STX3 (syntaxin-3) is a tail-anchored Qa-SNARE of the syntaxin family. Its N-terminal Habc regulatory region binds Munc18-family proteins, and its SNARE motif pairs with SNAP25-family proteins and VAMPs to form trans-SNARE complexes that fuse transport vesicles with the plasma membrane. Alternative splicing of the C-terminal exons yields syntaxin 3A, the apical plasma-membrane syntaxin of polarized epithelia that fuses apical carriers and is required for enterocyte brush-border integrity, and syntaxin 3B, the t-SNARE of retinal ribbon synapses that drives synaptic vesicle exocytosis in photoreceptors and bipolar cells; a soluble splice form lacking the anchor has a reported nuclear role. In neurons syntaxin 3 also mediates postsynaptic exocytosis. The donkey gene model A0A9L0J901 (289 aa) is a non-canonical transcript that joins the syntaxin 3B exon for the C-terminal half of the SNARE motif to the syntaxin 3A transmembrane anchor; it retains a complete Habc region, SNARE motif and tail anchor.
Summary: SNARE binding: the SNARE motif of syntaxin 3 pairs with SNAP25-family and VAMP partners.
Reason: Donkey STX3 belongs to the syntaxin-3 subfamily (PANTHER PTHR19957:SF34) and the TreeGrafter transfer comes from a node inside that subfamily. The benchmark model carries the syntaxin 3B version of the C-terminal half of the SNARE motif; mouse syntaxin 3B binds SNAP25 (with lower affinity than syntaxin 1A) and assembles with SNAP25 and VAMP2 into fusion-competent complexes, so SNARE binding holds for this exon combination as well as for syntaxin 3A.
vesicles containing syntaxin 3B and SNAP25 could fuse with vesicles containing synaptobrevin2/VAMP2, demonstrating that syntaxin 3B can function as a t-SNARE.
Summary: Helical-bundle zippering fusogenic activity (t-SNARE activity) is the core molecular activity of syntaxin 3.
Reason: The SNARE motif zippers with SNAP25 and VAMP2 to drive bilayer fusion. This was shown directly for syntaxin 3B in a reconstituted liposome fusion assay, which is the relevant form for the SNARE-motif exon of A0A9L0J901, and syntaxin 3A is the apical fusion receptor of enterocytes. The donkey model keeps an intact Habc region, SNARE motif and tail anchor, and the activity is placed by PAINT at the syntaxin family node (PTN000461349).
vesicles containing syntaxin 3B and SNAP25 could fuse with vesicles containing synaptobrevin2/VAMP2, demonstrating that syntaxin 3B can function as a t-SNARE.
Summary: ARBA cytoplasm annotation for an integral, tail-anchored membrane protein.
Reason: The benchmark model has a C-terminal tail anchor and functions on the plasma membrane and transport vesicles; its cytosolic domain faces the cytoplasm but the protein is not a soluble cytoplasmic protein. The soluble, anchor-less splice form (Stx3S) is nuclear and is a different transcript; A0A9L0J901 keeps the anchor. The ARBA cytoplasm term is not supported for this product.
Summary: Plasma membrane is the target membrane of syntaxin 3: apical plasma membrane for 3A, presynaptic plasma membrane of ribbon terminals for 3B.
Reason: Both major splice forms act on the plasma membrane (PAINT IBD at PTN000461524, which includes human STX3). The benchmark model uses the syntaxin 3A anchor exon; since it mixes 3A and 3B exons, the general plasma membrane term is the most specific location that can be transferred without assuming which polarized domain it reaches.
Summary: Intracellular protein transport is a deep syntaxin-family PAINT assertion (PTN000461349) propagated via InterPro and PANTHER.
Reason: PAINT curators placed this term at the syntaxin family root, so it is a deliberate family-level judgement. For syntaxin 3 it reflects delivery of apical membrane cargo by the vesicles it fuses: STX3 loss causes subapical vesicle accumulation and microvillus inclusions in enterocytes. The term is indirect relative to the fusion step and is kept as non-core.
Summary: Exocytosis is a core process for the plasma-membrane syntaxin 3.
Reason: Exocytosis is placed by PAINT at the plasma-membrane syntaxin node (PTN000461524). Syntaxin 3A fuses apical exocytic carriers, and syntaxin 3B, whose SNARE-motif exon A0A9L0J901 carries, is required for synaptic vesicle exocytosis at ribbon synapses.
Summary: Vesicle fusion is the core process executed by syntaxin 3-containing SNARE complexes.
Reason: Syntaxin 3 supplies the Qa helix of the trans-SNARE bundle that fuses vesicles with the plasma membrane; vesicle fusion is placed by PAINT at the syntaxin family node (PTN000461349) and is demonstrated in vitro for syntaxin 3B.
vesicles containing syntaxin 3B and SNAP25 could fuse with vesicles containing synaptobrevin2/VAMP2, demonstrating that syntaxin 3B can function as a t-SNARE.
