id: P56817
gene_symbol: BACE1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
alternative_products:
- name: A (BACE-1A, BAC-501)
  id: P56817-1
- name: B (BACE-1B, BACE-I-476)
  id: P56817-2
  sequence_note: VSP_005223
- name: C (BACE-1C, BACE-I-457)
  id: P56817-3
  sequence_note: VSP_005222
- name: D (BACE-1D, BACE-I-432)
  id: P56817-4
  sequence_note: VSP_005222, VSP_005223
- name: '5'
  id: P56817-5
  sequence_note: VSP_047092, VSP_047093
- name: '6'
  id: P56817-6
  sequence_note: VSP_047092, VSP_047093, VSP_005223
existing_annotations:
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0016485
    label: protein processing
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0004190
    label: aspartic-type endopeptidase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0050435
    label: amyloid-beta metabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005802
    label: trans-Golgi network
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0006509
    label: membrane protein ectodomain proteolysis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0004190
    label: aspartic-type endopeptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0006508
    label: proteolysis
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0030424
    label: axon
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0030659
    label: cytoplasmic vesicle membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0045121
    label: membrane raft
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0055037
    label: recycling endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10677483
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12901838
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15466887
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20354142
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22801501
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23701002
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25957769
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26053850
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26840340
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29507146
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30538620
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0004175
    label: endopeptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005802
    label: trans-Golgi network
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0006509
    label: membrane protein ectodomain proteolysis
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0008021
    label: synaptic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0010288
    label: response to lead ion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0031410
    label: cytoplasmic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0036269
    label: swimming behavior
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0042987
    label: amyloid precursor protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0043523
    label: regulation of neuron apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0050435
    label: amyloid-beta metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0050804
    label: modulation of chemical synaptic transmission
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0050966
    label: detection of mechanical stimulus involved in sensory perception of 
      pain
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0060134
    label: prepulse inhibition
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0071280
    label: cellular response to copper ion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0071287
    label: cellular response to manganese ion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0098686
    label: hippocampal mossy fiber to CA3 synapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: is_active_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0098793
    label: presynapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: is_active_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0099171
    label: presynaptic modulation of chemical synaptic transmission
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0140448
    label: signaling receptor ligand precursor processing
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:1904646
    label: cellular response to amyloid-beta
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:1990418
    label: response to insulin-like growth factor stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0008798
    label: beta-aspartyl-peptidase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5692495
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0034205
    label: amyloid-beta formation
  evidence_type: IDA
  original_reference_id: PMID:10677483
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005768
    label: endosome
  evidence_type: EXP
  original_reference_id: PMID:11466313
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005768
    label: endosome
  evidence_type: EXP
  original_reference_id: PMID:15886016
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: EXP
  original_reference_id: PMID:15615712
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: EXP
  original_reference_id: PMID:11466313
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: EXP
  original_reference_id: PMID:17425515
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: EXP
  original_reference_id: PMID:11466313
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: EXP
  original_reference_id: PMID:11466313
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: EXP
  original_reference_id: PMID:17425515
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0030659
    label: cytoplasmic vesicle membrane
  evidence_type: EXP
  original_reference_id: PMID:11466313
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0030659
    label: cytoplasmic vesicle membrane
  evidence_type: EXP
  original_reference_id: PMID:15886016
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0045121
    label: membrane raft
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0120283
    label: protein serine/threonine kinase binding
  evidence_type: IPI
  original_reference_id: PMID:24305806
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:1990000
    label: amyloid fibril formation
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-977225
  qualifier: involved_in
  review:
    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.
    action: MODIFY
    proposed_replacement_terms:
    - id: GO:0034205
      label: amyloid-beta formation
    - id: GO:0042987
      label: amyloid precursor protein catabolic 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.
