ID SNP25_HUMAN Reviewed; 206 AA. AC P60880; B2RAU4; D3DW16; D3DW17; P13795; P36974; P70557; P70558; Q53EM2; AC Q5U0B5; Q8IXK3; Q96FM2; Q9BR45; DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 13-APR-2004, sequence version 1. DT 27-MAR-2024, entry version 193. DE RecName: Full=Synaptosomal-associated protein 25; DE Short=SNAP-25; DE AltName: Full=Super protein; DE Short=SUP; DE AltName: Full=Synaptosomal-associated 25 kDa protein; GN Name=SNAP25; Synonyms=SNAP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Fetal brain, and Temporal cortex; RX PubMed=8112622; DOI=10.1016/0378-1119(94)90773-0; RA Bark I.C., Wilson M.C.; RT "Human cDNA clones encoding two different isoforms of the nerve terminal RT protein SNAP-25."; RL Gene 139:291-292(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Frontal cortex; RX PubMed=8056350; DOI=10.1016/0378-1119(94)90027-2; RA Zhao N., Hashida H., Takahashi N., Sakaki Y.; RT "Cloning and sequence analysis of the human SNAP25 cDNA."; RL Gene 145:313-314(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING. RC TISSUE=Skeletal muscle; RX PubMed=8760387; DOI=10.1042/bj3170945; RA Jagadish M.N., Fernandez C.S., Hewish D.R., Macaulay S.L., Gough K.H., RA Grusovin J., Verkuylen A., Cosgrove L., Alafaci A., Frenkel M.J., RA Ward C.W.; RT "Insulin-responsive tissues contain the core complex protein SNAP-25 RT (synaptosomal-associated protein 25) A and B isoforms in addition to RT syntaxin 4 and synaptobrevins 1 and 2."; RL Biochem. J. 317:945-954(1996). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Amygdala, and Hippocampus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION) BY C.BOTULINUM NEUROTOXIN TYPES RP A; C AND E. RX PubMed=9886085; DOI=10.1046/j.1471-4159.1999.0720327.x; RA Vaidyanathan V.V., Yoshino K., Jahnz M., Doerries C., Bade S., RA Nauenburg S., Niemann H., Binz T.; RT "Proteolysis of SNAP-25 isoforms by botulinum neurotoxin types A, C, and E: RT domains and amino acid residues controlling the formation of enzyme- RT substrate complexes and cleavage."; RL J. Neurochem. 72:327-337(1999). RN [11] RP PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION) BY C.BOTULINUM NEUROTOXIN TYPE RP C, AND MUTAGENESIS OF GLN-152; ILE-156; ASP-166 AND ALA-199. RX PubMed=17718519; DOI=10.1021/bi701162d; RA Jin R., Sikorra S., Stegmann C.M., Pich A., Binz T., Brunger A.T.; RT "Structural and biochemical studies of botulinum neurotoxin serotype C1 RT light chain protease: implications for dual substrate specificity."; RL Biochemistry 46:10685-10693(2007). RN [12] RP PUTATIVE IRON-SULFUR CLUSTER. RX PubMed=18375205; DOI=10.1016/j.febslet.2008.03.028; RA Huang Q., Hong X., Hao Q.; RT "SNAP-25 is also an iron-sulfur protein."; RL FEBS Lett. 582:1431-1436(2008). RN [13] RP ASSOCIATION WITH THE BLOC-1 COMPLEX, AND INTERACTION WITH BLOC1S6. RX PubMed=19546860; DOI=10.1038/mp.2009.58; RA Ghiani C.A., Starcevic M., Rodriguez-Fernandez I.A., Nazarian R., RA Cheli V.T., Chan L.N., Malvar J.S., de Vellis J., Sabatti C., RA Dell'Angelica E.C.; RT "The dysbindin-containing complex (BLOC-1) in brain: developmental RT regulation, interaction with SNARE proteins and role in neurite RT outgrowth."; RL Mol. Psychiatry 15:204-215(2010). RN [14] RP INTERACTION WITH ALPHA-SYNUCLEIN/SNCA. RX PubMed=20798282; DOI=10.1126/science.1195227; RA Burre J., Sharma M., Tsetsenis T., Buchman V., Etherton M.R., Suedhof T.C.; RT "Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro."; RL Science 329:1663-1667(2010). RN [15] RP INTERACTION WITH PRRT2. RX PubMed=22832103; DOI=10.1016/j.celrep.2011.11.001; RA Lee H.Y., Huang Y., Bruneau N., Roll P., Roberson E.D., Hermann M., RA Quinn E., Maas J., Edwards R., Ashizawa T., Baykan B., Bhatia K., RA Bressman S., Bruno M.K., Brunt E.R., Caraballo R., Echenne B., Fejerman N., RA Frucht S., Gurnett C.A., Hirsch E., Houlden H., Jankovic J., Lee W.L., RA Lynch D.R., Mohammed S., Mueller U., Nespeca M.P., Renner D., Rochette J., RA Rudolf G., Saiki S., Soong B.W., Swoboda K.J., Tucker S., Wood N., RA Hanna M., Bowcock A.M., Szepetowski P., Fu Y.H., Ptacek L.J.; RT "Mutations in the gene PRRT2 cause paroxysmal kinesigenic dyskinesia with RT infantile convulsions."; RL Cell Rep. 1:2-12(2012). RN [16] RP INTERACTION WITH PRRT2. RX PubMed=25915028; DOI=10.3390/ijms16059134; RA Li M., Niu F., Zhu X., Wu X., Shen N., Peng X., Liu Y.; RT "PRRT2 Mutant Leads to Dysfunction of Glutamate Signaling."; RL Int. J. Mol. Sci. 16:9134-9151(2015). RN [17] RP INTERACTION WITH ZDHHC17. RX PubMed=28882895; DOI=10.1074/jbc.m117.799650; RA Lemonidis K., MacLeod R., Baillie G.S., Chamberlain L.H.; RT "Peptide array based screening reveals a large number of proteins RT interacting with the ankyrin repeat domain of the zDHHC17 S- RT acyltransferase."; RL J. Biol. Chem. 292:17190-17202(2017). RN [18] RP INVOLVEMENT IN CMS18, VARIANT CMS18 ASN-67, AND CHARACTERIZATION OF VARIANT RP CMS18 ASN-67. RX PubMed=25381298; DOI=10.1212/wnl.0000000000001079; RA Shen X.M., Selcen D., Brengman J., Engel A.G.; RT "Mutant SNAP25B causes myasthenia, cortical hyperexcitability, ataxia, and RT intellectual disability."; RL Neurology 83:2247-2255(2014). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 11-81 AND 141-202 IN COMPLEX WITH RP STX1A; CPLX1 AND VAMP2, AND STRUCTURE BY NMR. RX PubMed=11832227; DOI=10.1016/s0896-6273(02)00583-4; RA Chen X., Tomchick D.R., Kovrigin E., Arac D., Machius M., Suedhof T.C., RA Rizo J.; RT "Three-dimensional structure of the complexin/SNARE complex."; RL Neuron 33:397-409(2002). RN [20] {ECO:0007744|PDB:1XTG} RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 146-204 IN COMPLEX WITH INACTIVE RP C.BOTULINUM NEUROTOXIN A LIGHT CHAIN, PROTEOLYTIC CLEAVAGE (MICROBIAL RP INFECTION) BY C.BOTULINUM NEUROTOXIN TYPE A, AND MUTAGENESIS OF ILE-156; RP MET-167 AND MET-202. RX PubMed=15592454; DOI=10.1038/nature03123; RA Breidenbach M.A., Brunger A.T.; RT "Substrate recognition strategy for botulinum neurotoxin serotype A."; RL Nature 432:925-929(2004). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 111-120 IN COMPLEX WITH ZDHHC17, RP PALMITOYLATION, AND MUTAGENESIS OF VAL-112; VAL-113; SER-115; GLN-116; RP PRO-117 AND ARG-119. RX PubMed=28757145; DOI=10.1016/j.str.2017.06.018; RA Verardi R., Kim J.S., Ghirlando R., Banerjee A.; RT "Structural basis for substrate recognition by the ankyrin repeat domain of RT human DHHC17 palmitoyltransferase."; RL Structure 0:0-0(2017). CC -!- FUNCTION: t-SNARE involved in the molecular regulation of CC neurotransmitter release. May play an important role in the synaptic CC function of specific neuronal systems. Associates with proteins CC involved in vesicle docking and membrane fusion. Regulates plasma CC membrane recycling through its interaction with CENPF. Modulates the CC gating characteristics of the delayed rectifier voltage-dependent CC potassium channel KCNB1 in pancreatic beta cells. CC {ECO:0000250|UniProtKB:P60881}. CC -!