id: Q96AJ9
gene_symbol: VTI1A
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  VTI1A encodes a VTI1-family SNARE that mediates vesicle transport through interactions with
  target-membrane SNAREs and promotes membrane fusion. Its best-supported core function is SNAP
  receptor/SNARE-complex activity in retrograde trafficking from endosomes or late endosomes to the
  trans-Golgi network/Golgi, with related roles in Golgi/TGN membrane traffic and selected
  non-conventional cell-surface trafficking routes. VTI1A also has direct support in
  autophagy/autophagosome context through STX13/Vti1a-associated autophagic flux, but it is not an
  ESCRT-III complex component.
alternative_products:
- name: '2'
  id: Q96AJ9-2
- name: '1'
  id: Q96AJ9-1
  sequence_note: VSP_039848
existing_annotations:
- term:
    id: GO:0006891
    label: intra-Golgi vesicle-mediated transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'Supported core VTI1A SNARE-mediated trafficking process: intra-Golgi vesicle-mediated transport.'
    action: ACCEPT
    reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
    supported_by:
    - &id001
      reference_id: UniProt:Q96AJ9
      supporting_text: Involved in vesicular transport from the late endosomes to the trans-Golgi network
    - &id002
      reference_id: PMID:18195106
      supporting_text: complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
    - &id003
      reference_id: PMID:18195106
      supporting_text: implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
    - &id004
      reference_id: UniProt:Q96AJ9
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0006896
    label: Golgi to vacuole transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: The yeast-derived Golgi-to-vacuole term captures a trafficking idea but is not the best human VTI1A process term.
    action: MODIFY
    reason: Human evidence supports endosome/late-endosome to trans-Golgi network retrograde transport rather than a literal Golgi-to-vacuole process.
    supported_by:
    - *id001
    - *id002
    - *id003
    proposed_replacement_terms:
    - id: GO:0042147
      label: retrograde transport, endosome to Golgi
- term:
    id: GO:0016236
    label: macroautophagy
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'Directly supported autophagy/autophagosome context for VTI1A: macroautophagy.'
    action: ACCEPT
    reason: PMID:24095276 directly reports Vti1a knockdown blocking autophagic flux in the STX13/CHMP2B context and GOA includes autophagosome localization from that study.
    supported_by: &id010
    - 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: blocks autophagic flux
- term:
    id: GO:0042147
    label: retrograde transport, endosome to Golgi
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'Supported core VTI1A SNARE-mediated trafficking process: retrograde transport, endosome to Golgi.'
    action: ACCEPT
    reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
    supported_by:
    - *id001
    - *id002
    - *id003
    - *id004
- term:
    id: GO:0048280
    label: vesicle fusion with Golgi apparatus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'Supported core VTI1A SNARE-mediated trafficking process: vesicle fusion with Golgi apparatus.'
    action: ACCEPT
    reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
    supported_by:
    - *id001
    - *id002
    - *id003
    - *id004
- term:
    id: GO:0000149
    label: SNARE binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: The annotation reflects SNARE-partner interactions, but SNAP receptor activity is the more informative molecular-function term for VTI1A.
    action: MODIFY
    reason: VTI1A is a SNARE whose core molecular function is SNAP receptor/SNARE complex activity in membrane fusion; SNARE binding alone is less precise.
    supported_by:
    - &id005
      reference_id: UniProt:Q96AJ9
      supporting_text: mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
    - &id006
      reference_id: UniProt:Q96AJ9
      supporting_text: to promote fusion of the lipid bilayers
    - *id002
    proposed_replacement_terms:
    - id: GO:0005484
      label: SNAP receptor activity
- term:
    id: GO:0005484
    label: SNAP receptor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Supported as the core VTI1A molecular function.
    action: ACCEPT
    reason: VTI1A is a SNARE/SNAP receptor that forms cognate SNARE complexes for membrane fusion and vesicle transport.
