SNAP25

File:Exocytosis-machinery.jpg

SNAP-25, a Q-SNARE protein, is anchored to the cytosolic face of membranes via palmitoyl side chains covalently bound to cysteine amino acid residues in the central linker domain of the molecule. This means that SNAP-25 does not contain a trans-membrane domain.{{cite journal | vauthors = Chapman ER, An S, Barton N, Jahn R | title = SNAP-25, a t-SNARE which binds to both syntaxin and synaptobrevin via domains that may form coiled coils | journal = The Journal of Biological Chemistry | volume = 269 | issue = 44 | pages = 27427–32 | date = November 1994 | doi = 10.1016/S0021-9258(18)47003-2 | pmid = 7961655 | doi-access = free }}

SNAP-25 has been identified to contribute two{{cite journal | vauthors = Ungar D, Hughson FM | title = SNARE protein structure and function | journal = Annual Review of Cell and Developmental Biology | volume = 19 | issue = 1 | pages = 493–517 | year = 2003 | pmid = 14570579 | doi = 10.1146/annurev.cellbio.19.110701.155609 | publisher = Annual Reviews }} α-helices to the SNARE complex, a four-α-helix domain complex.{{cite journal | vauthors = Pevsner J, Hsu SC, Braun JE, Calakos N, Ting AE, Bennett MK, Scheller RH | title = Specificity and regulation of a synaptic vesicle docking complex | journal = Neuron | volume = 13 | issue = 2 | pages = 353–61 | date = August 1994 | pmid = 8060616 | doi = 10.1016/0896-6273(94)90352-2 | s2cid = 46713725 | doi-access = free }} The SNARE complex participates in vesicle fusion, which involves the docking, priming and merging of a vesicle with the cell membrane to initiate an exocytotic event. Synaptobrevin, a protein that is a part of the vesicle-associated membrane protein (VAMP) family, and syntaxin-1 also help form the SNARE complex by each contributing a single α-helix. SNAP-25 assembles with synaptobrevin and syntaxin-1, and the selective binding of these proteins enables vesicle docking and fusion to occur at active zones on the plasma membrane.{{cite journal | vauthors = Calakos N, Bennett MK, Peterson KE, Scheller RH | title = Protein-protein interactions contributing to the specificity of intracellular vesicular trafficking | journal = Science | volume = 263 | issue = 5150 | pages = 1146–9 | date = February 1994 | pmid = 8108733 | doi = 10.1126/science.8108733 | bibcode = 1994Sci...263.1146C }} The energy needed for fusion to occur, results from the assembly of the SNARE proteins along with additional Sec1/Munc18-like (SM) proteins.{{cite journal | vauthors = Südhof TC, Rizo J | title = Synaptic vesicle exocytosis | journal = Cold Spring Harbor Perspectives in Biology | volume = 3 | issue = 12 | pages = a005637 | date = December 2011 | pmid = 22026965 | pmc = 3225952 | doi = 10.1101/cshperspect.a005637 }}

To form the SNARE complex, synaptobrevin, syntaxin-1, and SNAP-25 associate and begin to wrap around each other to form a coiled coil quaternary structure. The α-helices of both synaptobrevin and syntaxin-1 bind to those of SNAP-25. Synaptobrevin binds the α-helix near the C-terminus of SNAP-25, while syntaxin-1 binds the α-helix near the N-terminus. Dissociation of the SNARE complex is driven by ATPase N-ethylmaleimide-sensitive fusion (NSF) protein.

SNAP-25 inhibits presynaptic P-, Q-, and L-type voltage-gated calcium channels{{cite journal | vauthors = Hodel A | title = SNAP-25 | journal = The International Journal of Biochemistry & Cell Biology | volume = 30 | issue = 10 | pages = 1069–73 | date = October 1998 | pmid = 9785471 | doi = 10.1016/S1357-2725(98)00079-X }} and interacts with the synaptotagmin C2B domain in a Ca²⁺-independent fashion.{{cite journal | vauthors = Chapman ER | title = Synaptotagmin: a Ca(2+) sensor that triggers exocytosis? | journal = Nature Reviews. Molecular Cell Biology | volume = 3 | issue = 7 | pages = 498–508 | date = July 2002 | pmid = 12094216 | doi = 10.1038/nrm855 | url = http://www.physiology.wisc.edu/chapman/papers/naturereview.pdf | url-status = dead | s2cid = 12384262 | archive-url = https://web.archive.org/web/20060829001053/http://www.physiology.wisc.edu/chapman/papers/naturereview.pdf | archive-date = August 29, 2006 }} In glutamatergic synapses, SNAP-25 decreases the Ca²⁺ responsiveness, while it is normally absent in GABAergic synapses.{{cite journal | vauthors = Verderio C, Pozzi D, Pravettoni E, Inverardi F, Schenk U, Coco S, Proux-Gillardeaux V, Galli T, Rossetto O, Frassoni C, Matteoli M | display-authors = 6 | title = SNAP-25 modulation of calcium dynamics underlies differences in GABAergic and glutamatergic responsiveness to depolarization | journal = Neuron | volume = 41 | issue = 4 | pages = 599–610 | date = February 2004 | pmid = 14980208 | doi = 10.1016/S0896-6273(04)00077-7 | s2cid = 16171280 | doi-access = free }}

Two isoforms (mRNA splice variants) of SNAP-25 exist, which are SNAP-25a and SNAP-25b. The two isoforms differ by nine amino acid residues, including a re-localization of one of the four palmitoylated cysteine residues involved in membrane attachment.{{cite journal | vauthors = Nagy G, Milosevic I, Fasshauer D, Müller EM, de Groot BL, Lang T, Wilson MC, Sørensen JB | display-authors = 6 | title = Alternative splicing of SNAP-25 regulates secretion through nonconservative substitutions in the SNARE domain | journal = Molecular Biology of the Cell | volume = 16 | issue = 12 | pages = 5675–85 | date = December 2005 | pmid = 16195346 | pmc = 1289412 | doi = 10.1091/mbc.E05-07-0595 }} The major characteristics of these two forms are outlined in the table below.

