Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000149 SNARE binding	IBA GO_REF:0000033	MODIFY	Summary: The annotation reflects real SNARE-partner interactions, but SNAP receptor activity is the more informative molecular-function term for syntaxin-12. Reason: STX12 is a syntaxin-family SNARE whose core role is SNAP receptor/SNARE activity in vesicle docking and membrane fusion; SNARE binding alone is less precise. Proposed replacements: SNAP receptor activity Supporting Evidence: UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes. UniProt:Q86Y82 Together with SNARE STX6, promotes movement of vesicles from endosomes to the cell membrane PMID:19546860 including SNAP-25 and syntaxin 13, was demonstrated
GO:0008021 synaptic vesicle	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Supported or plausible neuronal/endosomal recycling context, but not the primary conserved STX12 function: synaptic vesicle. Reason: The main conserved role is endosomal/recycling SNARE-mediated vesicle docking and fusion; synaptic/postsynaptic rows are specialized neuronal contexts. Supporting Evidence: UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes. UniProt:Q86Y82 Together with SNARE STX6, promotes movement of vesicles from endosomes to the cell membrane UniProt:Q86Y82 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit
GO:0098837 postsynaptic recycling endosome	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Supported or plausible neuronal/endosomal recycling context, but not the primary conserved STX12 function: postsynaptic recycling endosome. Reason: The main conserved role is endosomal/recycling SNARE-mediated vesicle docking and fusion; synaptic/postsynaptic rows are specialized neuronal contexts. Supporting Evidence: UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes. UniProt:Q86Y82 Together with SNARE STX6, promotes movement of vesicles from endosomes to the cell membrane UniProt:Q86Y82 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit
GO:0030672 synaptic vesicle membrane	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Supported or plausible neuronal/endosomal recycling context, but not the primary conserved STX12 function: synaptic vesicle membrane. Reason: The main conserved role is endosomal/recycling SNARE-mediated vesicle docking and fusion; synaptic/postsynaptic rows are specialized neuronal contexts. Supporting Evidence: UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes. UniProt:Q86Y82 Together with SNARE STX6, promotes movement of vesicles from endosomes to the cell membrane UniProt:Q86Y82 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit
GO:0000045 autophagosome assembly	IBA GO_REF:0000033	ACCEPT	Summary: Directly supported PN-relevant autophagy context for STX12: autophagosome assembly. Reason: PMID:24095276 directly supports STX13/STX12 localization to LC3-positive phagophores and a requirement for autophagic flux/phagophore maturation. 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 participates in the maturation of phagophores into closed autophagosomes
GO:0048278 vesicle docking	IBA GO_REF:0000033	ACCEPT	Summary: Supported core STX12 vesicle-trafficking/SNARE function: vesicle docking. Reason: STX12 is a syntaxin SNARE that promotes endosomal vesicle movement, docking, and fusion with target membranes. Supporting Evidence: UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes. UniProt:Q86Y82 Together with SNARE STX6, promotes movement of vesicles from endosomes to the cell membrane PMID:19546860 proteins that control membrane fusion
GO:0000139 Golgi membrane	IEA GO_REF:0000044	ACCEPT	Summary: Supported core localization for an endosomal/recycling syntaxin SNARE: Golgi membrane. Reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12. Supporting Evidence: UniProt:Q86Y82 Endosome membrane UniProt:Q86Y82 Recycling endosome membrane UniProt:Q86Y82 Golgi apparatus membrane
GO:0005484 SNAP receptor activity	IEA GO_REF:0000002	ACCEPT	Summary: Supported core STX12 vesicle-trafficking/SNARE function: SNAP receptor activity. Reason: STX12 is a syntaxin SNARE that promotes endosomal vesicle movement, docking, and fusion with target membranes. Supporting Evidence: UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes. UniProt:Q86Y82 Together with SNARE STX6, promotes movement of vesicles from endosomes to the cell membrane PMID:19546860 proteins that control membrane fusion
GO:0006886 intracellular protein transport	IEA GO_REF:0000002	ACCEPT	Summary: Supported core STX12 vesicle-trafficking/SNARE function: intracellular protein transport. Reason: STX12 is a syntaxin SNARE that promotes endosomal vesicle movement, docking, and fusion with target membranes. Supporting Evidence: UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes. UniProt:Q86Y82 Together with SNARE STX6, promotes movement of vesicles from endosomes to the cell membrane PMID:19546860 proteins that control membrane fusion
GO:0010008 endosome membrane	IEA GO_REF:0000044	ACCEPT	Summary: Supported core localization for an endosomal/recycling syntaxin SNARE: endosome membrane. Reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12. Supporting Evidence: UniProt:Q86Y82 Endosome membrane UniProt:Q86Y82 Recycling endosome membrane UniProt:Q86Y82 Golgi apparatus membrane
