id: Q969Q5
gene_symbol: RAB24
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  RAB24 encodes an atypical Rab-family small GTPase that is predominantly GTP-bound and has low
  intrinsic GTPase activity. Its best-supported protein-homeostasis role is at late basal autophagy:
  RAB24 targets to autophagic vacuoles/autophagosome membranes and is required for maturation and/or
  clearance of late autophagic compartments under nutrient-rich basal conditions, without being
  required for short starvation-induced autophagosome formation. Broader cytosolic, membrane,
  endocytic, and mouse-oocyte/spindle annotations are secondary contexts rather than the core RAB24
  function.
existing_annotations:
- term:
    id: GO:0005776
    label: autophagosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: autophagosome is a core RAB24 autophagy-associated location.
    action: ACCEPT
    reason: RAB24 localizes to autophagic vacuoles/autophagic compartments and the autophagosome membrane context is directly relevant to its basal autophagic-compartment maturation/clearance role.
    supported_by:
    - reference_id: PMID:26325487
      supporting_text: localization of RAB24 to autophagic vacuoles
    - reference_id: PMID:26325487
      supporting_text: maturation and/or clearance of autophagic compartments under nutrient-rich conditions
    - reference_id: PMID:10660536
      supporting_text: Posttranslational geranylgeranylation of Rab24
    - reference_id: PMID:26325487
      supporting_text: targeting of RAB24 to autophagic compartments
- term:
    id: GO:0030139
    label: endocytic vesicle
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Endocytic-vesicle activity is plausible Rab-effector context but not the core RAB24 PN function; falcon adds RAB24-specific late-endosomal (Rab7/RILP) degradation evidence.
    action: KEEP_AS_NON_CORE
    reason: The IBA inference derives from a broad Rab/endocytic-vesicle family context. Beyond the rabenosyn-5 family-recognition data, the falcon deep research surfaces a more RAB24-specific late-endosomal role - RAB24 colocalizes with Rab7/LAMP1 and forms a complex with Rab7/RILP to support endosome-to-lysosome degradation (Amaya 2016). This strengthens an endocytic/late-endosomal context but remains a degradative late-compartment role rather than a defined early endocytic-vesicle trafficking step, so the core RAB24-specific process evidence is still autophagic-compartment maturation/clearance. The underlying Amaya 2016 paper is not in the cache and was not independently verified, so this is retained as non-core rather than promoted.
    supported_by:
    - reference_id: PMID:16034420
      supporting_text: Rab GTPases interact with functionally diverse effectors
    - reference_id: PMID:16034420
      supporting_text: rabenosyn-5 can achieve highly selective recognition
    - reference_id: file:human/RAB24/RAB24-deep-research-falcon.md
      supporting_text: RAB24 localizes to late endosomal compartments, where it colocalizes with markers such as Rab7 and LAMP1
    - reference_id: file:human/RAB24/RAB24-deep-research-falcon.md
      supporting_text: Forms a complex with Rab7 and RILP on late endosomal membranes
- term:
    id: GO:0000421
    label: autophagosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: autophagosome membrane is a core RAB24 autophagy-associated location, supported by immuno-EM on both limiting membranes.
    action: ACCEPT
    reason: RAB24 localizes to autophagic vacuoles/autophagic compartments and the autophagosome membrane context is directly relevant to its basal autophagic-compartment maturation/clearance role. The falcon deep research adds that immuno-EM places RAB24 on both the inner and outer limiting membranes of autophagosomes/autophagic vacuoles, reinforcing this membrane localization.
    supported_by:
    - reference_id: PMID:26325487
      supporting_text: localization of RAB24 to autophagic vacuoles
    - reference_id: PMID:26325487
      supporting_text: maturation and/or clearance of autophagic compartments under nutrient-rich conditions
    - reference_id: PMID:10660536
      supporting_text: Posttranslational geranylgeranylation of Rab24
    - reference_id: PMID:26325487
      supporting_text: targeting of RAB24 to autophagic compartments
    - reference_id: file:human/RAB24/RAB24-deep-research-falcon.md
      supporting_text: RAB24 localizes to both the inner and outer limiting membranes of autophagosomes and autophagic vacuoles
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: GTPase activity is consistent with RAB24 being an atypical Rab-family small GTPase.
