Synaptotagmin-1 (p65) is a single-pass integral membrane protein of synaptic vesicles and neuroendocrine dense-core vesicles, with a short intravesicular N-terminus, one transmembrane helix, a juxtamembrane linker and two cytoplasmic C2 domains (C2A, C2B). The C2 domains bind Ca2+ (about five ions in total) and, in a Ca2+-dependent manner, insert into membranes containing anionic phospholipids (phosphatidylserine, PIP2) and bind the neuronal t-SNAREs and assembled SNARE complex. Through these interactions Syt1 tethers vesicles to the presynaptic plasma membrane, clamps premature fusion, and on Ca2+ influx triggers SNARE-mediated fusion, acting as the principal Ca2+ sensor for fast synchronous neurotransmitter release; it also contributes to dense-core vesicle exocytosis in neuroendocrine cells. Secondary roles include binding the AP-2 and stonin-2 endocytic adaptors for its own retrieval during synaptic vesicle endocytosis, Ca2+-promoted self-association, and serving as a host receptor for botulinum neurotoxins B and G.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000149 SNARE binding | IBA GO_REF:0000033 | ACCEPT | Summary: Synaptotagmin-family IBA for SNARE binding; Syt1 binds t-SNAREs (syntaxin-1/SNAP-25) and assembled SNARE complexes. Reason: Rat Syt1 binds membrane-embedded t-SNARE heterodimers weakly without Ca2+ and strongly with Ca2+, and SNARE binding by the C2B domain is required for fusion triggering. The PAINT node placement on the synaptotagmin family is consistent with this; Syt1 is a well-characterised descendant with its own experimental support. Supporting Evidence: PMID:20688915 In contrast, rat SYT1, fly SYT1, and fly SYT4 all exhibited weak t-SNARE binding activity in the absence of Ca2+ and much stronger binding in the presence of Ca2+ PMID:27083046 we show that the C2B domain interacts simultaneously with acidic membranes and SNARE complexes via the top Ca(2+)-binding loops, the side polybasic patch, and the bottom face in response to Ca(2+) |
| GO:0000149 SNARE binding | IDA PMID:12860971 Identification of synaptotagmin effectors via acute inhibiti... | ACCEPT | Summary: Cracked PC12 assays: inhibition of secretion by syt C2 domains correlated with t-SNARE (syntaxin-SNAP-25) binding. Reason: Direct biochemical evidence (full text read) that Syt1 C2 domains bind syntaxin-SNAP-25 t-SNARE heterodimers; SNARE binding is a core effector interaction of the Ca2+ sensor. Supporting Evidence: PMID:12860971 Inhibition was closely correlated with syntaxin-SNAP-25 and phosphatidylinositol 4,5-bisphosphate (PIP2)-binding activity PMID:12860971 These data suggest that syts trigger fusion via their Ca2+-regulated interactions with t-SNAREs and PIP2, target molecules known to play critical roles in exocytosis |
| GO:0000149 SNARE binding | IDA PMID:18508778 Analysis of the synaptotagmin family during reconstituted me... | ACCEPT | Summary: Reconstituted fusion study (full text read): Syt1 binds membrane-embedded t-SNAREs in a Ca2+-promoted manner. Reason: Ca2+-promoted t-SNARE binding by Syt1 correlates with its ability to stimulate fusion; core effector interaction. Supporting Evidence: PMID:18508778 Biochemical analysis revealed a strong correlation between the ability of syt isoforms to bind 1,2-dioleoyl phosphatidylserine (PS) and t-SNAREs in a Ca(2+)-promoted manner with their abilities to enhance fusion |
| GO:0000149 SNARE binding | IDA PMID:19132534 Direct interaction of SNARE complex binding protein synaphin... | ACCEPT | Summary: Syt1 directly binds complexin and co-immunoprecipitates with complexin and SNAREs from brain membranes. Reason: Abstract-only, but the abstract states a complex of synaphin, synaptotagmin 1 and SNAREs; SNARE binding by Syt1 is independently established, so the row is accepted. Supporting Evidence: PMID:19132534 Immunoprecipitation experiments with brain membrane extracts showed the presence of a complex consisting of synaphin, synaptotagmin 1, and SNAREs |
| GO:0000149 SNARE binding | IDA PMID:22711810 Cis- and trans-membrane interactions of synaptotagmin-1. | ACCEPT | Summary: Membrane tethering assays dissecting Syt1 binding to acidic lipids and SNAREs. Reason: Abstract states Syt1 binds acidic membrane lipids and SNAREs; consistent with the body of evidence for SNARE binding. Supporting Evidence: PMID:22711810 In neurotransmission synaptotagmin-1 tethers synaptic vesicles to the presynaptic plasma membrane by binding to acidic membrane lipids and SNAREs and promotes rapid SNARE-mediated fusion upon Ca(2+) triggering |
| GO:0000149 SNARE binding | IMP PMID:27083046 Synaptotagmin-1 C2B domain interacts simultaneously with SNA... | ACCEPT | Summary: C2B domain binds SNARE complexes and acidic membranes simultaneously; mutations disrupting this abolish fusion triggering. Reason: Full text read; mutational evidence that SNARE binding by C2B is required for function. Supporting Evidence: PMID:27083046 we show that the C2B domain interacts simultaneously with acidic membranes and SNARE complexes via the top Ca(2+)-binding loops, the side polybasic patch, and the bottom face in response to Ca(2+) |
| GO:0000149 SNARE binding | IPI PMID:12526776 Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1... | ACCEPT | Summary: Ca2+ induces binding of Syt1 C2 domains to SNAP-25 and synaptobrevin/SNARE proteins. Reason: Abstract states Ca2+-induced SNARE binding of the Syt1 C2 domains; consistent with other direct evidence. Supporting Evidence: PMID:12526776 Ca(2+) induces binding of the synaptotagmin C(2) domains to SNARE proteins, whereas Sr(2+) even at high concentrations does not |
| GO:0000149 SNARE binding | IPI PMID:12526776 Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1... | ACCEPT | Summary: Ca2+ induces binding of Syt1 C2 domains to SNAP-25 and synaptobrevin/SNARE proteins. Reason: Abstract states Ca2+-induced SNARE binding of the Syt1 C2 domains; consistent with other direct evidence. Supporting Evidence: PMID:12526776 Ca(2+) induces binding of the synaptotagmin C(2) domains to SNARE proteins, whereas Sr(2+) even at high concentrations does not |
| GO:0000149 SNARE binding | IPI PMID:20688915 Rat and Drosophila synaptotagmin 4 have opposite effects dur... | ACCEPT | Summary: Rat SYT1 used as positive control showed Ca2+-promoted t-SNARE (syntaxin-1A/SNAP-25B) binding. Reason: Full text read: rat SYT1 exhibited weak t-SNARE binding without Ca2+ and much stronger binding with Ca2+. Supporting Evidence: PMID:20688915 In contrast, rat SYT1, fly SYT1, and fly SYT4 all exhibited weak t-SNARE binding activity in the absence of Ca2+ and much stronger binding in the presence of Ca2+ |
| GO:0001786 phosphatidylserine binding | IDA PMID:12860971 Identification of synaptotagmin effectors via acute inhibiti... | ACCEPT | Summary: Syt1 C2 domains bind acidic phospholipids including PS in response to Ca2+. Reason: Ca2+-dependent PS binding is a core part of the Ca2+ sensor mechanism; cracked PC12 data relate syt function to lipid effectors. Supporting Evidence: PMID:12860971 These data suggest that syts trigger fusion via their Ca2+-regulated interactions with t-SNAREs and PIP2, target molecules known to play critical roles in exocytosis PMID:8253763 Our results show that this C2 domain by itself binds Ca2+ and phospholipids with high affinity (half-maximal binding at 4-6 microM free Ca2+) and exhibits strong positive cooperativity |
| GO:0001786 phosphatidylserine binding | IDA PMID:18508778 Analysis of the synaptotagmin family during reconstituted me... | ACCEPT | Summary: Syt1 binds PS-containing liposomes in a Ca2+-promoted manner. Reason: Full text read; PS binding correlates with fusion stimulation. Supporting Evidence: PMID:18508778 Biochemical analysis revealed a strong correlation between the ability of syt isoforms to bind 1,2-dioleoyl phosphatidylserine (PS) and t-SNAREs in a Ca(2+)-promoted manner with their abilities to enhance fusion |
| GO:0001786 phosphatidylserine binding | IDA PMID:20688915 Rat and Drosophila synaptotagmin 4 have opposite effects dur... | ACCEPT | Summary: Rat SYT1 bound PS-harboring liposomes in a Ca2+-dependent manner and not PS-free liposomes. Reason: Full text read; direct co-flotation evidence. Supporting Evidence: PMID:20688915 Rat SYT4 failed to bind PS-harboring liposomes; in contrast, fly SYT4, rat SYT1, and fly SYT1 all bound to PS-harboring vesicles in a Ca2+-dependent manner |
| GO:0005509 calcium ion binding | IDA PMID:15340165 Crystallographic identification of Ca2+ and Sr2+ coordinatio... | MODIFY | Summary: Crystal structures of the C2B domain show two or three bound Ca2+ ions coordinated by conserved aspartates. Reason: Syt1 binds Ca2+ (three ions per subunit across C2A and C2B) and the binding is the trigger for its function: Ca2+ binding converts the C2 domains into membrane- and SNARE-binding effectors. The more informative child term calcium ion sensor activity (GO:0061891), already carried by this gene, captures this; calcium ion binding is correct but less specific than the evidence supports. Proposed replacements: calcium ion sensor activity Supporting Evidence: PMID:15340165 The side chains of four highly conserved aspartic acids (D303, D309, D363, and D365) and two main chain oxygens (M302:O and Y364:O), together with water molecules, are in direct contact with two bound Ca(2+) ions (sites 1 and 2) |
| GO:0005509 calcium ion binding | IDA PMID:22447935 Phosphatidylinositol 4,5-bisphosphate increases Ca2+ affinit... | MODIFY | Summary: PIP2 increases the Ca2+ affinity of Syt1 by more than 40-fold. Reason: Syt1 binds Ca2+ (three ions per subunit across C2A and C2B) and the binding is the trigger for its function: Ca2+ binding converts the C2 domains into membrane- and SNARE-binding effectors. The more informative child term calcium ion sensor activity (GO:0061891), already carried by this gene, captures this; calcium ion binding is correct but less specific than the evidence supports. Proposed replacements: calcium ion sensor activity Supporting Evidence: PMID:22447935 PIP(2) binding reduced the apparent dissociation constant for Ca(2+) from βΌ250 to <5 ΞΌM |
| GO:0005509 calcium ion binding | IEA GO_REF:0000107 | MODIFY | Summary: Electronic (Ensembl orthology) transfer of calcium ion binding. Reason: Syt1 binds Ca2+ (three ions per subunit across C2A and C2B) and the binding is the trigger for its function: Ca2+ binding converts the C2 domains into membrane- and SNARE-binding effectors. The more informative child term calcium ion sensor activity (GO:0061891), already carried by this gene, captures this; calcium ion binding is correct but less specific than the evidence supports. Proposed replacements: calcium ion sensor activity Supporting Evidence: UniProtKB:P21707 Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domains. PMID:8253763 Our results show that this C2 domain by itself binds Ca2+ and phospholipids with high affinity (half-maximal binding at 4-6 microM free Ca2+) and exhibits strong positive cooperativity |
| GO:0005509 calcium ion binding | IMP PMID:22711810 Cis- and trans-membrane interactions of synaptotagmin-1. | MODIFY | Summary: Ca2+-binding-site variants of membrane-anchored Syt1 were used in tethering assays. Reason: Syt1 binds Ca2+ (three ions per subunit across C2A and C2B) and the binding is the trigger for its function: Ca2+ binding converts the C2 domains into membrane- and SNARE-binding effectors. The more informative child term calcium ion sensor activity (GO:0061891), already carried by this gene, captures this; calcium ion binding is correct but less specific than the evidence supports. Proposed replacements: calcium ion sensor activity Supporting Evidence: PMID:22711810 In neurotransmission synaptotagmin-1 tethers synaptic vesicles to the presynaptic plasma membrane by binding to acidic membrane lipids and SNAREs and promotes rapid SNARE-mediated fusion upon Ca(2+) triggering PMID:15340165 The side chains of four highly conserved aspartic acids (D303, D309, D363, and D365) and two main chain oxygens (M302:O and Y364:O), together with water molecules, are in direct contact with two bound Ca(2+) ions (sites 1 and 2) |
| GO:0005509 calcium ion binding | IMP PMID:9570782 Functional analysis of the C2A domain of synaptotagmin 1: im... | MODIFY | Summary: Alanine scanning of the C2A domain analysed Ca2+-dependent phospholipid and syntaxin binding. Reason: Syt1 binds Ca2+ (three ions per subunit across C2A and C2B) and the binding is the trigger for its function: Ca2+ binding converts the C2 domains into membrane- and SNARE-binding effectors. The more informative child term calcium ion sensor activity (GO:0061891), already carried by this gene, captures this; calcium ion binding is correct but less specific than the evidence supports. Proposed replacements: calcium ion sensor activity Supporting Evidence: PMID:8253763 Our results show that this C2 domain by itself binds Ca2+ and phospholipids with high affinity (half-maximal binding at 4-6 microM free Ca2+) and exhibits strong positive cooperativity |
| GO:0005509 calcium ion binding | ISO GO_REF:0000121 | MODIFY | Summary: ISO transfer of calcium ion binding from mouse Syt1. Reason: Syt1 binds Ca2+ (three ions per subunit across C2A and C2B) and the binding is the trigger for its function: Ca2+ binding converts the C2 domains into membrane- and SNARE-binding effectors. The more informative child term calcium ion sensor activity (GO:0061891), already carried by this gene, captures this; calcium ion binding is correct but less specific than the evidence supports. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:99667 SUPPORTS TRANSFER Mouse Syt1 is the 1:1 ortholog with identical Ca2+-binding C2 domains; the transfer is sound but the term is broader than calcium ion sensor activity. Proposed replacements: calcium ion sensor activity Supporting Evidence: UniProtKB:P21707 Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domains. PMID:1589771 synaptotagmin, a highly conserved synaptic vesicle protein, binds calcium at physiological concentrations in a complex with negatively charged phospholipids |
| GO:0005509 calcium ion binding | TAS PMID:2333096 Phospholipid binding by a synaptic vesicle protein homologou... | MODIFY | Summary: TAS from the original p65 cloning paper, which described PKC C2-like regions and phospholipid/calmodulin binding. Reason: Syt1 binds Ca2+ (three ions per subunit across C2A and C2B) and the binding is the trigger for its function: Ca2+ binding converts the C2 domains into membrane- and SNARE-binding effectors. The more informative child term calcium ion sensor activity (GO:0061891), already carried by this gene, captures this; calcium ion binding is correct but less specific than the evidence supports. Proposed replacements: calcium ion sensor activity Supporting Evidence: PMID:1589771 synaptotagmin, a highly conserved synaptic vesicle protein, binds calcium at physiological concentrations in a complex with negatively charged phospholipids PMID:2333096 The structure and properties of p65 suggest that it may have a role in mediating membrane interactions during synaptic vesicle exocytosis |
| GO:0005513 detection of calcium ion | IDA PMID:22229667 The importance of an asymmetric distribution of acidic lipid... | KEEP AS NON CORE | Summary: In vitro lipid-mixing and single-vesicle assays show Syt1 senses Ca2+ to enhance docking/fusion when PS is asymmetric. Reason: Syt1 does receive a Ca2+ stimulus and convert it into a molecular signal; the process term restates the calcium ion sensor activity at the BP level. Kept as non-core because the core process is calcium-dependent activation of synaptic vesicle fusion. Supporting Evidence: PMID:22229667 Thus for Syt1 to function as a Ca2+ sensor, a charge asymmetry appears to be important and this may play a role in steering Syt1 to productively trans bind to the plasma membrane |
