Affinage

SNAPIN

SNARE-associated protein Snapin · UniProt O95295

Length
136 aa
Mass
14.9 kDa
Annotated
2026-04-28
68 papers in source corpus 38 papers cited in narrative 38 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SNAPIN is a multifunctional adaptor protein that integrates SNARE-dependent exocytosis with dynein-mediated retrograde transport and lysosomal homeostasis. It directly binds SNAP-25/SNAP-23 through its C-terminal helical domain to stabilize SNARE complex assembly and promote synaptotagmin coupling, thereby controlling the size of the readily releasable vesicle pool and synchronous neurotransmitter release; PKA phosphorylation at Ser-50 enhances this interaction, while LRRK2 phosphorylation at Thr-117 inhibits it (PMID:10195194, PMID:11283605, PMID:23949442, PMID:19217378). SNAPIN also functions as a dynein motor adaptor that couples late endosomes to the retrograde transport machinery, directing BACE1, TrkB/BDNF signaling endosomes, and lysosomes toward the soma; loss of this adaptor function impairs lysosomal maturation, autophagy flux, and neuronal survival, with additional phosphoregulation by p38α-MAPK (Ser-112) and DYRK3 (Thr-14) tuning transport efficiency (PMID:20920785, PMID:22840395, PMID:24373968, PMID:34118085, PMID:36585413). As a stable subunit of the BLOC-1 complex, SNAPIN participates in biogenesis of lysosome-related organelles and endosomal sorting in concert with dysbindin, linking its trafficking functions to lysosomal acidification and organelle positioning (PMID:15102850, PMID:27929705, PMID:26108535).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 High

    Identification of SNAPIN as a SNAP-25-binding protein that modulates SNARE–synaptotagmin coupling established it as a novel component of the exocytotic machinery.

    Evidence Yeast two-hybrid, GST pulldown, co-IP, and microinjection into SCG neurons with electrophysiology

    PMID:10195194

    Open questions at the time
    • Endogenous stoichiometry of Snapin within SNARE complexes unknown
    • Mechanism by which Snapin-CT inhibits synaptotagmin association not resolved at structural level
  2. 2001 High

    Discovery that PKA phosphorylates Snapin at Ser-50 to enhance SNAP-25 binding and increase release-competent vesicles revealed the first regulated switch on Snapin function.

    Evidence In vitro kinase assay, S50D phosphomimetic mutagenesis, capacitance measurements in chromaffin cells, in vivo phosphorylation in hippocampal slices

    PMID:11283605 PMID:15269257

    Open questions at the time
    • Phosphatase responsible for Ser-50 dephosphorylation not identified
    • Whether PKA-Snapin axis operates identically in non-neuronal secretory cells was initially unclear
  3. 2003 High

    Demonstration that Snapin is ubiquitously expressed and binds SNAP-23/syntaxin-4 broadened its role beyond neurons to general regulated exocytosis.

    Evidence Co-IP, subcellular fractionation, and GFP fusion imaging in adipocytes

    PMID:12877659

    Open questions at the time
    • Functional consequence for GLUT4 trafficking only shown later
    • Whether Snapin-SNAP-23 complex is regulated by the same phosphorylation events as Snapin-SNAP-25 was not tested
  4. 2004 High

    Assignment of Snapin as a BLOC-1 subunit linked its function to lysosome-related organelle biogenesis and explained its genetic reduction in pallid mice.

    Evidence Reciprocal co-IP, size-exclusion chromatography, yeast two-hybrid, and pallid mouse model

    PMID:15102850

    Open questions at the time
    • Whether Snapin has BLOC-1-independent functions in lysosomal trafficking was not distinguished
    • Structural basis of Snapin integration into BLOC-1 unknown
  5. 2005 High

    Snapin knockout mice confirmed an essential role in calcium-dependent exocytosis by showing impaired synaptotagmin-1–SNAP-25 association and reduced releasable vesicle pools in chromaffin cells.

    Evidence Snapin KO mouse, co-IP, capacitance measurements, vesicle pool analysis, subcellular fractionation, rescue

    PMID:16280592

    Open questions at the time
    • Neonatal lethality precluded analysis in mature synapses in vivo
    • Contribution to asynchronous release not characterized
  6. 2006 High

    Identification of Snapin interactions with dysbindin at presynaptic vesicles and with RyR2 channels expanded its partner network to calcium homeostasis and schizophrenia-linked pathways.

    Evidence In vitro binding, brain co-IP, immunoelectron microscopy (dysbindin); GST pulldown, ryanodine binding assay (RyR2)

    PMID:16723744 PMID:16980328

    Open questions at the time
    • Functional consequence of Snapin-RyR2 interaction in cardiomyocytes not demonstrated in vivo
    • Whether dysbindin stabilizes Snapin through direct protection from degradation was not resolved until 2008
  7. 2007 High

    Interaction with the exocyst subunit Exo70 and demonstration that Snapin depletion inhibits insulin-stimulated GLUT4 trafficking revealed a role in regulated membrane insertion beyond classical exocytosis.

