STX3 (human, Q13277) notes

2026-10-21 — Full re-review, independent of the ProtNLM2 predictions

Context: Q13277 is the closest experimentally characterised relative of the
HORSE STX3 benchmark gene (A0A3Q2H352); both sit in PANTHER subfamily
PTHR19957:SF34 (SYNTAXIN-3) per interpro/panther/PTHR19957/PTHR19957-entries.csv
(rat Q08849, mouse Q64704 and human Q13277 are the three reviewed members listed).
ProtNLM2 output was not opened or used.

Deep research

just deep-research-falcon human STX3 --fallback perplexity-lite failed on
2026-10-21: falcon raised "Failed to authenticate" and the perplexity-lite
fallback returned HTTP 401 (insufficient quota). No deep-research file exists.
The review is built from cached publications in publications/ (GOA-cited
papers plus 13 already-cached STX3 papers) and the UniProt record.

Evolutionary grounding (PAINT)

From interpro/panther/PTHR19957/PTHR19957-paint.tsv:

• PTN000461349 (family-wide syntaxin node, no taxon constraint): IBD for
  SNARE binding (GO:0000149), helical-bundle zippering fusogenic activity
  (GO:0005484), SNARE complex (GO:0031201), vesicle fusion (GO:0006906),
  intracellular protein transport (GO:0006886) and endomembrane system
  (GO:0012505). Q13277 is itself a seed for GO:0012505.
• PTN000461524 (plasma-membrane syntaxin clade, taxon:2759): IBD for plasma
  membrane (GO:0005886; Q13277 is a seed) and exocytosis (GO:0006887, dated
  20260828, i.e. newer than the GOA snapshot; the human gene has no GOA
  exocytosis row yet). Proposed as NEW, backed by the PAINT node plus mast-cell,
  beta-cell and enterocyte experiments.
• PTN002717040 (Euteleostomi STX3 orthology node, taxon:117571), seeded only by
  mouse Stx3 (MGI:103077): postsynapse (GO:0098794) and exocytic insertion of
  neurotransmitter receptor to postsynaptic membrane (GO:0098967). This is a
  narrow, STX3-orthologue node; the evidence is murine and there is no human
  experiment. Kept as non-core.

Horse STX3 inherits PTN000461349 and PTN000461524 annotations.

What is experimentally established in human

• Apical plasma membrane t-SNARE of epithelia: localisation in human Caco-2
  cells and intestinal epithelium [PMID:11003604; PMID:9701566]; loss-of-function
  causes variant microvillus inclusion disease with subapical vesicle
  accumulation PMID:24726755.
• Needed for apical delivery of sucrase-isomaltase in Caco-2 PMID:11003604.
• Complex with Munc18-2 (STXBP2) at the apical membrane [PMID:9701566;
  PMID:10788461]; in neutrophils Munc18-2 interacts with STX3 on granules
  PMID:18588921.
• HeLa knockdown reduces surface integrin and accumulates integrins in
  cytoplasmic vesicles PMID:21720706; downstream adhesion, chemotaxis and
  survival effects are indirect.
• Retina: human STX3 (mostly STX3B) in photoreceptor inner and outer segments
  and ribbon synapse terminals PMID:33974130; patient variants affecting
  STX3B cause early-onset retinal dystrophy.
• Soluble isoform Stx3S (Q13277-3) enters the nucleus via RanBP5/IPO5, binds
  ETV4 and ATF2, and alters gene expression PMID:29475951.

Established only in other species (rodent/fish) and carried by orthology

• t-SNARE fusogenic activity of STX3B with SNAP25 and VAMP2 in vitro (mouse
  retina proteins) PMID:18683220.
• Mast cell compound exocytosis (mouse cKO) PMID:30563839; STX3 silencing
  blocks granule fusion in mast cells PMID:24323579.
• Insulin newcomer granule exocytosis (mouse islets, INS-1) PMID:23132338.
• CFTR exocytosis in rat jejunum and Caco-2 PMID:20844248.
• Photoreceptor OS protein trafficking (mouse cKO) PMID:32778589.
• Axonal targeting in rat hippocampal neurons PMID:27662481.

Decisions of note

• GO:0090174 organelle membrane fusion (IMP, PMID:24726755) -> MODIFY to
  GO:0099500 vesicle fusion to plasma membrane; the defect is in fusion of
  apical vesicles with the apical plasma membrane.
• Positive regulation of cell adhesion / chemotaxis / cell proliferation (IMP,
  PMID:21720706): downstream phenotypes of integrin delivery; marked
  over-annotated. The abstract reports apoptosis, not proliferation, and the
  soluble isoform paper reports the opposite sign (Stx3S knockdown promotes
  proliferation).
• Vacuole (TAS, PMID:16339081): abstract does not mention vacuoles; may refer
  to the vacuolar apical compartment of non-polarised cells, which is not the
  GO lytic vacuole. UNDECIDED.
• Cell-cell junction (IDA, PMID:15576373): abstract is about STX4; full text
  not cached. UNDECIDED rather than overrule.
• All GO:0005515 rows removed per the protein-binding policy, except
  PMID:29475951, modified to DNA-binding transcription factor binding
  (ETV4, ATF2).