SNAP-25 not only plays a role in synaptogenesis and the exocytotic release of neurotransmitters, but it also affects spine morphogenesis and density, post synaptic receptor trafficking and neuronal plasticity. Other non-neuronal processes such as metabolism can also be affected by SNAP-25 protein expression.{{cite journal | vauthors = Houenou J, Boisgontier J, Henrion A, d'Albis MA, Dumaine A, Linke J, Wessa M, Daban C, Hamdani N, Delavest M, Llorca PM, Lançon C, Schürhoff F, Szöke A, Le Corvoisier P, Barau C, Poupon C, Etain B, Leboyer M, Jamain S | display-authors = 6 | title = SNAP25 At-Risk Variant for Bipolar Disorder and Schizophrenia | journal = The Journal of Neuroscience | volume = 37 | issue = 43 | pages = 10389–10397 | date = October 2017 | pmid = 28972123 | pmc = 6596626 | doi = 10.1523/JNEUROSCI.1040-17.2017 }}{{cite journal | vauthors = Antonucci F, Corradini I, Fossati G, Tomasoni R, Menna E, Matteoli M | title = SNAP-25, a Known Presynaptic Protein with Emerging Postsynaptic Functions | language = en | journal = Frontiers in Synaptic Neuroscience | volume = 8 | pages = 7 | date = 2016 | pmid = 27047369 | pmc = 4805587 | doi = 10.3389/fnsyn.2016.00007 | doi-access = free }}

Individuals harboring pathogenic heterozygous de novo missense or loss-of-function variants in SNAP-25 often present with an early-onset developmental and epileptic encephalopathy. The core symptoms comprise intellectual disability ranging between mild to profound and early-onset seizures mostly occurring before the age of two years. Further recurrent symptoms include movement disorders, cerebral visual impairment, and brain atrophy.{{cite journal | vauthors = Klöckner C, Sticht H, Zacher P, Popp B, Babcock HE, Bakker DP, Barwick K, Bonfert MV, Bönnemann CG, Brilstra EH, Chung WK, Clarke AJ, Devine P, Donkervoort S, Fraser JL, Friedman J, Gates A, Ghoumid J, Hobson E, Horvath G, Keller-Ramey J, Keren B, Kurian MA, Lee V, Leppig KA, Lundgren J, McDonald MT, McLaughlin HM, McTague A, Mefford HC, Mignot C, Mikati MA, Nava C, Raymond FL, Sampson JR, Sanchis-Juan A, Shashi V, Shieh JT, Shinawi M, Slavotinek A, Stödberg T, Stong N, Sullivan JA, Taylor AC, Toler TL, van den Boogaard MJ, van der Crabben SN, van Gassen KL, van Jaarsveld RH, Van Ziffle J, Wadley AF, Wagner M, Wigby K, Wortmann SB, Zarate YA, Møller RS, Lemke JR, Platzer K | display-authors = 6 | title = De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy | journal = Genetics in Medicine | volume = 23 | issue = 4 | pages = 653–660 | date = April 2021 | pmid = 33299146 | doi = 10.1038/s41436-020-01020-w | s2cid = 228087433 | url = https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=60808 | doi-access = free }} Electrophysiological studies identified aberrant spontaneous neurotransmission as causative and suggest that structurally clustered pathogenic variants lead to similar synaptic phenotypes.{{cite journal | vauthors = Alten B, Zhou Q, Shin OH, Esquivies L, Lin PY, White KI, Sun R, Chung WK, Monteggia LM, Brunger AT, Kavalali ET | display-authors = 6 | title = Role of Aberrant Spontaneous Neurotransmission in SNAP25-Associated Encephalopathies | journal = Neuron | volume = 109 | issue = 1 | pages = 59–72.e5 | date = January 2021 | pmid = 33147442 | pmc = 7790958 | doi = 10.1016/j.neuron.2020.10.012 }}