    Evidence Co-IP, domain mapping, RNAi, and glucose uptake assay in adipocytes

    PMID:17947242

    Open questions at the time
    • Whether Snapin acts as an adaptor between exocyst and SNARE complexes simultaneously is unclear
    • In vivo metabolic phenotype of Snapin loss not tested
  8. 2009 High

    Structure-function analysis using Snapin-deficient neurons and the C66A dimerization mutant dissected dual roles in vesicle priming (RRP size) and synchronous fusion, establishing that Snapin dimerization is required for full function.

    Evidence Snapin KO cortical neurons, C66A rescue, whole-cell patch clamp electrophysiology

    PMID:19217378

    Open questions at the time
    • Atomic-resolution structure of Snapin dimer on the SNARE complex unavailable
    • Whether desynchronized release reflects a direct synaptotagmin coupling defect or indirect priming defect was not fully separated
  9. 2010 High

    Discovery that Snapin acts as a dynein motor adaptor for late endosomes established a second major function — retrograde axonal transport — independent of its SNARE-binding role.

    Evidence Snapin KO mice, live-cell imaging of late endosome transport in neurons, dynein co-IP, rescue

    PMID:20920785

    Open questions at the time
    • Whether Snapin binds dynein and SNARE complexes simultaneously or in mutually exclusive modes unclear
    • Structural basis of Snapin-dynein interaction not resolved
  10. 2011 High

    Extension to TrkB signaling endosome transport and to insulin granule exocytosis in pancreatic β-cells demonstrated that Snapin's dynein-adaptor and SNARE-modulator functions operate across distinct cell types and physiological contexts.

    Evidence Compartmentalized neuron cultures with live TrkB imaging plus Snapin KO (TrkB); phosphomimetic Snapin rescue of GSIS in diabetic islets (insulin)

    PMID:21356520 PMID:22840395

    Open questions at the time
    • Whether Snapin phosphorylation at Ser-50 is the sole incretin effector mechanism not excluded
    • Relative contribution of Snapin to TrkB vs. other neurotrophin receptor retrograde transport unknown
  11. 2012 High

    Biophysical reconstitution showed that Ser-50 phosphomimicry destabilizes helical tetramer assemblies and favors the dimer form that binds SNARE complexes most strongly, providing a structural mechanism for PKA-mediated enhancement of exocytosis. Concurrently, Drosophila genetics placed Snapin in presynaptic homeostatic plasticity alongside dysbindin.

    Evidence Recombinant CD, fluorescence anisotropy, SEC, in vitro SNARE binding (biophysics); Drosophila snapin mutant electrophysiology and double mutant analysis (genetics)

    PMID:22471585 PMID:22723711

    Open questions at the time
    • High-resolution structure of Snapin dimer–SNARE complex not available
    • Whether Snapin oligomeric state is dynamically regulated in living cells unknown
  12. 2013 High

    LRRK2 phosphorylation of Snapin at Thr-117 was shown to inhibit SNAP-25 binding and reduce exocytosis, providing a Parkinson's disease-linked kinase input that opposes the PKA pathway; separately, Snapin's dynein-adaptor role was extended to BACE1 retrograde transport relevant to Alzheimer's disease.

    Evidence In vitro kinase assay, T117D mutagenesis, neuronal capacitance (LRRK2); Snapin KO mice, hAPP neurons, BACE1 live imaging and Aβ measurement (BACE1)

    PMID:23949442 PMID:24373968

    Open questions at the time
    • Whether LRRK2 and PKA phosphorylation events on Snapin are coordinated in vivo unknown
    • BACE1 findings in mouse models not yet validated in human neurons
  13. 2015 High

    Integration of Snapin's dynein-adaptor and BLOC-1/dysbindin-binding functions showed that these converge to control synaptic vesicle positional priming and Ca²⁺ sensitivity of release through AP-3-dependent endosomal sorting.

    Evidence Snapin KO neurons, SV-targeted Ca²⁺ sensor, dynein-binding mutants, live imaging

    PMID:26108535

    Open questions at the time
    • Molecular handoff between BLOC-1 sorting and dynein transport not structurally resolved
    • Whether AP-3-dependent mechanism operates outside CNS synapses unclear
  14. 2016 High

    Snapin silencing in macrophages impaired lysosomal acidification (via proton leak) and cathepsin D activation without blocking endosome–lysosome fusion, establishing a direct role in lysosomal functional integrity and autophagy flux.

    Evidence siRNA in primary human macrophages, ratiometric pH assay, cathepsin D activation, autophagy flux

    PMID:27929705

    Open questions at the time
    • Molecular mechanism by which Snapin prevents proton leak not identified
    • Whether lysosomal acidification defect is BLOC-1-dependent or independent unknown
  15. 2021 High

    p38α-MAPK phosphorylation of Snapin at Ser-112 was shown to inhibit retrograde BACE1 transport and increase synaptic BACE1 accumulation, establishing a stress-kinase input that modulates Snapin's dynein-adaptor function.

