SYP

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0030672 synaptic vesicle membrane	IBA GO_REF:0000033	ACCEPT	Summary: Synaptophysin is one of the most abundant integral membrane proteins on synaptic vesicles, with the MARVEL domain spanning the membrane four times. This is the core and defining localization of this protein. Reason: This represents the primary and core cellular localization of synaptophysin. The deep research confirms synaptophysin resides on synaptic vesicle membranes as its main location, and UniProt annotates it as "synaptic vesicle membrane" with experimental evidence. The IBA annotation is well-supported and represents core function. Supporting Evidence: PMID:10620806 synaptophysin as a major specifically cholesterol-binding protein in PC12 cells and brain synaptic vesicles file:human/SYP/SYP-deep-research-perplexity.md Synaptophysin (SYP), encoded by the SYP gene (UniProt P08247), is one of the most abundant integral membrane proteins residing on synaptic vesicles in neurons file:human/SYP/SYP-deep-research-falcon.md SYP localizes predominantly to the synaptic vesicle membrane in presynaptic terminals and is widely used as a marker of synapse density, synaptogenesis, and neuronal maturation
GO:0048786 presynaptic active zone	IBA GO_REF:0000033	ACCEPT	Summary: Synaptophysin localizes to presynaptic active zones, the specialized regions where synaptic vesicles dock and fuse with the presynaptic membrane. This is well-supported by structural and functional studies. Reason: The presynaptic active zone is the site where synaptic vesicles cluster and undergo exocytosis. Multiple studies confirm synaptophysin's presence at this location. This is a core localization for synaptophysin function in neurotransmitter release. Supporting Evidence: file:human/SYP/SYP-deep-research-perplexity.md Synaptophysin is localized almost exclusively to synaptic vesicles within presynaptic nerve terminals
GO:0048168 regulation of neuronal synaptic plasticity	IBA GO_REF:0000033	ACCEPT	Summary: Synaptophysin regulates both short-term and long-term synaptic plasticity through its roles in vesicle endocytosis, vesicle clustering, and modulation of release probability. Reason: Multiple lines of evidence support synaptophysin's role in synaptic plasticity. The deep research documents its involvement in regulating synaptic vesicle dynamics which directly impacts plasticity. UniProt also notes this function. This is a core biological process for synaptophysin. Supporting Evidence: file:human/SYP/SYP-deep-research-perplexity.md Involved in the regulation of short-term and long-term synaptic plasticity (By similarity) file:human/SYP/SYP-uniprot.txt Possibly involved in structural functions as organizing other membrane components or in targeting the vesicles to the plasma membrane. Involved in the regulation of short-term and long-term synaptic plasticity
GO:0008021 synaptic vesicle	IEA GO_REF:0000120	ACCEPT	Summary: Synaptophysin is a major component of synaptic vesicles. This IEA annotation correctly captures the organellar localization, though the more specific "synaptic vesicle membrane" term is preferred. Reason: While "synaptic vesicle membrane" is more specific and preferred, this broader term is also correct. Synaptophysin is definitively located on synaptic vesicles. Keeping this annotation as it may be useful in some contexts, though it duplicates information captured by the membrane-specific term. Supporting Evidence: PMID:10620806 brain synaptic vesicles
GO:0016020 membrane	IEA GO_REF:0000120	ACCEPT	Summary: Synaptophysin is a multi-pass integral membrane protein with four transmembrane domains. This annotation is correct but overly general. Reason: While extremely broad, this annotation is technically correct - synaptophysin is a membrane protein. However, more specific terms like "synaptic vesicle membrane" provide much more biological insight. Accepting as it may be used in broad queries, though it provides minimal functional information. Supporting Evidence: file:human/SYP/SYP-uniprot.txt Multi-pass membrane protein
GO:0030672 synaptic vesicle membrane	IEA GO_REF:0000120	ACCEPT	Summary: Duplicate of the IBA annotation for GO:0030672. This represents the core localization of synaptophysin. Reason: This is a duplicate annotation with different evidence code (IEA vs IBA). Both are correct. The IBA annotation has stronger phylogenetic support, but keeping this IEA annotation as well is acceptable since it represents core function. Supporting Evidence: PMID:10620806 brain synaptic vesicles