| GO:0005515 protein binding | IPI PMID:10737807 Direct interaction between synaptotagmin and the intracellul... | REMOVE | Summary: Syt1 co-immunoprecipitates with and binds the I-II loop of neuronal sodium channel alpha (Scn2a) / associated Scn1b. Reason: Bare protein binding is uninformative; per project policy it is removed. Removal does not dispute the reported interaction. The interaction has no established functional consequence that supports a more specific MF term. Supporting Evidence: PMID:10737807 Synaptotagmin, a synaptic vesicle protein involved in Ca(2+)-regulated exocytosis, displayed direct high affinity interaction with neuronal sodium channels |
| GO:0005515 protein binding | IPI PMID:10737807 Direct interaction between synaptotagmin and the intracellul... | REMOVE | Summary: Syt1 co-immunoprecipitates with and binds the I-II loop of neuronal sodium channel alpha (Scn2a) / associated Scn1b. Reason: Bare protein binding is uninformative; per project policy it is removed. Removal does not dispute the reported interaction. The interaction has no established functional consequence that supports a more specific MF term. Supporting Evidence: PMID:10737807 Synaptotagmin, a synaptic vesicle protein involved in Ca(2+)-regulated exocytosis, displayed direct high affinity interaction with neuronal sodium channels |
| GO:0005515 protein binding | IPI PMID:11454741 Human stoned B interacts with AP-2 and synaptotagmin and fac... | REMOVE | Summary: Human stoned B (STON2) mu-homology domain binds Syt1. Reason: Bare protein binding is uninformative; per project policy it is removed. Removal does not dispute the reported interaction. The stonin-2 interaction is a cargo-recognition step for Syt1 endocytosis; it is captured in the review by regulation of endocytosis. Supporting Evidence: PMID:11454741 A domain with homology to the medium chain of adaptor complexes binds directly to both AP-2 and synaptotagmin and competes with AP-2 for the same binding site within synaptotagmin |
| GO:0005515 protein binding | IPI PMID:11502761 The AP2 binding site of synaptotagmin 1 is not an internaliz... | MODIFY | Summary: C2B domain of Syt1 binds the AP-2 clathrin adaptor (Ap2a2). Reason: The partner is the AP-2 adaptor complex; AP-2 adaptor complex binding is the informative MF supported by this paper and by 9830048. Proposed replacements: AP-2 adaptor complex binding Supporting Evidence: PMID:11502761 Thus, internalization of synaptotagmin 1 is controlled by the presence of a latent internalization signal in the COOH-terminal region and a regulatory region in the C2B domain PMID:9830048 The C2B domain mediates Ca2+-triggered synaptotagmin oligomerization, binds AP-2 and is important for the interaction of synaptotagmin with Ca2+ channels |
| GO:0005515 protein binding | IPI PMID:17190793 Synaptotagmin-12, a synaptic vesicle phosphoprotein that mod... | REMOVE | Summary: Syt12 forms a complex with Syt1 on synaptic vesicles. Reason: Bare protein binding is uninformative; per project policy it is removed. Removal does not dispute the reported interaction. Heteromeric synaptotagmin association is captured by the hetero-oligomerization rows. Supporting Evidence: PMID:17190793 In synaptic vesicles, synaptotagmin-12 forms a complex with synaptotagmin-1 that prevents synaptotagmin-1 from interacting with SNARE complexes |
| GO:0005515 protein binding | IPI PMID:18046461 JNK phosphorylates synaptotagmin-4 and enhances Ca2+-evoked ... | REMOVE | Summary: IntAct-curated Syt1-Syt4 interaction from a paper on JNK phosphorylation of Syt4. Reason: Bare protein binding is uninformative; per project policy it is removed. Removal does not dispute the reported interaction. Abstract-only; Syt1-Syt4 hetero-oligomerization is captured elsewhere in this review. Supporting Evidence: PMID:9830048 Ca2+ promoted the hetero-oligomerization of synaptotagmin I with synaptotagmins III and IV |
| GO:0005515 protein binding | IPI PMID:18166656 Molecular basis of synaptic vesicle cargo recognition by the... | REMOVE | Summary: Syt1 basic surface clusters bind the C. elegans stonin UNC-41B / stonin 2 mu-homology domain. Reason: Bare protein binding is uninformative; per project policy it is removed. Removal does not dispute the reported interaction. Supporting Evidence: PMID:18166656 The interaction involves the direct association of clusters of basic residues on the surface of the cytoplasmic domain of synaptotagmin 1 and a beta strand within the mu-homology domain of stonin 2 |
| GO:0005515 protein binding | IPI PMID:20173763 Single-molecule FRET-derived model of the synaptotagmin 1-SN... | MODIFY | Summary: smFRET-derived model of the Syt1-SNARE complex (partners SNAP-25 and synaptobrevin-2). Reason: The partners are SNARE proteins assembled in the SNARE complex, so the informative term is SNARE binding. Proposed replacements: SNARE binding Supporting Evidence: PMID:20173763 SNARE binding results in narrower intrasynaptotagmin FRET distributions and less frequent transitions between states |
| GO:0005515 protein binding | IPI PMID:20173763 Single-molecule FRET-derived model of the synaptotagmin 1-SN... | MODIFY | Summary: smFRET-derived model of the Syt1-SNARE complex (partners SNAP-25 and synaptobrevin-2). Reason: The partners are SNARE proteins assembled in the SNARE complex, so the informative term is SNARE binding. Proposed replacements: SNARE binding Supporting Evidence: PMID:20173763 SNARE binding results in narrower intrasynaptotagmin FRET distributions and less frequent transitions between states |
| GO:0005515 protein binding | IPI PMID:23792689 A Bcl-xL-Drp1 complex regulates synaptic vesicle membrane dy... | REMOVE | Summary: Co-immunoprecipitation reported in a study of Bcl-xL/Drp1 in synaptic vesicle endocytosis. Reason: Bare protein binding is uninformative; per project policy it is removed. Removal does not dispute the reported interaction. Syt1 was used as a vesicle membrane marker in this study. Supporting Evidence: PMID:23792689 co-immunoprecipitated with the specific vesicle membrane protein synaptotagmin |
| GO:0005515 protein binding | IPI PMID:25964652 The juxtamembrane region of synaptotagmin 1 interacts with d... | REMOVE | Summary: The juxtamembrane region of Syt1 binds the PH domain of dynamin 1. Reason: Bare protein binding is uninformative; per project policy it is removed. Removal does not dispute the reported interaction. A role in endocytic fission is captured by regulation of endocytosis. Supporting Evidence: PMID:25964652 We now demonstrate that the jxm region of Syt1 interacts directly with the pleckstrin homology (PH) domain of the endocytic protein dynamin 1 |
| GO:0005515 protein binding | IPI PMID:26280336 Architecture of the synaptotagmin-SNARE machinery for neuron... | MODIFY | Summary: Crystal structures of Syt1 bound to the neuronal SNARE complex (partner syntaxin-1A). Reason: The partner is the assembled SNARE complex; SNARE binding is the informative term. Proposed replacements: SNARE binding Supporting Evidence: PMID:26280336 The structures reveal several interfaces, including a large, specific, Ca(2+)-independent and conserved interface |
| GO:0005515 protein binding | IPI PMID:26437117 Synaptotagmin-1 and -7 Are Redundantly Essential for Maintai... | MODIFY | Summary: Syt1 binds SNARE complexes; top-loop mutations reduce SNARE binding and RRP maintenance. Reason: The partner is the SNARE complex; SNARE binding is the informative term. Proposed replacements: SNARE binding Supporting Evidence: PMID:26437117 Both synaptotagmins bound to SNARE complexes; SNARE complex binding was reduced by the top-loop mutations that impaired RRP maintenance |
| GO:0005515 protein binding | IPI PMID:28057568 Localization of Rab3A-binding site on C2A domain of synaptot... | MODIFY | Summary: Rab3A binds the Syt1 C2A domain (R199/K200 site) and C2B polylysine motif. Reason: Rab3A is a small GTPase; small GTPase binding is a more informative MF than bare protein binding (abstract-only). Proposed replacements: small GTPase binding Supporting Evidence: PMID:28057568 Our previous study demonstrated that Rab3A, a small GTP-binding protein, is a new interacting partner of Syt I and could bind to both of the C2 domains |
| GO:0005515 protein binding | IPI PMID:8567678 The V0 sector of the V-ATPase, synaptobrevin, and synaptophy... | REMOVE | Summary: IntAct-curated Syt1-synaptobrevin association from a study of the V-ATPase/synaptobrevin/synaptophysin complex. Reason: Bare protein binding is uninformative; per project policy it is removed. Removal does not dispute the reported interaction. Abstract does not mention synaptotagmin; SNARE binding is covered elsewhere. Supporting Evidence: PMID:20173763 SNARE binding results in narrower intrasynaptotagmin FRET distributions and less frequent transitions between states |
| GO:0005515 protein binding | IPI PMID:8910372 Isoform-specific, calcium-regulated interaction of the synap... | REMOVE | Summary: Syt1 C2B directly binds the SV2A N-terminus; binding is inhibited by Ca2+. Reason: Bare protein binding is uninformative; per project policy it is removed. Removal does not dispute the reported interaction. Supporting Evidence: PMID:8910372 The interaction between SV2 and synaptotagmin is direct, specific to SV2A, and inhibited by calcium with an EC50 of approximately 10 microM |
| GO:0005515 protein binding | IPI PMID:9830048 Delineation of the oligomerization, AP-2 binding, and synpri... | MODIFY | Summary: C2B dilysine region mediates AP-2 binding. Reason: The partner (Ap2a2) is an AP-2 adaptor complex subunit; AP-2 adaptor complex binding is the informative term. Proposed replacements: AP-2 adaptor complex binding Supporting Evidence: PMID:9830048 The C2B domain mediates Ca2+-triggered synaptotagmin oligomerization, binds AP-2 and is important for the interaction of synaptotagmin with Ca2+ channels |
| GO:0005515 protein binding | IPI PMID:9830048 Delineation of the oligomerization, AP-2 binding, and synpri... | REMOVE | Summary: Ca2+-promoted hetero-oligomerization of Syt1 with Syt3 and Syt4. Reason: Bare protein binding is uninformative; per project policy it is removed. Removal does not dispute the reported interaction. Captured by protein heterooligomerization rows from the same paper. Supporting Evidence: PMID:9830048 Ca2+ promoted the hetero-oligomerization of synaptotagmin I with synaptotagmins III and IV |
| GO:0005515 protein binding | IPI PMID:9830048 Delineation of the oligomerization, AP-2 binding, and synpri... | REMOVE | Summary: Ca2+-promoted hetero-oligomerization of Syt1 with Syt3 and Syt4. Reason: Bare protein binding is uninformative; per project policy it is removed. Removal does not dispute the reported interaction. Captured by protein heterooligomerization rows from the same paper. Supporting Evidence: PMID:9830048 Ca2+ promoted the hetero-oligomerization of synaptotagmin I with synaptotagmins III and IV |
| GO:0005515 protein binding | IPI PMID:9830048 Delineation of the oligomerization, AP-2 binding, and synpri... | REMOVE | Summary: Syt1 C2B binds the synprint region of the N-type Ca2+ channel alpha1B subunit. Reason: Bare protein binding is uninformative; per project policy it is removed. Removal does not dispute the reported interaction. No regulatory consequence for channel activity is shown, so no channel-regulator MF is warranted. Supporting Evidence: PMID:9830048 The C2B domain mediates Ca2+-triggered synaptotagmin oligomerization, binds AP-2 and is important for the interaction of synaptotagmin with Ca2+ channels |
| GO:0005516 calmodulin binding | IDA PMID:2333096 Phospholipid binding by a synaptic vesicle protein homologou... | KEEP AS NON CORE | Summary: Original p65 paper reported calmodulin binding by the cytoplasmic domain. Reason: Abstract-only but explicit; calmodulin binding is a minor, functionally unexplained property. Supporting Evidence: PMID:2333096 The binding specificity resembles PKC, except that p65 also binds calmodulin |
| GO:0005543 phospholipid binding | IDA PMID:2333096 Phospholipid binding by a synaptic vesicle protein homologou... | MODIFY | Summary: Recombinant p65 cytoplasmic domain binds acidic phospholipids. Reason: Syt1 binds anionic phospholipids (PS, PIP2) through its C2 domains in a Ca2+-dependent manner; the specific term calcium-dependent phospholipid binding (GO:0005544), already accepted for this gene, is better supported than generic phospholipid/lipid binding. Proposed replacements: calcium-dependent phospholipid binding Supporting Evidence: PMID:2333096 The cytoplasmic domain of recombinant p65 binds acidic phospholipids with a specificity indicating an interaction of p65 with the hydrophobic core as well as the headgroups of the phospholipids PMID:1589771 synaptotagmin, a highly conserved synaptic vesicle protein, binds calcium at physiological concentrations in a complex with negatively charged phospholipids |
| GO:0005543 phospholipid binding | IDA PMID:9830048 Delineation of the oligomerization, AP-2 binding, and synpri... | MODIFY | Summary: C2B domain phospholipid interactions analysed alongside oligomerization and AP-2 binding. Reason: Syt1 binds anionic phospholipids (PS, PIP2) through its C2 domains in a Ca2+-dependent manner; the specific term calcium-dependent phospholipid binding (GO:0005544), already accepted for this gene, is better supported than generic phospholipid/lipid binding. Proposed replacements: calcium-dependent phospholipid binding Supporting Evidence: PMID:8253763 Our results show that this C2 domain by itself binds Ca2+ and phospholipids with high affinity (half-maximal binding at 4-6 microM free Ca2+) and exhibits strong positive cooperativity |
| GO:0005543 phospholipid binding | IEA GO_REF:0000107 | MODIFY | Summary: Electronic transfer of phospholipid binding. Reason: Syt1 binds anionic phospholipids (PS, PIP2) through its C2 domains in a Ca2+-dependent manner; the specific term calcium-dependent phospholipid binding (GO:0005544), already accepted for this gene, is better supported than generic phospholipid/lipid binding. Proposed replacements: calcium-dependent phospholipid binding Supporting Evidence: UniProtKB:P21707 The first C2 domain mediates Ca(2+)-dependent phospholipid binding. |
| GO:0005543 phospholipid binding | ISO GO_REF:0000121 | MODIFY | Summary: ISO transfer of phospholipid binding from human SYT1. Reason: Syt1 binds anionic phospholipids (PS, PIP2) through its C2 domains in a Ca2+-dependent manner; the specific term calcium-dependent phospholipid binding (GO:0005544), already accepted for this gene, is better supported than generic phospholipid/lipid binding. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P21579 SUPPORTS TRANSFER Human SYT1 is the 1:1 ortholog; the transfer is sound but generic. Proposed replacements: calcium-dependent phospholipid binding Supporting Evidence: UniProtKB:P21707 The first C2 domain mediates Ca(2+)-dependent phospholipid binding. PMID:1589771 synaptotagmin, a highly conserved synaptic vesicle protein, binds calcium at physiological concentrations in a complex with negatively charged phospholipids |
| GO:0005544 calcium-dependent phospholipid binding | IBA GO_REF:0000033 | ACCEPT | Summary: Synaptotagmin-family IBA for calcium-dependent phospholipid binding. Reason: Core activity of the Syt1 C2 domains, directly demonstrated for rat Syt1. Supporting Evidence: PMID:8253763 Our results show that this C2 domain by itself binds Ca2+ and phospholipids with high affinity (half-maximal binding at 4-6 microM free Ca2+) and exhibits strong positive cooperativity UniProtKB:P21707 The first C2 domain mediates Ca(2+)-dependent phospholipid binding. |