    Evidence In vitro kinase assay, mass spectrometry site ID, S112A mutagenesis, live axonal transport imaging, APP-transgenic mouse

    PMID:34118085

    Open questions at the time
    • Whether Ser-112 phosphorylation affects transport of other Snapin cargoes (TrkB, lysosomes) not tested
    • Therapeutic potential of targeting p38α-Snapin axis not validated
  16. 2022 High

    DYRK3 phosphorylation of Snapin at Thr-14 enhances dynein and synaptotagmin-1 binding, positively modulating mitochondrial retrograde transport and synaptic vesicle recycling pool size — the first kinase shown to stimulate rather than inhibit Snapin's transport function.

    Evidence In vitro kinase assay, T14 mutagenesis, co-IP, live mitochondrial transport imaging in cortical neurons, SV pool assay

    PMID:36585413

    Open questions at the time
    • Whether DYRK3 phosphorylation is stimulus-regulated in vivo unknown
    • How Thr-14 phosphorylation structurally alters Snapin conformation not resolved
  17. 2025 Medium

    CK1δ-mediated hyperphosphorylation of Snapin was linked to disrupted lysosomal positioning and acidification in neurons, with pharmacological CK1δ inhibition rescuing these defects — connecting Snapin phosphoregulation to neurodegeneration pathways.

    Evidence CK1δ kinase assay, lysosomal pH assay, live imaging of lysosomal motility, CK1δ inhibitor rescue

    PMID:41567242

    Open questions at the time
    • Specific CK1δ phosphorylation sites on Snapin not mapped by mass spectrometry
    • Whether CK1δ-Snapin axis operates in non-HIV neurodegeneration contexts unclear
    • Single lab finding awaiting independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of Snapin in complex with SNARE proteins or dynein, and a unified model explaining how its multiple phosphorylation sites are integrated to coordinate exocytosis, retrograde transport, and lysosomal function, remain major open questions.
  • No atomic-resolution structure of Snapin bound to any partner complex
  • How Snapin partitions between SNARE-complex, BLOC-1, and dynein-adaptor pools in the same cell is unknown
  • Combinatorial phosphorylation code integrating PKA, LRRK2, p38α, DYRK3, and CK1δ inputs not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0031410 cytoplasmic vesicle 5 GO:0005886 plasma membrane 3 GO:0005764 lysosome 2 GO:0005794 Golgi apparatus 1 GO:0005829 cytosol 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 8 R-HSA-112316 Neuronal System 5 R-HSA-162582 Signal Transduction 3 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-9612973 Autophagy 2
Partners
ADCY6CACNA1DDCTN1DTNBP1EXOC7LRRK2SNAP23SNAP25
Complex memberships
BLOC-1SNARE complex (via SNAP-25/SNAP-23)