    supported_by:
    - *id005
    - *id006
    - *id002
    - &id007
      reference_id: PMID:19138172
      supporting_text: KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: 'True or plausible but broad/specialized VTI1A location: endoplasmic reticulum membrane.'
    action: KEEP_AS_NON_CORE
    reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
    supported_by:
    - *id005
    - *id006
    - *id007
- term:
    id: GO:0012507
    label: ER to Golgi transport vesicle membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Supported location for VTI1A in non-conventional ER/Golgi or trafficking-vesicle routes.
    action: ACCEPT
    reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
    supported_by:
    - *id007
    - &id011
      reference_id: PMID:19138172
      supporting_text: inhibited Kv4/KChIP1traffic to the plasma membrane
    - reference_id: UniProt:Q96AJ9
      supporting_text: Cytoplasmic vesicle
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: 'Supported compartment for VTI1A SNARE-mediated trafficking: late endosome membrane.'
    action: ACCEPT
    reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
    supported_by:
    - *id001
    - *id002
    - *id003
    - reference_id: UniProt:Q96AJ9
      supporting_text: Cytoplasmic vesicle
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'Supported Golgi/TGN location for VTI1A: Golgi membrane.'
    action: ACCEPT
    reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
    supported_by:
    - *id004
    - &id008
      reference_id: PMID:23677696
      supporting_text: syntaxin 6, syntaxin 16, and Vti1a also disrupted the Golgi ribbon structure
    - &id009
      reference_id: PMID:23677696
      supporting_text: normal retrograde trafficking from the early endosome to the TGN
    - reference_id: UniProt:Q96AJ9
      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 as the core VTI1A molecular function.
    action: ACCEPT
    reason: VTI1A is a SNARE/SNAP receptor that forms cognate SNARE complexes for membrane fusion and vesicle transport.
    supported_by:
    - *id005
    - *id006
    - *id002
    - *id007
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: 'True or plausible but broad/specialized VTI1A location: cytoplasm.'
    action: KEEP_AS_NON_CORE
    reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
    supported_by:
    - *id005
    - *id006
    - *id007
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: located_in
  review:
    summary: 'Supported Golgi/TGN location for VTI1A: Golgi apparatus.'
    action: ACCEPT
    reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
    supported_by:
    - *id004
    - *id008
    - *id009
    - reference_id: UniProt:Q96AJ9
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: located_in
  review:
    summary: 'True or plausible but broad/specialized VTI1A location: cytosol.'
    action: KEEP_AS_NON_CORE
    reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
    supported_by:
    - *id005
    - *id006
    - *id007
- term:
    id: GO:0006886
    label: intracellular protein transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: 'Supported core VTI1A SNARE-mediated trafficking process: intracellular protein transport.'
    action: ACCEPT
    reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
    supported_by:
    - *id001
    - *id002
    - *id003
    - *id004
- term:
    id: GO:0012505
    label: endomembrane system
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: 'True or plausible but broad/specialized VTI1A location: endomembrane system.'
    action: KEEP_AS_NON_CORE
    reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
    supported_by:
    - *id005
    - *id006
    - *id007
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: located_in
  review:
    summary: 'True or plausible but broad/specialized VTI1A location: membrane.'
    action: KEEP_AS_NON_CORE
    reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
    supported_by:
    - *id005
    - *id006
    - *id007
- term:
    id: GO:0016192
    label: vesicle-mediated transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: 'Supported core VTI1A SNARE-mediated trafficking process: vesicle-mediated transport.'
    action: ACCEPT
    reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
    supported_by:
    - *id001
    - *id002
    - *id003
    - *id004
- term:
    id: GO:0016197
    label: endosomal transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: 'Supported core VTI1A SNARE-mediated trafficking process: endosomal transport.'
    action: ACCEPT
    reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
    supported_by:
    - *id001
    - *id002
    - *id003
    - *id004
- term:
    id: GO:0031410
    label: cytoplasmic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Supported cytoplasmic vesicle localization for VTI1A trafficking routes.