GO:0012505 endomembrane system	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: True but broad localization for membrane-associated STX12: endomembrane system. Reason: More specific endosome, early/recycling endosome membrane, Golgi membrane, and phagophore locations better capture STX12 biology. Supporting Evidence: UniProt:Q86Y82 Endosome membrane UniProt:Q86Y82 Recycling endosome membrane PMID:24095276 Knockdown of syntaxin 13 (STX13) or its binding partner Vti1a in mammalian cells caused LC3-positive puncta to accumulate
GO:0016020 membrane	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: True but broad localization for membrane-associated STX12: membrane. Reason: More specific endosome, early/recycling endosome membrane, Golgi membrane, and phagophore locations better capture STX12 biology. Supporting Evidence: UniProt:Q86Y82 Endosome membrane UniProt:Q86Y82 Recycling endosome membrane PMID:24095276 Knockdown of syntaxin 13 (STX13) or its binding partner Vti1a in mammalian cells caused LC3-positive puncta to accumulate
GO:0016192 vesicle-mediated transport	IEA GO_REF:0000002	ACCEPT	Summary: Supported core STX12 vesicle-trafficking/SNARE function: vesicle-mediated transport. Reason: STX12 is a syntaxin SNARE that promotes endosomal vesicle movement, docking, and fusion with target membranes. Supporting Evidence: UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes. UniProt:Q86Y82 Together with SNARE STX6, promotes movement of vesicles from endosomes to the cell membrane PMID:19546860 proteins that control membrane fusion
GO:0031410 cytoplasmic vesicle	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: True but broad localization for membrane-associated STX12: cytoplasmic vesicle. Reason: More specific endosome, early/recycling endosome membrane, Golgi membrane, and phagophore locations better capture STX12 biology. Supporting Evidence: UniProt:Q86Y82 Endosome membrane UniProt:Q86Y82 Recycling endosome membrane PMID:24095276 Knockdown of syntaxin 13 (STX13) or its binding partner Vti1a in mammalian cells caused LC3-positive puncta to accumulate
GO:0031901 early endosome membrane	IEA GO_REF:0000044	ACCEPT	Summary: Supported core localization for an endosomal/recycling syntaxin SNARE: early endosome membrane. Reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12. Supporting Evidence: UniProt:Q86Y82 Endosome membrane UniProt:Q86Y82 Recycling endosome membrane UniProt:Q86Y82 Golgi apparatus membrane
GO:0055038 recycling endosome membrane	IEA GO_REF:0000044	ACCEPT	Summary: Supported core localization for an endosomal/recycling syntaxin SNARE: recycling endosome membrane. Reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12. Supporting Evidence: UniProt:Q86Y82 Endosome membrane UniProt:Q86Y82 Recycling endosome membrane UniProt:Q86Y82 Golgi apparatus membrane
GO:0061025 membrane fusion	IEA GO_REF:0000108	ACCEPT	Summary: Supported core STX12 vesicle-trafficking/SNARE function: membrane fusion. Reason: STX12 is a syntaxin SNARE that promotes endosomal vesicle movement, docking, and fusion with target membranes. Supporting Evidence: UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes. UniProt:Q86Y82 Together with SNARE STX6, promotes movement of vesicles from endosomes to the cell membrane PMID:19546860 proteins that control membrane fusion
GO:0005515 protein binding	IPI PMID:15469992 Association of ABCA1 with syntaxin 13 and flotillin-1 and en...	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function. Reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms. Supporting Evidence: file:human/STX12/STX12-notes.md Generic `protein binding` rows should be marked over-annotated even when the interaction itself is real. UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes. PMID:15469992 ABCA1 forms a complex with syntaxin 13 and flotillin-1
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function. Reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms. Supporting Evidence: file:human/STX12/STX12-notes.md Generic `protein binding` rows should be marked over-annotated even when the interaction itself is real. UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes.
GO:0005515 protein binding	IPI PMID:26359495 The Q-soluble N-Ethylmaleimide-sensitive Factor Attachment P...	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function. Reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms. Supporting Evidence: file:human/STX12/STX12-notes.md Generic `protein binding` rows should be marked over-annotated even when the interaction itself is real. UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function. Reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms. Supporting Evidence: file:human/STX12/STX12-notes.md Generic `protein binding` rows should be marked over-annotated even when the interaction itself is real. UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function. Reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms. Supporting Evidence: file:human/STX12/STX12-notes.md Generic `protein binding` rows should be marked over-annotated even when the interaction itself is real. UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function. Reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms. Supporting Evidence: file:human/STX12/STX12-notes.md Generic `protein binding` rows should be marked over-annotated even when the interaction itself is real. UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function. Reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms. Supporting Evidence: file:human/STX12/STX12-notes.md Generic `protein binding` rows should be marked over-annotated even when the interaction itself is real. UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function. Reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms. Supporting Evidence: file:human/STX12/STX12-notes.md Generic `protein binding` rows should be marked over-annotated even when the interaction itself is real. UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function. Reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms. Supporting Evidence: file:human/STX12/STX12-notes.md Generic `protein binding` rows should be marked over-annotated even when the interaction itself is real. UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes.
GO:0005794 Golgi apparatus	IDA GO_REF:0000052	ACCEPT	Summary: Supported core localization for an endosomal/recycling syntaxin SNARE: Golgi apparatus. Reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12. Supporting Evidence: UniProt:Q86Y82 Endosome membrane UniProt:Q86Y82 Recycling endosome membrane UniProt:Q86Y82 Golgi apparatus membrane
GO:0000139 Golgi membrane	ISS GO_REF:0000024	ACCEPT	Summary: Supported core localization for an endosomal/recycling syntaxin SNARE: Golgi membrane. Reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12. Supporting Evidence: UniProt:Q86Y82 Endosome membrane UniProt:Q86Y82 Recycling endosome membrane UniProt:Q86Y82 Golgi apparatus membrane
GO:0010008 endosome membrane	ISS GO_REF:0000024	ACCEPT	Summary: Supported core localization for an endosomal/recycling syntaxin SNARE: endosome membrane. Reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12. Supporting Evidence: UniProt:Q86Y82 Endosome membrane UniProt:Q86Y82 Recycling endosome membrane UniProt:Q86Y82 Golgi apparatus membrane
GO:0012505 endomembrane system	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: True but broad localization for membrane-associated STX12: endomembrane system. Reason: More specific endosome, early/recycling endosome membrane, Golgi membrane, and phagophore locations better capture STX12 biology. Supporting Evidence: UniProt:Q86Y82 Endosome membrane UniProt:Q86Y82 Recycling endosome membrane PMID:24095276 Knockdown of syntaxin 13 (STX13) or its binding partner Vti1a in mammalian cells caused LC3-positive puncta to accumulate
GO:0031901 early endosome membrane	ISS GO_REF:0000024	ACCEPT	Summary: Supported core localization for an endosomal/recycling syntaxin SNARE: early endosome membrane. Reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12. Supporting Evidence: UniProt:Q86Y82 Endosome membrane UniProt:Q86Y82 Recycling endosome membrane UniProt:Q86Y82 Golgi apparatus membrane
GO:0055038 recycling endosome membrane	ISS GO_REF:0000024	ACCEPT	Summary: Supported core localization for an endosomal/recycling syntaxin SNARE: recycling endosome membrane. Reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12. Supporting Evidence: UniProt:Q86Y82 Endosome membrane UniProt:Q86Y82 Recycling endosome membrane UniProt:Q86Y82 Golgi apparatus membrane
GO:0032456 endocytic recycling	ISS GO_REF:0000024	ACCEPT	Summary: Supported core STX12 vesicle-trafficking/SNARE function: endocytic recycling. Reason: STX12 is a syntaxin SNARE that promotes endosomal vesicle movement, docking, and fusion with target membranes. Supporting Evidence: UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes. UniProt:Q86Y82 Together with SNARE STX6, promotes movement of vesicles from endosomes to the cell membrane PMID:19546860 proteins that control membrane fusion
GO:0055037 recycling endosome	ISS GO_REF:0000024	ACCEPT	Summary: Supported core localization for an endosomal/recycling syntaxin SNARE: recycling endosome. Reason: These locations match the UniProt-supported endosome, early endosome, recycling endosome, and Golgi membrane localization of STX12. Supporting Evidence: UniProt:Q86Y82 Endosome membrane UniProt:Q86Y82 Recycling endosome membrane UniProt:Q86Y82 Golgi apparatus membrane
GO:0000045 autophagosome assembly	IMP PMID:24095276 Syntaxin 13, a genetic modifier of mutant CHMP2B in frontote...	ACCEPT	Summary: Directly supported PN-relevant autophagy context for STX12: autophagosome assembly. Reason: PMID:24095276 directly supports STX13/STX12 localization to LC3-positive phagophores and a requirement for autophagic flux/phagophore maturation. 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 participates in the maturation of phagophores into closed autophagosomes
GO:0000407 phagophore assembly site	IMP PMID:24095276 Syntaxin 13, a genetic modifier of mutant CHMP2B in frontote...	ACCEPT	Summary: Directly supported PN-relevant autophagy context for STX12: phagophore assembly site. Reason: PMID:24095276 directly supports STX13/STX12 localization to LC3-positive phagophores and a requirement for autophagic flux/phagophore maturation. 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 participates in the maturation of phagophores into closed autophagosomes