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Snapin directly binds SNAP-25 and associates with the SNARE complex through this interaction; the C-terminal domain of Snapin (Snapin-CT) blocks synaptotagmin association with the SNARE complex, and introduction of Snapin-CT into presynaptic SCG neurons reversibly inhibited synaptic transmission. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, microinjection into SCG neurons with electrophysiological readout Nature neuroscience High 10195194
2001 PKA phosphorylates Snapin at serine 50, significantly increasing its binding to SNAP-25 and enhancing synaptotagmin association with the SNARE complex; the phosphomimetic S50D mutant increases the number of release-competent vesicles in chromaffin cells. Site-directed mutagenesis, in vitro kinase assay, co-immunoprecipitation, capacitance measurements in chromaffin cells, in vivo phosphorylation in hippocampal slices Nature cell biology High 11283605
2003 Snapin is ubiquitously expressed (not brain-specific), interacts with SNAP-23 via its C-terminal helical domain, forms a ternary complex with SNAP-23 and syntaxin-4, and exists in both cytosolic and peripheral membrane-bound pools in adipocytes. Protein-protein interaction assays, subcellular fractionation, co-immunoprecipitation, GFP fusion live imaging The Biochemical journal High 12877659
2004 Snapin is a subunit of BLOC-1 (Biogenesis of Lysosome-related Organelles Complex-1); it co-immunoprecipitates and co-fractionates with known BLOC-1 subunits (Pallidin, Muted, Cappuccino, Dysbindin), and its steady-state level is reduced in pallid mouse cells carrying a Pallidin mutation. Co-immunoprecipitation, size exclusion chromatography, yeast two-hybrid, antibody detection in mouse/human cells The Journal of biological chemistry High 15102850
2004 Snapin interacts with the N-terminus (aa 1-86) of type VI adenylyl cyclase (ACVI) via residues 33-51 of Snapin, and Snapin expression specifically reverses PKC-mediated suppression of ACVI activity without affecting PKA or calcium inhibition. Yeast two-hybrid, co-immunoprecipitation, mutational analysis, adenylyl cyclase activity assay in hippocampal neurons The Journal of biological chemistry High 15319443
2004 PKA-dependent phosphorylation of Snapin (via S50D mimetic) in hippocampal neurons decreases the size of the readily releasable vesicle pool, increases release probability per vesicle, and increases synaptic depression rate during high-frequency stimulation. Overexpression of phosphomimetic/phosphodead Snapin mutants in hippocampal neurons, electrophysiology (patch clamp, EPSCs) The Journal of neuroscience High 15269257
2005 Snapin knockout mice show impaired synaptotagmin-1 association with SNAP-25, a decreased number of releasable vesicle pools, and significantly reduced calcium-dependent exocytosis in embryonic chromaffin cells; Snapin is enriched in large dense-core vesicles and associates with synaptotagmin-1. Snapin knockout mouse generation, co-immunoprecipitation, capacitance measurements (patch clamp), vesicle pool analysis, subcellular fractionation, rescue by Snapin re-expression The Journal of neuroscience High 16280592
2005 Snapin binds cypin via its C-terminal coiled-coil domain (H2) at cypin's CRMP homology domain, competes with tubulin for cypin binding, reduces microtubule assembly, and overexpression of Snapin in hippocampal neurons decreases primary dendrite number and increases branching probability. Yeast two-hybrid, affinity chromatography, co-immunoprecipitation, microtubule assembly assay, overexpression in primary hippocampal neurons with morphometry Molecular biology of the cell High 16120643
2005 EBAG9 interacts with Snapin and decreases phosphorylation of Snapin, which in turn diminishes Snapin association with SNAP-25 and SNAP-23, inhibiting regulated large dense-core vesicle secretion from PC12 cells. Yeast two-hybrid, co-immunoprecipitation, phosphorylation assay, secretion assay (neuropeptide Y release from PC12 cells) Molecular biology of the cell Medium 15635093
2006 Dysbindin-1 binds Snapin in vitro and in the mouse/human brain; both proteins are concentrated in synaptic vesicle membrane-enriched fractions and are present in presynaptic vesicle compartments by immunoelectron microscopy. In vitro binding, co-immunoprecipitation in brain lysates, tissue fractionation, immunoelectron microscopy Human molecular genetics High 16980328
2006 Snapin binds to RyR2 at residues 4596-4765 via a hydrophobic segment; this interaction is isoform-nonspecific (also occurs with RyR1 and RyR3), sensitizes the RyR1 channel to Ca2+ activation, and the RyR binding site on Snapin overlaps with the SNAP-25 binding site. GST pulldown, native ryanodine receptor interaction, [3H]ryanodine binding assay, deletion analysis, competition experiments Journal of cell science High 16723744
2006 CK1δ interacts with Snapin, phosphorylates Snapin in vitro, and both proteins co-localize in the perinuclear region where Snapin associates with Golgi membranes. Yeast two-hybrid, co-immunoprecipitation, in vitro kinase assay, immunofluorescence co-localization FEBS letters Medium 17101137
2007 Snapin interacts with Exo70 subunit of the exocyst via an N-terminal coiled-coil domain in Exo70 and C-terminal helical region in Snapin; Exo70 competes with SNAP-23 for Snapin binding; siRNA depletion of Snapin in adipocytes inhibits insulin-stimulated GLUT4 trafficking and glucose uptake. Co-immunoprecipitation, pulldown assays, domain mapping, RNAi, glucose uptake assay in adipocytes The Journal of biological chemistry High 17947242
2007 Snapin interacts with the C-terminus of alpha1A-adrenoceptor and co-immunoprecipitates with TRPC6 and alpha1A-AR; co-transfection of Snapin augments alpha1A-AR-stimulated sustained Ca2+ influx via TRPC6 channels by increasing TRPC6 recruitment to the cell surface. Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, intracellular Ca2+ measurements, cell surface biotinylation The Journal of biological chemistry Medium 17684020
