BACE1 encodes beta-secretase 1, a single-pass type I membrane aspartyl endopeptidase that initiates amyloidogenic processing of amyloid precursor protein. BACE1 cleaves APP at the beta-secretase site to generate soluble beta-cleaved APP and the membrane C-terminal fragment that is subsequently processed by gamma-secretase to produce amyloid-beta peptides. The enzyme is enriched in the trans-Golgi network and endosomal trafficking system, with pools at the cell surface, plasma membrane, recycling endosomes, late endosomes, and lysosomes; sorting through these compartments strongly controls access to APP and BACE1 degradation. BACE1 also cleaves other neuronal membrane substrates, contributing to synaptic, axonal, sensory, and behavioral phenotypes that are downstream of its protease and trafficking biology.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005768 endosome | IBA GO_REF:0000033 | ACCEPT | Summary: endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005768 (endosome), the IBA annotation with qualifier is_active_in from GO_REF:0000033 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0016485 protein processing | IBA GO_REF:0000033 | ACCEPT | Summary: protein processing is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0016485 (protein processing), the IBA annotation with qualifier involved_in from GO_REF:0000033 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0004190 aspartic-type endopeptidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: aspartic-type endopeptidase activity is retained as a core molecular-function annotation for BACE1; it captures activity or binding specificity within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0004190 (aspartic-type endopeptidase activity), the IBA annotation with qualifier enables from GO_REF:0000033 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: plasma membrane is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005886 (plasma membrane), the IBA annotation with qualifier is_active_in from GO_REF:0000033 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0050435 amyloid-beta metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: amyloid-beta metabolic process is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0050435 (amyloid-beta metabolic process), the IBA annotation with qualifier involved_in from GO_REF:0000033 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005802 trans-Golgi network | IBA GO_REF:0000033 | ACCEPT | Summary: trans-Golgi network is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005802 (trans-Golgi network), the IBA annotation with qualifier is_active_in from GO_REF:0000033 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0006509 membrane protein ectodomain proteolysis | IBA GO_REF:0000033 | ACCEPT | Summary: membrane protein ectodomain proteolysis is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0006509 (membrane protein ectodomain proteolysis), the IBA annotation with qualifier involved_in from GO_REF:0000033 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0004190 aspartic-type endopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: aspartic-type endopeptidase activity is retained as a core molecular-function annotation for BACE1; it captures activity or binding specificity within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0004190 (aspartic-type endopeptidase activity), the IEA annotation with qualifier enables from GO_REF:0000120 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005764 lysosome | IEA GO_REF:0000044 | ACCEPT | Summary: lysosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005764 (lysosome), the IEA annotation with qualifier located_in from GO_REF:0000044 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005768 endosome | IEA GO_REF:0000120 | ACCEPT | Summary: endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005768 (endosome), the IEA annotation with qualifier located_in from GO_REF:0000120 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005769 early endosome | IEA GO_REF:0000120 | ACCEPT | Summary: early endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005769 (early endosome), the IEA annotation with qualifier located_in from GO_REF:0000120 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005770 late endosome | IEA GO_REF:0000044 | ACCEPT | Summary: late endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005770 (late endosome), the IEA annotation with qualifier located_in from GO_REF:0000044 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | ACCEPT | Summary: endoplasmic reticulum is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005783 (endoplasmic reticulum), the IEA annotation with qualifier located_in from GO_REF:0000044 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | ACCEPT | Summary: Golgi apparatus is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005794 (Golgi apparatus), the IEA annotation with qualifier located_in from GO_REF:0000044 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: plasma membrane is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005886 (plasma membrane), the IEA annotation with qualifier located_in from GO_REF:0000120 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | ACCEPT | Summary: proteolysis is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0006508 (proteolysis), the IEA annotation with qualifier involved_in from GO_REF:0000002 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0009986 cell surface | IEA GO_REF:0000120 | ACCEPT | Summary: cell surface is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0009986 (cell surface), the IEA annotation with qualifier located_in from GO_REF:0000120 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0016020 membrane | IEA GO_REF:0000120 | ACCEPT | Summary: membrane is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0016020 (membrane), the IEA annotation with qualifier located_in from GO_REF:0000120 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0030424 axon | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: axon is retained as a non-core cellular-component/localization annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0030424 (axon), the IEA annotation with qualifier located_in from GO_REF:0000120 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0030425 