GO:0005515 protein binding	IPI PMID:24095276 Syntaxin 13, a genetic modifier of mutant CHMP2B in frontote...	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function. Reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms. Supporting Evidence: file:human/STX12/STX12-notes.md Generic `protein binding` rows should be marked over-annotated even when the interaction itself is real. UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes. PMID:24095276 Knockdown of syntaxin 13 (STX13) or its binding partner Vti1a
GO:0031982 vesicle	IMP PMID:24095276 Syntaxin 13, a genetic modifier of mutant CHMP2B in frontote...	MODIFY	Summary: The vesicle localization is supported but too broad for the direct autophagy evidence. Reason: The same study more specifically places STX13/STX12 on LC3-positive phagophores; phagophore assembly site is the better location term. Proposed replacements: phagophore assembly site 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 participates in the maturation of phagophores into closed autophagosomes
GO:0005515 protein binding	IPI PMID:19546860 The dysbindin-containing complex (BLOC-1) in brain: developm...	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function. Reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms. Supporting Evidence: file:human/STX12/STX12-notes.md Generic `protein binding` rows should be marked over-annotated even when the interaction itself is real. UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes. PMID:19546860 including SNAP-25 and syntaxin 13, was demonstrated
GO:0031201 SNARE complex	IDA PMID:19546860 The dysbindin-containing complex (BLOC-1) in brain: developm...	ACCEPT	Summary: Supported as a core SNARE-complex context for syntaxin-12. Reason: STX12 is a SNARE and UniProt reports complex formation with STX6, VAMP4, and VTI1A; the BLOC-1 paper also discusses syntaxin 13-containing SNARE complexes. Supporting Evidence: UniProt:Q86Y82 Identified in a complex containing STX6, STX12, VAMP4 and VTI1A PMID:19546860 SNARE complex containing both syntaxin 13 and SNAP-25
GO:0031083 BLOC-1 complex	IDA PMID:19546860 The dysbindin-containing complex (BLOC-1) in brain: developm...	KEEP AS NON CORE	Summary: BLOC-1 association is supported but is a non-core interaction/localization context for STX12. Reason: STX12 interacts with BLOC-1-linked trafficking machinery, but it is not a BLOC-1 complex subunit and this should not define its core function. Supporting Evidence: PMID:19546860 including SNAP-25 and syntaxin 13, was demonstrated PMID:19546860 BLOC-1... involved in intracellular membrane trafficking and organelle biogenesis
GO:0005515 protein binding	IPI PMID:12191018 Pallidin is a component of a multi-protein complex involved ...	MARK AS OVER ANNOTATED	Summary: The underlying interaction may be real, but GO:0005515 is too generic to describe STX12 molecular function. Reason: STX12 function is better captured by SNAP receptor activity, SNARE complex context, vesicle docking, membrane fusion, and endosomal/autophagy trafficking terms. Supporting Evidence: file:human/STX12/STX12-notes.md Generic `protein binding` rows should be marked over-annotated even when the interaction itself is real. UniProt:Q86Y82 SNARE promoting fusion of transport vesicles with target membranes.
GO:0033344 cholesterol efflux	IDA PMID:15469992 Association of ABCA1 with syntaxin 13 and flotillin-1 and en...	KEEP AS NON CORE	Summary: Supported ABCA1/macrophage context, but non-core for STX12: cholesterol efflux. Reason: PMID:15469992 supports a direct ABCA1/cholesterol/phagocytosis context, but this is cargo- and cell-context-specific relative to STX12 core SNARE trafficking. Supporting Evidence: PMID:15469992 ABCA1 forms a complex with syntaxin 13 and flotillin-1 PMID:15469992 Silencing of syntaxin 13 by small interfering RNA (siRNA) led to reduced ABCA1 protein levels
GO:0045121 membrane raft	IDA PMID:15469992 Association of ABCA1 with syntaxin 13 and flotillin-1 and en...	KEEP AS NON CORE	Summary: Supported ABCA1/macrophage context, but non-core for STX12: membrane raft. Reason: PMID:15469992 supports a direct ABCA1/cholesterol/phagocytosis context, but this is cargo- and cell-context-specific relative to STX12 core SNARE trafficking. Supporting Evidence: PMID:15469992 ABCA1 forms a complex with syntaxin 13 and flotillin-1 PMID:15469992 Silencing of syntaxin 13 by small interfering RNA (siRNA) led to reduced ABCA1 protein levels
GO:0045335 phagocytic vesicle	IDA PMID:15469992 Association of ABCA1 with syntaxin 13 and flotillin-1 and en...	KEEP AS NON CORE	Summary: Supported ABCA1/macrophage context, but non-core for STX12: phagocytic vesicle. Reason: PMID:15469992 supports a direct ABCA1/cholesterol/phagocytosis context, but this is cargo- and cell-context-specific relative to STX12 core SNARE trafficking. Supporting Evidence: PMID:15469992 ABCA1 forms a complex with syntaxin 13 and flotillin-1 PMID:15469992 Silencing of syntaxin 13 by small interfering RNA (siRNA) led to reduced ABCA1 protein levels
GO:0050821 protein stabilization	IDA PMID:15469992 Association of ABCA1 with syntaxin 13 and flotillin-1 and en...	MARK AS OVER ANNOTATED	Summary: The ABCA1 experiment supports a specific effect on ABCA1 stability, not a general STX12 protein-stabilization function. Reason: This row overgeneralizes a context-specific ABCA1 phenotype; STX12 core function is SNARE-mediated trafficking. Supporting Evidence: PMID:15469992 ABCA1 forms a complex with syntaxin 13 and flotillin-1 PMID:15469992 Silencing of syntaxin 13 by small interfering RNA (siRNA) led to reduced ABCA1 protein levels

