Amyloid-beta precursor protein (APP) is a type I transmembrane protein that undergoes complex proteolytic processing to generate multiple bioactive fragments with distinct biological functions. APP is a paradigm for regulated intramembrane proteolysis (RIP). The protein has both alternative splice isoforms (APP695/751/770 differing in presence of KPI domain) and undergoes proteolytic cleavage via two competing pathways: (1) non-amyloidogenic (alpha-secretase) producing neuroprotective sAPPalpha, and (2) amyloidogenic (beta-secretase/BACE1) producing Abeta peptides associated with Alzheimer's disease. Full-length APP functions as a cell adhesion molecule, regulates neurite outgrowth, synapse formation, and copper/zinc homeostasis. The AICD fragment functions in nuclear signaling. Key biological insight: sAPPalpha is NEUROPROTECTIVE while Abeta is NEUROTOXIC - antagonistic functions from the same gene product. The isoforms and cleavage products are distinct molecular species with distinct activities, and a claim about one of them does not hold of the others.
Curated functional classes representing distinct biological activities. These may be splice variants, cleavage products, or other forms with different functions.
APP_695_NEURONALAPP_KPI_CONTAININGAPP_SAPP_ALPHAPRO_0000000115 (residues 18-687) APP_SAPP_BETAPRO_0000000116 (residues 18-671) APP_ABETA42PRO_0000000118 (residues 672-713) APP_ABETA40PRO_0000000119 (residues 672-711) APP_AICDPRO_0000000123, PRO_0000000124, PRO_0000000125 (residues 712-770 / 714-770 / 721-770) APP_N_APPPRO_0000381968 (residues 18-286) | GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0007409 axonogenesis | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation. Full-length APP regulates axon development. APP knockout mice show defects in axonogenesis. sAPPalpha promotes neurite outgrowth while full-length APP with Fe65/Mena inhibits branching to ensure directional growth (PMID:10188929, App-deep-research-perplexity.md). Reason: Core biological process. Well-supported by knockout studies and mechanistic understanding. Supporting Evidence: file:mouse/App/App-deep-research-perplexity.md provider: perplexity file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007417 central nervous system development | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference (IBA) from GO_REF:0000033. IBA annotations undergo extensive phylogenetic review and are generally reliable. Reason: IBA annotation supported by phylogenetic analysis. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005769 early endosome | IBA GO_REF:0000033 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005102 signaling receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference (IBA) from GO_REF:0000033. IBA annotations undergo extensive phylogenetic review and are generally reliable. Reason: IBA annotation supported by phylogenetic analysis. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030546 signaling receptor activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: Abeta42 activates FPR2 (formyl peptide receptor 2), inducing chemotaxis and oxidant stress in phagocytes (PMID:11316806). Note: this is primarily an Abeta cleavage product function. Reason: Supported by PMID:11316806, though applies to Abeta rather than full-length APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045121 membrane raft | IBA GO_REF:0000033 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0009986 cell surface | IBA GO_REF:0000033 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005790 smooth endoplasmic reticulum | IEA GO_REF:0000108 | ACCEPT | Summary: Electronic annotation (IEA) based on GO_REF:0000108. Consistent with APP biology and supported by computational inference. Reason: IEA annotation consistent with known APP functions. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050918 positive chemotaxis | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: positive chemotaxis is at most a cleavage-product or context-specific APP-family effect, not a core function of full-length App. Reason: Global App annotation to positive chemotaxis overstates the gene-level role; APP biology often depends on processing state and specific fragments rather than full-length APP acting directly in this process. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md attributing phenotypes to **full-length APP versus specific fragments** |
| GO:0004867 serine-type endopeptidase inhibitor activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation (IEA) based on GO_REF:0000120. Consistent with APP biology and supported by computational inference. Reason: IEA annotation consistent with known APP functions. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation (IEA) based on GO_REF:0000044. Consistent with APP biology and supported by computational inference. Reason: IEA annotation consistent with known APP functions. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation (IEA) based on GO_REF:0000044. Consistent with APP biology and supported by computational inference. Reason: IEA annotation consistent with known APP functions. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005769 early endosome | IEA GO_REF:0000044 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005905 clathrin-coated pit | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation (IEA) based on GO_REF:0000120. Consistent with APP biology and supported by computational inference. Reason: IEA annotation consistent with known APP functions. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006897 endocytosis | IEA GO_REF:0000043 | ACCEPT | Summary: APP undergoes clathrin-mediated endocytosis via its YENPTY motif. APP also regulates NMDA receptor endocytosis through Abeta-mediated signaling (PMID:16025111, UniProt P12023). Reason: Core function - APP endocytosis is essential for its processing and signaling. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006915 apoptotic process | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: apoptotic process reflects fragment- and stress-context APP biology rather than a primary full-length APP function. Reason: APP fragments such as N-APP, sAPP beta, A beta, or AICD can affect neuronal survival or stress pathways, but apoptosis is not the core molecular role of App. Supporting Evidence: file:mouse/App/App-notes.md sAPPΞ² has 10-100x less activity and may be pro-apoptotic via DR6 binding |
| GO:0007155 cell adhesion | IEA GO_REF:0000043 | ACCEPT | Summary: APP functions as a cell adhesion molecule through homophilic and heterophilic interactions. Trans-synaptic APP dimerization mediates cell-cell adhesion (App-deep-research-perplexity.md). Reason: Core function - APP is a bona fide cell adhesion molecule. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007219 Notch signaling pathway | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: APP and Notch share gamma-secretase processing machinery, so this is an indirect processing-context link rather than a core App pathway role. Reason: Retain as non-core because secretase biology connects APP and Notch, but APP is not a canonical Notch-pathway component. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md framing APP and Notch as shared substrates that create safety constraints for secretase inhibition |
| GO:0008201 heparin binding | IEA GO_REF:0000120 | ACCEPT | Summary: IBA annotation for heparin binding. APP contains two heparin-binding domains in E1 and E2 regions. High-affinity site in E1 GFLD and lower-affinity site in E2 (App-deep-research-perplexity.md). Reason: Core molecular function. Heparin binding mediates APP interactions with ECM and affects processing. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0009986 cell surface | IEA GO_REF:0000120 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010604 positive regulation of macromolecule metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: positive regulation of macromolecule metabolic process is too broad for a primary App annotation and likely reflects indirect fragment-mediated signaling. Reason: The term is a broad downstream readout; APP is better captured by trafficking, adhesion/scaffold, binding, and regulated proteolysis/fragment biology terms. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md APP function emerges from 1) **Compartmentalized trafficking** that determines which proteases/partners APP meets |
| GO:0012505 endomembrane system | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic annotation (IEA) based on GO_REF:0000117. Consistent with APP biology and supported by computational inference. Reason: IEA annotation consistent with known APP functions. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0016020 membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030198 extracellular matrix organization | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IBA annotation. APP interacts with ECM components (heparin, collagen, laminin) and may influence ECM organization. However, this is a secondary consequence of APP cell adhesion functions rather than core function (App-deep-research-perplexity.md). Reason: Downstream effect of APP cell adhesion and heparin-binding activities. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030414 peptidase inhibitor activity | IEA GO_REF:0000043 | ACCEPT | Summary: Electronic annotation (IEA) based on GO_REF:0000043. Consistent with APP biology and supported by computational inference. Reason: IEA annotation consistent with known APP functions. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030426 growth cone | IEA GO_REF:0000044 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000120 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043005 neuron projection | IEA GO_REF:0000117 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043204 perikaryon | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation (IEA) based on GO_REF:0000044. Consistent with APP biology and supported by computational inference. Reason: IEA annotation consistent with known APP functions. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | ACCEPT | Summary: Electronic annotation (IEA) based on GO_REF:0000043. Consistent with APP biology and supported by computational inference. Reason: IEA annotation consistent with known APP functions. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0046914 transition metal ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Electronic annotation (IEA) based on GO_REF:0000002. Consistent with APP biology and supported by computational inference. Reason: IEA annotation consistent with known APP functions. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0051246 regulation of protein metabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic annotation (IEA) based on GO_REF:0000117. Consistent with APP biology and supported by computational inference. Reason: IEA annotation consistent with known APP functions. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0099503 secretory vesicle | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic annotation (IEA) based on GO_REF:0000117. Consistent with APP biology and supported by computational inference. Reason: IEA annotation consistent with known APP functions. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0140677 molecular function activator activity | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic annotation (IEA) based on GO_REF:0000117. Consistent with APP biology and supported by computational inference. Reason: IEA annotation consistent with known APP functions. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:10460257 Disabled-1 binds to the cytoplasmic domain of amyloid precur... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:10460257 Disabled-1 binds to the cytoplasmic domain of amyloid precursor-like protein 1. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:11517249 c-Jun N-terminal kinase (JNK)-interacting protein-1b/islet-b... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:11517249 c-Jun N-terminal kinase (JNK)-interacting protein-1b/islet-brain-1 scaffolds Alzheimer's amyloid precursor protein with JNK. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:11724784 Jun NH2-terminal kinase (JNK) interacting protein 1 (JIP1) b... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:11724784 Nov 27. Jun NH2-terminal kinase (JNK) interacting protein 1 (JIP1) binds the cytoplasmic domain of the Alzheimer's beta-amyloid precursor protein (APP). file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:11877420 Tyrosine phosphorylation of the beta-amyloid precursor prote... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:11877420 2002 Mar 4. Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic tail promotes interaction with Shc. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:12826668 Crystal structures of the Dab homology domains of mouse disa... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:12826668 2003 Jun 24. Crystal structures of the Dab homology domains of mouse disabled 1 and 2. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:16193067 Homo- and heterodimerization of APP family members promotes ... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:16193067 Sep 29. Homo- and heterodimerization of APP family members promotes intercellular adhesion. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:16407538 Interaction of the cytosolic domains of sorLA/LR11 with the ... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:16407538 Interaction of the cytosolic domains of sorLA/LR11 with the amyloid precursor protein (APP) and beta-secretase beta-site APP-cleaving enzyme. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:17934213 The in vivo brain interactome of the amyloid precursor prote... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:17934213 Epub 2007 Oct 13. The in vivo brain interactome of the amyloid precursor protein. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:20573181 Progressive accumulation of amyloid-beta oligomers in Alzhei... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:20573181 2010 Jun 22. Progressive accumulation of amyloid-beta oligomers in Alzheimer's disease and in amyloid precursor protein transgenic mice is accompanied by selective alterations in synaptic scaffold proteins. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:20817278 Iron-export ferroxidase activity of Ξ²-amyloid precursor prot... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:20817278 Iron-export ferroxidase activity of Ξ²-amyloid precursor protein is inhibited by zinc in Alzheimer's disease. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:20925061 Molecular characterization of a trafficking organelle: disse... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:20925061 Molecular characterization of a trafficking organelle: dissecting the axonal paths of calsyntenin-1 transport vesicles. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:21368882 TGF-Ξ² induces TIAF1 self-aggregation via type II receptor-in... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:21368882 TGF-Ξ² induces TIAF1 self-aggregation via type II receptor-independent signaling that leads to generation of amyloid Ξ² plaques in Alzheimer's disease. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:23283322 Sortilin and SorLA display distinct roles in processing and ... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:23283322 Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:23585889 Generation of amyloid-Ξ² is reduced by the interaction of cal... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:23585889 Generation of amyloid-Ξ² is reduced by the interaction of calreticulin with amyloid precursor protein, presenilin and nicastrin. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:23719799 A tetra(ethylene glycol) derivative of benzothiazole aniline... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:23719799 A tetra(ethylene glycol) derivative of benzothiazole aniline enhances Ras-mediated spinogenesis. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:26960425 Yeast Two-Hybrid Screening for Proteins that Interact with t... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:26960425 Mar 9. Yeast Two-Hybrid Screening for Proteins that Interact with the Extracellular Domain of Amyloid Precursor Protein. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:19242475 Cellular prion protein mediates impairment of synaptic plast... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:19242475 Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:20133875 Synthetic amyloid-beta oligomers impair long-term memory ind... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:20133875 Synthetic amyloid-beta oligomers impair long-term memory independently of cellular prion protein. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:21113149 Reversing EphB2 depletion rescues cognitive functions in Alz... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:21113149 Reversing EphB2 depletion rescues cognitive functions in Alzheimer model. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000122 negative regulation of transcription by RNA polymerase II | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001664 G protein-coupled receptor binding | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001774 microglial cell activation | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001878 response to yeast | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0002265 astrocyte activation involved in immune response | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003682 chromatin binding | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0004867 serine-type endopeptidase inhibitor activity | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005102 signaling receptor binding | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005109 frizzled binding | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005158 insulin receptor binding | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005178 integrin binding | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005615 extracellular space | ISO GO_REF:0000119 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005641 nuclear envelope lumen | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005737 cytoplasm | ISO GO_REF:0000119 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005739 mitochondrion | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005764 lysosome | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005768 endosome | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005769 early endosome | ISO GO_REF:0000119 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005783 endoplasmic reticulum | ISO GO_REF:0000119 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005794 Golgi apparatus | ISO GO_REF:0000119 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | ISO GO_REF:0000119 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006357 regulation of transcription by RNA polymerase II | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007186 G protein-coupled receptor signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007611 learning or memory | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007612 learning | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007613 memory | ISO GO_REF:0000119 | ACCEPT | Summary: APP is required for normal memory. APP knockout mice show age-related cognitive deficits. sAPPalpha and picomolar Abeta enhance memory while Abeta oligomers impair memory (PMID:10188929, PMID:19118188, PMID:18568035). Reason: Core function supported by behavioral studies in knockout mice. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008285 negative regulation of cell population proliferation | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008306 associative learning | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0009986 cell surface | ISO GO_REF:0000119 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010468 regulation of gene expression | ISO GO_REF:0000119 | ACCEPT | Summary: AICD functions as transcriptional regulator via Fe65-Tip60 complex. Regulates genes involved in neurogenesis, apoptosis, and Abeta metabolism (PMID:12074840, App-deep-research-perplexity.md). Reason: Core AICD function. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010628 positive regulation of gene expression | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010629 negative regulation of gene expression | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0014005 microglia development | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0019722 calcium-mediated signaling | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0019731 antibacterial humoral response | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Abeta has antimicrobial activity against bacteria. However, this is specifically an Abeta function, not full-length APP. Reason: Over-annotation - specifically Abeta function. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0019732 antifungal humoral response | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Abeta has antifungal activity. However, this is specifically an Abeta function, not full-length APP. Reason: Over-annotation - specifically Abeta function. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0019899 enzyme binding | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030178 negative regulation of Wnt signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030425 dendrite | ISO GO_REF:0000119 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030546 signaling receptor activator activity | ISO GO_REF:0000119 | ACCEPT | Summary: Abeta42 activates FPR2 (formyl peptide receptor 2), inducing chemotaxis and oxidant stress in phagocytes (PMID:11316806). Note: this is primarily an Abeta cleavage product function. Reason: Supported by PMID:11316806, though applies to Abeta rather than full-length APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0031583 phospholipase D-activating G protein-coupled receptor signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0031901 early endosome membrane | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0032224 positive regulation of synaptic transmission, cholinergic | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0032722 positive regulation of chemokine production | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0032729 positive regulation of type II interferon production | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0032731 positive regulation of interleukin-1 beta production | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0032755 positive regulation of interleukin-6 production | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0032760 positive regulation of tumor necrosis factor production | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Abeta promotes TNF production via RAGE-mediated pathway (PMID:12808450). This is an Abeta-specific function, not intrinsic to full-length APP. Reason: Over-annotation - specifically Abeta function. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0032930 positive regulation of superoxide anion generation | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0032991 protein-containing complex | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0033130 acetylcholine receptor binding | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0034121 regulation of toll-like receptor signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0034185 apolipoprotein binding | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0034361 very-low-density lipoprotein particle | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0034362 low-density lipoprotein particle | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0034363 intermediate-density lipoprotein particle | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0034364 high-density lipoprotein particle | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0042056 chemoattractant activity | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0042802 identical protein binding | ISO GO_REF:0000119 | ACCEPT | Summary: APP forms homodimers through E1 domain interactions. Dimerization is enhanced by copper binding and heparin. Trans-dimerization mediates cell-cell adhesion at synapses (PMID:16193067, App-deep-research-perplexity.md). Reason: Core molecular function - APP dimerization is functionally important for synaptic adhesion. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0042803 protein homodimerization activity | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043005 neuron projection | ISO GO_REF:0000119 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043065 positive regulation of apoptotic process | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043395 heparan sulfate proteoglycan binding | ISO GO_REF:0000119 | ACCEPT | Summary: APP binds heparan sulfate proteoglycans including GPC1 via its heparin-binding domains. This interaction affects APP processing and copper delivery to GPC1 (UniProt P12023). Reason: Supported by APP heparin-binding domain structure and HSPG interactions. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043410 positive regulation of MAPK cascade | ISO GO_REF:0000119 | ACCEPT | Summary: APP promotes MAPK activation. APP-NCAM interaction activates ERK1/2. sAPPalpha activates MAPK signaling for neuroprotection (App-deep-research-perplexity.md). Reason: Core signaling function supported by mechanistic evidence. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043525 positive regulation of neuron apoptotic process | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Abeta oligomers and C31/AICD fragments promote neuronal apoptosis. However, sAPPalpha is NEUROPROTECTIVE. Full-length APP has complex, context-dependent effects on survival. This annotation represents only the pro-apoptotic Abeta/AICD side (UniProt P12023, App-deep-research-perplexity.md). Reason: Over-annotation - conflates opposing effects of different APP products. sAPPalpha is protective. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0044297 cell body | ISO GO_REF:0000119 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045087 innate immune response | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Abeta has antimicrobial properties and activates innate immune responses. While interesting, this is primarily an Abeta function rather than full-length APP function. Reason: Over-annotation - primarily Abeta function. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045121 membrane raft | ISO GO_REF:0000119 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045429 positive regulation of nitric oxide biosynthetic process | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045666 positive regulation of neuron differentiation | ISO GO_REF:0000119 | ACCEPT | Summary: sAPPalpha and Abeta at low concentrations promote neural stem cell proliferation and neuron differentiation (PMID:15190117, App-deep-research-perplexity.md). Reason: Supported by experimental evidence showing neurogenic effects of APP products. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045745 positive regulation of G protein-coupled receptor signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045752 positive regulation of Toll signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045821 positive regulation of glycolytic process | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000119 | ACCEPT | Summary: AICD-Fe65-Tip60 complex activates transcription of target genes including neprilysin (PMID:15944124, App-deep-research-perplexity.md). Reason: Core AICD signaling function supported by mechanistic evidence. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0046330 positive regulation of JNK cascade | ISO GO_REF:0000119 | ACCEPT | Summary: APP intracellular domain interacts with JIP1 (MAPK8IP1), which scaffolds JNK signaling (PMID:11517249, PMID:11724784). Reason: Supported by documented APP-JIP1 interaction. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0046875 ephrin receptor binding | ISO GO_REF:0000119 | ACCEPT | Summary: Abeta42 interacts with EphB2 receptor. This interaction may contribute to synaptic dysfunction in AD (IntAct: EBI-14022231). Reason: Supported by protein interaction data. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0046982 protein heterodimerization activity | ISO GO_REF:0000119 | ACCEPT | Summary: APP heterodimerizes with APLP1 and APLP2. These interactions contribute to functional redundancy among APP family members (IntAct data, App-deep-research-perplexity.md). Reason: Core function - APP family heterodimerization is functionally important. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048018 receptor ligand activity | ISO GO_REF:0000119 | ACCEPT | Summary: sAPPalpha and N-APP fragments function as ligands for receptors. sAPPalpha may act through neurotrophin receptors. N-APP binds DR6 for axon pruning signaling (App-deep-research-perplexity.md). Reason: Supported by evidence for APP fragments functioning as signaling ligands. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048143 astrocyte activation | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Abeta activates astrocytes. Reactive gliosis is seen in APP knockout mice but also with Abeta accumulation. Complex relationship between APP and astrocyte activation. Reason: Over-annotation - primarily Abeta-mediated effect. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048169 regulation of long-term neuronal synaptic plasticity | ISO GO_REF:0000119 | ACCEPT | Summary: APP regulates LTP and LTD. APP knockout impairs LTP. sAPPalpha enhances LTP while Abeta oligomers inhibit LTP and enhance LTD (PMID:18568035, PMID:19118188, App-deep-research-perplexity.md). Reason: Core function - central to APP physiology and Alzheimer's pathology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048471 perinuclear region of cytoplasm | ISO GO_REF:0000119 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050729 positive regulation of inflammatory response | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Abeta peptides activate inflammatory responses in microglia and astrocytes. This is primarily an Abeta cleavage product function, not intrinsic to full-length APP (App-deep-research-perplexity.md). Reason: Over-annotation - specifically Abeta function, not full-length APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050786 RAGE receptor binding | ISO GO_REF:0000119 | ACCEPT | Summary: Abeta binds RAGE (AGER), mediating Abeta transport across blood-brain barrier and neuroinflammatory responses. Note: primarily Abeta function (App-deep-research-perplexity.md). Reason: Well-documented Abeta-RAGE interaction with pathological significance. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050808 synapse organization | ISO GO_REF:0000119 | ACCEPT | Summary: APP is essential for synapse formation and maintenance. Trans-synaptic APP dimerization promotes synaptogenesis. APP knockout mice show synaptic deficits (PMID:10188929, App-deep-research-perplexity.md). Reason: Core biological function supported by knockout phenotypes and mechanistic studies. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050829 defense response to Gram-negative bacterium | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Abeta has antimicrobial properties. This is specifically an Abeta cleavage product function. Reason: Over-annotation - specifically Abeta function. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050830 defense response to Gram-positive bacterium | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Abeta has antimicrobial properties. This is specifically an Abeta cleavage product function. Reason: Over-annotation - specifically Abeta function. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050850 positive regulation of calcium-mediated signaling | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0051044 positive regulation of membrane protein ectodomain proteolysis | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0051087 protein-folding chaperone binding | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0051247 positive regulation of protein metabolic process | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0051260 protein homooligomerization | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0051262 protein tetramerization | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0051425 PTB domain binding | ISO GO_REF:0000119 | ACCEPT | Summary: APP cytoplasmic tail contains YENPTY motif that binds PTB domain proteins including Fe65, X11/Mint, Dab1, Numb, and others. This is a core mechanism for APP intracellular signaling (UniProt P12023, App-deep-research-perplexity.md). Reason: Core molecular function - YENPTY motif is essential for APP signaling. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0051580 regulation of neurotransmitter uptake | ISO GO_REF:0000119 | ACCEPT | Summary: APP regulates glutamate uptake. Presenilin-1 and APP affect neuronal glutamate transporter function (PMID:15009636). Reason: Supported by experimental evidence. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0055096 low-density lipoprotein particle mediated signaling | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0061844 antimicrobial humoral immune response mediated by antimicrobial peptide | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Abeta functions as antimicrobial peptide. This is specifically Abeta function, not full-length APP. Reason: Over-annotation - specifically Abeta function. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0070206 protein trimerization | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | ISO GO_REF:0000119 | ACCEPT | Summary: APP activates ERK1/2 through NCAM1 interaction and other mechanisms. Important for neurite outgrowth signaling (App-deep-research-perplexity.md). Reason: Supported by mechanistic studies. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0070381 endosome to plasma membrane transport vesicle | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0090026 positive regulation of monocyte chemotaxis | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: A beta peptide derived from APP can bind Frizzled near the Wnt-binding site and inhibit canonical Wnt signaling, but this is a fragment-specific pathway effect rather than a core full-length APP function. Reason: Retain as supported non-core biology because the evidence concerns A beta-mediated inhibition of Frizzled/Wnt signaling, not a primary receptor-like function of full-length App/APP. Supporting Evidence: PMID:18234671 Abeta binds to the Fz cysteine-rich domain at or in close proximity to the Wnt-binding site and inhibits the canonical Wnt signaling pathway |
| GO:0098793 presynapse | ISO GO_REF:0000119 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0098794 postsynapse | ISO GO_REF:0000119 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0098815 modulation of excitatory postsynaptic potential | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0106003 amyloid-beta complex | ISO GO_REF:0000119 | ACCEPT | Summary: Abeta peptides derived from APP form oligomeric and fibrillar complexes. This is a characteristic property of Abeta cleavage products. Reason: Accurate localization for Abeta products. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0120283 protein serine/threonine kinase binding | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0141137 positive regulation of gene expression, epigenetic | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0141163 positive regulation of cAMP/PKA signal transduction | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0150003 regulation of spontaneous synaptic transmission | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1900181 negative regulation of protein localization to nucleus | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1900221 regulation of amyloid-beta clearance | ISO GO_REF:0000119 | ACCEPT | Summary: APP and its interactions with LRP1 and other receptors affect Abeta clearance across the blood-brain barrier (App-deep-research-perplexity.md). Reason: Supported by evidence for APP role in Abeta metabolism. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1900272 negative regulation of long-term synaptic potentiation | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Abeta oligomers inhibit LTP (PMID:18568035, PMID:19242475). However, this is specifically an Abeta function, not full-length APP. sAPPalpha actually ENHANCES LTP. Annotation conflates opposing functions of different APP products. Reason: Over-annotation - specifically Abeta oligomer function. Full-length APP/sAPPalpha have opposite effect. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1900273 positive regulation of long-term synaptic potentiation | ISO GO_REF:0000119 | ACCEPT | Summary: sAPPalpha enhances LTP. Picomolar Abeta also positively modulates LTP, while high concentrations inhibit it (PMID:19118188). Full-length APP is required for normal LTP (App-deep-research-perplexity.md). Reason: Supported by evidence for sAPPalpha and low-concentration Abeta effects. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1900454 positive regulation of long-term synaptic depression | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Abeta oligomers enhance LTD via mGluR-dependent mechanism (PMID:18568035, PMID:19242475). This is specifically an Abeta oligomer function, not a property of full-length APP. Reason: Over-annotation - specifically Abeta oligomer function, not full-length APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1902894 negative regulation of miRNA transcription | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1902950 regulation of dendritic spine maintenance | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1902951 negative regulation of dendritic spine maintenance | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1902993 positive regulation of amyloid precursor protein catabolic process | ISO GO_REF:0000119 | ACCEPT | Summary: Accurate annotation - APP is subject to regulated catabolism by secretases and degradation machinery. Reason: Core biology of APP processing. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1903381 regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1903523 negative regulation of blood circulation | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Abeta affects vascular function including endothelin production and blood-brain barrier transport (PMID:12808450). This is primarily Abeta pathophysiology, not full-length APP function. Reason: Over-annotation - specifically Abeta-mediated vascular effects. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1904022 positive regulation of G protein-coupled receptor internalization | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1904472 positive regulation of endothelin production | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Abeta via RAGE increases endothelin production (PMID:12808450). This is Abeta pathophysiology, not intrinsic APP function. Reason: Over-annotation - specifically Abeta function. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1904591 positive regulation of protein import | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1904646 cellular response to amyloid-beta | ISO GO_REF:0000119 | ACCEPT | Summary: Cells respond to Abeta through multiple receptors including RAGE, FPR2, PrP. This annotation acknowledges APP as the Abeta source. Reason: Accurate - reflects Abeta signaling biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1905606 regulation of presynapse assembly | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1905898 positive regulation of response to endoplasmic reticulum stress | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1905906 regulation of amyloid fibril formation | ISO GO_REF:0000119 | ACCEPT | Summary: APP processing pathways regulate amyloid fibril formation. Copper/zinc binding affects Abeta aggregation properties. Reason: Accurate - APP and its processing regulate amyloid formation. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1905908 positive regulation of amyloid fibril formation | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: While Abeta forms amyloid fibrils, full-length APP does not intrinsically promote fibril formation. Copper binding to APP actually reduces Abeta production. Reason: Misleading - suggests APP promotes its own pathological processing. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1990000 amyloid fibril formation | ISO GO_REF:0000119 | ACCEPT | Summary: APP is the precursor to Abeta which forms amyloid fibrils. This is a well-characterized property of the Abeta cleavage product (App-deep-research-perplexity.md). Reason: Accurate annotation - APP is the source of amyloid-forming Abeta. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1990535 neuron projection maintenance | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1990777 lipoprotein particle | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:2000406 positive regulation of T cell migration | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:2000463 positive regulation of excitatory postsynaptic potential | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:2001238 positive regulation of extrinsic apoptotic signaling pathway | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Abeta and C-terminal fragments can activate extrinsic apoptotic pathways. However, sAPPalpha is neuroprotective. This annotation misrepresents the full biology of APP (App-deep-research-perplexity.md). Reason: Over-annotation - does not reflect neuroprotective sAPPalpha functions. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043408 regulation of MAPK cascade | ISO GO_REF:0000096 | ACCEPT | Summary: APP activates MAPK cascade through multiple mechanisms including interaction with NCAM1 and Ras signaling (PMID:15190117, App-deep-research-perplexity.md). Reason: Supported by experimental evidence for APP-mediated MAPK activation. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1902951 negative regulation of dendritic spine maintenance | ISO GO_REF:0000096 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008270 zinc ion binding | ISO GO_REF:0000096 | ACCEPT | Summary: APP binds zinc via residues in the copper binding site (His457, His507, His511). Zinc binding regulates APP processing and affects Abeta aggregation (UniProt P12023, App-deep-research-perplexity.md). Reason: Core molecular function supported by structural and biochemical evidence. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001878 response to yeast | ISO GO_REF:0000096 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005615 extracellular space | ISO GO_REF:0000096 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005737 cytoplasm | ISO GO_REF:0000096 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006816 calcium ion transport | ISO GO_REF:0000096 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0009986 cell surface | ISO GO_REF:0000096 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0016504 peptidase activator activity | ISO GO_REF:0000096 | MODIFY | Summary: The current term, peptidase activator activity, does not match the best-supported APP protease-related activity. APP is chiefly a substrate of secretases; the APP751/APP770 isoforms instead have a Kunitz protease inhibitor domain. Reason: Replace this broad/incorrect activator term with serine-type endopeptidase inhibitor activity for KPI-containing isoforms. The neuronal APP695 isoform lacks the KPI domain, so this should be treated as isoform-restricted rather than a general APP activity. Proposed replacements: serine-type endopeptidase inhibitor activity Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0019731 antibacterial humoral response | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Abeta has antimicrobial activity against bacteria. However, this is specifically an Abeta function, not full-length APP. Reason: Over-annotation - specifically Abeta function. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0019732 antifungal humoral response | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Abeta has antifungal activity. However, this is specifically an Abeta function, not full-length APP. Reason: Over-annotation - specifically Abeta function. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030424 axon | ISO GO_REF:0000096 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030426 growth cone | ISO GO_REF:0000096 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0044304 main axon | ISO GO_REF:0000096 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045087 innate immune response | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Abeta has antimicrobial properties and activates innate immune responses. While interesting, this is primarily an Abeta function rather than full-length APP function. Reason: Over-annotation - primarily Abeta function. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050829 defense response to Gram-negative bacterium | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Abeta has antimicrobial properties. This is specifically an Abeta cleavage product function. Reason: Over-annotation - specifically Abeta function. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050830 defense response to Gram-positive bacterium | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Abeta has antimicrobial properties. This is specifically an Abeta cleavage product function. Reason: Over-annotation - specifically Abeta function. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0051247 positive regulation of protein metabolic process | ISO GO_REF:0000096 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0061844 antimicrobial humoral immune response mediated by antimicrobial peptide | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Abeta functions as antimicrobial peptide. This is specifically Abeta function, not full-length APP. Reason: Over-annotation - specifically Abeta function. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | ISO GO_REF:0000096 | ACCEPT | Summary: APP activates ERK1/2 through NCAM1 interaction and other mechanisms. Important for neurite outgrowth signaling (App-deep-research-perplexity.md). Reason: Supported by mechanistic studies. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0070555 response to interleukin-1 | ISO GO_REF:0000096 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0070851 growth factor receptor binding | ISO GO_REF:0000096 | ACCEPT | Summary: APP E1 domain has growth factor-like structure and APP interacts with growth factor receptors. APP-NCAM1 interaction activates MAPK pathway (App-deep-research-perplexity.md). Reason: Supported by structural similarity and receptor interactions. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0071874 cellular response to norepinephrine stimulus | ISO GO_REF:0000096 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0097449 astrocyte projection | ISO GO_REF:0000096 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0098992 neuronal dense core vesicle | ISO GO_REF:0000096 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0110088 hippocampal neuron apoptotic process | ISO GO_REF:0000096 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1905945 regulation of response to calcium ion | ISO GO_REF:0000096 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1990761 growth cone lamellipodium | ISO GO_REF:0000096 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1990812 growth cone filopodium | ISO GO_REF:0000096 | ACCEPT | Summary: Sequence orthology annotation (ISO) based on human APP. APP is highly conserved between mouse and human with similar functions. Reason: ISO annotation supported by sequence conservation and functional similarity between mouse and human APP. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:24305806 Pharmacologic inhibition of ROCK2 suppresses amyloid-Ξ² produ... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:24305806 Pharmacologic inhibition of ROCK2 suppresses amyloid-Ξ² production in an Alzheimer's disease mouse model. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005615 extracellular space | NAS PMID:18568035 Amyloid-beta protein dimers isolated directly from Alzheimer... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:18568035 We extracted soluble amyloid-beta protein (Abeta) oligomers directly from the cerebral cortex of subjects with Alzheimer's disease file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | NAS PMID:18568035 Amyloid-beta protein dimers isolated directly from Alzheimer... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:18568035 reduced dendritic spine density in normal rodent hippocampus file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043408 regulation of MAPK cascade | ISS GO_REF:0000114 | ACCEPT | Summary: APP activates MAPK cascade through multiple mechanisms including interaction with NCAM1 and Ras signaling (PMID:15190117, App-deep-research-perplexity.md). Reason: Supported by experimental evidence for APP-mediated MAPK activation. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043408 regulation of MAPK cascade | IDA PMID:15190117 Neurogenic effect of beta-amyloid peptide in the development... | ACCEPT | Summary: APP activates MAPK cascade through multiple mechanisms including interaction with NCAM1 and Ras signaling (PMID:15190117, App-deep-research-perplexity.md). Reason: Supported by experimental evidence for APP-mediated MAPK activation. Supporting Evidence: PMID:15190117 Neurogenic effect of beta-amyloid peptide in the development of neural stem cells. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045666 positive regulation of neuron differentiation | IDA PMID:15190117 Neurogenic effect of beta-amyloid peptide in the development... | ACCEPT | Summary: sAPPalpha and Abeta at low concentrations promote neural stem cell proliferation and neuron differentiation (PMID:15190117, App-deep-research-perplexity.md). Reason: Supported by experimental evidence showing neurogenic effects of APP products. Supporting Evidence: PMID:15190117 Neurogenic effect of beta-amyloid peptide in the development of neural stem cells. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1900272 negative regulation of long-term synaptic potentiation | IDA PMID:18568035 Amyloid-beta protein dimers isolated directly from Alzheimer... | MARK AS OVER ANNOTATED | Summary: Abeta oligomers inhibit LTP (PMID:18568035, PMID:19242475). However, this is specifically an Abeta function, not full-length APP. sAPPalpha actually ENHANCES LTP. Annotation conflates opposing functions of different APP products. Reason: Over-annotation - specifically Abeta oligomer function. Full-length APP/sAPPalpha have opposite effect. Supporting Evidence: PMID:18568035 The oligomers potently inhibited long-term potentiation (LTP), enhanced long-term depression (LTD) and reduced dendritic spine density in normal rodent hippocampus file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1900272 negative regulation of long-term synaptic potentiation | NAS PMID:19242475 Cellular prion protein mediates impairment of synaptic plast... | MARK AS OVER ANNOTATED | Summary: Abeta oligomers inhibit LTP (PMID:18568035, PMID:19242475). However, this is specifically an Abeta function, not full-length APP. sAPPalpha actually ENHANCES LTP. Annotation conflates opposing functions of different APP products. Reason: Over-annotation - specifically Abeta oligomer function. Full-length APP/sAPPalpha have opposite effect. Supporting Evidence: PMID:19242475 At nanomolar concentrations, soluble amyloid-beta oligomers block hippocampal long-term potentiation, cause dendritic spine retraction from pyramidal cells and impair rodent spatial memory file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1900454 positive regulation of long-term synaptic depression | NAS PMID:19242475 Cellular prion protein mediates impairment of synaptic plast... | MARK AS OVER ANNOTATED | Summary: Abeta oligomers enhance LTD via mGluR-dependent mechanism (PMID:18568035, PMID:19242475). This is specifically an Abeta oligomer function, not a property of full-length APP. Reason: Over-annotation - specifically Abeta oligomer function, not full-length APP. Supporting Evidence: PMID:18568035 enhanced long-term depression (LTD) PMID:19242475 Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1902951 negative regulation of dendritic spine maintenance | NAS PMID:22820466 Alzheimer amyloid-Ξ² oligomer bound to postsynaptic prion pro... | ACCEPT | Summary: Annotation (NAS) from PMID:22820466. Consistent with APP biology. Reason: Annotation with evidence code NAS. Supporting Evidence: PMID:22820466 AΞ²-induced dendritic spine loss and lactate dehydrogenase release required both PrP(C) and Fyn file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:30902970 Complex formation of APP with GABA(B) receptors links axonal... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:30902970 Complex formation of APP with GABA(B) receptors links axonal trafficking to amyloidogenic processing. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0009986 cell surface | IDA PMID:30902970 Complex formation of APP with GABA(B) receptors links axonal... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:30902970 Complex formation with GBRs stabilizes APP at the cell surface and reduces proteolysis of APP to AΞ² file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010467 gene expression | IMP PMID:30902970 Complex formation of APP with GABA(B) receptors links axonal... | ACCEPT | Summary: AICD regulates gene expression through transcriptional and translational mechanisms. AICD can regulate p53 translation via IRES binding (PMID:30902970, App-deep-research-perplexity.md). Reason: Supported by evidence for AICD transcriptional and translational regulation. Supporting Evidence: PMID:30902970 Complex formation of APP with GABA(B) receptors links axonal trafficking to amyloidogenic processing. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0019904 protein domain specific binding | IDA PMID:30902970 Complex formation of APP with GABA(B) receptors links axonal... | ACCEPT | Summary: APP binds to the sushi-domain of GABA(B) receptors with nanomolar affinity. Dinamarca et al. (2019) demonstrated domain-specific binding. Reason: Experimental annotation (IDA) with literature support. Supporting Evidence: PMID:30902970 sequence-related epitopes in APP, AJAP-1 and PIANP bind with nanomolar affinities to the N-terminal sushi-domain of presynaptic GBRs file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030424 axon | IMP PMID:30902970 Complex formation of APP with GABA(B) receptors links axonal... | ACCEPT | Summary: APP loss impairs axonal GBR expression. Dinamarca et al. (2019) showed APP regulates axonal trafficking of GABA(B) receptors. Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:30902970 selectively the genetic loss of APP impaired GBR-mediated presynaptic inhibition and axonal GBR expression file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0097708 intracellular vesicle | IDA PMID:30902970 Complex formation of APP with GABA(B) receptors links axonal... | ACCEPT | Summary: APP associates with cargo vesicles for axonal transport. Dinamarca et al. (2019) showed APP/GBR complex in cargo vesicles linked to trafficking motor. Reason: Experimental annotation (IDA) with literature support. Supporting Evidence: PMID:30902970 APP associates with JIP and calsyntenin proteins that link the APP/GBR complex in cargo vesicles to the axonal trafficking motor file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1905607 negative regulation of presynapse assembly | IMP PMID:30902970 Complex formation of APP with GABA(B) receptors links axonal... | ACCEPT | Summary: APP loss impairs presynaptic GBR function. Dinamarca et al. (2019) showed APP is required for presynaptic inhibition via GBR. Reason: Experimental annotation (IMP) with literature support. Supporting Evidence: PMID:30902970 selectively the genetic loss of APP impaired GBR-mediated presynaptic inhibition and axonal GBR expression file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048786 presynaptic active zone | IEP PMID:23815291 Amyloid precursor proteins are constituents of the presynapt... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:23815291 Amyloid precursor proteins are constituents of the presynaptic active zone. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048786 presynaptic active zone | IDA PMID:23815291 Amyloid precursor proteins are constituents of the presynapt... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:23815291 Amyloid precursor proteins are constituents of the presynaptic active zone. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0019901 protein kinase binding | IPI PMID:24305806 Pharmacologic inhibition of ROCK2 suppresses amyloid-Ξ² produ... | ACCEPT | Summary: APP cytoplasmic domain interacts with multiple kinases including CDK5, GSK3beta. APP is phosphorylated at multiple sites affecting its trafficking and processing (PMID:24305806, UniProt P12023). Reason: Supported by documented kinase interactions and phosphorylation sites. Supporting Evidence: PMID:24305806 Pharmacologic inhibition of ROCK2 suppresses amyloid-Ξ² production in an Alzheimer's disease mouse model. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:18650440 Structure of the C-terminal phosphotyrosine interaction doma... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:18650440 2008 Jul 23. Structure of the C-terminal phosphotyrosine interaction domain of Fe65L1 complexed with the cytoplasmic tail of amyloid precursor protein reveals a novel peptide binding mode. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005783 endoplasmic reticulum | ISS GO_REF:0000024 | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030198 extracellular matrix organization | IGI PMID:15385965 Cortical dysplasia resembling human type 2 lissencephaly in ... | KEEP AS NON CORE | Summary: IBA annotation. APP interacts with ECM components (heparin, collagen, laminin) and may influence ECM organization. However, this is a secondary consequence of APP cell adhesion functions rather than core function (App-deep-research-perplexity.md). Reason: Downstream effect of APP cell adhesion and heparin-binding activities. Supporting Evidence: PMID:15385965 Sep 23. Cortical dysplasia resembling human type 2 lissencephaly in mice lacking all three APP family members. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030900 forebrain development | IGI PMID:15385965 Cortical dysplasia resembling human type 2 lissencephaly in ... | ACCEPT | Summary: APP family is essential for forebrain development. Triple knockout (APP/APLP1/APLP2) mice show cortical dysplasia resembling type 2 lissencephaly (PMID:15385965, PMID:10200318). Reason: Core developmental function demonstrated by knockout phenotypes. Supporting Evidence: PMID:15385965 Sep 23. Cortical dysplasia resembling human type 2 lissencephaly in mice lacking all three APP family members. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:15944124 Presenilin-dependent transcriptional control of the Abeta-de... | UNDECIDED | Summary: Cannot be adjudicated here: PMID:15944124 is cached abstract-only. Prior observation, not a verdict: AICD-containing complexes can regulate transcription, but APP/AICD is not a sequence-specific DNA-binding transcription factor. Reason: PMID:15944124 is cached abstract-only, so the curator's experimental evidence cannot be inspected here; per CLAUDE.md an experimental annotation is not overruled on that basis. Recorded observation, not a verdict: The cited AICD-Fe65-Tip60 literature supports transcriptional regulation through adaptor/cofactor complexes, not direct RNA polymerase II cis-regulatory region sequence-specific DNA binding by APP itself. Supporting Evidence: file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0042802 identical protein binding | ISO PMID:23986251 Synaptic protein Ξ±1-takusan mitigates amyloid-Ξ²-induced syna... | REMOVE | Summary: APP homodimerization is real, but PMID:23986251 is an alpha1-takusan/tau/PSD-95 paper and does not support this App annotation. Reason: Remove this specific evidence row because the cited PMID does not demonstrate APP identical protein binding; APP-family homodimerization is retained through correctly supported evidence elsewhere. Supporting Evidence: PMID:23986251 Synaptic protein Ξ±1-takusan mitigates amyloid-Ξ²-induced synaptic loss via interaction with tau and postsynaptic density-95 at postsynaptic sites. |
| GO:0030424 axon | IDA PMID:25631124 TREM2 regulates microglial cell activation in response to de... | UNDECIDED | Summary: Cannot be adjudicated here: PMID:25631124 is cached abstract-only. Prior observation, not a verdict: PMID:25631124 is a TREM2 demyelination paper and does not support App axonal localization. Reason: PMID:25631124 is cached abstract-only, so the curator's experimental evidence cannot be inspected here; per CLAUDE.md an experimental annotation is not overruled on that basis. Recorded observation, not a verdict: This row was flagged because the cited paper is about Trem2-dependent microglial activation, not APP localization to axons. App axonal/neuron-projection localization is retained through correctly supported rows such as PMID:16301330. Supporting Evidence: PMID:25631124 TREM2 regulates microglial cell activation in response to demyelination in vivo. |
| GO:0005515 protein binding | IPI PMID:22685302 Down syndrome cell adhesion molecule (DSCAM) associates with... | REMOVE | Summary: PMID:22685302 describes a DSCAM-UNC5C interaction and does not support an App protein-binding annotation. Reason: Remove this specific IPI evidence row because the cited paper concerns DSCAM and UNC5C rather than APP; generic App protein-binding rows remain over-annotated when the cited interaction is real. Supporting Evidence: PMID:22685302 Down syndrome cell adhesion molecule (DSCAM) associates with uncoordinated-5C (UNC5C) in netrin-1-mediated growth cone collapse. |
| GO:0008021 synaptic vesicle | IDA PMID:25438880 Pre-synaptic localization of the Ξ³-secretase-inhibiting prot... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:25438880 Pre-synaptic localization of the Ξ³-secretase-inhibiting protein p24Ξ±2 in the mammalian brain. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0032760 positive regulation of tumor necrosis factor production | IGI PMID:12808450 RAGE mediates amyloid-beta peptide transport across the bloo... | MARK AS OVER ANNOTATED | Summary: Abeta promotes TNF production via RAGE-mediated pathway (PMID:12808450). This is an Abeta-specific function, not intrinsic to full-length APP. Reason: Over-annotation - specifically Abeta function. Supporting Evidence: PMID:12808450 RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1903523 negative regulation of blood circulation | IGI PMID:12808450 RAGE mediates amyloid-beta peptide transport across the bloo... | MARK AS OVER ANNOTATED | Summary: Abeta affects vascular function including endothelin production and blood-brain barrier transport (PMID:12808450). This is primarily Abeta pathophysiology, not full-length APP function. Reason: Over-annotation - specifically Abeta-mediated vascular effects. Supporting Evidence: PMID:12808450 RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1904472 positive regulation of endothelin production | IGI PMID:12808450 RAGE mediates amyloid-beta peptide transport across the bloo... | MARK AS OVER ANNOTATED | Summary: Abeta via RAGE increases endothelin production (PMID:12808450). This is Abeta pathophysiology, not intrinsic APP function. Reason: Over-annotation - specifically Abeta function. Supporting Evidence: PMID:12808450 RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030546 signaling receptor activator activity | IDA PMID:11316806 Amyloid-beta induces chemotaxis and oxidant stress by acting... | ACCEPT | Summary: Abeta42 activates FPR2 (formyl peptide receptor 2), inducing chemotaxis and oxidant stress in phagocytes (PMID:11316806). Note: this is primarily an Abeta cleavage product function. Reason: Supported by PMID:11316806, though applies to Abeta rather than full-length APP. Supporting Evidence: PMID:11316806 2001 Apr 20. Amyloid-beta induces chemotaxis and oxidant stress by acting at formylpeptide receptor 2, a G protein-coupled receptor expressed in phagocytes and brain. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005798 Golgi-associated vesicle | IDA PMID:23931995 Activity-induced convergence of APP and BACE-1 in acidic mic... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:23931995 Activity-induced convergence of APP and BACE-1 in acidic microdomains via an endocytosis-dependent pathway. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0055037 recycling endosome | IDA PMID:23931995 Activity-induced convergence of APP and BACE-1 in acidic mic... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:23931995 Activity-induced convergence of APP and BACE-1 in acidic microdomains via an endocytosis-dependent pathway. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005769 early endosome | IDA PMID:25592972 An aberrant sugar modification of BACE1 blocks its lysosomal... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:25592972 An aberrant sugar modification of BACE1 blocks its lysosomal targeting in Alzheimer's disease. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050890 cognition | IDA PMID:25592972 An aberrant sugar modification of BACE1 blocks its lysosomal... | ACCEPT | Summary: APP is required for normal cognition. APP knockout mice show cognitive deficits that worsen with age (PMID:10188929, PMID:25592972). Reason: Core function - central to understanding APP's physiological role. Supporting Evidence: PMID:25592972 An aberrant sugar modification of BACE1 blocks its lysosomal targeting in Alzheimer's disease. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:16227578 F-spondin interaction with the apolipoprotein E receptor Apo... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:16227578 F-spondin interaction with the apolipoprotein E receptor ApoEr2 affects processing of amyloid precursor protein. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0009986 cell surface | IDA PMID:16227578 F-spondin interaction with the apolipoprotein E receptor Apo... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:16227578 F-spondin interaction with the apolipoprotein E receptor ApoEr2 affects processing of amyloid precursor protein. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:21084623 Identification of NEEP21 as a Γ-amyloid precursor protein-in... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:21084623 Identification of NEEP21 as a Γ-amyloid precursor protein-interacting protein in vivo that modulates amyloidogenic processing in vitro. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:20637285 Megalin interacts with APP and the intracellular adapter pro... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:20637285 2010 Jul 14. Megalin interacts with APP and the intracellular adapter protein FE65 in neurons. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050750 low-density lipoprotein particle receptor binding | IPI PMID:22383525 Low-density lipoprotein receptor represents an apolipoprotei... | ACCEPT | Summary: APP interacts with LRP1, ApoER2, and LDLR family members. These interactions regulate APP trafficking and link APP to reelin signaling pathway (PMID:22383525, App-deep-research-perplexity.md). Reason: Well-documented interactions with functional significance. Supporting Evidence: PMID:22383525 2012 Mar 1. Low-density lipoprotein receptor represents an apolipoprotein E-independent pathway of AΞ² uptake and degradation by astrocytes. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007613 memory | TAS PMID:19118188 Picomolar amyloid-beta positively modulates synaptic plastic... | ACCEPT | Summary: APP is required for normal memory. APP knockout mice show age-related cognitive deficits. sAPPalpha and picomolar Abeta enhance memory while Abeta oligomers impair memory (PMID:10188929, PMID:19118188, PMID:18568035). Reason: Core function supported by behavioral studies in knockout mice. Supporting Evidence: PMID:19118188 Picomolar amyloid-beta positively modulates synaptic plasticity and memory in hippocampus. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060291 long-term synaptic potentiation | TAS PMID:19118188 Picomolar amyloid-beta positively modulates synaptic plastic... | ACCEPT | Summary: APP is involved in LTP. APP knockout mice show impaired LTP (PMID:10188929). sAPPalpha can rescue LTP deficits (PMID:19118188, App-deep-research-perplexity.md). Reason: Core function supported by knockout and rescue experiments. Supporting Evidence: PMID:19118188 Picomolar amyloid-beta positively modulates synaptic plasticity and memory in hippocampus. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:27460146 VPS35 regulates cell surface recycling and signaling of dopa... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:27460146 Epub 2016 May 21. VPS35 regulates cell surface recycling and signaling of dopamine receptor D1. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005911 cell-cell junction | IDA PMID:23793062 The lymphoid lineage-specific actin-uncapping protein Rltpr ... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:23793062 The lymphoid lineage-specific actin-uncapping protein Rltpr is essential for costimulation via CD28 and the development of regulatory T cells. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043235 receptor complex | ISO PMID:23382219 Structural basis for endosomal trafficking of diverse transm... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:23382219 Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030134 COPII-coated ER to Golgi transport vesicle | IDA PMID:19966784 Sec24b selectively sorts Vangl2 to regulate planar cell pola... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:19966784 2009 Dec 6. Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closure. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010971 positive regulation of G2/M transition of mitotic cell cycle | IMP PMID:15561424 Lengthening of G2/mitosis in cortical precursors from mice l... | KEEP AS NON CORE | Summary: APP affects cell cycle progression in cortical precursors. APP knockout lengthens G2/M phase (PMID:15561424). Reason: Supported by experimental evidence but not core neuronal function. Supporting Evidence: PMID:15561424 In APP-deficient cortical precursors, the duration of mitosis is increased and a higher proportion of cortical precursor cells contained nuclei in late G2 file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:16314516 Amyloid precursor proteins anchor CPEB to membranes and prom... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:16314516 Amyloid precursor proteins anchor CPEB to membranes and promote polyadenylation-induced translation. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:20497468 Interaction of a novel mitochondrial protein, 4-nitrophenylp... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:20497468 Interaction of a novel mitochondrial protein, 4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1), with the amyloid precursor protein family. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0016020 membrane | IDA PMID:10845772 Developmental regulation of amyloid precursor protein at the... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:10845772 Developmental regulation of amyloid precursor protein at the neuromuscular junction in mouse skeletal muscle. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0016020 membrane | IDA PMID:15886206 Spatial segregation of gamma-secretase and substrates in dis... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:15886206 2005 May 10. Spatial segregation of gamma-secretase and substrates in distinct membrane domains. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0016020 membrane | IDA PMID:9535056 Profiles of amyloid precursor and presenilin 2-like proteins... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:9535056 Profiles of amyloid precursor and presenilin 2-like proteins are correlated during development of the mouse hypothalamus. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:21795536 LRAD3, a novel low-density lipoprotein receptor family membe... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:21795536 LRAD3, a novel low-density lipoprotein receptor family member that modulates amyloid precursor protein trafficking. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | IDA PMID:15009636 Presenilin-1 and intracellular calcium stores regulate neuro... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:15009636 Presenilin-1 and intracellular calcium stores regulate neuronal glutamate uptake. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006979 response to oxidative stress | IGI PMID:16478525 Mutations in amyloid precursor protein and presenilin-1 gene... | ACCEPT | Summary: Experimental annotation (IGI) from PMID:16478525. Supported by direct experimental evidence. Reason: Experimental annotation (IGI) with literature support. Supporting Evidence: PMID:16478525 Mutations in amyloid precursor protein and presenilin-1 genes increase the basal oxidative stress in murine neuronal cells and lead to increased sensitivity to oxidative stress mediated by amyloid beta-peptide (1-42), HO and kainic acid: implications for Alzheimer's disease. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0051402 neuron apoptotic process | IGI PMID:16478525 Mutations in amyloid precursor protein and presenilin-1 gene... | KEEP AS NON CORE | Summary: APP products have complex effects on neuronal survival. C31 and AICD enhance apoptosis (PMID:15677459). Abeta induces neurotoxicity. However, sAPPalpha is neuroprotective (PMID:16478525, App-deep-research-perplexity.md). Reason: Complex biology - different products have opposing effects. Supporting Evidence: PMID:16478525 Mutations in amyloid precursor protein and presenilin-1 genes increase the basal oxidative stress in murine neuronal cells and lead to increased sensitivity to oxidative stress mediated by amyloid beta-peptide (1-42), HO and kainic acid: implications for Alzheimer's disease. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008203 cholesterol metabolic process | IMP PMID:17920016 Amyloid precursor protein regulates brain apolipoprotein E a... | ACCEPT | Summary: APP regulates brain cholesterol and apolipoprotein E metabolism through LRP1 interactions (PMID:17920016). Reason: Supported by experimental evidence linking APP to lipid metabolism. Supporting Evidence: PMID:17920016 Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008203 cholesterol metabolic process | IGI PMID:17920016 Amyloid precursor protein regulates brain apolipoprotein E a... | ACCEPT | Summary: APP regulates brain cholesterol and apolipoprotein E metabolism through LRP1 interactions (PMID:17920016). Reason: Supported by experimental evidence linking APP to lipid metabolism. Supporting Evidence: PMID:17920016 Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010468 regulation of gene expression | IDA PMID:12074840 Abeta-degrading endopeptidase, neprilysin, in mouse brain: s... | ACCEPT | Summary: AICD functions as transcriptional regulator via Fe65-Tip60 complex. Regulates genes involved in neurogenesis, apoptosis, and Abeta metabolism (PMID:12074840, App-deep-research-perplexity.md). Reason: Core AICD function. Supporting Evidence: PMID:12074840 Abeta-degrading endopeptidase, neprilysin, in mouse brain: synaptic and axonal localization inversely correlating with Abeta pathology. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008088 axo-dendritic transport | IGI PMID:20829454 Tau reduction prevents Abeta-induced defects in axonal trans... | ACCEPT | Summary: APP functions as kinesin-1 membrane receptor, mediating axonal transport of BACE1, presenilin-1 and other cargo. AICD interacts with kinesin light chains (PMID:11740561, PMID:20829454, UniProt P12023). Reason: Core function - APP is a well-characterized cargo receptor for axonal transport. Supporting Evidence: PMID:20829454 Tau reduction prevents Abeta-induced defects in axonal transport. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:18278038 A TAG1-APP signalling pathway through Fe65 negatively modula... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:18278038 A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045665 negative regulation of neuron differentiation | IDA PMID:18278038 A TAG1-APP signalling pathway through Fe65 negatively modula... | ACCEPT | Summary: Full-length APP with TAG1 and Fe65 negatively modulates neurogenesis. AICD overexpression suppresses adult hippocampal neurogenesis (PMID:18278038, App-deep-research-perplexity.md). Reason: Supported by evidence - different APP products have opposing effects on neurogenesis. Supporting Evidence: PMID:18278038 A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045665 negative regulation of neuron differentiation | IGI PMID:18278038 A TAG1-APP signalling pathway through Fe65 negatively modula... | ACCEPT | Summary: Full-length APP with TAG1 and Fe65 negatively modulates neurogenesis. AICD overexpression suppresses adult hippocampal neurogenesis (PMID:18278038, App-deep-research-perplexity.md). Reason: Supported by evidence - different APP products have opposing effects on neurogenesis. Supporting Evidence: PMID:18278038 A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:17727637 Characterization of the adaptor protein ARH expression in th... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:17727637 Epub 2007 Aug 28. Characterization of the adaptor protein ARH expression in the brain and ARH molecular interactions. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:17121854 Essential roles for Fe65, Alzheimer amyloid precursor-bindin... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:17121854 Nov 22. Essential roles for Fe65, Alzheimer amyloid precursor-binding protein, in the cellular response to DNA damage. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IGI PMID:15944124 Presenilin-dependent transcriptional control of the Abeta-de... | ACCEPT | Summary: AICD-Fe65-Tip60 complex activates transcription of target genes including neprilysin (PMID:15944124, App-deep-research-perplexity.md). Reason: Core AICD signaling function supported by mechanistic evidence. Supporting Evidence: PMID:15944124 Neprilysin activity is restored by transient expression of PS1 or PS2 and by expression of the amyloid intracellular domain (AICD), which is cogenerated with Abeta, during gamma-secretase cleavage of betaAPP file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:15944124 Presenilin-dependent transcriptional control of the Abeta-de... | ACCEPT | Summary: AICD-Fe65-Tip60 complex activates transcription of target genes including neprilysin (PMID:15944124, App-deep-research-perplexity.md). Reason: Core AICD signaling function supported by mechanistic evidence. Supporting Evidence: PMID:15944124 Neprilysin gene promoters are transactivated by AICDs from APP-like proteins (APP, APLP1, and APLP2), but not by Abeta or by the gamma-secretase cleavage products of Notch, N- or E- cadherins file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006468 protein phosphorylation | IMP PMID:16025111 Regulation of NMDA receptor trafficking by amyloid-beta. | REMOVE | Summary: MISANNOTATION: APP does NOT catalyze phosphorylation. PMID:16025111 describes DEPHOSPHORYLATION of NR2B by phosphatases PP2B and STEP, triggered by Abeta. APP has no kinase activity (UniProt P12023). Reason: Incorrect annotation - APP triggers dephosphorylation, not phosphorylation, and has no kinase activity. Supporting Evidence: PMID:16025111 Regulation of NMDA receptor trafficking by amyloid-beta. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006897 endocytosis | IMP PMID:16025111 Regulation of NMDA receptor trafficking by amyloid-beta. | ACCEPT | Summary: APP undergoes clathrin-mediated endocytosis via its YENPTY motif. APP also regulates NMDA receptor endocytosis through Abeta-mediated signaling (PMID:16025111, UniProt P12023). Reason: Core function - APP endocytosis is essential for its processing and signaling. Supporting Evidence: PMID:16025111 Regulation of NMDA receptor trafficking by amyloid-beta. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0035235 ionotropic glutamate receptor signaling pathway | IMP PMID:16025111 Regulation of NMDA receptor trafficking by amyloid-beta. | ACCEPT | Summary: IBA annotation. APP processing affects NMDA receptor trafficking and function. Abeta promotes NMDA receptor endocytosis via alpha7 nicotinic receptor, PP2B and STEP pathway (PMID:16025111). sAPPalpha facilitates NMDAR currents (App-deep-research-perplexity.md). Reason: Supported by mechanistic studies showing APP/Abeta regulation of NMDAR trafficking. Supporting Evidence: PMID:16025111 Regulation of NMDA receptor trafficking by amyloid-beta. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043005 neuron projection | IDA PMID:16301330 Coordinated transport of phosphorylated amyloid-beta precurs... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:16301330 The accumulation of JIP-1 and pAPP in neurites requires kinesin-1 file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006417 regulation of translation | IDA PMID:16314516 Amyloid precursor proteins anchor CPEB to membranes and prom... | ACCEPT | Summary: APP anchors CPEB1 to membranes and promotes polyadenylation-induced translation (PMID:16314516). Reason: Supported by mechanistic evidence for APP-CPEB interaction. Supporting Evidence: PMID:16314516 Amyloid precursor proteins anchor CPEB to membranes and promote polyadenylation-induced translation. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0180011 cytosolic mRNA polyadenylation | IDA PMID:16314516 Amyloid precursor proteins anchor CPEB to membranes and prom... | ACCEPT | Summary: APP promotes cytoplasmic polyadenylation via CPEB1 interaction (PMID:16314516). Reason: Supported by mechanistic evidence. Supporting Evidence: PMID:16314516 Amyloid precursor proteins anchor CPEB to membranes and promote polyadenylation-induced translation. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005794 Golgi apparatus | IDA PMID:16018997 The ciliary rootlet interacts with kinesin light chains and ... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:16018997 The ciliary rootlet interacts with kinesin light chains and may provide a scaffold for kinesin-1 vesicular cargos. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0035253 ciliary rootlet | IDA PMID:16018997 The ciliary rootlet interacts with kinesin light chains and ... | KEEP AS NON CORE | Summary: APP was reported enriched along rootletin fibers and recruited along ciliary rootlets in a kinesin/rootletin trafficking study. Reason: The IDA evidence supports ciliary rootlet localization/recruitment, but this is an unusual trafficking-associated component rather than a core APP localization such as membrane, endosome, axon, dendrite, or synapse. Supporting Evidence: PMID:16018997 APP and presenilin 1 along ciliary rootlets |
| GO:0001967 suckling behavior | IGI PMID:9461064 Generation of APLP2 KO mice and early postnatal lethality in... | KEEP AS NON CORE | Summary: APP/APLP2 double knockouts die postnatally with suckling defects (PMID:9461064). Reason: Non-core - reflects severe nervous system dysfunction in double KO. Supporting Evidence: PMID:9461064 Approximately 80% of double KO mice die within the first week after birth, suggesting that APLP2 and APP are required for early postnatal development file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007617 mating behavior | IGI PMID:9461064 Generation of APLP2 KO mice and early postnatal lethality in... | KEEP AS NON CORE | Summary: APP/APLP2 double knockouts show mating behavior deficits (PMID:9461064). Reflects pleiotropic effects of APP family loss. Reason: Non-core - behavioral consequence of nervous system dysfunction. Supporting Evidence: PMID:9461064 Adult double KO mice mate poorly, despite apparent normal ovarian and testicular development file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007626 locomotory behavior | IGI PMID:9461064 Generation of APLP2 KO mice and early postnatal lethality in... | KEEP AS NON CORE | Summary: Locomotory defects in App-family mutants are a downstream consequence of disrupted neuronal/synaptic function, not a core APP molecular function. Reason: Distal behavioural phenotype of APP loss; non-core per the behaviour-annotation rubric. Supporting Evidence: PMID:9461064 show difficulty in righting, ataxia, spinning behavior, and a head tilt, suggesting a deficit in balance and/or strength |
| GO:0008344 adult locomotory behavior | IMP PMID:8001115 Behavioral and anatomical deficits in mice homozygous for a ... | KEEP AS NON CORE | Summary: Locomotor and balance deficits (righting difficulty, ataxia, spinning) in App and App-family knockout mice are distal neurological consequences of impaired APP synaptic/neuronal function, not a direct molecular activity of APP. Reason: Phenotype-driven behavioural readout downstream of APP's neuronal role; retained as non-core per the behaviour-annotation rubric (cf. Tuba1a). Supporting Evidence: PMID:8001115 Behavioral and anatomical deficits in mice homozygous for a modified beta-amyloid precursor protein gene. |
| GO:0016199 axon midline choice point recognition | IMP PMID:8001115 Behavioral and anatomical deficits in mice homozygous for a ... | ACCEPT | Summary: Experimental annotation (IMP) from PMID:8001115. Supported by direct experimental evidence. Reason: Experimental annotation (IMP) with literature support. Supporting Evidence: PMID:8001115 Behavioral and anatomical deficits in mice homozygous for a modified beta-amyloid precursor protein gene. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030900 forebrain development | IMP PMID:8001115 Behavioral and anatomical deficits in mice homozygous for a ... | ACCEPT | Summary: APP family is essential for forebrain development. Triple knockout (APP/APLP1/APLP2) mice show cortical dysplasia resembling type 2 lissencephaly (PMID:15385965, PMID:10200318). Reason: Core developmental function demonstrated by knockout phenotypes. Supporting Evidence: PMID:8001115 Behavioral and anatomical deficits in mice homozygous for a modified beta-amyloid precursor protein gene. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0031175 neuron projection development | IDA PMID:8083748 Peptides containing the RERMS sequence of amyloid beta/A4 pr... | ACCEPT | Summary: IBA annotation. APP and its proteolytic products regulate both axon and dendrite development. sAPPalpha promotes neurite outgrowth. Well-supported by APP knockout phenotypes (PMID:8083748, PMID:9390996, App-deep-research-perplexity.md). Reason: Core biological process. Multiple lines of evidence support APP role in neurite development. Supporting Evidence: PMID:8083748 Peptides containing the RERMS sequence of amyloid beta/A4 protein precursor bind cell surface and promote neurite extension. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:8207383 Embryonic expression pattern of amyloid protein precursor su... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:8207383 Immunohistochemical analysis revealed the temporal and spatial expression pattern of the amyloid protein precursor (APP) during the development of the mouse embryo file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050885 neuromuscular process controlling balance | IGI PMID:9461064 Generation of APLP2 KO mice and early postnatal lethality in... | ACCEPT | Summary: APP knockout affects balance (PMID:9461064). APP is important for neuromuscular junction function (App-deep-research-perplexity.md). Reason: Supported by knockout phenotypes and NMJ localization. Supporting Evidence: PMID:9461064 show difficulty in righting, ataxia, spinning behavior, and a head tilt, suggesting a deficit in balance and/or strength file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0051563 smooth endoplasmic reticulum calcium ion homeostasis | IGI PMID:12431992 Capacitive calcium entry is directly attenuated by mutant pr... | ACCEPT | Summary: Experimental annotation (IGI) from PMID:12431992. Supported by direct experimental evidence. Reason: Experimental annotation (IGI) with literature support. Supporting Evidence: PMID:12431992 Nov 12. Capacitive calcium entry is directly attenuated by mutant presenilin-1, independent of the expression of the amyloid precursor protein. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:16227582 Transforming growth factor beta2 is a neuronal death-inducin... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' annotation. APP interacts with numerous specific proteins (Fe65, X11/Mint, Dab1, etc.) via its YENPTY motif. These specific interactions should be annotated instead of generic protein binding. Reason: Too generic - specific binding partners (PTB domain proteins, secretases, etc.) should be annotated. Supporting Evidence: PMID:16227582 Transforming growth factor beta2 is a neuronal death-inducing ligand for amyloid-beta precursor protein. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005737 cytoplasm | IDA PMID:10845772 Developmental regulation of amyloid precursor protein at the... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:10845772 Developmental regulation of amyloid precursor protein at the neuromuscular junction in mouse skeletal muscle. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006878 intracellular copper ion homeostasis | IMP PMID:10526140 Copper levels are increased in the cerebral cortex and liver... | ACCEPT | Summary: APP binds copper and affects copper homeostasis. APP knockout increases brain copper levels. APP delivers copper to GPC1 (PMID:10526140, PMID:15447675, UniProt P12023). Reason: Core function supported by knockout phenotypes and biochemical evidence. Supporting Evidence: PMID:10526140 Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006878 intracellular copper ion homeostasis | IGI PMID:15447675 Gene knockout of amyloid precursor protein and amyloid precu... | ACCEPT | Summary: APP binds copper and affects copper homeostasis. APP knockout increases brain copper levels. APP delivers copper to GPC1 (PMID:10526140, PMID:15447675, UniProt P12023). Reason: Core function supported by knockout phenotypes and biochemical evidence. Supporting Evidence: PMID:15447675 Gene knockout of amyloid precursor protein and amyloid precursor-like protein-2 increases cellular copper levels in primary mouse cortical neurons and embryonic fibroblasts. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008344 adult locomotory behavior | IMP PMID:10188929 Age-related cognitive deficits, impaired long-term potentiat... | KEEP AS NON CORE | Summary: Locomotor and balance deficits (righting difficulty, ataxia, spinning) in App and App-family knockout mice are distal neurological consequences of impaired APP synaptic/neuronal function, not a direct molecular activity of APP. Reason: Phenotype-driven behavioural readout downstream of APP's neuronal role; retained as non-core per the behaviour-annotation rubric (cf. Tuba1a). Supporting Evidence: PMID:10188929 Another six mice from the same population that were showing weight loss and hypolocomotor activity exhibited a marked reactive gliosis |
| GO:0008344 adult locomotory behavior | IMP PMID:7758106 beta-Amyloid precursor protein-deficient mice show reactive ... | KEEP AS NON CORE | Summary: Locomotor and balance deficits (righting difficulty, ataxia, spinning) in App and App-family knockout mice are distal neurological consequences of impaired APP synaptic/neuronal function, not a direct molecular activity of APP. Reason: Phenotype-driven behavioural readout downstream of APP's neuronal role; retained as non-core per the behaviour-annotation rubric (cf. Tuba1a). Supporting Evidence: PMID:7758106 beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. |
