Syntaxin-3 is a tail-anchored Qa-SNARE (t-SNARE) of the syntaxin family that drives fusion of transport vesicles and secretory granules with the plasma membrane. It assembles a four-helix SNARE complex with a Qbc-SNARE (SNAP-23 or SNAP-25) and a vesicular R-SNARE (VAMP family), and its activity is controlled by the SM protein Munc18-2 (STXBP2). The ubiquitous splice form STX3A sits on the apical plasma membrane of polarised epithelia, through an N-terminal FMDE apical targeting motif. There it mediates apical delivery of membrane and secreted proteins, which is needed to build the enterocyte brush border; biallelic loss causes microvillus inclusion disease. In secretory immune and endocrine cells STX3 is on secretory granules and mediates regulated and compound (granule-granule) exocytosis. The retina-specific form STX3B is the t-SNARE of photoreceptor and bipolar-cell ribbon synapses and is needed to traffic outer segment proteins in photoreceptors. Variants affecting STX3B cause early-onset retinal dystrophy. In neurons STX3 is enriched in the axonal plasma membrane. A soluble splice form lacking the transmembrane anchor (Stx3S) enters the nucleus and modulates transcription through binding of ETV4 and ATF2.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000149 SNARE binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000461349 (family-wide syntaxin node). STX3 binds the cognate SNAREs SNAP-23 and VAMP/cellubrevin at the apical membrane and SNAP25/VAMP2 as STX3B. Reason: SNARE binding is the defining property of syntaxins and is inherited from the PAINT node the whole PTHR19957 family descends from. Human STX3 complexes with SNAP-23 and cellubrevin in Caco-2 cells, and STX3B pairs with SNAP25 and VAMP2. Supporting Evidence: PMID:9701566 Increasing the amount of Munc-18-2 bound to syntaxin 3 by overexpression results in a marked decrease in the SNARE proteins SNAP-23 and cellubrevin bound to the syntaxin. PMID:18683220 vesicles containing syntaxin 3B and SNAP25 could fuse with vesicles containing synaptobrevin2/VAMP2, demonstrating that syntaxin 3B can function as a t-SNARE |
| GO:0001750 photoreceptor outer segment | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Photoreceptor outer segment, transferred from mouse Stx3 (Ensembl Compara IEA, ISS). Human retina immunolabelling shows STX3 in rod and cone outer segments. Reason: Human retinal sections label STX3 in outer segments as well as inner segments (in mouse only inner segments are labelled). The fusion function in photoreceptors is placed in the inner segment, where outer segment proteins are delivered, so the outer segment location is kept as non-core. Supporting Evidence: PMID:33974130 Strong STX3 immunolabeling of photoreceptor inner and rhodopsin-labeled outer segments was observed in the human retina |
| GO:0001750 photoreceptor outer segment | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Photoreceptor outer segment, transferred from mouse Stx3 (Ensembl Compara IEA, ISS). Human retina immunolabelling shows STX3 in rod and cone outer segments. Reason: Human retinal sections label STX3 in outer segments as well as inner segments (in mouse only inner segments are labelled). The fusion function in photoreceptors is placed in the inner segment, where outer segment proteins are delivered, so the outer segment location is kept as non-core. Supporting Evidence: PMID:33974130 Strong STX3 immunolabeling of photoreceptor inner and rhodopsin-labeled outer segments was observed in the human retina |
| GO:0001917 photoreceptor inner segment | IEA GO_REF:0000107 | ACCEPT | Summary: Photoreceptor inner segment, transferred from mouse Stx3. Confirmed in human retina by immunohistochemistry. Reason: STX3 (largely STX3B) is in human photoreceptor inner segments, and in mouse it is needed to traffic rhodopsin, PRPH2 and ROM1 from the inner segment to the outer segment. Human patients with variants affecting STX3B develop retinal dystrophy. Supporting Evidence: PMID:33974130 Strong STX3 immunolabeling of photoreceptor inner and rhodopsin-labeled outer segments was observed in the human retina PMID:32778589 STX3 is an essential part of the trafficking pathway for both disc (rhodopsin) and rim (PRPH2/ROM1) components of the OS |
| GO:0001917 photoreceptor inner segment | ISS GO_REF:0000024 | ACCEPT | Summary: Photoreceptor inner segment, transferred from mouse Stx3. Confirmed in human retina by immunohistochemistry. Reason: STX3 (largely STX3B) is in human photoreceptor inner segments, and in mouse it is needed to traffic rhodopsin, PRPH2 and ROM1 from the inner segment to the outer segment. Human patients with variants affecting STX3B develop retinal dystrophy. Supporting Evidence: PMID:33974130 Strong STX3 immunolabeling of photoreceptor inner and rhodopsin-labeled outer segments was observed in the human retina PMID:32778589 STX3 is an essential part of the trafficking pathway for both disc (rhodopsin) and rim (PRPH2/ROM1) components of the OS |
