VTI1A

UniProt ID: Q96AJ9
Organism: Homo sapiens
Review Status: COMPLETE
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Gene 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.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0006891 intra-Golgi vesicle-mediated transport
IBA
GO_REF:0000033 		ACCEPT
Summary: Supported core VTI1A SNARE-mediated trafficking process: intra-Golgi vesicle-mediated transport.
Reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
Supporting Evidence:
UniProt:Q96AJ9
Involved in vesicular transport from the late endosomes to the trans-Golgi network
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:18195106
implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0006896 Golgi to vacuole transport
IBA
GO_REF:0000033 		MODIFY
Summary: The yeast-derived Golgi-to-vacuole term captures a trafficking idea but is not the best human VTI1A process term.
Reason: Human evidence supports endosome/late-endosome to trans-Golgi network retrograde transport rather than a literal Golgi-to-vacuole process.
Supporting Evidence:
UniProt:Q96AJ9
Involved in vesicular transport from the late endosomes to the trans-Golgi network
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:18195106
implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
GO:0016236 macroautophagy
IBA
GO_REF:0000033 		ACCEPT
Summary: Directly supported autophagy/autophagosome context for VTI1A: macroautophagy.
Reason: PMID:24095276 directly reports Vti1a knockdown blocking autophagic flux in the STX13/CHMP2B context and GOA includes autophagosome localization from that study.
Supporting Evidence:
PMID:24095276
Knockdown of syntaxin 13 (STX13) or its binding partner Vti1a in mammalian cells caused LC3-positive puncta to accumulate
PMID:24095276
blocks autophagic flux
GO:0042147 retrograde transport, endosome to Golgi
IBA
GO_REF:0000033 		ACCEPT
Summary: Supported core VTI1A SNARE-mediated trafficking process: retrograde transport, endosome to Golgi.
Reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
Supporting Evidence:
UniProt:Q96AJ9
Involved in vesicular transport from the late endosomes to the trans-Golgi network
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:18195106
implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0048280 vesicle fusion with Golgi apparatus
IBA
GO_REF:0000033 		ACCEPT
Summary: Supported core VTI1A SNARE-mediated trafficking process: vesicle fusion with Golgi apparatus.
Reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
Supporting Evidence:
UniProt:Q96AJ9
Involved in vesicular transport from the late endosomes to the trans-Golgi network
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:18195106
implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0000149 SNARE binding
IBA
GO_REF:0000033 		MODIFY
Summary: The annotation reflects SNARE-partner interactions, but SNAP receptor activity is the more informative molecular-function term for VTI1A.
Reason: VTI1A is a SNARE whose core molecular function is SNAP receptor/SNARE complex activity in membrane fusion; SNARE binding alone is less precise.
Proposed replacements: SNAP receptor activity
Supporting Evidence:
UniProt:Q96AJ9
mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
UniProt:Q96AJ9
to promote fusion of the lipid bilayers
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
GO:0005484 SNAP receptor activity
IBA
GO_REF:0000033 		ACCEPT
Summary: Supported as the core VTI1A molecular function.
Reason: VTI1A is a SNARE/SNAP receptor that forms cognate SNARE complexes for membrane fusion and vesicle transport.
Supporting Evidence:
UniProt:Q96AJ9
mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
UniProt:Q96AJ9
to promote fusion of the lipid bilayers
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:19138172
KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7
GO:0005789 endoplasmic reticulum membrane
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: True or plausible but broad/specialized VTI1A location: endoplasmic reticulum membrane.
Reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
Supporting Evidence:
UniProt:Q96AJ9
mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
UniProt:Q96AJ9
to promote fusion of the lipid bilayers
PMID:19138172
KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7
GO:0012507 ER to Golgi transport vesicle membrane
IBA
GO_REF:0000033 		ACCEPT
Summary: Supported location for VTI1A in non-conventional ER/Golgi or trafficking-vesicle routes.
Reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
Supporting Evidence:
PMID:19138172
KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7
PMID:19138172
inhibited Kv4/KChIP1traffic to the plasma membrane
UniProt:Q96AJ9
Cytoplasmic vesicle
GO:0031902 late endosome membrane
IBA
GO_REF:0000033 		ACCEPT
Summary: Supported compartment for VTI1A SNARE-mediated trafficking: late endosome membrane.
Reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
Supporting Evidence:
UniProt:Q96AJ9
Involved in vesicular transport from the late endosomes to the trans-Golgi network
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:18195106
implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
UniProt:Q96AJ9
Cytoplasmic vesicle
GO:0000139 Golgi membrane
IEA
GO_REF:0000044 		ACCEPT