dendrite | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: dendrite is retained as a non-core cellular-component/localization annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0030425 (dendrite), the IEA annotation with qualifier located_in from GO_REF:0000120 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0030659 cytoplasmic vesicle membrane | IEA GO_REF:0000044 | ACCEPT | Summary: cytoplasmic vesicle membrane is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0030659 (cytoplasmic vesicle membrane), the IEA annotation with qualifier located_in from GO_REF:0000044 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0045121 membrane raft | IEA GO_REF:0000044 | ACCEPT | Summary: membrane raft is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0045121 (membrane raft), the IEA annotation with qualifier located_in from GO_REF:0000044 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0055037 recycling endosome | IEA GO_REF:0000120 | ACCEPT | Summary: recycling endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0055037 (recycling endosome), the IEA annotation with qualifier located_in from GO_REF:0000120 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005515 protein binding | IPI PMID:10677483 Human aspartic protease memapsin 2 cleaves the beta-secretas... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:10677483 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0005515 protein binding | IPI PMID:12901838 Presenilin-1 interacts directly with the beta-site amyloid p... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:12901838 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0005515 protein binding | IPI PMID:15466887 Demonstration of BACE (beta-secretase) phosphorylation and i... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:15466887 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0005515 protein binding | IPI PMID:20354142 Proteomic identification of sorting nexin 6 as a negative re... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:20354142 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0005515 protein binding | IPI PMID:22801501 A mutation in APP protects against Alzheimer's disease and a... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:22801501 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0005515 protein binding | IPI PMID:23701002 BRI2 interacts with BACE1 and regulates its cellular levels ... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:23701002 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0005515 protein binding | IPI PMID:25957769 Clec4g (LSECtin) interacts with BACE1 and suppresses AΞ² gene... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:25957769 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0005515 protein binding | IPI PMID:26053850 The Golgi-Localized Ξ³-Ear-Containing ARF-Binding (GGA) Prote... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:26053850 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0005515 protein binding | IPI PMID:26840340 Identification of Human Islet Amyloid Polypeptide as a BACE2... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:26840340 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0005515 protein binding | IPI PMID:29507146 Ξ²-Secretase BACE1 Promotes Surface Expression and Function o... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:29507146 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0005515 protein binding | IPI PMID:30538620 Visualization of Alzheimer's Disease Related Ξ±-/Ξ²-/Ξ³-Secreta... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:30538620 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:32814053 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0004175 endopeptidase activity | IEA GO_REF:0000107 | ACCEPT | Summary: endopeptidase activity is retained as a core molecular-function annotation for BACE1; it captures activity or binding specificity within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0004175 (endopeptidase activity), the IEA annotation with qualifier enables from GO_REF:0000107 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005802 trans-Golgi network | IEA GO_REF:0000107 | ACCEPT | Summary: trans-Golgi network is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005802 (trans-Golgi network), the IEA annotation with qualifier located_in from GO_REF:0000107 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0006509 membrane protein ectodomain proteolysis | IEA GO_REF:0000120 | ACCEPT | Summary: membrane protein ectodomain proteolysis is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0006509 (membrane protein ectodomain proteolysis), the IEA annotation with qualifier involved_in from GO_REF:0000120 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0008021 synaptic vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: synaptic vesicle is retained as a non-core cellular-component/localization annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0008021 (synaptic vesicle), the IEA annotation with qualifier located_in from GO_REF:0000107 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0008233 peptidase activity | IEA GO_REF:0000107 | ACCEPT | Summary: peptidase activity is retained as a core molecular-function annotation for BACE1; it captures activity or binding specificity within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0008233 (peptidase activity), the IEA annotation with qualifier enables from GO_REF:0000107 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0010288 response to lead ion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: response to lead ion is retained as a non-core biological-process annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0010288 (response to lead ion), the IEA annotation with qualifier involved_in from GO_REF:0000107 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: cytoplasmic vesicle is retained as a non-core cellular-component/localization annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0031410 (cytoplasmic vesicle), the IEA annotation with qualifier located_in from GO_REF:0000107 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0036269 swimming behavior | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: swimming behavior is retained as a non-core