| GO:0005484 helical-bundle zippering fusogenic activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000461349 for helical-bundle zippering fusogenic activity (formerly SNAP receptor activity), the core t-SNARE activity of syntaxins. Reason: STX3 is a Qa-SNARE. STX3B with SNAP25 drives fusion with VAMP2 vesicles in vitro, and human STX3 loss abolishes apical vesicle fusion in enterocytes. Supporting Evidence: PMID:18683220 vesicles containing syntaxin 3B and SNAP25 could fuse with vesicles containing synaptobrevin2/VAMP2, demonstrating that syntaxin 3B can function as a t-SNARE PMID:24726755 STX3 is an apical receptor involved in membrane fusion of apical vesicles in enterocytes. |
| GO:0005484 helical-bundle zippering fusogenic activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping from the SNARE/syntaxin domains to helical-bundle zippering fusogenic activity. Reason: Consistent with the IBA and with the experimental evidence for t-SNARE function. Supporting Evidence: PMID:18683220 vesicles containing syntaxin 3B and SNAP25 could fuse with vesicles containing synaptobrevin2/VAMP2, demonstrating that syntaxin 3B can function as a t-SNARE file:human/STX3/STX3-uniprot.txt Belongs to the syntaxin family. |
| GO:0005515 protein binding | IPI PMID:17693260 SARA-regulated vesicular targeting underlies formation of th... | REMOVE | Summary: IPI with SARA (ZFYVE9), reported to interact directly with syntaxin 3 during rod disc biogenesis. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. Supporting Evidence: PMID:17693260 SARA, through its direct interaction with PI3P, rhodopsin, and SNARE protein syntaxin 3 |
| GO:0005515 protein binding | IPI PMID:18588921 Involvement of Munc18 isoforms in the regulation of granule ... | REMOVE | Summary: IPI with Munc18-2 (STXBP2) in human neutrophils. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. Supporting Evidence: PMID:18588921 Munc18-2 interacts with the target-SNARE syntaxin 3 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:26359495 The Q-soluble N-Ethylmaleimide-sensitive Factor Attachment P... | REMOVE | Summary: IPI from the SNAP-47 study. The cached abstract names SNAP-47 binding to STX5, STX1 and VAMPs; the STX3 interaction is presumably in the full text. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:29475951 Soluble syntaxin 3 functions as a transcriptional regulator. | MODIFY | Summary: IPI from the soluble Stx3S study: Stx3S binds RanBP5 (IPO5) and the transcription factors ETV4 and ATF2. Reason: The paper supports a more informative function than bare protein binding: the soluble isoform binds the DNA-binding transcription factors ETV4 and ATF2. This is a property of the soluble isoform Q13277-3 and is not part of the membrane-fusion core. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:29475951 Soluble Stx3S binds to the nuclear import factor RanBP5 (RAN-binding protein 5), targets to the nucleus, and interacts physically and functionally with several transcription factors, including ETV4 (ETS variant 4) and ATF2 (activating transcription factor 2). |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: High-throughput interactome screen (yeast two-hybrid or proteomic map) reporting STX3 as a binary or complex partner. Reason: Per the GO:0005515 policy, bare protein binding is uninformative and is removed. Removal does not dispute the reported interaction. The informative STX3 activities (SNARE binding, t-SNARE fusogenic activity) are captured by other rows. |
| GO:0005634 nucleus | EXP PMID:29475951 Soluble syntaxin 3 functions as a transcriptional regulator. | KEEP AS NON CORE | Summary: Nucleus, shown for the soluble isoform Stx3S (Q13277-3, which lacks the transmembrane anchor). Reason: Experimentally shown for the soluble splice isoform only. The canonical membrane-anchored isoforms are at the plasma membrane. Supporting Evidence: PMID:29475951 Soluble Stx3S binds to the nuclear import factor RanBP5 (RAN-binding protein 5), targets to the nucleus, and interacts physically and functionally with several transcription factors, including ETV4 (ETS variant 4) and ATF2 (activating transcription factor 2). |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nucleus from the UniProt subcellular location mapping, which derives from the isoform 3 experiment. Reason: Same basis as the EXP row: true of the soluble isoform, peripheral to the core function. Supporting Evidence: PMID:29475951 Soluble Stx3S binds to the nuclear import factor RanBP5 (RAN-binding protein 5), targets to the nucleus, and interacts physically and functionally with several transcription factors, including ETV4 (ETS variant 4) and ATF2 (activating transcription factor 2). |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | TOO GENERAL | Summary: Cytoplasm from an ARBA rule. Reason: STX3 is a tail-anchored membrane protein. Its intracellular pools are on secretory granules and vesicles, which are part of the cytoplasm, so this term is entailed by the more specific secretory granule location kept in this review and adds nothing. |
