SYN1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0030672 synaptic vesicle membrane	IBA GO_REF:0000033	ACCEPT	Summary: Synapsin-1 is a peripheral membrane protein that associates with synaptic vesicle membranes through its N-terminal domain A, which binds phospholipids with preference for negatively charged species [PMID:2110562, UniProt]. The protein coats synaptic vesicles and is concentrated at presynaptic terminals associated with SV clusters [Sansevrino 2023, Longfield 2024]. Reason: This is a core annotation for SYN1. The protein is well-established as a synaptic vesicle-associated protein that binds SV membranes extrinsically through its domain A. Deep research confirms SYN1 is concentrated at presynaptic terminals and enriched on SV clusters. IBA annotation is phylogenetically sound for this conserved function. Supporting Evidence: PMID:2110562 Synapsin I is a peripheral membrane protein of synaptic vesicles that mediates their attachment to the cytoskeleton. file:human/SYN1/SYN1-deep-research-falcon.md Synapsin-1 is concentrated at presynaptic terminals and enriched on SV clusters.
GO:0097091 synaptic vesicle clustering	IBA GO_REF:0000033	ACCEPT	Summary: Synaptic vesicle clustering is the primary function of synapsin-1. The protein maintains SV clusters within presynaptic boutons through multivalent interactions with vesicle membranes and actin, and through self-oligomerization. Recent studies show SYN1 drives vesicle condensation via liquid-liquid phase separation (LLPS) [Alfken 2024, Sansevrino 2023]. Loss of synapsin family members increases reserve SV mobility [Longfield 2024]. Reason: This is the core biological process function of SYN1. Deep research extensively documents that synapsin maintains SV clustering and the reserve pool; loss or knockout increases SV mobility and reduces vesicle packing. The IBA annotation correctly captures this conserved, central function across the synapsin family. Supporting Evidence: file:human/SYN1/SYN1-deep-research-falcon.md Synapsin-1 scaffolds SVs into dynamic clusters that form a reserve pool, modulating short-term plasticity by regulating SV mobility and availability for release. file:human/SYN1/SYN1-deep-research-falcon.md In synapsin triple knockout neurons, reserve-pool SV mobility increases; re-expression of synapsin capable of higher-order assembly restores immobilization and nanoclustering.
GO:0050808 synapse organization	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Synapsin-1 contributes to synapse organization through its role in maintaining synaptic vesicle pools and presynaptic structure. The protein is involved in synaptogenesis and regulation of axon outgrowth [PMID:21441247, UniProt]. However, this is a broader term than the more specific function of synaptic vesicle clustering. Reason: While SYN1 does contribute to synapse organization, this is a relatively broad term. The more specific function is synaptic vesicle clustering (GO:0097091). Synapse organization represents a higher-level process that SYN1 participates in, but is not its primary specific function. Keep as non-core to reflect the broader involvement without overstating specificity. Supporting Evidence: PMID:21441247 Here we report a Q555X mutation in synapsin 1 (SYN1), an X-linked gene encoding for a neuron-specific phosphoprotein implicated in the regulation of neurotransmitter release and synaptogenesis.
GO:0003779 actin binding	IEA GO_REF:0000043	ACCEPT	Summary: Synapsin-1 domain C binds actin, which is essential for its function in tethering synaptic vesicles to the cytoskeleton [PMID:2110562, UniProt]. The actin binding allows synapsin to crosslink SVs to the actin cytoskeleton and is regulated by phosphorylation. Reason: Actin binding is a well-documented molecular function of synapsin-1. The UniProt entry explicitly annotates domain C (residues 113-420) as actin-binding. Deep research confirms domain C interfaces for actin along with vesicle lipids. This IEA from UniProt keywords is accurate. Supporting Evidence: PMID:2110562 Synapsin I is a peripheral membrane protein of synaptic vesicles that mediates their attachment to the cytoskeleton. file:human/SYN1/SYN1-deep-research-falcon.md Synapsin-1's domain C binds ATP/ADP (calcium-facilitated) and actin.