| GO:0005544 calcium-dependent phospholipid binding | IDA PMID:1589771 Synaptotagmin: a calcium sensor on the synaptic vesicle surf... | ACCEPT | Summary: Synaptotagmin binds Ca2+ at physiological concentrations in a complex with negatively charged phospholipids. Reason: Founding biochemical evidence for the Ca2+ sensor. Supporting Evidence: PMID:1589771 synaptotagmin, a highly conserved synaptic vesicle protein, binds calcium at physiological concentrations in a complex with negatively charged phospholipids |
| GO:0005544 calcium-dependent phospholipid binding | IDA PMID:22711810 Cis- and trans-membrane interactions of synaptotagmin-1. | ACCEPT | Summary: Ca2+-dependent cis/trans binding of membrane-anchored Syt1 to anionic lipid membranes. Reason: Consistent with established Ca2+/phospholipid binding. Supporting Evidence: PMID:22711810 In neurotransmission synaptotagmin-1 tethers synaptic vesicles to the presynaptic plasma membrane by binding to acidic membrane lipids and SNAREs and promotes rapid SNARE-mediated fusion upon Ca(2+) triggering |
| GO:0005544 calcium-dependent phospholipid binding | IDA PMID:7791877 Ca(2+)-dependent and -independent activities of neural and n... | ACCEPT | Summary: C2A domains of Syt I and other isoforms bind phospholipids with EC50 3-6 uM Ca2+. Reason: Abstract-only but explicit. Supporting Evidence: PMID:7791877 its phospholipid binding is triggered at lower calcium concentrations (EC50 = 3-6 microM) than those required for exocytosis |
| GO:0005544 calcium-dependent phospholipid binding | IDA PMID:8253763 A single C2 domain from synaptotagmin I is sufficient for hi... | ACCEPT | Summary: The isolated C2A domain binds Ca2+ and negatively charged phospholipids with high affinity and positive cooperativity. Reason: Direct biochemical evidence; core activity. Supporting Evidence: PMID:8253763 Our results show that this C2 domain by itself binds Ca2+ and phospholipids with high affinity (half-maximal binding at 4-6 microM free Ca2+) and exhibits strong positive cooperativity |
| GO:0005544 calcium-dependent phospholipid binding | IEA GO_REF:0000120 | ACCEPT | Summary: UniProt-keyword/subcellular IEA for calcium-dependent phospholipid binding. Reason: Consistent with experimental evidence. Supporting Evidence: UniProtKB:P21707 The first C2 domain mediates Ca(2+)-dependent phospholipid binding. |
| GO:0005544 calcium-dependent phospholipid binding | IMP PMID:24973220 The juxtamembrane linker of full-length synaptotagmin 1 cont... | ACCEPT | Summary: Full-length reconstituted Syt1 captures anionic-lipid vesicles in a Ca2+-dependent manner; linker GXXXG mutants reduce capture. Reason: Abstract-only; consistent with core activity. Supporting Evidence: PMID:24973220 The total internal reflection fluorescence-based vesicle binding assay demonstrates that full-length Syt1 that is reconstituted into supported lipid bilayers will capture vesicles containing negatively charged lipid in a Ca(2+)-dependent manner |
| GO:0005544 calcium-dependent phospholipid binding | IMP PMID:8253763 A single C2 domain from synaptotagmin I is sufficient for hi... | ACCEPT | Summary: The isolated C2A domain binds Ca2+ and negatively charged phospholipids with high affinity and positive cooperativity. Reason: Direct biochemical evidence; core activity. Supporting Evidence: PMID:8253763 Our results show that this C2 domain by itself binds Ca2+ and phospholipids with high affinity (half-maximal binding at 4-6 microM free Ca2+) and exhibits strong positive cooperativity |
| GO:0005544 calcium-dependent phospholipid binding | ISO GO_REF:0000121 | ACCEPT | Summary: ISO transfer of calcium-dependent phospholipid binding from mouse Syt1. Reason: Sound orthology transfer of the core activity. Supporting Evidence: PMID:8253763 Our results show that this C2 domain by itself binds Ca2+ and phospholipids with high affinity (half-maximal binding at 4-6 microM free Ca2+) and exhibits strong positive cooperativity |
| GO:0005546 phosphatidylinositol-4,5-bisphosphate binding | IDA PMID:12860971 Identification of synaptotagmin effectors via acute inhibiti... | ACCEPT | Summary: Syt C2 domains bind PIP2; inhibition of secretion correlated with PIP2 binding. Reason: Full text read; PIP2 binding by the C2B polybasic patch is a core effector interaction. Supporting Evidence: PMID:12860971 Inhibition was closely correlated with syntaxin-SNAP-25 and phosphatidylinositol 4,5-bisphosphate (PIP2)-binding activity |
| GO:0005546 phosphatidylinositol-4,5-bisphosphate binding | IDA PMID:22447935 Phosphatidylinositol 4,5-bisphosphate increases Ca2+ affinit... | ACCEPT | Summary: PIP2 binds the C2B polybasic patch (Kd ~20 uM) and increases Ca2+ affinity. Reason: Direct quantitative binding evidence. Supporting Evidence: PMID:22447935 We found that PIP(2) bound to the well conserved polybasic patch of the C2B domain with an apparent dissociation constant of βΌ20 ΞΌM |
| GO:0005737 cytoplasm | IDA PMID:10967100 Nadrin, a novel neuron-specific GTPase-activating protein in... | MODIFY | Summary: Syt1 used as a neurite-terminus marker colocalising with Nadrin in PC12 cells. Reason: Syt1 is an integral membrane protein of synaptic vesicles; "cytoplasm" is true only in the sense that the vesicles are cytoplasmic. The informative location is synaptic vesicle membrane (GO:0030672), already accepted for this gene. Proposed replacements: synaptic vesicle membrane Supporting Evidence: PMID:10967100 In PC12 cells, Nadrin colocalized with synaptotagmin in the neurite termini and also with cortical actin filaments in the subplasmalemmal regions UniProtKB:P21707 Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | MODIFY | Summary: UniProt subcellular-location mapping to cytoplasm. Reason: Syt1 is an integral membrane protein of synaptic vesicles; "cytoplasm" is true only in the sense that the vesicles are cytoplasmic. The informative location is synaptic vesicle membrane (GO:0030672), already accepted for this gene. Proposed replacements: synaptic vesicle membrane Supporting Evidence: UniProtKB:P21707 Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | MODIFY | Summary: ISO transfer of cytoplasm from human SYT1. Reason: Syt1 is an integral membrane protein of synaptic vesicles; "cytoplasm" is true only in the sense that the vesicles are cytoplasmic. The informative location is synaptic vesicle membrane (GO:0030672), already accepted for this gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P21579 SUPPORTS TRANSFER Human SYT1 cytoplasm annotation reflects vesicle localisation; transferable but too coarse. Proposed replacements: synaptic vesicle membrane Supporting Evidence: UniProtKB:P21707 Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology transfer of Golgi apparatus. Reason: Golgi localisation of Syt1 reflects biosynthetic transit (the protein is N- and O-glycosylated) rather than a site of function; synaptic-vesicle and dense-core-vesicle membranes are where it acts. No experimental Golgi evidence exists for rat Syt1; the organelle claim is peripheral and over-propagated. Supporting Evidence: UniProtKB:P21707 Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane PMID:14715137 mutation of the N-terminal N-glycosylation site of synaptotagmin 1 redirects synaptotagmin 1 from vesicles to the plasma membrane |
| GO:0005794 Golgi apparatus | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: ISO transfer of Golgi apparatus from mouse Syt1. Reason: Golgi localisation of Syt1 reflects biosynthetic transit (the protein is N- and O-glycosylated) rather than a site of function; synaptic-vesicle and dense-core-vesicle membranes are where it acts. No experimental Golgi evidence exists for rat Syt1; the organelle claim is peripheral and over-propagated. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:99667 SOURCE WEAK OR INFERRED Mouse Golgi annotation likely reflects biosynthetic transit or overexpression, not a functional location. Supporting Evidence: UniProtKB:P21707 Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Synaptotagmin-family IBA for plasma membrane. Reason: A minority pool of Syt1 resides on the presynaptic plasma membrane after exocytosis before retrieval, and glycosylation-deficient Syt1 is missorted there; but the primary location is the vesicle membrane, so plasma membrane is non-core. The family node also includes plasma-membrane isoforms such as Syt7. Supporting Evidence: PMID:14715137 Synaptotagmins 1 and 7 are candidate Ca(2+) sensors for exocytosis localized to synaptic vesicles and plasma membranes, respectively PMID:14715137 mutation of the N-terminal N-glycosylation site of synaptotagmin 1 redirects synaptotagmin 1 from vesicles to the plasma membrane |
| GO:0005886 plasma membrane | IDA PMID:18179895 Molecular cytogenetic analysis and resequencing of contactin... | KEEP AS NON CORE | Summary: IDA from a CNTNAP2/autism resequencing paper with brain subcellular fractionation. Reason: The cached full text mentions synaptotagmin only in figures (used as a fractionation marker), so the exact observation cannot be checked here; deferring to the curator, since a minor surface pool of Syt1 on the presynaptic plasma membrane is well established. The primary location is the vesicle membrane, so this is non-core. Supporting Evidence: PMID:14715137 Synaptotagmins 1 and 7 are candidate Ca(2+) sensors for exocytosis localized to synaptic vesicles and plasma membranes, respectively |
| GO:0006855 xenobiotic transmembrane transport | IMP PMID:35914553 Synaptotagmin 1-mediated cell membrane penetration and dopam... | MARK AS OVER ANNOTATED | Summary: Syt1 luminal domain acts as a receptor for the spider toxin LETX-VI, which enters PC12 cells via the exo-/endocytic vesicle cycle. Reason: Abstract-only. Syt1 is described as a receptor that is co-internalised by endocytosis; it does not transport the toxin across a membrane. The term xenobiotic transmembrane transport overstates the role; the observation is a host-receptor property analogous to its role as a botulinum toxin receptor. Supporting Evidence: PMID:35914553 during which vesicular transmembrane protein synaptotagmin 1 (Syt1) functions as a receptor, with its vesicle luminal domain interacting with the C-terminal region of LETX-VI |
| GO:0006906 vesicle fusion | IDA PMID:24001110 The synaptotagmin 1 linker may function as an electrostatic ... | ACCEPT | Summary: Single-vesicle docking/content-mixing assays: the Syt1 linker is essential for Ca2+-independent docking and Ca2+-dependent fusion pore opening. Reason: Reconstituted liposome fusion assays show Syt1 is required for and accelerates SNARE-mediated fusion. The in vitro system is not a synapse, so vesicle fusion is as precise as this evidence allows; the in vivo process is captured by calcium-dependent activation of synaptic vesicle fusion. Supporting Evidence: PMID:24001110 we found that the linker region of Syt1 is essential for its two signature functions: Ca2+-independent vesicle docking and Ca2+-dependent fusion pore opening |
| GO:0006906 vesicle fusion | IMP PMID:24001110 The synaptotagmin 1 linker may function as an electrostatic ... | ACCEPT | Summary: Single-vesicle docking/content-mixing assays: the Syt1 linker is essential for Ca2+-independent docking and Ca2+-dependent fusion pore opening. Reason: Reconstituted liposome fusion assays show Syt1 is required for and accelerates SNARE-mediated fusion. The in vitro system is not a synapse, so vesicle fusion is as precise as this evidence allows; the in vivo process is captured by calcium-dependent activation of synaptic vesicle fusion. Supporting Evidence: PMID:24001110 we found that the linker region of Syt1 is essential for its two signature functions: Ca2+-independent vesicle docking and Ca2+-dependent fusion pore opening |
| GO:0006906 vesicle fusion | IMP PMID:27083046 Synaptotagmin-1 C2B domain interacts simultaneously with SNA... | ACCEPT | Summary: C2B mutants disrupting simultaneous SNARE/membrane binding abolish triggering of liposome fusion. Reason: Reconstituted liposome fusion assays show Syt1 is required for and accelerates SNARE-mediated fusion. The in vitro system is not a synapse, so vesicle fusion is as precise as this evidence allows; the in vivo process is captured by calcium-dependent activation of synaptic vesicle fusion. Supporting Evidence: PMID:27083046 we show that the C2B domain interacts simultaneously with acidic membranes and SNARE complexes via the top Ca(2+)-binding loops, the side polybasic patch, and the bottom face in response to Ca(2+) |
| GO:0007269 neurotransmitter secretion | ISO GO_REF:0000121 | MODIFY | Summary: ISO transfer of neurotransmitter secretion from mouse Syt1. Reason: Mouse Syt1 knockout selectively abolishes the fast synchronous component of release; the more specific synchronous neurotransmitter secretion (GO:0071911), already carried by this gene, captures the role. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:99667 SUPPORTS TRANSFER Mouse Syt1 knockout phenotype supports transfer; term broader than warranted. Proposed replacements: synchronous neurotransmitter secretion Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired UniProtKB:P21707 Calcium sensor that participates in triggering neurotransmitter release at the synapse |
| GO:0008021 synaptic vesicle | IDA PMID:18179895 Molecular cytogenetic analysis and resequencing of contactin... | MODIFY | Summary: Syt1 used as a synaptic-vesicle fraction marker in brain subfractionation. Reason: Syt1 is an integral synaptic vesicle membrane protein (single TM helix, cytoplasmic C2 domains); synaptic vesicle membrane (GO:0030672) is the more specific location and is already accepted. Proposed replacements: synaptic vesicle membrane Supporting Evidence: PMID:7298720 bind a 65,000-dalton protein, which is exposed on the outer surface of brain synaptic vesicles UniProtKB:P21707 Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane |
| GO:0008021 synaptic vesicle | IEA GO_REF:0000107 | MODIFY | Summary: Electronic transfer of synaptic vesicle. Reason: Syt1 is an integral synaptic vesicle membrane protein (single TM helix, cytoplasmic C2 domains); synaptic vesicle membrane (GO:0030672) is the more specific location and is already accepted. Proposed replacements: synaptic vesicle membrane Supporting Evidence: UniProtKB:P21707 Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane |
| GO:0008021 synaptic vesicle | ISO GO_REF:0000121 | MODIFY | Summary: ISO transfer of synaptic vesicle from mouse Syt1. Reason: Syt1 is an integral synaptic vesicle membrane protein (single TM helix, cytoplasmic C2 domains); synaptic vesicle membrane (GO:0030672) is the more specific location and is already accepted. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:99667 SUPPORTS TRANSFER Sound transfer; membrane sub-compartment is known. Proposed replacements: synaptic vesicle membrane Supporting Evidence: UniProtKB:P21707 Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane |
| GO:0008289 lipid binding | IEA GO_REF:0000107 | MODIFY | Summary: Electronic transfer of lipid binding. Reason: Syt1 binds anionic phospholipids (PS, PIP2) through its C2 domains in a Ca2+-dependent manner; the specific term calcium-dependent phospholipid binding (GO:0005544), already accepted for this gene, is better supported than generic phospholipid/lipid binding. Proposed replacements: calcium-dependent phospholipid binding Supporting Evidence: UniProtKB:P21707 The first C2 domain mediates Ca(2+)-dependent phospholipid binding. |