    action: ACCEPT
    reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
    supported_by:
    - reference_id: UniProt:Q96AJ9
      supporting_text: Cytoplasmic vesicle
    - *id007
- term:
    id: GO:0061025
    label: membrane fusion
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: 'Supported core VTI1A SNARE-mediated trafficking process: membrane fusion.'
    action: ACCEPT
    reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
    supported_by:
    - *id001
    - *id002
    - *id003
    - *id004
- term:
    id: GO:0098588
    label: bounding membrane of organelle
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: 'True or plausible but broad/specialized VTI1A location: bounding membrane of organelle.'
    action: KEEP_AS_NON_CORE
    reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
    supported_by:
    - *id005
    - *id006
    - *id007
- term:
    id: GO:0032456
    label: endocytic recycling
  evidence_type: IMP
  original_reference_id: PMID:23677696
  qualifier: involved_in
  review:
    summary: The phenotype in the cited Golgi-ribbon paper is better described as early-endosome-to-TGN retrograde traffic than generic endocytic recycling.
    action: MODIFY
    reason: PMID:23677696 links Vti1a to the VAMP4/STX6/STX16 SNARE pathway for early-endosome-to-TGN retrograde trafficking and Golgi organization.
    supported_by:
    - *id004
    - *id008
    - *id009
    proposed_replacement_terms:
    - id: GO:0042147
      label: retrograde transport, endosome to Golgi
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24095276
  qualifier: enables
  review:
    summary: The STX12/VTI1A interaction is relevant, but GO:0005515 is too generic for VTI1A molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The useful curation should describe VTI1A as a SNAP receptor/SNARE component in membrane traffic and autophagy-associated trafficking, not generic protein binding.
    supported_by:
    - reference_id: file:human/VTI1A/VTI1A-notes.md
      supporting_text: Generic protein binding is too vague for VTI1A; the useful function is SNARE-mediated membrane traffic.
    - reference_id: PMID:24095276
      supporting_text: Knockdown of syntaxin 13 (STX13) or its binding partner Vti1a
- term:
    id: GO:0005776
    label: autophagosome
  evidence_type: IDA
  original_reference_id: PMID:24095276
  qualifier: located_in
  review:
    summary: 'Directly supported autophagy/autophagosome context for VTI1A: autophagosome.'
    action: ACCEPT
    reason: PMID:24095276 directly reports Vti1a knockdown blocking autophagic flux in the STX13/CHMP2B context and GOA includes autophagosome localization from that study.
    supported_by: *id010
- term:
    id: GO:0006914
    label: autophagy
  evidence_type: IMP
  original_reference_id: PMID:24095276
  qualifier: involved_in
  review:
    summary: 'Directly supported autophagy/autophagosome context for VTI1A: autophagy.'
    action: ACCEPT
    reason: PMID:24095276 directly reports Vti1a knockdown blocking autophagic flux in the STX13/CHMP2B context and GOA includes autophagosome localization from that study.
    supported_by: *id010
- term:
    id: GO:0032588
    label: trans-Golgi network membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6811431
  qualifier: located_in
  review:
    summary: 'Supported Golgi/TGN location for VTI1A: trans-Golgi network membrane.'
    action: ACCEPT
    reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
    supported_by:
    - *id004
    - *id008
    - *id009
    - reference_id: UniProt:Q96AJ9
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0032588
    label: trans-Golgi network membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6814671
  qualifier: located_in
  review:
    summary: 'Supported Golgi/TGN location for VTI1A: trans-Golgi network membrane.'
    action: ACCEPT
    reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
    supported_by:
    - *id004
    - *id008
    - *id009
    - reference_id: UniProt:Q96AJ9
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0032588
    label: trans-Golgi network membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6814674
  qualifier: located_in
  review:
    summary: 'Supported Golgi/TGN location for VTI1A: trans-Golgi network membrane.'
