id: P51150
gene_symbol: Rab7
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
description: >-
  Mouse Rab7 (official symbol Rab7a; UniProt P51150) is a Rab-family small GTPase
  (EC 3.6.5.2) and the direct ortholog of human RAB7A. It is the master regulator
  of the late endocytic pathway, cycling between an inactive GDP-bound (cytosolic)
  state and an active GTP-bound (membrane-associated) state. GTP-loading by the
  Mon1-Ccz1 GEF on maturing endosomes (the Rab5-to-Rab7 conversion) recruits
  effectors including RILP, the HOPS tethering complex, retromer, FYCO1, PLEKHM1
  and ORP1L to drive early-to-late endosome maturation, late endosome-lysosome
  fusion, autophagosome-lysosome fusion, phagosome maturation, retrograde
  endosome-to-Golgi transport and lysosome positioning. It is inactivated by
  TBC-domain GAPs. Mouse studies have established physiological roles in lipophagy
  and beta-adrenergic lipolysis in adipocytes, synaptic AMPA-receptor trafficking
  during long-term depression in neurons, osteoclast ruffled-border function and
  bone resorption, and secretory-lysosome trafficking. In vivo work in mouse liver
  using LysoTag mice further confirms Rab7 as a mediator of late endosomal
  maturation, where its loss diverts cargo away from the degradative route and
  increases the cytosolic escape of lipid nanoparticles (PMID:41814093).

existing_annotations:
# ============ IBA ANNOTATIONS (PHYLOGENETIC) ============
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Rab7 is a canonical lysosomal marker and effector platform. UniProt lists
      lysosome membrane localization with experimental support across orthologs.
    action: ACCEPT
    reason: >-
      Core localization where Rab7 exerts its regulatory function in fusion and
      cargo degradation; supported by phylogenetic conservation and experimental
      data in mouse.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Late endosome is the canonical site of active Rab7, where it is GTP-loaded
      by Mon1-Ccz1 during the Rab5-to-Rab7 conversion.
    action: ACCEPT
    reason: >-
      Defining core localization for Rab7, confirmed by many mouse IDA studies in
      this review.
- term:
    id: GO:0008333
    label: endosome to lysosome transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      The core biological process for Rab7: it controls maturation of late
      endosomes and their fusion with lysosomes for cargo degradation. In vivo
      mouse liver data confirm Rab7 as a mediator of late endosomal maturation.
    action: ACCEPT
    reason: >-
      Core biological function, strongly supported across orthologs and directly
      in mouse.
    supported_by:
      - reference_id: PMID:41814093
        supporting_text: "Loss of Rab7, a mediator of late endosomal maturation, increased LNP escape."
      - reference_id: file:mouse/Rab7/Rab7-deep-research-manual.md
        supporting_text: Manual synthesis of mouse Rab7/Rab7a literature supports
          the conserved late-endosome maturation and endosome-to-lysosome routing
          function.
- term:
    id: GO:0045335
    label: phagocytic vesicle
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Rab7 is recruited to phagosomes and regulates phagosome maturation.
    action: ACCEPT
    reason: >-
      Core function in phagosome maturation; conserved across the Rab7 ortholog
      group.
- term:
    id: GO:0090385
    label: phagosome-lysosome fusion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Rab7 is required for phagosome-lysosome fusion and phagolysosome
      maturation.
    action: ACCEPT
    reason: >-
      Core function in innate immunity / pathogen degradation, conserved across
      orthologs.
# ============ IEA ANNOTATIONS (AUTOMATED) ============
- term:
    id: GO:0000421
    label: autophagosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Rab7 localizes to autophagosome membranes and is required for
      autophagosome-lysosome fusion.
    action: ACCEPT
    reason: >-
      Core localization for the autophagy role of Rab7; consistent with
      phagophore assembly site annotation in this review.
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Rab7 has intrinsic GTPase activity (EC 3.6.5.2) hydrolyzing GTP to GDP,
      accelerated by TBC-domain GAPs.
    action: ACCEPT
    reason: >-
      Core molecular function, fundamental to the molecular-switch behavior;
      directly demonstrated for mouse Rab7 (PMID:16855591).
- term:
    id: GO:0003925
    label: G protein activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    summary: >-
      Rab7 functions as a G protein, cycling between active GTP-bound and inactive
      GDP-bound states to regulate membrane trafficking.
    action: ACCEPT
    reason: >-
      Accurate core molecular function for a Rab-family small GTPase.
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      GTP binding activates Rab7 and enables membrane association and effector
      recruitment.
    action: ACCEPT
    reason: >-
      Core molecular function of the GTPase cycle.
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Rab7 localizes to lysosomal membranes as a peripheral membrane protein on
      the cytoplasmic face.
    action: ACCEPT
    reason: >-
      Core localization, confirmed experimentally in mouse (e.g. PMID:28063257).
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: >-
      Late endosome localization predicted by ARBA, consistent with abundant
      experimental evidence.
    action: ACCEPT
    reason: >-
      Canonical core localization.
- term:
    id: GO:0005811
    label: lipid droplet
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Rab7 localizes to lipid droplets during lipophagy, directly demonstrated in
      mouse adipocytes.
    action: ACCEPT
    reason: >-
      Valid localization related to lipophagy; experimentally supported in mouse
      (PMID:23708524).
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Rab7 localizes to endosome membranes, primarily late endosome membranes.
    action: ACCEPT
    reason: >-
      Accurate localization; the more specific late endosome membrane term is also
      annotated.
- term:
    id: GO:0030670
    label: phagocytic vesicle membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Rab7 localizes to phagosomal membranes during phagosome maturation.
    action: ACCEPT
    reason: >-
      Core localization for the phagosome maturation function.
- term:
    id: GO:0031410
    label: cytoplasmic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Rab7 localizes to multiple types of cytoplasmic vesicles.
    action: ACCEPT
    reason: >-
      Accurate but general; more specific vesicle annotations are present.
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Late endosome membrane is the canonical site for active Rab7.
    action: ACCEPT
    reason: >-
      Core localization where Rab7 recruits effectors for maturation and
      transport.
- term:
    id: GO:0031966
    label: mitochondrial membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Rab7 can be recruited to mitochondrial membranes during mitophagy and at
      ER-mitochondria/endosome contact sites.
    action: KEEP_AS_NON_CORE
    reason: >-
      Context-dependent localization during mitophagy rather than constitutive
      mitochondrial residence.