Core Functions

Syntaxin/SNARE-mediated vesicle docking and membrane fusion in endosomal recycling and intracellular membrane trafficking.

Molecular Function:

SNAP receptor activity

Directly Involved In:

vesicle docking membrane fusion endocytic recycling intracellular protein transport vesicle-mediated transport

Cellular Locations:

endosome membrane early endosome membrane recycling endosome membrane Golgi membrane

Supporting Evidence:

UniProt:Q86Y82
SNARE promoting fusion of transport vesicles with target membranes.
UniProt:Q86Y82
Together with SNARE STX6, promotes movement of vesicles from endosomes to the cell membrane
PMID:19546860
proteins that control membrane fusion

SNARE-mediated phagophore/autophagosome assembly or maturation in the autophagy pathway.

Molecular Function:

SNAP receptor activity

Directly Involved In:

autophagosome assembly

Cellular Locations:

phagophore assembly site

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
participates in the maturation of phagophores into closed autophagosomes

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

Provides electronic assignment of SNARE/vesicle-trafficking GO terms to STX12 via InterPro syntaxin-family domain mapping, consistent with STX12's core SNARE function.

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

Transfers endosome/recycling-endosome/Golgi localization and endocytic recycling annotations to STX12 from experimentally characterised orthologous syntaxins by curator judgment of sequence similarity.

GO_REF:0000033

Annotation inferences using phylogenetic trees

PAINT/IBA phylogenetic-inference annotations propagate SNARE-family molecular function (SNARE binding) and endosomal-recycling process/location terms to STX12 from experimentally annotated syntaxin orthologs.

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 endosome membrane, early endosome membrane, recycling endosome membrane, and Golgi membrane localizations for STX12 based on UniProt subcellular-location vocabulary, consistent with experimental IDA/ISS evidence.

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

Curates immunofluorescence-based Golgi apparatus localization for STX12 consistent with 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 STX12 via inter-ontology logical inference, consistent with STX12's core SNARE-mediated fusion role.

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

ARBA machine-learning rule assigns cytoplasmic vesicle localization to STX12 based on generalized sequence/annotation features; broadly consistent with STX12's vesicle-membrane localization but generic.

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

Combined-IEA pipeline provides broad endomembrane-system and membrane localizations for STX12; correct but generic relative to the specific endosome/Golgi terms.

PMID:12191018

Pallidin is a component of a multi-protein complex involved in the biogenesis of lysosome-related organelles.

Pallidin/BLOC-1 biology provides background for BLOC-1 interaction rows, but not a core STX12 function.

PMID:15469992

Association of ABCA1 with syntaxin 13 and flotillin-1 and enhanced phagocytosis in tangier cells.

Syntaxin 13 associates with ABCA1/flotillin-1; STX13 knockdown reduces ABCA1 protein and apoA-I-dependent phospholipid efflux.

PMID:19546860

The dysbindin-containing complex (BLOC-1) in brain: developmental regulation, interaction with SNARE proteins and role in neurite outgrowth.

BLOC-1 interacts with syntaxin 13 and other SNARE proteins, supporting a BLOC-1/SNARE trafficking context.

PMID:24095276

Syntaxin 13, a genetic modifier of mutant CHMP2B in frontotemporal dementia, is required for autophagosome maturation.

STX13/STX12 knockdown blocks autophagic flux, causes LC3/Atg5 puncta accumulation, and supports phagophore maturation into closed autophagosomes.

PMID:25416956

A proteome-scale map of the human interactome network.

Rolland et al. HI-II-14 proteome-scale yeast two-hybrid map reports an STX12 protein-protein interaction. High-throughput dataset; only bare protein-binding evidence, not a specific molecular function.

"A proteome-scale map of the human interactome network."

PMID:26359495

The Q-soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor (Q-SNARE) SNAP-47 Regulates Trafficking of Selected Vesicle-associated Membrane Proteins (VAMPs).

SNAP-47 and selected SNARE/VAMP trafficking interactions support a SNARE interaction context but not generic protein-binding curation.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

Huttlin et al. BioPlex 2.0 affinity-purification-mass-spectrometry human interactome records STX12 co-purifying partners. High-throughput dataset; only bare protein-binding evidence, not a specific molecular function.

"Architecture of the human interactome defines protein communities and disease networks."

PMID:31515488

Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.

Fragoza et al. yeast-two-hybrid screen of population variants includes STX12 interaction data. High-throughput dataset; only bare protein-binding evidence, not a specific molecular function.

"Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations."

PMID:32296183

A reference map of the human binary protein interactome.

Luck et al. HuRI reference binary interactome (yeast two-hybrid) records STX12 interactions. High-throughput dataset; only bare protein-binding evidence, not a specific molecular function.