| GO:0005773 vacuole | TAS PMID:16339081 Syntaxins 3 and 4 are concentrated in separate clusters on t... | UNDECIDED | Summary: Vacuole (TAS) citing a study of syntaxin 3 and 4 plasma membrane clusters. Reason: The cached abstract (full text not cached) says nothing about vacuoles. The statement may refer to the vacuolar apical compartment of non-polarised epithelial cells, which is not the GO lytic vacuole. No other evidence places human STX3 on vacuoles, so without the full text this cannot be judged. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000461524, the plasma-membrane syntaxin clade (Q13277 is one of the seeds). Reason: STX3 is a plasma membrane t-SNARE, apical in polarised epithelia and at the axonal or presynaptic membrane in neurons. Supporting Evidence: PMID:16339081 Syntaxins 3 and 4 localize to the apical and basolateral plasma membrane, respectively, of epithelial cells where they mediate vesicle fusion. PMID:27662481 We show that syntaxin 3 localizes to the axonal plasma membrane, particularly to axonal tips |
| GO:0005886 plasma membrane | IDA PMID:21720706 Syntaxins 3 and 4 mediate vesicular trafficking of Ξ±5Ξ²1 and ... | ACCEPT | Summary: Plasma membrane IDA in HeLa and PANC-1 cells, where STX3 co-localises with GM1 at the leading edge. Reason: Directly observed in human cells; consistent with the IBA. Supporting Evidence: PMID:21720706 In migrating HeLa and PANC-1 cells, syntaxins 2, 3 and 4 co-localized with the lipid raft constituent GM1 ganglioside at the leading edge. |
| GO:0005886 plasma membrane | IEA GO_REF:0000117 | ACCEPT | Summary: Plasma membrane from an ARBA rule. Reason: Consistent with experimental evidence and the IBA. Supporting Evidence: PMID:16339081 Syntaxins 3 and 4 localize to the apical and basolateral plasma membrane, respectively, of epithelial cells where they mediate vesicle fusion. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9014052 | ACCEPT | Summary: Reactome TAS for the plasma membrane location (TXLNA binding to syntaxin 3). Reason: The location is correct and is supported by direct experiments. Supporting Evidence: PMID:16339081 Syntaxins 3 and 4 localize to the apical and basolateral plasma membrane, respectively, of epithelial cells where they mediate vesicle fusion. |
| GO:0005911 cell-cell junction | IDA PMID:15576373 Protease-activated receptor-1 activation of endothelial cell... | UNDECIDED | Summary: Cell-cell junction IDA citing a study of PAR-1-induced syntaxin 4 and Munc18c phosphorylation in human lung microvascular endothelial cells. Reason: The abstract confirms that STX3 is expressed in these endothelial cells and that STX3 knockdown did not affect Weibel-Palade body exocytosis. It does not describe STX3 at cell-cell junctions. Full text is not cached, so the curator's localisation call cannot be checked and is not overruled. Supporting Evidence: PMID:15576373 We identified the presence of syntaxin 4, syntaxin 3, and the high affinity syntaxin 4-regulatory protein Munc18c in human lung microvascular endothelial cells. |
| GO:0006886 intracellular protein transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Intracellular protein transport (IBA from PTN000461349; InterPro2GO IEA). Reason: STX3-mediated fusion delivers membrane protein cargo: sucrase-isomaltase to the enterocyte apical surface, integrins to the HeLa surface, and PRPH2/rhodopsin to photoreceptor outer segments. Cargo delivery follows from the fusion activity, so the term is kept as non-core beside the accepted fusion terms. Supporting Evidence: PMID:11003604 strongly suggesting that Syn3 is necessary for efficient delivery of proteins to the apical surface of intestinal cells PMID:21720706 siRNA knockdown (KD) of syntaxins 3 and 4, but not of syntaxin 2, in HeLa cells reduced cell surface expression of Ξ±5Ξ²1 and Ξ±3Ξ²1 integrins and accumulated the integrins in cytoplasmic vesicles PMID:32778589 STX3 is an essential part of the trafficking pathway for both disc (rhodopsin) and rim (PRPH2/ROM1) components of the OS |