biological-process annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0036269 (swimming behavior), the IEA annotation with qualifier involved_in from GO_REF:0000107 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0042987 amyloid precursor protein catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: amyloid precursor protein catabolic process is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0042987 (amyloid precursor protein catabolic process), the IEA annotation with qualifier involved_in from GO_REF:0000107 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: neuronal cell body is retained as a non-core cellular-component/localization annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0043025 (neuronal cell body), the IEA annotation with qualifier located_in from GO_REF:0000107 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0043523 regulation of neuron apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: regulation of neuron apoptotic process is retained as a non-core biological-process annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0043523 (regulation of neuron apoptotic process), the IEA annotation with qualifier involved_in from GO_REF:0000107 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0050435 amyloid-beta metabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: amyloid-beta metabolic process is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0050435 (amyloid-beta metabolic process), the IEA annotation with qualifier involved_in from GO_REF:0000107 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0050804 modulation of chemical synaptic transmission | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: modulation of chemical synaptic transmission is retained as a non-core biological-process annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0050804 (modulation of chemical synaptic transmission), the IEA annotation with qualifier involved_in from GO_REF:0000107 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0050966 detection of mechanical stimulus involved in sensory perception of pain | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: detection of mechanical stimulus involved in sensory perception of pain is retained as a non-core biological-process annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0050966 (detection of mechanical stimulus involved in sensory perception of pain), the IEA annotation with qualifier involved_in from GO_REF:0000107 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0060134 prepulse inhibition | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: prepulse inhibition is retained as a non-core biological-process annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0060134 (prepulse inhibition), the IEA annotation with qualifier involved_in from GO_REF:0000107 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0071280 cellular response to copper ion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: cellular response to copper ion is retained as a non-core biological-process annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0071280 (cellular response to copper ion), the IEA annotation with qualifier involved_in from GO_REF:0000107 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0071287 cellular response to manganese ion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: cellular response to manganese ion is retained as a non-core biological-process annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0071287 (cellular response to manganese ion), the IEA annotation with qualifier involved_in from GO_REF:0000107 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0098686 hippocampal mossy fiber to CA3 synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: hippocampal mossy fiber to CA3 synapse is retained as a non-core cellular-component/localization annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0098686 (hippocampal mossy fiber to CA3 synapse), the IEA annotation with qualifier is_active_in from GO_REF:0000107 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0098793 presynapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: presynapse is retained as a non-core cellular-component/localization annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0098793 (presynapse), the IEA annotation with qualifier is_active_in from GO_REF:0000107 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0099171 presynaptic modulation of chemical synaptic transmission | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: presynaptic modulation of chemical synaptic transmission is retained as a non-core biological-process annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0099171 (presynaptic modulation of chemical synaptic transmission), the IEA annotation with qualifier involved_in from GO_REF:0000107 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0140448 signaling receptor ligand precursor processing | IEA GO_REF:0000107 | ACCEPT | Summary: signaling receptor ligand precursor processing is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0140448 (signaling receptor ligand precursor processing), the IEA annotation with qualifier involved_in from GO_REF:0000107 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:1904646 cellular response to amyloid-beta | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: cellular response to amyloid-beta is retained as a non-core biological-process annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:1904646 (cellular response to amyloid-beta), the IEA annotation with qualifier involved_in from GO_REF:0000107 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:1990418 response to insulin-like growth factor stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: response to insulin-like growth factor stimulus is retained as a non-core biological-process annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:1990418 (response to insulin-like growth factor stimulus), the IEA annotation with qualifier involved_in from GO_REF:0000107 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0008798 beta-aspartyl-peptidase activity | TAS Reactome:R-HSA-5692495 | ACCEPT | Summary: beta-aspartyl-peptidase activity is retained as a core molecular-function annotation for BACE1; it captures activity