2008 Loss of dysbindin in sandy (sdy) mice reduces steady-state Snapin protein levels; a 30-residue peptide in dysbindin (aa 90-119) mediates interaction with Snapin, indicating dysbindin stabilizes Snapin in hippocampal neurons. Western blot in sdy mouse brain, peptide mapping, co-immunoprecipitation Schizophrenia research Medium 18774265
2009 Snapin deficiency in cortical neurons results in desynchronized (multiple-peaked, slower rise and decay) EPSCs and a reduced readily releasable pool; the dimerization-defective C66A Snapin mutant with impaired SNAP-25 and synaptotagmin interactions selectively reduces RRP size with less effect on synchrony, revealing dual roles in vesicle priming and synchronous fusion. Snapin-deficient mouse neurons, whole-cell patch clamp electrophysiology, rescue with Snapin-C66A mutant, mini-EPSC recording Neuron High 19217378
2009 Snapin associates with late endocytic compartments and interacts with late endosomal SNARE proteins syntaxin 8 and Vti1b; snapin gene deletion leads to accumulation of LAMP-1, syntaxin 8, and Vti1b in late endocytic organelles. Co-immunoprecipitation, subcellular fractionation, snapin KO mouse, Western blot Bioscience reports Medium 19335339
2010 Snapin acts as a dynein motor adaptor for late endosomes, directly coupling late endosomes to the dynein complex to mediate retrograde transport; snapin KO impairs retrograde transport, lysosomal maturation, and autophagy-lysosomal function, leading to reduced neuron viability. Snapin KO mice, live-cell imaging of late endosome transport in neurons, dynein co-immunoprecipitation, rescue by snapin transgene reintroduction Neuron (commentary); primary data cited from Cai et al., Neuron 2010 High 20920785
2011 Snapin mediates retrograde axonal transport of TrkB signaling endosomes by acting as a dynein adaptor; deleting snapin or disrupting Snapin-dynein interaction abolishes TrkB retrograde transport, impairs BDNF-induced retrograde signaling to the nucleus, and decreases dendritic growth of cortical neurons. Snapin KO mice, compartmentalized neuron cultures, live imaging of TrkB endosome transport, dynein co-IP, nuclear signaling assay, dendritic morphometry, rescue by snapin gene reintroduction Cell reports High 22840395
2011 Snapin mediates incretin (GLP-1) action on insulin secretion: PKA-dependent phosphorylation of Snapin increases interactions among insulin secretory vesicle-associated proteins, potentiating glucose-stimulated insulin secretion (GSIS); phosphorylation of Snapin is reduced in diabetic islets, and a phosphomimetic Snapin mutant restores GSIS. Pancreatic islet studies, phosphorylation assay, co-immunoprecipitation, overexpression of phosphomimetic mutant, insulin secretion assay, diabetic mouse model Cell metabolism High 21356520
2011 AC6 (type VI adenylyl cyclase) regulates neurite outgrowth by forming a complex with Snapin and SNAP-25 via its N-terminus; complex formation depends on AC6-N and Snapin phosphorylation state; disrupting this complex (via Snapin knockdown or AC6-binding-deficient Snapin mutant) reverses AC6-mediated inhibition of neurite extension. Pulldown assays, immunoprecipitation-AC activity assay, overexpression of Snapin mutants, siRNA knockdown, neurite outgrowth measurement in Neuro2A and hippocampal neurons, AC6 KO mouse Molecular and cellular biology High 21986494
2012 Snapin loss blocks both rapid and long-term homeostatic modulation of presynaptic vesicle release at the Drosophila NMJ following inhibition of postsynaptic glutamate receptors; genetic evidence indicates Snapin functions in concert with dysbindin and that Snapin-SNAP25 interaction is required for synaptic homeostasis. Drosophila snapin mutant electrophysiology, pharmacological inhibition of GluRs, GluRIIA genetic deletion, double mutant analysis (snapin;dysbindin), synapse morphology analysis The Journal of neuroscience High 22723711
2012 Atg14L (Barkor) directly binds Snapin and co-localizes with it to facilitate endosome maturation; Atg14L knockdown delays late endocytic trafficking (retarded surface receptor degradation), rescued by wild-type Atg14L or Beclin 1-binding mutant but not by a Snapin-binding-deficient Atg14L mutant. Co-immunoprecipitation, co-localization, siRNA knockdown, receptor degradation kinetics assay, domain-specific rescue experiments Journal of cell science High 22797916
2013 LRRK2 interacts with Snapin via its ROC and N-terminal domains and phosphorylates Snapin at threonine 117; T117D phosphomimetic Snapin reduces its interaction with SNAP-25, decreases synaptotagmin-SNARE complex association in brain lysates, and reduces the readily releasable vesicle pool and exocytosis in hippocampal neurons. Yeast two-hybrid, GST pulldown, in vitro kinase assay, co-immunoprecipitation, mutagenesis, capacitance measurements in neurons Experimental & molecular medicine High 23949442
2013 Snapin, as a dynein adaptor for late endosomes, mediates BACE1 retrograde transport to lysosomes for degradation; snapin deficiency or disruption of Snapin-dynein coupling reduces BACE1 lysosomal targeting, enhancing APP cleavage and Aβ generation; overexpressing Snapin in hAPP neurons reduces β-site cleavage by enhancing BACE1 turnover. Snapin KO mice, hAPP mutant neurons, live imaging of BACE1-containing endosome transport, dynein co-IP, BACE1 degradation assay, APP cleavage/Aβ measurement, gene rescue Cell reports High 24373968
2013 In C. elegans, SNPN-1 (Snapin) promotes vesicle priming (docking/fusion-competency) at NMJs independently of synaptotagmin (snt-1), as snt-1;snpn-1 double mutants show additive docking defects; this supports SNPN-1 stabilizing SNARE complex formation upstream of synaptotagmin. C. elegans snpn-1 mutant electrophysiology, electron microscopy of docked vesicles, snt-1;snpn-1 double mutant analysis PloS one High 23469084