| GO:0006886 intracellular protein transport | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Intracellular protein transport (IBA from PTN000461349; InterPro2GO IEA). Reason: STX3-mediated fusion delivers membrane protein cargo: sucrase-isomaltase to the enterocyte apical surface, integrins to the HeLa surface, and PRPH2/rhodopsin to photoreceptor outer segments. Cargo delivery follows from the fusion activity, so the term is kept as non-core beside the accepted fusion terms. Supporting Evidence: PMID:11003604 strongly suggesting that Syn3 is necessary for efficient delivery of proteins to the apical surface of intestinal cells PMID:21720706 siRNA knockdown (KD) of syntaxins 3 and 4, but not of syntaxin 2, in HeLa cells reduced cell surface expression of Ξ±5Ξ²1 and Ξ±3Ξ²1 integrins and accumulated the integrins in cytoplasmic vesicles PMID:32778589 STX3 is an essential part of the trafficking pathway for both disc (rhodopsin) and rim (PRPH2/ROM1) components of the OS |
| GO:0006906 vesicle fusion | IBA GO_REF:0000033 | ACCEPT | Summary: Vesicle fusion IBA from PTN000461349. Reason: This is STX3's core process. Human loss-of-function blocks fusion of apical vesicles, and STX3 silencing blocks granule fusion in mast cells. Supporting Evidence: PMID:24726755 STX3 is an apical receptor involved in membrane fusion of apical vesicles in enterocytes. PMID:24323579 silencing of STX3 inhibited fusion |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:21720706 Syntaxins 3 and 4 mediate vesicular trafficking of Ξ±5Ξ²1 and ... | MARK AS OVER ANNOTATED | Summary: Positive regulation of cell population proliferation (IMP, HeLa knockdown of STX3 and STX4). Reason: The abstract reports that STX3/STX4 knockdown triggered apoptosis. It does not report proliferation, and any growth effect is downstream of integrin delivery. Inhibiting the soluble Stx3S isoform has the opposite effect, increasing proliferation. STX3 does not perform a step of a proliferation process. Supporting Evidence: PMID:21720706 KD of syntaxins 3 and 4 inhibited cell adhesion to fibronectin, suppressed chemotactic cell migration and triggered apoptosis PMID:29475951 Inhibition of endogenous Stx3S expression alters the expression of cancer-associated genes and promotes cell proliferation. |
| GO:0010468 regulation of gene expression | IDA PMID:29475951 Soluble syntaxin 3 functions as a transcriptional regulator. | KEEP AS NON CORE | Summary: Regulation of gene expression (IDA), shown for the soluble nuclear isoform Stx3S. Reason: A distinct function of the soluble splice isoform, which binds ETV4/ATF2 in the nucleus. Not part of the SNARE function. Supporting Evidence: PMID:29475951 Soluble Stx3S binds to the nuclear import factor RanBP5 (RAN-binding protein 5), targets to the nucleus, and interacts physically and functionally with several transcription factors, including ETV4 (ETS variant 4) and ATF2 (activating transcription factor 2). PMID:29475951 Inhibition of endogenous Stx3S expression alters the expression of cancer-associated genes and promotes cell proliferation. |
| GO:0012505 endomembrane system | IBA GO_REF:0000033 | TOO GENERAL | Summary: Endomembrane system IBA from PTN000461349 (Q13277 is a seed). Reason: True but uninformative: the accepted plasma membrane, apical plasma membrane and secretory granule locations entail it. |
| GO:0016020 membrane | IEA GO_REF:0000120 | TOO GENERAL | Summary: Membrane (combined IEA). Reason: Entailed by the accepted plasma membrane and apical plasma membrane locations. |
| GO:0016192 vesicle-mediated transport | IEA GO_REF:0000002 | TOO GENERAL | Summary: Vesicle-mediated transport (InterPro2GO). Reason: Entailed by the accepted vesicle fusion and vesicle fusion to plasma membrane terms. |
| GO:0016324 apical plasma membrane | EXP PMID:24726755 Loss of syntaxin 3 causes variant microvillus inclusion dise... | ACCEPT | Summary: Apical plasma membrane (EXP) from the variant MVID study. Reason: The apical plasma membrane is where STX3A acts in enterocytes. Supporting Evidence: PMID:24726755 STX3 is an apical receptor involved in membrane fusion of apical vesicles in enterocytes. |
| GO:0016324 apical plasma membrane | IDA PMID:16339081 Syntaxins 3 and 4 are concentrated in separate clusters on t... | ACCEPT | Summary: Apical plasma membrane IDA. Reason: Apical localisation of syntaxin 3 in polarised epithelia is well established, including human Caco-2 cells. Supporting Evidence: PMID:16339081 Syntaxins 3 and 4 localize to the apical and basolateral plasma membrane, respectively, of epithelial cells where they mediate vesicle fusion. PMID:11003604 This chimera (Syn3TfR) was localized to the apical membrane |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Apical plasma membrane (combined IEA). Reason: Consistent with experimental evidence. Supporting Evidence: PMID:16785322 In polarized epithelial cells, syntaxin 3 localizes to the apical plasma membrane and is involved in membrane fusion of apical trafficking pathways. |
| GO:0030027 lamellipodium | IDA PMID:21720706 Syntaxins 3 and 4 mediate vesicular trafficking of Ξ±5Ξ²1 and ... | KEEP AS NON CORE | Summary: Lamellipodium IDA: STX3 at the leading edge of migrating HeLa/PANC-1 cells. Reason: Observed directly in human cells, but peripheral to the polarised-epithelium and photoreceptor functions. Supporting Evidence: PMID:21720706 In migrating HeLa and PANC-1 cells, syntaxins 2, 3 and 4 co-localized with the lipid raft constituent GM1 ganglioside at the leading edge. |