GO:0031410 cytoplasmic vesicle	IEA GO_REF:0000043	ACCEPT	Summary: Synaptic vesicles are a type of cytoplasmic vesicle. This annotation is correct but very general compared to the more specific "synaptic vesicle" term. Reason: While this is a correct parent term of "synaptic vesicle", it provides limited specific information about synaptophysin's function. However, it may be useful for broader queries about cytoplasmic vesicle proteins. Accepting as technically correct though not informative about the specific biology.
GO:0043005 neuron projection	IEA GO_REF:0000120	ACCEPT	Summary: Synaptic vesicles are found in neuronal projections (axons, dendrites). Synaptophysin is primarily in presynaptic terminals at the ends of axons. Reason: This is correct - synaptophysin-containing synaptic vesicles are located within neuron projections, particularly in axon terminals. This is supported by the IDA annotation with PMID:8838578 as well. Represents accurate biology though not the most specific localization term. Supporting Evidence: file:human/SYP/SYP-uniprot.txt Expressed in the brain, with expression in the hippocampus, the neuropil in the dentate gyrus
GO:0045202 synapse	IEA GO_REF:0000120	ACCEPT	Summary: Synaptophysin is located at synapses, specifically in the presynaptic compartment where synaptic vesicles reside. Reason: This is correct - synaptophysin is a synaptic protein. The more specific terms like "presynapse" or "synaptic vesicle membrane" provide better resolution, but this broader term is also accurate and useful for general synapse protein queries. Supporting Evidence: PMID:8838578 from hippocampal synapses
GO:0010807 regulation of synaptic vesicle priming	IEA GO_REF:0000107	REMOVE	Summary: Synaptic vesicle priming is the process that makes vesicles fusion-competent. Synaptophysin regulates release probability but acts downstream of priming steps. Reason: The deep research indicates that synaptophysin family members act downstream of the final steps in vesicle priming, not in regulating priming itself. The elevated release probability in quadruple knockout mice occurs after priming is complete, indicating synaptophysin functions as an inhibitor of fusion rather than a regulator of the priming process. The Falcon deep research independently reinforces this picture: knockout studies show synaptophysin is not strictly essential for neurotransmitter release, and the well-supported molecular role is in synaptobrevin/VAMP2 retrieval during endocytosis rather than vesicle priming. This annotation conflates priming regulation with fusion regulation and should be removed. Supporting Evidence: file:human/SYP/SYP-deep-research-perplexity.md synaptophysin family members ordinarily play an inhibitory role in neurotransmission, acting downstream of the final steps in vesicle priming and upstream of the actual fusion event file:human/SYP/SYP-deep-research-falcon.md knockout studies show synaptophysin is not strictly essential for neurotransmitter release, indicating redundancy and/or context-dependent roles
GO:0031594 neuromuscular junction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Synaptophysin is present at neuromuscular junctions, which are specialized synapses between motor neurons and muscle fibers. Reason: While synaptophysin is indeed present at neuromuscular junctions, this is not its primary or most studied localization. The majority of synaptophysin research focuses on central nervous system synapses. This annotation is correct but represents a non-core aspect of synaptophysin biology. Supporting Evidence: file:human/SYP/SYP-deep-research-perplexity.md Synaptophysin is localized almost exclusively to synaptic vesicles within presynaptic nerve terminals, though the protein is also found on various other small synaptic-like microvesicles and secretory vesicles in neuroendocrine tissues