- term:
    id: GO:0033162
    label: melanosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Rab7 localizes to melanosome membranes; melanosomes are lysosome-related
      organelles.
    action: KEEP_AS_NON_CORE
    reason: >-
      Cell-type-specific localization relevant to melanocyte biology and
      lysosome-related organelle biogenesis.
- term:
    id: GO:0098588
    label: bounding membrane of organelle
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: >-
      Rab7 localizes to the bounding membranes of various organelles as a
      peripheral membrane protein.
    action: ACCEPT
    reason: >-
      Accurate general localization consistent with Rab7 membrane-association
      pattern.
# ============ ISO ANNOTATIONS (ORTHOLOG TRANSFER) ============
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  qualifier: located_in
  review:
    summary: >-
      Lysosomal membrane localization transferred from experimentally
      characterized orthologs.
    action: ACCEPT
    reason: >-
      Core localization, well supported.
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: located_in
  review:
    summary: >-
      Lysosomal membrane localization transferred from human ortholog.
    action: ACCEPT
    reason: >-
      Core localization, consistent with mouse experimental data.
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  qualifier: located_in
  review:
    summary: >-
      Late endosome membrane localization transferred from orthologs.
    action: ACCEPT
    reason: >-
      Core localization.
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: located_in
  review:
    summary: >-
      Late endosome membrane localization transferred from human ortholog.
    action: ACCEPT
    reason: >-
      Core localization.
- term:
    id: GO:0033162
    label: melanosome membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: located_in
  review:
    summary: >-
      Melanosome membrane localization transferred from human ortholog.
    action: KEEP_AS_NON_CORE
    reason: >-
      Cell-type-specific localization in melanocytes (lysosome-related organelle).
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: enables
  review:
    summary: >-
      GTPase activity transferred from human ortholog; also directly demonstrated
      for mouse Rab7.
    action: ACCEPT
    reason: >-
      Core molecular function.
- term:
    id: GO:0003925
    label: G protein activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: enables
  review:
    summary: >-
      G protein (molecular switch) activity transferred from human ortholog.
    action: ACCEPT
    reason: >-
      Core molecular function for a Rab GTPase.
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  qualifier: enables
  review:
    summary: >-
      GTP binding transferred from experimentally characterized orthologs.
    action: ACCEPT
    reason: >-
      Core molecular function.
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: enables
  review:
    summary: >-
      GTP binding transferred from human ortholog.
    action: ACCEPT
    reason: >-
      Core molecular function.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: located_in
  review:
    summary: >-
      Mitochondrial association during mitophagy / at contact sites, transferred
      from human ortholog.
    action: KEEP_AS_NON_CORE
    reason: >-
      Context-dependent localization, not constitutive.
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: colocalizes_with
  review:
    summary: >-
      Lysosome colocalization transferred from human ortholog.
    action: ACCEPT
    reason: >-
      Core localization.
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: located_in
  review:
    summary: >-
      Lysosome localization transferred from human ortholog.
    action: ACCEPT
    reason: >-
      Core localization.
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: is_active_in
  review:
    summary: >-
      Active Rab7 functions on the lysosomal membrane (ortholog transfer).
    action: ACCEPT
    reason: >-
      Core site of action.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: colocalizes_with
  review:
    summary: >-
      Late endosome colocalization transferred from human ortholog.
    action: ACCEPT
    reason: >-
      Core localization.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  qualifier: located_in
  review:
    summary: >-
      Late endosome localization transferred from orthologs.
    action: ACCEPT
    reason: >-
      Canonical core localization.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: located_in
  review:
    summary: >-
      Late endosome localization transferred from human ortholog.
    action: ACCEPT
    reason: >-
      Canonical core localization.
- term:
    id: GO:0006622
    label: protein targeting to lysosome
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Rab7 targets cargo proteins to the lysosome for degradation (ortholog
      transfer).
    action: ACCEPT
    reason: >-
      Core function in degradative trafficking.
- term:
    id: GO:0007174
    label: epidermal growth factor catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Rab7 mediates EGF/EGFR degradation through the endolysosomal pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Specific instance of the general endosome-to-lysosome degradative function.
- term:
    id: GO:0008333
    label: endosome to lysosome transport
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Endosome-to-lysosome transport transferred from human ortholog.
    action: ACCEPT
    reason: >-
      Core biological function.
- term:
    id: GO:0009617
    label: response to bacterium
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Rab7 participates in responses to intracellular bacteria via phagosome
      maturation.
    action: KEEP_AS_NON_CORE
    reason: >-
      Downstream physiological consequence of the core phagosome maturation
      function.
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: is_active_in
  review:
    summary: >-
      Active Rab7 functions on the endosome membrane (ortholog transfer).
    action: ACCEPT
    reason: >-
      Core site of action.
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: located_in
  review:
    summary: >-
      Endosome membrane localization transferred from human ortholog.
    action: ACCEPT
    reason: >-
      Core localization.
- term:
    id: GO:0019003
    label: GDP binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  qualifier: enables
  review:
    summary: >-
      Rab7 binds GDP in its inactive cytosolic state (ortholog transfer).
    action: ACCEPT
    reason: >-
      Core molecular function of the GTPase cycle.
- term:
    id: GO:0019003
    label: GDP binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: enables
  review:
    summary: >-
      GDP binding transferred from human ortholog.
    action: ACCEPT
    reason: >-
      Core molecular function.
- term:
    id: GO:0019076
    label: viral release from host cell
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Rab7 endolysosomal function is co-opted during certain viral life cycles
      (e.g. HIV-1).
    action: KEEP_AS_NON_CORE
    reason: >-
      Host-pathogen exploitation of Rab7 function rather than a primary
      biological role.
- term:
    id: GO:0022615
    label: protein to membrane docking
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Rab7 mediates docking of the retromer coat complex to endosomal membranes.
    action: ACCEPT
    reason: >-
      Core function in retromer recruitment and cargo sorting.
- term:
    id: GO:0030672
    label: synaptic vesicle membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  qualifier: is_active_in
  review:
    summary: >-
      Rab7 activity at synaptic vesicle membranes / presynaptic endosomes
      (ortholog transfer).
    action: KEEP_AS_NON_CORE
    reason: >-
      Neuron-specific localization relevant to synaptic recycling and neuropathy.