Summary: Supported Golgi/TGN location for VTI1A: Golgi membrane.
Reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
Supporting Evidence:
UniProt:Q96AJ9
Golgi apparatus membrane
PMID:23677696
syntaxin 6, syntaxin 16, and Vti1a also disrupted the Golgi ribbon structure
PMID:23677696
normal retrograde trafficking from the early endosome to the TGN
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0005484 SNAP receptor activity
IEA
GO_REF:0000002 		ACCEPT
Summary: Supported as the core VTI1A molecular function.
Reason: VTI1A is a SNARE/SNAP receptor that forms cognate SNARE complexes for membrane fusion and vesicle transport.
Supporting Evidence:
UniProt:Q96AJ9
mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
UniProt:Q96AJ9
to promote fusion of the lipid bilayers
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:19138172
KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7
GO:0005737 cytoplasm
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: True or plausible but broad/specialized VTI1A location: cytoplasm.
Reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
Supporting Evidence:
UniProt:Q96AJ9
mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
UniProt:Q96AJ9
to promote fusion of the lipid bilayers
PMID:19138172
KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7
GO:0005794 Golgi apparatus
IEA
GO_REF:0000002 		ACCEPT
Summary: Supported Golgi/TGN location for VTI1A: Golgi apparatus.
Reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
Supporting Evidence:
UniProt:Q96AJ9
Golgi apparatus membrane
PMID:23677696
syntaxin 6, syntaxin 16, and Vti1a also disrupted the Golgi ribbon structure
PMID:23677696
normal retrograde trafficking from the early endosome to the TGN
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0005829 cytosol
IEA
GO_REF:0000108 		KEEP AS NON CORE
Summary: True or plausible but broad/specialized VTI1A location: cytosol.
Reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
Supporting Evidence:
UniProt:Q96AJ9
mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
UniProt:Q96AJ9
to promote fusion of the lipid bilayers
PMID:19138172
KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7
GO:0006886 intracellular protein transport
IEA
GO_REF:0000002 		ACCEPT
Summary: Supported core VTI1A SNARE-mediated trafficking process: intracellular protein transport.
Reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
Supporting Evidence:
UniProt:Q96AJ9
Involved in vesicular transport from the late endosomes to the trans-Golgi network
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:18195106
implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0012505 endomembrane system
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: True or plausible but broad/specialized VTI1A location: endomembrane system.
Reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
Supporting Evidence:
UniProt:Q96AJ9
mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
UniProt:Q96AJ9
to promote fusion of the lipid bilayers
PMID:19138172
KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7
GO:0016020 membrane
IEA
GO_REF:0000002 		KEEP AS NON CORE
Summary: True or plausible but broad/specialized VTI1A location: membrane.
Reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
Supporting Evidence:
UniProt:Q96AJ9
mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
UniProt:Q96AJ9
to promote fusion of the lipid bilayers
PMID:19138172
KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7
GO:0016192 vesicle-mediated transport
IEA
GO_REF:0000002 		ACCEPT
Summary: Supported core VTI1A SNARE-mediated trafficking process: vesicle-mediated transport.
Reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
Supporting Evidence:
UniProt:Q96AJ9
Involved in vesicular transport from the late endosomes to the trans-Golgi network
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:18195106
implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0016197 endosomal transport
IEA
GO_REF:0000117 		ACCEPT
Summary: Supported core VTI1A SNARE-mediated trafficking process: endosomal transport.
Reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
Supporting Evidence:
UniProt:Q96AJ9
Involved in vesicular transport from the late endosomes to the trans-Golgi network
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:18195106
implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0031410 cytoplasmic vesicle
IEA
GO_REF:0000044 		ACCEPT
Summary: Supported cytoplasmic vesicle localization for VTI1A trafficking routes.
Reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
Supporting Evidence:
UniProt:Q96AJ9
Cytoplasmic vesicle
PMID:19138172
KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7
GO:0061025 membrane fusion
IEA
GO_REF:0000117 		ACCEPT
Summary: Supported core VTI1A SNARE-mediated trafficking process: membrane fusion.
Reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
Supporting Evidence:
UniProt:Q96AJ9
Involved in vesicular transport from the late endosomes to the trans-Golgi network
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:18195106
implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0098588 bounding membrane of organelle
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: True or plausible but broad/specialized VTI1A location: bounding membrane of organelle.
Reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
Supporting Evidence:
UniProt:Q96AJ9
mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
UniProt:Q96AJ9
to promote fusion of the lipid bilayers
PMID:19138172
KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7
GO:0032456 endocytic recycling
IMP
PMID:23677696
VAMP4 is required to maintain the ribbon structure of the Go... 		MODIFY
Summary: The phenotype in the cited Golgi-ribbon paper is better described as early-endosome-to-TGN retrograde traffic than generic endocytic recycling.
Reason: PMID:23677696 links Vti1a to the VAMP4/STX6/STX16 SNARE pathway for early-endosome-to-TGN retrograde trafficking and Golgi organization.
Supporting Evidence:
UniProt:Q96AJ9
Golgi apparatus membrane
PMID:23677696
syntaxin 6, syntaxin 16, and Vti1a also disrupted the Golgi ribbon structure
PMID:23677696
normal retrograde trafficking from the early endosome to the TGN
GO:0005515 protein binding
IPI
PMID:24095276
Syntaxin 13, a genetic modifier of mutant CHMP2B in frontote... 		MARK AS OVER ANNOTATED
Summary: The STX12/VTI1A interaction is relevant, but GO:0005515 is too generic for VTI1A molecular function.
Reason: The useful curation should describe VTI1A as a SNAP receptor/SNARE component in membrane traffic and autophagy-associated trafficking, not generic protein binding.
Supporting Evidence:
file:human/VTI1A/VTI1A-notes.md
Generic protein binding is too vague for VTI1A; the useful function is SNARE-mediated membrane traffic.
PMID:24095276
Knockdown of syntaxin 13 (STX13) or its binding partner Vti1a
GO:0005776 autophagosome
IDA
PMID:24095276
Syntaxin 13, a genetic modifier of mutant CHMP2B in frontote... 		ACCEPT
Summary: Directly supported autophagy/autophagosome context for VTI1A: autophagosome.
Reason: PMID:24095276 directly reports Vti1a knockdown blocking autophagic flux in the STX13/CHMP2B context and GOA includes autophagosome localization from that study.
Supporting Evidence:
PMID:24095276
Knockdown of syntaxin 13 (STX13) or its binding partner Vti1a in mammalian cells caused LC3-positive puncta to accumulate
PMID:24095276
blocks autophagic flux
GO:0006914 autophagy
IMP
PMID:24095276
Syntaxin 13, a genetic modifier of mutant CHMP2B in frontote... 		ACCEPT
Summary: Directly supported autophagy/autophagosome context for VTI1A: autophagy.
Reason: PMID:24095276 directly reports Vti1a knockdown blocking autophagic flux in the STX13/CHMP2B context and GOA includes autophagosome localization from that study.
Supporting Evidence:
PMID:24095276
Knockdown of syntaxin 13 (STX13) or its binding partner Vti1a in mammalian cells caused LC3-positive puncta to accumulate
PMID:24095276
blocks autophagic flux
GO:0032588 trans-Golgi network membrane
TAS
Reactome:R-HSA-6811431 		ACCEPT
Summary: Supported Golgi/TGN location for VTI1A: trans-Golgi network membrane.
Reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
Supporting Evidence:
UniProt:Q96AJ9
Golgi apparatus membrane
PMID:23677696
syntaxin 6, syntaxin 16, and Vti1a also disrupted the Golgi ribbon structure
PMID:23677696
normal retrograde trafficking from the early endosome to the TGN
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0032588 trans-Golgi network membrane
TAS
Reactome:R-HSA-6814671 		ACCEPT
Summary: Supported Golgi/TGN location for VTI1A: trans-Golgi network membrane.
Reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
Supporting Evidence:
UniProt:Q96AJ9
Golgi apparatus membrane
PMID:23677696
syntaxin 6, syntaxin 16, and Vti1a also disrupted the Golgi ribbon structure
PMID:23677696
normal retrograde trafficking from the early endosome to the TGN
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0032588 trans-Golgi network membrane
TAS
Reactome:R-HSA-6814674 		ACCEPT
Summary: Supported Golgi/TGN location for VTI1A: trans-Golgi network membrane.
Reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
Supporting Evidence:
UniProt:Q96AJ9
Golgi apparatus membrane
PMID:23677696
syntaxin 6, syntaxin 16, and Vti1a also disrupted the Golgi ribbon structure
PMID:23677696
normal retrograde trafficking from the early endosome to the TGN
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0032588 trans-Golgi network membrane
TAS
Reactome:R-HSA-6814676 		ACCEPT
Summary: Supported Golgi/TGN location for VTI1A: trans-Golgi network membrane.
Reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
Supporting Evidence:
UniProt:Q96AJ9
Golgi apparatus membrane
PMID:23677696
syntaxin 6, syntaxin 16, and Vti1a also disrupted the Golgi ribbon structure
PMID:23677696
normal retrograde trafficking from the early endosome to the TGN
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0032588 trans-Golgi network membrane
TAS
Reactome:R-HSA-6814678 		ACCEPT
Summary: Supported Golgi/TGN location for VTI1A: trans-Golgi network membrane.
Reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
Supporting Evidence:
UniProt:Q96AJ9
Golgi apparatus membrane
PMID:23677696
syntaxin 6, syntaxin 16, and Vti1a also disrupted the Golgi ribbon structure
PMID:23677696
normal retrograde trafficking from the early endosome to the TGN
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0032588 trans-Golgi network membrane
TAS
Reactome:R-HSA-6814682 		ACCEPT