"A reference map of the human binary protein interactome."

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

Huttlin et al. BioPlex 3.0 dual (HEK293T/HCT116) affinity-purification-mass-spectrometry interactome records STX12 interactions. High-throughput dataset; only bare protein-binding evidence, not a specific molecular function.

"Dual proteome-scale networks reveal cell-specific remodeling of the human interactome."

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

OpenCell endogenous split-mNeonGreen tagging with live-cell imaging and IP-MS records STX12 subcellular localization and interaction partners at endogenous levels. Supports vesicular/endosomal localization; high-throughput screen provides only bare protein-binding evidence for the interaction rows.

"OpenCell: Endogenous tagging for the cartography of human cellular organization."

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics.

Schaffer et al. multimodal cell-map integration of BioPlex/OpenCell/CellMap data reports STX12 community membership. High-throughput dataset; provides only bare protein-binding-level evidence, not a specific molecular function.

"Multimodal cell maps as a foundation for structural and functional genomics."

UniProt:Q86Y82

UniProt entry for STX12 (Q86Y82)

STX12 is a syntaxin-family SNARE on endosomal/Golgi/recycling-endosome membranes that promotes transport vesicle fusion and endosomal recycling.

file:human/STX12/STX12-notes.md

Local curation notes for STX12

Local synthesis treats SNARE/endosomal trafficking as core, direct autophagy evidence as PN-relevant, and ESCRT-III complex membership as inappropriate for STX12.

Suggested Experiments

Experiment: Rescue STX12 knockdown in autophagy assays with wild-type STX12 and SNARE-domain or membrane-anchor mutants, measuring LC3 turnover, Atg5 puncta, and closed autophagosome formation.

Hypothesis: The autophagy phenotype depends on STX12 SNARE activity and membrane targeting rather than a scaffolding-only interaction.

Experiment: Define endogenous STX12-containing SNARE complexes during basal and induced autophagy using proximity labeling or immunoprecipitation under crosslinking conditions.

Hypothesis: STX12 uses a context-specific SNARE-partner set at phagophores that differs from its endosomal recycling complexes.

Experiment: Test whether STX12 perturbation changes ESCRT-III recruitment, persistence, or turnover at autophagy-related membranes after CHMP2B perturbation.

Hypothesis: STX12 modifies ESCRT-III-linked autophagy phenotypes indirectly through phagophore membrane traffic rather than by being an ESCRT-III complex component.

📚 Additional Documentation

Notes

(STX12-notes.md)

STX12 notes

Local evidence reviewed

just fetch-gene human STX12 created the review stub, UniProt record, GOA table, cached publications, and PANTHER family data. GOA seeded 46 annotations, dominated by SNARE/endosomal membrane trafficking terms, autophagosome assembly/phagophore localization rows, BLOC-1/SNARE-complex rows, ABCA1/cholesterol/phagocytosis context, and generic protein-binding rows.
just deep-research-falcon human STX12 timed out after 600 seconds and did not produce a usable report. The review below is based on local UniProt, GOA, cached publication, PANTHER, Reactome, and PN-context evidence.
UniProt identifies STX12/syntaxin-12 as a syntaxin-family SNARE. Its function comment says it is a "SNARE promoting fusion of transport vesicles with target membranes" and, with STX6, promotes vesicle movement from endosomes to the cell membrane [UniProt:Q86Y82, "Together with SNARE STX6, promotes movement of vesicles from endosomes to the cell membrane"]. This supports core endosomal/recycling vesicle docking/fusion rather than generic binding.
UniProt places STX12 on endosome, Golgi, early endosome, and recycling endosome membranes [UniProt:Q86Y82, "Endosome membrane"; UniProt:Q86Y82, "Recycling endosome membrane"]. These are the most informative core locations; membrane, endomembrane system, and cytoplasmic vesicle are true but less specific.
Direct autophagy evidence comes from the syntaxin 13/STX13 paper. Knockdown of STX13 or VTI1A in mammalian cells caused LC3-positive puncta accumulation and blocked autophagic flux [PMID:24095276, "Knockdown of syntaxin 13 (STX13) or its binding partner Vti1a... blocks autophagic flux"]. STX13 was present on LC3-positive phagophores, and the authors conclude that it participates in phagophore maturation into closed autophagosomes [PMID:24095276, "participates in the maturation of phagophores into closed autophagosomes"].
BLOC-1 interaction evidence supports a non-core trafficking/regulatory context. The BLOC-1 brain paper reports selective biochemical interaction between BLOC-1 and SNARE proteins including syntaxin 13 [PMID:19546860, "interaction between brain BLOC-1 and a few members of the SNARE... including SNAP-25 and syntaxin 13"]. It also frames BLOC-1 as involved in intracellular membrane trafficking and organelle biogenesis [PMID:19546860, "BLOC-1... involved in intracellular membrane trafficking and organelle biogenesis"].
ABCA1/cholesterol rows are direct but context-specific. In macrophage/foam-cell experiments, syntaxin 13 associated with ABCA1, and STX13 siRNA reduced ABCA1 protein and apoA-I-dependent phospholipid efflux [PMID:15469992, "Silencing of syntaxin 13 by small interfering RNA (siRNA) led to reduced ABCA1 protein levels"]. This supports a non-core ABCA1/cholesterol-efflux context, not a general cholesterol-efflux or protein-stabilization core function for STX12.
Protein-binding rows mostly capture direct or high-throughput interactors: ABCA1, VTI1A, BLOC-1 subunits, SNAP29/SNAP47, syntaxins, and broad binary-interactome partners. These interactions are useful context, but GO:0005515 protein binding is too generic for the review. More informative functions are SNAP receptor activity/SNARE-mediated vesicle docking and membrane fusion.
The PN projection to GO:0000815 ESCRT III complex should not be added for STX12. STX12 is a syntaxin/SNARE that genetically and functionally intersects with ESCRT-III-related autophagosome maturation, but it is not an ESCRT-III complex subunit.