2015 Snapin acts as a dynein adaptor mediating retrograde transport of late endosomes (LEs) and interacts with dysbindin (a BLOC-1 subunit); dynein-binding-defective Snapin mutants induce SV accumulation at presynaptic terminals; Snapin-dysbindin interaction regulates SV positional priming through BLOC-1/AP-3-dependent endosomal sorting, controlling both SV pool size and Ca2+ sensitivity of release. Snapin KO neurons, SV-targeted Ca2+ sensor, dynein-binding mutants, overexpression studies, live imaging, snapin-dysbindin interaction assays The EMBO journal High 26108535
2016 SNAPIN silencing in macrophages causes swollen lysosomes with impaired cathepsin D activation, lysosomal proton leak (modest H+ pump activity reduction), and impaired autophagy flux/autophagosome maturation, without blocking endosome-lysosome fusion. siRNA knockdown in primary human macrophages, ratiometric fluorescence lysosomal pH assay, cathepsin D activation assay, autophagy flux assay, lysosomal morphology Autophagy High 27929705
2016 Snapin directly interacts with Cav1.3 calcium channel; Snapin overexpression reduces total and membrane Cav1.3 expression via ubiquitin-proteasomal degradation and decreases ICa-L density; SNAP-23 competitively reverses Snapin-induced Cav1.3 downregulation. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, overexpression in atrial myocytes and heterologous system, electrophysiology (whole-cell patch clamp), ubiquitin-proteasome inhibitor studies Cellular signalling Medium 27915047
2016 Snapin mediates insulin granule docking to the plasma membrane through its C-terminal H2 domain binding to the N-terminal Sn-1 domain of SNAP-25; syntaxin-1A is only recruited to the Snapin-SNAP-25 complex upon secretory stimulation, not at rest. Co-immunoprecipitation under resting and stimulated conditions, domain mapping, pancreatic beta-cell functional assays Biochemical and biophysical research communications Medium 26946359
2017 Snapin directly interacts with the C-terminus of the dopamine transporter (DAT), is co-expressed with DAT in dopaminergic neurons, and its interaction causes decreased DAT uptake activity; Snapin downregulation in mice increases DAT levels and transport activity, increasing dopamine concentration and locomotor response to amphetamine. Yeast two-hybrid, co-immunoprecipitation, 3D interaction modeling, DAT uptake assay, Snapin knockdown mouse, locomotor behavioral assay Neuropsychopharmacology Medium 28905875
2017 In dendritic cells, Snapin promotes retrograde maturation of endosomes and dampens TLR8 signaling; Snapin inhibition enhances co-localization of HIV-1 with TLR8+ early endosomes, triggers a pro-inflammatory response, and inhibits HIV-1 trans-infection of CD4+ T cells. Phosphoproteomic screen, siRNA secondary screen, confocal microscopy, flow cytometry, TLR8 signaling assays The EMBO journal Medium 28923824
2021 Snapin directly interacts with the long C-terminal variant of Cav1.3 (Cav1.3L) but not the short variant; Snapin co-expression increases Cav1.3L peak current density ~2-fold without altering gating properties, by increasing channel opening probability rather than membrane expression. Yeast two-hybrid, electrophysiology in HEK-293 and Xenopus oocytes, luminometry for membrane expression, on-gating current analysis International journal of molecular sciences Medium 34681928
2021 p38α-MAPK directly phosphorylates Snapin at serine 112; this phosphorylation inhibits retrograde axonal transport of BACE1 and increases BACE1 activity and protein levels at synaptic terminals; S112A replacement abolishes p38α-MAPK knockdown-induced BACE1 reduction. In vitro kinase assay, mass spectrometry, site-directed mutagenesis, live axonal transport imaging in neurons, APP-transgenic mouse model, BACE1 activity assay FASEB journal High 34118085
2022 DYRK3 directly phosphorylates Snapin at threonine 14, increasing Snapin's interaction with dynein and synaptotagmin-1; T14 phosphorylation positively modulates mitochondrial retrograde transport in cortical neurons and increases the recycling pool size of synaptic vesicles. Yeast two-hybrid, in vitro kinase assay, site-directed mutagenesis, co-immunoprecipitation, live mitochondrial transport imaging in cortical neurons, synaptic vesicle pool assay Cell death discovery High 36585413
2025 CK1δ phosphorylates SNAPIN, and Vpr-induced CK1δ activation leads to SNAPIN hyperphosphorylation, disrupting lysosomal positioning and motility in neurons; selective CK1δ inhibition restores lysosomal acidification, positioning, and mitophagy. CK1δ kinase assay, phosphorylation studies, lysosomal pH assay, live imaging of lysosomal motility, CK1δ inhibitor rescue, SNAPIN interaction assays iScience Medium 41567242
2025 Snapin binds cystathionine β-synthase (CBS) and disrupts H2S metabolic homeostasis after mild TBI, reducing endogenous H2S levels; decreased H2S limits S-sulfhydration of pro-CTSD (cathepsin D), promoting its maturation into active CTSD and inducing PANoptosis; conditional Snapin knockdown attenuates neurodegeneration and PANoptosis. Molecular docking, co-immunoprecipitation, modified biotin switch assay (S-sulfhydration detection), AAV-shSnapin knockdown, H2S electrode measurement, Western blot, behavioral tests in CCI mouse model Journal of advanced research Medium 41558604
2012 Mutation of Cys-66 abolishes Snapin subunit dimerization; mutation of Ser-50 to Asp (phosphomimetic S50D) destabilizes alpha-helical structure and tetrameric assemblies, favoring dimer-SNARE complex interaction; in vitro, S50D exhibits the strongest binding to the SNARE complex, consistent with enhanced cellular activity of PKA-phosphorylated Snapin. Recombinant protein purification, circular dichroism, fluorescence anisotropy, thermal stability assay, size exclusion chromatography, in vitro SNARE binding Biochemistry High 22471585