    action: ACCEPT
    reason: RAB24 is a Rab small GTPase; the evidence also cautions that it has unusually low GTP hydrolysis and is predominantly GTP-bound, but this does not negate the Rab GTPase/GTP-binding molecular-function annotation.
    supported_by:
    - reference_id: PMID:10660536
      supporting_text: Rab24 exists predominantly in the GTP state
    - reference_id: PMID:10660536
      supporting_text: The low GTPase activity is related to the presence of serine instead of glutamine
- term:
    id: GO:0003925
    label: G protein activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: G protein activity is consistent with RAB24 being an atypical Rab-family small GTPase.
    action: ACCEPT
    reason: RAB24 is a Rab small GTPase; the evidence also cautions that it has unusually low GTP hydrolysis and is predominantly GTP-bound, but this does not negate the Rab GTPase/GTP-binding molecular-function annotation.
    supported_by:
    - reference_id: PMID:10660536
      supporting_text: Rab24 exists predominantly in the GTP state
    - reference_id: PMID:10660536
      supporting_text: The low GTPase activity is related to the presence of serine instead of glutamine
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: GTP binding is consistent with RAB24 being an atypical Rab-family small GTPase.
    action: ACCEPT
    reason: RAB24 is a Rab small GTPase; the evidence also cautions that it has unusually low GTP hydrolysis and is predominantly GTP-bound, but this does not negate the Rab GTPase/GTP-binding molecular-function annotation.
    supported_by:
    - reference_id: PMID:10660536
      supporting_text: Rab24 exists predominantly in the GTP state
    - reference_id: PMID:10660536
      supporting_text: The low GTPase activity is related to the presence of serine instead of glutamine
- term:
    id: GO:0005819
    label: spindle
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: spindle is transferred mouse oocyte/spindle biology and is not the central proteostasis function.
    action: KEEP_AS_NON_CORE
    reason: UniProt and GOA support this as by-similarity mouse-oocyte/meiosis context. It may be biologically real in a reproductive setting, but it is secondary to RAB24 basal autophagic-compartment maturation/clearance for the human PN review.
    supported_by:
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: Involved in the modulation of meiotic apparatus assembly and meiotic progression during oocyte maturation
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: possibly through regulation of kinetochore-microtubule interaction
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: cytosol is a broad RAB24 localization/context annotation.
    action: KEEP_AS_NON_CORE
    reason: RAB24 can be cytosolic and membrane-associated, with perinuclear/autophagic-compartment localization reported by similarity, but these broad terms should not be treated as the core location when autophagosome/autophagosome membrane is available.
    supported_by:
    - reference_id: PMID:10660536
      supporting_text: Posttranslational geranylgeranylation of Rab24
    - reference_id: PMID:26325487
      supporting_text: targeting of RAB24 to autophagic compartments
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: Only about 20% is recovered in the particulate fraction
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: membrane is a broad RAB24 localization/context annotation.
    action: KEEP_AS_NON_CORE
    reason: RAB24 can be cytosolic and membrane-associated, with perinuclear/autophagic-compartment localization reported by similarity, but these broad terms should not be treated as the core location when autophagosome/autophagosome membrane is available.
    supported_by:
    - reference_id: PMID:10660536
      supporting_text: Posttranslational geranylgeranylation of Rab24
    - reference_id: PMID:26325487
      supporting_text: targeting of RAB24 to autophagic compartments
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: Only about 20% is recovered in the particulate fraction
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: perinuclear region of cytoplasm is a broad RAB24 localization/context annotation.
    action: KEEP_AS_NON_CORE
    reason: RAB24 can be cytosolic and membrane-associated, with perinuclear/autophagic-compartment localization reported by similarity, but these broad terms should not be treated as the core location when autophagosome/autophagosome membrane is available.
    supported_by:
    - reference_id: PMID:10660536
      supporting_text: Posttranslational geranylgeranylation of Rab24
    - reference_id: PMID:26325487
      supporting_text: targeting of RAB24 to autophagic compartments
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: Only about 20% is recovered in the particulate fraction
- term:
    id: GO:0098588
    label: bounding membrane of organelle
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: bounding membrane of organelle is a broad RAB24 localization/context annotation.
