id: Q86Y82
gene_symbol: STX12
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  STX12 encodes syntaxin-12/syntaxin-13, a syntaxin-family SNARE on endosomal, early endosomal,
  recycling endosomal, and Golgi membranes. Its core function is SNAP receptor/SNARE-mediated vesicle
  docking and membrane fusion in endosomal recycling and intracellular membrane traffic. Direct
  evidence also supports a role at LC3-positive phagophores/autophagosome assembly or maturation,
  likely as an autophagy-specific output of its SNARE trafficking activity. STX12 is distinct from
  ESCRT-III machinery.
existing_annotations:
- term:
    id: GO:0000149
    label: SNARE binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: The annotation reflects real SNARE-partner interactions, but SNAP receptor activity is the more informative molecular-function term for syntaxin-12.
    action: MODIFY
    reason: STX12 is a syntaxin-family SNARE whose core role is SNAP receptor/SNARE activity in vesicle docking and membrane fusion; SNARE binding alone is less precise.
    supported_by:
    - &id001
      reference_id: UniProt:Q86Y82
      supporting_text: SNARE promoting fusion of transport vesicles with target membranes.
    - &id002
      reference_id: UniProt:Q86Y82
      supporting_text: Together with SNARE STX6, promotes movement of vesicles from endosomes to the cell membrane
    - reference_id: PMID:19546860
      supporting_text: including SNAP-25 and syntaxin 13, was demonstrated
    proposed_replacement_terms:
    - id: GO:0005484
      label: SNAP receptor activity
- term:
    id: GO:0008021
    label: synaptic vesicle
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: 'Supported or plausible neuronal/endosomal recycling context, but not the primary conserved STX12 function: synaptic vesicle.'
    action: KEEP_AS_NON_CORE
    reason: The main conserved role is endosomal/recycling SNARE-mediated vesicle docking and fusion; synaptic/postsynaptic rows are specialized neuronal contexts.
    supported_by:
    - *id001
    - *id002
    - reference_id: UniProt:Q86Y82
      supporting_text: controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit
- term:
    id: GO:0098837
    label: postsynaptic recycling endosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: 'Supported or plausible neuronal/endosomal recycling context, but not the primary conserved STX12 function: postsynaptic recycling endosome.'
    action: KEEP_AS_NON_CORE
    reason: The main conserved role is endosomal/recycling SNARE-mediated vesicle docking and fusion; synaptic/postsynaptic rows are specialized neuronal contexts.
    supported_by:
    - *id001
    - *id002
    - reference_id: UniProt:Q86Y82
      supporting_text: controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit
- term:
    id: GO:0030672
    label: synaptic vesicle membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: 'Supported or plausible neuronal/endosomal recycling context, but not the primary conserved STX12 function: synaptic vesicle membrane.'
    action: KEEP_AS_NON_CORE
    reason: The main conserved role is endosomal/recycling SNARE-mediated vesicle docking and fusion; synaptic/postsynaptic rows are specialized neuronal contexts.
    supported_by:
    - *id001
    - *id002
    - reference_id: UniProt:Q86Y82
      supporting_text: controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit
- term:
    id: GO:0000045
    label: autophagosome assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'Directly supported PN-relevant autophagy context for STX12: autophagosome assembly.'
    action: ACCEPT
    reason: PMID:24095276 directly supports STX13/STX12 localization to LC3-positive phagophores and a requirement for autophagic flux/phagophore maturation.
    supported_by: &id009
    - &id005
      reference_id: PMID:24095276
      supporting_text: Knockdown of syntaxin 13 (STX13) or its binding partner Vti1a in mammalian cells caused LC3-positive puncta to accumulate
    - reference_id: PMID:24095276
      supporting_text: participates in the maturation of phagophores into closed autophagosomes
- term:
    id: GO:0048278
    label: vesicle docking
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'Supported core STX12 vesicle-trafficking/SNARE function: vesicle docking.'
    action: ACCEPT
    reason: STX12 is a syntaxin SNARE that promotes endosomal vesicle movement, docking, and fusion with target membranes.
    supported_by:
    - *id001
    - *id002
    - reference_id: PMID:19546860
      supporting_text: proteins that control membrane fusion
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'Supported core localization for an endosomal/recycling syntaxin SNARE: Golgi membrane.'
    action: ACCEPT
    reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12.