| GO:0008289 lipid binding | ISO GO_REF:0000121 | MODIFY | Summary: ISO transfer of lipid binding from human SYT1. Reason: Syt1 binds anionic phospholipids (PS, PIP2) through its C2 domains in a Ca2+-dependent manner; the specific term calcium-dependent phospholipid binding (GO:0005544), already accepted for this gene, is better supported than generic phospholipid/lipid binding. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P21579 SUPPORTS TRANSFER Human SYT1 is the 1:1 ortholog; the transfer is sound but generic. Proposed replacements: calcium-dependent phospholipid binding Supporting Evidence: UniProtKB:P21707 The first C2 domain mediates Ca(2+)-dependent phospholipid binding. PMID:1589771 synaptotagmin, a highly conserved synaptic vesicle protein, binds calcium at physiological concentrations in a complex with negatively charged phospholipids |
| GO:0014059 regulation of dopamine secretion | IEA GO_REF:0000107 | MODIFY | Summary: Electronic transfer of regulation of dopamine secretion. Reason: Syt1 knockdown in PC12 cells reduces Ca2+-dependent dopamine release, so its role is positive; positive regulation of dopamine secretion (GO:0033603), carried by this gene from PMID:28370453, is the more specific supported term. Dopamine release is a neuroendocrine/cell-type context of the core Ca2+-sensor activity. Proposed replacements: positive regulation of dopamine secretion Supporting Evidence: PMID:28370453 Syt I knockdown weakened the Ca2+ -dependent dopamine release, suggesting that Syt I plays a positive regulatory role in the cellular process |
| GO:0014059 regulation of dopamine secretion | ISO GO_REF:0000121 | MODIFY | Summary: ISO transfer of regulation of dopamine secretion from mouse Syt1. Reason: Syt1 knockdown in PC12 cells reduces Ca2+-dependent dopamine release, so its role is positive; positive regulation of dopamine secretion (GO:0033603), carried by this gene from PMID:28370453, is the more specific supported term. Dopamine release is a neuroendocrine/cell-type context of the core Ca2+-sensor activity. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:99667 SUPPORTS TRANSFER Mouse data on Syt1 in dopamine release support transfer; direction is positive. Proposed replacements: positive regulation of dopamine secretion Supporting Evidence: PMID:28370453 Syt I knockdown weakened the Ca2+ -dependent dopamine release, suggesting that Syt I plays a positive regulatory role in the cellular process |
| GO:0014069 postsynaptic density | IDA PMID:28686803 The calcium sensor synaptotagmin 1 is expressed and regulate... | KEEP AS NON CORE | Summary: Immunogold EM detects Syt1 at the postsynaptic density of CA1 synapses. Reason: Immunogold EM (abstract-only) detects Syt1 in hippocampal postsynaptic spines on cytoplasmic vesicles and at the PSD. A genuine but minor localisation with no established function; non-core. Supporting Evidence: PMID:28686803 We report for the first time that synaptotagmin 1 is present in rat hippocampal postsynaptic spines, both on cytoplasmic vesicles and at the postsynaptic density |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: InterPro-based IEA for membrane. Reason: Syt1 is an integral synaptic vesicle membrane protein (single TM helix, cytoplasmic C2 domains); synaptic vesicle membrane (GO:0030672) is the more specific location and is already accepted. Proposed replacements: synaptic vesicle membrane Supporting Evidence: UniProtKB:P21707 Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane |
| GO:0016050 vesicle organization | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Electronic transfer of vesicle organization. Reason: Vesicle organization (assembly/arrangement/disassembly of a vesicle) is not something Syt1 does; its docking and fusion roles are captured by vesicle membrane tethering activity and calcium-dependent activation of synaptic vesicle fusion. The term likely derives from vesicle docking/pool phenotypes. Supporting Evidence: PMID:24001110 we found that the linker region of Syt1 is essential for its two signature functions: Ca2+-independent vesicle docking and Ca2+-dependent fusion pore opening |
| GO:0016050 vesicle organization | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: ISO transfer of vesicle organization from human SYT1. Reason: Vesicle organization (assembly/arrangement/disassembly of a vesicle) is not something Syt1 does; its docking and fusion roles are captured by vesicle membrane tethering activity and calcium-dependent activation of synaptic vesicle fusion. The term likely derives from vesicle docking/pool phenotypes. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P21579 SOURCE WEAK OR INFERRED Donor annotation likely rests on docking/vesicle-pool phenotypes rather than a vesicle-organizing activity. Supporting Evidence: PMID:24001110 we found that the linker region of Syt1 is essential for its two signature functions: Ca2+-independent vesicle docking and Ca2+-dependent fusion pore opening |
| GO:0016079 synaptic vesicle exocytosis | IEA GO_REF:0000117 | MODIFY | Summary: Electronic (InterPro) mapping to synaptic vesicle exocytosis. Reason: Syt1 acts in synaptic vesicle exocytosis specifically as the Ca2+ trigger for fusion; calcium-dependent activation of synaptic vesicle fusion (GO:0099502, is_a synaptic vesicle exocytosis), accepted for this gene, is the more specific term. Proposed replacements: calcium-dependent activation of synaptic vesicle fusion Supporting Evidence: UniProtKB:P21707 Calcium sensor that participates in triggering neurotransmitter release at the synapse |
| GO:0016079 synaptic vesicle exocytosis | ISO GO_REF:0000121 | MODIFY | Summary: ISO transfer of synaptic vesicle exocytosis from mouse Syt1. Reason: Syt1 acts in synaptic vesicle exocytosis specifically as the Ca2+ trigger for fusion; calcium-dependent activation of synaptic vesicle fusion (GO:0099502, is_a synaptic vesicle exocytosis), accepted for this gene, is the more specific term. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:99667 SUPPORTS TRANSFER Mouse Syt1 KO data support the transfer; the term is broader than warranted. Proposed replacements: calcium-dependent activation of synaptic vesicle fusion Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired |
| GO:0016079 synaptic vesicle exocytosis | TAS PMID:2333096 Phospholipid binding by a synaptic vesicle protein homologou... | MODIFY | Summary: TAS from the original p65 paper proposing a role in synaptic vesicle exocytosis. Reason: Syt1 acts in synaptic vesicle exocytosis specifically as the Ca2+ trigger for fusion; calcium-dependent activation of synaptic vesicle fusion (GO:0099502, is_a synaptic vesicle exocytosis), accepted for this gene, is the more specific term. Proposed replacements: calcium-dependent activation of synaptic vesicle fusion Supporting Evidence: PMID:2333096 The structure and properties of p65 suggest that it may have a role in mediating membrane interactions during synaptic vesicle exocytosis |
| GO:0016192 vesicle-mediated transport | IBA GO_REF:0000033 | MODIFY | Summary: Synaptotagmin-family IBA for vesicle-mediated transport. Reason: Very general; the family-level process for Syt1 is Ca2+-triggered synaptic vesicle fusion. Refined to calcium-dependent activation of synaptic vesicle fusion. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000001283 SUPPORTS TRANSFER Deep synaptotagmin-family node; vesicle-mediated transport is true for all members but generic. Proposed replacements: calcium-dependent activation of synaptic vesicle fusion Supporting Evidence: UniProtKB:P21707 Calcium sensor that participates in triggering neurotransmitter release at the synapse PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired |
| GO:0016192 vesicle-mediated transport | IDA PMID:14715137 N-glycosylation is essential for vesicular targeting of syna... | MODIFY | Summary: N-glycosylation directs Syt1 to synaptic vesicles; plasma-membrane-mislocalised Syt1 suppresses the readily releasable pool. Reason: The paper mainly shows how Syt1 itself is targeted (as cargo), but also treats it as a vesicle Ca2+ sensor for exocytosis. Vesicle-mediated transport is true but very general; the specific process in which Syt1 acts is calcium-dependent activation of synaptic vesicle fusion. Proposed replacements: calcium-dependent activation of synaptic vesicle fusion Supporting Evidence: PMID:14715137 Synaptotagmins 1 and 7 are candidate Ca(2+) sensors for exocytosis localized to synaptic vesicles and plasma membranes, respectively |
| GO:0017075 syntaxin-1 binding | IDA PMID:12526776 Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1... | ACCEPT | Summary: Ca2+-dependent binding of Syt1 C2 domains to syntaxin-1/SNARE proteins. Reason: Abstract-only; consistent with direct evidence from multiple labs. Supporting Evidence: PMID:12526776 Ca(2+) induces binding of the synaptotagmin C(2) domains to SNARE proteins, whereas Sr(2+) even at high concentrations does not |
| GO:0017075 syntaxin-1 binding | IPI PMID:10397765 Functional and biochemical analysis of the C2 domains of syn... | ACCEPT | Summary: Syt I C2A domain binds syntaxin-1A in a Ca2+-dependent manner. Reason: Full text read. Supporting Evidence: PMID:10397765 In contrast, the Syt I C2A domain bound Stx 1a in a calcium-dependent manner |
| GO:0017156 calcium-ion regulated exocytosis | TAS PMID:2333096 Phospholipid binding by a synaptic vesicle protein homologou... | MODIFY | Summary: TAS from the original p65 paper. Reason: Syt1 is the Ca2+ sensor for fast neurotransmitter exocytosis; fast, calcium ion-dependent exocytosis of neurotransmitter (GO:0098746), a descendant already carried, is more specific. Proposed replacements: fast, calcium ion-dependent exocytosis of neurotransmitter Supporting Evidence: PMID:2333096 The structure and properties of p65 suggest that it may have a role in mediating membrane interactions during synaptic vesicle exocytosis PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired |
| GO:0017158 regulation of calcium ion-dependent exocytosis | IBA GO_REF:0000033 | MODIFY | Summary: Synaptotagmin-family IBA for regulation of calcium ion-dependent exocytosis. Reason: Syt1 promotes Ca2+-triggered exocytosis of synaptic vesicles and dense-core vesicles (knockdown reduces, it does not enhance, release). The positive child term (GO:0045956), accepted for this gene from PMID:21551071, is better supported than undirected regulation. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000001283 SUPPORTS TRANSFER Deep family node covers stimulatory and inhibitory isoforms, hence undirected; Syt1 is stimulatory. Proposed replacements: positive regulation of calcium ion-dependent exocytosis Supporting Evidence: PMID:17686463 We conclude that Syt I and Syt IX function redundantly in Ca(2+)-sensing and fusion pore dilation on LDCVs in PC12 cells PMID:18508778 Syts I-III, V-VII, IX, and X stimulated fusion in response to Ca2+ |
| GO:0017158 regulation of calcium ion-dependent exocytosis | IEA GO_REF:0000107 | MODIFY | Summary: Electronic transfer of regulation of calcium ion-dependent exocytosis. Reason: Syt1 promotes Ca2+-triggered exocytosis of synaptic vesicles and dense-core vesicles (knockdown reduces, it does not enhance, release). The positive child term (GO:0045956), accepted for this gene from PMID:21551071, is better supported than undirected regulation. Proposed replacements: positive regulation of calcium ion-dependent exocytosis Supporting Evidence: PMID:17686463 We conclude that Syt I and Syt IX function redundantly in Ca(2+)-sensing and fusion pore dilation on LDCVs in PC12 cells |
| GO:0017158 regulation of calcium ion-dependent exocytosis | IMP PMID:11751925 Synaptotagmin IX regulates Ca2+-dependent secretion in PC12 ... | MODIFY | Summary: Antibodies against Syt I or Syt IX C2A inhibit Ca2+-dependent NE release from permeabilised PC12 cells. Reason: Syt1 promotes Ca2+-triggered exocytosis of synaptic vesicles and dense-core vesicles (knockdown reduces, it does not enhance, release). The positive child term (GO:0045956), accepted for this gene from PMID:21551071, is better supported than undirected regulation. Proposed replacements: positive regulation of calcium ion-dependent exocytosis Supporting Evidence: PMID:11751925 Antibodies directed against the C2A domain of either Syt IX or Syt I inhibited Ca(2+)-dependent NE release in permeable PC12 cells indicating that both Syt proteins function in dense-core vesicle exocytosis |
| GO:0017158 regulation of calcium ion-dependent exocytosis | IMP PMID:12860971 Identification of synaptotagmin effectors via acute inhibiti... | MODIFY | Summary: Syt C2 domains inhibit Ca2+-triggered exocytosis from cracked PC12 cells. Reason: Syt1 promotes Ca2+-triggered exocytosis of synaptic vesicles and dense-core vesicles (knockdown reduces, it does not enhance, release). The positive child term (GO:0045956), accepted for this gene from PMID:21551071, is better supported than undirected regulation. Proposed replacements: positive regulation of calcium ion-dependent exocytosis Supporting Evidence: PMID:12860971 These data suggest that syts trigger fusion via their Ca2+-regulated interactions with t-SNAREs and PIP2, target molecules known to play critical roles in exocytosis |
| GO:0017158 regulation of calcium ion-dependent exocytosis | IMP PMID:17686463 Synaptotagmin I and IX function redundantly in controlling f... | MODIFY | Summary: Combined knockdown of Syt I and Syt IX reduces Ca2+-dependent LDCV exocytosis in PC12 cells. Reason: Syt1 promotes Ca2+-triggered exocytosis of synaptic vesicles and dense-core vesicles (knockdown reduces, it does not enhance, release). The positive child term (GO:0045956), accepted for this gene from PMID:21551071, is better supported than undirected regulation. Proposed replacements: positive regulation of calcium ion-dependent exocytosis Supporting Evidence: PMID:17686463 We conclude that Syt I and Syt IX function redundantly in Ca(2+)-sensing and fusion pore dilation on LDCVs in PC12 cells |
| GO:0017158 regulation of calcium ion-dependent exocytosis | ISO GO_REF:0000121 | MODIFY | Summary: ISO transfer from mouse Syt1. Reason: Syt1 promotes Ca2+-triggered exocytosis of synaptic vesicles and dense-core vesicles (knockdown reduces, it does not enhance, release). The positive child term (GO:0045956), accepted for this gene from PMID:21551071, is better supported than undirected regulation. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:99667 SUPPORTS TRANSFER Sound transfer; direction is positive. Proposed replacements: positive regulation of calcium ion-dependent exocytosis Supporting Evidence: PMID:17686463 We conclude that Syt I and Syt IX function redundantly in Ca(2+)-sensing and fusion pore dilation on LDCVs in PC12 cells |
| GO:0019905 syntaxin binding | IDA PMID:7791877 Ca(2+)-dependent and -independent activities of neural and n... | KEEP AS NON CORE | Summary: Syts interact with neural and non-neural syntaxins. Reason: Binding to non-neuronal syntaxins is at the right level of generality (several isoforms); syntaxin-1 binding is accepted separately as core. Supporting Evidence: PMID:7791877 All Syts tested share a common domain structure, with a cytoplasmic region composed of two C2 domains that interacts with clathrin-AP2 (Kd = 0.1-1.0 nM) and with neural and non-neural syntaxins |
| GO:0019905 syntaxin binding | IPI PMID:10397765 Functional and biochemical analysis of the C2 domains of syn... | KEEP AS NON CORE | Summary: Syt I C2A binds syntaxin isoforms 2 and 4 in a Ca2+-dependent manner. Reason: Full text read; binding to non-neuronal syntaxins in vitro, with no established physiological role. Supporting Evidence: PMID:10397765 In the presence of calcium, strong binding to the C2A domain of Syt I is observed with Stx 1a and Stx 4 PMID:10397765 In contrast, lower levels of calcium-dependent binding are observed with Stx 2 and Stx 3 |
| GO:0019905 syntaxin binding | IPI PMID:10397765 Functional and biochemical analysis of the C2 domains of syn... | KEEP AS NON CORE | Summary: Syt I C2A binds syntaxin isoforms 2 and 4 in a Ca2+-dependent manner. Reason: Full text read; binding to non-neuronal syntaxins in vitro, with no established physiological role. Supporting Evidence: PMID:10397765 In the presence of calcium, strong binding to the C2A domain of Syt I is observed with Stx 1a and Stx 4 PMID:10397765 In contrast, lower levels of calcium-dependent binding are observed with Stx 2 and Stx 3 |