Curation synthesis

The core role of STX12 is syntaxin-family SNARE activity in endosomal/recycling membrane trafficking: vesicle docking, membrane fusion, and endocytic recycling from endosomes toward target membranes. Core locations are early/recycling endosome membrane, endosome membrane, and Golgi membrane.

The autophagy annotation is directly supported and biologically important in the PN context. It should be retained as a supported non-primary output of the STX12 SNARE trafficking role, focused on phagophore/autophagosome maturation rather than ESCRT-III complex membership.

BLOC-1, ABCA1/cholesterol efflux, phagocytic vesicle/membrane raft, and neuronal postsynaptic/synaptic vesicle annotations are best treated as context-specific or non-core. Generic protein binding rows should be marked over-annotated even when the interaction itself is real.

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 LC3-positive phagophore/autophagosome role as PN-relevant and noted that STX12 should not be annotated as an ESCRT-III complex component.

Pn Notes

(STX12-pn-notes.md)

STX12 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q86Y82
AIGR review status: COMPLETE
Review batch: proteostasis-pr-1217 (PR 1217)
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/STX12/STX12-ai-review.yaml
AIGR review HTML: present - genes/human/STX12/STX12-ai-review.html
Gene notes: present - genes/human/STX12/STX12-notes.md
GOA TSV: present - genes/human/STX12/STX12-goa.tsv
UniProt record: present - genes/human/STX12/STX12-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/STX12.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/STX12.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

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

AIGR Review Snapshot

Description: STX12 encodes syntaxin-12/syntaxin-13, a syntaxin-family SNARE on endosomal, early endosomal, recycling endosomal, and Golgi membranes. Its core function is SNAP receptor/SNARE-mediated vesicle docking and membrane fusion in endosomal recycling and intracellular membrane traffic. Direct evidence also supports a role at LC3-positive phagophores/autophagosome assembly or maturation, likely as an autophagy-specific output of its SNARE trafficking activity. STX12 is distinct from ESCRT-III machinery.
Existing/core annotation action counts: ACCEPT: 20; KEEP_AS_NON_CORE: 11; MARK_AS_OVER_ANNOTATED: 13; MODIFY: 2

PN Consistency Summary

Consistency: CONTRADICTION flagged. PN row 3 projects GO:0000815 ESCRT III complex membership as ok_for_propagation, but the review YAML and notes explicitly reject this ("The PN projection to GO:0000815 should not be added for STX12… it is not an ESCRT-III complex subunit"). STX12 is a syntaxin/SNARE that genetically/functionally intersects ESCRT-III (CHMP2B modifier) but is not a component. GOA has no GO:0000815 for STX12 (confirmed). The other PN mapping (GO:0000045) is fully consistent — review ACCEPTs GO:0000045 + GO:0000407 phagophore assembly site (IMP, PMID:24095276).
PN story / NEW pressure: PN over-reaches on ESCRT-III membership. GO:0000815 is verified real but is a CC for the membrane-scission complex; STX12 is a modulator, not a subunit → projecting membership over-annotates. The autophagy-sealing story is already captured (GO:0000045, already_in_goa). Conclude: PN GO:0000815 over-reaches; do NOT propagate to STX12.
Evidence alignment: Strong overlap on autophagy: PN's "Syntaxin 13… required for autophagosome maturation" = review PMID:24095276 (core). PN's MDPI "Key Regulators of Autophagosome Closure" review is not in supported_by (secondary). Review enriches with SNARE/endosomal-recycling evidence (UniProt, PMID:19546860).
Verdict: Consistent on the autophagosome-assembly mapping; PN row-3 ESCRT-III-component projection conflicts with the review and is an over-annotation. No gene-YAML edit warranted (review already rejects it correctly); the fix belongs in the PN mapping. Recommended edits: none to STX12-ai-review.yaml; flag PN microautophagy "ESCRT-III complex component" node to exclude STX12 / reclassify as ESCRT-III modulator.