Consistent with the regulation of synaptic Ca²⁺ responsiveness, heterozygous deletion of the SNAP-25 gene in mice results in a hyperactive phenotype similar to attention deficit hyperactivity disorder (ADHD). In heterozygous mice, a decrease in hyperactivity is observed with dextroamphetamine (or Dexedrine), an active ingredient in the ADHD drug Adderall. Homozygous deletions of the SNAP-25 gene are lethal. An additional study indicated that incorporation of a SNAP-25 transgene back into the heterozygous SNAP-25 mutant mouse can rescue normal activity levels similar to wildtype mice. This suggests that low protein levels of SNAP-25 can be a cause of hyper-kinetic behavior.{{cite journal | vauthors = Steffensen SC, Henriksen SJ, Wilson MC | title = Transgenic rescue of SNAP-25 restores dopamine-modulated synaptic transmission in the coloboma mutant | journal = Brain Research | volume = 847 | issue = 2 | pages = 186–95 | date = November 1999 | pmid = 10575087 | doi = 10.1016/S0006-8993(99)02023-5 | s2cid = 41368865 }} Subsequent studies have suggested that at least some of the SNAP-25 gene mutations in humans might predispose to ADHD.{{cite journal | vauthors = Brophy K, Hawi Z, Kirley A, Fitzgerald M, Gill M | title = Synaptosomal-associated protein 25 (SNAP-25) and attention deficit hyperactivity disorder (ADHD): evidence of linkage and association in the Irish population | journal = Molecular Psychiatry | volume = 7 | issue = 8 | pages = 913–7 | year = 2002 | pmid = 12232787 | doi = 10.1038/sj.mp.4001092 | doi-access = free | hdl = 2262/36350 | hdl-access = free }}{{cite journal | vauthors = Mill J, Curran S, Kent L, Gould A, Huckett L, Richards S, Taylor E, Asherson P | display-authors = 6 | title = Association study of a SNAP-25 microsatellite and attention deficit hyperactivity disorder | journal = American Journal of Medical Genetics | volume = 114 | issue = 3 | pages = 269–71 | date = April 2002 | pmid = 11920846 | doi = 10.1002/ajmg.10253 }} Identification of polymorphisms in the 3’ untranslated region of the SNAP-25 gene was established in linkage studies with families that had been pre-diagnosed ADHD.{{cite journal | vauthors = Barr CL, Feng Y, Wigg K, Bloom S, Roberts W, Malone M, Schachar R, Tannock R, Kennedy JL | display-authors = 6 | title = Identification of DNA variants in the SNAP-25 gene and linkage study of these polymorphisms and attention-deficit hyperactivity disorder | journal = Molecular Psychiatry | volume = 5 | issue = 4 | pages = 405–9 | date = July 2000 | pmid = 10889551 | doi = 10.1038/sj.mp.4000733 | s2cid = 22779309 | doi-access = free }}

Studies in the post mortem brains of patients with Schizophrenia have shown that altered protein levels of SNAP-25 are specific to regions of the brain. Reduced SNAP-25 protein expression has been observed in the hippocampus as well as an area of the frontal lobe known as Broadman's area 10 whereas SNAP-25 expression has increased in both the cingulate cortex and prefrontal lobe of Broadman's area 9. The varying levels of SNAP-25 protein found in different areas of the brain have been thought to contribute to the conflicting psychological behaviors (depressive vs. hyperactive) expressed in some Schizophrenic patients.{{cite journal | vauthors = Corradini I, Verderio C, Sala M, Wilson MC, Matteoli M | title = SNAP-25 in neuropsychiatric disorders | journal = Annals of the New York Academy of Sciences | volume = 1152 | issue = 1 | pages = 93–9 | date = January 2009 | pmid = 19161380 | pmc = 2706123 | doi = 10.1111/j.1749-6632.2008.03995.x | bibcode = 2009NYASA1152...93C }}{{cite journal | vauthors = Gabriel SM, Haroutunian V, Powchik P, Honer WG, Davidson M, Davies P, Davis KL | title = Increased concentrations of presynaptic proteins in the cingulate cortex of subjects with schizophrenia | journal = Archives of General Psychiatry | volume = 54 | issue = 6 | pages = 559–66 | date = June 1997 | pmid = 9193197 | doi = 10.1001/archpsyc.1997.01830180077010 }}{{cite journal | vauthors = Thompson PM, Sower AC, Perrone-Bizzozero NI | title = Altered levels of the synaptosomal associated protein SNAP-25 in schizophrenia | journal = Biological Psychiatry | volume = 43 | issue = 4 | pages = 239–43 | date = February 1998 | pmid = 9513732 | doi = 10.1016/S0006-3223(97)00204-7 | s2cid = 20347660 }}{{cite journal | vauthors = Thompson PM, Egbufoama S, Vawter MP | title = SNAP-25 reduction in the hippocampus of patients with schizophrenia | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 27 | issue = 3 | pages = 411–7 | date = May 2003 | pmid = 12691775 | doi = 10.1016/S0278-5846(03)00027-7 | s2cid = 1051797 }}