| GO:0030100 regulation of endocytosis | IMP PMID:11502761 The AP2 binding site of synaptotagmin 1 is not an internaliz... | KEEP AS NON CORE | Summary: C2B domain regulates the C-terminal internalization signal of Syt1 in PC12 cells. Reason: Syt1 contributes to coupling exocytosis to endocytosis via AP-2/stonin-2 binding; real but secondary to the Ca2+-sensor role. Supporting Evidence: PMID:11502761 Thus, internalization of synaptotagmin 1 is controlled by the presence of a latent internalization signal in the COOH-terminal region and a regulatory region in the C2B domain |
| GO:0030141 secretory granule | IDA PMID:15015935 RNA interference-mediated silencing of synaptotagmin IX, but... | MODIFY | Summary: Syt I and IX co-reside on the same secretory vesicles in PC12 cells. Reason: In neuroendocrine cells Syt1 resides on dense-core secretory granules; dense core granule (GO:0031045, is_a secretory granule), accepted for this gene, is more specific. Proposed replacements: dense core granule Supporting Evidence: PMID:15015935 it has been shown by immunoaffinity purification and immunocytochemistry that Syts I and IX, but not Syt IV, are present on the same secretory vesicles in PC12 cells |
| GO:0030141 secretory granule | IEA GO_REF:0000107 | MODIFY | Summary: Electronic transfer of secretory granule. Reason: In neuroendocrine cells Syt1 resides on dense-core secretory granules; dense core granule (GO:0031045, is_a secretory granule), accepted for this gene, is more specific. Proposed replacements: dense core granule Supporting Evidence: PMID:22366033 Subcellular localization analysis by sucrose density gradient fractionation showed that chorein and synaptotagmin I were located in dense-core vesicles (DCVs), which contain dopamine |
| GO:0030141 secretory granule | ISO GO_REF:0000121 | MODIFY | Summary: ISO transfer of secretory granule from mouse Syt1. Reason: In neuroendocrine cells Syt1 resides on dense-core secretory granules; dense core granule (GO:0031045, is_a secretory granule), accepted for this gene, is more specific. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:99667 SUPPORTS TRANSFER Sound transfer; granule type is known. Proposed replacements: dense core granule Supporting Evidence: PMID:22366033 Subcellular localization analysis by sucrose density gradient fractionation showed that chorein and synaptotagmin I were located in dense-core vesicles (DCVs), which contain dopamine |
| GO:0030276 clathrin binding | IDA PMID:7791877 Ca(2+)-dependent and -independent activities of neural and n... | KEEP AS NON CORE | Summary: Syt cytoplasmic regions interact with clathrin-AP2 with high affinity. Reason: Abstract-only; likely reflects the AP-2 interaction within clathrin-AP2 complexes; secondary endocytic role. Supporting Evidence: PMID:7791877 All Syts tested share a common domain structure, with a cytoplasmic region composed of two C2 domains that interacts with clathrin-AP2 (Kd = 0.1-1.0 nM) and with neural and non-neural syntaxins |
| GO:0030348 syntaxin-3 binding | IPI PMID:10397765 Functional and biochemical analysis of the C2 domains of syn... | KEEP AS NON CORE | Summary: Lower-level Ca2+-dependent binding of Syt I C2A to syntaxin-3. Reason: Full text read; in vitro binding to a non-neuronal syntaxin with no established physiological role. Supporting Evidence: PMID:10397765 In contrast, lower levels of calcium-dependent binding are observed with Stx 2 and Stx 3 |
| GO:0030424 axon | IBA GO_REF:0000033 | MODIFY | Summary: Syt1/2-subfamily IBA for axon. Reason: Syt1 is concentrated in presynaptic nerve terminals on synaptic vesicles; terminal bouton (GO:0043195), accepted for this gene by HDA, is the more specific neuronal location (part of axon). Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000740739 SUPPORTS TRANSFER Syt1/2 subfamily node; presynaptic-terminal localisation is conserved, axon is coarse. Proposed replacements: terminal bouton Supporting Evidence: PMID:7298720 Immunocytochemical experiments at the electron microscope level demonstrate that these antibodies bind the vesicles in many different types of nerve terminals |
| GO:0030424 axon | IEA GO_REF:0000107 | MODIFY | Summary: Electronic transfer of axon. Reason: Syt1 is concentrated in presynaptic nerve terminals on synaptic vesicles; terminal bouton (GO:0043195), accepted for this gene by HDA, is the more specific neuronal location (part of axon). Proposed replacements: terminal bouton Supporting Evidence: PMID:7298720 Immunocytochemical experiments at the electron microscope level demonstrate that these antibodies bind the vesicles in many different types of nerve terminals |
| GO:0030424 axon | ISO GO_REF:0000121 | MODIFY | Summary: ISO transfer of axon from mouse Syt1. Reason: Syt1 is concentrated in presynaptic nerve terminals on synaptic vesicles; terminal bouton (GO:0043195), accepted for this gene by HDA, is the more specific neuronal location (part of axon). Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:99667 SUPPORTS TRANSFER Sound but coarse. Proposed replacements: terminal bouton Supporting Evidence: PMID:7298720 Immunocytochemical experiments at the electron microscope level demonstrate that these antibodies bind the vesicles in many different types of nerve terminals |
| GO:0030658 transport vesicle membrane | IEA GO_REF:0000044 | MODIFY | Summary: UniProt subcellular-location mapping to transport vesicle membrane. Reason: Syt1 is an integral synaptic vesicle membrane protein (single TM helix, cytoplasmic C2 domains); synaptic vesicle membrane (GO:0030672) is the more specific location and is already accepted. Proposed replacements: synaptic vesicle membrane Supporting Evidence: UniProtKB:P21707 Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane |
| GO:0030672 synaptic vesicle membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Syt1/2 subfamily IBA for synaptic vesicle membrane. Reason: Syt1 is an integral synaptic vesicle membrane protein with cytoplasmic C2 domains; the core site of its Ca2+-sensor function. Supporting Evidence: UniProtKB:P21707 Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane PMID:7298720 bind a 65,000-dalton protein, which is exposed on the outer surface of brain synaptic vesicles |
| GO:0030672 synaptic vesicle membrane | IDA PMID:23792689 A Bcl-xL-Drp1 complex regulates synaptic vesicle membrane dy... | ACCEPT | Summary: Syt1 co-immunoprecipitated as the vesicle membrane protein marker. Reason: Syt1 is an integral synaptic vesicle membrane protein with cytoplasmic C2 domains; the core site of its Ca2+-sensor function. Supporting Evidence: PMID:23792689 co-immunoprecipitated with the specific vesicle membrane protein synaptotagmin |
| GO:0030672 synaptic vesicle membrane | IDA PMID:7298720 Identification of a synaptic vesicle-specific membrane prote... | ACCEPT | Summary: The 65-kDa antigen is exposed on the outer surface of brain synaptic vesicles. Reason: Syt1 is an integral synaptic vesicle membrane protein with cytoplasmic C2 domains; the core site of its Ca2+-sensor function. Supporting Evidence: PMID:7298720 bind a 65,000-dalton protein, which is exposed on the outer surface of brain synaptic vesicles |
| GO:0030672 synaptic vesicle membrane | IEA GO_REF:0000120 | ACCEPT | Summary: UniProt subcellular-location IEA. Reason: Syt1 is an integral synaptic vesicle membrane protein with cytoplasmic C2 domains; the core site of its Ca2+-sensor function. Supporting Evidence: UniProtKB:P21707 Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane |
| GO:0030672 synaptic vesicle membrane | ISO GO_REF:0000121 | ACCEPT | Summary: ISO transfer from mouse Syt1. Reason: Syt1 is an integral synaptic vesicle membrane protein with cytoplasmic C2 domains; the core site of its Ca2+-sensor function. Supporting Evidence: UniProtKB:P21707 Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane |
| GO:0030672 synaptic vesicle membrane | TAS PMID:2333096 Phospholipid binding by a synaptic vesicle protein homologou... | ACCEPT | Summary: TAS: p65 is a synaptic vesicle-specific protein. Reason: Syt1 is an integral synaptic vesicle membrane protein with cytoplasmic C2 domains; the core site of its Ca2+-sensor function. Supporting Evidence: PMID:2333096 The structure and properties of p65 suggest that it may have a role in mediating membrane interactions during synaptic vesicle exocytosis |
| GO:0031045 dense core granule | IBA GO_REF:0000033 | ACCEPT | Summary: Syt1/2 subfamily IBA for dense core granule. Reason: In neuroendocrine cells Syt1 resides on dense-core vesicles, where it acts redundantly with Syt9 as a Ca2+ sensor for LDCV exocytosis; a genuine functional location. Supporting Evidence: PMID:17686463 We conclude that Syt I and Syt IX function redundantly in Ca(2+)-sensing and fusion pore dilation on LDCVs in PC12 cells |
| GO:0031045 dense core granule | IDA PMID:11751925 Synaptotagmin IX regulates Ca2+-dependent secretion in PC12 ... | ACCEPT | Summary: Syt I and IX localise to dense-core vesicles in PC12 cells. Reason: In neuroendocrine cells Syt1 resides on dense-core vesicles, where it acts redundantly with Syt9 as a Ca2+ sensor for LDCV exocytosis; a genuine functional location. Supporting Evidence: PMID:11751925 Antibodies directed against the C2A domain of either Syt IX or Syt I inhibited Ca(2+)-dependent NE release in permeable PC12 cells indicating that both Syt proteins function in dense-core vesicle exocytosis |
| GO:0031045 dense core granule | IDA PMID:21551071 Release mode of large and small dense-core vesicles specifie... | ACCEPT | Summary: Syt isoforms including Syt1 sort to dense-core vesicle populations of different size. Reason: In neuroendocrine cells Syt1 resides on dense-core vesicles, where it acts redundantly with Syt9 as a Ca2+ sensor for LDCV exocytosis; a genuine functional location. Supporting Evidence: PMID:21551071 We show that these isoforms sort to populations of dense-core vesicles that differ in size |
| GO:0031045 dense core granule | IDA PMID:22366033 Subcellular localization and putative role of VPS13A/chorein... | ACCEPT | Summary: Sucrose gradients place Syt1 with chorein in dopamine-containing DCVs. Reason: In neuroendocrine cells Syt1 resides on dense-core vesicles, where it acts redundantly with Syt9 as a Ca2+ sensor for LDCV exocytosis; a genuine functional location. Supporting Evidence: PMID:22366033 Subcellular localization analysis by sucrose density gradient fractionation showed that chorein and synaptotagmin I were located in dense-core vesicles (DCVs), which contain dopamine |
| GO:0031045 dense core granule | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic transfer of dense core granule. Reason: In neuroendocrine cells Syt1 resides on dense-core vesicles, where it acts redundantly with Syt9 as a Ca2+ sensor for LDCV exocytosis; a genuine functional location. Supporting Evidence: PMID:17686463 We conclude that Syt I and Syt IX function redundantly in Ca(2+)-sensing and fusion pore dilation on LDCVs in PC12 cells |
| GO:0031045 dense core granule | ISO GO_REF:0000121 | ACCEPT | Summary: ISO transfer from mouse Syt1. Reason: In neuroendocrine cells Syt1 resides on dense-core vesicles, where it acts redundantly with Syt9 as a Ca2+ sensor for LDCV exocytosis; a genuine functional location. Supporting Evidence: PMID:17686463 We conclude that Syt I and Syt IX function redundantly in Ca(2+)-sensing and fusion pore dilation on LDCVs in PC12 cells |
| GO:0031201 SNARE complex | IDA PMID:23663838 Rapid fusion of synaptic vesicles with reconstituted target ... | MARK AS OVER ANNOTATED | Summary: Purified rat synaptic vesicles fuse with t-SNARE bilayers; Ca2+ boosts fusion partly via synaptotagmin. Reason: Full text read. The study is a fusion assay; it does not show that Syt1 is a stable subunit of the SNARE complex. Syt1 binds the SNARE complex (captured by SNARE binding) rather than being one of the four-helix-bundle components. Supporting Evidence: PMID:23663838 Calcium boosts fusion through a combined general electrostatic and synaptotagmin-specific mechanism PMID:26280336 The structures reveal several interfaces, including a large, specific, Ca(2+)-independent and conserved interface |
| GO:0031338 regulation of vesicle fusion | IMP PMID:24001110 The synaptotagmin 1 linker may function as an electrostatic ... | MODIFY | Summary: Linker mutations alter Syt1-dependent docking and fusion pore opening in vitro. Reason: Syt1 promotes fusion in response to Ca2+; positive regulation of vesicle fusion (GO:0031340), accepted for this gene, is the more specific child. Proposed replacements: positive regulation of vesicle fusion Supporting Evidence: PMID:24001110 we found that the linker region of Syt1 is essential for its two signature functions: Ca2+-independent vesicle docking and Ca2+-dependent fusion pore opening |
| GO:0031340 positive regulation of vesicle fusion | IDA PMID:18508778 Analysis of the synaptotagmin family during reconstituted me... | ACCEPT | Summary: Syt I stimulates SNARE-catalysed membrane fusion in response to Ca2+. Reason: Full text read; direct reconstitution evidence. Supporting Evidence: PMID:18508778 Syts I-III, V-VII, IX, and X stimulated fusion in response to Ca2+ |
| GO:0031340 positive regulation of vesicle fusion | IDA PMID:20688915 Rat and Drosophila synaptotagmin 4 have opposite effects dur... | ACCEPT | Summary: Rat SYT1 promotes Ca2+-dependent fusion of SNARE liposomes. Reason: Full text read. Supporting Evidence: PMID:20688915 Although rat SYT1 promotes fusion in the presence of Ca2+, this isoform also serves to clamp or inhibit fusion in the absence of Ca2+ |
| GO:0031340 positive regulation of vesicle fusion | IDA PMID:33468652 Synaptotagmin-1-, Munc18-1-, and Munc13-1-dependent liposome... | ACCEPT | Summary: Syt1 strongly stimulates Munc18-1/Munc13-1-dependent liposome fusion with few SNAREs. Reason: Abstract explicit. Supporting Evidence: PMID:33468652 synaptotagmin-1 strongly stimulates fusion under these conditions. Such stimulation depends on Ca2+ binding to the two C2 domains of synaptotagmin-1 |
| GO:0031629 synaptic vesicle fusion to presynaptic active zone membrane | IDA PMID:22810233 SNAREpin assembly by Munc18-1 requires previous vesicle dock... | ACCEPT | Summary: Syt1 docks vesicles prior to Munc18-1-accelerated SNAREpin assembly and fusion. Reason: Reconstitution evidence (abstract-only) placing Syt1 in the docking/fusion sequence; consistent with its core process. Supporting Evidence: PMID:22810233 vesicle docking by synaptotagmin 1 is a prerequisite for Munc18-1 to accelerate trans-SNARE complex (SNAREpin) assembly and membrane fusion |
| GO:0031629 synaptic vesicle fusion to presynaptic active zone membrane | IDA PMID:23663838 Rapid fusion of synaptic vesicles with reconstituted target ... | ACCEPT | Summary: Purified rat synaptic vesicles fuse rapidly with t-SNARE bilayers; Ca2+ acts partly through synaptotagmin. Reason: Full text read; native SVs with Syt1. Supporting Evidence: PMID:23663838 Calcium boosts fusion through a combined general electrostatic and synaptotagmin-specific mechanism |
| GO:0033603 positive regulation of dopamine secretion | IMP PMID:28370453 Rab3A Inhibition of Ca(2+) -Dependent Dopamine Release From ... | KEEP AS NON CORE | Summary: Syt1 knockdown weakens Ca2+-dependent dopamine release from PC12 cells. Reason: Abstract-only; dopamine release is a cell-type context of the core Ca2+-sensor function. Supporting Evidence: PMID:28370453 Syt I knockdown weakened the Ca2+ -dependent dopamine release, suggesting that Syt I plays a positive regulatory role in the cellular process |