or binding specificity within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0008798 (beta-aspartyl-peptidase activity), the TAS annotation with qualifier enables from Reactome:R-HSA-5692495 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0034205 amyloid-beta formation | IDA PMID:10677483 Human aspartic protease memapsin 2 cleaves the beta-secretas... | ACCEPT | Summary: amyloid-beta formation is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0034205 (amyloid-beta formation), the IDA annotation with qualifier involved_in from PMID:10677483 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: plasma membrane is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005886 (plasma membrane), the IDA annotation with qualifier located_in from GO_REF:0000052 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005768 endosome | EXP PMID:11466313 The transmembrane domain of the Alzheimer's beta-secretase (... | ACCEPT | Summary: endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005768 (endosome), the EXP annotation with qualifier located_in from PMID:11466313 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005768 endosome | EXP PMID:15886016 GGA proteins regulate retrograde transport of BACE1 from end... | ACCEPT | Summary: endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005768 (endosome), the EXP annotation with qualifier located_in from PMID:15886016 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005769 early endosome | EXP PMID:15615712 GGA proteins mediate the recycling pathway of memapsin 2 (BA... | ACCEPT | Summary: early endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005769 (early endosome), the EXP annotation with qualifier located_in from PMID:15615712 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005783 endoplasmic reticulum | EXP PMID:11466313 The transmembrane domain of the Alzheimer's beta-secretase (... | ACCEPT | Summary: endoplasmic reticulum is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005783 (endoplasmic reticulum), the EXP annotation with qualifier located_in from PMID:11466313 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005783 endoplasmic reticulum | EXP PMID:17425515 A reversible form of lysine acetylation in the ER and Golgi ... | ACCEPT | Summary: endoplasmic reticulum is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005783 (endoplasmic reticulum), the EXP annotation with qualifier located_in from PMID:17425515 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005886 plasma membrane | EXP PMID:11466313 The transmembrane domain of the Alzheimer's beta-secretase (... | ACCEPT | Summary: plasma membrane is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005886 (plasma membrane), the EXP annotation with qualifier located_in from PMID:11466313 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0009986 cell surface | EXP PMID:11466313 The transmembrane domain of the Alzheimer's beta-secretase (... | ACCEPT | Summary: cell surface is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0009986 (cell surface), the EXP annotation with qualifier located_in from PMID:11466313 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0009986 cell surface | EXP PMID:17425515 A reversible form of lysine acetylation in the ER and Golgi ... | ACCEPT | Summary: cell surface is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0009986 (cell surface), the EXP annotation with qualifier located_in from PMID:17425515 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0030659 cytoplasmic vesicle membrane | EXP PMID:11466313 The transmembrane domain of the Alzheimer's beta-secretase (... | ACCEPT | Summary: cytoplasmic vesicle membrane is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0030659 (cytoplasmic vesicle membrane), the EXP annotation with qualifier located_in from PMID:11466313 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0030659 cytoplasmic vesicle membrane | EXP PMID:15886016 GGA proteins regulate retrograde transport of BACE1 from end... | ACCEPT | Summary: cytoplasmic vesicle membrane is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0030659 (cytoplasmic vesicle membrane), the EXP annotation with qualifier located_in from PMID:15886016 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0045121 membrane raft | ISS GO_REF:0000024 | ACCEPT | Summary: membrane raft is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0045121 (membrane raft), the ISS annotation with qualifier located_in from GO_REF:0000024 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0120283 protein serine/threonine kinase binding | IPI PMID:24305806 Pharmacologic inhibition of ROCK2 suppresses amyloid-Ξ² produ... | KEEP AS NON CORE | Summary: protein serine/threonine kinase binding is retained as a non-core molecular-function annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0120283 (protein serine/threonine kinase binding), the IPI annotation with qualifier enables from PMID:24305806 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:1990000 amyloid fibril formation | TAS Reactome:R-HSA-977225 | MODIFY | Summary: amyloid fibril formation is directionally related to BACE1 biology but is not the best curation target; amyloid-beta formation, amyloid precursor protein catabolic process better captures the specific supported function or process. Reason: For GO:1990000 (amyloid fibril formation), the TAS annotation with qualifier involved_in from Reactome:R-HSA-977225 supports a relationship to BACE1, but the current term is less precise than amyloid-beta formation, amyloid precursor protein catabolic process for the evidence and for the synthesized core/non-core role of BACE1. The MODIFY action preserves the biological intent while pointing curators to the more informative GO term. Proposed replacements: amyloid-beta formation amyloid precursor protein catabolic process |