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: Synapsin-1 contains an ATP-binding domain (domain C) that is structurally characterized as an ATP-grasp fold. The InterPro domains IPR020898 (Synapsin_ATP-bd_dom) and IPR013815 (ATP_grasp_subdomain_1) support this annotation. ATP binding is calcium-facilitated. Reason: ATP binding is supported by the domain architecture of synapsin-1. The protein has a well-characterized ATP-binding domain (domain C) with ATP-grasp fold structure. Deep research explicitly states domain C binds ATP/ADP. This IEA from InterPro mapping is accurate. Supporting Evidence: file:human/SYN1/SYN1-deep-research-falcon.md Synapsin-1's domain C binds ATP/ADP (calcium-facilitated) and actin.
GO:0005794 Golgi apparatus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt annotates Golgi apparatus localization based on subcellular location vocabulary mapping. This likely reflects transient localization during biosynthesis or trafficking rather than the primary functional localization at presynaptic terminals. Reason: While UniProt does note Golgi localization (by similarity), the primary functional localization of synapsin-1 is at presynaptic terminals and synaptic vesicles. Golgi localization may represent biosynthetic pathway rather than functional location. Keep as non-core to acknowledge this minor localization without implying it is primary. Supporting Evidence: file:human/SYN1/SYN1-uniprot.txt Golgi apparatus
GO:0007268 chemical synaptic transmission	IEA GO_REF:0000117	ACCEPT	Summary: Synapsin-1 plays a key role in regulating synaptic transmission by controlling synaptic vesicle pools and neurotransmitter release dynamics. Mutations cause impaired synaptic function [PMID:21441247, PMID:23406870]. Reason: Chemical synaptic transmission is the broader biological context in which SYN1 functions. The protein's role in regulating SV trafficking and neurotransmitter release directly supports this process. Both literature and the TAS annotation from PMID:2110562 support this involvement. Supporting Evidence: PMID:23406870 Synapsins (Syns) are synaptic vesicle (SV) phosphoproteins that play multiple roles in synaptic transmission and plasticity (1).
GO:0007269 neurotransmitter secretion	IEA GO_REF:0000002	ACCEPT	Summary: Synapsin-1 regulates neurotransmitter secretion by controlling the availability of synaptic vesicles for release. It maintains the reserve pool and regulates SV mobilization to the readily releasable pool. The Q555X mutant causes imbalances in release dynamics [PMID:23406870]. Reason: Neurotransmitter secretion is a core process that SYN1 regulates. The protein's function in SV clustering and reserve pool maintenance directly controls neurotransmitter release. This is well-supported by multiple publications. Supporting Evidence: PMID:23406870 Syns are implicated in the regulation of SV trafficking between the reserve pool (RP) and the readily releasable pool (RRP) and in facilitating the post-docking steps of release.
GO:0008021 synaptic vesicle	IEA GO_REF:0000120	ACCEPT	Summary: Synapsin-1 is a synaptic vesicle protein that coats SVs and maintains their clustering. This localization is fundamental to the protein's function. Reason: Synaptic vesicle localization is the primary cellular component annotation for SYN1. The protein is well-established as a synaptic vesicle protein that coats SVs. This is also supported by the TAS annotation from PMID:16141272. Supporting Evidence: PMID:2110562 Synapsin I is a peripheral membrane protein of synaptic vesicles that mediates their attachment to the cytoskeleton.