    supported_by:
    - &id003
      reference_id: UniProt:Q86Y82
      supporting_text: Endosome membrane
    - &id004
      reference_id: UniProt:Q86Y82
      supporting_text: Recycling endosome membrane
    - reference_id: UniProt:Q86Y82
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0005484
    label: SNAP receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: 'Supported core STX12 vesicle-trafficking/SNARE function: SNAP receptor activity.'
    action: ACCEPT
    reason: STX12 is a syntaxin SNARE that promotes endosomal vesicle movement, docking, and fusion with target membranes.
    supported_by:
    - *id001
    - *id002
    - reference_id: PMID:19546860
      supporting_text: proteins that control membrane fusion
- term:
    id: GO:0006886
    label: intracellular protein transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: 'Supported core STX12 vesicle-trafficking/SNARE function: intracellular protein transport.'
    action: ACCEPT
    reason: STX12 is a syntaxin SNARE that promotes endosomal vesicle movement, docking, and fusion with target membranes.
    supported_by:
    - *id001
    - *id002
    - reference_id: PMID:19546860
      supporting_text: proteins that control membrane fusion
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'Supported core localization for an endosomal/recycling syntaxin SNARE: endosome membrane.'
    action: ACCEPT
    reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12.
    supported_by:
    - *id003
    - *id004
    - reference_id: UniProt:Q86Y82
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0012505
    label: endomembrane system
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: 'True but broad localization for membrane-associated STX12: endomembrane system.'
    action: KEEP_AS_NON_CORE
    reason: More specific endosome, early/recycling endosome membrane, Golgi membrane, and phagophore locations better capture STX12 biology.
    supported_by:
    - *id003
    - *id004
    - *id005
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: 'True but broad localization for membrane-associated STX12: membrane.'
    action: KEEP_AS_NON_CORE
    reason: More specific endosome, early/recycling endosome membrane, Golgi membrane, and phagophore locations better capture STX12 biology.
    supported_by:
    - *id003
    - *id004
    - *id005
- term:
    id: GO:0016192
    label: vesicle-mediated transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: 'Supported core STX12 vesicle-trafficking/SNARE function: vesicle-mediated transport.'
    action: ACCEPT
    reason: STX12 is a syntaxin SNARE that promotes endosomal vesicle movement, docking, and fusion with target membranes.
    supported_by:
    - *id001
    - *id002
    - reference_id: PMID:19546860
      supporting_text: proteins that control membrane fusion
- term:
    id: GO:0031410
    label: cytoplasmic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: 'True but broad localization for membrane-associated STX12: cytoplasmic vesicle.'
    action: KEEP_AS_NON_CORE
    reason: More specific endosome, early/recycling endosome membrane, Golgi membrane, and phagophore locations better capture STX12 biology.
    supported_by:
    - *id003
    - *id004
    - *id005
- term:
    id: GO:0031901
    label: early endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'Supported core localization for an endosomal/recycling syntaxin SNARE: early endosome membrane.'
    action: ACCEPT
    reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12.
    supported_by:
    - *id003
    - *id004
    - reference_id: UniProt:Q86Y82
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0055038
    label: recycling endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'Supported core localization for an endosomal/recycling syntaxin SNARE: recycling endosome membrane.'
    action: ACCEPT
    reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12.
    supported_by:
    - *id003
    - *id004
    - reference_id: UniProt:Q86Y82
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0061025
    label: membrane fusion
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: involved_in
  review:
    summary: 'Supported core STX12 vesicle-trafficking/SNARE function: membrane fusion.'
    action: ACCEPT
    reason: STX12 is a syntaxin SNARE that promotes endosomal vesicle movement, docking, and fusion with target membranes.
    supported_by:
    - *id001
    - *id002
    - reference_id: PMID:19546860
      supporting_text: proteins that control membrane fusion
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15469992
  qualifier: enables
  review:
    summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms.
    supported_by:
    - &id006
      reference_id: file:human/STX12/STX12-notes.md
      supporting_text: Generic `protein binding` rows should be marked over-annotated even when the interaction itself is real.
    - &id007
      reference_id: UniProt:Q86Y82
      supporting_text: SNARE promoting fusion of transport vesicles with target membranes.