GO:0042169 SH2 domain binding	IEA GO_REF:0000107	ACCEPT	Summary: SH2 domains bind phosphotyrosine-containing sequences. Synaptophysin is heavily phosphorylated on tyrosine residues in its C-terminal domain, providing potential SH2 domain binding sites. Reason: The deep research confirms that synaptophysin is heavily phosphorylated by tyrosine kinases (Src and Fyn) and contains nine putative tyrosine phosphorylation sites within the YG(P/Q) repeats in its C-terminal domain. Phosphotyrosine residues are canonical SH2 domain binding sites. While the specific functional significance of SH2 domain interactions is not fully characterized, the molecular capacity for SH2 domain binding is well-supported by the phosphorylation evidence. Supporting Evidence: file:human/SYP/SYP-deep-research-perplexity.md The protein is heavily phosphorylated by tyrosine kinases in the nerve terminal; The C-terminal cytoplasmic domain contains nine putative tyrosine phosphorylation sites within the YG(P/Q) repeats; synaptophysin is a major tyrosine phosphoprotein on synaptic vesicles and is phosphorylated by the non-receptor tyrosine kinases Src and Fyn
GO:0042734 presynaptic membrane	IEA GO_REF:0000107	ACCEPT	Summary: During synaptic vesicle exocytosis, synaptophysin transiently becomes part of the presynaptic plasma membrane before being retrieved by endocytosis. Reason: This is correct - following vesicle fusion, synaptic vesicle membrane proteins including synaptophysin are incorporated into the presynaptic plasma membrane until they are retrieved by endocytosis. This is a transient but functionally important localization that is part of the vesicle cycle. Supporting Evidence: file:human/SYP/SYP-deep-research-perplexity.md Synaptophysin regulates two kinetically distinct phases of synaptic vesicle endocytosis: endocytosis that occurs during sustained neuronal activity and endocytosis that occurs following the cessation of stimulation
GO:0042802 identical protein binding	IEA GO_REF:0000107	ACCEPT	Summary: Synaptophysin forms hexamers, which requires identical protein binding (homohexamer formation). Reason: Synaptophysin forms hexameric structures, which is well-documented. UniProt states "Homohexamer or homotetramer". This represents an important aspect of synaptophysin's molecular organization and function. Supporting Evidence: file:human/SYP/SYP-deep-research-perplexity.md Electron microscopy and single-particle three-dimensional reconstruction studies have established that synaptophysin forms hexameric ring-like complexes. The hexameric structure exhibits six-fold symmetry with six spokes radiating from a central hub file:human/SYP/SYP-uniprot.txt Homohexamer or homotetramer file:human/SYP/SYP-deep-research-falcon.md In synaptophysin knockout neurons, sybII-pHluorin was stranded on the cell surface and retrieval kinetics were significantly impaired; re-expression of synaptophysin rescued retrieval
GO:0043195 terminal bouton	IEA GO_REF:0000107	ACCEPT	Summary: Terminal boutons are the presynaptic nerve terminals containing synaptic vesicles. This is a key localization for synaptophysin. Reason: Terminal boutons are where synaptic vesicles cluster and undergo exocytosis. This is a correct and functionally relevant localization for synaptophysin. Well-supported by the biology of the protein. Supporting Evidence: file:human/SYP/SYP-deep-research-perplexity.md Synaptophysin is localized almost exclusively to synaptic vesicles within presynaptic nerve terminals
GO:0044306 neuron projection terminus	IEA GO_REF:0000107	ACCEPT	Summary: Neuron projection terminus includes axon terminals and dendritic tips. Synaptophysin is primarily in axon terminals (presynaptic). Reason: This is correct - synaptophysin is found at neuron projection termini, specifically at presynaptic terminals. This is a valid but somewhat general anatomical term for where synaptophysin functions.
GO:0048169 regulation of long-term neuronal synaptic plasticity	IEA GO_REF:0000107	ACCEPT	Summary: Synaptophysin regulates long-term synaptic plasticity through its effects on synaptic vesicle dynamics and neurotransmitter release. Reason: The deep research and UniProt both support synaptophysin's role in regulating long-term synaptic plasticity. There is also an ISS annotation for the same term, providing additional support. This represents a core biological process for synaptophysin. Supporting Evidence: file:human/SYP/SYP-uniprot.txt Involved in the regulation of short-term and long-term synaptic plasticity file:human/SYP/SYP-deep-research-perplexity.md Synaptophysin plays a previously unsuspected role in regulating activity-dependent synapse formation