The blind-drunk (Bdr) mouse model which has a point mutations in the SNAP-25b protein has provided a complex phenotype involving behaviors such as an abnormal circadian rhythm,{{cite journal | vauthors = Oliver PL, Sobczyk MV, Maywood ES, Edwards B, Lee S, Livieratos A, Oster H, Butler R, Godinho SI, Wulff K, Peirson SN, Fisher SP, Chesham JE, Smith JW, Hastings MH, Davies KE, Foster RG | display-authors = 6 | title = Disrupted circadian rhythms in a mouse model of schizophrenia | journal = Current Biology | volume = 22 | issue = 4 | pages = 314–9 | date = February 2012 | pmid = 22264613 | pmc = 3356578 | doi = 10.1016/j.cub.2011.12.051 }} uncoordinated gait, and disinterest in new objects/toys.{{cite journal | vauthors = Jeans AF, Oliver PL, Johnson R, Capogna M, Vikman J, Molnár Z, Babbs A, Partridge CJ, Salehi A, Bengtsson M, Eliasson L, Rorsman P, Davies KE | display-authors = 6 | title = A dominant mutation in Snap25 causes impaired vesicle trafficking, sensorimotor gating, and ataxia in the blind-drunk mouse | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 7 | pages = 2431–6 | date = February 2007 | pmid = 17283335 | pmc = 1793901 | doi = 10.1073/pnas.0610222104 | bibcode = 2007PNAS..104.2431J | doi-access = free }} Another mouse model generated from Cre-LoxP recombination, showed that conditional knockout (cKO) of the SNAP-25 gene in the forebrain, showed inactive SNAP-25 gene expression in glutamatergic neurons. However, significant glutamate levels were found in the cortex of these cKO mice.{{cite journal | vauthors = Yang H, Zhang M, Shi J, Zhou Y, Wan Z, Wang Y, Wan Y, Li J, Wang Z, Fei J | display-authors = 6 | title = Brain-Specific SNAP-25 Deletion Leads to Elevated Extracellular Glutamate Level and Schizophrenia-Like Behavior in Mice | journal = Neural Plasticity | volume = 2017 | pages = 4526417 | date = 2017 | pmid = 29318050 | pmc = 5727794 | doi = 10.1155/2017/4526417 | doi-access = free }} These mice also exhibited deficient social skills, impaired learning and memory, enhanced kinesthetic activity, a reduced startle response, impaired self-care, nursing ability and nest-building skills. Antipsychotic drugs such as Clozapine and Riluzole have been shown to significantly reduce the schizophrenic phenotype expressed in SNAP-25 cKO mice.

Individuals with Alzhiemer's disease have been shown to have decreased presynaptic protein levels and impaired synaptic function in neurons. SNAP-25 can be used as a biomarker in the cerebral spinal fluid (CSF) of patients exhibiting different variations of Alzheimer's disease (prodromal Alzheimer's and overt Alzheimer's). Increased levels of SNAP-25 protein were observed in patients with Alzheimer's compared to control individuals. Additionally, the presence of truncated SNAP-25 protein can be seen in the CSF of some patients with this disease. {{cite journal | vauthors = Brinkmalm A, Brinkmalm G, Honer WG, Frölich L, Hausner L, Minthon L, Hansson O, Wallin A, Zetterberg H, Blennow K, Öhrfelt A | display-authors = 6 | title = SNAP-25 is a promising novel cerebrospinal fluid biomarker for synapse degeneration in Alzheimer's disease | journal = Molecular Neurodegeneration | volume = 9 | pages = 53 | date = November 2014 | pmid = 25418885 | pmc = 4253625 | doi = 10.1186/1750-1326-9-53 | doi-access = free }} In five distinct regions of the brain, low levels of SNAP-25 can be seen in patients with Alzheimer's.{{cite journal | vauthors = Greber S, Lubec G, Cairns N, Fountoulakis M | title = Decreased levels of synaptosomal associated protein 25 in the brain of patients with Down syndrome and Alzheimer's disease | journal = Electrophoresis | volume = 20 | issue = 4–5 | pages = 928–34 | date = 1999 | pmid = 10344268 | doi = 10.1002/(SICI)1522-2683(19990101)20:4/5<928::AID-ELPS928>3.0.CO;2-Z | s2cid = 22531212 }}

A single nucleotide polymorphism in the SNAP-25 gene promoter has been shown to influence the expression levels of the SNAP-25b isoform in the prefrontal cortex. Increased levels of SNAP-25b have been shown to impair synaptic transmission and maturation which could lead to early-onset bipolar disorder (EOBD).The most abundant isoform of SNAP-25 is SNAP-25a during the early weeks of development in mice however in adulthood there is a change and the SNAP-25b isoform increases in the brain. This is shown to correlate with adolescent humans being increasingly diagnosed with EOBD during puberty.{{cite journal | vauthors = Etain B, Dumaine A, Mathieu F, Chevalier F, Henry C, Kahn JP, Deshommes J, Bellivier F, Leboyer M, Jamain S | display-authors = 6 | title = A SNAP25 promoter variant is associated with early-onset bipolar disorder and a high expression level in brain | journal = Molecular Psychiatry | volume = 15 | issue = 7 | pages = 748–55 | date = July 2010 | pmid = 19125158 | pmc = 2937032 | doi = 10.1038/mp.2008.148 }} It has been suggested that early-onset bipolar disorder is more closely linked to Schizophrenia than to Bipolar Disorder itself. The single nucleotide polymorphism of SNAP-25 (rs6039769) associated with EOBD has been shown to increase the risk of patients developing Schizophrenia.

A genome wide association study pointed to the rs362584 polymorphism in the gene as possibly associated with the personality trait neuroticism.{{cite journal | vauthors = Terracciano A, Sanna S, Uda M, Deiana B, Usala G, Busonero F, Maschio A, Scally M, Patriciu N, Chen WM, Distel MA, Slagboom EP, Boomsma DI, Villafuerte S, Sliwerska E, Burmeister M, Amin N, Janssens AC, van Duijn CM, Schlessinger D, Abecasis GR, Costa PT | display-authors = 6 | title = Genome-wide association scan for five major dimensions of personality | journal = Molecular Psychiatry | volume = 15 | issue = 6 | pages = 647–56 | date = June 2010 | pmid = 18957941 | pmc = 2874623 | doi = 10.1038/mp.2008.113 }} Botulinum toxins A, C and E cleave SNAP-25,{{cite journal | vauthors = Aoki KR, Guyer B | title = Botulinum toxin type A and other botulinum toxin serotypes: a comparative review of biochemical and pharmacological actions | journal = European Journal of Neurology | volume = 8 | pages = 21–9 | date = November 2001 | issue = Suppl 5 | pmid = 11851731 | doi = 10.1046/j.1468-1331.2001.00035.x | s2cid = 36829902 }} leading to paralysis in clinically developed botulism.