- SUBUNIT: Part of the SNARE core complex containing SNAP25, VAMP2 and CC STX1A; this complex constitutes the basic catalytic machinery of the CC complex neurotransmitter release apparatus (PubMed:11832227). Recruited CC to the SNARE complex following binding of the SNARE complex component CC STX1A to STXBP1 (By similarity). This complex binds CPLX1 CC (PubMed:11832227). Found in a complex containing SYT1, SV2B and CC syntaxin-1 (By similarity). Found in a ternary complex with STX1A and CC VAMP8 (By similarity). Interacts with HSC70 and with SYT9, forming a CC complex with DNAJC5 (By similarity). The interaction with SYT9 is CC inhibited in presence of calcium (By similarity). Isoform 1 and isoform CC 2 interact with BLOC1S6 (PubMed:19546860). Interacts with CENPF (By CC similarity). Interacts with EQTN (By similarity). Interacts with HGS CC (By similarity). Interacts with KCNB1 (via N-terminus); reduces the CC voltage-dependent potassium channel KCNB1 activity in pancreatic beta CC cells (By similarity). Interacts with OTOF (By similarity). Interacts CC with RIMS1 (By similarity). Interacts with SNAPIN (By similarity). CC Interacts with STXBP6 (By similarity). Interacts with TRIM9 (By CC similarity). Interacts with ZDHHC13 (via ANK repeats) (By similarity). CC Interacts with ZDHHC17 (via ANK repeats) (PubMed:28882895, CC PubMed:28757145). Associates with the BLOC-1 complex (PubMed:19546860). CC Interacts with PLCL1 (via C2 domain) (By similarity). Interacts with CC PRRT2; this interaction may impair the formation of the SNARE complex CC (PubMed:22832103, PubMed:25915028). Interacts with alpha-synuclein/SNCA CC (PubMed:20798282). Interacts with PRPH2 (By similarity). Interacts with CC ROM1 (By similarity). Interacts with STX3 (By similarity). CC {ECO:0000250|UniProtKB:P60879, ECO:0000250|UniProtKB:P60881, CC ECO:0000269|PubMed:11832227, ECO:0000269|PubMed:19546860, CC ECO:0000269|PubMed:20798282, ECO:0000269|PubMed:22832103, CC ECO:0000269|PubMed:25915028, ECO:0000269|PubMed:28757145, CC ECO:0000269|PubMed:28882895}. CC -!- INTERACTION: CC P60880; Q16623: STX1A; NbExp=3; IntAct=EBI-524785, EBI-712466; CC P60880; Q8IUH5: ZDHHC17; NbExp=3; IntAct=EBI-524785, EBI-524753; CC P60880; PRO_0000449622 [P0DTD1]: rep; Xeno; NbExp=3; IntAct=EBI-524785, EBI-25475862; CC P60880-2; O14810: CPLX1; NbExp=6; IntAct=EBI-12177361, EBI-2691813; CC P60880-2; P42858: HTT; NbExp=9; IntAct=EBI-12177361, EBI-466029; CC P60880-2; O75558: STX11; NbExp=3; IntAct=EBI-12177361, EBI-714135; CC P60880-2; Q8N4C7: STX19; NbExp=3; IntAct=EBI-12177361, EBI-8484990; CC P60880-2; Q16623: STX1A; NbExp=5; IntAct=EBI-12177361, EBI-712466; CC P60880-2; Q9BRT2: UQCC2; NbExp=3; IntAct=EBI-12177361, EBI-1054584; CC P60880-2; Q13360-2: ZNF177; NbExp=3; IntAct=EBI-12177361, EBI-12272076; CC P60880-2; P32851: Stx1a; Xeno; NbExp=4; IntAct=EBI-12177361, EBI-539720; CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region CC {ECO:0000250|UniProtKB:P60879}. Cell membrane CC {ECO:0000250|UniProtKB:P60881}; Lipid-anchor CC {ECO:0000250|UniProtKB:P60879}. Synapse, synaptosome CC {ECO:0000250|UniProtKB:P60879}. Photoreceptor inner segment CC {ECO:0000250|UniProtKB:P60879}. Note=Membrane association requires CC palmitoylation. Expressed throughout cytoplasm, concentrating at the CC perinuclear region. Colocalizes with KCNB1 at the cell membrane (By CC similarity). Colocalizes with PLCL1 at the cell membrane (By CC similarity). {ECO:0000250|UniProtKB:P60879, CC ECO:0000250|UniProtKB:P60881}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Comment=Isoforms differ by the usage of two alternative homologous CC exons (5a and 5b) which code for positions 56 to 94 and differ only CC in 9 positions out of 39.; CC Name=1; Synonyms=SNAP-25b; CC IsoId=P60880-1, P13795-1; Sequence=Displayed; CC Name=2; Synonyms=SNAP-25a; CC IsoId=P60880-2, P13795-2; Sequence=VSP_006186; CC -!