GO:0048172 regulation of short-term neuronal synaptic plasticity	IEA GO_REF:0000107	ACCEPT	Summary: Synaptophysin regulates short-term synaptic plasticity through its control of vesicle endocytosis kinetics and release probability. Reason: Well-supported by multiple sources. Synaptophysin knockout neurons show exacerbated synaptic depression during sustained stimulation, directly demonstrating a role in short-term plasticity. This is a core biological process. Supporting Evidence: file:human/SYP/SYP-deep-research-perplexity.md In synaptophysin knockout neurons exposed to sustained high-frequency stimulation, the observed endocytic defects exacerbate synaptic depression and substantially delay the replenishment of the readily releasable pool of synaptic vesicles file:human/SYP/SYP-uniprot.txt Involved in the regulation of short-term and long-term synaptic plasticity file:human/SYP/SYP-deep-research-falcon.md synaptophysin is not required for overall exocytosis or recycling pool size, but is required for kinetically efficient endocytosis and to mitigate activity-dependent synaptic depression during sustained stimulation
GO:0048471 perinuclear region of cytoplasm	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: This annotation suggests synaptophysin localizes to the perinuclear region. This is atypical for a synaptic vesicle protein and may represent biosynthetic intermediates. Reason: Synaptophysin is primarily localized to synaptic vesicles at nerve terminals, not the perinuclear region. However, newly synthesized synaptophysin may transiently pass through the perinuclear region during biosynthesis and transport. This is not a core functional localization but may be technically correct for biosynthetic trafficking. Marking as non-core.
GO:0048786 presynaptic active zone	IEA GO_REF:0000107	ACCEPT	Summary: Duplicate annotation of the IBA GO:0048786 term. Synaptophysin localizes to presynaptic active zones. Reason: This duplicates the IBA annotation for the same term. Both are correct. The presynaptic active zone is where synaptic vesicles undergo exocytosis, making this a core localization for synaptophysin. Supporting Evidence: file:human/SYP/SYP-deep-research-perplexity.md Synaptophysin is localized almost exclusively to synaptic vesicles within presynaptic nerve terminals
GO:0050804 modulation of chemical synaptic transmission	IEA GO_REF:0000107	ACCEPT	Summary: Synaptophysin modulates synaptic transmission by regulating vesicle dynamics, release probability, and synaptic plasticity. Reason: This is well-supported. Synaptophysin regulates multiple aspects of synaptic transmission including endocytosis kinetics, release probability, and synaptic plasticity. This is a core biological process, though the more specific terms about vesicle endocytosis and plasticity regulation provide more detailed information. Supporting Evidence: file:human/SYP/SYP-deep-research-perplexity.md The role of synaptophysin and related family members in regulating the probability of neurotransmitter release has been definitively established through studies of mice lacking multiple family members
GO:0060076 excitatory synapse	IEA GO_REF:0000107	ACCEPT	Summary: Synaptophysin is found at excitatory synapses, though it is also present at inhibitory synapses. This annotation captures one important class of synapses where synaptophysin functions. Reason: Synaptophysin is present at excitatory synapses, including glutamatergic synapses. However, it is not exclusive to excitatory synapses - it is also found at inhibitory synapses. This annotation is correct but not comprehensive of all synapse types where synaptophysin is found. Supporting Evidence: file:human/SYP/SYP-deep-research-perplexity.md Synaptophysin (SYP), encoded by the SYP gene (UniProt P08247), is one of the most abundant integral membrane proteins residing on synaptic vesicles in neurons