- term:
    id: GO:0004190
    label: aspartic-type endopeptidase activity
  evidence_type: IDA
  original_reference_id: PMID:10531052
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0016485
    label: protein processing
  evidence_type: IDA
  original_reference_id: PMID:10531052
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15286784
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0034205
    label: amyloid-beta formation
  evidence_type: IDA
  original_reference_id: PMID:24352696
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0042987
    label: amyloid precursor protein catabolic process
  evidence_type: ISS
  original_reference_id: PMID:20704561
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IDA
  original_reference_id: PMID:23109336
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: IDA
  original_reference_id: PMID:23109336
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:23109336
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005802
    label: trans-Golgi network
  evidence_type: IDA
  original_reference_id: PMID:23109336
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IDA
  original_reference_id: PMID:23109336
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15886016
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: IDA
  original_reference_id: PMID:15886016
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005802
    label: trans-Golgi network
  evidence_type: IDA
  original_reference_id: PMID:15886016
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IDA
  original_reference_id: PMID:15886016
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0055037
    label: recycling endosome
  evidence_type: IDA
  original_reference_id: PMID:15886016
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IDA
  original_reference_id: PMID:16033761
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IDA
  original_reference_id: PMID:27084579
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IDA
  original_reference_id: PMID:27302062
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: IDA
  original_reference_id: PMID:27084579
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: IDA
  original_reference_id: PMID:27302062
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:16033761
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:27084579
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:27302062
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0055037
    label: recycling endosome
  evidence_type: IDA
  original_reference_id: PMID:27084579
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0055037
    label: recycling endosome
  evidence_type: IDA
  original_reference_id: PMID:27302062
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: part_of
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0004175
    label: endopeptidase activity
  evidence_type: IDA
  original_reference_id: PMID:10677483
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0006508
    label: proteolysis
  evidence_type: IDA
  original_reference_id: PMID:10677483
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0050435
    label: amyloid-beta metabolic process
  evidence_type: IDA
  original_reference_id: PMID:10677483
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0043525
    label: positive regulation of neuron apoptotic process
  evidence_type: IGI
  original_reference_id: PMID:29371969
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27179792
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: IDA
  original_reference_id: PMID:24305806
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17573534
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5692934
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5692941
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693086
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693001
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0070931
    label: Golgi-associated vesicle lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693071
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0070931
    label: Golgi-associated vesicle lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693081
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693071
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5692495
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5692941
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0070931
    label: Golgi-associated vesicle lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693086
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0070931
    label: Golgi-associated vesicle lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5693092
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0006509
    label: membrane protein ectodomain proteolysis
  evidence_type: IDA
  original_reference_id: PMID:18353773
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22709416
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19011241
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24612608
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:24612608
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005771
    label: multivesicular body
  evidence_type: IDA
  original_reference_id: PMID:24612608
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:24612608
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0001540
    label: amyloid-beta binding
  evidence_type: IPI
  original_reference_id: PMID:16407538
  qualifier: enables
  review:
    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.
    action: MODIFY
    proposed_replacement_terms:
    - id: GO:0042987
      label: amyloid precursor protein catabolic process
    - id: GO:0004190
      label: aspartic-type endopeptidase activity
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16407538
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: IDA
  original_reference_id: PMID:8562317
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IDA
  original_reference_id: PMID:12586838
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:12586838
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: IPI
  original_reference_id: PMID:12586838
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IDA
  original_reference_id: PMID:11466313
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005802
    label: trans-Golgi network
  evidence_type: IDA
  original_reference_id: PMID:11466313
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IDA
  original_reference_id: PMID:10531052
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IDA
  original_reference_id: PMID:10531052
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0006508
    label: proteolysis
  evidence_type: IDA
  original_reference_id: PMID:10531052
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0006509
    label: membrane protein ectodomain proteolysis
  evidence_type: TAS
  original_reference_id: PMID:12354787
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: NAS
  original_reference_id: PMID:10531052
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0050435
    label: amyloid-beta metabolic process
  evidence_type: IDA
  original_reference_id: PMID:15080893
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: PMID:10887202
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    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.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with 
    GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to
    orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular 
    Location vocabulary mapping, accompanied by conservative changes to GO terms
    applied by UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data
    to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:human/BACE1/BACE1-deep-research-falcon.md
  title: Falcon deep research report for BACE1
  findings:
  - statement: >-
      The grounded Falcon (Edison) report corroborates the review's core picture of
      BACE1 as the rate-limiting beta-secretase that initiates amyloidogenic APP
      processing, and refines it by surfacing BACE1's complementary amyloidolytic
      cleavage of longer amyloid-beta species at the beta34 site.
