targeting by APPL1 and APPL2: dynamic scaffolds tha... | KEEP AS NON CORE | Summary: Homodimerization through the BAR domain. Reason: Dimerization is a structural feature of the BAR-PH scaffold rather than its signaling function. Supporting Evidence: PMID:18034774 the APPL minimal BAR domains were necessary and sufficient for mediating APPL-APPL interactions |
| GO:0043422 protein kinase B binding | IBA GO_REF:0000033 | ACCEPT | Summary: Protein kinase B binding. APPL1 binds AKT through its PTB domain. Reason: Binding of AKT (especially inactive AKT2) is central to APPL1's adaptor function in insulin and adiponectin signaling. The IBA agrees. Supporting Evidence: PMID:10490823 APPL interacts with the inactive form of AKT2 PMID:17848569 In primary rat adipocytes and skeletal muscle, APPL1 and Akt2 formed a complex that was dissociated upon insulin stimulation in both tissues. |
| GO:0043422 protein kinase B binding | IPI PMID:17848569 The interaction of Akt with APPL1 is required for insulin-st... | ACCEPT | Summary: Protein kinase B binding. APPL1 binds AKT through its PTB domain. Reason: Binding of AKT (especially inactive AKT2) is central to APPL1's adaptor function in insulin and adiponectin signaling. The IBA agrees. Supporting Evidence: PMID:10490823 APPL interacts with the inactive form of AKT2 PMID:17848569 In primary rat adipocytes and skeletal muscle, APPL1 and Akt2 formed a complex that was dissociated upon insulin stimulation in both tissues. |
| GO:0044354 macropinosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ruffle, early phagosome, macropinosome and phagocytic vesicle locations, mostly transferred from mouse macrophage studies. Reason: In mouse macrophages APPL1 is recruited to ruffles, macropinosomes and early phagosomes, all of which are Rab5-positive, peripheral, membrane-proximal compartments. These are context-specific sites of the same endosomal adaptor function. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Cell projection, ruffle |
| GO:0044354 macropinosome | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ruffle, early phagosome, macropinosome and phagocytic vesicle locations, mostly transferred from mouse macrophage studies. Reason: In mouse macrophages APPL1 is recruited to ruffles, macropinosomes and early phagosomes, all of which are Rab5-positive, peripheral, membrane-proximal compartments. These are context-specific sites of the same endosomal adaptor function. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Cell projection, ruffle |
| GO:0044877 protein-containing complex binding | IPI PMID:15016378 APPL proteins link Rab5 to nuclear signal transduction via a... | KEEP AS NON CORE | Summary: Binding of the NuRD/MeCP1 complex in the nucleus. Reason: APPL1 interacts with the NuRD complex after moving to the nucleus. This is a secondary nuclear role. Supporting Evidence: PMID:15016378 interacts with the nucleosome remodeling and histone deacetylase multiprotein complex NuRD/MeCP1 |
| GO:0045088 regulation of innate immune response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Immune and motility roles transferred from mouse APPL1 (TLR4 and Fc-gamma receptor signaling in macrophages, macropinocytosis, cytokine production, HGF-driven fibroblast migration). Reason: These are by-similarity, cell-type-specific outcomes of APPL1 adaptor function at Rab5-positive membranes in mouse cells. They are plausible but peripheral to the core endosomal adaptor role. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). |
| GO:0045088 regulation of innate immune response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Immune and motility roles transferred from mouse APPL1 (TLR4 and Fc-gamma receptor signaling in macrophages, macropinocytosis, cytokine production, HGF-driven fibroblast migration). Reason: These are by-similarity, cell-type-specific outcomes of APPL1 adaptor function at Rab5-positive membranes in mouse cells. They are plausible but peripheral to the core endosomal adaptor role. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). |
| GO:0045335 phagocytic vesicle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Ruffle, early phagosome, macropinosome and phagocytic vesicle locations, mostly transferred from mouse macrophage studies. Reason: In mouse macrophages APPL1 is recruited to ruffles, macropinosomes and early phagosomes, all of which are Rab5-positive, peripheral, membrane-proximal compartments. These are context-specific sites of the same endosomal adaptor function. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Cell projection, ruffle |