| GO:0030141 secretory granule | IEA GO_REF:0000107 | ACCEPT | Summary: Secretory granule, transferred from rodent orthologs (Ensembl Compara). Reason: STX3 sits on secretory granules in mast cells, beta cells and neutrophils, and human neutrophil granule IDA rows exist. Accepted because granule-resident STX3 drives granule-granule (compound) fusion, part of its secretory-cell core function. Supporting Evidence: PMID:24323579 both Munc18-2 and STX3 are located on the granule surface PMID:18588921 both Munc18-2 and Munc18-3 were often located in close proximity to their respective SNARE-binding partners syntaxin 3 and syntaxin 4 |
| GO:0030425 dendrite | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Dendrite, transferred from rodent orthologs. Reason: There is rodent evidence for STX3 in dendritic and postsynaptic compartments, but none from human. In rat hippocampal neurons STX3 is mainly axonal. Kept as non-core. Supporting Evidence: PMID:39408994 syntaxin 3 has been postulated to be present in the postsynaptic spines of conventional synapses and to have an important role in some types of synaptic plasticity |
| GO:0030426 growth cone | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Growth cone (ISS from rodent). Reason: Rat neurons show STX3 enriched at axonal tips. A neuronal location only, peripheral to the core. Supporting Evidence: PMID:27662481 We show that syntaxin 3 localizes to the axonal plasma membrane, particularly to axonal tips |
| GO:0031175 neuron projection development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neuron projection development (ISS from rodent). Reason: STX3 overexpression increases axonal growth in rat hippocampal neurons, plausibly by supplying membrane through fusion. Neuronal, non-core. Supporting Evidence: PMID:27662481 overexpression of syntaxin 3 results in increased axonal growth |
| GO:0031201 SNARE complex | IBA GO_REF:0000033 | ACCEPT | Summary: SNARE complex (IBA from PTN000461349). Reason: STX3 forms SNARE complexes with SNAP-23 and VAMPs in epithelia and with SNAP25/VAMP2 as STX3B. The Munc18-2 data show that the composition of the human apical STX3 SNARE complex is regulated. Supporting Evidence: PMID:9701566 Increasing the amount of Munc-18-2 bound to syntaxin 3 by overexpression results in a marked decrease in the SNARE proteins SNAP-23 and cellubrevin bound to the syntaxin. PMID:18683220 vesicles containing syntaxin 3B and SNAP25 could fuse with vesicles containing synaptobrevin2/VAMP2, demonstrating that syntaxin 3B can function as a t-SNARE |
| GO:0031201 SNARE complex | IEA GO_REF:0000107 | ACCEPT | Summary: SNARE complex (Ensembl Compara transfer from mouse). Reason: STX3 forms SNARE complexes with SNAP-23 and VAMPs in epithelia and with SNAP25/VAMP2 as STX3B. The Munc18-2 data show that the composition of the human apical STX3 SNARE complex is regulated. Supporting Evidence: PMID:9701566 Increasing the amount of Munc-18-2 bound to syntaxin 3 by overexpression results in a marked decrease in the SNARE proteins SNAP-23 and cellubrevin bound to the syntaxin. PMID:18683220 vesicles containing syntaxin 3B and SNAP25 could fuse with vesicles containing synaptobrevin2/VAMP2, demonstrating that syntaxin 3B can function as a t-SNARE |
| GO:0031201 SNARE complex | ISS GO_REF:0000024 | ACCEPT | Summary: SNARE complex (ISS from rodent). Reason: STX3 forms SNARE complexes with SNAP-23 and VAMPs in epithelia and with SNAP25/VAMP2 as STX3B. The Munc18-2 data show that the composition of the human apical STX3 SNARE complex is regulated. Supporting Evidence: PMID:9701566 Increasing the amount of Munc-18-2 bound to syntaxin 3 by overexpression results in a marked decrease in the SNARE proteins SNAP-23 and cellubrevin bound to the syntaxin. PMID:18683220 vesicles containing syntaxin 3B and SNAP25 could fuse with vesicles containing synaptobrevin2/VAMP2, demonstrating that syntaxin 3B can function as a t-SNARE |
| GO:0042470 melanosome | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Melanosome, transferred from orthologs (originally organelle proteomics). Reason: No functional study places STX3 on melanosomes. Proteomic detection of an abundant plasma membrane/granule SNARE in melanosome fractions does not show a melanosome role. |
| GO:0042581 specific granule | IDA PMID:18588921 Involvement of Munc18 isoforms in the regulation of granule ... | KEEP AS NON CORE | Summary: Specific granule IDA in human neutrophils (immunogold, subcellular fractionation). Reason: Neutrophil granules carry STX3 together with Munc18-2. This is a real, cell-type-specific location. Supporting Evidence: PMID:18588921 both Munc18-2 and Munc18-3 were often located in close proximity to their respective SNARE-binding partners syntaxin 3 and syntaxin 4 |