    supporting_text: >-
      BACE1 serves as the initiating and rate-limiting enzyme in the amyloidogenic
      processing pathway of amyloid precursor protein
- id: PMID:10531052
  title: Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the
    transmembrane aspartic protease BACE.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached abstract directly establishes BACE1 as the 
      transmembrane aspartyl protease mediating APP beta-secretase cleavage.
- id: PMID:10677483
  title: Human aspartic protease memapsin 2 cleaves the beta-secretase site of 
    beta-amyloid precursor protein.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached abstract supports memapsin 2/BACE1 cleavage of the APP 
      beta-secretase site and frames the reaction as rate-limiting for 
      amyloid-beta production.
- id: PMID:10887202
  title: Characterization of Alzheimer's beta -secretase protein BACE. A pepsin 
    family member with unusual properties.
  findings: []
- id: PMID:11466313
  title: The transmembrane domain of the Alzheimer's beta-secretase (BACE1) 
    determines its late Golgi localization and access to beta -amyloid precursor
    protein (APP) substrate.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached abstract supports BACE1 late-Golgi/endosomal 
      localization and the requirement for compartment access to APP substrate.
- id: PMID:12354787
  title: The disintegrin/metalloprotease ADAM 10 is essential for Notch 
    signalling but not for alpha-secretase activity in fibroblasts.
  findings: []
- id: PMID:12586838
  title: Identification of phospholipid scramblase 1 as a novel interacting 
    molecule with beta -secretase (beta -site amyloid precursor protein (APP) 
    cleaving enzyme (BACE)).
  findings: []
- id: PMID:12901838
  title: Presenilin-1 interacts directly with the beta-site amyloid protein 
    precursor cleaving enzyme (BACE1).
  findings: []
- id: PMID:15080893
  title: BACE (beta-secretase) modulates the processing of APLP2 in vivo.
  findings: []
- id: PMID:15286784
  title: Reticulon family members modulate BACE1 activity and amyloid-beta 
    peptide generation.
  findings: []
- id: PMID:15466887
  title: Demonstration of BACE (beta-secretase) phosphorylation and its 
    interaction with GGA1 in cells by fluorescence-lifetime imaging microscopy.
  findings: []
- id: PMID:15615712
  title: GGA proteins mediate the recycling pathway of memapsin 2 (BACE).
  findings: []
- id: PMID:15886016
  title: GGA proteins regulate retrograde transport of BACE1 from endosomes to 
    the trans-Golgi network.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached abstract supports GGA1-dependent retrograde transport 
      of internalized BACE1 from endosomes to the trans-Golgi network.
- id: PMID:16033761
  title: BACE is degraded via the lysosomal pathway.
  findings: []
- id: PMID:16407538
  title: Interaction of the cytosolic domains of sorLA/LR11 with the amyloid 
    precursor protein (APP) and beta-secretase beta-site APP-cleaving enzyme.
  findings: []
- id: PMID:17425515
  title: A reversible form of lysine acetylation in the ER and Golgi lumen 
    controls the molecular stabilization of BACE1.
  findings: []
- id: PMID:17573534
  title: Cellular prion protein regulates beta-secretase cleavage of the 
    Alzheimer's amyloid precursor protein.
  findings: []
- id: PMID:18353773
  title: A novel sorting nexin modulates endocytic trafficking and 
    alpha-secretase cleavage of the amyloid precursor protein.
  findings: []
- id: PMID:19011241
  title: Two endoplasmic reticulum (ER)/ER Golgi intermediate compartment-based 
    lysine acetyltransferases post-translationally regulate BACE1 levels.
  findings: []
- id: PMID:20354142
  title: Proteomic identification of sorting nexin 6 as a negative regulator of 
    BACE1-mediated APP processing.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached abstract supports SNX6 association with BACE1 and 
      negative regulation of BACE1-mediated APP processing through trafficking.