| GO:0036465 synaptic vesicle recycling | IMP PMID:25705886 Identification of a human synaptotagmin-1 mutation that pert... | KEEP AS NON CORE | Summary: A dominant-negative human SYT1 variant (I368T) slows SV fusion and alters SV endocytosis kinetics. Reason: Abstract-only; endocytic contribution is real but secondary. Supporting Evidence: PMID:25705886 Expression of the I368T variant also altered the kinetics of synaptic vesicle endocytosis |
| GO:0042584 chromaffin granule membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location IEA for chromaffin granule membrane. Reason: Supported by UniProt curated location; neuroendocrine context. Supporting Evidence: UniProtKB:P21707 Cytoplasmic vesicle, secretory vesicle, chromaffin granule membrane |
| GO:0042734 presynaptic membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: UniProt-mapped presynaptic membrane. Reason: Syt1 acts by bridging the vesicle to the presynaptic plasma membrane and a small pool is transiently present on it after exocytosis; the protein itself resides in the vesicle membrane, so presynaptic membrane is non-core. Supporting Evidence: PMID:22711810 In neurotransmission synaptotagmin-1 tethers synaptic vesicles to the presynaptic plasma membrane by binding to acidic membrane lipids and SNAREs and promotes rapid SNARE-mediated fusion upon Ca(2+) triggering |
| GO:0042734 presynaptic membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO transfer of presynaptic membrane from human/mouse SYT1. Reason: Syt1 acts by bridging the vesicle to the presynaptic plasma membrane and a small pool is transiently present on it after exocytosis; the protein itself resides in the vesicle membrane, so presynaptic membrane is non-core. Supporting Evidence: PMID:22711810 In neurotransmission synaptotagmin-1 tethers synaptic vesicles to the presynaptic plasma membrane by binding to acidic membrane lipids and SNAREs and promotes rapid SNARE-mediated fusion upon Ca(2+) triggering |
| GO:0042734 presynaptic membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO transfer of presynaptic membrane from human/mouse SYT1. Reason: Syt1 acts by bridging the vesicle to the presynaptic plasma membrane and a small pool is transiently present on it after exocytosis; the protein itself resides in the vesicle membrane, so presynaptic membrane is non-core. Supporting Evidence: PMID:22711810 In neurotransmission synaptotagmin-1 tethers synaptic vesicles to the presynaptic plasma membrane by binding to acidic membrane lipids and SNAREs and promotes rapid SNARE-mediated fusion upon Ca(2+) triggering |
| GO:0042802 identical protein binding | EXP PMID:38177243 The juxtamembrane linker of synaptotagmin 1 regulates Ca(2+)... | KEEP AS NON CORE | Summary: The Syt1 juxtamembrane linker self-associates into condensates. Reason: Syt1 self-associates: Ca2+-triggered C2B-mediated dimerisation, linker GXXXG-mediated oligomerisation, and LLPS of the linker. Real but its physiological role remains debated; non-core. Supporting Evidence: PMID:38177243 this linker segment harbors a lysine-rich, intrinsically disordered region that is necessary and sufficient to mediate liquid-liquid phase separation (LLPS) |
| GO:0042802 identical protein binding | IDA PMID:24973220 The juxtamembrane linker of full-length synaptotagmin 1 cont... | KEEP AS NON CORE | Summary: Full-length Syt1 oligomerises in membranes via a linker GXXXG motif. Reason: Syt1 self-associates: Ca2+-triggered C2B-mediated dimerisation, linker GXXXG-mediated oligomerisation, and LLPS of the linker. Real but its physiological role remains debated; non-core. Supporting Evidence: PMID:24973220 Pulse dipolar EPR spectroscopy provides evidence that purified full-length Syt1 is oligomerized in the membrane, and mutagenesis indicates that a glycine zipper/GXXXG motif within the linker helps mediate oligomerization |
| GO:0042802 identical protein binding | IPI PMID:8621455 A novel function for the second C2 domain of synaptotagmin. ... | KEEP AS NON CORE | Summary: Ca2+ triggers dimerisation of synaptotagmin via C2B. Reason: Syt1 self-associates: Ca2+-triggered C2B-mediated dimerisation, linker GXXXG-mediated oligomerisation, and LLPS of the linker. Real but its physiological role remains debated; non-core. Supporting Evidence: PMID:8621455 We report that Ca2+ causes synaptotagmin to oligomerize, primarily forming dimers, via its second C2 domain |
| GO:0042802 identical protein binding | IPI PMID:9830048 Delineation of the oligomerization, AP-2 binding, and synpri... | KEEP AS NON CORE | Summary: C2B region mediating Ca2+-triggered oligomerisation mapped. Reason: Syt1 self-associates: Ca2+-triggered C2B-mediated dimerisation, linker GXXXG-mediated oligomerisation, and LLPS of the linker. Real but its physiological role remains debated; non-core. Supporting Evidence: PMID:9830048 The C2B domain mediates Ca2+-triggered synaptotagmin oligomerization, binds AP-2 and is important for the interaction of synaptotagmin with Ca2+ channels |
| GO:0043005 neuron projection | IEA GO_REF:0000107 | MODIFY | Summary: Electronic transfer of neuron projection. Reason: Neuron projection is correct but general; Syt1 acts in presynaptic terminals (terminal bouton) and, in PC12 cells, neurite tips (neuron projection terminus), both carried by this gene. Proposed replacements: terminal bouton neuron projection terminus Supporting Evidence: PMID:7298720 Immunocytochemical experiments at the electron microscope level demonstrate that these antibodies bind the vesicles in many different types of nerve terminals PMID:10397765 Syt IV colocalizes with Syt I in the tips of the neurites |
| GO:0043005 neuron projection | ISO GO_REF:0000121 | MODIFY | Summary: ISO transfer of neuron projection from mouse Syt1. Reason: Neuron projection is correct but general; Syt1 acts in presynaptic terminals (terminal bouton) and, in PC12 cells, neurite tips (neuron projection terminus), both carried by this gene. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:99667 SUPPORTS TRANSFER Sound but coarse. Proposed replacements: terminal bouton neuron projection terminus Supporting Evidence: PMID:7298720 Immunocytochemical experiments at the electron microscope level demonstrate that these antibodies bind the vesicles in many different types of nerve terminals PMID:10397765 Syt IV colocalizes with Syt I in the tips of the neurites |
| GO:0043195 terminal bouton | HDA PMID:24876496 Composition of isolated synaptic boutons reveals the amounts... | ACCEPT | Summary: Quantitative proteomics/imaging of isolated synaptic boutons includes Syt1. Reason: Syt1 is among the abundant exocytotic proteins of terminal boutons; core neuronal location. Supporting Evidence: PMID:24876496 super-resolution fluorescence microscopy to localize the proteins |
| GO:0044306 neuron projection terminus | IDA PMID:10397765 Functional and biochemical analysis of the C2 domains of syn... | KEEP AS NON CORE | Summary: Syt I localises to neurite tips in PC12 cells. Reason: Full text read; neuroendocrine-cell context. Supporting Evidence: PMID:10397765 Syt IV colocalizes with Syt I in the tips of the neurites |
| GO:0045211 postsynaptic membrane | IDA PMID:28686803 The calcium sensor synaptotagmin 1 is expressed and regulate... | KEEP AS NON CORE | Summary: Immunogold EM detects Syt1 in postsynaptic spines. Reason: Immunogold EM (abstract-only) detects Syt1 in hippocampal postsynaptic spines on cytoplasmic vesicles and at the PSD. A genuine but minor localisation with no established function; non-core. Supporting Evidence: PMID:28686803 We report for the first time that synaptotagmin 1 is present in rat hippocampal postsynaptic spines, both on cytoplasmic vesicles and at the postsynaptic density |
| GO:0045956 positive regulation of calcium ion-dependent exocytosis | IDA PMID:21551071 Release mode of large and small dense-core vesicles specifie... | ACCEPT | Summary: Syt1-bearing dense-core vesicles in PC12 cells fuse in response to stimulation; Syt isoform specifies release mode. Reason: Full text available; Syt1 functions as a Ca2+ sensor promoting DCV exocytosis. Supporting Evidence: PMID:21551071 We show that these isoforms sort to populations of dense-core vesicles that differ in size PMID:17686463 We conclude that Syt I and Syt IX function redundantly in Ca(2+)-sensing and fusion pore dilation on LDCVs in PC12 cells |
| GO:0046929 negative regulation of neurotransmitter secretion | IMP PMID:9570782 Functional analysis of the C2A domain of synaptotagmin 1: im... | KEEP AS NON CORE | Summary: Injected recombinant C2A fragments inhibit secretion via a polylysine motif. Reason: The IMP is a dominant-negative fragment experiment, which by itself would not show a negative role. However, Syt1 genuinely clamps spontaneous and Ca2+-independent fusion (deletion massively increases spontaneous release), so a negative regulatory contribution to neurotransmitter secretion holds; non-core relative to its activator role. Supporting Evidence: PMID:9570782 Our analyses reveal that a polylysine motif at residues 189-192 confers an inhibitory effect on secretion by recombinant synaptotagmin C2A fragments PMID:19412166 Paradoxically, Syt1 deletions (as opposed to point mutations) massively increased spontaneous release PMID:20688915 Although rat SYT1 promotes fusion in the presence of Ca2+, this isoform also serves to clamp or inhibit fusion in the absence of Ca2+ |
| GO:0046982 protein heterodimerization activity | IPI PMID:10397765 Functional and biochemical analysis of the C2 domains of syn... | KEEP AS NON CORE | Summary: Syt IV C2B hetero-oligomerises with Syt I. Reason: Full text read; in vitro heteromerisation. Supporting Evidence: PMID:10397765 Conversely, the C2B domain of Syt IV contains calcium binding properties, which permit homo-oligomerization as well as hetero-oligomerization with Syt I |
| GO:0048306 calcium-dependent protein binding | IDA PMID:10397765 Functional and biochemical analysis of the C2 domains of syn... | KEEP AS NON CORE | Summary: Syt I C2A binds syntaxin-1A in a Ca2+-dependent manner. Reason: Ca2+-dependent protein binding is true (Ca2+-promoted SNARE/syntaxin binding, Ca2+-triggered oligomerisation) but the informative activities are captured by SNARE binding and syntaxin-1 binding; non-core. Supporting Evidence: PMID:10397765 In contrast, the Syt I C2A domain bound Stx 1a in a calcium-dependent manner |
| GO:0048306 calcium-dependent protein binding | IDA PMID:20688915 Rat and Drosophila synaptotagmin 4 have opposite effects dur... | KEEP AS NON CORE | Summary: Rat SYT1 shows Ca2+-stimulated t-SNARE binding. Reason: Ca2+-dependent protein binding is true (Ca2+-promoted SNARE/syntaxin binding, Ca2+-triggered oligomerisation) but the informative activities are captured by SNARE binding and syntaxin-1 binding; non-core. Supporting Evidence: PMID:20688915 In contrast, rat SYT1, fly SYT1, and fly SYT4 all exhibited weak t-SNARE binding activity in the absence of Ca2+ and much stronger binding in the presence of Ca2+ |
| GO:0048306 calcium-dependent protein binding | IDA PMID:22711810 Cis- and trans-membrane interactions of synaptotagmin-1. | KEEP AS NON CORE | Summary: Ca2+-dependent interactions of membrane-anchored Syt1 with SNAREs. Reason: Ca2+-dependent protein binding is true (Ca2+-promoted SNARE/syntaxin binding, Ca2+-triggered oligomerisation) but the informative activities are captured by SNARE binding and syntaxin-1 binding; non-core. Supporting Evidence: PMID:22711810 In neurotransmission synaptotagmin-1 tethers synaptic vesicles to the presynaptic plasma membrane by binding to acidic membrane lipids and SNAREs and promotes rapid SNARE-mediated fusion upon Ca(2+) triggering |
| GO:0048306 calcium-dependent protein binding | IDA PMID:9830048 Delineation of the oligomerization, AP-2 binding, and synpri... | KEEP AS NON CORE | Summary: Ca2+-promoted hetero-oligomerisation of Syt1 with Syt3/Syt4. Reason: Ca2+-dependent protein binding is true (Ca2+-promoted SNARE/syntaxin binding, Ca2+-triggered oligomerisation) but the informative activities are captured by SNARE binding and syntaxin-1 binding; non-core. Supporting Evidence: PMID:9830048 Ca2+ promoted the hetero-oligomerization of synaptotagmin I with synaptotagmins III and IV |
| GO:0048306 calcium-dependent protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer. Reason: Ca2+-dependent protein binding is true (Ca2+-promoted SNARE/syntaxin binding, Ca2+-triggered oligomerisation) but the informative activities are captured by SNARE binding and syntaxin-1 binding; non-core. Supporting Evidence: PMID:12526776 Ca(2+) induces binding of the synaptotagmin C(2) domains to SNARE proteins, whereas Sr(2+) even at high concentrations does not |
| GO:0048306 calcium-dependent protein binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO transfer from mouse Syt1. Reason: Ca2+-dependent protein binding is true (Ca2+-promoted SNARE/syntaxin binding, Ca2+-triggered oligomerisation) but the informative activities are captured by SNARE binding and syntaxin-1 binding; non-core. Supporting Evidence: PMID:12526776 Ca(2+) induces binding of the synaptotagmin C(2) domains to SNARE proteins, whereas Sr(2+) even at high concentrations does not |
| GO:0048786 presynaptic active zone | IDA PMID:28686803 The calcium sensor synaptotagmin 1 is expressed and regulate... | KEEP AS NON CORE | Summary: Immunogold EM localises Syt1 at the presynaptic active zone region. Reason: Docked synaptic vesicles carrying Syt1 sit at the active zone, where Syt1 acts; the accepted core location is the vesicle membrane, so the active-zone term is kept as non-core context. Supporting Evidence: PMID:28686803 We report for the first time that synaptotagmin 1 is present in rat hippocampal postsynaptic spines, both on cytoplasmic vesicles and at the postsynaptic density PMID:22711810 In neurotransmission synaptotagmin-1 tethers synaptic vesicles to the presynaptic plasma membrane by binding to acidic membrane lipids and SNAREs and promotes rapid SNARE-mediated fusion upon Ca(2+) triggering |
| GO:0048791 calcium ion-regulated exocytosis of neurotransmitter | ISO GO_REF:0000121 | MODIFY | Summary: ISO transfer of calcium ion-regulated exocytosis of neurotransmitter from mouse Syt1. Reason: Syt1 specifically mediates the fast component; fast, calcium ion-dependent exocytosis of neurotransmitter (GO:0098746, is_a GO:0048791) is the more specific term already carried. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:99667 SUPPORTS TRANSFER Mouse KO data support the transfer at the more specific level. Proposed replacements: fast, calcium ion-dependent exocytosis of neurotransmitter Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired |
| GO:0050750 low-density lipoprotein particle receptor binding | IEA GO_REF:0000107 | UNDECIDED | Summary: Electronic transfer of low-density lipoprotein particle receptor binding. Reason: No experimental basis for LDL receptor binding by Syt1 could be found in the cached literature or by PubMed search; the human source annotation could not be traced. Undecided. Supporting Evidence: UniProtKB:P21707 Belongs to the synaptotagmin family. |
| GO:0050750 low-density lipoprotein particle receptor binding | ISO GO_REF:0000121 | UNDECIDED | Summary: ISO transfer of low-density lipoprotein particle receptor binding from human SYT1. Reason: No experimental basis for LDL receptor binding by Syt1 could be found in the cached literature or by PubMed search; the human source annotation could not be traced. Undecided. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P21579 UNRESOLVED The publication behind the human SYT1 LDL-receptor-binding annotation was not traced in this session. Supporting Evidence: UniProtKB:P21707 Belongs to the synaptotagmin family. |