- TISSUE SPECIFICITY: Neurons of the neocortex, hippocampus, piriform CC cortex, anterior thalamic nuclei, pontine nuclei, and granule cells of CC the cerebellum. CC -!- PTM: Palmitoylated (PubMed:28757145). Cys-85 appears to be the main CC site, and palmitoylation is required for membrane association (By CC similarity). {ECO:0000250|UniProtKB:P60879, CC ECO:0000269|PubMed:28757145}. CC -!- PTM: (Microbial infection) Targeted and hydrolyzed by C.botulinum CC neurotoxin type A (BoNT/A, botA) which hydrolyzes the 197-Gln-|-Arg-198 CC bond and inhibits neurotransmitter release (PubMed:15592454, CC PubMed:9886085). {ECO:0000269|PubMed:9886085, CC ECO:0000305|PubMed:15592454}. CC -!- PTM: (Microbial infection) Targeted and hydrolyzed by C.botulinum CC neurotoxin type C (BoNT/C) which hydrolyzes the 198-Arg-|-Ala-199 bond CC and inhibits neurotransmitter release (PubMed:9886085, CC PubMed:17718519). C.botulinum type C only rarely infects humans. CC {ECO:0000269|PubMed:17718519, ECO:0000269|PubMed:9886085}. CC -!- PTM: (Microbial infection) Targeted and hydrolyzed by C.botulinum CC neurotoxin type E (BoNT/E) which hydrolyzes the 180-Arg-|-Ile-181 bond CC and inhibits neurotransmitter release (PubMed:9886085). CC {ECO:0000269|PubMed:9886085}. CC -!- DISEASE: Myasthenic syndrome, congenital, 18 (CMS18) [MIM:616330]: A CC form of congenital myasthenic syndrome, a group of disorders CC characterized by failure of neuromuscular transmission, including pre- CC synaptic, synaptic, and post-synaptic disorders that are not of CC autoimmune origin. Clinical features are easy fatigability and muscle CC weakness affecting the axial and limb muscles (with hypotonia in early- CC onset forms), the ocular muscles (leading to ptosis and CC ophthalmoplegia), and the facial and bulbar musculature (affecting CC sucking and swallowing, and leading to dysphonia). The symptoms CC fluctuate and worsen with physical effort. CMS18 is an autosomal CC dominant presynaptic disorder clinically characterized by early-onset CC muscle weakness and easy fatigability associated with delayed CC psychomotor development and ataxia. {ECO:0000269|PubMed:25381298}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- MISCELLANEOUS: When cloned and expressed in E.coli, where protein CC palmitoylation does not occur, Cys-85, Cys-88, Cys-90 and Cys-92 in the CC protein sequence readily form an iron-sulfur cluster. CC {ECO:0000269|PubMed:18375205}. CC -!- SIMILARITY: Belongs to the SNAP-25 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L19760; AAC37545.1; -; mRNA. DR EMBL; L19761; AAC37546.1; -; mRNA. DR EMBL; D21267; BAA22370.1; -; mRNA. DR EMBL; BT019684; AAV38490.1; -; mRNA. DR EMBL; AK223617; BAD97337.1; -; mRNA. DR EMBL; AK289647; BAF82336.1; -; mRNA. DR EMBL; AK314359; BAG36991.1; -; mRNA. DR EMBL; AL023913; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471133; EAX10346.1; -; Genomic_DNA. DR EMBL; CH471133; EAX10349.1; -; Genomic_DNA. DR EMBL; CH471133; EAX10350.1; -; Genomic_DNA. DR EMBL; CH471133; EAX10352.1; -; Genomic_DNA. DR EMBL; BC010647; AAH10647.1; -; mRNA. DR CCDS; CCDS13109.1; -. [P60880-2] DR