    action: KEEP_AS_NON_CORE
    reason: RAB24 can be cytosolic and membrane-associated, with perinuclear/autophagic-compartment localization reported by similarity, but these broad terms should not be treated as the core location when autophagosome/autophagosome membrane is available.
    supported_by:
    - reference_id: PMID:10660536
      supporting_text: Posttranslational geranylgeranylation of Rab24
    - reference_id: PMID:26325487
      supporting_text: targeting of RAB24 to autophagic compartments
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: Only about 20% is recovered in the particulate fraction
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20562859
  qualifier: enables
  review:
    summary: Generic protein binding does not describe the actual RAB24 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The interaction record may identify a binding partner, but protein binding is uninformative as a GO molecular function. RAB24 should be represented by Rab-family GTPase/GTP-binding activity and, where evidence is specific, autophagic-compartment localization/process terms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Generic protein binding does not describe the actual RAB24 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The interaction record may identify a binding partner, but protein binding is uninformative as a GO molecular function. RAB24 should be represented by Rab-family GTPase/GTP-binding activity and, where evidence is specific, autophagic-compartment localization/process terms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Generic protein binding does not describe the actual RAB24 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The interaction record may identify a binding partner, but protein binding is uninformative as a GO molecular function. RAB24 should be represented by Rab-family GTPase/GTP-binding activity and, where evidence is specific, autophagic-compartment localization/process terms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: Generic protein binding does not describe the actual RAB24 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The interaction record may identify a binding partner, but protein binding is uninformative as a GO molecular function. RAB24 should be represented by Rab-family GTPase/GTP-binding activity and, where evidence is specific, autophagic-compartment localization/process terms.
- term:
    id: GO:0001556
    label: oocyte maturation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: oocyte maturation is transferred mouse oocyte/spindle biology and is not the central proteostasis function.
    action: KEEP_AS_NON_CORE
    reason: UniProt and GOA support this as by-similarity mouse-oocyte/meiosis context. It may be biologically real in a reproductive setting, but it is secondary to RAB24 basal autophagic-compartment maturation/clearance for the human PN review.
    supported_by:
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: Involved in the modulation of meiotic apparatus assembly and meiotic progression during oocyte maturation
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: possibly through regulation of kinetochore-microtubule interaction
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: cytoplasm is a broad RAB24 localization/context annotation.
    action: KEEP_AS_NON_CORE
    reason: RAB24 can be cytosolic and membrane-associated, with perinuclear/autophagic-compartment localization reported by similarity, but these broad terms should not be treated as the core location when autophagosome/autophagosome membrane is available.
    supported_by:
    - reference_id: PMID:10660536
      supporting_text: Posttranslational geranylgeranylation of Rab24
    - reference_id: PMID:26325487
      supporting_text: targeting of RAB24 to autophagic compartments
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: Only about 20% is recovered in the particulate fraction
- term:
    id: GO:0005776
    label: autophagosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: autophagosome is a core RAB24 autophagy-associated location.
    action: ACCEPT
    reason: RAB24 localizes to autophagic vacuoles/autophagic compartments and the autophagosome membrane context is directly relevant to its basal autophagic-compartment maturation/clearance role.
    supported_by:
    - reference_id: PMID:26325487
      supporting_text: localization of RAB24 to autophagic vacuoles
    - reference_id: PMID:26325487
      supporting_text: maturation and/or clearance of autophagic compartments under nutrient-rich conditions
    - reference_id: PMID:10660536
      supporting_text: Posttranslational geranylgeranylation of Rab24
    - reference_id: PMID:26325487
      supporting_text: targeting of RAB24 to autophagic compartments
- term:
    id: GO:0006914
    label: autophagy
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Generic autophagy is too broad for the RAB24-specific evidence.
    action: MODIFY
    reason: The RAB24-specific study places the function at maturation and/or clearance of late autophagic compartments under basal nutrient-rich conditions, while formation and short starvation-induced autophagy are not affected. Replace the broad autophagy term with autophagosome maturation.