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Identification of snapin and three novel proteins (BLOS1, BLOS2, and BLOS3/reduced pigmentation) as subunits of biogenesis of lysosome-related organelles complex-1 (BLOC-1). The Journal of biological chemistry 219 15102850
1999 Snapin: a SNARE-associated protein implicated in synaptic transmission. Nature neuroscience 207 10195194
2001 Phosphorylation of Snapin by PKA modulates its interaction with the SNARE complex. Nature cell biology 141 11283605
2006 Dysbindin-1 is a synaptic and microtubular protein that binds brain snapin. Human molecular genetics 127 16980328
2012 Snapin recruits dynein to BDNF-TrkB signaling endosomes for retrograde axonal transport and is essential for dendrite growth of cortical neurons. Cell reports 117 22840395
2008 Dysbindin deficiency in sandy mice causes reduction of snapin and displays behaviors related to schizophrenia. Schizophrenia research 105 18774265
2011 Snapin mediates incretin action and augments glucose-dependent insulin secretion. Cell metabolism 97 21356520
2005 The role of Snapin in neurosecretion: snapin knock-out mice exhibit impaired calcium-dependent exocytosis of large dense-core vesicles in chromaffin cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 91 16280592
2003 Identification and characterization of Snapin as a ubiquitously expressed SNARE-binding protein that interacts with SNAP23 in non-neuronal cells. The Biochemical journal 71 12877659
2009 Snapin facilitates the synchronization of synaptic vesicle fusion. Neuron 70 19217378
2004 Effects of PKA-mediated phosphorylation of Snapin on synaptic transmission in cultured hippocampal neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 15269257
2013 Snapin-mediated BACE1 retrograde transport is essential for its degradation in lysosomes and regulation of APP processing in neurons. Cell reports 51 24373968
2012 Snapin is critical for presynaptic homeostatic plasticity. The Journal of neuroscience : the official journal of the Society for Neuroscience 51 22723711
2013 LRRK2 phosphorylates Snapin and inhibits interaction of Snapin with SNAP-25. Experimental & molecular medicine 49 23949442
2012 Beclin-1-interacting autophagy protein Atg14L targets the SNARE-associated protein Snapin to coordinate endocytic trafficking. Journal of cell science 45 22797916
2008 CREB3L4, INTS3, and SNAPAP are targets for the 1q21 amplicon frequently detected in hepatocellular carcinoma. Cancer genetics and cytogenetics 43 18068530
2005 A novel role for snapin in dendrite patterning: interaction with cypin. Molecular biology of the cell 43 16120643
2004 Reinvestigation of the role of snapin in neurotransmitter release. The Journal of biological chemistry 42 15084593
2015 Regulation of synaptic activity by snapin-mediated endolysosomal transport and sorting. The EMBO journal 41 26108535
2016 SNAPIN is critical for lysosomal acidification and autophagosome maturation in macrophages. Autophagy 40 27929705
2007 Snapin interacts with the Exo70 subunit of the exocyst and modulates GLUT4 trafficking. The Journal of biological chemistry 40 17947242
2005 EBAG9 adds a new layer of control on large dense-core vesicle exocytosis via interaction with Snapin. Molecular biology of the cell 39 15635093
2004 Regulation of type VI adenylyl cyclase by Snapin, a SNAP25-binding protein. The Journal of biological chemistry 38 15319443
2007 Snapin, a new regulator of receptor signaling, augments alpha1A-adrenoceptor-operated calcium influx through TRPC6. The Journal of biological chemistry 36 17684020
2012 SNAPIN: an endogenous Toll-like receptor ligand in rheumatoid arthritis. Annals of the rheumatic diseases 31 22523426
2003 Snapin interacts with the N-terminus of regulator of G protein signaling 7. Biochemical and biophysical research communications 31 12659861
2013 Transmembrane prostatic acid phosphatase (TMPAP) interacts with snapin and deficient mice develop prostate adenocarcinoma. PloS one 30 24039861
2006 Casein kinase 1 delta (CK1delta) interacts with the SNARE associated protein snapin. FEBS letters 27 17101137
2011 Uncovering the role of Snapin in regulating autophagy-lysosomal function. Autophagy 24 21233602
2007 The UT-A1 urea transporter interacts with snapin, a SNARE-associated protein. The Journal of biological chemistry 23 17702749
2006 Ryanodine receptor interaction with the SNARE-associated protein snapin. Journal of cell science 23 16723744
2011 Human cytomegalovirus primase UL70 specifically interacts with cellular factor Snapin. Journal of virology 22 21917956
2009 Novel regulation of adenylyl cyclases by direct protein-protein interactions: insights from snapin and ric8a. Neuro-Signals 22 19202347
2013 Differential roles for snapin and synaptotagmin in the synaptic vesicle cycle. PloS one 21 23469084
2009 Snapin associates with late endocytic compartments and interacts with late endosomal SNAREs. Bioscience reports 21 19335339