GO:0031410 cytoplasmic vesicle	IEA GO_REF:0000043	ACCEPT	Summary: This is a parent term of synaptic vesicle. While accurate, it is less specific than the more appropriate synaptic vesicle (GO:0008021) annotation. Reason: Accurate but redundant with the more specific synaptic vesicle annotation. IEA annotations at this level are acceptable as they reflect the general vesicle association, though synaptic vesicle is more informative. Supporting Evidence: file:human/SYN1/SYN1-uniprot.txt Cytoplasmic vesicle
GO:0045202 synapse	IEA GO_REF:0000120	ACCEPT	Summary: Synapsin-1 is localized to synapses, specifically at presynaptic terminals. This is a parent term that encompasses the more specific presynapse localization. Reason: Synapse localization is accurate and well-supported. The protein is concentrated at synapses, specifically at the presynaptic compartment. This general localization term is appropriate. Supporting Evidence: file:human/SYN1/SYN1-uniprot.txt SUBCELLULAR LOCATION: Synapse
GO:0050804 modulation of chemical synaptic transmission	IEA GO_REF:0000117	ACCEPT	Summary: Synapsin-1 modulates synaptic transmission by regulating short-term plasticity through its control of SV pool dynamics. The Q555X mutation causes altered short-term plasticity responses [PMID:23406870]. Reason: Modulation of synaptic transmission is a core function of SYN1. The protein's role in controlling SV reserve pool and release dynamics directly modulates synaptic transmission strength and short-term plasticity. Supporting Evidence: PMID:23406870 We identified distinct physiological changes in quantal parameters, release dynamics and STP at inhibitory and excitatory synapses.
GO:0098793 presynapse	IEA GO_REF:0000120	ACCEPT	Summary: Synapsin-1 is predominantly localized to the presynapse where it associates with synaptic vesicle clusters. This is the primary functional location of the protein. Reason: Presynapse localization is the core cellular component annotation for SYN1. This is supported by IDA evidence from PMID:21441247 as well. The protein functions at presynaptic terminals to regulate SV pools. Supporting Evidence: PMID:21441247 Here we report a Q555X mutation in synapsin 1 (SYN1), an X-linked gene encoding for a neuron-specific phosphoprotein implicated in the regulation of neurotransmitter release and synaptogenesis.
GO:0000795 synaptonemal complex	IEA GO_REF:0000107	REMOVE	Summary: The synaptonemal complex is a meiosis-specific structure involved in chromosome pairing. Synapsin-1 is a neuronal protein involved in synaptic vesicle trafficking, not meiosis. This appears to be an erroneous annotation, possibly from confusion between "synaptic" and "synaptonemal". Reason: This annotation is likely incorrect. The synaptonemal complex is a meiotic structure unrelated to synaptic vesicle biology. SYN1 is expressed specifically in neurons and functions at presynaptic terminals. There is no evidence supporting synaptonemal complex localization, and this may represent a mapping error based on terminological similarity. Supporting Evidence: file:human/SYN1/SYN1-deep-research-falcon.md Synapsin-1 is concentrated at presynaptic terminals and enriched on SV clusters.
GO:0014069 postsynaptic density	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Synapsin-1 is predominantly a presynaptic protein. While some proteomic studies may detect it in postsynaptic density preparations due to contamination or transient interactions, its primary localization and function is presynaptic. Reason: SYN1 is well-established as a presynaptic protein that associates with synaptic vesicles. The postsynaptic density annotation likely comes from proteomic studies that detected SYN1, possibly due to contamination of postsynaptic preparations with presynaptic material. The primary functional localization is presynaptic. Supporting Evidence: file:human/SYN1/SYN1-deep-research-falcon.md Localization: Synapsin-1 is concentrated at presynaptic terminals. PMID:23406870 No changes in miniature EPSC (mEPSC) and miniature IPSC (mIPSC) amplitude, as well as in their rise and decay times, were observed
GO:0019901 protein kinase binding	IEA GO_REF:0000107	ACCEPT	Summary: Synapsin-1 is a substrate for multiple protein kinases including PKA, CaMK2, and MAPK. Its phosphorylation by these kinases regulates its function. The protein likely binds these kinases during phosphorylation events. Reason: Protein kinase binding is supported by the extensive phosphorylation of SYN1 by multiple kinases. The protein is a well-documented substrate of PKA, CaMK1, CaMK2, and MAPK/ERK. This annotation is also present with ISS evidence (GO_REF:0000024). Supporting Evidence: file:human/SYN1/SYN1-uniprot.txt Substrate of different protein kinases file:human/SYN1/SYN1-deep-research-falcon.md Phosphorylation by PKA/CaMKI/IV (site 1), CaMKII (sites 2/3), and MAPK/Cdk (sites 6/7) toggles synapsin's binding to membranes and actin.