| GO:0004190 aspartic-type endopeptidase activity | IDA PMID:10531052 Beta-secretase cleavage of Alzheimer's amyloid precursor pro... | ACCEPT | Summary: aspartic-type endopeptidase activity is retained as a core molecular-function annotation for BACE1; it captures activity or binding specificity within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0004190 (aspartic-type endopeptidase activity), the IDA annotation with qualifier enables from PMID:10531052 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0016485 protein processing | IDA PMID:10531052 Beta-secretase cleavage of Alzheimer's amyloid precursor pro... | ACCEPT | Summary: protein processing is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0016485 (protein processing), the IDA annotation with qualifier involved_in from PMID:10531052 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005515 protein binding | IPI PMID:15286784 Reticulon family members modulate BACE1 activity and amyloid... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:15286784 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0034205 amyloid-beta formation | IDA PMID:24352696 MicroRNA-339-5p down-regulates protein expression of Ξ²-site ... | ACCEPT | Summary: amyloid-beta formation is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0034205 (amyloid-beta formation), the IDA annotation with qualifier involved_in from PMID:24352696 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0042987 amyloid precursor protein catabolic process | ISS PMID:20704561 The ATP-binding cassette transporter-2 (ABCA2) increases end... | ACCEPT | Summary: amyloid precursor protein catabolic process is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0042987 (amyloid precursor protein catabolic process), the ISS annotation with qualifier involved_in from PMID:20704561 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005764 lysosome | IDA PMID:23109336 BACE1 protein endocytosis and trafficking are differentially... | ACCEPT | Summary: lysosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005764 (lysosome), the IDA annotation with qualifier located_in from PMID:23109336 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005769 early endosome | IDA PMID:23109336 BACE1 protein endocytosis and trafficking are differentially... | ACCEPT | Summary: early endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005769 (early endosome), the IDA annotation with qualifier located_in from PMID:23109336 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005770 late endosome | IDA PMID:23109336 BACE1 protein endocytosis and trafficking are differentially... | ACCEPT | Summary: late endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005770 (late endosome), the IDA annotation with qualifier located_in from PMID:23109336 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005802 trans-Golgi network | IDA PMID:23109336 BACE1 protein endocytosis and trafficking are differentially... | ACCEPT | Summary: trans-Golgi network is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005802 (trans-Golgi network), the IDA annotation with qualifier located_in from PMID:23109336 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0009986 cell surface | IDA PMID:23109336 BACE1 protein endocytosis and trafficking are differentially... | ACCEPT | Summary: cell surface is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0009986 (cell surface), the IDA annotation with qualifier located_in from PMID:23109336 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005515 protein binding | IPI PMID:15886016 GGA proteins regulate retrograde transport of BACE1 from end... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:15886016 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0005769 early endosome | IDA PMID:15886016 GGA proteins regulate retrograde transport of BACE1 from end... | ACCEPT | Summary: early endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005769 (early endosome), the IDA annotation with qualifier located_in from PMID:15886016 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005802 trans-Golgi network | IDA PMID:15886016 GGA proteins regulate retrograde transport of BACE1 from end... | ACCEPT | Summary: trans-Golgi network is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005802 (trans-Golgi network), the IDA annotation with qualifier located_in from PMID:15886016 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0009986 cell surface | IDA PMID:15886016 GGA proteins regulate retrograde transport of BACE1 from end... | ACCEPT | Summary: cell surface is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0009986 (cell surface), the IDA annotation with qualifier located_in from PMID:15886016 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0055037 recycling endosome | IDA PMID:15886016 GGA proteins regulate retrograde transport of BACE1 from end... | ACCEPT | Summary: recycling endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0055037 (recycling endosome), the IDA annotation with qualifier located_in from PMID:15886016 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005764 lysosome | IDA PMID:16033761 BACE is degraded via the lysosomal pathway. | ACCEPT | Summary: lysosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005764 (lysosome), the IDA annotation with qualifier located_in from PMID:16033761 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005764 lysosome | IDA PMID:27084579 SEPT8 modulates Ξ²-amyloidogenic processing of APP by affecti... | ACCEPT | Summary: lysosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005764 (lysosome), the IDA annotation with qualifier located_in from PMID:27084579 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005764 lysosome | IDA PMID:27302062 The Endosome-associated Deubiquitinating Enzyme USP8 Regulat... | ACCEPT | Summary: lysosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005764 (lysosome), the IDA annotation with qualifier located_in from PMID:27302062 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005769 early endosome | IDA PMID:27084579 SEPT8 modulates Ξ²-amyloidogenic processing of APP by affecti... | ACCEPT | Summary: early endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005769 (early endosome), the IDA annotation with qualifier located_in from PMID:27084579 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005769 early endosome | IDA PMID:27302062 The Endosome-associated Deubiquitinating Enzyme USP8 Regulat... | ACCEPT | Summary: early endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005769 (early endosome), the IDA annotation with qualifier located_in from PMID:27302062 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005770 late endosome | IDA PMID:16033761 