Deletion of the SNAP-25b isoform has been shown to cause developmental abnormalities and seizures in mice. High levels of SNAP-25a and the protein syntaxin appear to be linked to seizures found in infantile-epilepsy. SNAP-25 knock-in mice have distinct phenotypic behavior similar to the fits and seizures of epileptic patients, as well as anxiety.{{cite journal | vauthors = Rohena L, Neidich J, Truitt Cho M, Gonzalez KD, Tang S, Devinsky O, Chung WK | title = Mutation in SNAP25 as a novel genetic cause of epilepsy and intellectual disability | journal = Rare Diseases | volume = 1 | issue = 1 | pages = e26314 | date = 2013 | pmid = 25003006 | pmc = 3932847 | doi = 10.4161/rdis.26314 }}

In the coloboma hyperactive mutant mouse model where SNAP-25 protein levels are reduced to 50% of the normal level, depolarized neurotransmitter release of dopamine and serotonin were reduced as well as glutamate release. The reduction in glutamate levels can lead to deficient memory and increased learning disabilities.{{cite journal | vauthors = Raber J, Mehta PP, Kreifeldt M, Parsons LH, Weiss F, Bloom FE, Wilson MC | title = Coloboma hyperactive mutant mice exhibit regional and transmitter-specific deficits in neurotransmission | journal = Journal of Neurochemistry | volume = 68 | issue = 1 | pages = 176–86 | date = January 1997 | pmid = 8978724 | doi = 10.1046/j.1471-4159.1997.68010176.x | s2cid = 25505619 | doi-access = free }} Certain polymorphisms of SNAP-25 (rs363043, rs353016, rs363039, rs363050) have been shown to affect the cognitive behavior, specifically the Intelligence Quotient (IQ)), of patients without pre-existing neurological diseases.{{cite journal | vauthors = Gosso MF, de Geus EJ, van Belzen MJ, Polderman TJ, Heutink P, Boomsma DI, Posthuma D | title = The SNAP-25 gene is associated with cognitive ability: evidence from a family-based study in two independent Dutch cohorts | journal = Molecular Psychiatry | volume = 11 | issue = 9 | pages = 878–86 | date = September 2006 | pmid = 16801949 | doi = 10.1038/sj.mp.4001868 | s2cid = 437158 | url = https://research.vu.nl/en/publications/ff55aca0-6740-44e1-99bb-79b7dc2d39c5 }}

SNAP-25 protein expression can be altered by sex hormone levels in neonatal rats. Male rats that received an antiestrogen drug showed a 30% decrease in SNAP-25 levels and females treated with estrogen or testosterone showed a 30% increase in SNAP-25 levels.{{cite journal | vauthors = Lustig RH, Hua P, Wilson MC, Federoff HJ | title = Ontogeny, sex dimorphism, and neonatal sex hormone determination of synapse-associated messenger RNAs in rat brain | journal = Brain Research. Molecular Brain Research | volume = 20 | issue = 1–2 | pages = 101–10 | date = October 1993 | pmid = 8255171 | doi = 10.1016/0169-328X(93)90114-5 }} This suggests that synaptosomal proteins, such as SNAP-25, may have a dependence on neonatal hormone levels during brain development in rats. An additional study, showed that SNAP-25 levels in the hippocampus of the brain in neonatal mice were altered if the mother had been exposed to human influenza virus during pregnancy.{{cite journal | vauthors = Fatemi SH, Sidwell R, Kist D, Akhter P, Meltzer HY, Bailey K, Thuras P, Sedgwick J | display-authors = 6 | title = Differential expression of synaptosome-associated protein 25 kDa [SNAP-25] in hippocampi of neonatal mice following exposure to human influenza virus in utero | journal = Brain Research | volume = 800 | issue = 1 | pages = 1–9 | date = July 1998 | pmid = 9685568 | doi = 10.1016/S0006-8993(98)00450-8 | s2cid = 36917316 }}

Loss is lethal to Drosophila, but can be fully substituted by overexpression of the related SNAP-24.