| GO:0046324 regulation of D-glucose import across plasma membrane | IMP PMID:17848569 The interaction of Akt with APPL1 is required for insulin-st... | KEEP AS NON CORE | Summary: Regulation of insulin-stimulated glucose uptake and GLUT4 delivery to the plasma membrane. Reason: APPL1 knockdown reduces insulin-stimulated glucose uptake and GLUT4 translocation in adipocytes. These are downstream metabolic outputs of its insulin-signaling adaptor function. Supporting Evidence: PMID:17848569 APPL1 knockdown suppressed Akt phosphorylation, glucose uptake, and Glut4 translocation PMID:24879834 The adaptor protein APPL1 potentiates insulin-stimulated Akt activation and downstream actions. |
| GO:0046326 positive regulation of D-glucose import across plasma membrane | IMP PMID:24879834 The adaptor protein APPL2 inhibits insulin-stimulated glucos... | KEEP AS NON CORE | Summary: Regulation of insulin-stimulated glucose uptake and GLUT4 delivery to the plasma membrane. Reason: APPL1 knockdown reduces insulin-stimulated glucose uptake and GLUT4 translocation in adipocytes. These are downstream metabolic outputs of its insulin-signaling adaptor function. Supporting Evidence: PMID:17848569 APPL1 knockdown suppressed Akt phosphorylation, glucose uptake, and Glut4 translocation PMID:24879834 The adaptor protein APPL1 potentiates insulin-stimulated Akt activation and downstream actions. |
| GO:0048023 positive regulation of melanin biosynthetic process | IMP PMID:21291857 Interactions between GIPC-APPL and GIPC-TRP1 regulate melano... | KEEP AS NON CORE | Summary: APPL1 supports melanogenesis and associates with intracellular vesicles in melanocytes. Reason: APPL knockdown decreases tyrosinase levels and melanogenesis in human melanocytes. This is a cell-type-specific trafficking effect. Supporting Evidence: PMID:21291857 Knockdown of either GIPC or APPL inhibits melanogenesis by decreasing tyrosinase protein levels and enzyme activity. |
| GO:0048487 beta-tubulin binding | IDA PMID:26583432 APPL proteins promote TGFΞ²-induced nuclear transport of the ... | KEEP AS NON CORE | Summary: TGF-beta-induced nuclear transport of the TGFBR1 intracellular domain along microtubules, which depends on APPL1. Reason: In prostate and breast cancer cells, APPL proteins are needed for nuclear translocation of TbetaRI-ICD and associate with beta-tubulin. This is a specialized, context-dependent signaling role. Supporting Evidence: PMID:26583432 APPL1 and APPL2 are required for TGFΞ²-induced nuclear translocation of TΞ²RI-ICD PMID:26583432 we found that APPL1 associates with microtubules and that this interaction is promoted by TRAF6 |
| GO:0051050 positive regulation of transport | IEA GO_REF:0000117 | TOO GENERAL | Summary: Positive regulation of transport, from an automated association rule. Reason: The term is true but uninformative. Positive regulation of D-glucose import across the plasma membrane, kept elsewhere in this review, already entails it. Supporting Evidence: PMID:17848569 APPL1 knockdown suppressed Akt phosphorylation, glucose uptake, and Glut4 translocation |
| GO:0070062 extracellular exosome | HDA PMID:18570454 Proteomic analysis of exosomes from human neural stem cells ... | KEEP AS NON CORE | Summary: Detected in proteomes of exosomes from neural stem cells and urine. Reason: As a cytosolic endosomal adaptor, APPL1 can be included in exosomes formed from endosomal compartments. This is incidental cargo, not a functional extracellular location, and APPL1 is not secreted. Supporting Evidence: PMID:19056867 Here, we used LC-MS/MS to profile the proteome of human urinary exosomes. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Detected in proteomes of exosomes from neural stem cells and urine. Reason: As a cytosolic endosomal adaptor, APPL1 can be included in exosomes formed from endosomal compartments. This is incidental cargo, not a functional extracellular location, and APPL1 is not secreted. Supporting Evidence: PMID:19056867 Here, we used LC-MS/MS to profile the proteome of human urinary exosomes. |
| GO:0097708 intracellular vesicle | IDA PMID:21291857 Interactions between GIPC-APPL and GIPC-TRP1 regulate melano... | KEEP AS NON CORE | Summary: APPL1 supports melanogenesis and associates with intracellular vesicles in melanocytes. Reason: APPL knockdown decreases tyrosinase levels and melanogenesis in human melanocytes. This is a cell-type-specific trafficking effect. Supporting Evidence: PMID:21291857 Knockdown of either GIPC or APPL inhibits melanogenesis by decreasing tyrosinase protein levels and enzyme activity. |