    proposed_replacement_terms:
    - id: GO:0097352
      label: autophagosome maturation
    supported_by:
    - reference_id: PMID:26325487
      supporting_text: localization of RAB24 to autophagic vacuoles
    - reference_id: PMID:26325487
      supporting_text: maturation and/or clearance of autophagic compartments under nutrient-rich conditions
    - reference_id: PMID:26325487
      supporting_text: Formation of autophagosomes is shown to be unaffected by RAB24-silencing with siRNA
- term:
    id: GO:0008608
    label: attachment of spindle microtubules to kinetochore
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: attachment of spindle microtubules to kinetochore is transferred mouse oocyte/spindle biology and is not the central proteostasis function.
    action: KEEP_AS_NON_CORE
    reason: UniProt and GOA support this as by-similarity mouse-oocyte/meiosis context. It may be biologically real in a reproductive setting, but it is secondary to RAB24 basal autophagic-compartment maturation/clearance for the human PN review.
    supported_by:
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: Involved in the modulation of meiotic apparatus assembly and meiotic progression during oocyte maturation
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: possibly through regulation of kinetochore-microtubule interaction
- term:
    id: GO:0140013
    label: meiotic nuclear division
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: meiotic nuclear division is transferred mouse oocyte/spindle biology and is not the central proteostasis function.
    action: KEEP_AS_NON_CORE
    reason: UniProt and GOA support this as by-similarity mouse-oocyte/meiosis context. It may be biologically real in a reproductive setting, but it is secondary to RAB24 basal autophagic-compartment maturation/clearance for the human PN review.
    supported_by:
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: Involved in the modulation of meiotic apparatus assembly and meiotic progression during oocyte maturation
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: possibly through regulation of kinetochore-microtubule interaction
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: cytosol is a broad RAB24 localization/context annotation.
    action: KEEP_AS_NON_CORE
    reason: RAB24 can be cytosolic and membrane-associated, with perinuclear/autophagic-compartment localization reported by similarity, but these broad terms should not be treated as the core location when autophagosome/autophagosome membrane is available.
    supported_by:
    - reference_id: PMID:10660536
      supporting_text: Posttranslational geranylgeranylation of Rab24
    - reference_id: PMID:26325487
      supporting_text: targeting of RAB24 to autophagic compartments
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: Only about 20% is recovered in the particulate fraction
- term:
    id: GO:0003925
    label: G protein activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: G protein activity is consistent with RAB24 being an atypical Rab-family small GTPase.
    action: ACCEPT
    reason: RAB24 is a Rab small GTPase; the evidence also cautions that it has unusually low GTP hydrolysis and is predominantly GTP-bound, but this does not negate the Rab GTPase/GTP-binding molecular-function annotation.
    supported_by:
    - reference_id: PMID:10660536
      supporting_text: Rab24 exists predominantly in the GTP state
    - reference_id: PMID:10660536
      supporting_text: The low GTPase activity is related to the presence of serine instead of glutamine
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: GTPase activity is consistent with RAB24 being an atypical Rab-family small GTPase.
    action: ACCEPT
    reason: RAB24 is a Rab small GTPase; the evidence also cautions that it has unusually low GTP hydrolysis and is predominantly GTP-bound, but this does not negate the Rab GTPase/GTP-binding molecular-function annotation.
    supported_by:
    - reference_id: PMID:10660536
      supporting_text: Rab24 exists predominantly in the GTP state
    - reference_id: PMID:10660536
      supporting_text: The low GTPase activity is related to the presence of serine instead of glutamine
- term:
    id: GO:0016020
    label: membrane
  evidence_type: EXP
  original_reference_id: PMID:10660536
  qualifier: located_in
  review:
    summary: membrane is a broad RAB24 localization/context annotation.
    action: KEEP_AS_NON_CORE
    reason: RAB24 can be cytosolic and membrane-associated, with perinuclear/autophagic-compartment localization reported by similarity, but these broad terms should not be treated as the core location when autophagosome/autophagosome membrane is available.
    supported_by:
    - reference_id: PMID:10660536
      supporting_text: Posttranslational geranylgeranylation of Rab24
    - reference_id: PMID:26325487
      supporting_text: targeting of RAB24 to autophagic compartments
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: Only about 20% is recovered in the particulate fraction
- term:
    id: GO:0001556
    label: oocyte maturation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: oocyte maturation is transferred mouse oocyte/spindle biology and is not the central proteostasis function.