GO:0098685 Schaffer collateral - CA1 synapse	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Schaffer collateral-CA1 synapses are excitatory synapses in the hippocampus. Synaptophysin is expressed in hippocampal synapses. Reason: While synaptophysin is indeed present at Schaffer collateral-CA1 synapses in the hippocampus, this represents just one specific synapse type out of many where synaptophysin functions. This is an overly specific anatomical annotation that does not represent core function. Keeping as non-core to reflect that synaptophysin is a general synaptic protein, not specific to this synapse type. Supporting Evidence: file:human/SYP/SYP-uniprot.txt Expressed in the brain, with expression in the hippocampus, the neuropil in the dentate gyrus, where expression is higher in the outer half of the molecular layer than in the inner half, and in the neuropil of CA4 and CA3
GO:0098793 presynapse	IEA GO_REF:0000107	ACCEPT	Summary: Synaptophysin is exclusively a presynaptic protein, localized to presynaptic terminals and synaptic vesicles. Reason: This is a core localization term for synaptophysin. It is definitively a presynaptic protein, not found in postsynaptic compartments. This annotation correctly captures the presynaptic specificity of synaptophysin. Supporting Evidence: file:human/SYP/SYP-deep-research-perplexity.md Synaptophysin is localized almost exclusively to synaptic vesicles within presynaptic nerve terminals
GO:0005515 protein binding	IPI PMID:17500595 Huntingtin interacting proteins are genetic modifiers of neu...	REMOVE	Summary: This is a generic protein binding annotation based on interaction with huntingtin. While technically correct, it provides minimal functional information. Reason: The term "protein binding" is too generic and uninformative. Synaptophysin has specific, functionally important protein interactions (synaptobrevin-2/VAMP2, synapsin, dynamin, V-ATPase) that should be annotated with more specific molecular function terms. This generic annotation from a huntingtin interactome study does not capture meaningful biology about synaptophysin's core functions. Removing in favor of more specific molecular function annotations. Supporting Evidence: PMID:17500595 Huntingtin interacting proteins are genetic modifiers of neurodegeneration.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Generic protein binding annotation from a binary protein interactome study. Uninformative about specific synaptophysin function. Reason: Same rationale as the previous protein binding annotation - this is too generic to be useful. The specific binding partners and their functional significance (e.g., synaptobrevin-2 binding for vesicle retrieval, cholesterol binding for membrane organization) are what matter for understanding synaptophysin biology. This generic annotation should be removed. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Generic protein binding annotation from a neurodegenerative disease protein interactome study. Not informative about synaptophysin function. Reason: Third instance of the generic "protein binding" term. As with the previous two, this provides no meaningful functional information about synaptophysin. The specific molecular functions (cholesterol binding, specific protein-protein interactions with VAMP2, etc.) are much more informative and should be preferred. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0043005 neuron projection	IDA PMID:8838578 Disappearance of actin-binding protein, drebrin, from hippoc...	ACCEPT	Summary: This IDA annotation confirms synaptophysin localization to neuron projections based on direct experimental evidence in hippocampal synapses. Reason: This has direct experimental support from PMID:8838578 which demonstrated synaptophysin in hippocampal synapses. The IDA evidence code indicates direct experimental evidence, which is stronger than the IEA annotation for the same term. This is a valid localization annotation. Supporting Evidence: PMID:8838578 from hippocampal synapses
GO:0008021 synaptic vesicle	ISS GO_REF:0000024	ACCEPT	Summary: This ISS annotation for synaptic vesicle localization is based on sequence similarity to orthologous genes. This is correct and represents core localization. Reason: Duplicate of the IEA annotation for the same term, but with ISS evidence code indicating inference from sequence similarity to orthologs. Both are correct. Synaptophysin is definitively a synaptic vesicle protein.
GO:0043005 neuron projection	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation for neuron projection localization based on orthology. This is correct. Reason: This is the third annotation for neuron projection (IEA, IDA, and now ISS). All are correct and supported. The multiple lines of evidence strengthen confidence in this localization. Keeping as it represents valid annotation with orthology-based support.