- term:
    id: GO:0030904
    label: retromer complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: colocalizes_with
  review:
    summary: >-
      Rab7 colocalizes with the retromer complex on endosomes (ortholog transfer).
    action: ACCEPT
    reason: >-
      Core function; Rab7 recruits retromer for cargo sorting.
- term:
    id: GO:0031267
    label: small GTPase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  qualifier: enables
  review:
    summary: >-
      Rab7 can interact with other small GTPases in Rab cascade regulation.
    action: KEEP_AS_NON_CORE
    reason: >-
      Secondary function; Rab7 primarily recruits dedicated effectors.
- term:
    id: GO:0032935
    label: sterol sensor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: contributes_to
  review:
    summary: >-
      Rab7 contributes to sterol sensing via the ORP1L complex (contributes_to
      qualifier).
    action: KEEP_AS_NON_CORE
    reason: >-
      ORP1L carries the sterol-sensing domain; Rab7 scaffolds the complex rather
      than directly sensing sterol.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: part_of
  review:
    summary: >-
      Rab7 forms complexes with multiple effectors (RILP, ORP1L, PLEKHM1,
      retromer, HOPS).
    action: ACCEPT
    reason: >-
      Accurate, though general; specific complex memberships are also captured.
- term:
    id: GO:0036466
    label: synaptic vesicle recycling via endosome
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  qualifier: involved_in
  review:
    summary: >-
      Rab7 involvement in synaptic vesicle recycling via endosomes (ortholog
      transfer).
    action: KEEP_AS_NON_CORE
    reason: >-
      Neuron-specific process, not a ubiquitous Rab7 function.
- term:
    id: GO:0042147
    label: retrograde transport, endosome to Golgi
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Rab7-dependent retromer recruitment drives endosome-to-Golgi retrograde
      transport (e.g. CI-M6PR).
    action: ACCEPT
    reason: >-
      Core function downstream of retromer recruitment.
- term:
    id: GO:0042632
    label: cholesterol homeostasis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Rab7-ORP1L coordinates cholesterol sensing and late endosome positioning.
    action: KEEP_AS_NON_CORE
    reason: >-
      Specialized function mediated by the ORP1L effector; not the primary
      degradative role.
- term:
    id: GO:0045022
    label: early endosome to late endosome transport
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Rab7 controls the Rab5-to-Rab7 conversion that matures early endosomes into
      late endosomes. Confirmed in vivo in mouse liver as a mediator of late
      endosomal maturation.
    action: ACCEPT
    reason: >-
      Core function; loss of Rab7 perturbs endosomal maturation in vivo.
    supported_by:
      - reference_id: PMID:41814093
        supporting_text: "Loss of Rab7, a mediator of late endosomal maturation, increased LNP escape."
- term:
    id: GO:0045335
    label: phagocytic vesicle
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: located_in
  review:
    summary: >-
      Phagocytic vesicle localization transferred from human ortholog.
    action: ACCEPT
    reason: >-
      Consistent with the phagosome maturation function.
- term:
    id: GO:0045453
    label: bone resorption
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  qualifier: involved_in
  review:
    summary: >-
      Rab7 is required for osteoclast ruffled-border function and bone resorption,
      directly demonstrated in mouse osteoclasts.
    action: KEEP_AS_NON_CORE
    reason: >-
      Cell-type-specific physiological role; the ruffled border is a
      lysosome-related compartment dependent on Rab7-mediated trafficking.
- term:
    id: GO:0045732
    label: positive regulation of protein catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Rab7-mediated endolysosomal and autophagic flux promotes protein
      degradation.
    action: ACCEPT
    reason: >-
      Direct consequence of the core degradative trafficking function.
- term:
    id: GO:0048524
    label: positive regulation of viral process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Rab7 endolysosomal function can be exploited to promote viral processes.
    action: KEEP_AS_NON_CORE
    reason: >-
      Host-pathogen interaction rather than a primary biological role.
- term:
    id: GO:0061462
    label: protein localization to lysosome
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Rab7 directs protein cargo to the lysosome.
    action: ACCEPT
    reason: >-
      Core function in lysosomal targeting.
- term:
    id: GO:0090120
    label: lysosome to ER cholesterol transport
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Rab7-ORP1L complex regulates cholesterol transport from lysosomes to the ER.
    action: KEEP_AS_NON_CORE
    reason: >-
      Specialized lipid-homeostasis function mediated by the ORP1L effector.
- term:
    id: GO:0090383
    label: phagosome acidification
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Rab7 regulates phagosomal acidification during maturation.
    action: ACCEPT
    reason: >-
      Part of the core phagosome maturation function.
- term:
    id: GO:0090385
    label: phagosome-lysosome fusion
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Phagosome-lysosome fusion transferred from human ortholog.
    action: ACCEPT
    reason: >-
      Core function in phagolysosome formation.
- term:
    id: GO:0097208
    label: alveolar lamellar body
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  qualifier: located_in
  review:
    summary: >-
      Rab7 localization to alveolar lamellar bodies (lysosome-related organelles
      of type II pneumocytes).
    action: KEEP_AS_NON_CORE
    reason: >-
      Cell-type-specific localization.
- term:
    id: GO:0098830
    label: presynaptic endosome
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  qualifier: is_active_in
  review:
    summary: >-
      Rab7 activity at presynaptic endosomes (ortholog transfer).
    action: KEEP_AS_NON_CORE
    reason: >-
      Neuron-specific localization relevant to synaptic function.
- term:
    id: GO:0099638
    label: endosome to plasma membrane protein transport
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Rab7 can influence recycling of cargo to the plasma membrane.
    action: KEEP_AS_NON_CORE
    reason: >-
      Secondary function; the primary Rab7 role is degradative trafficking.
- term:
    id: GO:1903542
    label: negative regulation of exosomal secretion
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Rab7 can negatively regulate exosome secretion by directing MVBs toward
      lysosomal degradation.
    action: KEEP_AS_NON_CORE
    reason: >-
      Context-dependent regulatory role affecting exosome biogenesis.
- term:
    id: GO:1903543
    label: positive regulation of exosomal secretion
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: involved_in
  review:
    summary: >-
      Rab7 can also positively regulate exosome secretion in the
      syndecan-syntenin-ALIX pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Context-dependent; Rab7 has opposing effects on exosome release depending
      on pathway.