2014 Chlamydia psittaci inclusion membrane protein IncB associates with host protein Snapin. International journal of medical microbiology : IJMM 20 24751478
2011 Type VI adenylyl cyclase regulates neurite extension by binding to Snapin and Snap25. Molecular and cellular biology 20 21986494
2010 EHD1 is a synaptic protein that modulates exocytosis through binding to snapin. Molecular and cellular neurosciences 15 20696250
2017 Snapin promotes HIV-1 transmission from dendritic cells by dampening TLR8 signaling. The EMBO journal 14 28923824
2022 DYRK3 phosphorylates SNAPIN to regulate axonal retrograde transport and neurotransmitter release. Cell death discovery 13 36585413
2013 Modulation of the cellular distribution of human cytomegalovirus helicase by cellular factor Snapin. Journal of virology 13 23885069
2011 Snapin deficiency is associated with developmental defects of the central nervous system. Bioscience reports 13 20946101
2016 Physical and functional interaction of Snapin with Cav1.3 calcium channel impacts channel protein trafficking in atrial myocytes. Cellular signalling 12 27915047
2021 P38α-MAPK phosphorylates Snapin and reduces Snapin-mediated BACE1 transportation in APP-transgenic mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 11 34118085
2018 Interaction of porcine reproductive and respiratory syndrome virus major envelope proteins GP5 and M with the cellular protein Snapin. Virus research 11 29577951
2010 Snapin snaps into the dynein complex for late endosome-lysosome trafficking and autophagy. Neuron 11 20920785
2016 Snapin mediates insulin secretory granule docking, but not trans-SNARE complex formation. Biochemical and biophysical research communications 9 26946359
2016 Host protein Snapin interacts with human cytomegalovirus pUL130 and affects viral DNA replication. Journal of biosciences 9 27240978
2009 The SNARE-associated component SNAPIN binds PUMILIO2 and NANOS1 proteins in human male germ cells. Molecular human reproduction 9 19168546
2017 Structural and Functional Characterization of the Interaction of Snapin with the Dopamine Transporter: Differential Modulation of Psychostimulant Actions. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 8 28905875
2015 Snapin interacts with G-protein coupled receptor PKR2. Biochemical and biophysical research communications 7 26687946
2014 Interaction between the human cytomegalovirus‑encoded UL142 and cellular Snapin proteins. Molecular medicine reports 7 25369979
2012 Mutation of Ser-50 and Cys-66 in Snapin modulates protein structure and stability. Biochemistry 7 22471585
2010 Functional characterization of the central hydrophilic linker region of the urea transporter UT-A1: cAMP activation and snapin binding. American journal of physiology. Cell physiology 7 20457831
2021 SNAPIN Regulates Cell Cycle Progression to Promote Pancreatic β Cell Growth. Frontiers in endocrinology 6 34194388
2006 Interaction between Snapin and G-CSF receptor. Cytokine 6 16595180
2023 The role of snapin in regulation of brain homeostasis. Neural regeneration research 5 38103234
2013 Snapin, positive regulator of stimulation- induced Ca²⁺ release through RyR, is necessary for HIV-1 replication in T cells. PloS one 5 24130701
2006 Modeling of the potential coiled-coil structure of snapin protein and its interaction with SNARE complex. Bioinformation 4 17597906
2021 Snapin Specifically Up-Regulates Cav1.3 Ca2+ Channel Variant with a Long Carboxyl Terminus. International journal of molecular sciences 2 34681928
2025 Autism-Associated PTCHD1 Missense Variants Bind to the SNARE-Associated Protein SNAPIN but Exhibit Impaired Subcellular Trafficking. Biological psychiatry global open science 1 40475291
2023 Interaction between the VP2 protein of deformed wing virus and host snapin protein and its effect on viral replication. Frontiers in microbiology 1 36846748
2026 Snapin mediates neuronal PANoptosis after mild traumatic brain injury via H2S-dependent S-sulfhydration of CTSD. Journal of advanced research 0 41558604
2025 CK1δ-Dependent SNAPIN Dysregulation Drives Lysosomal Failure in HIV-1 Vpr-Exposed Neurons: A Targetable Mechanism in HAND. bioRxiv : the preprint server for biology 0 40791547
2025 Bi-allelic deleterious variants in SNAPIN, which encodes a retrograde dynein adaptor, cause a prenatal-onset neurodevelopmental disorder. American journal of human genetics 0 40930097
2025 SNAPIN Facilitates Progression of Hepatocellular Carcinoma by Hindering Ferroptosis Through KEAP1 Degradation Promotion. Cancer science 0 41190709
2025 Targeted NanoBiT Screening Identifies a Novel Interaction Between SNAPIN and Influenza A Virus M1 Protein. Biology 0 41463543
2025 CK1δ-dependent SNAPIN dysregulation drives lysosomal failure in HIV-1 Vpr-exposed neurons: A targetable mechanism in HAND. iScience 0 41567242