    - reference_id: PMID:15469992
      supporting_text: ABCA1 forms a complex with syntaxin 13 and flotillin-1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms.
    supported_by: &id008
    - *id006
    - *id007
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26359495
  qualifier: enables
  review:
    summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms.
    supported_by: *id008
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms.
    supported_by: *id008
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms.
    supported_by: *id008
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms.
    supported_by: *id008
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms.
    supported_by: *id008
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms.
    supported_by: *id008
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms.
    supported_by: *id008
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: 'Supported core localization for an endosomal/recycling syntaxin SNARE: Golgi apparatus.'
    action: ACCEPT
    reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12.
    supported_by:
    - *id003
    - *id004
    - reference_id: UniProt:Q86Y82
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'Supported core localization for an endosomal/recycling syntaxin SNARE: Golgi membrane.'
    action: ACCEPT
    reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12.
    supported_by:
    - *id003
    - *id004
    - reference_id: UniProt:Q86Y82
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'Supported core localization for an endosomal/recycling syntaxin SNARE: endosome membrane.'
    action: ACCEPT
    reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12.
    supported_by:
    - *id003
    - *id004
    - reference_id: UniProt:Q86Y82
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0012505
    label: endomembrane system
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'True but broad localization for membrane-associated STX12: endomembrane system.'
    action: KEEP_AS_NON_CORE
    reason: More specific endosome, early/recycling endosome membrane, Golgi membrane, and phagophore locations better capture STX12 biology.
    supported_by:
    - *id003
    - *id004
    - *id005
- term:
    id: GO:0031901
    label: early endosome membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'Supported core localization for an endosomal/recycling syntaxin SNARE: early endosome membrane.'
    action: ACCEPT
    reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12.
    supported_by:
    - *id003
    - *id004
    - reference_id: UniProt:Q86Y82
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0055038
    label: recycling endosome membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'Supported core localization for an endosomal/recycling syntaxin SNARE: recycling endosome membrane.'
    action: ACCEPT
    reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12.
    supported_by:
    - *id003
    - *id004
    - reference_id: UniProt:Q86Y82
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0032456
    label: endocytic recycling
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'Supported core STX12 vesicle-trafficking/SNARE function: endocytic recycling.'
    action: ACCEPT
    reason: STX12 is a syntaxin SNARE that promotes endosomal vesicle movement, docking, and fusion with target membranes.
    supported_by:
    - *id001
    - *id002
    - reference_id: PMID:19546860
      supporting_text: proteins that control membrane fusion
- term:
    id: GO:0055037
    label: recycling endosome
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'Supported core localization for an endosomal/recycling syntaxin SNARE: recycling endosome.'
    action: ACCEPT
    reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12.
    supported_by:
    - *id003
    - *id004
    - reference_id: UniProt:Q86Y82
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0000045
    label: autophagosome assembly
  evidence_type: IMP
  original_reference_id: PMID:24095276
  qualifier: involved_in
  review:
    summary: 'Directly supported PN-relevant autophagy context for STX12: autophagosome assembly.'
    action: ACCEPT
    reason: PMID:24095276 directly supports STX13/STX12 localization to LC3-positive phagophores and a requirement for autophagic flux/phagophore maturation.
    supported_by: *id009
- term:
    id: GO:0000407
    label: phagophore assembly site
  evidence_type: IMP
  original_reference_id: PMID:24095276
  qualifier: located_in
  review:
    summary: 'Directly supported PN-relevant autophagy context for STX12: phagophore assembly site.'
    action: ACCEPT
    reason: PMID:24095276 directly supports STX13/STX12 localization to LC3-positive phagophores and a requirement for autophagic flux/phagophore maturation.
    supported_by: *id009
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24095276
  qualifier: enables
  review:
    summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms.
    supported_by:
    - *id006
    - *id007
    - reference_id: PMID:24095276
      supporting_text: Knockdown of syntaxin 13 (STX13) or its binding partner Vti1a
- term:
    id: GO:0031982
    label: vesicle
  evidence_type: IMP
  original_reference_id: PMID:24095276
  qualifier: located_in
  review:
    summary: The vesicle localization is supported but too broad for the direct autophagy evidence.
    action: MODIFY
    reason: The same study more specifically places STX13/STX12 on LC3-positive phagophores; phagophore assembly site is the better location term.
    supported_by: *id009
    proposed_replacement_terms:
    - id: GO:0000407
      label: phagophore assembly site
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19546860
  qualifier: enables
  review:
    summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms.