Summary: Endomembrane system is a broad syntaxin-family PAINT localization (PTN000461349).
Reason: Syntaxins reside on endomembranes and syntaxin 3 cycles on transport vesicles to and from the plasma membrane. No vesicle compartment more specific than this can be transferred to this non-canonical donkey model, and the functional location is the plasma membrane (accepted), so this broad term is kept as non-core.
Summary: SNARE complex membership is the structural basis of the t-SNARE function.
Reason: Syntaxin 3 contributes the Qa helix of SNARE complexes with SNAP25-family proteins and VAMPs; this is placed by PAINT at the syntaxin family node (PTN000461349) and mouse Stx3 has an IDA annotation to SNARE complex.
vesicles containing syntaxin 3B and SNAP25 could fuse with vesicles containing synaptobrevin2/VAMP2, demonstrating that syntaxin 3B can function as a t-SNARE.
Summary: Postsynapse is a syntaxin-3-specific PAINT assertion (PTN002717040) seeded by mouse Stx3 SynGO evidence.
Reason: The PAINT node sits inside the syntaxin-3 lineage and its donor is mouse Stx3 (MGI:103077) with SynGO IDA, grounded in hippocampal studies showing postsynaptic syntaxin-3 fusion machinery, so donkey STX3 inherits it by descent; a single well-characterised donor is adequate support. Which splice form acts postsynaptically is not established. This neuronal location is real but peripheral to the epithelial and ribbon-synapse fusion roles.
Together, these results identify critical roles for syntaxin-3, SNAP-47 and synaptobrevin-2 as components of a unique postsynaptic SNARE-mediated vesicle fusion machinery that is required for the delivery of AMPARs to the plasma membrane during LTP.
GO:0098967 exocytic insertion of neurotransmitter receptor to postsynaptic membrane
IEA GO_REF:0000118
KEEP AS NON CORE
Summary: Exocytic insertion of neurotransmitter receptors into the postsynaptic membrane is a syntaxin-3-specific PAINT assertion (PTN002717040).
Reason: Syntaxin 3 performs the fusion step of this exocytosis, so this is participation rather than necessity; the donor is mouse Stx3 SynGO IDA at a node inside the syntaxin-3 lineage. It is a neuronal application of the core plasma-membrane fusion activity and is kept as non-core.
we demonstrate that the Q-SNARE proteins syntaxin-3 and SNAP-47 are required for regulated AMPAR exocytosis during LTP but not for constitutive basal AMPAR exocytosis.
Together, these results identify critical roles for syntaxin-3, SNAP-47 and synaptobrevin-2 as components of a unique postsynaptic SNARE-mediated vesicle fusion machinery that is required for the delivery of AMPARs to the plasma membrane during LTP.
Summary: Plasma membrane bounded cell projection is a broad ARBA term; rodent Stx3 is found in dendrites and photoreceptor inner segments.
Reason: Rodent syntaxin-3 is found in dendrites and localizes to photoreceptor inner segments, which are cell projections, so the term is not wrong. Those more specific compartments are cell-type and splice-form specific and cannot be assigned to this non-canonical donkey model, so the broad term is kept as non-core rather than refined.
Localized to the inner and outer plexiform layers, the cell body and the inner segments of photoreceptors.
Core Functions
Plasma-membrane Qa-SNARE that assembles with SNAP25-family and VAMP partners into SNARE complexes and drives fusion of exocytic vesicles with the plasma membrane (apical carriers for the 3A form, synaptic vesicles at ribbon synapses for the 3B form).
vesicles containing syntaxin 3B and SNAP25 could fuse with vesicles containing synaptobrevin2/VAMP2, demonstrating that syntaxin 3B can function as a t-SNARE.
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Assessment of 2 ProtNLM2 GO predictions for donkey STX3 (A0A9L0J901), a full-length tail-anchored syntaxin with 92% identity to human syntaxin-3 isoform A. Both predictions are correct but generic, and both terms are already in the donkey GOA record beside more specific annotations (plasma membrane; vesicle fusion and exocytosis), so both are scored LSP. ProtNLM2 also emitted a non-GO subcellular location ("Membrane") for this accession, which is not scored here.
LSP — Less precise than existing annotation Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-10-14
Review rationale: The donkey protein has a Phobius-predicted C-terminal transmembrane anchor (264-288), the tail anchor expected for a syntaxin, so membrane is correct. Human STX3 isoform A, to which the donkey sequence corresponds over its full length, localizes to the apical plasma membrane. Donkey GOA already carries both membrane and the more specific plasma membrane, so the prediction is correct but less precise than an existing annotation.
LSP — Less precise than existing annotation Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-10-14
Review rationale: The donkey protein conserves the t-SNARE (SNARE motif) domain, and human STX3 is the apical receptor that mediates fusion of apical vesicles, so vesicle-mediated transport is correct. Donkey GOA already contains this exact term (InterPro2GO) together with the more specific vesicle fusion and exocytosis (TreeGrafter), both descendants of the predicted term. The prediction is therefore correct but less precise than existing annotation.