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SNAP-25 has been shown to interact with:

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• CPLX1,{{cite journal | vauthors = Hu K, Carroll J, Rickman C, Davletov B | title = Action of complexin on SNARE complex | journal = The Journal of Biological Chemistry | volume = 277 | issue = 44 | pages = 41652–6 | date = November 2002 | pmid = 12200427 | doi = 10.1074/jbc.M205044200 | doi-access = free }}
• ITSN1,{{cite journal | vauthors = Okamoto M, Schoch S, Südhof TC | title = EHSH1/intersectin, a protein that contains EH and SH3 domains and binds to dynamin and SNAP-25. A protein connection between exocytosis and endocytosis? | journal = The Journal of Biological Chemistry | volume = 274 | issue = 26 | pages = 18446–54 | date = June 1999 | pmid = 10373452 | doi = 10.1074/jbc.274.26.18446 | doi-access = free }}
• KIF5B,{{cite journal | vauthors = Diefenbach RJ, Diefenbach E, Douglas MW, Cunningham AL | title = The heavy chain of conventional kinesin interacts with the SNARE proteins SNAP25 and SNAP23 | journal = Biochemistry | volume = 41 | issue = 50 | pages = 14906–15 | date = December 2002 | pmid = 12475239 | doi = 10.1021/bi026417u }}
• SNAPAP and
• STX11,{{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | display-authors = 6 | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 | s2cid = 4427026 | bibcode = 2005Natur.437.1173R }}
• STX1A,{{cite journal | vauthors = Chen X, Tomchick DR, Kovrigin E, Araç D, Machius M, Südhof TC, Rizo J | title = Three-dimensional structure of the complexin/SNARE complex | journal = Neuron | volume = 33 | issue = 3 | pages = 397–409 | date = January 2002 | pmid = 11832227 | doi = 10.1016/s0896-6273(02)00583-4 | url = https://epublications.marquette.edu/cgi/viewcontent.cgi?article=1227&context=chem_fac | s2cid = 17878965 | doi-access = free }}{{cite journal | vauthors = Ilardi JM, Mochida S, Sheng ZH | title = Snapin: a SNARE-associated protein implicated in synaptic transmission | journal = Nature Neuroscience | volume = 2 | issue = 2 | pages = 119–24 | date = February 1999 | pmid = 10195194 | doi = 10.1038/5673 | s2cid = 25524692 }}{{cite journal | vauthors = Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE | display-authors = 6 | title = A human protein-protein interaction network: a resource for annotating the proteome | journal = Cell | volume = 122 | issue = 6 | pages = 957–68 | date = September 2005 | pmid = 16169070 | doi = 10.1016/j.cell.2005.08.029 | hdl-access = free | s2cid = 8235923 | hdl = 11858/00-001M-0000-0010-8592-0 }}{{cite journal | vauthors = Dulubova I, Sugita S, Hill S, Hosaka M, Fernandez I, Südhof TC, Rizo J | title = A conformational switch in syntaxin during exocytosis: role of munc18 | journal = The EMBO Journal | volume = 18 | issue = 16 | pages = 4372–82 | date = August 1999 | pmid = 10449403 | pmc = 1171512 | doi = 10.1093/emboj/18.16.4372 }}{{cite journal | vauthors = McMahon HT, Missler M, Li C, Südhof TC | title = Complexins: cytosolic proteins that regulate SNAP receptor function | journal = Cell | volume = 83 | issue = 1 | pages = 111–9 | date = October 1995 | pmid = 7553862 | doi = 10.1016/0092-8674(95)90239-2 | s2cid = 675343 | doi-access = free }}{{cite journal | vauthors = Gonelle-Gispert C, Molinete M, Halban PA, Sadoul K | title = Membrane localization and biological activity of SNAP-25 cysteine mutants in insulin-secreting cells | journal = Journal of Cell Science | volume = 113 ( Pt 18) | issue = 18 | pages = 3197–205 | date = September 2000 | doi = 10.1242/jcs.113.18.3197 | pmid = 10954418 | url = https://archive-ouverte.unige.ch/unige:8762 }}{{cite journal | vauthors = Li Y, Chin LS, Weigel C, Li L | title = Spring, a novel RING finger protein that regulates synaptic vesicle exocytosis | journal = The Journal of Biological Chemistry | volume = 276 | issue = 44 | pages = 40824–33 | date = November 2001 | pmid = 11524423 | doi = 10.1074/jbc.M106141200 | doi-access = free }}{{cite journal | vauthors = Chapman ER, An S, Barton N, Jahn R | title = SNAP-25, a t-SNARE which binds to both syntaxin and synaptobrevin via domains that may form coiled coils | journal = The Journal of Biological Chemistry | volume = 269 | issue = 44 | pages = 27427–32 | date = November 1994 | doi = 10.1016/S0021-9258(18)47003-2 | pmid = 7961655 | doi-access = free }}
• STX2,
• STX4,{{cite journal | vauthors = Hata Y, Südhof TC | title = A novel ubiquitous form of Munc-18 interacts with multiple syntaxins. Use of the yeast two-hybrid system to study interactions between proteins involved in membrane traffic | journal = The Journal of Biological Chemistry | volume = 270 | issue = 22 | pages = 13022–8 | date = June 1995 | pmid = 7768895 | doi = 10.1074/jbc.270.22.13022 | doi-access = free }}{{cite journal | vauthors = Ravichandran V, Chawla A, Roche PA | title = Identification of a novel syntaxin- and synaptobrevin/VAMP-binding protein, SNAP-23, expressed in non-neuronal tissues | journal = The Journal of Biological Chemistry | volume = 271 | issue = 23 | pages = 13300–3 | date = June 1996 | pmid = 8663154 | doi = 10.1074/jbc.271.23.13300 | doi-access = free }}{{cite journal | vauthors = Steegmaier M, Yang B, Yoo JS, Huang B, Shen M, Yu S, Luo Y, Scheller RH | display-authors = 6 | title = Three novel proteins of the syntaxin/SNAP-25 family | journal = The Journal of Biological Chemistry | volume = 273 | issue = 51 | pages = 34171–9 | date = December 1998 | pmid = 9852078 | doi = 10.1074/jbc.273.51.34171 | doi-access = free }}{{cite journal | vauthors = Reed GL, Houng AK, Fitzgerald ML | title = Human platelets contain SNARE proteins and a Sec1p homologue that interacts with syntaxin 4 and is phosphorylated after thrombin activation: implications for platelet secretion | journal = Blood | volume = 93 | issue = 8 | pages = 2617–26 | date = April 1999 | pmid = 10194441 | doi = 10.1182/blood.V93.8.2617 }}
• SYT1,{{cite journal | vauthors = Gerona RR, Larsen EC, Kowalchyk JA, Martin TF | title = The C terminus of SNAP25 is essential for Ca(2+)-dependent binding of synaptotagmin to SNARE complexes | journal = The Journal of Biological Chemistry | volume = 275 | issue = 9 | pages = 6328–36 | date = March 2000 | pmid = 10692432 | doi = 10.1074/jbc.275.9.6328 | doi-access = free }}{{cite journal | vauthors = Zhang X, Kim-Miller MJ, Fukuda M, Kowalchyk JA, Martin TF | title = Ca2+-dependent synaptotagmin binding to SNAP-25 is essential for Ca2+-triggered exocytosis | journal = Neuron | volume = 34 | issue = 4 | pages = 599–611 | date = May 2002 | pmid = 12062043 | doi = 10.1016/s0896-6273(02)00671-2 | s2cid = 16768299 | doi-access = free }}
• Syntaxin 3,
• TRIM9, and
• VAMP2.{{cite journal | vauthors = Hao JC, Salem N, Peng XR, Kelly RB, Bennett MK | title = Effect of mutations in vesicle-associated membrane protein (VAMP) on the assembly of multimeric protein complexes | journal = The Journal of Neuroscience | volume = 17 | issue = 5 | pages = 1596–603 | date = March 1997 | pmid = 9030619 | pmc = 6573372 | doi = 10.1523/JNEUROSCI.17-05-01596.1997 }}
• Synaptotagmin binds SNAP-25 and syntaxins in the presence of Ca{{sup|2+}} (and thus the entire SNARE complex)