    action: ACCEPT
    reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
    supported_by:
    - *id004
    - *id008
    - *id009
    - reference_id: UniProt:Q96AJ9
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0032588
    label: trans-Golgi network membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6814676
  qualifier: located_in
  review:
    summary: 'Supported Golgi/TGN location for VTI1A: trans-Golgi network membrane.'
    action: ACCEPT
    reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
    supported_by:
    - *id004
    - *id008
    - *id009
    - reference_id: UniProt:Q96AJ9
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0032588
    label: trans-Golgi network membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6814678
  qualifier: located_in
  review:
    summary: 'Supported Golgi/TGN location for VTI1A: trans-Golgi network membrane.'
    action: ACCEPT
    reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
    supported_by:
    - *id004
    - *id008
    - *id009
    - reference_id: UniProt:Q96AJ9
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0032588
    label: trans-Golgi network membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6814682
  qualifier: located_in
  review:
    summary: 'Supported Golgi/TGN location for VTI1A: trans-Golgi network membrane.'
    action: ACCEPT
    reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
    supported_by:
    - *id004
    - *id008
    - *id009
    - reference_id: UniProt:Q96AJ9
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0032588
    label: trans-Golgi network membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6814683
  qualifier: located_in
  review:
    summary: 'Supported Golgi/TGN location for VTI1A: trans-Golgi network membrane.'
    action: ACCEPT
    reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
    supported_by:
    - *id004
    - *id008
    - *id009
    - reference_id: UniProt:Q96AJ9
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0032588
    label: trans-Golgi network membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6814684
  qualifier: located_in
  review:
    summary: 'Supported Golgi/TGN location for VTI1A: trans-Golgi network membrane.'
    action: ACCEPT
    reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
    supported_by:
    - *id004
    - *id008
    - *id009
    - reference_id: UniProt:Q96AJ9
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6811431
  qualifier: located_in
  review:
    summary: 'Supported Golgi/TGN location for VTI1A: Golgi membrane.'
    action: ACCEPT
    reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
    supported_by:
    - *id004
    - *id008
    - *id009
    - reference_id: UniProt:Q96AJ9
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6811433
  qualifier: located_in
  review:
    summary: 'Supported Golgi/TGN location for VTI1A: Golgi membrane.'
    action: ACCEPT
    reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
    supported_by:
    - *id004
    - *id008
    - *id009
    - reference_id: UniProt:Q96AJ9
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0050882
    label: voluntary musculoskeletal movement
  evidence_type: IMP
  original_reference_id: PMID:22958904
  qualifier: involved_in
  review:
    summary: The cited paper supports VAMP1, not VTI1A, in hereditary spastic ataxia/movement phenotypes.
    action: REMOVE
    reason: The cached PMID identifies VAMP1 as the responsible gene and contains no VTI1A support; this phenotype should not be propagated to VTI1A.
    supported_by:
    - reference_id: PMID:22958904
      supporting_text: identifies vesicle-associated membrane protein 1 (VAMP1)
- term:
    id: GO:0006888
    label: endoplasmic reticulum to Golgi vesicle-mediated transport
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Supported as a non-conventional ER/Golgi or early secretory trafficking context for VTI1A.
    action: ACCEPT
    reason: PMID:19138172 supports a VAMP7/Vti1a route for KChIP1/Kv4 traffic distinct from conventional VSVG traffic.
    supported_by:
    - *id007
    - *id011
    - *id005
    - *id006
- term:
    id: GO:0048280
    label: vesicle fusion with Golgi apparatus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'Supported core VTI1A SNARE-mediated trafficking process: vesicle fusion with Golgi apparatus.'
    action: ACCEPT
    reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
    supported_by:
    - *id001
    - *id002
    - *id003
    - *id004
- term:
    id: GO:0005768
    label: endosome
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'Supported compartment for VTI1A SNARE-mediated trafficking: endosome.'
    action: ACCEPT
    reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
    supported_by:
    - *id001
    - *id002
    - *id003
    - reference_id: UniProt:Q96AJ9
      supporting_text: Cytoplasmic vesicle
- term:
    id: GO:0008021
    label: synaptic vesicle
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'True or plausible but broad/specialized VTI1A location: synaptic vesicle.'