Full Consistency Review

UniProt: Q86Y82 (syntaxin-12/13) · batch: proteostasis-pr-1217 · review status: COMPLETE
PN placement: 3 rows, ALP. (1) …Autophagosome closure maturation… → Sealing of autophagophore membrane → ESCRT-III complex activity modulator; (2) …Sealing… → Localization of the ESCRT-III complex; (3) …Microautophagy → General microautophagy machinery → ESCRT-III complex component. PN-node mapping: sealing group=mapped→GO:0000045 autophagosome assembly; ESCRT-III-modulator leaf=context_only→GO:0000815; ESCRT-III-localization leaf=no_mapping; microautophagy ESCRT-III-component leaf=mapped/ok_for_propagation→GO:0000815 ESCRT III complex (more_specific_than_existing_goa).
Consistency: CONTRADICTION flagged. PN row 3 projects GO:0000815 ESCRT III complex membership as ok_for_propagation, but the review YAML and notes explicitly reject this ("The PN projection to GO:0000815 should not be added for STX12… it is not an ESCRT-III complex subunit"). STX12 is a syntaxin/SNARE that genetically/functionally intersects ESCRT-III (CHMP2B modifier) but is not a component. GOA has no GO:0000815 for STX12 (confirmed). The other PN mapping (GO:0000045) is fully consistent — review ACCEPTs GO:0000045 + GO:0000407 phagophore assembly site (IMP, PMID:24095276).
PN story / NEW pressure: PN over-reaches on ESCRT-III membership. GO:0000815 is verified real but is a CC for the membrane-scission complex; STX12 is a modulator, not a subunit → projecting membership over-annotates. The autophagy-sealing story is already captured (GO:0000045, already_in_goa). Conclude: PN GO:0000815 over-reaches; do NOT propagate to STX12.
Mapping strategy: The microautophagy "ESCRT-III complex component" leaf should NOT include STX12 (analogous to the TOMM20/RAB7A "broader/wrong-bucket" precedent — here it's a misclassification of an ESCRT modulator as a component). Recommend the PN node exclude STX12 or relabel it as an ESCRT-III modulator (consistent with row-1 context_only).
Evidence alignment: Strong overlap on autophagy: PN's "Syntaxin 13… required for autophagosome maturation" = review PMID:24095276 (core). PN's MDPI "Key Regulators of Autophagosome Closure" review is not in supported_by (secondary). Review enriches with SNARE/endosomal-recycling evidence (UniProt, PMID:19546860).
Verdict: Consistent on the autophagosome-assembly mapping; PN row-3 ESCRT-III-component projection conflicts with the review and is an over-annotation. No gene-YAML edit warranted (review already rejects it correctly); the fix belongs in the PN mapping. Recommended edits: none to STX12-ai-review.yaml; flag PN microautophagy "ESCRT-III complex component" node to exclude STX12 / reclassify as ESCRT-III modulator.

PN Dossier Context

review_batch: proteostasis-pr-1217
review_yaml: genes/human/STX12/STX12-ai-review.yaml
PN workbook rows: 3

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

UniProt: Q86Y82
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 VTI1A. Knockdown of STX12 or its binding partner VTI1A leads to accumulation of the autophagy marker LC3, affects autophagosome maturation, and blocks autophagic flux. Also, is a recycling endosome SNARE that regulates autophagosome closure and acts upstream of ESCRT-III.
PN references (titles):
- Syntaxin 13, a Genetic Modifier of Mutant CHMP2B in Frontotemporal Dementia, Is Required for Autophagosome Maturation - ScienceDirect
- Cells | Free Full-Text | Key Regulators of Autophagosome Closure (mdpi.com)
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 | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | Localization of the ESCRT-III complex

UniProt: Q86Y82
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 VTI1A. Knockdown of STX12 or its binding partner VTI1A leads to accumulation of the autophagy marker LC3, affects autophagosome maturation, and blocks autophagic flux. Also, is a recycling endosome SNARE that regulates autophagosome closure and acts upstream of ESCRT-III.
PN references (titles):
- Syntaxin 13, a Genetic Modifier of Mutant CHMP2B in Frontotemporal Dementia, Is Required for Autophagosome Maturation - ScienceDirect
- Cells | Free Full-Text | Key Regulators of Autophagosome Closure (mdpi.com)
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|Localization of the ESCRT-III complex
  status=no_mapping scope= GO=[]
  rationale: This PN leaf groups factors that affect ESCRT-III localization during sealing, but the current member set mixes endosomal sorting and SNARE trafficking genes rather than one clean shared autophagy-specific GO term.
- [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 3: Autophagy-Lysosome Pathway | Microautophagy | General microautophagy machinery | ESCRT-III complex component

UniProt: Q86Y82
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 (3)

GO:0000045 autophagosome assembly | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
GO:0000045 autophagosome assembly | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | 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.

📄 View Raw YAML

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

STX12

Gene Description