GO:0006897 endocytosis	ISS GO_REF:0000024	MODIFY	Summary: Synaptophysin plays a critical role in synaptic vesicle endocytosis, specifically regulating the kinetics of vesicle retrieval from the plasma membrane. Reason: While endocytosis is correct, this term is too broad. Synaptophysin specifically regulates synaptic vesicle endocytosis. There should be a more specific term like "synaptic vesicle endocytosis" or "regulation of synaptic vesicle endocytosis" that better captures the specific biology. The broad endocytosis term dilutes the specific functional insight. Proposed replacements: synaptic vesicle endocytosis Supporting Evidence: file:human/SYP/SYP-deep-research-perplexity.md One of the most thoroughly characterized functions of synaptophysin is its essential role in regulating the kinetics of synaptic vesicle endocytosis, the process by which synaptic vesicle membrane and cargo are retrieved from the presynaptic plasma membrane following exocytotic fusion file:human/SYP/SYP-deep-research-falcon.md synaptophysin is not required for overall exocytosis or recycling pool size, but is required for kinetically efficient endocytosis and to mitigate activity-dependent synaptic depression during sustained stimulation file:human/SYP/SYP-deep-research-falcon.md post-stimulus recovery after stimulation was faster in wild-type than synaptophysin knockout neurons (time constant 5.60 s WT vs 12.8 s syp−/−), consistent with slowed vesicle retrieval/reacidification dynamics in the absence of synaptophysin
GO:2000474 regulation of opioid receptor signaling pathway	ISS GO_REF:0000024	REMOVE	Summary: This annotation suggests synaptophysin regulates opioid receptor signaling based on sequence similarity to orthologs. This is not supported in the primary human synaptophysin literature. Reason: The deep research provides no evidence for synaptophysin playing a role in regulating opioid receptor signaling pathways. Synaptophysin is a general synaptic vesicle protein functioning in endocytosis, membrane organization, and vesicle dynamics across all synapse types, not specifically in opioid signaling. This ISS annotation likely represents an over-interpretation of data from model organism studies or reflects an indirect relationship. Without direct evidence of a specific role in opioid receptor signaling regulation, this annotation should be removed as it does not represent core synaptophysin function.
GO:0048169 regulation of long-term neuronal synaptic plasticity	ISS GO_REF:0000024	ACCEPT	Summary: Duplicate of the IEA annotation for the same term. Synaptophysin regulates long-term synaptic plasticity. Reason: This is the second annotation for this term (first was IEA). Both are correct and well-supported. The ISS evidence provides additional support based on orthology. This represents a core biological process for synaptophysin. Supporting Evidence: file:human/SYP/SYP-uniprot.txt Involved in the regulation of short-term and long-term synaptic plasticity
GO:0048172 regulation of short-term neuronal synaptic plasticity	ISS GO_REF:0000024	ACCEPT	Summary: Duplicate of the IEA annotation for the same term. Synaptophysin regulates short-term synaptic plasticity. Reason: This is the second annotation for this term. Both are correct. Short-term synaptic plasticity regulation is a core function of synaptophysin, well-documented in knockout studies showing exacerbated synaptic depression. Supporting Evidence: file:human/SYP/SYP-deep-research-perplexity.md In synaptophysin knockout neurons exposed to sustained high-frequency stimulation, the observed endocytic defects exacerbate synaptic depression