GO:0030424 axon	IEA GO_REF:0000107	ACCEPT	Summary: Synapsin-1 redistributes into the axon during action potential firing as it dissociates from synaptic vesicles. This localization is consistent with its presynaptic function at axon terminals. Reason: Axon localization is appropriate for SYN1. The protein localizes to presynaptic terminals at axon endings and redistributes along the axon during synaptic activity. UniProt notes that it dissociates from SVs and redistributes into the axon during AP firing. Supporting Evidence: file:human/SYN1/SYN1-uniprot.txt Dissociates from synaptic vesicles and redistributes into the axon during action potential firing
GO:0030425 dendrite	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: While synapsin-1 is predominantly presynaptic, some studies may have detected it in dendrites. However, its primary localization and function is at presynaptic terminals, not dendrites. Reason: SYN1 is well-characterized as a presynaptic protein. Dendritic localization is not its primary site of function. Any dendritic detection may represent minor amounts or experimental artifacts. The protein is not known to have a functional role in dendrites. Supporting Evidence: file:human/SYN1/SYN1-deep-research-falcon.md Localization: Synapsin-1 is concentrated at presynaptic terminals.
GO:0030672 synaptic vesicle membrane	IEA GO_REF:0000107	ACCEPT	Summary: Duplicate of the IBA annotation above. Synapsin-1 associates with synaptic vesicle membranes through its domain A phospholipid binding. Reason: This annotation is correct and consistent with the IBA annotation. Multiple evidence types supporting the same annotation is appropriate. Supporting Evidence: PMID:2110562 Synapsin I is a peripheral membrane protein of synaptic vesicles that mediates their attachment to the cytoskeleton.
GO:0042802 identical protein binding	IEA GO_REF:0000107	ACCEPT	Summary: Synapsin-1 forms homodimers and can oligomerize. This self-association is important for its function in SV clustering and is mediated in part by domain E. UniProt notes homodimer formation. Reason: Identical protein binding (homodimerization) is documented for SYN1. UniProt states "Homodimer (By similarity)". This self-association contributes to SV clustering through synapsin multimerization. Supporting Evidence: file:human/SYN1/SYN1-uniprot.txt SUBUNIT: Homodimer (By similarity). PMID:23406870 Because SV clustering and maintenance of the RP are believed to occur partly through oligomerization of SynI with other Syns (1), we asked whether the Q555X mutation influenced the ability of SynI to oligomerize with other Syn isoforms.
GO:0044297 cell body	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Synapsin-1 is synthesized in the neuronal cell body before transport to presynaptic terminals. Some localization to the cell body may be detected, but the functional localization is at presynaptic terminals. Reason: Cell body localization likely represents biosynthetic or trafficking intermediates rather than the functional location. The primary site of SYN1 function is at presynaptic terminals. Keep as non-core to acknowledge this minor localization. Supporting Evidence: file:human/SYN1/SYN1-uniprot.txt Tissue enriched (brain)
GO:0048306 calcium-dependent protein binding	IEA GO_REF:0000107	ACCEPT	Summary: Synapsin-1 ATP binding is calcium-facilitated, and its interactions with membranes and other proteins are regulated by calcium-dependent phosphorylation. The protein's activity is modulated by calcium signaling. Reason: Calcium-dependent protein binding is consistent with SYN1 biology. The protein's ATP binding is calcium-facilitated, and CaMK2 phosphorylation is calcium-dependent. These calcium-dependent interactions are central to SYN1 function. Supporting Evidence: file:human/SYN1/SYN1-deep-research-falcon.md Synapsin-1's domain C binds ATP/ADP (calcium-facilitated) and actin.
