SNAP23 (synaptosome-associated protein 23) is the ubiquitously expressed member of the SNAP-25 family of Qbc t-SNAREs (PANTHER subfamily PTHR19305:SF4, distinct from the neuronal SNAP25 subfamily). Full-length SNAP23 is anchored to the plasma membrane by palmitoylation of a cysteine-rich linker and contributes two SNARE motifs (Qb and Qc) to the four-helix trans-SNARE bundle with syntaxins (for example STX4, STX11) and VAMPs, driving fusion of transport and secretory vesicles with the plasma membrane in non-neuronal cells such as immune, epithelial and muscle cells. This donkey entry (A0A8C4M285) is a 97-residue product of an alternative SNAP23 transcript that shares the first four exons with the full-length transcript and then ends in an alternative terminal exon. It contains the N-terminal (Qb) SNARE motif and the palmitoylated cysteine linker, ends with a short unrelated tail (FNIRSRAQ), and lacks the C-terminal (Qc) SNARE motif. The full-length donkey SNAP23 product is represented by UniProt A0A8C4M333 (211 residues).
Summary: Full-length SNAP23 is a t-SNARE with SNARE fusogenic activity, but this 97-residue product carries only the first of its two SNARE motifs.
Reason: The activity is well supported for full-length SNAP23 in the same PANTHER subfamily (SF4; human IDA, and SNAP23 binds syntaxins and VAMPs). SNAP23 donates both a Qb and a Qc helix to the SNARE bundle; the isolated N-terminal SNARE motif assembles into a heterotetramer only when the C-terminal motif is supplied separately. The donkey product A0A8C4M285 is an alternative-terminal-exon product that lacks the region corresponding to human 90..211, including the Qc SNARE motif, so it cannot by itself supply the SNAP23 contribution to a fusogenic bundle. There is no evidence on whether this product is expressed, so the TreeGrafter claim (which is made for the gene, not the splice form) cannot be confirmed or refuted for this gene product.
Summary: SNAP23 is anchored to the plasma membrane by palmitoylation of its cysteine-rich linker; all five linker cysteines are present in this product.
Reason: Plasma membrane localization is experimentally established for SNAP23 orthologs in the same PANTHER subfamily (human, mouse) and depends on the palmitoylated cysteine linker, which lies in the exons this product shares with full-length SNAP23 and is fully conserved here. The localization therefore applies to this truncated product, although its membrane association has not been tested directly.
Summary: Full-length SNAP23 mediates exocytic fusion of vesicles with the plasma membrane; participation of this truncated product is not established.
Reason: Same basis as the fusogenic activity row. Exocytosis is a correct process for the SNAP23 gene (SNAP23 drives constitutive and stimulated transport-vesicle fusion with the plasma membrane, for example TLR4 delivery in macrophages), but this product lacks the C-terminal SNARE motif, so its participation cannot be inferred.
The donkey entry therefore represents a truncated SNAP23 gene product with only one of the two SNARE motifs that SNAP23 contributes to a SNARE four-helix bundle.
Summary: Synaptic vesicle priming is a function of the neuronal paralog SNAP25; SNAP23, the ubiquitous non-neuronal SNAP-25-family t-SNARE in a separate PANTHER subfamily, does not support a primed vesicle pool.
Reason: On human SNAP23 this term is only an IBA, from PAINT node PTN000447754 seeded by Drosophila Snap25, a pre-duplication ortholog of both vertebrate SNAP25 and SNAP23. SNAP23 sits in PTHR19305:SF4, separate from the SNAP25 subfamily (SF5), and after the duplication it specialised in non-neuronal exocytosis. The direct test argues against priming. When overexpressed in Snap25-null chromaffin cells, SNAP23 did not support a standing pool of primed vesicles. In Snap25-null neurons it supported only asynchronous release. No study shows SNAP23 priming synaptic vesicles under endogenous conditions. This truncated product also lacks the second SNARE motif.
Summary: Full-length SNAP23 is a SNARE complex subunit; whether this single-SNARE-motif product joins SNARE complexes is unknown.
Reason: Correct for the SNAP23 gene (human IDA/IPI). The isolated N-terminal SNARE motif of SNAP23, which this product retains, can enter a heterotetrameric SNARE complex in vitro when a separate C-terminal motif is provided, and also forms homotetramers. So incorporation of this product into SNARE complexes is biochemically conceivable but has not been examined, and its expression is unverified.