CCDS; CCDS13110.1; -. DR PIR; I53735; I53735. DR PIR; I67823; I67823. DR RefSeq; NP_001309831.1; NM_001322902.1. [P60880-2] DR RefSeq; NP_001309832.1; NM_001322903.1. [P60880-1] DR RefSeq; NP_001309833.1; NM_001322904.1. [P60880-1] DR RefSeq; NP_001309834.1; NM_001322905.1. [P60880-1] DR RefSeq; NP_001309835.1; NM_001322906.1. [P60880-1] DR RefSeq; NP_001309836.1; NM_001322907.1. [P60880-1] DR RefSeq; NP_001309837.1; NM_001322908.1. [P60880-1] DR RefSeq; NP_001309838.1; NM_001322909.1. [P60880-1] DR RefSeq; NP_001309839.1; NM_001322910.1. [P60880-1] DR RefSeq; NP_003072.2; NM_003081.4. [P60880-2] DR RefSeq; NP_570824.1; NM_130811.3. [P60880-1] DR RefSeq; XP_005260865.1; XM_005260808.4. DR RefSeq; XP_016883510.1; XM_017028021.1. DR RefSeq; XP_016883511.1; XM_017028022.1. [P60880-2] DR PDB; 1KIL; X-ray; 2.30 A; C=10-81, D=139-204. DR PDB; 1XTG; X-ray; 2.10 A; B=146-204. DR PDB; 2N1T; NMR; -; C=7-83, D=131-204. DR PDB; 3DDA; X-ray; 1.50 A; B=197-202. DR PDB; 3DDB; X-ray; 1.60 A; B=198-202. DR PDB; 3RK2; X-ray; 2.20 A; C/G=7-82, D/H=141-203. DR PDB; 3RK3; X-ray; 3.50 A; C=7-82, D=141-203. DR PDB; 3RL0; X-ray; 3.80 A; C/G/K/O/S/W/a/e=7-82, D/H/L/P/T/X/b/f=141-203. DR PDB; 3ZUR; X-ray; 2.71 A; A/B=145-206. DR PDB; 5W7I; X-ray; 2.10 A; B/D=111-120. DR PDB; 5W7J; X-ray; 2.20 A; B/D=111-120. DR PDB; 6JLH; X-ray; 2.37 A; B/D=154-170. DR PDBsum; 1KIL; -. DR PDBsum; 1XTG; -. DR PDBsum; 2N1T; -. DR PDBsum; 3DDA; -. DR PDBsum; 3DDB; -. DR PDBsum; 3RK2; -. DR PDBsum; 3RK3; -. DR PDBsum; 3RL0; -. DR PDBsum; 3ZUR; -. DR PDBsum; 5W7I; -. DR PDBsum; 5W7J; -. DR PDBsum; 6JLH; -. DR AlphaFoldDB; P60880; -. DR BMRB; P60880; -. DR SMR; P60880; -. DR BioGRID; 112500; 54. DR CORUM; P60880; -. DR DIP; DIP-34554N; -. DR IntAct; P60880; 63. DR MINT; P60880; -. DR STRING; 9606.ENSP00000254976; -. DR ChEMBL; CHEMBL2364159; -. DR DrugBank; DB00083; Botulinum toxin type A. DR DrugBank; DB16820; Letibotulinumtoxina. DR DrugCentral; P60880; -. DR TCDB; 1.F.1.1.1; the synaptosomal vesicle fusion pore (svf-pore) family. DR GlyGen; P60880; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P60880; -. DR PhosphoSitePlus; P60880; -. DR SwissPalm; P60880; -. DR BioMuta; SNAP25; -. DR DMDM; 46397726; -. DR EPD; P60880; -. DR jPOST; P60880; -. DR MassIVE; P60880; -. DR MaxQB; P60880; -. DR PaxDb; 9606-ENSP00000254976; -. DR PeptideAtlas; P60880; -. DR ProteomicsDB; 57231; -. DR ProteomicsDB; 57232; -. [P60880-2] DR Pumba; P60880; -. DR Antibodypedia; 713; 1317 antibodies from 48 providers. DR DNASU; 6616; -. DR Ensembl; ENST00000254976.7; ENSP00000254976.3; ENSG00000132639.15. [P60880-1] DR Ensembl; ENST00000304886.6; ENSP00000307341.2; ENSG00000132639.15. [P60880-2] DR Ensembl; ENST00000685131.1; ENSP00000508837.1; ENSG00000132639.15. [P60880-1] DR Ensembl; ENST00000687785.1; ENSP00000510219.1; ENSG00000132639.15. [P60880-1] DR Ensembl; ENST00000689757.1; ENSP00000509312.1; ENSG00000132639.15. [P60880-1] DR Ensembl; ENST00000689858.1; ENSP00000510663.1; ENSG00000132639.15. [P60880-1] DR Ensembl; ENST00000690812.1; ENSP00000509287.1; ENSG00000132639.15. [P60880-1] DR Ensembl; ENST00000691161.1; ENSP00000510109.1; ENSG00000132639.15. [P60880-1] DR Ensembl; ENST00000691353.1; ENSP00000509759.1; ENSG00000132639.15. [P60880-1] DR Ensembl; ENST00000691665.1; ENSP00000508541.1; ENSG00000132639.15. [P60880-1] DR Ensembl; ENST00000692411.1; ENSP00000508939.1; ENSG00000132639.15. [P60880-1] DR Ensembl; ENST00000693325.1; ENSP00000510558.1; ENSG00000132639.15. [P60880-1] DR