GO:0048499 synaptic vesicle membrane organization	NAS PMID:10620806 Cholesterol binds to synaptophysin and is required for bioge...	ACCEPT	Summary: Synaptophysin organizes the synaptic vesicle membrane through cholesterol binding, formation of hexameric structures, and regulation of membrane elasticity and curvature. Reason: This is strongly supported by PMID:10620806 which demonstrates cholesterol binding and role in vesicle biogenesis. The deep research extensively documents synaptophysin's role as a membrane organizer and elastomer. This is a core molecular function of synaptophysin. Supporting Evidence: PMID:10620806 specific interactions between cholesterol and SLMV membrane proteins, such as synaptophysin, contribute to both the segregation of SLMV membrane constituents from plasma-membrane constituents, and the induction of synaptic-vesicle curvature file:human/SYP/SYP-deep-research-perplexity.md synaptophysin functions as an elastomer of the synaptic vesicle membrane, regulating both the intrinsic curvature and the elastic properties that allow vesicles to expand when loaded with neurotransmitters file:human/SYP/SYP-deep-research-falcon.md The SYP–VAMP2 complex is considered a hallmark of synaptic vesicle maturation and depends on membrane cholesterol
GO:0015485 cholesterol binding	IDA PMID:10620806 Cholesterol binds to synaptophysin and is required for bioge...	ACCEPT	Summary: Synaptophysin is a major cholesterol-binding protein on synaptic vesicles. Cholesterol binding is essential for synaptic vesicle biogenesis and membrane organization. Reason: This is directly demonstrated by PMID:10620806 using photoactivatable cholesterol labeling. This is a core molecular function of synaptophysin with important implications for vesicle biogenesis and membrane properties. Well-supported with direct experimental evidence. Supporting Evidence: PMID:10620806 We identify synaptophysin as a major specifically cholesterol-binding protein in PC12 cells and brain synaptic vesicles file:human/SYP/SYP-deep-research-perplexity.md Synaptophysin functions as a major cholesterol-binding protein on synaptic vesicles, with cholesterol being an essential cofactor for synaptophysin function in synaptic vesicle biogenesis file:human/SYP/SYP-deep-research-falcon.md Reviews describe synaptophysin as a synaptic vesicle cholesterol-binding protein and report that cholesterol content influences the synaptophysin–synaptobrevin interaction
GO:0016188 synaptic vesicle maturation	NAS PMID:10620806 Cholesterol binds to synaptophysin and is required for bioge...	ACCEPT	Summary: Synaptophysin is involved in synaptic vesicle maturation, the process by which newly formed vesicles acquire their characteristic properties and protein composition. Reason: PMID:10620806 demonstrates synaptophysin's role in synaptic vesicle biogenesis from the plasma membrane, which is part of vesicle maturation. The cholesterol-binding function and membrane organizing properties contribute to vesicle maturation. This represents a core biological process. Supporting Evidence: PMID:10620806 blocks the biogenesis of synaptic-like microvesicles (SLMVs) from the plasma membrane file:human/SYP/SYP-deep-research-perplexity.md The synaptophysin/synaptogyrin family proteins collectively play a redundant role in determining the characteristic small size of synaptic vesicles file:human/SYP/SYP-deep-research-falcon.md The SYP–VAMP2 complex is considered a hallmark of synaptic vesicle maturation and depends on membrane cholesterol
GO:0030672 synaptic vesicle membrane	NAS PMID:1975480 Synaptophysin: structure of the human gene and assignment to...	ACCEPT	Summary: Third annotation for the core synaptic vesicle membrane localization, this time with NAS evidence from an early paper characterizing the human SYP gene. Reason: This is the third annotation for this core localization term (IBA, IEA, and now NAS). All are correct. PMID:1975480 is an early paper on the structure of the human synaptophysin gene. The NAS evidence code indicates non-traceable author statement, which is appropriate for well-established facts. Core localization. Supporting Evidence: PMID:1975480 structure of the human gene

Gene Description

Existing Annotations Review

Core Functions

Binding cholesterol to organize synaptic vesicle membrane lipid composition and induce membrane curvature during vesicle biogenesis

Forming hexameric ring complexes that capture and retrieve synaptobrevin-2 during activity-dependent synaptic vesicle endocytosis

Regulating synaptic vesicle membrane elasticity to enable neurotransmitter-dependent expansion and control fusion kinetics

References

Deep Research

Falcon

Perplexity

📚 Additional Documentation

Annotation Review Report

Annotation Review Summary

Core Functions Synthesis

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