| GO:0050806 positive regulation of synaptic transmission | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Orthology transfer (IEA/ISO/ISS) of positive regulation of synaptic transmission from mouse Syt1. Reason: Positive regulation of synaptic transmission is the physiological consequence of Syt1 acting as the Ca2+ trigger for release; true but downstream of the core process; non-core. Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired |
| GO:0050806 positive regulation of synaptic transmission | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Orthology transfer (IEA/ISO/ISS) of positive regulation of synaptic transmission from mouse Syt1. Reason: Positive regulation of synaptic transmission is the physiological consequence of Syt1 acting as the Ca2+ trigger for release; true but downstream of the core process; non-core. Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired |
| GO:0050806 positive regulation of synaptic transmission | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Orthology transfer (IEA/ISO/ISS) of positive regulation of synaptic transmission from mouse Syt1. Reason: Positive regulation of synaptic transmission is the physiological consequence of Syt1 acting as the Ca2+ trigger for release; true but downstream of the core process; non-core. Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired |
| GO:0051205 protein insertion into membrane | IMP PMID:11805296 C2A activates a cryptic Ca(2+)-triggered membrane penetratio... | MARK AS OVER ANNOTATED | Summary: Ca2+-binding loops of C2A and C2B penetrate lipid bilayers. Reason: Full text read. Membrane penetration of the Syt1 C2 loops is part of its Ca2+-dependent phospholipid-binding activity, not a process of inserting proteins into membranes; the BP term overstates and mis-frames the finding. Supporting Evidence: PMID:11805296 Surprisingly, these reporters revealed that, analogous to C2A, a Ca(2+)-binding loop in C2B directly penetrates into lipid bilayers |
| GO:0051259 protein complex oligomerization | IDA PMID:24973220 The juxtamembrane linker of full-length synaptotagmin 1 cont... | KEEP AS NON CORE | Summary: Full-length Syt1 oligomerises in membranes via the linker. Reason: Syt1 self-associates: Ca2+-triggered C2B-mediated dimerisation, linker GXXXG-mediated oligomerisation, and LLPS of the linker. Real but its physiological role remains debated; non-core. Supporting Evidence: PMID:24973220 Pulse dipolar EPR spectroscopy provides evidence that purified full-length Syt1 is oligomerized in the membrane, and mutagenesis indicates that a glycine zipper/GXXXG motif within the linker helps mediate oligomerization |
| GO:0051291 protein heterooligomerization | IPI PMID:9830048 Delineation of the oligomerization, AP-2 binding, and synpri... | KEEP AS NON CORE | Summary: Ca2+-promoted hetero-oligomerisation of Syt1 with Syt3 and Syt4. Reason: Real in vitro heteromerisation; physiological role not established; non-core. Supporting Evidence: PMID:9830048 Ca2+ promoted the hetero-oligomerization of synaptotagmin I with synaptotagmins III and IV |
| GO:0051291 protein heterooligomerization | IPI PMID:9830048 Delineation of the oligomerization, AP-2 binding, and synpri... | KEEP AS NON CORE | Summary: Ca2+-promoted hetero-oligomerisation of Syt1 with Syt3 and Syt4. Reason: Real in vitro heteromerisation; physiological role not established; non-core. Supporting Evidence: PMID:9830048 Ca2+ promoted the hetero-oligomerization of synaptotagmin I with synaptotagmins III and IV |
| GO:0051592 response to calcium ion | IDA PMID:18508778 Analysis of the synaptotagmin family during reconstituted me... | MODIFY | Summary: Syt I confers Ca2+ responsiveness to SNARE-catalysed fusion. Reason: Response to calcium ion is correct but general; Syt1 detects the Ca2+ stimulus directly, so detection of calcium ion (GO:0005513, is_a response to calcium ion), carried by this gene, is more specific. Proposed replacements: detection of calcium ion Supporting Evidence: PMID:18508778 Syts I-III, V-VII, IX, and X stimulated fusion in response to Ca2+ |
| GO:0051966 regulation of synaptic transmission, glutamatergic | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Orthology transfer of regulation of glutamatergic synaptic transmission from mouse Syt1. Reason: Syt1 is the fast Ca2+ sensor at glutamatergic (and GABAergic) synapses; the synaptic-transmission term is a downstream physiological readout; non-core. Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired |
| GO:0051966 regulation of synaptic transmission, glutamatergic | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Orthology transfer of regulation of glutamatergic synaptic transmission from mouse Syt1. Reason: Syt1 is the fast Ca2+ sensor at glutamatergic (and GABAergic) synapses; the synaptic-transmission term is a downstream physiological readout; non-core. Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired |
| GO:0051966 regulation of synaptic transmission, glutamatergic | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Orthology transfer of regulation of glutamatergic synaptic transmission from mouse Syt1. Reason: Syt1 is the fast Ca2+ sensor at glutamatergic (and GABAergic) synapses; the synaptic-transmission term is a downstream physiological readout; non-core. Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired |
| GO:0060076 excitatory synapse | IDA PMID:19730411 Neuroligin-1 performs neurexin-dependent and neurexin-indepe... | KEEP AS NON CORE | Summary: Syt1 used as a presynaptic marker in a neuroligin-1 synapse-formation study. Reason: Syt1 is present at excitatory presynaptic terminals; a correct but contextual location. Supporting Evidence: PMID:7298720 Immunocytochemical experiments at the electron microscope level demonstrate that these antibodies bind the vesicles in many different types of nerve terminals |
| GO:0060080 inhibitory postsynaptic potential | IMP PMID:35701163 Polybasic Patches in Both C2 Domains of Synaptotagmin-1 Are ... | MARK AS OVER ANNOTATED | Summary: Syt1 polybasic patch mutants reduce evoked IPSCs in cultured Syt1-KO cortical neurons. Reason: Full text read. Evoked IPSC amplitude is a readout of presynaptic GABA release triggered by Syt1; the postsynaptic potential itself is generated by postsynaptic GABA receptors. Necessity for the outcome is not participation in the postsynaptic process. Supporting Evidence: PMID:35701163 Synaptotagmin-1 (Syt1) is a vesicular calcium sensor required for synchronous neurotransmitter release |
| GO:0061588 calcium activated phospholipid scrambling | IDA PMID:22229667 The importance of an asymmetric distribution of acidic lipid... | REMOVE | Summary: PS asymmetry between t- and v-SNARE liposomes required for Ca2+-dependent Syt1 stimulation of docking/fusion. Reason: Full text read for both papers. Calcium activated phospholipid scrambling is defined as movement of phospholipids from one leaflet of the plasma membrane to the other. 21610074 shows lateral demixing of PS within bilayers by Syt1 C2 domains, and 22229667 shows that an asymmetric distribution of PS between the two fusing membranes is required for Ca2+ stimulation; neither shows transbilayer movement, and Syt1 has no scramblase domain. The term is a mis-mapping of the finding. Supporting Evidence: PMID:22229667 Thus for Syt1 to function as a Ca2+ sensor, a charge asymmetry appears to be important and this may play a role in steering Syt1 to productively trans bind to the plasma membrane PMID:22229667 The single-vesicle-fusion assay indicates that the Ca2+-dependent enhancement was mainly on docking, whereas its effect on lipid mixing was small |
| GO:0061588 calcium activated phospholipid scrambling | IMP PMID:21610074 Synaptotagmin 1 modulates lipid acyl chain order in lipid bi... | REMOVE | Summary: Syt1 C2 domains demix PS laterally and disorder its acyl chains. Reason: Full text read for both papers. Calcium activated phospholipid scrambling is defined as movement of phospholipids from one leaflet of the plasma membrane to the other. 21610074 shows lateral demixing of PS within bilayers by Syt1 C2 domains, and 22229667 shows that an asymmetric distribution of PS between the two fusing membranes is required for Ca2+ stimulation; neither shows transbilayer movement, and Syt1 has no scramblase domain. The term is a mis-mapping of the finding. Supporting Evidence: PMID:21610074 These data suggest that syt1 might facilitate SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors)-mediated membrane fusion by phase separating PS file:rat/Syt1/Syt1-deep-research-manual.md Neither paper reports transbilayer lipid movement. |
| GO:0061669 spontaneous neurotransmitter secretion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ISO transfer of spontaneous neurotransmitter secretion from mouse Syt1. Reason: In mouse cortical neurons Ca2+ binding to Syt1 triggers most spontaneous release, while Syt1 deletion also unclamps a second sensor; Syt1 genuinely acts in spontaneous release, but evoked synchronous release is its core role. Supporting Evidence: PMID:19412166 in addition to serving as a Ca2+ sensor for spontaneous and evoked release, Syt1 clamped a second, more sensitive Ca2+ sensor for spontaneous release |
| GO:0061891 calcium ion sensor activity | EXP PMID:24001110 The synaptotagmin 1 linker may function as an electrostatic ... | ACCEPT | Summary: Syt1 is a major Ca2+ sensor; the linker is required for Ca2+-dependent fusion pore opening. Reason: Syt1 binds Ca2+ through its C2 domains and responds by binding membranes/SNAREs to trigger fusion: the defining activity of the gene. Supporting Evidence: PMID:24001110 we found that the linker region of Syt1 is essential for its two signature functions: Ca2+-independent vesicle docking and Ca2+-dependent fusion pore opening |
| GO:0061891 calcium ion sensor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Synaptotagmin-family IBA for calcium ion sensor activity. Reason: Syt1 binds Ca2+ through its C2 domains and responds by binding membranes/SNAREs to trigger fusion: the defining activity of the gene. Supporting Evidence: UniProtKB:P21707 Calcium sensor that participates in triggering neurotransmitter release at the synapse PMID:8253763 Our results show that this C2 domain by itself binds Ca2+ and phospholipids with high affinity (half-maximal binding at 4-6 microM free Ca2+) and exhibits strong positive cooperativity |
| GO:0061891 calcium ion sensor activity | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic transfer of calcium ion sensor activity. Reason: Syt1 binds Ca2+ through its C2 domains and responds by binding membranes/SNAREs to trigger fusion: the defining activity of the gene. Supporting Evidence: UniProtKB:P21707 Calcium sensor that participates in triggering neurotransmitter release at the synapse |
| GO:0061891 calcium ion sensor activity | ISO GO_REF:0000121 | ACCEPT | Summary: ISO transfer from mouse Syt1. Reason: Syt1 binds Ca2+ through its C2 domains and responds by binding membranes/SNAREs to trigger fusion: the defining activity of the gene. Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired |
| GO:0070382 exocytic vesicle | IBA GO_REF:0000033 | MODIFY | Summary: Synaptotagmin-family IBA for exocytic vesicle. Reason: Exocytic vesicle is correct; for Syt1 the specific location is synaptic vesicle membrane (and dense-core vesicles in neuroendocrine cells), both accepted in this review. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000001283 SUPPORTS TRANSFER Deep family node covering isoforms on diverse exocytic vesicles; Syt1-specific vesicle type is known. Proposed replacements: synaptic vesicle membrane dense core granule Supporting Evidence: UniProtKB:P21707 Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane |
| GO:0071277 cellular response to calcium ion | IMP PMID:12526776 Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1... | MODIFY | Summary: In Syt1 KO mice the fast component of Ca2+- and Sr2+-induced release is impaired. Reason: Cellular response to calcium ion is correct but general; Syt1 directly detects the Ca2+ signal, captured by detection of calcium ion (GO:0005513). Proposed replacements: detection of calcium ion Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired |
| GO:0071911 synchronous neurotransmitter secretion | ISO GO_REF:0000121 | ACCEPT | Summary: ISO transfer of synchronous neurotransmitter secretion from mouse Syt1. Reason: Syt1 KO abolishes fast synchronous release; core process. Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired PMID:35701163 Synaptotagmin-1 (Syt1) is a vesicular calcium sensor required for synchronous neurotransmitter release |
| GO:0097708 intracellular vesicle | IDA PMID:14715137 N-glycosylation is essential for vesicular targeting of syna... | MODIFY | Summary: Glycosylation-dependent targeting of Syt1 to intracellular vesicles. Reason: Syt1 is an integral synaptic vesicle membrane protein (single TM helix, cytoplasmic C2 domains); synaptic vesicle membrane (GO:0030672) is the more specific location and is already accepted. Proposed replacements: synaptic vesicle membrane Supporting Evidence: PMID:14715137 mutation of the N-terminal N-glycosylation site of synaptotagmin 1 redirects synaptotagmin 1 from vesicles to the plasma membrane |
| GO:0098686 hippocampal mossy fiber to CA3 synapse | IDA PMID:7298720 Identification of a synaptic vesicle-specific membrane prote... | KEEP AS NON CORE | Summary: Antibodies to the 65-kDa antigen label vesicles in many nerve-terminal types. Reason: A correct but contextual synapse type; Syt1 is present in most CNS presynaptic terminals. Supporting Evidence: PMID:7298720 Immunocytochemical experiments at the electron microscope level demonstrate that these antibodies bind the vesicles in many different types of nerve terminals |
| GO:0098746 fast, calcium ion-dependent exocytosis of neurotransmitter | IEA GO_REF:0000107 | ACCEPT | Summary: Orthology transfer of fast, calcium ion-dependent exocytosis of neurotransmitter from mouse Syt1. Reason: Syt1 is the Ca2+ sensor for the fast synchronous component of neurotransmitter release; core process. Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired PMID:26437117 In forebrain neurons, Ca(2+) triggers exocytosis of readily releasable vesicles by binding to synaptotagmin-1 and -7, thereby inducing fast and slow vesicle exocytosis, respectively |
| GO:0098746 fast, calcium ion-dependent exocytosis of neurotransmitter | ISO GO_REF:0000121 | ACCEPT | Summary: Orthology transfer of fast, calcium ion-dependent exocytosis of neurotransmitter from mouse Syt1. Reason: Syt1 is the Ca2+ sensor for the fast synchronous component of neurotransmitter release; core process. Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired PMID:26437117 In forebrain neurons, Ca(2+) triggers exocytosis of readily releasable vesicles by binding to synaptotagmin-1 and -7, thereby inducing fast and slow vesicle exocytosis, respectively |
| GO:0098746 fast, calcium ion-dependent exocytosis of neurotransmitter | ISS GO_REF:0000024 | ACCEPT | Summary: Orthology transfer of fast, calcium ion-dependent exocytosis of neurotransmitter from mouse Syt1. Reason: Syt1 is the Ca2+ sensor for the fast synchronous component of neurotransmitter release; core process. Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired PMID:26437117 In forebrain neurons, Ca(2+) triggers exocytosis of readily releasable vesicles by binding to synaptotagmin-1 and -7, thereby inducing fast and slow vesicle exocytosis, respectively |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Orthology transfer of glutamatergic synapse. Reason: Syt1 acts at glutamatergic presynaptic terminals; contextual location. Supporting Evidence: PMID:7298720 Immunocytochemical experiments at the electron microscope level demonstrate that these antibodies bind the vesicles in many different types of nerve terminals |