- term:
    id: GO:1905394
    label: retromer complex binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  qualifier: enables
  review:
    summary: >-
      Rab7 recruits/binds the retromer complex on endosomes for cargo sorting.
    action: ACCEPT
    reason: >-
      Core molecular function specifying the retromer interaction.
# ============ EXPERIMENTAL (MOUSE) ANNOTATIONS ============
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: EXP
  original_reference_id: PMID:16855591
  qualifier: enables
  review:
    summary: >-
      Biochemical study of TBC-domain GAPs directly characterizing Rab7 GTP
      hydrolysis, including the intrinsic GTPase activity accelerated by GAPs.
    action: ACCEPT
    reason: >-
      Core molecular function with direct experimental support.
    supported_by:
      - reference_id: PMID:16855591
        supporting_text: "TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism."
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: EXP
  original_reference_id: PMID:28063257
  qualifier: located_in
  review:
    summary: >-
      Experimental localization of Rab7 to the lysosomal membrane in an autophagy
      screen; Rab7 is cited as the defining marker of late endosomes and lysosomes.
    action: ACCEPT
    reason: >-
      Core localization, experimentally supported.
    supported_by:
      - reference_id: PMID:28063257
        supporting_text: "late endosomes (Rab7, Rab9), lysosomes (Rab7) and others"
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: >-
      Endosome membrane localization by sequence similarity to characterized
      orthologs.
    action: ACCEPT
    reason: >-
      Core localization.
- term:
    id: GO:0031410
    label: cytoplasmic vesicle
  evidence_type: EXP
  original_reference_id: PMID:23179371
  qualifier: located_in
  review:
    summary: >-
      Rab7 on cytoplasmic vesicles in a study of CMT2B mutant interaction with
      peripherin; the paper notes Rab7a localizes to late endosomes and controls
      transport to late endosomes/lysosomes and maturation of phagosomes and
      autophagosomes.
    action: ACCEPT
    reason: >-
      Accurate, though general; consistent with vesicular Rab7 localization.
    supported_by:
      - reference_id: PMID:23179371
        supporting_text: "RAB7A is localized to late endosomes and controls transport to late endosomes and lysosomes as well as maturation of phagosomes and autophagosomes"
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: >-
      Late endosome membrane localization by sequence similarity.
    action: ACCEPT
    reason: >-
      Core localization.
- term:
    id: GO:0031966
    label: mitochondrial membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: >-
      Mitochondrial membrane association by sequence similarity (mitophagy /
      contact-site context).
    action: KEEP_AS_NON_CORE
    reason: >-
      Context-dependent localization.
- term:
    id: GO:0033162
    label: melanosome membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: >-
      Melanosome membrane localization by sequence similarity.
    action: KEEP_AS_NON_CORE
    reason: >-
      Cell-type-specific (melanocyte) localization.
- term:
    id: GO:0003925
    label: G protein activity
  evidence_type: IDA
  original_reference_id: PMID:16855591
  qualifier: enables
  review:
    summary: >-
      Direct demonstration of Rab7 nucleotide-dependent G protein behavior in the
      GAP study.
    action: ACCEPT
    reason: >-
      Core molecular function, directly supported.
    supported_by:
      - reference_id: PMID:16855591
        supporting_text: "TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:38744829
  qualifier: enables
  review:
    summary: >-
      Interaction between Rab7 and the effector RUFY4 in osteoclasts.
    action: REMOVE
    reason: >-
      GO:0005515 protein binding is uninformative. RUFY4 is a characterized Rab7
      effector for autophagy/lysosome tethering; the functional role is captured
      by trafficking terms.
    supported_by:
      - reference_id: PMID:38744829
        supporting_text: "Recent studies have shown that RUFY4 is an effector of small GTPases such as Rab7"
- term:
    id: GO:0098943
    label: neurotransmitter receptor transport, postsynaptic endosome to lysosome
  evidence_type: IDA
  original_reference_id: PMID:24217640
  qualifier: involved_in
  review:
    summary: >-
      SynGO annotation associating Rab7 with postsynaptic endosome-to-lysosome
      AMPA-receptor trafficking during long-term depression.
    action: KEEP_AS_NON_CORE
    reason: >-
      Revisited in the human/mouse Deliverome comparison. The accessible PMID
      text supports AMPA-receptor movement into late endosomal/lysosomal
      compartments during LTD, which is compatible with Rab7's conserved
      endosome-to-lysosome role. However, the paper emphasizes
      stargazin/AP-2/AP-3A rather than a Rab7-specific perturbation, so this
      should be retained only as a SynGO neuronal-context annotation and not
      treated as core Rab7 biology.
    supported_by:
      - reference_id: PMID:24217640
        supporting_text: "stargazin-AP-3A abrogates the late endosomal/lysosomal
          trafficking of AMPA receptors"
- term:
    id: GO:0098943
    label: neurotransmitter receptor transport, postsynaptic endosome to lysosome
  evidence_type: IMP
  original_reference_id: PMID:24217640
  qualifier: involved_in
  review:
    summary: >-
      SynGO IMP annotation for Rab7 in AMPA-receptor degradative trafficking
      during LTD.
    action: KEEP_AS_NON_CORE
    reason: >-
      Revisited in the human/mouse Deliverome comparison. The PMID supports
      activity-dependent AMPA-receptor routing from early endosomes toward
      late endosomes/lysosomes, a route Rab7 generally controls. Because the
      accessible text identifies stargazin/AP-2/AP-3A as the experimental
      focus and does not give Rab7-specific mechanistic evidence, retain this
      as non-core and indirect.
    supported_by:
      - reference_id: PMID:24217640
        supporting_text: "transport from the cell surface to early endosomes and
          from early endosomes to late endosomes/lysosomes"
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: IDA
  original_reference_id: PMID:24217640
  qualifier: is_active_in
  review:
    summary: >-
      SynGO annotation placing Rab7 at glutamatergic synapses in AMPA-receptor
      trafficking.
    action: KEEP_AS_NON_CORE
    reason: >-
      The source is a hippocampal LTD/AMPAR-trafficking study, so the
      glutamatergic-synapse context is biologically plausible for the SynGO
      annotation. It is not a core Rab7 localization, and the accessible text
      does not provide direct Rab7 localization or perturbation evidence, so
      retain only as a context-specific neuronal annotation.