The donkey entry therefore represents a truncated SNAP23 gene product with only one of the two SNARE motifs that SNAP23 contributes to a SNARE four-helix bundle.
GO:0031629 synaptic vesicle fusion to presynaptic active zone membrane
IEA GO_REF:0000118
MARK AS OVER ANNOTATED
Summary: Synaptic vesicle fusion at the active zone is mediated by the neuronal paralog SNAP25; SNAP23 cannot support synchronous evoked release.
Reason: As for synaptic vesicle priming, human SNAP23 carries this term only by IBA from node PTN000447754, seeded by Drosophila Snap25, a pre-duplication ortholog. In rescue experiments SNAP23 supports only asynchronous release, not synchronous release, and it is not an endogenous active-zone SNARE. The donkey product also lacks the second SNARE motif.
Summary: This location is inferred logically from the synaptic vesicle priming annotation rather than from observation.
Reason: The row is derived from GO:0016082 synaptic vesicle priming, which is itself marked as an over-annotation for SNAP23; the inferred presynaptic location inherits that weakness. SNAP23 is ubiquitously expressed and characterised at the plasma membrane of non-neuronal cells.
Unlike SNAP-25, SNAP-23 was expressed in all tissues examined.
Core Functions
Palmitoyl-anchored plasma membrane protein carrying the N-terminal (Qb) SNARE motif of SNAP23. Full-length SNAP23 is a Qbc t-SNARE for vesicle fusion with the plasma membrane, but whether this alternative-terminal-exon product, which lacks the Qc SNARE motif, contributes to SNARE function is unknown.
Q: Is the 97-residue SNAP23 product (A0A8C4M285, ending in the divergent tail FNIRSRAQ) a real transcript product of the donkey SNAP23 gene or a gene-model artefact, and if expressed, does it act as a dominant-negative regulator of SNAP23-dependent SNARE assembly?
Q: Should the synaptic vesicle priming and synaptic vesicle fusion to presynaptic active zone membrane assertions at PAINT node PTN000447754 (seeded by Drosophila Snap25) be blocked for the vertebrate SNAP23 subfamily (PTHR19305:SF4), given that SNAP23 does not support a primed vesicle pool or synchronous release in Snap25-null rescue experiments?
Suggested Experiments
Experiment: RT-PCR or long-read sequencing of donkey tissue RNA to test for a SNAP23 transcript encoding the 97-residue product, followed by co-immunoprecipitation with STX4 and VAMP3/VAMP8 to test SNARE complex incorporation.
External Prediction Reviews
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 the single ProtNLM2 GO prediction for the 97-residue donkey SNAP23 product A0A8C4M285, which retains the N-terminal SNARE motif and the palmitoylated cysteine linker of SNAP23 but lacks the C-terminal SNARE motif. The prediction membrane (GO:0016020) is true of the SNAP23 gene but is scored NPI for this product, which lacks proline 119, the DHHC17 recognition residue that full-length SNAP23 requires for membrane association. ProtNLM2 also emitted a subcellular location of Membrane, subject to the same caveat; no function text was emitted. Non-GO outputs are noted, not scored.
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-10-14
DOMAIN ARCHITECTURE MISMATCH
Review rationale: Membrane is true of the SNAP23 gene, whose full-length product is a palmitoyl-anchored peripheral plasma-membrane protein, but this 97-residue product lacks a feature that membrane association requires. Donkey residues 1..89 match human SNAP23 1..89 and keep the Qb SNARE motif and all five linker cysteines; the product then ends in an 8-residue alternative-exon tail and lacks the region corresponding to human 90..211. That region contains proline 119, the DHHC17 palmitoyl-transferase recognition residue. In mast cells the P119A mutation alone shifts full-length SNAP23 completely to the cytosol, as does loss of the linker cysteines, so membrane anchoring needs both the cysteines and the downstream P119 motif. Without P119 this product is not expected to be palmitoylated by DHHC17 or to associate with membranes, so the prediction is scored as a product-level architecture mismatch. Membrane association of this product has not been tested directly.
PMID:31260699: "either some or all cysteine residues in the linker region of SNAP-23 are required for anchoring of SNAP-23 to the plasma membrane in mast cells"
PMID:31260699: "The P119A mutation completely shifted localization of SNAP-23 to cytosol"