GO:0048666 neuron development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Synapsin-1 is involved in axon outgrowth and synaptogenesis during neuron development. The Q555X mutation caused delayed axon elongation [PMID:21441247]. However, this is a broader developmental process. Reason: While SYN1 does contribute to neuron development through its roles in axon outgrowth and synaptogenesis, this is a broad developmental term. The core function of SYN1 is in regulating synaptic vesicle dynamics at mature synapses. Keep as non-core. Supporting Evidence: PMID:21441247 Here we report a Q555X mutation in synapsin 1 (SYN1), an X-linked gene encoding for a neuron-specific phosphoprotein implicated in the regulation of neurotransmitter release and synaptogenesis. file:human/SYN1/SYN1-uniprot.txt Also involved in the regulation of axon outgrowth and synaptogenesis
GO:0048786 presynaptic active zone	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: While synapsin-1 is presynaptic, it is primarily associated with the reserve pool of synaptic vesicles that are more distant from the active zone. During stimulation, SYN1 redistributes toward the active zone. The active zone itself is distinct from the SV reserve pool where SYN1 primarily resides. Reason: SYN1 is primarily associated with synaptic vesicle clusters in the reserve pool, which is distinct from the active zone. While it may transiently localize near the active zone during vesicle mobilization, the active zone per se is not its primary localization. The protein redistributes toward the AZ during stimulation. Supporting Evidence: PMID:23406870 At rest, the distribution of WT-hSynI was comparable with that reported for the endogenous protein (27) and was characterized by fewer metal particles located near the plasma membrane, when compared with those located in the more central region of the synapse.
GO:0050808 synapse organization	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Duplicate of the IBA annotation above. SYN1 contributes to synapse organization through its role in maintaining synaptic vesicle pools. Reason: Consistent with the IBA annotation review above. This is a broader term than the more specific synaptic vesicle clustering function. Supporting Evidence: PMID:21441247 Here we report a Q555X mutation in synapsin 1 (SYN1), an X-linked gene encoding for a neuron-specific phosphoprotein implicated in the regulation of neurotransmitter release and synaptogenesis.
GO:0098685 Schaffer collateral - CA1 synapse	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: This is a specific synapse type in the hippocampus. While synapsin-1 is expressed in hippocampal neurons and likely present at Schaffer collateral synapses, this is an overly specific localization term for a broadly expressed synaptic protein. Reason: SYN1 is broadly expressed in neurons throughout the brain, not specifically at Schaffer collateral-CA1 synapses. While it is present at these synapses (as it is at most glutamatergic synapses), annotating a specific synapse type is overly specific for a generally expressed synaptic vesicle protein. Supporting Evidence: file:human/SYN1/SYN1-uniprot.txt Tissue enriched (brain)
GO:0098693 regulation of synaptic vesicle cycle	IEA GO_REF:0000107	ACCEPT	Summary: Synapsin-1 regulates the synaptic vesicle cycle by controlling SV clustering, reserve pool maintenance, and mobilization of vesicles for release. This is a core function. Reason: Regulation of the synaptic vesicle cycle is a core function of SYN1. The protein controls SV trafficking between reserve and readily releasable pools, which is central to the SV cycle. Supporting Evidence: PMID:23406870 Syns are implicated in the regulation of SV trafficking between the reserve pool (RP) and the readily releasable pool (RRP) and in facilitating the post-docking steps of release.
GO:0098850 extrinsic component of synaptic vesicle membrane	IEA GO_REF:0000107	ACCEPT	Summary: Synapsin-1 is a peripheral membrane protein that associates extrinsically with synaptic vesicle membranes through its N-terminal domain A. Reason: This is an accurate and specific cellular component term for SYN1. The protein is a peripheral (extrinsic) membrane protein that binds the cytoplasmic surface of SV membranes, not a transmembrane protein. Supporting Evidence: PMID:2110562 Synapsin I is a peripheral membrane protein of synaptic vesicles that mediates their attachment to the cytoskeleton.
GO:0099504 synaptic vesicle cycle	IEA GO_REF:0000107	ACCEPT	Summary: Synapsin-1 participates in the synaptic vesicle cycle by regulating SV clustering, reserve pool dynamics, and vesicle availability for release. Reason: Participation in the synaptic vesicle cycle is well-established for SYN1. The protein regulates key steps in the cycle including reserve pool maintenance and SV mobilization. Supporting Evidence: PMID:15217342 Neurotransmitter release is mediated by exocytosis of synaptic vesicles at the presynaptic active zone of nerve terminals.