| GO:0008344 adult locomotory behavior | IMP PMID:9754878 Neurobehavioral development, adult openfield exploration and... | KEEP AS NON CORE | Summary: Locomotor and balance deficits (righting difficulty, ataxia, spinning) in App and App-family knockout mice are distal neurological consequences of impaired APP synaptic/neuronal function, not a direct molecular activity of APP. Reason: Phenotype-driven behavioural readout downstream of APP's neuronal role; retained as non-core per the behaviour-annotation rubric (cf. Tuba1a). Supporting Evidence: PMID:9754878 Neurobehavioral development, adult openfield exploration and swimming navigation learning in mice with a modified beta-amyloid precursor protein gene. |
| GO:0016358 dendrite development | IMP PMID:10188929 Age-related cognitive deficits, impaired long-term potentiat... | ACCEPT | Summary: APP regulates dendrite development. APP knockout mice show reduced dendritic marker density. APP is localized to dendrites and affects dendritic spine plasticity (PMID:10188929, PMID:9390996, App-deep-research-perplexity.md). Reason: Core function supported by knockout phenotypes. Supporting Evidence: PMID:10188929 a profound loss of immunoreactivities for the presynaptic terminal vesicle marker proteins synaptophysin and synapsin and the dendritic marker microtubule-associated protein-2 in many brain areas file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0016358 dendrite development | IGI PMID:15689559 Defective neuromuscular synapses in mice lacking amyloid pre... | ACCEPT | Summary: APP regulates dendrite development. APP knockout mice show reduced dendritic marker density. APP is localized to dendrites and affects dendritic spine plasticity (PMID:10188929, PMID:9390996, App-deep-research-perplexity.md). Reason: Core function supported by knockout phenotypes. Supporting Evidence: PMID:15689559 Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-Like protein 2. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0031594 neuromuscular junction | IDA PMID:10845772 Developmental regulation of amyloid precursor protein at the... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:10845772 Developmental regulation of amyloid precursor protein at the neuromuscular junction in mouse skeletal muscle. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0040014 regulation of multicellular organism growth | IMP PMID:9754878 Neurobehavioral development, adult openfield exploration and... | ACCEPT | Summary: Experimental annotation (IMP) from PMID:9754878. Supported by direct experimental evidence. Reason: Experimental annotation (IMP) with literature support. Supporting Evidence: PMID:9754878 Neurobehavioral development, adult openfield exploration and swimming navigation learning in mice with a modified beta-amyloid precursor protein gene. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048669 collateral sprouting in absence of injury | IGI PMID:15689559 Defective neuromuscular synapses in mice lacking amyloid pre... | ACCEPT | Summary: APP affects axon sprouting at NMJ (PMID:15689559). Related to APP's role in axon guidance and NMJ development. Reason: Supported by experimental evidence. Supporting Evidence: PMID:15689559 Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-Like protein 2. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0051124 synaptic assembly at neuromuscular junction | IGI PMID:15689559 Defective neuromuscular synapses in mice lacking amyloid pre... | ACCEPT | Summary: APP is required for normal NMJ formation. APP interacts with LRP4 and promotes MuSK phosphorylation. APP/APLP2 double KO has severe NMJ defects (PMID:15689559, App-deep-research-perplexity.md). Reason: Core function at NMJ supported by knockout phenotypes. Supporting Evidence: PMID:15689559 Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-Like protein 2. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007409 axonogenesis | IMP PMID:9390996 The beta-amyloid precursor protein of Alzheimer's disease en... | ACCEPT | Summary: IBA annotation. Full-length APP regulates axon development. APP knockout mice show defects in axonogenesis. sAPPalpha promotes neurite outgrowth while full-length APP with Fe65/Mena inhibits branching to ensure directional growth (PMID:10188929, App-deep-research-perplexity.md). Reason: Core biological process. Well-supported by knockout studies and mechanistic understanding. Supporting Evidence: PMID:9390996 The beta-amyloid precursor protein of Alzheimer's disease enhances neuron viability and modulates neuronal polarity. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0016020 membrane | IDA PMID:12927782 Both raft- and non-raft proteins associate with CHAPS-insolu... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:12927782 Both raft- and non-raft proteins associate with CHAPS-insoluble complexes: some APP in large complexes. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0016322 neuron remodeling | IMP PMID:10219973 Mechanisms contributing to the deficits in hippocampal synap... | ACCEPT | Summary: APP regulates structural synaptic plasticity including dendritic spine density and morphology. APP deficiency impairs synaptic remodeling (PMID:10219973, App-deep-research-perplexity.md). Reason: Supported by evidence for APP role in structural plasticity. Supporting Evidence: PMID:10219973 Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0016358 dendrite development | IMP PMID:9390996 The beta-amyloid precursor protein of Alzheimer's disease en... | ACCEPT | Summary: APP regulates dendrite development. APP knockout mice show reduced dendritic marker density. APP is localized to dendrites and affects dendritic spine plasticity (PMID:10188929, PMID:9390996, App-deep-research-perplexity.md). Reason: Core function supported by knockout phenotypes. Supporting Evidence: PMID:9390996 The beta-amyloid precursor protein of Alzheimer's disease enhances neuron viability and modulates neuronal polarity. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045177 apical part of cell | IDA PMID:15561424 Lengthening of G2/mitosis in cortical precursors from mice l... | ACCEPT | Summary: APP localizes apically in cortical precursor cells during interphase. Lopez-Sanchez et al. (2005) showed APP protein concentrated in apical domains. Reason: Supported by localization studies. Supporting Evidence: PMID:15561424 APP protein is concentrated within their apical domains during interphase file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045931 positive regulation of mitotic cell cycle | IMP PMID:15561424 Lengthening of G2/mitosis in cortical precursors from mice l... | KEEP AS NON CORE | Summary: APP affects cell cycle in neural precursors. Lopez-Sanchez et al. (2005) showed APP knockout lengthens mitosis in cortical precursors. Reason: Non-core function - APP is primarily studied in post-mitotic neurons. Supporting Evidence: PMID:15561424 during cortical development APP plays a role in controlling cell cycle progression, particularly affecting G2 and mitosis file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050803 regulation of synapse structure or activity | IMP PMID:10219973 Mechanisms contributing to the deficits in hippocampal synap... | ACCEPT | Summary: Experimental annotation (IMP) from PMID:10219973. Supported by direct experimental evidence. Reason: Experimental annotation (IMP) with literature support. Supporting Evidence: PMID:10219973 Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0051233 spindle midzone | IDA PMID:15561424 Lengthening of G2/mitosis in cortical precursors from mice l... | KEEP AS NON CORE | Summary: APP localizes to spindle midzone during mitosis in cortical precursors. Lopez-Sanchez et al. (2005) showed APP re-localizes during mitosis. Reason: Non-core - atypical localization in dividing cells. Supporting Evidence: PMID:15561424 during mitosis, APP re-localizes to the peripheral space surrounding the metaphase plate file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008542 visual learning | IMP PMID:10338291 No hippocampal neuron or synaptic bouton loss in learning-im... | ACCEPT | Summary: APP knockout mice show visual learning deficits (PMID:10338291). Reflects cognitive impairment. Reason: Supported by behavioral studies. Supporting Evidence: PMID:10338291 No hippocampal neuron or synaptic bouton loss in learning-impaired aged beta-amyloid precursor protein-null mice. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030900 forebrain development | IMP PMID:10200318 Genetic background changes the pattern of forebrain commissu... | ACCEPT | Summary: APP family is essential for forebrain development. Triple knockout (APP/APLP1/APLP2) mice show cortical dysplasia resembling type 2 lissencephaly (PMID:15385965, PMID:10200318). Reason: Core developmental function demonstrated by knockout phenotypes. Supporting Evidence: PMID:10200318 independently of genetic background, both lack and underexpression of betaAPP are associated with reduced brain weight and reduced size of forebrain commissures file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008088 axo-dendritic transport | IMP PMID:11740561 Kinesin-mediated axonal transport of a membrane compartment ... | ACCEPT | Summary: APP functions as kinesin-1 membrane receptor, mediating axonal transport of BACE1, presenilin-1 and other cargo. AICD interacts with kinesin light chains (PMID:11740561, PMID:20829454, UniProt P12023). Reason: Core function - APP is a well-characterized cargo receptor for axonal transport. Supporting Evidence: PMID:11740561 The fast anterograde axonal transport of this compartment is mediated by APP and kinesin-I file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030424 axon | IDA PMID:11740561 Kinesin-mediated axonal transport of a membrane compartment ... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:11740561 Proteolytic processing of APP can occur in the compartment in vitro and in vivo in axons file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030424 axon | IDA PMID:15745965 Axonal transport, amyloid precursor protein, kinesin-1, and ... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:15745965 Axonal transport, amyloid precursor protein, kinesin-1, and the processing apparatus: revisited. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0031410 cytoplasmic vesicle | IDA PMID:11740561 Kinesin-mediated axonal transport of a membrane compartment ... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:11740561 we identify an axonal membrane compartment that contains APP, beta-secretase and presenilin-1 file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0031410 cytoplasmic vesicle | IDA PMID:15745965 Axonal transport, amyloid precursor protein, kinesin-1, and ... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:15745965 Axonal transport, amyloid precursor protein, kinesin-1, and the processing apparatus: revisited. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0016020 membrane | TAS PMID:11877420 Tyrosine phosphorylation of the beta-amyloid precursor prote... | ACCEPT | Summary: Cellular component annotation supported by APP trafficking and localization studies. APP is found in multiple cellular compartments consistent with its complex processing pathway (UniProt P12023, App-deep-research-perplexity.md). Reason: Well-documented localization consistent with APP biology. Supporting Evidence: PMID:11877420 2002 Mar 4. Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic tail promotes interaction with Shc. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0098631 cell adhesion mediator activity | NAS | NEW | Summary: APP-family trans-interaction promotes cell-cell adhesion, making cell adhesion mediator activity a more specific proposed molecular function than generic identical protein binding. Reason: PMID:16193067 directly supports APP-family homo/heterodimerization and trans-cellular adhesion; this term better captures the biologically informative molecular role used in core_functions. Supporting Evidence: PMID:16193067 trans-interaction of APP family proteins promotes cell-cell adhesion file:mouse/App/App-deep-research-falcon.md APP has a large luminal/extracellular N-terminus, E1/E2 regions involved in dimerization/adhesion |
| GO:0005507 copper ion binding | NAS | NEW | Summary: APP has a copper-binding ectodomain/CuBD and the mouse UniProt record carries amyloid copper-binding InterPro domains; copper binding is a specific molecular function not captured by the broader transition-metal binding annotation. Reason: The term is directly supported by APP domain architecture and mouse genetic/biochemical literature. It is retained as a conservative NEW molecular-function proposal rather than relying on the broader transition metal ion binding parent. Supporting Evidence: PMID:10526140 Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice. file:mouse/App/App-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
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