    supported_by:
      - reference_id: PMID:24217640
        supporting_text: "necessary for low-frequency stimulus-evoked LTD in CA1
          hippocampal neurons"
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: IMP
  original_reference_id: PMID:24217640
  qualifier: is_active_in
  review:
    summary: >-
      SynGO IMP annotation for Rab7 functional role at glutamatergic synapses
      (LTD).
    action: KEEP_AS_NON_CORE
    reason: >-
      The PMID supports postsynaptic AMPA-receptor trafficking during LTD in
      hippocampal neurons, but the accessible text centers on stargazin and
      adaptor complexes rather than Rab7-specific evidence. Retain the SynGO
      row as a non-core neuronal-context annotation and avoid using it as a
      primary assertion about Rab7 function.
    supported_by:
      - reference_id: PMID:24217640
        supporting_text: "postsynaptic AMPA receptor trafficking mediates LTD"
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:35353806
  qualifier: located_in
  review:
    summary: >-
      Rab7 on late endosomes in a study of TMED2/SMO trafficking, by
      super-resolution 3D-STORM imaging.
    action: ACCEPT
    reason: >-
      Core localization, experimentally observed.
    supported_by:
      - reference_id: PMID:35353806
        supporting_text: "Dual color 3D-STORM analysis showing ERP72 (C), RCAS1 (D) and RAB7 (E) distribution"
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IDA
  original_reference_id: PMID:23708524
  qualifier: colocalizes_with
  review:
    summary: >-
      Rab7 colocalizes with lysosomal membranes during autolysosomal lipid
      degradation in adipocytes.
    action: ACCEPT
    reason: >-
      Core localization, experimentally supported in mouse.
    supported_by:
      - reference_id: PMID:23708524
        supporting_text: "RAB7 plays a pivotal role in the regulation of this autolysosome-mediated lipid degradation in fat cells."
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:23708524
  qualifier: located_in
  review:
    summary: >-
      Inactive GDP-bound Rab7 is cytosolic; observed in the lipolysis/lipophagy
      study.
    action: ACCEPT
    reason: >-
      Consistent with the GTPase cycle (cytosolic GDP-bound pool).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29712939
  qualifier: enables
  review:
    summary: >-
      Interaction supporting V-ATPase a3-dependent Rab7 recruitment to secretory
      lysosomes.
    action: REMOVE
    reason: >-
      GO:0005515 protein binding is uninformative; the functional relationship is
      captured by recruitment/localization terms.
    supported_by:
      - reference_id: PMID:29712939
        supporting_text: "Rab7, a small GTPase involved in organelle trafficking."
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: >-
      Mitochondrial association by sequence similarity (mitophagy context).
    action: KEEP_AS_NON_CORE
    reason: >-
      Context-dependent localization, not constitutive.
- term:
    id: GO:0099638
    label: endosome to plasma membrane protein transport
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      Rab7 influence on plasma-membrane-directed cargo transport by sequence
      similarity.
    action: KEEP_AS_NON_CORE
    reason: >-
      Secondary function relative to the core degradative role.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:27390154
  qualifier: located_in
  review:
    summary: >-
      Rab7 used as the late endosomal marker in a melanocyte WASH/strumpellin
      colocalization study.
    action: ACCEPT
    reason: >-
      Core localization, experimentally observed.
    supported_by:
      - reference_id: PMID:27390154
        supporting_text: "a significant increase in the colocalization of WASH and the late endosomal marker Rab7"
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IDA
  original_reference_id: PMID:29712939
  qualifier: is_active_in
  review:
    summary: >-
      Active Rab7 functions on (secretory) lysosomes, recruited in a V-ATPase
      a3-dependent manner.
    action: ACCEPT
    reason: >-
      Core site of action, experimentally supported in mouse.
    supported_by:
      - reference_id: PMID:29712939
        supporting_text: "Essential Role of the a3 Isoform of V-ATPase in Secretory Lysosome Trafficking via Rab7 Recruitment."
- term:
    id: GO:0051650
    label: establishment of vesicle localization
  evidence_type: IMP
  original_reference_id: PMID:29712939
  qualifier: acts_upstream_of_or_within_positive_effect
  review:
    summary: >-
      Rab7 recruitment is required for proper trafficking/positioning of secretory
      lysosomes (V-ATPase a3-dependent).
    action: ACCEPT
    reason: >-
      Consistent with the established Rab7 role in vesicle/organelle positioning.
    supported_by:
      - reference_id: PMID:29712939
        supporting_text: "Essential Role of the a3 Isoform of V-ATPase in Secretory Lysosome Trafficking via Rab7 Recruitment."
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:25592972
  qualifier: located_in
  review:
    summary: >-
      Rab7 used as a late-endosome marker in subcellular fractionation in a study
      of BACE1 lysosomal targeting.
    action: ACCEPT
    reason: >-
      Core localization, experimentally observed.
    supported_by:
      - reference_id: PMID:25592972
        supporting_text: "immunoblotted for BACE1, APP, rab5, or rab7"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27777970
  qualifier: enables
  review:
    summary: >-
      Rab7 binds the PLEKHM1/DEF8 lysosome-positioning effector complex.
    action: REMOVE
    reason: >-
      GO:0005515 protein binding is uninformative. PLEKHM1 is a well-characterized
      Rab7 effector; the function is captured by lysosome positioning/trafficking
      terms.
    supported_by:
      - reference_id: PMID:27777970
        supporting_text: "PLEKHM1 binds to RAB7 and is critical for lysosome trafficking."
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IDA
  original_reference_id: PMID:26582200
  qualifier: located_in
  review:
    summary: >-
      Rab7 on endosomes in a study of Lifeguard/Fas signaling.
    action: ACCEPT
    reason: >-
      Accurate, though general; more specific late endosome terms are also
      annotated.