Summary: Supported Golgi/TGN location for VTI1A: trans-Golgi network membrane.
Reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
Supporting Evidence:
UniProt:Q96AJ9
Golgi apparatus membrane
PMID:23677696
syntaxin 6, syntaxin 16, and Vti1a also disrupted the Golgi ribbon structure
PMID:23677696
normal retrograde trafficking from the early endosome to the TGN
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0032588 trans-Golgi network membrane
TAS
Reactome:R-HSA-6814683 		ACCEPT
Summary: Supported Golgi/TGN location for VTI1A: trans-Golgi network membrane.
Reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
Supporting Evidence:
UniProt:Q96AJ9
Golgi apparatus membrane
PMID:23677696
syntaxin 6, syntaxin 16, and Vti1a also disrupted the Golgi ribbon structure
PMID:23677696
normal retrograde trafficking from the early endosome to the TGN
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0032588 trans-Golgi network membrane
TAS
Reactome:R-HSA-6814684 		ACCEPT
Summary: Supported Golgi/TGN location for VTI1A: trans-Golgi network membrane.
Reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
Supporting Evidence:
UniProt:Q96AJ9
Golgi apparatus membrane
PMID:23677696
syntaxin 6, syntaxin 16, and Vti1a also disrupted the Golgi ribbon structure
PMID:23677696
normal retrograde trafficking from the early endosome to the TGN
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0000139 Golgi membrane
TAS
Reactome:R-HSA-6811431 		ACCEPT
Summary: Supported Golgi/TGN location for VTI1A: Golgi membrane.
Reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
Supporting Evidence:
UniProt:Q96AJ9
Golgi apparatus membrane
PMID:23677696
syntaxin 6, syntaxin 16, and Vti1a also disrupted the Golgi ribbon structure
PMID:23677696
normal retrograde trafficking from the early endosome to the TGN
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0000139 Golgi membrane
TAS
Reactome:R-HSA-6811433 		ACCEPT
Summary: Supported Golgi/TGN location for VTI1A: Golgi membrane.
Reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
Supporting Evidence:
UniProt:Q96AJ9
Golgi apparatus membrane
PMID:23677696
syntaxin 6, syntaxin 16, and Vti1a also disrupted the Golgi ribbon structure
PMID:23677696
normal retrograde trafficking from the early endosome to the TGN
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0050882 voluntary musculoskeletal movement
IMP
PMID:22958904
VAMP1 mutation causes dominant hereditary spastic ataxia in ... 		REMOVE
Summary: The cited paper supports VAMP1, not VTI1A, in hereditary spastic ataxia/movement phenotypes.
Reason: The cached PMID identifies VAMP1 as the responsible gene and contains no VTI1A support; this phenotype should not be propagated to VTI1A.
Supporting Evidence:
PMID:22958904
identifies vesicle-associated membrane protein 1 (VAMP1)
GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport
ISS
GO_REF:0000024 		ACCEPT
Summary: Supported as a non-conventional ER/Golgi or early secretory trafficking context for VTI1A.
Reason: PMID:19138172 supports a VAMP7/Vti1a route for KChIP1/Kv4 traffic distinct from conventional VSVG traffic.
Supporting Evidence:
PMID:19138172
KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7
PMID:19138172
inhibited Kv4/KChIP1traffic to the plasma membrane
UniProt:Q96AJ9
mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
UniProt:Q96AJ9
to promote fusion of the lipid bilayers
GO:0048280 vesicle fusion with Golgi apparatus
ISS
GO_REF:0000024 		ACCEPT
Summary: Supported core VTI1A SNARE-mediated trafficking process: vesicle fusion with Golgi apparatus.
Reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
Supporting Evidence:
UniProt:Q96AJ9
Involved in vesicular transport from the late endosomes to the trans-Golgi network
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:18195106
implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0005768 endosome
ISS
GO_REF:0000024 		ACCEPT
Summary: Supported compartment for VTI1A SNARE-mediated trafficking: endosome.
Reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
Supporting Evidence:
UniProt:Q96AJ9
Involved in vesicular transport from the late endosomes to the trans-Golgi network
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:18195106
implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
UniProt:Q96AJ9
Cytoplasmic vesicle
GO:0008021 synaptic vesicle
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: True or plausible but broad/specialized VTI1A location: synaptic vesicle.
Reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
Supporting Evidence:
UniProt:Q96AJ9
mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
UniProt:Q96AJ9
to promote fusion of the lipid bilayers
PMID:19138172
KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7
GO:0030136 clathrin-coated vesicle
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: True or plausible but broad/specialized VTI1A location: clathrin-coated vesicle.
Reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
Supporting Evidence:
UniProt:Q96AJ9
mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
UniProt:Q96AJ9
to promote fusion of the lipid bilayers
PMID:19138172
KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7
GO:0031201 SNARE complex
ISS
GO_REF:0000024 		ACCEPT