| GO:0098978 glutamatergic synapse | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Orthology transfer of glutamatergic synapse. Reason: Syt1 acts at glutamatergic presynaptic terminals; contextual location. Supporting Evidence: PMID:7298720 Immunocytochemical experiments at the electron microscope level demonstrate that these antibodies bind the vesicles in many different types of nerve terminals |
| GO:0099023 vesicle tethering complex | IDA PMID:22810233 SNAREpin assembly by Munc18-1 requires previous vesicle dock... | MARK AS OVER ANNOTATED | Summary: Syt1 docks vesicles prior to Munc18-1 action. Reason: Syt1 itself tethers/docks vesicles (vesicle membrane tethering activity, accepted for this gene); the abstracts do not show it is a subunit of a tethering protein complex. Complex membership is over-stated. Supporting Evidence: PMID:22810233 vesicle docking by synaptotagmin 1 is a prerequisite for Munc18-1 to accelerate trans-SNARE complex (SNAREpin) assembly and membrane fusion |
| GO:0099023 vesicle tethering complex | IDA PMID:24973220 The juxtamembrane linker of full-length synaptotagmin 1 cont... | MARK AS OVER ANNOTATED | Summary: Full-length Syt1 oligomerises and captures vesicles in a Ca2+-dependent manner. Reason: Syt1 itself tethers/docks vesicles (vesicle membrane tethering activity, accepted for this gene); the abstracts do not show it is a subunit of a tethering protein complex. Complex membership is over-stated. Supporting Evidence: PMID:24973220 The total internal reflection fluorescence-based vesicle binding assay demonstrates that full-length Syt1 that is reconstituted into supported lipid bilayers will capture vesicles containing negatively charged lipid in a Ca(2+)-dependent manner |
| GO:0099502 calcium-dependent activation of synaptic vesicle fusion | IBA GO_REF:0000033 | ACCEPT | Summary: Syt1/2 subfamily IBA. Reason: Syt1 binds Ca2+ and triggers fusion of primed synaptic vesicles with the presynaptic membrane; this is the core process. Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired |
| GO:0099502 calcium-dependent activation of synaptic vesicle fusion | IDA PMID:22229667 The importance of an asymmetric distribution of acidic lipid... | ACCEPT | Summary: Ca2+-dependent Syt1 stimulation of docking/fusion in reconstituted assays. Reason: Syt1 binds Ca2+ and triggers fusion of primed synaptic vesicles with the presynaptic membrane; this is the core process. Supporting Evidence: PMID:22229667 Thus for Syt1 to function as a Ca2+ sensor, a charge asymmetry appears to be important and this may play a role in steering Syt1 to productively trans bind to the plasma membrane |
| GO:0099502 calcium-dependent activation of synaptic vesicle fusion | IDA PMID:23663838 Rapid fusion of synaptic vesicles with reconstituted target ... | ACCEPT | Summary: Ca2+ boosts fusion of purified SVs with t-SNARE bilayers through a synaptotagmin-specific mechanism. Reason: Syt1 binds Ca2+ and triggers fusion of primed synaptic vesicles with the presynaptic membrane; this is the core process. Supporting Evidence: PMID:23663838 Calcium boosts fusion through a combined general electrostatic and synaptotagmin-specific mechanism |
| GO:0099502 calcium-dependent activation of synaptic vesicle fusion | IDA PMID:24973220 The juxtamembrane linker of full-length synaptotagmin 1 cont... | ACCEPT | Summary: Reconstituted full-length Syt1 captures vesicles in a Ca2+-dependent manner. Reason: Syt1 binds Ca2+ and triggers fusion of primed synaptic vesicles with the presynaptic membrane; this is the core process. Supporting Evidence: PMID:24973220 The total internal reflection fluorescence-based vesicle binding assay demonstrates that full-length Syt1 that is reconstituted into supported lipid bilayers will capture vesicles containing negatively charged lipid in a Ca(2+)-dependent manner |
| GO:0099502 calcium-dependent activation of synaptic vesicle fusion | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic transfer. Reason: Syt1 binds Ca2+ and triggers fusion of primed synaptic vesicles with the presynaptic membrane; this is the core process. Supporting Evidence: UniProtKB:P21707 Calcium sensor that participates in triggering neurotransmitter release at the synapse |
| GO:0099502 calcium-dependent activation of synaptic vesicle fusion | ISO GO_REF:0000121 | ACCEPT | Summary: ISO transfer from mouse Syt1. Reason: Syt1 binds Ca2+ and triggers fusion of primed synaptic vesicles with the presynaptic membrane; this is the core process. Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired |
| GO:0099523 presynaptic cytosol | IDA PMID:28686803 The calcium sensor synaptotagmin 1 is expressed and regulate... | MARK AS OVER ANNOTATED | Summary: Immunogold particles over presynaptic/postsynaptic cytoplasm. Reason: Syt1 is a single-pass integral membrane protein; gold particles over cytoplasm label vesicles (the abstract explicitly says cytoplasmic vesicles). A cytosol location is not consistent with its topology. Supporting Evidence: PMID:28686803 We report for the first time that synaptotagmin 1 is present in rat hippocampal postsynaptic spines, both on cytoplasmic vesicles and at the postsynaptic density UniProtKB:P21707 Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane |
| GO:0099524 postsynaptic cytosol | IDA PMID:28686803 The calcium sensor synaptotagmin 1 is expressed and regulate... | MARK AS OVER ANNOTATED | Summary: Immunogold particles over presynaptic/postsynaptic cytoplasm. Reason: Syt1 is a single-pass integral membrane protein; gold particles over cytoplasm label vesicles (the abstract explicitly says cytoplasmic vesicles). A cytosol location is not consistent with its topology. Supporting Evidence: PMID:28686803 We report for the first time that synaptotagmin 1 is present in rat hippocampal postsynaptic spines, both on cytoplasmic vesicles and at the postsynaptic density UniProtKB:P21707 Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane |
| GO:0140032 glycosylation-dependent protein binding | IMP PMID:14715137 N-glycosylation is essential for vesicular targeting of syna... | MARK AS OVER ANNOTATED | Summary: Mutating the N-glycosylation site of Syt1 redirects it from vesicles to the plasma membrane. Reason: Abstract-only. The finding is that Syt1 must itself be glycosylated for vesicular targeting; glycosylation-dependent protein binding means binding to a partner upon the partner being glycosylated. No glycan-dependent binding partner of Syt1 is identified in the abstract. Supporting Evidence: PMID:14715137 mutation of the N-terminal N-glycosylation site of synaptotagmin 1 redirects synaptotagmin 1 from vesicles to the plasma membrane |
| GO:0140693 molecular condensate scaffold activity | EXP PMID:38177243 The juxtamembrane linker of synaptotagmin 1 regulates Ca(2+)... | KEEP AS NON CORE | Summary: The Syt1 linker IDR is necessary and sufficient for liquid-liquid phase separation. Reason: The Syt1 juxtamembrane linker undergoes LLPS in vitro and in cells and condensates tune Ca2+ sensitivity. A real self-associative property with a proposed regulatory role; non-core. Supporting Evidence: PMID:38177243 this linker segment harbors a lysine-rich, intrinsically disordered region that is necessary and sufficient to mediate liquid-liquid phase separation (LLPS) PMID:38177243 Interestingly, condensate formation negatively regulates the Ca2+-sensitivity of syt1 |
| GO:0140693 molecular condensate scaffold activity | IDA PMID:38177243 The juxtamembrane linker of synaptotagmin 1 regulates Ca(2+)... | KEEP AS NON CORE | Summary: The Syt1 linker IDR is necessary and sufficient for liquid-liquid phase separation. Reason: The Syt1 juxtamembrane linker undergoes LLPS in vitro and in cells and condensates tune Ca2+ sensitivity. A real self-associative property with a proposed regulatory role; non-core. Supporting Evidence: PMID:38177243 this linker segment harbors a lysine-rich, intrinsically disordered region that is necessary and sufficient to mediate liquid-liquid phase separation (LLPS) PMID:38177243 Interestingly, condensate formation negatively regulates the Ca2+-sensitivity of syt1 |
| GO:0140694 membraneless organelle assembly | IDA PMID:38177243 The juxtamembrane linker of synaptotagmin 1 regulates Ca(2+)... | MARK AS OVER ANNOTATED | Summary: Syt1 forms droplets that fuse in living cells. Reason: Full text read. Syt1 condensates are a self-associated state of a membrane protein, not an identified membraneless organelle; the assembly term overstates the finding. Supporting Evidence: PMID:38177243 this linker segment harbors a lysine-rich, intrinsically disordered region that is necessary and sufficient to mediate liquid-liquid phase separation (LLPS) |
| GO:0150037 regulation of calcium-dependent activation of synaptic vesicle fusion | IMP PMID:33468652 Synaptotagmin-1-, Munc18-1-, and Munc13-1-dependent liposome... | MODIFY | Summary: Syt1 stimulates Munc18-1/Munc13-1-dependent liposome fusion in a Ca2+-binding-dependent manner. Reason: Syt1 is the Ca2+-dependent activator itself, not a regulator of that activation; calcium-dependent activation of synaptic vesicle fusion (GO:0099502) is the appropriate term. Proposed replacements: calcium-dependent activation of synaptic vesicle fusion Supporting Evidence: PMID:33468652 synaptotagmin-1 strongly stimulates fusion under these conditions. Such stimulation depends on Ca2+ binding to the two C2 domains of synaptotagmin-1 |
| GO:1903235 positive regulation of calcium ion-dependent exocytosis of neurotransmitter | IEA GO_REF:0000107 | ACCEPT | Summary: Orthology transfer of positive regulation of calcium ion-dependent exocytosis of neurotransmitter. Reason: Syt1 promotes Ca2+-triggered neurotransmitter exocytosis as its sensor; consistent with the core process. Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired UniProtKB:P21707 Calcium sensor that participates in triggering neurotransmitter release at the synapse |
| GO:1903235 positive regulation of calcium ion-dependent exocytosis of neurotransmitter | ISO GO_REF:0000121 | ACCEPT | Summary: Orthology transfer of positive regulation of calcium ion-dependent exocytosis of neurotransmitter. Reason: Syt1 promotes Ca2+-triggered neurotransmitter exocytosis as its sensor; consistent with the core process. Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired UniProtKB:P21707 Calcium sensor that participates in triggering neurotransmitter release at the synapse |
| GO:1903235 positive regulation of calcium ion-dependent exocytosis of neurotransmitter | ISS GO_REF:0000024 | ACCEPT | Summary: Orthology transfer of positive regulation of calcium ion-dependent exocytosis of neurotransmitter. Reason: Syt1 promotes Ca2+-triggered neurotransmitter exocytosis as its sensor; consistent with the core process. Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired UniProtKB:P21707 Calcium sensor that participates in triggering neurotransmitter release at the synapse |
| GO:1903305 regulation of regulated secretory pathway | IMP PMID:12526776 Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1... | MODIFY | Summary: Sr2+/Ca2+ binding to Syt1 C2B triggers fast release; KO impairs fast release. Reason: Regulation of regulated secretory pathway is broad; Syt1 positively regulates Ca2+-dependent neurotransmitter exocytosis (GO:1903235, a descendant via positive regulation of Ca2+-dependent exocytosis), accepted for this gene. Proposed replacements: positive regulation of calcium ion-dependent exocytosis of neurotransmitter Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired |
| GO:1903861 positive regulation of dendrite extension | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Orthology transfer from human SYT1 of positive regulation of dendrite extension. Reason: The human source relates to dendrite formation by melanocytes (UniProt by-similarity text), a peripheral non-neuronal role; kept as non-core. Supporting Evidence: UniProtKB:P21707 Plays a role in dendrite formation by melanocytes |
| GO:1903861 positive regulation of dendrite extension | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Orthology transfer from human SYT1 of positive regulation of dendrite extension. Reason: The human source relates to dendrite formation by melanocytes (UniProt by-similarity text), a peripheral non-neuronal role; kept as non-core. Supporting Evidence: UniProtKB:P21707 Plays a role in dendrite formation by melanocytes |
| GO:2000300 regulation of synaptic vesicle exocytosis | IBA GO_REF:0000033 | MODIFY | Summary: Syt1/2 subfamily IBA for regulation of synaptic vesicle exocytosis. Reason: Syt1 promotes synaptic vesicle exocytosis as its Ca2+ trigger; calcium-dependent activation of synaptic vesicle fusion (GO:0099502), a positive-regulation descendant, is the specific accepted term. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000740739 SUPPORTS TRANSFER Syt1/2 subfamily node; activator role conserved. Proposed replacements: calcium-dependent activation of synaptic vesicle fusion Supporting Evidence: PMID:12526776 We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired |
| GO:2000300 regulation of synaptic vesicle exocytosis | IDA PMID:28057568 Localization of Rab3A-binding site on C2A domain of synaptot... | MODIFY | Summary: Rab3A binding to Syt1 C2A proposed to regulate C2A-mediated fusion. Reason: Syt1 promotes synaptic vesicle exocytosis as its Ca2+ trigger; calcium-dependent activation of synaptic vesicle fusion (GO:0099502), a positive-regulation descendant, is the specific accepted term. Proposed replacements: calcium-dependent activation of synaptic vesicle fusion Supporting Evidence: PMID:28057568 Our previous study demonstrated that Rab3A, a small GTP-binding protein, is a new interacting partner of Syt I and could bind to both of the C2 domains UniProtKB:P21707 Calcium sensor that participates in triggering neurotransmitter release at the synapse |
| GO:7770062 vesicle membrane tethering activity | IDA PMID:22810233 SNAREpin assembly by Munc18-1 requires previous vesicle dock... | ACCEPT | Summary: Syt1 docks (tethers) SUVs to t-SNARE GUVs before Munc18-1-driven SNAREpin assembly. Reason: Syt1 bridges vesicle and target membranes by binding anionic lipids and SNAREs; supported by several independent reconstitutions. Core activity. Supporting Evidence: PMID:22810233 vesicle docking by synaptotagmin 1 is a prerequisite for Munc18-1 to accelerate trans-SNARE complex (SNAREpin) assembly and membrane fusion PMID:22711810 In neurotransmission synaptotagmin-1 tethers synaptic vesicles to the presynaptic plasma membrane by binding to acidic membrane lipids and SNAREs and promotes rapid SNARE-mediated fusion upon Ca(2+) triggering PMID:24001110 we found that the linker region of Syt1 is essential for its two signature functions: Ca2+-independent vesicle docking and Ca2+-dependent fusion pore opening |
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Download this section (compressed HTML)Q: Should the RGD calcium activated phospholipid scrambling (GO:0061588) rows be retired, given that the cited papers report lateral PS demixing and dependence on inter-membrane PS asymmetry rather than transbilayer movement?
Q: What is the evidence behind the human SYT1 low-density lipoprotein particle receptor binding annotation propagated to rat Syt1?
Q: Is the Ca2+-triggered oligomerisation / juxtamembrane-linker phase separation of Syt1 required for its Ca2+-sensor function in vivo, or a regulatory modulation of it?
Experiment: Test whether linker-LLPS-deficient Syt1 mutants that preserve membrane and SNARE binding rescue synchronous release and spontaneous-release clamping in Syt1-knockout neurons.
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