    supported_by:
    - *id006
    - *id007
    - reference_id: PMID:19546860
      supporting_text: including SNAP-25 and syntaxin 13, was demonstrated
- term:
    id: GO:0031201
    label: SNARE complex
  evidence_type: IDA
  original_reference_id: PMID:19546860
  qualifier: part_of
  review:
    summary: Supported as a core SNARE-complex context for syntaxin-12.
    action: ACCEPT
    reason: STX12 is a SNARE and UniProt reports complex formation with STX6, VAMP4, and VTI1A; the BLOC-1 paper also discusses syntaxin 13-containing SNARE complexes.
    supported_by:
    - reference_id: UniProt:Q86Y82
      supporting_text: Identified in a complex containing STX6, STX12, VAMP4 and VTI1A
    - reference_id: PMID:19546860
      supporting_text: SNARE complex containing both syntaxin 13 and SNAP-25
- term:
    id: GO:0031083
    label: BLOC-1 complex
  evidence_type: IDA
  original_reference_id: PMID:19546860
  qualifier: colocalizes_with
  review:
    summary: BLOC-1 association is supported but is a non-core interaction/localization context for STX12.
    action: KEEP_AS_NON_CORE
    reason: STX12 interacts with BLOC-1-linked trafficking machinery, but it is not a BLOC-1 complex subunit and this should not define its core function.
    supported_by:
    - reference_id: PMID:19546860
      supporting_text: including SNAP-25 and syntaxin 13, was demonstrated
    - reference_id: PMID:19546860
      supporting_text: BLOC-1... involved in intracellular membrane trafficking and organelle biogenesis
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12191018
  qualifier: enables
  review:
    summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms.
    supported_by: *id008
- term:
    id: GO:0033344
    label: cholesterol efflux
  evidence_type: IDA
  original_reference_id: PMID:15469992
  qualifier: involved_in
  review:
    summary: 'Supported ABCA1/macrophage context, but non-core for STX12: cholesterol efflux.'
    action: KEEP_AS_NON_CORE
    reason: PMID:15469992 supports a direct ABCA1/cholesterol/phagocytosis context, but this is cargo- and cell-context-specific relative to STX12 core SNARE trafficking.
    supported_by: &id010
    - reference_id: PMID:15469992
      supporting_text: ABCA1 forms a complex with syntaxin 13 and flotillin-1
    - reference_id: PMID:15469992
      supporting_text: Silencing of syntaxin 13 by small interfering RNA (siRNA) led to reduced ABCA1 protein levels
- term:
    id: GO:0045121
    label: membrane raft
  evidence_type: IDA
  original_reference_id: PMID:15469992
  qualifier: located_in
  review:
    summary: 'Supported ABCA1/macrophage context, but non-core for STX12: membrane raft.'
    action: KEEP_AS_NON_CORE
    reason: PMID:15469992 supports a direct ABCA1/cholesterol/phagocytosis context, but this is cargo- and cell-context-specific relative to STX12 core SNARE trafficking.
    supported_by: *id010
- term:
    id: GO:0045335
    label: phagocytic vesicle
  evidence_type: IDA
  original_reference_id: PMID:15469992
  qualifier: located_in
  review:
    summary: 'Supported ABCA1/macrophage context, but non-core for STX12: phagocytic vesicle.'
    action: KEEP_AS_NON_CORE
    reason: PMID:15469992 supports a direct ABCA1/cholesterol/phagocytosis context, but this is cargo- and cell-context-specific relative to STX12 core SNARE trafficking.
    supported_by: *id010
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IDA
  original_reference_id: PMID:15469992
  qualifier: involved_in
  review:
    summary: The ABCA1 experiment supports a specific effect on ABCA1 stability, not a general STX12 protein-stabilization function.
    action: MARK_AS_OVER_ANNOTATED
    reason: This row overgeneralizes a context-specific ABCA1 phenotype; STX12 core function is SNARE-mediated trafficking.
    supported_by: *id010
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings:
  - statement: Provides electronic assignment of SNARE/vesicle-trafficking GO terms
      to STX12 via InterPro syntaxin-family domain mapping, consistent with STX12's
      core SNARE function.
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings:
  - statement: Transfers endosome/recycling-endosome/Golgi localization and endocytic
      recycling annotations to STX12 from experimentally characterised orthologous
      syntaxins by curator judgment of sequence similarity.