| GO:0042582 azurophil granule | IDA PMID:18588921 Involvement of Munc18 isoforms in the regulation of granule ... | KEEP AS NON CORE | Summary: Azurophil granule IDA in human neutrophils (immunogold, subcellular fractionation). Reason: Neutrophil granules carry STX3 together with Munc18-2. This is a real, cell-type-specific location. Supporting Evidence: PMID:18588921 both Munc18-2 and Munc18-3 were often located in close proximity to their respective SNARE-binding partners syntaxin 3 and syntaxin 4 |
| GO:0042589 zymogen granule membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Zymogen granule membrane, transferred from rodent orthologs. Reason: A granule membrane location in pancreatic acinar cells, consistent with STX3's role in granule-granule (compound) fusion in other secretory cells. Not tested in human. Supporting Evidence: PMID:23132338 SYN-3 plays a role in the mediation of newcomer SG exocytosis and SG-SG fusion |
| GO:0043005 neuron projection | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neuron projection (ISS). Reason: Axonal localisation in rat neurons. Neuronal, non-core. Supporting Evidence: PMID:27662481 We show that syntaxin 3 localizes to the axonal plasma membrane, particularly to axonal tips |
| GO:0045785 positive regulation of cell adhesion | IMP PMID:21720706 Syntaxins 3 and 4 mediate vesicular trafficking of Ξ±5Ξ²1 and ... | MARK AS OVER ANNOTATED | Summary: Positive regulation of cell adhesion (IMP, HeLa knockdown). Reason: Reduced adhesion to fibronectin is a downstream consequence of reduced integrin delivery to the cell surface. STX3 performs the fusion step, not a regulatory step in adhesion. Supporting Evidence: PMID:21720706 KD of syntaxins 3 and 4 inhibited cell adhesion to fibronectin, suppressed chemotactic cell migration and triggered apoptosis PMID:21720706 siRNA knockdown (KD) of syntaxins 3 and 4, but not of syntaxin 2, in HeLa cells reduced cell surface expression of Ξ±5Ξ²1 and Ξ±3Ξ²1 integrins and accumulated the integrins in cytoplasmic vesicles |
| GO:0050544 arachidonate binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Arachidonate binding (ISS from rodent syntaxin 3). Reason: Transferred by HGNC-UCL from rodent work reporting that arachidonic acid binds syntaxin 3 and promotes its SNARE assembly during neurite outgrowth. The source paper is not cached here. The function may hold but is peripheral, so the transferred annotation is kept as non-core. |
| GO:0050804 modulation of chemical synaptic transmission | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Modulation of chemical synaptic transmission, transferred from mouse Stx3. Reason: STX3B is a ribbon-synapse t-SNARE and mouse Stx3 has been implicated in postsynaptic plasticity. No human synaptic physiology exists, so this is kept as non-core. Supporting Evidence: PMID:33974130 exhibited strong STX3 immunolabeling (Fig. 2aβd), consistent with a role for STX3 in neurotransmitter release PMID:39408994 syntaxin 3 has been postulated to be present in the postsynaptic spines of conventional synapses and to have an important role in some types of synaptic plasticity |
| GO:0050921 positive regulation of chemotaxis | IMP PMID:21720706 Syntaxins 3 and 4 mediate vesicular trafficking of Ξ±5Ξ²1 and ... | MARK AS OVER ANNOTATED | Summary: Positive regulation of chemotaxis (IMP, HeLa knockdown). Reason: The reduced chemotactic migration is a downstream phenotype of impaired integrin surface delivery, not a regulatory activity of STX3. Supporting Evidence: PMID:21720706 KD of syntaxins 3 and 4 inhibited cell adhesion to fibronectin, suppressed chemotactic cell migration and triggered apoptosis |
| GO:0061025 membrane fusion | IEA GO_REF:0000117 | TOO GENERAL | Summary: Membrane fusion from an ARBA rule. Reason: Entailed by the accepted vesicle fusion and vesicle fusion to plasma membrane terms. |
| GO:0070062 extracellular exosome | HDA PMID:11487543 Intestinal epithelial cells secrete exosome-like vesicles. | KEEP AS NON CORE | Summary: Extracellular exosome (HDA, exosome proteomics). Reason: Proteomic detection in intestinal or urinary exosomes is consistent with apical plasma membrane residence, but gives no functional information. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Extracellular exosome (HDA, exosome proteomics). Reason: Proteomic detection in intestinal or urinary exosomes is consistent with apical plasma membrane residence, but gives no functional information. |