- id: PMID:20704561
  title: The ATP-binding cassette transporter-2 (ABCA2) increases endogenous 
    amyloid precursor protein expression and Aβ fragment generation.
  findings: []
- id: PMID:22709416
  title: Sorting nexin 12 interacts with BACE1 and regulates BACE1-mediated APP 
    processing.
  findings: []
- id: PMID:22801501
  title: A mutation in APP protects against Alzheimer's disease and age-related 
    cognitive decline.
  findings: []
- id: PMID:23109336
  title: BACE1 protein endocytosis and trafficking are differentially regulated 
    by ubiquitination at lysine 501 and the Di-leucine motif in the carboxyl 
    terminus.
  findings: []
- id: PMID:23701002
  title: BRI2 interacts with BACE1 and regulates its cellular levels by 
    promoting its degradation and reducing its mRNA levels.
  findings: []
- id: PMID:24305806
  title: Pharmacologic inhibition of ROCK2 suppresses amyloid-β production in an
    Alzheimer's disease mouse model.
  findings: []
- id: PMID:24352696
  title: MicroRNA-339-5p down-regulates protein expression of β-site amyloid 
    precursor protein-cleaving enzyme 1 (BACE1) in human primary brain cultures 
    and is reduced in brain tissue specimens of Alzheimer disease subjects.
  findings: []
- id: PMID:24612608
  title: Flotillins bind to the dileucine sorting motif of β-site amyloid 
    precursor protein-cleaving enzyme 1 and influence its endosomal sorting.
  findings: []
- id: PMID:25957769
  title: Clec4g (LSECtin) interacts with BACE1 and suppresses Aβ generation.
  findings: []
- id: PMID:26053850
  title: The Golgi-Localized γ-Ear-Containing ARF-Binding (GGA) Proteins Alter 
    Amyloid-β Precursor Protein (APP) Processing through Interaction of Their 
    GAE Domain with the Beta-Site APP Cleaving Enzyme 1 (BACE1).
  findings: []
- id: PMID:26840340
  title: Identification of Human Islet Amyloid Polypeptide as a BACE2 Substrate.
  findings: []
- id: PMID:27084579
  title: SEPT8 modulates β-amyloidogenic processing of APP by affecting the 
    sorting and accumulation of BACE1.
  findings: []
- id: PMID:27179792
  title: BIN1 regulates BACE1 intracellular trafficking and amyloid-β 
    production.
  findings: []
- id: PMID:27302062
  title: The Endosome-associated Deubiquitinating Enzyme USP8 Regulates BACE1 
    Enzyme Ubiquitination and Degradation.
  findings: []
- id: PMID:29371969
  title: MiR-124 acts as a target for Alzheimer's disease by regulating BACE1.
  findings: []
- id: PMID:29507146
  title: β-Secretase BACE1 Promotes Surface Expression and Function of Kv3.4 at 
    Hippocampal Mossy Fiber Synapses.
  findings: []
- id: PMID:30538620
  title: Visualization of Alzheimer's Disease Related α-/β-/γ-Secretase Ternary 
    Complex by Bimolecular Fluorescence Complementation Based Fluorescence 
    Resonance Energy Transfer.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease 
    Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:8562317
  title: Inhibition of beta A4 production by specific modulation of 
    beta-secretase activity.