- term:
    id: GO:0005811
    label: lipid droplet
  evidence_type: IDA
  original_reference_id: PMID:23708524
  qualifier: located_in
  review:
    summary: >-
      Rab7 localizes to lipid droplets and the LD-associated pool drives their
      autophagic degradation during beta-adrenergic lipolysis in mouse adipocytes.
    action: ACCEPT
    reason: >-
      Experimentally supported localization underpinning the lipophagy function.
    supported_by:
      - reference_id: PMID:23708524
        supporting_text: "ADRB2 stimulation has caused a marked increase in the autophagy-targeted LDs for lysosomal degradation, which is dependent on the LD-associated RAB7"
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: IDA
  original_reference_id: PMID:23708524
  qualifier: located_in
  review:
    summary: >-
      Rab7 on late endosome membranes in the adipocyte lipolysis/lipophagy study.
    action: ACCEPT
    reason: >-
      Core localization, experimentally supported.
    supported_by:
      - reference_id: PMID:23708524
        supporting_text: "RAB7, being primarily associated with late endosomes, is
          a central factor in endosomal trafficking"
- term:
    id: GO:0061724
    label: lipophagy
  evidence_type: IMP
  original_reference_id: PMID:23708524
  qualifier: involved_in
  review:
    summary: >-
      Rab7 is required for autolysosome-mediated lipid-droplet degradation
      (lipophagy) in fat cells, shown by knockdown and dominant-negative mutant.
    action: ACCEPT
    reason: >-
      Directly demonstrated mouse function; a specialized branch of the core
      autophagy role.
    supported_by:
      - reference_id: PMID:23708524
        supporting_text: "RAB7 plays a pivotal role in the regulation of this autolysosome-mediated lipid degradation in fat cells."
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:24760869
  qualifier: located_in
  review:
    summary: >-
      Rab7 on late endosomes in a study of Nedd4-2/TrkA trafficking.
    action: ACCEPT
    reason: >-
      Core localization, experimentally observed.
- term:
    id: GO:0034045
    label: phagophore assembly site membrane
  evidence_type: IDA
  original_reference_id: PMID:19956673
  qualifier: located_in
  review:
    summary: >-
      Rab7 at the phagophore assembly site during formation of GAS-containing
      autophagosome-like vacuoles (GcAVs).
    action: ACCEPT
    reason: >-
      Consistent with the Rab7 role in autophagy.
    supported_by:
      - reference_id: PMID:19956673
        supporting_text: "Rab7, a member of the small GTPase Rab family, may be involved in GcAV formation"
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:24334765
  qualifier: located_in
  review:
    summary: >-
      Rab7 on late endosomes in a study of TMEM127 endolysosomal function.
    action: ACCEPT
    reason: >-
      Core localization, experimentally observed.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22467241
  qualifier: enables
  review:
    summary: >-
      Rab7 interaction in the context of ATP6AP1/Ac45 and osteoclast lysosomal
      trafficking.
    action: REMOVE
    reason: >-
      GO:0005515 protein binding is uninformative; the relevant function is
      lysosomal trafficking in osteoclasts.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:24035762
  qualifier: located_in
  review:
    summary: >-
      Rab7 used as a late-endosome marker (co-staining with NHE6) in a study of
      TrkB endosomal signaling.
    action: ACCEPT
    reason: >-
      Core localization, experimentally observed.
    supported_by:
      - reference_id: PMID:24035762
        supporting_text: "Rab7-associated endosomes (late endosomes)"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24549040
  qualifier: enables
  review:
    summary: >-
      Rab7 interaction in the context of C9ORF72 endosomal trafficking.
    action: REMOVE
    reason: >-
      GO:0005515 protein binding is uninformative; C9ORF72 regulates Rab-mediated
      endosomal trafficking, captured by trafficking terms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22275436
  qualifier: enables
  review:
    summary: >-
      Rab7 interaction in melanoregulin/RILP-p150Glued retrograde melanosome
      transport.
    action: REMOVE
    reason: >-
      GO:0005515 protein binding is uninformative; the RILP effector axis is
      captured by trafficking/transport terms.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:23028046
  qualifier: located_in
  review:
    summary: >-
      Rab7 on late endosomes in a macrophage anthrax-toxin/MLN64 study.
    action: ACCEPT
    reason: >-
      Core localization, experimentally observed.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:18656450
  qualifier: located_in
  review:
    summary: >-
      Cytoplasmic localization observed in a cGKII/Rab11 trafficking study.
    action: ACCEPT
    reason: >-
      Accurate but general; the cytosol and specific vesicular compartments are
      more informative and also annotated.
- term:
    id: GO:0045335
    label: phagocytic vesicle
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: >-
      Phagocytic vesicle localization by sequence similarity.
    action: ACCEPT
    reason: >-
      Consistent with the phagosome maturation function.
- term:
    id: GO:0090383
    label: phagosome acidification
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      Phagosome acidification by sequence similarity.
    action: ACCEPT
    reason: >-
      Part of the core phagosome maturation function.
- term:
    id: GO:0090385
    label: phagosome-lysosome fusion
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      Phagosome-lysosome fusion by sequence similarity.
    action: ACCEPT
    reason: >-
      Core function in phagolysosome formation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19368996
  qualifier: enables
  review:
    summary: >-
      Rab7 interaction in a study of the drs tumor suppressor in autophagy
      maturation.
    action: REMOVE
    reason: >-
      GO:0005515 protein binding is uninformative; the autophagy maturation role
      is captured by autophagy terms.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:19509052
  qualifier: located_in
  review:
    summary: >-
      Rab7 on late endosomes in a Derlin membrane-protein accumulation study.
    action: ACCEPT
    reason: >-
      Core localization, experimentally observed.
- term:
    id: GO:0045022
    label: early endosome to late endosome transport
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      Early-to-late endosome transport by sequence similarity (Rab5-to-Rab7
      conversion).
    action: ACCEPT
    reason: >-
      Core function in endosomal maturation.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:20943658
  qualifier: located_in
  review:
    summary: >-
      Rab7 marks the late endosomes to which Nmnat2 localizes.
    action: ACCEPT
    reason: >-
      Core localization, experimentally observed.
    supported_by:
      - reference_id: PMID:20943658
        supporting_text: "Nmnat2 localizes to Rab7-containing late endosomes"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12972561
  qualifier: enables
  review:
    summary: >-
      Identification of Rabring7 (BCA2/RNF115) as a Rab7 target protein with a
      RING finger motif.
    action: REMOVE
    reason: >-
      GO:0005515 protein binding is uninformative; this is a specific effector
      interaction whose function is better captured by other terms.