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings:
  - statement: PAINT/IBA phylogenetic-inference annotations propagate SNARE-family
      molecular function (SNARE binding) and endosomal-recycling process/location
      terms to STX12 from experimentally annotated syntaxin orthologs.
- 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:
  - statement: Provides electronic endosome membrane, early endosome membrane, recycling
      endosome membrane, and Golgi membrane localizations for STX12 based on UniProt
      subcellular-location vocabulary, consistent with experimental IDA/ISS evidence.
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings:
  - statement: Curates immunofluorescence-based Golgi apparatus localization for STX12
      consistent with experimental IDA evidence.
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links
  findings:
  - statement: Provides electronic membrane-fusion process annotation for STX12 via
      inter-ontology logical inference, consistent with STX12's core SNARE-mediated
      fusion role.
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings:
  - statement: ARBA machine-learning rule assigns cytoplasmic vesicle localization
      to STX12 based on generalized sequence/annotation features; broadly consistent
      with STX12's vesicle-membrane localization but generic.
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings:
  - statement: Combined-IEA pipeline provides broad endomembrane-system and membrane
      localizations for STX12; correct but generic relative to the specific endosome/Golgi
      terms.
- id: PMID:12191018
  title: Pallidin is a component of a multi-protein complex involved in the biogenesis of lysosome-related organelles.
  findings:
  - statement: Pallidin/BLOC-1 biology provides background for BLOC-1 interaction rows, but not a core STX12 function.
- id: PMID:15469992
  title: Association of ABCA1 with syntaxin 13 and flotillin-1 and enhanced phagocytosis in tangier cells.
  findings:
  - statement: Syntaxin 13 associates with ABCA1/flotillin-1; STX13 knockdown reduces ABCA1 protein and apoA-I-dependent phospholipid efflux.
- id: PMID:19546860
  title: 'The dysbindin-containing complex (BLOC-1) in brain: developmental regulation, interaction with SNARE proteins and role in neurite outgrowth.'
  findings:
  - statement: BLOC-1 interacts with syntaxin 13 and other SNARE proteins, supporting a BLOC-1/SNARE trafficking context.
- id: PMID:24095276
  title: Syntaxin 13, a genetic modifier of mutant CHMP2B in frontotemporal dementia, is required for autophagosome maturation.
  findings:
  - statement: STX13/STX12 knockdown blocks autophagic flux, causes LC3/Atg5 puncta accumulation, and supports phagophore maturation into closed autophagosomes.
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings:
  - statement: Rolland et al. HI-II-14 proteome-scale yeast two-hybrid map reports
      an STX12 protein-protein interaction. High-throughput dataset; only bare protein-binding
      evidence, not a specific molecular function.
    supporting_text: A proteome-scale map of the human interactome network.
    reference_section_type: ABSTRACT
- id: PMID:26359495
  title: The Q-soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor (Q-SNARE) SNAP-47 Regulates Trafficking of Selected Vesicle-associated Membrane Proteins (VAMPs).
  findings:
  - statement: SNAP-47 and selected SNARE/VAMP trafficking interactions support a SNARE interaction context but not generic protein-binding curation.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings:
  - statement: Huttlin et al. BioPlex 2.0 affinity-purification-mass-spectrometry human
      interactome records STX12 co-purifying partners. High-throughput dataset; only
      bare protein-binding evidence, not a specific molecular function.
    supporting_text: Architecture of the human interactome defines protein communities
      and disease networks.
    reference_section_type: ABSTRACT
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
  findings:
  - statement: Fragoza et al. yeast-two-hybrid screen of population variants includes
      STX12 interaction data. High-throughput dataset; only bare protein-binding evidence,
      not a specific molecular function.
    supporting_text: Extensive disruption of protein interactions by genetic variants
      across the allele frequency spectrum in human populations.
    reference_section_type: ABSTRACT
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings:
  - statement: Luck et al. HuRI reference binary interactome (yeast two-hybrid) records
      STX12 interactions. High-throughput dataset; only bare protein-binding evidence,
      not a specific molecular function.
    supporting_text: A reference map of the human binary protein interactome.
    reference_section_type: ABSTRACT
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings:
  - statement: Huttlin et al. BioPlex 3.0 dual (HEK293T/HCT116) affinity-purification-mass-spectrometry
      interactome records STX12 interactions. High-throughput dataset; only bare protein-binding
      evidence, not a specific molecular function.