    action: KEEP_AS_NON_CORE
    reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
    supported_by:
    - *id005
    - *id006
    - *id007
- term:
    id: GO:0030136
    label: clathrin-coated vesicle
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'True or plausible but broad/specialized VTI1A location: clathrin-coated vesicle.'
    action: KEEP_AS_NON_CORE
    reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
    supported_by:
    - *id005
    - *id006
    - *id007
- term:
    id: GO:0031201
    label: SNARE complex
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: part_of
  review:
    summary: Supported as a core SNARE-complex context for VTI1A.
    action: ACCEPT
    reason: VTI1A is part of STX10/STX16/VAMP3 and VAMP4/STX6/STX16 SNARE-complex contexts that mediate endosome-to-Golgi/TGN traffic.
    supported_by:
    - *id002
    - *id003
    - reference_id: UniProt:Q96AJ9
      supporting_text: Identified in a complex containing STX6, STX12, VAMP4 and VTI1A
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'True or plausible but broad/specialized VTI1A location: neuronal cell body.'
    action: KEEP_AS_NON_CORE
    reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
    supported_by:
    - *id005
    - *id006
    - *id007
- term:
    id: GO:0044306
    label: neuron projection terminus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'True or plausible but broad/specialized VTI1A location: neuron projection terminus.'
    action: KEEP_AS_NON_CORE
    reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
    supported_by:
    - *id005
    - *id006
    - *id007
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'True or plausible but broad/specialized VTI1A location: perinuclear region of cytoplasm.'
    action: KEEP_AS_NON_CORE
    reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
    supported_by:
    - *id005
    - *id006
    - *id007
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IDA
  original_reference_id: PMID:19224922
  qualifier: located_in
  review:
    summary: 'Supported Golgi/TGN location for VTI1A: Golgi apparatus.'
    action: ACCEPT
    reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
    supported_by:
    - *id004
    - *id008
    - *id009
    - reference_id: UniProt:Q96AJ9
      supporting_text: Golgi apparatus membrane
- term:
    id: GO:0042147
    label: retrograde transport, endosome to Golgi
  evidence_type: IMP
  original_reference_id: PMID:19224922
  qualifier: involved_in
  review:
    summary: 'Supported core VTI1A SNARE-mediated trafficking process: retrograde transport, endosome to Golgi.'
    action: ACCEPT
    reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
    supported_by:
    - *id001
    - *id002
    - *id003
    - *id004
- term:
    id: GO:0042147
    label: retrograde transport, endosome to Golgi
  evidence_type: IDA
  original_reference_id: PMID:18195106
  qualifier: involved_in
  review:
    summary: 'Supported core VTI1A SNARE-mediated trafficking process: retrograde transport, endosome to Golgi.'
    action: ACCEPT
    reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
    supported_by:
    - *id001
    - *id002
    - *id003
    - *id004
- term:
    id: GO:0005484
    label: SNAP receptor activity
  evidence_type: IDA
  original_reference_id: PMID:15215310
  qualifier: enables
  review:
    summary: Accepted for VTI1A on independent SNARE evidence; the cited PMID appears to describe GS15 rather than VTI1A.
    action: ACCEPT
    reason: VTI1A clearly has SNAP receptor activity from UniProt and other VTI1A-specific evidence, but the original GS15 PMID should be reviewed as a possible source/reference error.
    supported_by:
    - reference_id: UniProt:Q96AJ9
      supporting_text: mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
    - reference_id: UniProt:Q96AJ9
      supporting_text: to promote fusion of the lipid bilayers
    - &id012
      reference_id: PMID:18195106
      supporting_text: complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
    - &id013
      reference_id: PMID:15215310
      supporting_text: syntaxin 5, GS28, Ykt6, and GS15 exist as a unique SNARE complex
- term:
    id: GO:0031201
    label: SNARE complex
  evidence_type: TAS
  original_reference_id: PMID:15215310
  qualifier: part_of
  review:
    summary: Accepted for VTI1A on independent SNARE-complex evidence; the cited PMID appears to describe GS15 rather than VTI1A.