Ensembl; ENST00000706269.1; ENSP00000516314.1; ENSG00000132639.15. [P60880-2] DR GeneID; 6616; -. DR KEGG; hsa:6616; -. DR MANE-Select; ENST00000254976.7; ENSP00000254976.3; NM_130811.4; NP_570824.1. DR UCSC; uc002wnq.3; human. DR AGR; HGNC:11132; -. DR CTD; 6616; -. DR DisGeNET; 6616; -. DR GeneCards; SNAP25; -. DR HGNC; HGNC:11132; SNAP25. DR HPA; ENSG00000132639; Tissue enriched (brain). DR MalaCards; SNAP25; -. DR MIM; 600322; gene. DR MIM; 616330; phenotype. DR neXtProt; NX_P60880; -. DR OpenTargets; ENSG00000132639; -. DR Orphanet; 98914; Presynaptic congenital myasthenic syndromes. DR PharmGKB; PA35980; -. DR VEuPathDB; HostDB:ENSG00000132639; -. DR eggNOG; KOG3065; Eukaryota. DR GeneTree; ENSGT00950000182843; -. DR HOGENOM; CLU_096939_0_0_1; -. DR InParanoid; P60880; -. DR OMA; GMIQINE; -. DR OrthoDB; 388796at2759; -. DR PhylomeDB; P60880; -. DR TreeFam; TF315125; -. DR PathwayCommons; P60880; -. DR Reactome; R-HSA-181429; Serotonin Neurotransmitter Release Cycle. DR Reactome; R-HSA-181430; Norepinephrine Neurotransmitter Release Cycle. DR Reactome; R-HSA-210500; Glutamate Neurotransmitter Release Cycle. DR Reactome; R-HSA-212676; Dopamine Neurotransmitter Release Cycle. DR Reactome; R-HSA-264642; Acetylcholine Neurotransmitter Release Cycle. DR Reactome; R-HSA-422356; Regulation of insulin secretion. DR Reactome; R-HSA-449836; Other interleukin signaling. DR Reactome; R-HSA-5250968; Toxicity of botulinum toxin type A (botA). DR Reactome; R-HSA-5250971; Toxicity of botulinum toxin type C (botC). DR Reactome; R-HSA-5250992; Toxicity of botulinum toxin type E (botE). DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-888590; GABA synthesis, release, reuptake and degradation. DR Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea. DR SignaLink; P60880; -. DR SIGNOR; P60880; -. DR BioGRID-ORCS; 6616; 7 hits in 1152 CRISPR screens. DR ChiTaRS; SNAP25; human. DR EvolutionaryTrace; P60880; -. DR GeneWiki; SNAP25; -. DR GenomeRNAi; 6616; -. DR Pharos; P60880; Tclin. DR PRO; PR:P60880; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; P60880; Protein. DR Bgee; ENSG00000132639; Expressed in pons and 148 other cell types or tissues. DR ExpressionAtlas; P60880; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; IEA:Ensembl. DR GO; GO:0044295; C:axonal growth cone; IEA:Ensembl. DR GO; GO:0005938; C:cell cortex; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:ARUK-UCL. DR GO; GO:0005856; C:cytoskeleton; IDA:ARUK-UCL. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005768; C:endosome; IEA:Ensembl. DR GO; GO:0098888; C:extrinsic component of presynaptic membrane; IEA:Ensembl. DR GO; GO:0030175; C:filopodium; IEA:Ensembl. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0030426; C:growth cone; ISS:HGNC-UCL. DR GO; GO:0030027; C:lamellipodium; IEA:Ensembl. DR GO; GO:0016020; C:membrane; ISS:UniProtKB. DR GO; GO:0043005; C:neuron projection; ISS:HGNC-UCL. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0001917; C:photoreceptor inner segment; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0098794; C:postsynapse; IEA:Ensembl. DR GO; GO:0048787; C:presynaptic active zone membrane; IEA:Ensembl. DR GO; GO:0042734; C:presynaptic membrane; TAS:ParkinsonsUK-UCL. DR GO; GO:0097470; C:ribbon synapse; IEA:Ensembl. DR GO; GO:0031201; C:SNARE complex; IDA:UniProtKB. DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome. DR GO; GO:0008021; C:synaptic vesicle; IEA:Ensembl. DR GO; GO:0070044; C:synaptobrevin 