GO:0005515 protein binding	IPI PMID:23406870 Epileptogenic Q555X SYN1 mutant triggers imbalances in relea...	MODIFY	Summary: The PMID:23406870 paper demonstrates that SYN1 interacts with SYN2 through co-immunoprecipitation. The Q555X mutation virtually abolished the ability of SynI to interact with SynIIa and strongly reduced interaction with SynIIb. Reason: While the paper does demonstrate protein binding (specifically to SYN2), the generic "protein binding" term is not informative. A more specific term would be preferable, though the current GO may not have a perfect term. Consider keeping as is since the specific binding partner (SYN2) is documented. Proposed replacements: identical protein binding Supporting Evidence: PMID:23406870 We found that the Q555X truncation virtually abolished the ability of SynI to interact with SynIIa and strongly reduced the interaction with SynIIb.
GO:0098793 presynapse	IDA PMID:21441247 SYN1 loss-of-function mutations in autism and partial epilep...	ACCEPT	Summary: The paper demonstrates presynapse localization through immunofluorescence studies showing SYN1 targeting to nerve terminals. The variants had differential effects on nerve terminal targeting. Reason: Presynapse localization is directly demonstrated by PMID:21441247 through imaging of fluorescent SYN1 at presynaptic terminals. This is a core localization annotation. Supporting Evidence: PMID:21441247 The missense A550T and T567A mutants displayed impaired targeting to nerve terminals.
GO:2000300 regulation of synaptic vesicle exocytosis	IMP PMID:21441247 SYN1 loss-of-function mutations in autism and partial epilep...	ACCEPT	Summary: The paper shows that SYN1 mutations fail to rescue defects in synaptic vesicle pool size and trafficking in SynI knockout neurons. The Q555X mutant had dramatic impact on SV dynamics. Wild-type SYN1 rescued the knockout phenotype. Reason: This IMP annotation is well-supported by the paper. The rescue experiments demonstrate that SYN1 regulates SV exocytosis, as the mutants failed to rescue defects in SV pool size and trafficking while wild-type SYN1 did. Supporting Evidence: PMID:21441247 When expressed in synapsin I (SynI) knockout (KO) neurons, all the D-domain mutants failed in rescuing the impairment in the size and trafficking of synaptic vesicle pools, whereas the wild-type human SynI fully reverted the KO phenotype.
GO:0106006 cytoskeletal protein-membrane anchor activity	TAS PMID:2110562 The structure of the human synapsin I gene and protein.	ACCEPT	Summary: The paper describes synapsin I as mediating attachment of synaptic vesicles to the cytoskeleton. This molecular function captures SYN1's role in linking SVs to actin. Reason: This is an excellent molecular function annotation for SYN1. The protein links synaptic vesicle membranes to the actin cytoskeleton, serving as an anchor between the two. Supporting Evidence: PMID:2110562 Synapsin I is a peripheral membrane protein of synaptic vesicles that mediates their attachment to the cytoskeleton.
GO:0005856 cytoskeleton	IDA PMID:24327345 Intracellular distribution of differentially phosphorylated ...	UNDECIDED	Summary: PMID:24327345 is about DYRK1A, not SYN1. The paper mentions that DYRK1A phosphorylates synaptic proteins including synaptojanin 1 and amphiphysin I, and shows DYRK1A association with cytoskeleton. This may be a misassigned annotation. Reason: The cited paper is primarily about DYRK1A localization and phosphorylation, not SYN1. While it mentions SYN1 tangentially in the context of DYRK1A substrates, it does not directly demonstrate SYN1 cytoskeleton localization. However, SYN1 is known to bind actin (cytoskeleton). The annotation itself may be correct but the reference appears to be misassigned. Supporting Evidence: PMID:2110562 Synapsin I is a peripheral membrane protein of synaptic vesicles that mediates their attachment to the cytoskeleton.