| GO:0098978 glutamatergic synapse | IDA PMID:21236345 An APPL1/Akt signaling complex regulates dendritic spine and... | KEEP AS NON CORE | Summary: APPL1 localizes to dendritic spines and synapses and is required for spine and synapse formation in hippocampal neurons. Reason: Knockdown and rescue in cultured hippocampal neurons support an APPL1-AKT complex role in spine and synapse development. This is a tissue-specific role of the adaptor. Supporting Evidence: PMID:21236345 we show that APPL1 localizes to dendritic spines and synapses and regulates the development of these structures in hippocampal neurons |
| GO:0098978 glutamatergic synapse | IMP PMID:21236345 An APPL1/Akt signaling complex regulates dendritic spine and... | KEEP AS NON CORE | Summary: APPL1 localizes to dendritic spines and synapses and is required for spine and synapse formation in hippocampal neurons. Reason: Knockdown and rescue in cultured hippocampal neurons support an APPL1-AKT complex role in spine and synapse development. This is a tissue-specific role of the adaptor. Supporting Evidence: PMID:21236345 we show that APPL1 localizes to dendritic spines and synapses and regulates the development of these structures in hippocampal neurons |
| GO:0099558 maintenance of synapse structure | IDA PMID:21236345 An APPL1/Akt signaling complex regulates dendritic spine and... | KEEP AS NON CORE | Summary: APPL1 localizes to dendritic spines and synapses and is required for spine and synapse formation in hippocampal neurons. Reason: Knockdown and rescue in cultured hippocampal neurons support an APPL1-AKT complex role in spine and synapse development. This is a tissue-specific role of the adaptor. Supporting Evidence: PMID:21236345 we show that APPL1 localizes to dendritic spines and synapses and regulates the development of these structures in hippocampal neurons |
| GO:0099558 maintenance of synapse structure | IMP PMID:21236345 An APPL1/Akt signaling complex regulates dendritic spine and... | KEEP AS NON CORE | Summary: APPL1 localizes to dendritic spines and synapses and is required for spine and synapse formation in hippocampal neurons. Reason: Knockdown and rescue in cultured hippocampal neurons support an APPL1-AKT complex role in spine and synapse development. This is a tissue-specific role of the adaptor. Supporting Evidence: PMID:21236345 we show that APPL1 localizes to dendritic spines and synapses and regulates the development of these structures in hippocampal neurons |
| GO:1900017 positive regulation of cytokine production involved in inflammatory response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Immune and motility roles transferred from mouse APPL1 (TLR4 and Fc-gamma receptor signaling in macrophages, macropinocytosis, cytokine production, HGF-driven fibroblast migration). Reason: These are by-similarity, cell-type-specific outcomes of APPL1 adaptor function at Rab5-positive membranes in mouse cells. They are plausible but peripheral to the core endosomal adaptor role. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). |
| GO:1900017 positive regulation of cytokine production involved in inflammatory response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Immune and motility roles transferred from mouse APPL1 (TLR4 and Fc-gamma receptor signaling in macrophages, macropinocytosis, cytokine production, HGF-driven fibroblast migration). Reason: These are by-similarity, cell-type-specific outcomes of APPL1 adaptor function at Rab5-positive membranes in mouse cells. They are plausible but peripheral to the core endosomal adaptor role. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). |
| GO:1903076 regulation of protein localization to plasma membrane | IMP PMID:17848569 The interaction of Akt with APPL1 is required for insulin-st... | KEEP AS NON CORE | Summary: Regulation of insulin-stimulated glucose uptake and GLUT4 delivery to the plasma membrane. Reason: APPL1 knockdown reduces insulin-stimulated glucose uptake and GLUT4 translocation in adipocytes. These are downstream metabolic outputs of its insulin-signaling adaptor function. Supporting Evidence: PMID:17848569 APPL1 knockdown suppressed Akt phosphorylation, glucose uptake, and Glut4 translocation PMID:24879834 The adaptor protein APPL1 potentiates insulin-stimulated Akt activation and downstream actions. |