2-SNAP-25-syntaxin-1a complex; IEA:Ensembl. DR GO; GO:0070032; C:synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex; IBA:GO_Central. DR GO; GO:0070033; C:synaptobrevin 2-SNAP-25-syntaxin-1a-complexin II complex; IEA:Ensembl. DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome. DR GO; GO:0005802; C:trans-Golgi network; IEA:Ensembl. DR GO; GO:0008076; C:voltage-gated potassium channel complex; IEA:Ensembl. DR GO; GO:0048306; F:calcium-dependent protein binding; ISS:ParkinsonsUK-UCL. DR GO; GO:0008289; F:lipid binding; EXP:DisProt. DR GO; GO:0017022; F:myosin binding; IEA:Ensembl. DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl. DR GO; GO:0005484; F:SNAP receptor activity; IBA:GO_Central. DR GO; GO:0017075; F:syntaxin-1 binding; IPI:UniProtKB. DR GO; GO:0044325; F:transmembrane transporter binding; IEA:Ensembl. DR GO; GO:0005249; F:voltage-gated potassium channel activity; IEA:Ensembl. DR GO; GO:0008306; P:associative learning; IEA:Ensembl. DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl. DR GO; GO:0007268; P:chemical synaptic transmission; NAS:UniProtKB. DR GO; GO:0016197; P:endosomal transport; IEA:Ensembl. DR GO; GO:0098967; P:exocytic insertion of neurotransmitter receptor to postsynaptic membrane; IEA:Ensembl. DR GO; GO:0006887; P:exocytosis; IBA:GO_Central. DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl. DR GO; GO:0007616; P:long-term memory; IEA:Ensembl. DR GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl. DR GO; GO:0099590; P:neurotransmitter receptor internalization; IEA:Ensembl. DR GO; GO:0001504; P:neurotransmitter uptake; NAS:UniProtKB. DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl. DR GO; GO:0099525; P:presynaptic dense core vesicle exocytosis; IEA:Ensembl. DR GO; GO:0050796; P:regulation of insulin secretion; TAS:UniProtKB. DR GO; GO:0010975; P:regulation of neuron projection development; IEA:Ensembl. DR GO; GO:0051963; P:regulation of synapse assembly; IEA:Ensembl. DR GO; GO:0035493; P:SNARE complex assembly; IEA:Ensembl. DR GO; GO:0016081; P:synaptic vesicle docking; NAS:UniProtKB. DR GO; GO:0016079; P:synaptic vesicle exocytosis; TAS:ParkinsonsUK-UCL. DR GO; GO:0031629; P:synaptic vesicle fusion to presynaptic active zone membrane; IBA:GO_Central. DR GO; GO:0016082; P:synaptic vesicle priming; IBA:GO_Central. DR CDD; cd15885; SNARE_SNAP25C; 1. DR CDD; cd15894; SNARE_SNAP25N; 1. DR DisProt; DP02561; -. DR Gene3D; 1.20.5.110; -; 2. DR InterPro; IPR000928; SNAP-25_dom. DR InterPro; IPR039077; SNAP-25_N_SNARE_chord. DR InterPro; IPR000727; T_SNARE_dom. DR PANTHER; PTHR19305; SYNAPTOSOMAL ASSOCIATED PROTEIN; 1. DR PANTHER; PTHR19305:SF5; SYNAPTOSOMAL-ASSOCIATED PROTEIN 25; 1. DR Pfam; PF00835; SNAP-25; 1. DR SMART; SM00397; t_SNARE; 2. DR SUPFAM; SSF58038; SNARE fusion complex; 2. DR PROSITE; PS50192; T_SNARE; 2. DR Genevisible; P60880; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Coiled coil; KW Congenital myasthenic syndrome; Cytoplasm; Disease variant; KW Intellectual disability; Lipoprotein; Membrane; Palmitate; Phosphoprotein; KW Reference proteome; Repeat; Synapse; Synaptosome. FT CHAIN 1..206 FT /note="Synaptosomal-associated protein 25" FT /id="PRO_0000213587" FT DOMAIN 19..81 FT /note="t-SNARE coiled-coil homology 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00202" FT DOMAIN 140..202 FT /note="t-SNARE coiled-coil homology 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00202" FT REGION 1..75 FT /note="Interaction with