    action: ACCEPT
    reason: VTI1A is supported as a SNARE-complex component by VTI1A-specific evidence, but the original GS15 PMID should be reviewed as a possible source/reference error.
    supported_by:
    - *id012
    - &id014
      reference_id: PMID:18195106
      supporting_text: implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
    - reference_id: UniProt:Q96AJ9
      supporting_text: Identified in a complex containing STX6, STX12, VAMP4 and VTI1A
    - *id013
- term:
    id: GO:0042147
    label: retrograde transport, endosome to Golgi
  evidence_type: IDA
  original_reference_id: PMID:15215310
  qualifier: involved_in
  review:
    summary: Accepted for VTI1A on independent endosome-to-Golgi evidence; the cited PMID appears to describe GS15 rather than VTI1A.
    action: ACCEPT
    reason: VTI1A-specific evidence from UniProt and PMID:18195106 supports retrograde endosome-to-Golgi transport, but the original GS15 PMID should be reviewed as a possible source/reference error.
    supported_by:
    - reference_id: UniProt:Q96AJ9
      supporting_text: Involved in vesicular transport from the late endosomes to the trans-Golgi network
    - *id012
    - *id014
    - *id013
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings:
  - statement: Provides electronic SNARE-family (SNAP receptor activity, SNARE binding,
      vesicle-mediated transport) annotations for VTI1A via InterPro VTI1/SNARE-domain
      mapping.
- 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 experimentally-supported endosome/TGN localization and endosome-to-TGN
      trafficking process annotations to VTI1A from characterised orthologous SNAREs
      (Vti1a/Vti1b/Vti1) by curator judgment of sequence similarity.
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings:
  - statement: PAINT/IBA phylogenetic-inference annotations propagate SNAP receptor
      activity, SNARE binding, endosome-to-Golgi/TGN retrograde transport, and Golgi/endosome
      localization from experimentally annotated VTI1-family SNAREs to VTI1A.
- 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 Golgi apparatus, endosome, and TGN localizations
      for VTI1A from UniProt subcellular-location vocabulary, consistent with the
      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 VTI1A via
      inter-ontology logical inference, consistent with VTI1A's role as a SNARE catalysing
      vesicle-membrane fusion.
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings:
  - statement: ARBA machine-learning rule assigns broad vesicle/membrane-associated
      terms to VTI1A based on generalized sequence/annotation features; correct but
      non-specific relative to VTI1A's Golgi/endosome-SNARE role.
- id: PMID:15215310
  title: Participation of the syntaxin 5/Ykt6/GS28/GS15 SNARE complex in transport from the early/recycling endosome to the trans-Golgi network.
  findings:
  - statement: Accessible text supports a syntaxin5/Ykt6/GS28/GS15 complex, not VTI1A; VTI1A terms citing this PMID are accepted only on independent evidence and should be checked as possible source/reference errors.
- id: PMID:18195106
  title: A syntaxin 10-SNARE complex distinguishes two distinct transport routes from endosomes to the trans-Golgi in human cells.
  findings:
  - statement: STX10, STX16, Vti1a, and VAMP3 form a SNARE-complex route required for MPR transport from endosomes/late endosomes to the TGN/Golgi.
- id: PMID:19224922
  title: Differential effects of depletion of ARL1 and ARFRP1 on membrane trafficking between the trans-Golgi network and endosomes.
  findings:
  - statement: ARL1/ARFRP1 work supports Vti1a-containing SNARE involvement in Shiga-toxin retrograde transport downstream of ARL1.
- id: PMID:22958904
  title: VAMP1 mutation causes dominant hereditary spastic ataxia in Newfoundland families.
  findings:
  - statement: This is a VAMP1 spastic ataxia paper and does not support VTI1A movement annotation.