{{Div col end}}

{{Reflist|2}}

{{Refbegin| 2}}

• {{cite journal | vauthors = Hanson PI, Otto H, Barton N, Jahn R | title = The N-ethylmaleimide-sensitive fusion protein and alpha-SNAP induce a conformational change in syntaxin | journal = The Journal of Biological Chemistry | volume = 270 | issue = 28 | pages = 16955–61 | date = July 1995 | pmid = 7622514 | doi = 10.1074/jbc.270.28.16955 | doi-access = free }}
• {{cite journal | vauthors = Hata Y, Südhof TC | title = A novel ubiquitous form of Munc-18 interacts with multiple syntaxins. Use of the yeast two-hybrid system to study interactions between proteins involved in membrane traffic | journal = The Journal of Biological Chemistry | volume = 270 | issue = 22 | pages = 13022–8 | date = June 1995 | pmid = 7768895 | doi = 10.1074/jbc.270.22.13022 | doi-access = free }}
• {{cite journal | vauthors = Chapman ER, An S, Barton N, Jahn R | title = SNAP-25, a t-SNARE which binds to both syntaxin and synaptobrevin via domains that may form coiled coils | journal = The Journal of Biological Chemistry | volume = 269 | issue = 44 | pages = 27427–32 | date = November 1994 | doi = 10.1016/S0021-9258(18)47003-2 | pmid = 7961655 | doi-access = free }}
• {{cite journal | vauthors = Zhao N, Hashida H, Takahashi N, Sakaki Y | title = Cloning and sequence analysis of the human SNAP25 cDNA | journal = Gene | volume = 145 | issue = 2 | pages = 313–4 | date = August 1994 | pmid = 8056350 | doi = 10.1016/0378-1119(94)90027-2 }}
• {{cite journal | vauthors = Bark IC, Wilson MC | title = Human cDNA clones encoding two different isoforms of the nerve terminal protein SNAP-25 | journal = Gene | volume = 139 | issue = 2 | pages = 291–2 | date = February 1994 | pmid = 8112622 | doi = 10.1016/0378-1119(94)90773-0 }}
• {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
• {{cite journal | vauthors = Maglott DR, Feldblyum TV, Durkin AS, Nierman WC | title = Radiation hybrid mapping of SNAP, PCSK2, and THBD (human chromosome 20p) | journal = Mammalian Genome | volume = 7 | issue = 5 | pages = 400–1 | date = May 1996 | pmid = 8661740 | doi = 10.1007/s003359900120 | s2cid = 34951074 }}
• {{cite journal | vauthors = Ravichandran V, Chawla A, Roche PA | title = Identification of a novel syntaxin- and synaptobrevin/VAMP-binding protein, SNAP-23, expressed in non-neuronal tissues | journal = The Journal of Biological Chemistry | volume = 271 | issue = 23 | pages = 13300–3 | date = June 1996 | pmid = 8663154 | doi = 10.1074/jbc.271.23.13300 | doi-access = free }}
• {{cite journal | vauthors = Rettig J, Sheng ZH, Kim DK, Hodson CD, Snutch TP, Catterall WA | title = Isoform-specific interaction of the alpha1A subunits of brain Ca2+ channels with the presynaptic proteins syntaxin and SNAP-25 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 14 | pages = 7363–8 | date = July 1996 | pmid = 8692999 | pmc = 38990 | doi = 10.1073/pnas.93.14.7363 | bibcode = 1996PNAS...93.7363R | doi-access = free }}
• {{cite journal | vauthors = Jagadish MN, Fernandez CS, Hewish DR, Macaulay SL, Gough KH, Grusovin J, Verkuylen A, Cosgrove L, Alafaci A, Frenkel MJ, Ward CW | display-authors = 6 | title = Insulin-responsive tissues contain the core complex protein SNAP-25 (synaptosomal-associated protein 25) A and B isoforms in addition to syntaxin 4 and synaptobrevins 1 and 2 | journal = The Biochemical Journal | volume = 317 ( Pt 3) | issue = 3 | pages = 945–54 | date = August 1996 | pmid = 8760387 | pmc = 1217577 | doi = 10.1042/bj3170945 }}