    action: KEEP_AS_NON_CORE
    reason: UniProt and GOA support this as by-similarity mouse-oocyte/meiosis context. It may be biologically real in a reproductive setting, but it is secondary to RAB24 basal autophagic-compartment maturation/clearance for the human PN review.
    supported_by:
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: Involved in the modulation of meiotic apparatus assembly and meiotic progression during oocyte maturation
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: possibly through regulation of kinetochore-microtubule interaction
- term:
    id: GO:0008608
    label: attachment of spindle microtubules to kinetochore
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: attachment of spindle microtubules to kinetochore is transferred mouse oocyte/spindle biology and is not the central proteostasis function.
    action: KEEP_AS_NON_CORE
    reason: UniProt and GOA support this as by-similarity mouse-oocyte/meiosis context. It may be biologically real in a reproductive setting, but it is secondary to RAB24 basal autophagic-compartment maturation/clearance for the human PN review.
    supported_by:
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: Involved in the modulation of meiotic apparatus assembly and meiotic progression during oocyte maturation
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: possibly through regulation of kinetochore-microtubule interaction
- term:
    id: GO:0140013
    label: meiotic nuclear division
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: meiotic nuclear division is transferred mouse oocyte/spindle biology and is not the central proteostasis function.
    action: KEEP_AS_NON_CORE
    reason: UniProt and GOA support this as by-similarity mouse-oocyte/meiosis context. It may be biologically real in a reproductive setting, but it is secondary to RAB24 basal autophagic-compartment maturation/clearance for the human PN review.
    supported_by:
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: Involved in the modulation of meiotic apparatus assembly and meiotic progression during oocyte maturation
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: possibly through regulation of kinetochore-microtubule interaction
- term:
    id: GO:0000421
    label: autophagosome membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: autophagosome membrane is a core RAB24 autophagy-associated location.
    action: ACCEPT
    reason: RAB24 localizes to autophagic vacuoles/autophagic compartments and the autophagosome membrane context is directly relevant to its basal autophagic-compartment maturation/clearance role.
    supported_by:
    - reference_id: PMID:26325487
      supporting_text: localization of RAB24 to autophagic vacuoles
    - reference_id: PMID:26325487
      supporting_text: maturation and/or clearance of autophagic compartments under nutrient-rich conditions
    - reference_id: PMID:10660536
      supporting_text: Posttranslational geranylgeranylation of Rab24
    - reference_id: PMID:26325487
      supporting_text: targeting of RAB24 to autophagic compartments
- term:
    id: GO:0006914
    label: autophagy
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Generic autophagy is too broad for the RAB24-specific evidence.
    action: MODIFY
    reason: The RAB24-specific study places the function at maturation and/or clearance of late autophagic compartments under basal nutrient-rich conditions, while formation and short starvation-induced autophagy are not affected. Replace the broad autophagy term with autophagosome maturation.
    proposed_replacement_terms:
    - id: GO:0097352
      label: autophagosome maturation
    supported_by:
    - reference_id: PMID:26325487
      supporting_text: localization of RAB24 to autophagic vacuoles
    - reference_id: PMID:26325487
      supporting_text: maturation and/or clearance of autophagic compartments under nutrient-rich conditions
    - reference_id: PMID:26325487
      supporting_text: Formation of autophagosomes is shown to be unaffected by RAB24-silencing with siRNA
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: perinuclear region of cytoplasm is a broad RAB24 localization/context annotation.
    action: KEEP_AS_NON_CORE
    reason: RAB24 can be cytosolic and membrane-associated, with perinuclear/autophagic-compartment localization reported by similarity, but these broad terms should not be treated as the core location when autophagosome/autophagosome membrane is available.
    supported_by:
    - reference_id: PMID:10660536
      supporting_text: Posttranslational geranylgeranylation of Rab24
    - reference_id: PMID:26325487
      supporting_text: targeting of RAB24 to autophagic compartments
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: Only about 20% is recovered in the particulate fraction
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: Mitochondrion is not supported as a core RAB24 location.
    action: MARK_AS_OVER_ANNOTATED
    reason: This high-throughput proteome-derived row does not match the RAB24-specific localization/function evidence, which centers on cytosol, membrane association, and autophagic compartments.