BACE is degraded via the lysosomal pathway. | ACCEPT | Summary: late endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005770 (late endosome), the IDA annotation with qualifier located_in from PMID:16033761 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005770 late endosome | IDA PMID:27084579 SEPT8 modulates Ξ²-amyloidogenic processing of APP by affecti... | ACCEPT | Summary: late endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005770 (late endosome), the IDA annotation with qualifier located_in from PMID:27084579 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005770 late endosome | IDA PMID:27302062 The Endosome-associated Deubiquitinating Enzyme USP8 Regulat... | ACCEPT | Summary: late endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005770 (late endosome), the IDA annotation with qualifier located_in from PMID:27302062 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0055037 recycling endosome | IDA PMID:27084579 SEPT8 modulates Ξ²-amyloidogenic processing of APP by affecti... | ACCEPT | Summary: recycling endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0055037 (recycling endosome), the IDA annotation with qualifier located_in from PMID:27084579 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0055037 recycling endosome | IDA PMID:27302062 The Endosome-associated Deubiquitinating Enzyme USP8 Regulat... | ACCEPT | Summary: recycling endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0055037 (recycling endosome), the IDA annotation with qualifier located_in from PMID:27302062 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0009986 cell surface | ISS GO_REF:0000024 | ACCEPT | Summary: cell surface is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0009986 (cell surface), the ISS annotation with qualifier part_of from GO_REF:0000024 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0004175 endopeptidase activity | IDA PMID:10677483 Human aspartic protease memapsin 2 cleaves the beta-secretas... | ACCEPT | Summary: endopeptidase activity is retained as a core molecular-function annotation for BACE1; it captures activity or binding specificity within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0004175 (endopeptidase activity), the IDA annotation with qualifier enables from PMID:10677483 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0006508 proteolysis | IDA PMID:10677483 Human aspartic protease memapsin 2 cleaves the beta-secretas... | ACCEPT | Summary: proteolysis is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0006508 (proteolysis), the IDA annotation with qualifier involved_in from PMID:10677483 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0050435 amyloid-beta metabolic process | IDA PMID:10677483 Human aspartic protease memapsin 2 cleaves the beta-secretas... | ACCEPT | Summary: amyloid-beta metabolic process is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0050435 (amyloid-beta metabolic process), the IDA annotation with qualifier involved_in from PMID:10677483 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0043525 positive regulation of neuron apoptotic process | IGI PMID:29371969 MiR-124 acts as a target for Alzheimer's disease by regulati... | KEEP AS NON CORE | Summary: positive regulation of neuron apoptotic process is retained as a non-core biological-process annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0043525 (positive regulation of neuron apoptotic process), the IGI annotation with qualifier involved_in from PMID:29371969 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0005515 protein binding | IPI PMID:27179792 BIN1 regulates BACE1 intracellular trafficking and amyloid-Ξ²... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:27179792 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0005769 early endosome | IDA PMID:24305806 Pharmacologic inhibition of ROCK2 suppresses amyloid-Ξ² produ... | ACCEPT | Summary: early endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005769 (early endosome), the IDA annotation with qualifier located_in from PMID:24305806 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005515 protein binding | IPI PMID:17573534 Cellular prion protein regulates beta-secretase cleavage of ... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:17573534 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5692934 | ACCEPT | Summary: plasma membrane is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005886 (plasma membrane), the TAS annotation with qualifier located_in from Reactome:R-HSA-5692934 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5692941 | ACCEPT | Summary: plasma membrane is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005886 (plasma membrane), the TAS annotation with qualifier located_in from Reactome:R-HSA-5692941 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5693086 | ACCEPT | Summary: plasma membrane is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005886 (plasma membrane), the TAS annotation with qualifier located_in from Reactome:R-HSA-5693086 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-5693001 | KEEP AS NON CORE | Summary: endoplasmic reticulum lumen is retained as a non-core cellular-component/localization annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005788 (endoplasmic reticulum lumen), the TAS annotation with qualifier located_in from Reactome:R-HSA-5693001 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0070931 Golgi-associated vesicle lumen | TAS Reactome:R-HSA-5693071 | ACCEPT | Summary: Golgi-associated vesicle lumen is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0070931 (Golgi-associated vesicle lumen), the TAS annotation with qualifier located_in from Reactome:R-HSA-5693071 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0070931 Golgi-associated vesicle lumen | TAS Reactome:R-HSA-5693081 | ACCEPT | Summary: Golgi-associated vesicle lumen is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0070931 (Golgi-associated vesicle lumen), the TAS annotation with qualifier located_in from Reactome:R-HSA-5693081 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-5693071 | KEEP AS NON CORE | Summary: endoplasmic reticulum lumen is retained as a non-core cellular-component/localization annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005788 (endoplasmic reticulum lumen), the TAS annotation with qualifier located_in from Reactome:R-HSA-5693071 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-5692495 | ACCEPT | Summary: endosome membrane is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0010008 (endosome membrane), the TAS annotation with qualifier located_in from Reactome:R-HSA-5692495 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-5692941 | ACCEPT | Summary: endosome membrane is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0010008 (endosome membrane), the TAS annotation with qualifier located_in from Reactome:R-HSA-5692941 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0070931 Golgi-associated vesicle lumen | TAS Reactome:R-HSA-5693086 | ACCEPT | Summary: Golgi-associated vesicle lumen is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0070931 (Golgi-associated vesicle lumen), the TAS annotation with qualifier located_in from Reactome:R-HSA-5693086 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0070931 Golgi-associated vesicle lumen | TAS Reactome:R-HSA-5693092 | ACCEPT | Summary: Golgi-associated vesicle lumen is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0070931 (Golgi-associated vesicle lumen), the TAS annotation with qualifier located_in from Reactome:R-HSA-5693092 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0006509 membrane protein ectodomain proteolysis | IDA PMID:18353773 A novel sorting nexin modulates endocytic trafficking and al... | ACCEPT | Summary: membrane protein ectodomain proteolysis is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0006509 (membrane protein ectodomain proteolysis), the IDA annotation with qualifier involved_in from PMID:18353773 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005515 protein binding | IPI PMID:22709416 Sorting nexin 12 interacts with BACE1 and regulates BACE1-me... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:22709416 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0005515 protein binding | IPI PMID:19011241 Two endoplasmic reticulum (ER)/ER Golgi intermediate compart... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:19011241 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0005515 protein binding | IPI PMID:24612608 Flotillins bind to the dileucine sorting motif of Ξ²-site amy... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:24612608 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0005770 late endosome | IDA PMID:24612608 Flotillins bind to the dileucine sorting motif of Ξ²-site amy... | ACCEPT | Summary: late endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005770 (late endosome), the IDA annotation with qualifier located_in from PMID:24612608 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005771 multivesicular body | IDA PMID:24612608 Flotillins bind to the dileucine sorting motif of Ξ²-site amy... | KEEP AS NON CORE | Summary: multivesicular body is retained as a non-core cellular-component/localization annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005771 (multivesicular body), the IDA annotation with qualifier located_in from PMID:24612608 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0005886 plasma membrane | IDA PMID:24612608 Flotillins bind to the dileucine sorting motif of Ξ²-site amy... | ACCEPT | Summary: plasma membrane is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005886 (plasma membrane), the IDA annotation with qualifier located_in from PMID:24612608 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0001540 amyloid-beta binding | IPI PMID:16407538 Interaction of the cytosolic domains of sorLA/LR11 with the ... | MODIFY | Summary: amyloid-beta binding is directionally related to BACE1 biology but is not the best curation target; amyloid precursor protein catabolic process, aspartic-type endopeptidase activity better captures the specific supported function or process. Reason: For GO:0001540 (amyloid-beta binding), the IPI annotation with qualifier enables from PMID:16407538 supports a relationship to BACE1, but the current term is less precise than amyloid precursor protein catabolic process, aspartic-type endopeptidase activity for the evidence and for the synthesized core/non-core role of BACE1. The MODIFY action preserves the biological intent while pointing curators to the more informative GO term. Proposed replacements: amyloid precursor protein catabolic process aspartic-type endopeptidase activity |
| GO:0005515 protein binding | IPI PMID:16407538 Interaction of the cytosolic domains of sorLA/LR11 with the ... | MARK AS OVER ANNOTATED | Summary: protein binding is marked over-annotated for BACE1 because this molecular-function term is too generic, interaction-map-like, or weakly informative relative to the gene-specific biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005515 (protein binding), the IPI annotation with qualifier enables from PMID:16407538 may reflect a real assay result or interaction, but this GO term does not identify the specific protease, APP-processing, substrate-processing, or trafficking/localization annotation that explains BACE1's role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. |
| GO:0008233 peptidase activity | IDA PMID:8562317 Inhibition of beta A4 production by specific modulation of b... | ACCEPT | Summary: peptidase activity is retained as a core molecular-function annotation for BACE1; it captures activity or binding specificity within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0008233 (peptidase activity), the IDA annotation with qualifier enables from PMID:8562317 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005794 Golgi apparatus | IDA PMID:12586838 Identification of phospholipid scramblase 1 as a novel inter... | ACCEPT | Summary: Golgi apparatus is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005794 (Golgi apparatus), the IDA annotation with qualifier located_in from PMID:12586838 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005886 plasma membrane | IDA PMID:12586838 Identification of phospholipid scramblase 1 as a novel inter... | ACCEPT | Summary: plasma membrane is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005886 (plasma membrane), the IDA annotation with qualifier located_in from PMID:12586838 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0019899 enzyme binding | IPI PMID:12586838 Identification of phospholipid scramblase 1 as a novel inter... | KEEP AS NON CORE | Summary: enzyme binding is retained as a non-core molecular-function annotation for BACE1; it records a supported context, interaction, localization, or pathway branch that is secondary to BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0019899 (enzyme binding), the IPI annotation with qualifier enables from PMID:12586838 supports retaining the annotation, but the term describes a context-specific outcome or peripheral branch rather than the principal BACE1 function: membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. Keeping it as non-core prevents broad pathway participation from being promoted to core function. |