| GO:1905303 positive regulation of macropinocytosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Immune and motility roles transferred from mouse APPL1 (TLR4 and Fc-gamma receptor signaling in macrophages, macropinocytosis, cytokine production, HGF-driven fibroblast migration). Reason: These are by-similarity, cell-type-specific outcomes of APPL1 adaptor function at Rab5-positive membranes in mouse cells. They are plausible but peripheral to the core endosomal adaptor role. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). |
| GO:1905303 positive regulation of macropinocytosis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Immune and motility roles transferred from mouse APPL1 (TLR4 and Fc-gamma receptor signaling in macrophages, macropinocytosis, cytokine production, HGF-driven fibroblast migration). Reason: These are by-similarity, cell-type-specific outcomes of APPL1 adaptor function at Rab5-positive membranes in mouse cells. They are plausible but peripheral to the core endosomal adaptor role. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). |
| GO:1905450 negative regulation of Fc-gamma receptor signaling pathway involved in phagocytosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Immune and motility roles transferred from mouse APPL1 (TLR4 and Fc-gamma receptor signaling in macrophages, macropinocytosis, cytokine production, HGF-driven fibroblast migration). Reason: These are by-similarity, cell-type-specific outcomes of APPL1 adaptor function at Rab5-positive membranes in mouse cells. They are plausible but peripheral to the core endosomal adaptor role. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). |
| GO:1905450 negative regulation of Fc-gamma receptor signaling pathway involved in phagocytosis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Immune and motility roles transferred from mouse APPL1 (TLR4 and Fc-gamma receptor signaling in macrophages, macropinocytosis, cytokine production, HGF-driven fibroblast migration). Reason: These are by-similarity, cell-type-specific outcomes of APPL1 adaptor function at Rab5-positive membranes in mouse cells. They are plausible but peripheral to the core endosomal adaptor role. Supporting Evidence: file:human/APPL1/APPL1-uniprot.txt Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). |
| GO:2000045 regulation of G1/S transition of mitotic cell cycle | IDA PMID:15016378 APPL proteins link Rab5 to nuclear signal transduction via a... | KEEP AS NON CORE | Summary: Regulation of G1/S transition. APPL1 and APPL2 are needed for cell proliferation in a Rab5-dependent way. Reason: The Rab5-APPL endosome-to-nucleus pathway supports proliferation. This is a downstream cellular outcome. Supporting Evidence: PMID:15016378 Both APPL1 and APPL2 are essential for cell proliferation and their function requires Rab5 binding. |
| GO:2000045 regulation of G1/S transition of mitotic cell cycle | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Regulation of G1/S transition. APPL1 and APPL2 are needed for cell proliferation in a Rab5-dependent way. Reason: The Rab5-APPL endosome-to-nucleus pathway supports proliferation. This is a downstream cellular outcome. Supporting Evidence: PMID:15016378 Both APPL1 and APPL2 are essential for cell proliferation and their function requires Rab5 binding. |
| GO:0035591 signaling adaptor activity | IMP PMID:26073777 Loss-of-Function Mutations in APPL1 in Familial Diabetes Mel... | NEW | Summary: APPL1 is a non-catalytic adaptor that links receptors (insulin, adiponectin) to AKT2 activation. Reason: APPL1 has no catalytic domain. It brings signaling proteins together (AKT2, PI3K, ADIPOR1, Rab5) to enhance downstream signaling, and loss-of-function variants impair insulin-induced AKT2 activation. Signaling adaptor activity describes this function better than the many generic protein-binding rows. Supporting Evidence: PMID:26073777 APPL1 binds to AKT2, a key molecule in the insulin signaling pathway, thereby enhancing insulin-induced AKT2 activation and downstream signaling PMID:10490823 These data suggest that APPL is an adaptor that may tether inactive AKT2 to p110alpha in the cytoplasm |
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Q: How do the familial-diabetes APPL1 variants affect beta-cell insulin secretion as opposed to peripheral insulin sensitivity?
Experiment: Proximity labeling (APEX2-APPL1) of APPL endosomes in insulin-stimulated human adipocytes and beta cells, comparing wild-type and D94N APPL1.
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