• {{cite journal | vauthors = Betz A, Okamoto M, Benseler F, Brose N | title = Direct interaction of the rat unc-13 homologue Munc13-1 with the N terminus of syntaxin | journal = The Journal of Biological Chemistry | volume = 272 | issue = 4 | pages = 2520–6 | date = January 1997 | pmid = 8999968 | doi = 10.1074/jbc.272.4.2520 | doi-access = free }}
• {{cite journal | vauthors = Araki S, Tamori Y, Kawanishi M, Shinoda H, Masugi J, Mori H, Niki T, Okazawa H, Kubota T, Kasuga M | display-authors = 6 | title = Inhibition of the binding of SNAP-23 to syntaxin 4 by Munc18c | journal = Biochemical and Biophysical Research Communications | volume = 234 | issue = 1 | pages = 257–62 | date = May 1997 | pmid = 9168999 | doi = 10.1006/bbrc.1997.6560 | hdl = 20.500.14094/D2002245 | hdl-access = free }}
• {{cite journal | vauthors = Lane SR, Liu Y | title = Characterization of the palmitoylation domain of SNAP-25 | journal = Journal of Neurochemistry | volume = 69 | issue = 5 | pages = 1864–9 | date = November 1997 | pmid = 9349529 | doi = 10.1046/j.1471-4159.1997.69051864.x | s2cid = 6343703 | doi-access = free }}
• {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
• {{cite journal | vauthors = Okamoto M, Südhof TC | title = Mints, Munc18-interacting proteins in synaptic vesicle exocytosis | journal = The Journal of Biological Chemistry | volume = 272 | issue = 50 | pages = 31459–64 | date = December 1997 | pmid = 9395480 | doi = 10.1074/jbc.272.50.31459 | doi-access = free }}
• {{cite journal | vauthors = Low SH, Roche PA, Anderson HA, van Ijzendoorn SC, Zhang M, Mostov KE, Weimbs T|author6-link=Keith E. Mostov | title = Targeting of SNAP-23 and SNAP-25 in polarized epithelial cells | journal = The Journal of Biological Chemistry | volume = 273 | issue = 6 | pages = 3422–30 | date = February 1998 | pmid = 9452464 | doi = 10.1074/jbc.273.6.3422 | doi-access = free }}
• {{cite journal | vauthors = Poirier MA, Hao JC, Malkus PN, Chan C, Moore MF, King DS, Bennett MK | title = Protease resistance of syntaxin.SNAP-25.VAMP complexes. Implications for assembly and structure | journal = The Journal of Biological Chemistry | volume = 273 | issue = 18 | pages = 11370–7 | date = May 1998 | pmid = 9556632 | doi = 10.1074/jbc.273.18.11370 | doi-access = free }}
• {{cite journal | vauthors = Prekeris R, Klumperman J, Chen YA, Scheller RH | title = Syntaxin 13 mediates cycling of plasma membrane proteins via tubulovesicular recycling endosomes | journal = The Journal of Cell Biology | volume = 143 | issue = 4 | pages = 957–71 | date = November 1998 | pmid = 9817754 | pmc = 2132958 | doi = 10.1083/jcb.143.4.957 }}
• {{cite journal | vauthors = Gonelle-Gispert C, Halban PA, Niemann H, Palmer M, Catsicas S, Sadoul K | title = SNAP-25a and -25b isoforms are both expressed in insulin-secreting cells and can function in insulin secretion | journal = The Biochemical Journal | volume = 339 ( Pt 1) | issue = 1 | pages = 159–65 | date = April 1999 | pmid = 10085240 | pmc = 1220140 | doi = 10.1042/0264-6021:3390159 }}
• {{cite journal | vauthors = Ilardi JM, Mochida S, Sheng ZH | title = Snapin: a SNARE-associated protein implicated in synaptic transmission | journal = Nature Neuroscience | volume = 2 | issue = 2 | pages = 119–24 | date = February 1999 | pmid = 10195194 | doi = 10.1038/5673 | s2cid = 25524692 }}

{{Refend}}

• {{MeshName|SNAP25+Protein}}

{{PDB Gallery|geneid=6616}}

{{Vesicular transport proteins}}

{{Acetylcholine metabolism and transport modulators}}

{{InterPro content|IPR000928}}

{{DEFAULTSORT:Snap-25}}

Category:Integral membrane proteins

Category:Neural synapse

Category:Molecular neuroscience