    supported_by:
    - reference_id: file:human/RAB24/RAB24-uniprot.txt
      supporting_text: Cytoplasm, cytosol
    - reference_id: PMID:26325487
      supporting_text: localization of RAB24 to autophagic vacuoles
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798743
  qualifier: located_in
  review:
    summary: plasma membrane is Reactome degranulation context, not a specific RAB24 core location.
    action: MARK_AS_OVER_ANNOTATED
    reason: The reviewed RAB24 evidence supports autophagic-compartment/autophagosome membrane localization. Reactome secretory-granule/plasma-membrane context should not be propagated as a core RAB24 cellular-component annotation.
    supported_by:
    - reference_id: PMID:26325487
      supporting_text: localization of RAB24 to autophagic vacuoles
    - reference_id: PMID:26325487
      supporting_text: maturation and/or clearance of autophagic compartments under nutrient-rich conditions
- term:
    id: GO:0030667
    label: secretory granule membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798743
  qualifier: located_in
  review:
    summary: secretory granule membrane is Reactome degranulation context, not a specific RAB24 core location.
    action: MARK_AS_OVER_ANNOTATED
    reason: The reviewed RAB24 evidence supports autophagic-compartment/autophagosome membrane localization. Reactome secretory-granule/plasma-membrane context should not be propagated as a core RAB24 cellular-component annotation.
    supported_by:
    - reference_id: PMID:26325487
      supporting_text: localization of RAB24 to autophagic vacuoles
    - reference_id: PMID:26325487
      supporting_text: maturation and/or clearance of autophagic compartments under nutrient-rich conditions
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16034420
  qualifier: enables
  review:
    summary: Generic protein binding does not describe the actual RAB24 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The interaction record may identify a binding partner, but protein binding is uninformative as a GO molecular function. RAB24 should be represented by Rab-family GTPase/GTP-binding activity and, where evidence is specific, autophagic-compartment localization/process terms.
    supported_by:
    - reference_id: PMID:16034420
      supporting_text: Rab GTPases interact with functionally diverse effectors
    - reference_id: PMID:16034420
      supporting_text: rabenosyn-5 can achieve highly selective recognition
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:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10660536
  title: Rab24 is an atypical member of the Rab GTPase family. Deficient GTPase activity, GDP dissociation inhibitor interaction, and prenylation of Rab24 expressed in cultured cells.
  findings:
  - statement: Human Rab24 is predominantly GTP-bound, has low GTPase activity, is inefficiently prenylated, and is partly membrane-associated.
- id: PMID:16034420
  title: Structural basis of family-wide Rab GTPase recognition by rabenosyn-5.
  findings:
  - statement: Rabenosyn-5/ZFYVE20 recognizes Rab GTPases through selective Rab-effector interactions, providing context for the RAB24 interaction but not a specific GO molecular function beyond Rab GTPase activity.
- id: PMID:20562859
  title: Network organization of the human autophagy system.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: Reactome:R-HSA-6798743
  title: Exocytosis of secretory granule membrane proteins
  findings: []
- id: file:human/RAB24/RAB24-uniprot.txt
  title: UniProtKB record for human RAB24
  findings:
  - statement: UniProt summarizes RAB24 as an atypical Rab protein with low GTPase activity, predominant GTP-bound state, basal late-autophagic-vacuole clearance, and by-similarity oocyte meiotic apparatus context.
- id: file:human/RAB24/RAB24-notes.md
  title: RAB24 review notes
  findings:
  - statement: Manual PN-focused curation notes for RAB24; PN no-PMID rows were treated as context only.
- id: PMID:26325487
  title: RAB24 facilitates clearance of autophagic compartments during basal conditions.
  findings:
  - statement: RAB24 localizes to autophagic vacuoles/autophagic compartments and supports maturation/clearance of late basal autophagic compartments without affecting autophagosome formation.