Summary: Supported as a core SNARE-complex context for VTI1A.
Reason: VTI1A is part of STX10/STX16/VAMP3 and VAMP4/STX6/STX16 SNARE-complex contexts that mediate endosome-to-Golgi/TGN traffic.
Supporting Evidence:
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:18195106
implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
UniProt:Q96AJ9
Identified in a complex containing STX6, STX12, VAMP4 and VTI1A
GO:0043025 neuronal cell body
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: True or plausible but broad/specialized VTI1A location: neuronal cell body.
Reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
Supporting Evidence:
UniProt:Q96AJ9
mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
UniProt:Q96AJ9
to promote fusion of the lipid bilayers
PMID:19138172
KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7
GO:0044306 neuron projection terminus
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: True or plausible but broad/specialized VTI1A location: neuron projection terminus.
Reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
Supporting Evidence:
UniProt:Q96AJ9
mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
UniProt:Q96AJ9
to promote fusion of the lipid bilayers
PMID:19138172
KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7
GO:0048471 perinuclear region of cytoplasm
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: True or plausible but broad/specialized VTI1A location: perinuclear region of cytoplasm.
Reason: More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
Supporting Evidence:
UniProt:Q96AJ9
mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
UniProt:Q96AJ9
to promote fusion of the lipid bilayers
PMID:19138172
KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7
GO:0005794 Golgi apparatus
IDA
PMID:19224922
Differential effects of depletion of ARL1 and ARFRP1 on memb... 		ACCEPT
Summary: Supported Golgi/TGN location for VTI1A: Golgi apparatus.
Reason: This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
Supporting Evidence:
UniProt:Q96AJ9
Golgi apparatus membrane
PMID:23677696
syntaxin 6, syntaxin 16, and Vti1a also disrupted the Golgi ribbon structure
PMID:23677696
normal retrograde trafficking from the early endosome to the TGN
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0042147 retrograde transport, endosome to Golgi
IMP
PMID:19224922
Differential effects of depletion of ARL1 and ARFRP1 on memb... 		ACCEPT
Summary: Supported core VTI1A SNARE-mediated trafficking process: retrograde transport, endosome to Golgi.
Reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
Supporting Evidence:
UniProt:Q96AJ9
Involved in vesicular transport from the late endosomes to the trans-Golgi network
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:18195106
implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0042147 retrograde transport, endosome to Golgi
IDA
PMID:18195106
A syntaxin 10-SNARE complex distinguishes two distinct trans... 		ACCEPT
Summary: Supported core VTI1A SNARE-mediated trafficking process: retrograde transport, endosome to Golgi.
Reason: VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
Supporting Evidence:
UniProt:Q96AJ9
Involved in vesicular transport from the late endosomes to the trans-Golgi network
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:18195106
implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
UniProt:Q96AJ9
Golgi apparatus membrane
GO:0005484 SNAP receptor activity
IDA
PMID:15215310
Participation of the syntaxin 5/Ykt6/GS28/GS15 SNARE complex... 		ACCEPT
Summary: Accepted for VTI1A on independent SNARE evidence; the cited PMID appears to describe GS15 rather than VTI1A.
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.
Supporting Evidence:
UniProt:Q96AJ9
mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
UniProt:Q96AJ9
to promote fusion of the lipid bilayers
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:15215310
syntaxin 5, GS28, Ykt6, and GS15 exist as a unique SNARE complex
GO:0031201 SNARE complex
TAS
PMID:15215310
Participation of the syntaxin 5/Ykt6/GS28/GS15 SNARE complex... 		ACCEPT
Summary: Accepted for VTI1A on independent SNARE-complex evidence; the cited PMID appears to describe GS15 rather than VTI1A.
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.
Supporting Evidence:
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:18195106
implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
UniProt:Q96AJ9
Identified in a complex containing STX6, STX12, VAMP4 and VTI1A
PMID:15215310
syntaxin 5, GS28, Ykt6, and GS15 exist as a unique SNARE complex
GO:0042147 retrograde transport, endosome to Golgi
IDA
PMID:15215310
Participation of the syntaxin 5/Ykt6/GS28/GS15 SNARE complex... 		ACCEPT
Summary: Accepted for VTI1A on independent endosome-to-Golgi evidence; the cited PMID appears to describe GS15 rather than VTI1A.
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.
Supporting Evidence:
UniProt:Q96AJ9
Involved in vesicular transport from the late endosomes to the trans-Golgi network
PMID:18195106
complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
PMID:18195106
implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
PMID:15215310
syntaxin 5, GS28, Ykt6, and GS15 exist as a unique SNARE complex