| GO:0090174 organelle membrane fusion | IMP PMID:24726755 Loss of syntaxin 3 causes variant microvillus inclusion dise... | MODIFY | Summary: Organelle membrane fusion (IMP), from STX3 truncation in variant MVID patients and Caco-2 cells. Reason: The defect is a failure of apical vesicles to fuse with the apical plasma membrane, which leads to subapical vesicle accumulation. GO:0099500 vesicle fusion to plasma membrane states this more precisely than organelle membrane fusion. Proposed replacements: vesicle fusion to plasma membrane Supporting Evidence: PMID:24726755 STX3 is an apical receptor involved in membrane fusion of apical vesicles in enterocytes. |
| GO:0098685 Schaffer collateral - CA1 synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Schaffer collateral - CA1 synapse, transferred from mouse Stx3. Reason: Based on mouse hippocampal work on Stx3 in synaptic plasticity. Not tested in human. Non-core. Supporting Evidence: PMID:39408994 syntaxin 3 has been postulated to be present in the postsynaptic spines of conventional synapses and to have an important role in some types of synaptic plasticity |
| GO:0098793 presynapse | IDA PMID:27662481 The SNARE Protein Syntaxin 3 Confers Specificity for Polariz... | ACCEPT | Summary: Presynapse (SynGO IDA/IMP) from rat hippocampal neurons, where STX3 localises to the axonal plasma membrane and tips and is needed for axonal targeting of NgCAM. Reason: Presynaptic t-SNARE function is central to the retinal isoform STX3B, which sits at ribbon-synapse terminals in human retina. The SynGO curation of the hippocampal data is consistent with this. Accepted as a core location for the neuronal isoform. Supporting Evidence: PMID:27662481 We show that syntaxin 3 localizes to the axonal plasma membrane, particularly to axonal tips PMID:27662481 RNAi-mediated knockdown of endogenous syntaxin 3 leads to partial mistargeting of NgCAM PMID:33974130 exhibited strong STX3 immunolabeling (Fig. 2aβd), consistent with a role for STX3 in neurotransmitter release |
| GO:0098793 presynapse | IMP PMID:27662481 The SNARE Protein Syntaxin 3 Confers Specificity for Polariz... | ACCEPT | Summary: Presynapse (SynGO IDA/IMP) from rat hippocampal neurons, where STX3 localises to the axonal plasma membrane and tips and is needed for axonal targeting of NgCAM. Reason: Presynaptic t-SNARE function is central to the retinal isoform STX3B, which sits at ribbon-synapse terminals in human retina. The SynGO curation of the hippocampal data is consistent with this. Accepted as a core location for the neuronal isoform. Supporting Evidence: PMID:27662481 We show that syntaxin 3 localizes to the axonal plasma membrane, particularly to axonal tips PMID:27662481 RNAi-mediated knockdown of endogenous syntaxin 3 leads to partial mistargeting of NgCAM PMID:33974130 exhibited strong STX3 immunolabeling (Fig. 2aβd), consistent with a role for STX3 in neurotransmitter release |
| GO:0098794 postsynapse | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Postsynapse (IBA from PTN002717040, an STX3-orthologue node seeded only by mouse Stx3; Ensembl Compara IEA). Reason: PTN002717040 is an STX3-orthologue node within Euteleostomi, so the human gene is inside the clade. The evidence is murine only and the postsynaptic role is described as postulated, so it is kept as non-core. Supporting Evidence: PMID:39408994 syntaxin 3 has been postulated to be present in the postsynaptic spines of conventional synapses and to have an important role in some types of synaptic plasticity |
| GO:0098794 postsynapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Postsynapse (IBA from PTN002717040, an STX3-orthologue node seeded only by mouse Stx3; Ensembl Compara IEA). Reason: PTN002717040 is an STX3-orthologue node within Euteleostomi, so the human gene is inside the clade. The evidence is murine only and the postsynaptic role is described as postulated, so it is kept as non-core. Supporting Evidence: PMID:39408994 syntaxin 3 has been postulated to be present in the postsynaptic spines of conventional synapses and to have an important role in some types of synaptic plasticity |
| GO:0098967 exocytic insertion of neurotransmitter receptor to postsynaptic membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Exocytic insertion of neurotransmitter receptor to postsynaptic membrane (IBA from PTN002717040; Ensembl Compara IEA). Reason: Mouse Stx3 has been reported to mediate postsynaptic AMPA receptor exocytosis in plasticity, and STX3 is the fusogen in that step, so participation is plausible. There is no human evidence and it is peripheral to the epithelial and retinal roles. Supporting Evidence: PMID:39408994 syntaxin 3 has been postulated to be present in the postsynaptic spines of conventional synapses and to have an important role in some types of synaptic plasticity |