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:15588329
  qualifier: located_in
  review:
    summary: >-
      Rab7 used as the late endosomal marker in a juvenile neuronal ceroid
      lipofuscinosis cerebellar cell model.
    action: ACCEPT
    reason: >-
      Core localization, experimentally observed.
    supported_by:
      - reference_id: PMID:15588329
        supporting_text: "the late endosomal marker, Rab7"
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: ISO
  original_reference_id: PMID:15078902
  qualifier: located_in
  review:
    summary: >-
      Lysosome localization transferred from the retromer ortholog study, where
      the retromer subunit VPS26 colocalizes with Rab7.
    action: ACCEPT
    reason: >-
      Core localization.
    supported_by:
      - reference_id: PMID:15078902
        supporting_text: "modest colocalization between mVPS26 and GFP-rab7"
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: ISO
  original_reference_id: PMID:15078902
  qualifier: located_in
  review:
    summary: >-
      Late endosome localization transferred from the retromer ortholog study,
      where the retromer subunit VPS26 colocalizes with Rab7.
    action: ACCEPT
    reason: >-
      Core localization.
    supported_by:
      - reference_id: PMID:15078902
        supporting_text: "modest colocalization between mVPS26 and GFP-rab7"
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IDA
  original_reference_id: PMID:11172003
  qualifier: located_in
  review:
    summary: >-
      Rab7 on late endosomes in a study of the Rab4 effector Rabip4.
    action: ACCEPT
    reason: >-
      Core localization, experimentally observed.
- term:
    id: GO:0006886
    label: intracellular protein transport
  evidence_type: TAS
  original_reference_id: PMID:11042173
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      Rab7 general role in intracellular protein transport, from a Golgi membrane
      proteomics paper.
    action: KEEP_AS_NON_CORE
    reason: >-
      Too general; the specific endosome-to-lysosome and retrograde transport
      terms capture the actual function more precisely.
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IDA
  original_reference_id: PMID:11042173
  qualifier: located_in
  review:
    summary: >-
      Rab7 detected in a bulk proteomic characterization of abundant Golgi
      membrane proteins.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Rab7 is a late-endosome/lysosome GTPase; detection in a Golgi membrane
      fraction most plausibly reflects co-fractionation/contamination or transient
      retrograde-pathway association rather than a genuine steady-state Golgi pool.
      Not a core localization.

core_functions:
  - molecular_function:
      id: GO:0003924
      label: GTPase activity
    description: >-
      Rab7 functions as a small GTPase molecular switch (EC 3.6.5.2), cycling
      between an inactive GDP-bound (cytosolic) and an active GTP-bound
      (membrane-associated) state. Activation by the Mon1-Ccz1 GEF on maturing
      endosomes and inactivation by TBC-domain GAPs underpins its control of late
      endocytic trafficking, autophagy (including lipophagy), phagosome
      maturation and lysosome biogenesis.
    directly_involved_in:
      - id: GO:0008333
        label: endosome to lysosome transport
      - id: GO:0045022
        label: early endosome to late endosome transport
      - id: GO:0042147
        label: retrograde transport, endosome to Golgi
      - id: GO:0090385
        label: phagosome-lysosome fusion
      - id: GO:0061724
        label: lipophagy
    locations:
      - id: GO:0005770
        label: late endosome
      - id: GO:0005764
        label: lysosome
      - id: GO:0031902
        label: late endosome membrane
      - id: GO:0000421
        label: autophagosome membrane
      - id: GO:0005811
        label: lipid droplet
    supported_by:
      - reference_id: PMID:16855591
        supporting_text: "TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism."
      - reference_id: PMID:41814093
        supporting_text: "Loss of Rab7, a mediator of late endosomal maturation, increased LNP escape."
      - reference_id: PMID:23708524
        supporting_text: "RAB7 plays a pivotal role in the regulation of this autolysosome-mediated lipid degradation in fat cells."
  - molecular_function:
      id: GO:1905394
      label: retromer complex binding
    description: >-
      Active Rab7 recruits and binds the retromer complex on late endosomes,
      docking it to the membrane to drive cargo-selective endosome-to-Golgi
      retrograde transport.
    directly_involved_in:
      - id: GO:0042147
        label: retrograde transport, endosome to Golgi
      - id: GO:0022615
        label: protein to membrane docking
    locations:
      - id: GO:0005770
        label: late endosome

proposed_new_terms: []

suggested_questions:
  - question: >-
      The Nature Biotechnology study (PMID:41814093) shows that loss of Rab7
      increases cytosolic escape of lipid nanoparticles in mouse liver. Does Rab7
      activity define a general, druggable checkpoint that partitions endocytosed
      cargo between degradation and cytosolic escape, and can transient Rab7
      modulation be exploited to enhance therapeutic nucleic-acid delivery?
  - question: >-
      How are the tissue-specialized Rab7 functions (adipocyte lipophagy,
      synaptic AMPA-receptor turnover, osteoclast ruffled-border trafficking)
      differentially wired through distinct effectors despite a single ubiquitous
      GTPase switch?

suggested_experiments:
  - description: >-
      Use the LysoTag/Lysosomal Barcoding in vivo endosomal-escape assay
      (PMID:41814093) across conditional Rab7 (Rab7a) knockout tissues to quantify,
      in a tissue-resolved manner, how Rab7 loss shifts the balance between
      lysosomal degradation and cytosolic escape of endocytosed cargo.
  - description: >-
      Effector-interaction profiling (proximity labeling) of mouse Rab7 in
      adipocytes, neurons and osteoclasts to map the cell-type-specific effector
      modules that route the common Rab7 switch to lipophagy, synaptic receptor
      degradation and ruffled-border trafficking, respectively.

references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with GO
      terms
    findings: []
  - id: GO_REF:0000003
    title: Gene Ontology annotation based on Enzyme Commission mapping
    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:0000096
    title: Automated transfer of experimentally-verified manual GO annotation data to
      mouse-rat orthologs
    findings: []
  - id: GO_REF:0000117
    title: Electronic Gene Ontology annotations created by ARBA machine learning models
    findings: []
  - id: GO_REF:0000119
    title: Automated transfer of experimentally-verified manual GO annotation data to
      mouse-human orthologs
    findings: []
  - id: PMID:11042173
    title: Proteomics characterization of abundant Golgi membrane proteins.
    findings:
      - statement: Rab7 was detected in a bulk proteomic fraction of Golgi membranes
        supporting_text: "Proteomics characterization of abundant Golgi membrane proteins."