Core Functions

SNARE/SNAP-receptor-mediated vesicle fusion in retrograde endosome or late-endosome to trans-Golgi network/Golgi transport.

Molecular Function:
SNAP receptor activity
Directly Involved In:
retrograde transport, endosome to Golgi vesicle fusion with Golgi apparatus membrane fusion endosomal transport intracellular protein transport
Cellular Locations:
trans-Golgi network membrane Golgi membrane late endosome membrane endosome
Supporting Evidence:
  • UniProt:Q96AJ9
    Involved in vesicular transport from the late endosomes to the trans-Golgi network
  • PMID:18195106
    complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport
  • PMID:18195106
    implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3
  • UniProt:Q96AJ9
    mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane
  • UniProt:Q96AJ9
    to promote fusion of the lipid bilayers

SNARE-mediated autophagy/autophagosome trafficking in the STX13/Vti1a autophagic-flux context.

Molecular Function:
SNAP receptor activity
Directly Involved In:
autophagy macroautophagy
Cellular Locations:
autophagosome
Supporting Evidence:
  • PMID:24095276
    Knockdown of syntaxin 13 (STX13) or its binding partner Vti1a in mammalian cells caused LC3-positive puncta to accumulate
  • PMID:24095276
    blocks autophagic flux

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
  • Provides electronic SNARE-family (SNAP receptor activity, SNARE binding, vesicle-mediated transport) annotations for VTI1A via InterPro VTI1/SNARE-domain mapping.
GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  • 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.
GO_REF:0000033
Annotation inferences using phylogenetic trees
  • 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.
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  • Provides electronic Golgi apparatus, endosome, and TGN localizations for VTI1A from UniProt subcellular-location vocabulary, consistent with the experimental IDA evidence.
GO_REF:0000108
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
  • 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.
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
  • 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.
PMID:15215310
Participation of the syntaxin 5/Ykt6/GS28/GS15 SNARE complex in transport from the early/recycling endosome to the trans-Golgi network.
  • 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.
PMID:18195106
A syntaxin 10-SNARE complex distinguishes two distinct transport routes from endosomes to the trans-Golgi in human cells.
  • STX10, STX16, Vti1a, and VAMP3 form a SNARE-complex route required for MPR transport from endosomes/late endosomes to the TGN/Golgi.
PMID:19224922
Differential effects of depletion of ARL1 and ARFRP1 on membrane trafficking between the trans-Golgi network and endosomes.
  • ARL1/ARFRP1 work supports Vti1a-containing SNARE involvement in Shiga-toxin retrograde transport downstream of ARL1.
PMID:22958904
VAMP1 mutation causes dominant hereditary spastic ataxia in Newfoundland families.
  • This is a VAMP1 spastic ataxia paper and does not support VTI1A movement annotation.
PMID:23677696
VAMP4 is required to maintain the ribbon structure of the Golgi apparatus.
  • Vti1a depletion phenocopies VAMP4-cognate SNARE disruption of Golgi ribbon structure, supporting early-endosome-to-TGN retrograde traffic.
PMID:24095276
Syntaxin 13, a genetic modifier of mutant CHMP2B in frontotemporal dementia, is required for autophagosome maturation.
  • Vti1a knockdown with STX13 blocks autophagic flux and supports autophagy/autophagosome context.
Reactome:R-HSA-6811431
RAB6:GTP binds the GARP and COG complexes, t-SNAREs and endosome-derived vesicles
  • 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.
Reactome:R-HSA-6811433
The COG tethering complex interacts with numerous SNAREs at the Golgi membrane
  • 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.
Reactome:R-HSA-6814671
Fusion of late-endosome derived vesicles at the TGN
  • 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.
Reactome:R-HSA-6814674
Tethering of late endosome-derived vesicles by GARP, STX10:ST16:VTI1A and Golgins
  • RAB9-positive late-endosome-derived vesicles are tethered at the TGN by GARP, the golgin GCC2, and the STX10/STX16/VTI1A t-SNARE complex β€” the primary Reactome step in which VTI1A directly participates.
Reactome:R-HSA-6814676
SNAPs and NSF hexamer bind cis-SNARE at the TGN
  • After late-endosome-to-TGN fusion, the 4-membered cis-SNARE complex containing VTI1A binds Ξ±/Ξ³-SNAP and NSF hexamer, priming it for ATP-dependent disassembly.
Reactome:R-HSA-6814678
ATP hydrolysis by NSF disassembles the cis-SNARE at the TGN
  • 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.
Reactome:R-HSA-6814682
Fusion of early-endosome derived vesicles at the TGN
  • 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.
Reactome:R-HSA-6814683
NSF-dependent ATP hydrolysis disassembles the cis-SNARE at the TGN
  • 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.
Reactome:R-HSA-6814684
cis-SNARE binds SNAPs and NSF hexamer at the TGN
  • After early-endosome-derived vesicle fusion, the 4-membered cis-SNARE complex (containing VTI1A) binds Ξ±/Ξ³-SNAP and NSF hexamer at the TGN, priming it for ATP-dependent disassembly.
PMID:19138172
A VAMP7/Vti1a SNARE complex distinguishes a non-conventional traffic route to the cell surface used by KChIP1 and Kv4 potassium channels.
  • VAMP7/Vti1a defines a non-conventional KChIP1/Kv4 traffic pathway to the cell surface in HeLa and Neuro2A cells.
UniProt:Q96AJ9
UniProt entry for VTI1A (Q96AJ9)
  • VTI1A is a VTI1-family SNARE involved in vesicle transport, lipid-bilayer fusion, late-endosome-to-TGN transport, and non-conventional cell-surface trafficking.
file:human/VTI1A/VTI1A-notes.md
Local curation notes for VTI1A
  • Local synthesis identifies SNARE-mediated endosome-to-Golgi/TGN traffic as core, autophagy as PN-relevant, and ESCRT-III complex membership as inappropriate.

Suggested Questions for Experts

Q: Does VTI1A directly mediate phagophore closure/autophagosome assembly, or is the observed autophagy phenotype an indirect consequence of STX13-associated endosomal SNARE trafficking?

Q: Should VTI1A annotations citing PMID:15215310 be migrated to the GS15/BET1L gene rather than VTI1A?

Q: 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

Experiment: 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.

Experiment: 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.

Experiment: 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.

πŸ“š Additional Documentation

Notes

(VTI1A-notes.md)