    supporting_text: Dual proteome-scale networks reveal cell-specific remodeling of
      the human interactome.
    reference_section_type: ABSTRACT
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings:
  - statement: OpenCell endogenous split-mNeonGreen tagging with live-cell imaging and
      IP-MS records STX12 subcellular localization and interaction partners at endogenous
      levels. Supports vesicular/endosomal localization; high-throughput screen provides
      only bare protein-binding evidence for the interaction rows.
    supporting_text: 'OpenCell: Endogenous tagging for the cartography of human cellular
      organization.'
    reference_section_type: ABSTRACT
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings:
  - statement: Schaffer et al. multimodal cell-map integration of BioPlex/OpenCell/CellMap
      data reports STX12 community membership. High-throughput dataset; provides only
      bare protein-binding-level evidence, not a specific molecular function.
    supporting_text: Multimodal cell maps as a foundation for structural and functional
      genomics.
    reference_section_type: ABSTRACT
- id: UniProt:Q86Y82
  title: UniProt entry for STX12 (Q86Y82)
  findings:
  - statement: STX12 is a syntaxin-family SNARE on endosomal/Golgi/recycling-endosome membranes that promotes transport vesicle fusion and endosomal recycling.
- id: file:human/STX12/STX12-notes.md
  title: Local curation notes for STX12
  findings:
  - statement: Local synthesis treats SNARE/endosomal trafficking as core, direct autophagy evidence as PN-relevant, and ESCRT-III complex membership as inappropriate for STX12.
core_functions:
- description: Syntaxin/SNARE-mediated vesicle docking and membrane fusion in endosomal recycling and intracellular membrane trafficking.
  supported_by:
  - *id001
  - *id002
  - reference_id: PMID:19546860
    supporting_text: proteins that control membrane fusion
  molecular_function:
    id: GO:0005484
    label: SNAP receptor activity
  directly_involved_in:
  - id: GO:0048278
    label: vesicle docking
  - id: GO:0061025
    label: membrane fusion
  - id: GO:0032456
    label: endocytic recycling
  - id: GO:0006886
    label: intracellular protein transport
  - id: GO:0016192
    label: vesicle-mediated transport
  locations:
  - id: GO:0010008
    label: endosome membrane
  - id: GO:0031901
    label: early endosome membrane
  - id: GO:0055038
    label: recycling endosome membrane
  - id: GO:0000139
    label: Golgi membrane
- description: SNARE-mediated phagophore/autophagosome assembly or maturation in the autophagy pathway.
  supported_by: *id009
  molecular_function:
    id: GO:0005484
    label: SNAP receptor activity
  directly_involved_in:
  - id: GO:0000045
    label: autophagosome assembly
  locations:
  - id: GO:0000407
    label: phagophore assembly site
suggested_questions:
- question: Is the STX12 autophagy role best represented as autophagosome assembly/phagophore closure, or should a more specific autophagosome maturation term be used when GO definitions allow it?
- question: 'Which SNARE partners define the STX12 complex during phagophore maturation: VTI1A, STX6, SNAP29, SNAP47, or a distinct autophagy-specific SNARE set?'
- question: Does STX12 act upstream of ESCRT-III dysfunction only through membrane traffic, or does it physically coordinate with ESCRT-associated machinery during phagophore closure?
suggested_experiments:
- description: Rescue STX12 knockdown in autophagy assays with wild-type STX12 and SNARE-domain or membrane-anchor mutants, measuring LC3 turnover, Atg5 puncta, and closed autophagosome formation.
  hypothesis: The autophagy phenotype depends on STX12 SNARE activity and membrane targeting rather than a scaffolding-only interaction.
- description: Define endogenous STX12-containing SNARE complexes during basal and induced autophagy using proximity labeling or immunoprecipitation under crosslinking conditions.
  hypothesis: STX12 uses a context-specific SNARE-partner set at phagophores that differs from its endosomal recycling complexes.
- description: Test whether STX12 perturbation changes ESCRT-III recruitment, persistence, or turnover at autophagy-related membranes after CHMP2B perturbation.
  hypothesis: STX12 modifies ESCRT-III-linked autophagy phenotypes indirectly through phagophore membrane traffic rather than by being an ESCRT-III complex component.