GO:0046928 regulation of neurotransmitter secretion	TAS PMID:21563316 Synaptic vesicle trafficking and Parkinson's disease.	ACCEPT	Summary: PMID:21563316 is a review about synaptic vesicle trafficking and Parkinson's disease. It discusses how SV trafficking affects neurotransmitter release. SYN1's role in regulating neurotransmitter secretion through SV pool control is well-established. Reason: Regulation of neurotransmitter secretion is a core function of SYN1. The protein controls SV availability for release, directly regulating neurotransmitter secretion rates and dynamics. Supporting Evidence: PMID:21563316 Presynaptic terminals maintain neurotransmitter release during repeated rounds of stimulation using local recycling of synaptic vesicles (SV). file:human/SYN1/SYN1-uniprot.txt Acts as a regulator of synaptic vesicles trafficking, involved in the control of neurotransmitter release at the pre-synaptic terminal
GO:0005524 ATP binding	TAS PMID:15217342 The synaptic vesicle cycle.	ACCEPT	Summary: PMID:15217342 is a review of the synaptic vesicle cycle by Sudhof. While it discusses many SV proteins, the specific ATP binding activity of SYN1 is well-documented through its domain C ATP-grasp fold. Reason: ATP binding is well-established for SYN1 through its domain C ATP-binding site. Multiple sources confirm this molecular function. Supporting Evidence: file:human/SYN1/SYN1-deep-research-falcon.md Synapsin-1's domain C binds ATP/ADP (calcium-facilitated) and actin.
GO:2000300 regulation of synaptic vesicle exocytosis	NAS PMID:10099709 Genetics of synaptic vesicle function: toward the complete f...	ACCEPT	Summary: PMID:10099709 is a review on genetics of synaptic vesicle function. While it covers synaptic vesicle proteins including synapsins, the NAS evidence code indicates a non-traceable author statement. The function itself is well-supported by other evidence. Reason: Although NAS is a weaker evidence code, the annotation is correct and supported by stronger evidence (IMP from PMID:21441247). Regulation of SV exocytosis is a core function of SYN1. Supporting Evidence: PMID:10099709 Synaptic transmission starts with the release of neurotransmitters by exocytosis of synaptic vesicles.
GO:0008021 synaptic vesicle	TAS PMID:16141272 Real-time imaging of Rab3a and Rab5a reveals differential ro...	ACCEPT	Summary: PMID:16141272 is about Rab3a and Rab5a, not directly about SYN1. However, it discusses synaptic vesicle proteins in general. SYN1 localization to synaptic vesicles is well-established by other sources. Reason: Synaptic vesicle localization is accurate for SYN1, though this particular reference is not ideal. The annotation is well-supported by other evidence and is a core localization for the protein. Supporting Evidence: PMID:2110562 Synapsin I is a peripheral membrane protein of synaptic vesicles that mediates their attachment to the cytoskeleton.
GO:0019901 protein kinase binding	ISS GO_REF:0000024	ACCEPT	Summary: Protein kinase binding is inferred by sequence similarity. SYN1 is a substrate of multiple kinases and likely binds them during phosphorylation. Reason: Protein kinase binding is consistent with SYN1 being a major phosphoprotein substrate of PKA, CaMK2, and MAPK. The ISS annotation is appropriate. Supporting Evidence: file:human/SYN1/SYN1-uniprot.txt Substrate of different protein kinases
GO:0007268 chemical synaptic transmission	TAS PMID:2110562 The structure of the human synapsin I gene and protein.	ACCEPT	Summary: The Sudhof 1990 paper describes the structure of human synapsin I and its role as a synaptic vesicle protein involved in mediating SV attachment to the cytoskeleton, which is essential for synaptic transmission. Reason: Chemical synaptic transmission involvement is well-supported. SYN1's role in SV trafficking is essential for synaptic transmission. The TAS annotation from this foundational paper is appropriate. Supporting Evidence: PMID:2110562 Synapsin I is a peripheral membrane protein of synaptic vesicles that mediates their attachment to the cytoskeleton.

Gene Description

Existing Annotations Review

Core Functions

Synapsin-1 serves as a molecular anchor that links synaptic vesicle membranes to the actin cytoskeleton. Through its domain A (phospholipid binding) and domain C (actin binding), the protein tethers SVs to the cytoskeleton, maintaining the reserve pool of synaptic vesicles at presynaptic terminals.

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