| GO:0005794 Golgi apparatus | IDA PMID:11466313 The transmembrane domain of the Alzheimer's beta-secretase (... | ACCEPT | Summary: Golgi apparatus is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005794 (Golgi apparatus), the IDA annotation with qualifier located_in from PMID:11466313 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005802 trans-Golgi network | IDA PMID:11466313 The transmembrane domain of the Alzheimer's beta-secretase (... | ACCEPT | Summary: trans-Golgi network is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005802 (trans-Golgi network), the IDA annotation with qualifier located_in from PMID:11466313 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005768 endosome | IDA PMID:10531052 Beta-secretase cleavage of Alzheimer's amyloid precursor pro... | ACCEPT | Summary: endosome is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005768 (endosome), the IDA annotation with qualifier located_in from PMID:10531052 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005794 Golgi apparatus | IDA PMID:10531052 Beta-secretase cleavage of Alzheimer's amyloid precursor pro... | ACCEPT | Summary: Golgi apparatus is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005794 (Golgi apparatus), the IDA annotation with qualifier located_in from PMID:10531052 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0006508 proteolysis | IDA PMID:10531052 Beta-secretase cleavage of Alzheimer's amyloid precursor pro... | ACCEPT | Summary: proteolysis is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0006508 (proteolysis), the IDA annotation with qualifier involved_in from PMID:10531052 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0006509 membrane protein ectodomain proteolysis | TAS PMID:12354787 The disintegrin/metalloprotease ADAM 10 is essential for Not... | ACCEPT | Summary: membrane protein ectodomain proteolysis is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0006509 (membrane protein ectodomain proteolysis), the TAS annotation with qualifier involved_in from PMID:12354787 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0016020 membrane | NAS PMID:10531052 Beta-secretase cleavage of Alzheimer's amyloid precursor pro... | ACCEPT | Summary: membrane is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0016020 (membrane), the NAS annotation with qualifier located_in from PMID:10531052 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0050435 amyloid-beta metabolic process | IDA PMID:15080893 BACE (beta-secretase) modulates the processing of APLP2 in v... | ACCEPT | Summary: amyloid-beta metabolic process is retained as a core biological-process annotation for BACE1; it captures process participation within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0050435 (amyloid-beta metabolic process), the IDA annotation with qualifier involved_in from PMID:15080893 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
| GO:0005886 plasma membrane | TAS PMID:10887202 Characterization of Alzheimer's beta -secretase protein BACE... | ACCEPT | Summary: plasma membrane is retained as a core cellular-component/localization annotation for BACE1; it captures site of action or component context within the synthesized core biology: BACE1 beta-secretase/aspartyl endopeptidase activity, amyloidogenic APP processing, membrane-substrate proteolysis, and TGN/endosomal trafficking that controls substrate access and enzyme turnover. Reason: For GO:0005886 (plasma membrane), the TAS annotation with qualifier located_in from PMID:10887202 is consistent with BACE1's core role in membrane aspartyl endopeptidase activity that initiates beta-site APP cleavage in TGN/endosomal trafficking compartments. This action keeps the term because it provides a specific, evidence-backed protease, APP-processing, substrate-processing, or trafficking/localization annotation rather than only a downstream phenotype or generic interaction label. |
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Download this section (compressed HTML)Q: Which non-APP BACE1 substrates should be treated as core physiological BACE1 biology rather than downstream neuronal phenotypes?
Suggested experts: BACE1 substrate experts, GO protease curators
Q: How should BACE1 trafficking annotations distinguish compartments that control APP access from compartments involved mainly in BACE1 degradation?
Suggested experts: endosomal trafficking experts, APP processing experts
Q: Should BACE1's amyloidolytic cleavage of Abeta40/42 at the beta-34 site (generating non-toxic Abeta34) be captured distinctly from its amyloidogenic beta-site APP cleavage, given that the BACE1/APP ratio sets the balance between the two activities?
Suggested experts: amyloid-beta metabolism experts, GO protease curators
Experiment: Use endogenous BACE1 tagging and APP cleavage reporters to quantify beta-secretase activity after perturbing GGA, SNX6, BIN1, USP8, and lysosomal-routing pathways.
Hypothesis: BACE1 amyloidogenic output is controlled primarily by compartmental access to APP rather than total BACE1 abundance alone.
Type: compartment-resolved APP beta-cleavage assay
Experiment: Compare APP, CHL1, neuregulin, SEZ6-family, and other neuronal substrates in BACE1 wild-type and active-site mutant human neurons.
Hypothesis: Non-APP synaptic and behavioral phenotypes arise from distinct substrate classes but share the same aspartyl endopeptidase activity.
Type: multi-substrate protease activity assay
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