- id: file:human/RAB24/RAB24-deep-research-falcon.md
  title: Falcon deep research report for RAB24
  findings:
  - statement: LLM-synthesized literature report agreeing that RAB24 is an atypical Rab with low intrinsic GTPase activity, predominantly GTP-bound, prenylation-dependent membrane targeting, and a late-stage basal-autophagy clearance role; it additionally surfaces the Rab7/RILP late-endosomal degradation interaction (Amaya 2016) and immuno-EM localization to both inner and outer autophagic-vacuole membranes.
  reference_review:
    relevance: MEDIUM
    correctness: UNVERIFIED
    review_notes: >-
      LLM synthesis of secondary reviews; not independently verified against the primary papers, which
      are not all in the publications cache (e.g. Amaya 2016 Traffic, Ylä-Anttila 2018 Small GTPases).
      The report's RAB24-specific points (low GTPase activity, predominant GTP-bound state,
      prenylation-dependent targeting, late-stage basal-autophagic-compartment clearance, Rab7/RILP
      interaction, inner/outer autophagic-vacuole membranes) are consistent with the curated UniProt
      and PMID:26325487 / PMID:10660536 evidence. However, the report repeatedly imposes the canonical
      Rab GEF/GAP/GDI/effector cycle and a definitive autophagosome-lysosome "fusion" step onto RAB24
      despite its atypical, GTP-locked, poorly-hydrolysing, partly-non-prenylated biochemistry; those
      canonical-mechanism generalizations are not anchored to RAB24-specific data and were not adopted.
core_functions:
- molecular_function:
    id: GO:0003924
    label: GTPase activity
  description: RAB24 is an atypical Rab-family small GTPase whose GTP-bound state supports targeting to autophagic compartments and late basal autophagic-compartment maturation/clearance.
  directly_involved_in:
  - id: GO:0097352
    label: autophagosome maturation
  locations:
  - id: GO:0000421
    label: autophagosome membrane
  - id: GO:0005776
    label: autophagosome
  supported_by:
  - reference_id: PMID:10660536
    supporting_text: Rab24 exists predominantly in the GTP state
  - reference_id: PMID:10660536
    supporting_text: The low GTPase activity is related to the presence of serine instead of glutamine
  - reference_id: PMID:26325487
    supporting_text: localization of RAB24 to autophagic vacuoles
  - reference_id: PMID:26325487
    supporting_text: maturation and/or clearance of autophagic compartments under nutrient-rich conditions
  - reference_id: file:human/RAB24/RAB24-uniprot.txt
    supporting_text: RAB24 is required for the clearance of late autophagic vacuoles under basal conditions
  - reference_id: file:human/RAB24/RAB24-uniprot.txt
    supporting_text: It is not needed for starvation-induced autophagy
- molecular_function:
    id: GO:0005525
    label: GTP binding
  description: RAB24 nucleotide binding is required for its autophagic-compartment targeting, but the protein is atypical because it has weak GTP hydrolysis and remains predominantly GTP-bound.
  directly_involved_in:
  - id: GO:0097352
    label: autophagosome maturation
  locations:
  - id: GO:0000421
    label: autophagosome membrane
  supported_by:
  - reference_id: PMID:10660536
    supporting_text: Rab24 exists predominantly in the GTP state
  - reference_id: PMID:10660536
    supporting_text: The low GTPase activity is related to the presence of serine instead of glutamine
  - reference_id: PMID:26325487
    supporting_text: guanine nucleotide binding are necessary for the targeting of RAB24 to autophagic compartments
proposed_new_terms: []
suggested_questions:
- question: Should RAB24 be curated directly to GO:0097352 autophagosome maturation rather than the current broad GO:0006914 autophagy rows?
  experts:
  - GO autophagy editors
  - Rab trafficking experts
- question: Is there enough human-specific evidence to retain oocyte/meiosis/spindle annotations for RAB24 outside mouse by-similarity transfer?
  experts:
  - GO reproductive biology editors
  - UniProt curators
suggested_experiments:
- description: Measure basal autophagic flux and late autophagic-compartment clearance in human RAB24 knockout/rescue cells using wild-type, nucleotide-binding-defective, and prenylation-defective RAB24 variants.
  hypothesis: RAB24 nucleotide binding and membrane targeting are required for late basal autophagic-compartment maturation/clearance.
- description: Test whether endogenous human RAB24 is required for autophagosome-lysosome fusion, autolysosome acidification, or post-fusion cargo degradation using LC3/p62 flux reporters and lysosomal inhibitors.
  hypothesis: RAB24 acts late in basal autophagy after autophagosome formation rather than during autophagy induction.