VTI1A notes

Local evidence reviewed

  • just fetch-gene human VTI1A created the review stub, UniProt record, GOA table, cached publications, Reactome entries, and PANTHER family data. GOA seeded 53 annotations covering SNARE activity/complex membership, endosome-to-Golgi/TGN retrograde traffic, Golgi/TGN and endosomal locations, autophagy, neuronal/synaptic context, broad membrane/cytosol locations, and a movement phenotype.
  • just deep-research-falcon human VTI1A timed out after 600 seconds on 2026-06-02 and did not produce a Falcon report.
  • UniProt identifies VTI1A as a VTI1-family SNARE. Its function comment says it mediates vesicle transport through interactions with target-membrane SNAREs and promotes lipid-bilayer fusion [UniProt:Q96AJ9, "mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane"; UniProt:Q96AJ9, "to promote fusion of the lipid bilayers"]. This supports SNAP receptor/SNARE-complex activity as the core molecular function, not generic protein binding.
  • Direct endosome-to-TGN evidence is strong. The syntaxin-10 SNARE-complex paper reports that a complex of STX10, STX16, Vti1a, and VAMP3 is required for mannose 6-phosphate receptor transport from endosomes to Golgi/TGN [PMID:18195106, "STX10, STX16, Vti1a, and VAMP3 is required for this MPR transport"]. Soluble Vti1a inhibited MPR transport, and the authors concluded that this complex transports MPRs from late endosomes to the Golgi [PMID:18195106, "implicate a SNARE complex comprised of STX10, STX16, Vti1a, and VAMP3"].
  • A second trafficking route is supported by the VAMP7/Vti1a paper. KChIP1 vesicles colocalized with Vti1a and VAMP7, Vti1a knockdown inhibited Kv4/KChIP1 traffic to the plasma membrane, and the authors conclude that VAMP7/Vti1a defines a novel cell-surface traffic pathway [PMID:19138172, "KChIP1-expressing vesicles co-localized with the SNARE proteins Vti1a and VAMP7"; PMID:19138172, "inhibited Kv4/KChIP1traffic to the plasma membrane"].
  • Autophagy evidence comes from the STX13/Vti1a paper. The abstract reports that knockdown of syntaxin 13 or Vti1a caused LC3-positive puncta accumulation and blocked autophagic flux [PMID:24095276, "Knockdown of syntaxin 13 (STX13) or its binding partner Vti1a in mammalian cells caused LC3-positive puncta to accumulate"]. This supports VTI1A in autophagy/macroautophagy and autophagosome context, but the direct text available does not justify ESCRT-III complex membership.
  • The Golgi ribbon/endocytic recycling paper supports Vti1a as a VAMP4 cognate SNARE partner in early-endosome-to-TGN retrograde traffic and Golgi organization [PMID:23677696, "syntaxin 6, syntaxin 16, and Vti1a also disrupted the Golgi ribbon structure"; PMID:23677696, "normal retrograde trafficking from the early endosome to the TGN"]. The endocytic recycling row should be interpreted through this retrograde trafficking evidence.
  • PMID:15215310 is problematic for VTI1A. The accessible cached abstract is about syntaxin 5/Ykt6/GS28/GS15 and does not mention VTI1A [PMID:15215310, "syntaxin 5, GS28, Ykt6, and GS15 exist as a unique SNARE complex"]. Rows using this PMID are accepted for the term only because independent VTI1A evidence supports the same SNARE and endosome-to-Golgi conclusions; the cited PMID itself should be treated as a likely source/reference mismatch.
  • PMID:22958904 is a VAMP1 disease paper. The cache contains no VTI1A mention, and the abstract identifies VAMP1 as the responsible gene for hereditary spastic ataxia [PMID:22958904, "This report identifies vesicle-associated membrane protein 1 (VAMP1)... as the responsible gene"]. The VTI1A voluntary musculoskeletal movement annotation should be removed.
  • The PN projection to GO:0000815 ESCRT III complex should not be added for VTI1A. VTI1A is a SNARE that intersects with ESCRT/CHMP2B autophagy phenotypes through STX13/Vti1a trafficking, but it is not an ESCRT-III complex subunit.

Curation synthesis

The core role of VTI1A is SNARE-mediated vesicle docking/fusion in membrane trafficking, especially endosome/late-endosome to trans-Golgi network retrograde transport and related Golgi/TGN vesicle fusion. Core locations are Golgi/TGN membrane, late endosome/endosome, cytoplasmic vesicle, and ER-to-Golgi or alternative trafficking vesicles.

Autophagy/macroautophagy rows should be retained because Vti1a knockdown blocks autophagic flux in the STX13/CHMP2B context. The evidence supports autophagy and autophagosome context but does not establish ESCRT-III complex membership.

Rows from PMID:15215310 are likely mis-referenced or at least not confirmable from accessible text. The affected terms are still biologically supported by independent VTI1A evidence, but the PMID should not be treated as direct evidence for VTI1A. The movement phenotype from PMID:22958904 should be removed because it is attributable to VAMP1, not VTI1A.

Description cleanup note

The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.

  • Moved out of the YAML description: the prior wording described the autophagy/autophagosome context as PN-relevant and noted that VTI1A should not be annotated as an ESCRT-III complex component.

Pn Notes

(VTI1A-pn-notes.md)

VTI1A PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q96AJ9
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-pr-1217 (PR 1217)
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • 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.
  • Existing/core annotation action counts: ACCEPT: 37; KEEP_AS_NON_CORE: 11; MARK_AS_OVER_ANNOTATED: 1; MODIFY: 3; REMOVE: 1

PN Consistency Summary

  • Consistency: Mostly consistent on the trafficking/SNARE core (UniProt, PMID:18195106, deep-research notes, and review all agree on endosomeβ†’TGN retrograde SNARE function and autophagic-flux involvement via PMID:24095276). One hard contradiction: the PN type-node projects GO:0000815 ESCRT III complex as ok_for_propagation, but the review and notes explicitly state VTI1A "is not an ESCRT-III complex component" β€” it is a SNARE intersecting ESCRT/CHMP2B autophagy phenotypes only via STX13/Vti1a trafficking.
  • PN story / NEW pressure: PN frames VTI1A as an ESCRT-III modulator/component for phagophore sealing/microautophagy. Verified GO:0000815 (OLS) is a complex-membership CC term; asserting it for a SNARE over-reaches. The genuinely supported autophagy content (autophagy, macroautophagy, autophagosome) is already captured in existing annotations from PMID:24095276. Conclusion: over-reaches for ESCRT-III; autophagy role already captured.
  • Evidence alignment: Strong overlap. PN ref "Syntaxin 13… required for autophagosome maturation" = review PMID:24095276 (autophagy/autophagosome rows). PN "Role of Vti1a… nervous system disorders" (Frontiers review) is not separately cited in the YAML; the YAML adds primary SNARE papers (PMID:18195106, 19138172, 23677696) the PN rows omit.
  • Verdict: Trafficking core solid; PN ESCRT-III complex projection (GO:0000815) contradicts the review and is biologically wrong for a SNARE β€” demote to context_only/no propagation. Autophagy already captured; no new GO term warranted.