| GO:0098967 exocytic insertion of neurotransmitter receptor to postsynaptic membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Exocytic insertion of neurotransmitter receptor to postsynaptic membrane (IBA from PTN002717040; Ensembl Compara IEA). Reason: Mouse Stx3 has been reported to mediate postsynaptic AMPA receptor exocytosis in plasticity, and STX3 is the fusogen in that step, so participation is plausible. There is no human evidence and it is peripheral to the epithelial and retinal roles. Supporting Evidence: PMID:39408994 syntaxin 3 has been postulated to be present in the postsynaptic spines of conventional synapses and to have an important role in some types of synaptic plasticity |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Glutamatergic synapse, transferred from mouse. Reason: Consistent with the neuronal and synaptic STX3 literature. Non-core. Supporting Evidence: PMID:39408994 syntaxin 3 has been postulated to be present in the postsynaptic spines of conventional synapses and to have an important role in some types of synaptic plasticity |
| GO:0120025 plasma membrane bounded cell projection | IEA GO_REF:0000117 | TOO GENERAL | Summary: Plasma membrane bounded cell projection (ARBA). Reason: Entailed by the lamellipodium and neuron projection rows kept in this review. |
| GO:1903078 positive regulation of protein localization to plasma membrane | IMP PMID:21720706 Syntaxins 3 and 4 mediate vesicular trafficking of Ξ±5Ξ²1 and ... | KEEP AS NON CORE | Summary: Positive regulation of protein localization to plasma membrane (IMP; integrin delivery in HeLa). Reason: STX3 knockdown reduces surface integrins and leaves them in cytoplasmic vesicles, consistent with STX3 fusing integrin-carrying vesicles with the plasma membrane. GO curation conventionally captures this as positive regulation of protein localization. Kept as non-core. Supporting Evidence: PMID:21720706 siRNA knockdown (KD) of syntaxins 3 and 4, but not of syntaxin 2, in HeLa cells reduced cell surface expression of Ξ±5Ξ²1 and Ξ±3Ξ²1 integrins and accumulated the integrins in cytoplasmic vesicles |
| GO:2000010 positive regulation of protein localization to cell surface | IMP PMID:21720706 Syntaxins 3 and 4 mediate vesicular trafficking of Ξ±5Ξ²1 and ... | KEEP AS NON CORE | Summary: Positive regulation of protein localization to cell surface (IMP; integrin delivery in HeLa). Reason: Same evidence and rationale as the plasma-membrane localization row. Supporting Evidence: PMID:21720706 siRNA knockdown (KD) of syntaxins 3 and 4, but not of syntaxin 2, in HeLa cells reduced cell surface expression of Ξ±5Ξ²1 and Ξ±3Ξ²1 integrins and accumulated the integrins in cytoplasmic vesicles |
| GO:0006887 exocytosis | IBA GO_REF:0000033 | NEW | Summary: Proposed: exocytosis. PAINT node PTN000461524 (plasma-membrane syntaxins, from which human STX3 descends) now carries an IBD for exocytosis that has not yet propagated to the GOA snapshot. Reason: STX3 is the plasma membrane t-SNARE that performs the fusion step of exocytosis, so it does part of the work of the process. In other species it is required for regulated granule exocytosis in mast cells and beta cells and for cAMP/cGMP-stimulated CFTR exocytosis in enterocytes. In human, truncation abolishes apical vesicle fusion in enterocytes. The PTN000461524 node shows the PAINT curator placed exocytosis on the clade that contains STX3. Supporting Evidence: PMID:30563839 Stx3, and not Stx4, is crucial for MC exocytosis PMID:23132338 SYN-3 plays a role in the mediation of newcomer SG exocytosis and SG-SG fusion PMID:20844248 Silencing of syntaxin 3 by short hairpin RNA (shRNA) interference abrogated cyclic nucleotide-stimulated exocytosis of CFTR in cells. PMID:24726755 STX3 is an apical receptor involved in membrane fusion of apical vesicles in enterocytes. |
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Download this section (compressed HTML)Q: Is the human cell-cell junction IDA (PMID:15576373) based on STX3 imaging in the full text, or is it an STX4 observation attached to STX3?
Q: Should the soluble Stx3S transcriptional function be captured with an isoform-qualified DNA-binding transcription factor binding annotation, and does it act as a coactivator or corepressor of ETV4/ATF2 targets?
Q: Does human STX3 (as in mouse) take part in postsynaptic AMPA receptor exocytosis, or is the PTN002717040 inheritance a rodent-specific observation?
Experiment: In human intestinal organoids lacking STX3, rescue with wild-type STX3A versus SNARE-motif or FMDE-motif mutants and score apical delivery of sucrase-isomaltase and CFTR by surface biotinylation.
Hypothesis: Apical fusogenic activity of STX3A, not merely its presence, is needed for brush border protein delivery.
Experiment: Reconstitute STX3A versus STX3B with SNAP-23/SNAP25 and VAMP2/VAMP7/VAMP8 in liposome fusion assays to define the cognate R-SNARE specificity of each human isoform.
Hypothesis: The divergent C-terminal SNARE halves of STX3A and STX3B set different R-SNARE partner preferences.
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