- id: PMID:23677696
  title: VAMP4 is required to maintain the ribbon structure of the Golgi apparatus.
  findings:
  - statement: Vti1a depletion phenocopies VAMP4-cognate SNARE disruption of Golgi ribbon structure, supporting early-endosome-to-TGN retrograde traffic.
- id: PMID:24095276
  title: Syntaxin 13, a genetic modifier of mutant CHMP2B in frontotemporal dementia, is required for autophagosome maturation.
  findings:
  - statement: Vti1a knockdown with STX13 blocks autophagic flux and supports autophagy/autophagosome context.
- id: Reactome:R-HSA-6811431
  title: RAB6:GTP binds the GARP and COG complexes, t-SNAREs and endosome-derived vesicles
  findings:
  - statement: RAB6:GTP recruits the GARP tethering complex (VPS54/53/52/51) to the
      TGN, where GARP interacts with TGN SNAREs STX10 and STX16 and with a vesicle
      fraction containing the v-SNARE VAMP4; in the same pathway, the COG complex
      facilitates retrograde traffic in a STX6/STX16/VTI1A and VAMP4-dependent manner.
- id: Reactome:R-HSA-6811433
  title: The COG tethering complex interacts with numerous SNAREs at the Golgi membrane
  findings:
  - statement: The Golgi-localized COG tethering complex interacts with Golgi SNAREs
      STX6, STX16, GOSR1, GOSR2, BET1L, SNAP29, VPS45 and VTI1A during intra-Golgi
      and endosome-to-TGN retrograde vesicle capture.
- id: Reactome:R-HSA-6814671
  title: Fusion of late-endosome derived vesicles at the TGN
  findings:
  - statement: After capture at the TGN, late-endosome-derived vesicles undergo SNARE-mediated
      membrane fusion (involving VTI1A as part of the STX10/STX16/VTI1A t-SNARE complex)
      to deliver cargo and the resulting cis-SNARE to the TGN membrane.
- id: Reactome:R-HSA-6814674
  title: Tethering of late endosome-derived vesicles by GARP, STX10:ST16:VTI1A and Golgins
  findings:
  - statement: RAB9-positive late-endosome-derived vesicles are tethered at the TGN
      by GARP, the golgin GCC2, and the STX10/STX16/VTI1A t-SNARE complex — the primary
      Reactome step in which VTI1A directly participates.
- id: Reactome:R-HSA-6814676
  title: SNAPs and NSF hexamer bind cis-SNARE at the TGN
  findings:
  - statement: After late-endosome-to-TGN fusion, the 4-membered cis-SNARE complex
      containing VTI1A binds α/γ-SNAP and NSF hexamer, priming it for ATP-dependent
      disassembly.
- id: Reactome:R-HSA-6814678
  title: ATP hydrolysis by NSF disassembles the cis-SNARE at the TGN
  findings:
  - statement: NSF-driven ATP hydrolysis disassembles the post-fusion cis-SNARE complex
      containing VTI1A, releasing SNAREs (including VTI1A) for further rounds of endosome-to-TGN
      membrane fusion.
- id: Reactome:R-HSA-6814682
  title: Fusion of early-endosome derived vesicles at the TGN
  findings:
  - statement: Early-endosome-derived retrograde vesicles fuse at the TGN via a SNARE
      complex that includes VTI1A (with STX6, STX16, VAMP4), delivering cargo such
      as TGOLN2 and internalised toxins back to the Golgi.
- id: Reactome:R-HSA-6814683
  title: NSF-dependent ATP hydrolysis disassembles the cis-SNARE at the TGN
  findings:
  - statement: NSF-driven ATP hydrolysis disassembles the post-fusion cis-SNARE complex
      (containing VTI1A) after early-endosome-derived vesicle fusion at the TGN, recycling
      VTI1A and partner SNAREs.