Full Consistency Review

  • UniProt: Q96AJ9 Β· batch: proteostasis-pr-1217 Β· review status: COMPLETE
  • PN placement: ALP|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-III complex activity modulator and ALP|Microautophagy|General microautophagy machinery|ESCRT-III complex component ; PN-node mapping: group Sealing = mapped/ok_for_propagation β†’ GO:0000045 autophagosome assembly; type ESCRT-III complex component = mapped/ok_for_propagation β†’ GO:0000815 ESCRT III complex; class nodes context_only.
  • Consistency: Mostly consistent on the trafficking/SNARE core (UniProt, PMID:18195106, deep-research notes, and review all agree on endosomeβ†’TGN retrograde SNARE function and autophagic-flux involvement via PMID:24095276). One hard contradiction: the PN type-node projects GO:0000815 ESCRT III complex as ok_for_propagation, but the review and notes explicitly state VTI1A "is not an ESCRT-III complex component" β€” it is a SNARE intersecting ESCRT/CHMP2B autophagy phenotypes only via STX13/Vti1a trafficking.
  • PN story / NEW pressure: PN frames VTI1A as an ESCRT-III modulator/component for phagophore sealing/microautophagy. Verified GO:0000815 (OLS) is a complex-membership CC term; asserting it for a SNARE over-reaches. The genuinely supported autophagy content (autophagy, macroautophagy, autophagosome) is already captured in existing annotations from PMID:24095276. Conclusion: over-reaches for ESCRT-III; autophagy role already captured.
  • Mapping strategy: GO:0000815 should NOT propagate to VTI1A (recommend statusβ†’context_only for the microautophagy type-node, as the sibling "modulator" node already is). GO:0000045 autophagosome assembly (verified: phagophore-enclosure process) is narrower/different from the review's evidence, which supports flux/maturation (macroautophagy + autophagosome localization), not assembly β€” projection is a mismatch but at worst broader-context, lower priority than the ESCRT-III error.
  • Evidence alignment: Strong overlap. PN ref "Syntaxin 13… required for autophagosome maturation" = review PMID:24095276 (autophagy/autophagosome rows). PN "Role of Vti1a… nervous system disorders" (Frontiers review) is not separately cited in the YAML; the YAML adds primary SNARE papers (PMID:18195106, 19138172, 23677696) the PN rows omit.
  • Verdict: Trafficking core solid; PN ESCRT-III complex projection (GO:0000815) contradicts the review and is biologically wrong for a SNARE β€” demote to context_only/no propagation. Autophagy already captured; no new GO term warranted.

PN Dossier Context

  • review_batch: proteostasis-pr-1217
  • review_yaml: genes/human/VTI1A/VTI1A-ai-review.yaml
  • PN workbook rows: 2

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | ESCRT-III complex activity modulator

  • UniProt: Q96AJ9
  • In branches: ALP
  • Notes: Works with ESCRT-III complex (and is a genetic modifier for mutations in CHMP2B) for autophagosome closure, along with its binding partner STX12. Knockdown of STX12 or its binding partner VTI1A leads to accumulation of the autophagy marker LC3, affects autophagosome maturation, and blocks autophagic flux.
  • PN references (titles):
    • Syntaxin 13, a Genetic Modifier of Mutant CHMP2B in Frontotemporal Dementia, Is Required for Autophagosome Maturation - ScienceDirect
    • Frontiers | The Role of Vti1a in Biological Functions and Its Possible Role in Nervous System Disorders (frontiersin.org)
  • PN-node mapping records (path + ancestors):
    • [type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-III complex activity modulator
      status=context_only scope=too_broad_to_propagate GO=[GO:0000815 ESCRT III complex]
      rationale: Reviewed as an ESCRT-III activity modulator. It is related to ESCRT-III but should not project ESCRT-III complex membership to all members.
    • [group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0000045 autophagosome assembly]
      rationale: This group captures autophagophore closure/sealing, a late step in autophagosome assembly. Autophagosome assembly is the safer process target than autophagosome-lysosome fusion.
    • [class] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion
      status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
      rationale: This class is a late macroautophagy context, but the subtree mixes docking, fusion, localization, membrane-composition, and unknown late-stage roles. The class-level relation is useful for display while propagation is restricted to narrower mechanism nodes.
    • [branch] Autophagy-Lysosome Pathway
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 2: Autophagy-Lysosome Pathway | Microautophagy | General microautophagy machinery | ESCRT-III complex component

  • UniProt: Q96AJ9
  • In branches: ALP
  • PN-node mapping records (path + ancestors):
    • [type] Autophagy-Lysosome Pathway|Microautophagy|General microautophagy machinery|ESCRT-III complex component
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0000815 ESCRT III complex]
      rationale: This leaf is a component bucket for ESCRT-III machinery used in microautophagy contexts. The shared GO assertion is ESCRT III complex membership.
    • [group] Autophagy-Lysosome Pathway|Microautophagy|General microautophagy machinery
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
    • [class] Autophagy-Lysosome Pathway|Microautophagy
      status=context_only scope=too_broad_to_propagate GO=[GO:0016237 microautophagy]
      rationale: The class names a real GO process, but the subtree includes machinery components and mitochondrion-derived-vesicle contexts as well as process labels. Propagation is restricted to narrower nodes.
    • [branch] Autophagy-Lysosome Pathway
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Projected GO annotations (2)

  • GO:0000045 autophagosome assembly | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
  • GO:0000815 ESCRT III complex | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Microautophagy|General microautophagy machinery|ESCRT-III complex component

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

πŸ“„ View Raw YAML

 
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 β€” 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 Ξ±/Ξ³-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 Ξ±/Ξ³-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.