  findings: []
- id: Reactome:R-HSA-5692495
  title: BACE1 cleaves APP(18-770) to APP(18-671) and APP(672-770)
  findings: []
- id: Reactome:R-HSA-5692934
  title: BACE1 binds GGA1,2,3
  findings: []
- id: Reactome:R-HSA-5692941
  title: BACE1:GGA1,2,3 translocates from plasma membrane to endosome
  findings: []
- id: Reactome:R-HSA-5693001
  title: NAT8,8B acetylate BACE1
  findings: []
- id: Reactome:R-HSA-5693071
  title: BACE1 translocates from ER lumen to Golgi apparatus
  findings: []
- id: Reactome:R-HSA-5693081
  title: FURIN cleaves 7K-BACE1 to 7K-BACE1(46-501)
  findings: []
- id: Reactome:R-HSA-5693086
  title: BACE1(46-501) translocates from Golgi lumen to plasma membrane
  findings: []
- id: Reactome:R-HSA-5693092
  title: Unknown deacetylase deacetylates 7K-BACE1(46-501)
  findings: []
- id: Reactome:R-HSA-977225
  title: Amyloid fiber formation
  findings: []
core_functions:
- molecular_function:
    id: GO:0004190
    label: aspartic-type endopeptidase activity
  description: >-
    BACE1 is the membrane beta-secretase/aspartyl endopeptidase that cleaves APP at
    the beta-secretase site, initiating amyloidogenic APP processing and amyloid-beta
    production. Its access to APP is controlled by TGN, endosomal, recycling-endosomal,
    cell-surface, and lysosomal trafficking.
  directly_involved_in:
  - id: GO:0042987
    label: amyloid precursor protein catabolic process
  - id: GO:0034205
    label: amyloid-beta formation
  - id: GO:0050435
    label: amyloid-beta metabolic process
  - id: GO:0016485
    label: protein processing
  - id: GO:0006509
    label: membrane protein ectodomain proteolysis
  - id: GO:0140448
    label: signaling receptor ligand precursor processing
  locations:
  - id: GO:0005802
    label: trans-Golgi network
  - id: GO:0005768
    label: endosome
  - id: GO:0005769
    label: early endosome
  - id: GO:0005770
    label: late endosome
  - id: GO:0055037
    label: recycling endosome
  - id: GO:0005886
    label: plasma membrane
  - id: GO:0009986
    label: cell surface
  - id: GO:0005764
    label: lysosome
  supported_by:
  - reference_id: PMID:10531052
    supporting_text: >-
      Overexpression of this protease, termed BACE (for beta-site APP-cleaving enzyme)
      increased the amount of beta-secretase cleavage products
  - reference_id: PMID:10677483
    supporting_text: >-
      memapsin 2 cleaved the beta-secretase site of APP
  - reference_id: PMID:10677483
    supporting_text: >-
      catalyzes the rate-limiting step of the in vivo production of the beta-amyloid
      (Abeta) peptide
  - reference_id: PMID:15886016
    supporting_text: >-
      GGA1 regulates the retrograde transport of internalized BACE1 from endosomal
      compartments to the TGN
  - reference_id: PMID:20354142
    supporting_text: >-
      SNX6 negatively modulates BACE1-mediated cleavage of APP
  - reference_id: file:human/BACE1/BACE1-deep-research-falcon.md
    supporting_text: >-
      This amyloidolytic activity represents a clearance mechanism for toxic Aβ species,
      and the BACE1/APP ratio appears to be a primary determinant of the balance between
      amyloidogenic and amyloidolytic activities
proposed_new_terms: []
suggested_questions:
- question: >-
    Which non-APP BACE1 substrates should be treated as core physiological BACE1 biology
    rather than downstream neuronal phenotypes?
  experts:
  - BACE1 substrate experts
  - GO protease curators
- question: >-
    How should BACE1 trafficking annotations distinguish compartments that control
    APP access from compartments involved mainly in BACE1 degradation?
  experts:
  - endosomal trafficking experts
  - APP processing experts
- question: >-
    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?
  experts:
  - amyloid-beta metabolism experts
  - GO protease curators
suggested_experiments:
- description: >-
    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.
  experiment_type: compartment-resolved APP beta-cleavage assay
- description: >-
    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.
  experiment_type: multi-substrate protease activity assay