  - id: PMID:11172003
    title: A FYVE-finger-containing protein, Rabip4, is a Rab4 effector involved in
      early endosomal traffic.
    findings: []
  - id: PMID:12972561
    title: Rabring7, a novel Rab7 target protein with a RING finger motif.
    findings: []
  - id: PMID:15078902
    title: Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer.
    findings: []
  - id: PMID:15588329
    title: Membrane trafficking and mitochondrial abnormalities precede subunit c deposition
      in a cerebellar cell model of juvenile neuronal ceroid lipofuscinosis.
    findings: []
  - id: PMID:16855591
    title: TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger
      mechanism.
    findings:
      - statement: TBC-domain GAPs accelerate Rab7 GTP hydrolysis
        supporting_text: "TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism."
  - id: PMID:18656450
    title: Trafficking of cGMP-dependent protein kinase II via interaction with Rab11.
    findings: []
  - id: PMID:19368996
    title: The drs tumor suppressor is involved in the maturation process of autophagy
      induced by low serum.
    findings: []
  - id: PMID:19509052
    title: Derlin-dependent accumulation of integral membrane proteins at cell surfaces.
    findings: []
  - id: PMID:19956673
    title: An initial step of GAS-containing autophagosome-like vacuoles formation requires
      Rab7.
    findings: []
  - id: PMID:20943658
    title: Expression, localization, and biochemical characterization of nicotinamide
      mononucleotide adenylyltransferase 2.
    findings: []
  - id: PMID:22275436
    title: Melanoregulin regulates retrograde melanosome transport through interaction
      with the RILP-p150Glued complex in melanocytes.
    findings: []
  - id: PMID:22467241
    title: V-ATPase subunit ATP6AP1 (Ac45) regulates osteoclast differentiation, extracellular
      acidification, lysosomal trafficking, and protease exocytosis in osteoclast-mediated
      bone resorption.
    findings: []
  - id: PMID:23028046
    title: Cellular adaptation to anthrax lethal toxin-induced mitochondrial cholesterol
      enrichment, hyperpolarization, and reactive oxygen species generation through
      downregulating MLN64 in macrophages.
    findings: []
  - id: PMID:23179371
    title: Charcot-Marie-Tooth type 2B disease-causing RAB7A mutant proteins show altered
      interaction with the neuronal intermediate filament peripherin.
    findings: []
  - id: PMID:23708524
    title: β-adrenergic receptor-stimulated lipolysis requires the RAB7-mediated autolysosomal
      lipid degradation.
    findings:
      - statement: Rab7 is required for lipophagy of lipid droplets in fat cells
        supporting_text: "RAB7 plays a pivotal role in the regulation of this autolysosome-mediated lipid degradation in fat cells."
      - statement: LD-associated Rab7 mediates autophagic targeting of lipid droplets
        supporting_text: "ADRB2 stimulation has caused a marked increase in the autophagy-targeted LDs for lysosomal degradation, which is dependent on the LD-associated RAB7"
  - id: PMID:24035762
    title: Christianson syndrome protein NHE6 modulates TrkB endosomal signaling required
      for neuronal circuit development.
    findings: []
  - id: PMID:24217640
    title: Stargazin regulates AMPA receptor trafficking through adaptor protein complexes
      during long-term depression.
    findings: []
  - id: PMID:24334765
    title: The tumor susceptibility gene TMEM127 is mutated in renal cell carcinomas
      and modulates endolysosomal function.
    findings: []
  - id: PMID:24549040
    title: C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal dementia,
      regulates endosomal trafficking.
    findings: []
  - id: PMID:24760869
    title: In vivo regulation of NGF-mediated functions by Nedd4-2 ubiquitination of
      TrkA.
    findings: []
  - id: PMID:25592972
    title: An aberrant sugar modification of BACE1 blocks its lysosomal targeting in
      Alzheimer's disease.
    findings: []
  - id: PMID:26582200
    title: Lifeguard Inhibits Fas Ligand-mediated Endoplasmic Reticulum-Calcium Release
      Mandatory for Apoptosis in Type II Apoptotic Cells.
    findings: []
  - id: PMID:27390154
    title: Loss of strumpellin in the melanocytic lineage impairs the WASH Complex but
      does not affect coat colour.
    findings: []
  - id: PMID:27777970
    title: PLEKHM1/DEF8/RAB7 complex regulates lysosome positioning and bone homeostasis.
    findings:
      - statement: PLEKHM1 binds Rab7 and is critical for lysosome trafficking
        supporting_text: "PLEKHM1 binds to RAB7 and is critical for lysosome trafficking."
  - id: PMID:28063257
    title: Genetic screen in Drosophila muscle identifies autophagy-mediated T-tubule
      remodeling and a Rab2 role in autophagy.
    findings: []
  - id: PMID:29712939
    title: Essential Role of the a3 Isoform of V-ATPase in Secretory Lysosome Trafficking
      via Rab7 Recruitment.
    findings:
      - statement: Rab7 is a small GTPase involved in organelle trafficking, recruited
          to secretory lysosomes in a V-ATPase a3-dependent manner
        supporting_text: "Rab7, a small GTPase involved in organelle trafficking."
  - id: PMID:35353806
    title: TMED2 binding restricts SMO to the ER and Golgi compartments.
    findings: []
  - id: PMID:38744829
    title: RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal
      trafficking of osteoclasts.
    findings:
      - statement: RUFY4 is an effector of small GTPases including Rab7
        supporting_text: "Recent studies have shown that RUFY4 is an effector of small GTPases such as Rab7"
      - statement: Rab7 is enriched at the osteoclast ruffled border and required for
          bone resorption
        supporting_text: "Notably, Rab7 is highly expressed at the ruffled border of bone-resorbing osteoclasts and its knockdown disrupts both the targeting of vesicles to the ruffled border and bone resorption."
  - id: PMID:41814093
    title: In vivo endosomal escape assay identifies mechanisms for efficient hepatic
      LNP delivery.
    findings:
      - statement: Rab7 is a mediator of late endosomal maturation; its loss increases
          cytosolic escape of lipid nanoparticles in mouse liver
        supporting_text: "Loss of Rab7, a mediator of late endosomal maturation, increased LNP escape."
      - statement: LysoTag mice enable immunoisolation of liver lysosomes to quantify
          in vivo endosomal escape
        supporting_text: "we used LysoTag mice, which allow immunoisolation of liver lysosomes"
  - id: file:mouse/Rab7/Rab7-deep-research-manual.md
    title: Manual research synthesis for mouse Rab7 (deep-research providers unavailable)
    findings: []