- id: Reactome:R-HSA-6814684
  title: cis-SNARE binds SNAPs and NSF hexamer at the TGN
  findings:
  - statement: After early-endosome-derived vesicle fusion, the 4-membered cis-SNARE
      complex (containing VTI1A) binds α/γ-SNAP and NSF hexamer at the TGN, priming
      it for ATP-dependent disassembly.
- id: PMID:19138172
  title: A VAMP7/Vti1a SNARE complex distinguishes a non-conventional traffic route to the cell surface used by KChIP1 and Kv4 potassium channels.
  findings:
  - statement: VAMP7/Vti1a defines a non-conventional KChIP1/Kv4 traffic pathway to the cell surface in HeLa and Neuro2A cells.
- id: UniProt:Q96AJ9
  title: UniProt entry for VTI1A (Q96AJ9)
  findings:
  - statement: VTI1A is a VTI1-family SNARE involved in vesicle transport, lipid-bilayer fusion, late-endosome-to-TGN transport, and non-conventional cell-surface trafficking.
- id: file:human/VTI1A/VTI1A-notes.md
  title: Local curation notes for VTI1A
  findings:
  - statement: Local synthesis identifies SNARE-mediated endosome-to-Golgi/TGN traffic as core, autophagy as PN-relevant, and ESCRT-III complex membership as inappropriate.
core_functions:
- description: SNARE/SNAP-receptor-mediated vesicle fusion in retrograde endosome or late-endosome to trans-Golgi network/Golgi transport.
  supported_by:
  - *id001
  - *id002
  - *id003
  - *id005
  - *id006
  molecular_function:
    id: GO:0005484
    label: SNAP receptor activity
  directly_involved_in:
  - id: GO:0042147
    label: retrograde transport, endosome to Golgi
  - id: GO:0048280
    label: vesicle fusion with Golgi apparatus
  - id: GO:0061025
    label: membrane fusion
  - id: GO:0016197
    label: endosomal transport
  - id: GO:0006886
    label: intracellular protein transport
  locations:
  - id: GO:0032588
    label: trans-Golgi network membrane
  - id: GO:0000139
    label: Golgi membrane
  - id: GO:0031902
    label: late endosome membrane
  - id: GO:0005768
    label: endosome
- description: SNARE-mediated autophagy/autophagosome trafficking in the STX13/Vti1a autophagic-flux context.
  supported_by: *id010
  molecular_function:
    id: GO:0005484
    label: SNAP receptor activity
  directly_involved_in:
  - id: GO:0006914
    label: autophagy
  - id: GO:0016236
    label: macroautophagy
  locations:
  - id: GO:0005776
    label: autophagosome
suggested_questions:
- question: Does VTI1A directly mediate phagophore closure/autophagosome assembly, or is the observed autophagy phenotype an indirect consequence of STX13-associated endosomal SNARE trafficking?
- question: Should VTI1A annotations citing PMID:15215310 be migrated to the GS15/BET1L gene rather than VTI1A?
- question: 'Which VTI1A-containing SNARE complex is active in autophagy: STX13/STX12-VTI1A, STX10-STX16-VTI1A-VAMP3, VAMP7-VTI1A, or a distinct context-specific complex?'
suggested_experiments:
- description: Rescue VTI1A knockdown with wild-type and SNARE-domain/membrane-anchor mutants in MPR recycling, Golgi ribbon, and autophagic flux assays.
  hypothesis: VTI1A SNARE activity and membrane targeting are required for both endosome-to-TGN transport and autophagy-associated trafficking.
- description: Use endogenous tagging/proximity labeling during starvation or CHMP2B perturbation to identify VTI1A SNARE partners at autophagy-related membranes.
  hypothesis: VTI1A forms a context-specific SNARE complex during autophagic flux that can be separated from its canonical endosome-to-TGN complex.
- description: Compare VTI1A depletion with ESCRT-III perturbation for LC3 flux, phagophore closure, and ESCRT-III recruitment/turnover.
  hypothesis: VTI1A affects autophagy through membrane-fusion traffic rather than direct ESCRT-III complex membership.