CENPF" FT /evidence="ECO:0000250" FT REGION 1..23 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 111..120 FT /note="Interaction with ZDHHC17" FT /evidence="ECO:0000269|PubMed:28757145" FT SITE 180..181 FT /note="(Microbial infection) Cleavage; by C.botulinum FT neurotoxin type E (BoNT/E)" FT /evidence="ECO:0000269|PubMed:9886085" FT SITE 197..198 FT /note="(Microbial infection) Cleavage; by C.botulinum FT neurotoxin type A (BoNT/A, botA)" FT /evidence="ECO:0000269|PubMed:9886085, FT ECO:0000305|PubMed:15592454" FT SITE 198..199 FT /note="(Microbial infection) Cleavage; by C.botulinum FT neurotoxin type C (BoNT/C)" FT /evidence="ECO:0000269|PubMed:9886085, FT ECO:0000305|PubMed:15592454" FT MOD_RES 138 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P60879" FT MOD_RES 154 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P60879" FT MOD_RES 187 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P60879" FT LIPID 85 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250|UniProtKB:P60879" FT LIPID 88 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250|UniProtKB:P60879" FT LIPID 90 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250|UniProtKB:P60879" FT LIPID 92 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250|UniProtKB:P60879" FT VAR_SEQ 58..89 FT /note="ERIEEGMDQINKDMKEAEKNLTDLGKFCGLCV -> DRVEEGMNHINQDMKE FT AEKNLKDLGKCCGLFI (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8056350, FT ECO:0000303|PubMed:8112622, ECO:0000303|Ref.4" FT /id="VSP_006186" FT VARIANT 67 FT /note="I -> N (in CMS18; interferes with calcium-induced FT fusion; inhibits exocytosis of catecholamine-containing FT vesicles; dbSNP:rs1555794286)" FT /evidence="ECO:0000269|PubMed:25381298" FT /id="VAR_073698" FT MUTAGEN 112 FT /note="V->A: Mildly decreased binding affinity for FT ZDHHC17." FT /evidence="ECO:0000269|PubMed:28757145" FT MUTAGEN 113 FT /note="V->A: Mildly decreased binding affinity for FT ZDHHC17." FT /evidence="ECO:0000269|PubMed:28757145" FT MUTAGEN 115 FT /note="S->A: No effect on ZDHHC17 binding." FT /evidence="ECO:0000269|PubMed:28757145" FT MUTAGEN 116 FT /note="Q->A: Decreased binding affinity for ZDHHC17." FT /evidence="ECO:0000269|PubMed:28757145" FT MUTAGEN 117 FT /note="P->A: Decreased binding affinity for ZDHHC17." FT /evidence="ECO:0000269|PubMed:28757145" FT MUTAGEN 119 FT /note="R->A: No effect on ZDHHC17 binding." FT /evidence="ECO:0000269|PubMed:28757145" FT MUTAGEN 152 FT /note="Q->A: Decreased cleavage by C.botulinum BoNT/C, no FT change in cleavage by C.botulinum BoNT/A (botA)." FT /evidence="ECO:0000269|PubMed:17718519" FT MUTAGEN 156 FT /note="I->E: Small decrease in affinity for C.botulinum FT BoNT/A, increased efficiency of BoNT/C cleavage." FT /evidence="ECO:0000269|PubMed:15592454, FT ECO:0000269|PubMed:17718519" FT MUTAGEN 166 FT /note="D->A: Decreased cleavage by BoNT/C, no change in FT cleavage by BoNT/A." FT /evidence="ECO:0000269|PubMed:17718519" FT MUTAGEN 167 FT /note="M->E: Small decrease in affinity for C.botulinum FT BoNT/A." FT /evidence="ECO:0000269|PubMed:15592454" FT MUTAGEN 199 FT /note="A->R: Not cleaved by BoNT/C." FT /evidence="ECO:0000269|PubMed:17718519" FT MUTAGEN 202 FT /note="M->Y: Slight decrease in affinity for BoNT/A, FT increases kcat for BoNT/A." FT /evidence="ECO:0000269|PubMed:15592454" FT CONFLICT 44 FT /note="I -> V (in Ref. 5; BAD97337)" FT /evidence="ECO:0000305" FT HELIX 8..80 FT /evidence="ECO:0007829|PDB:3RK2" FT HELIX 148..167 FT /evidence="ECO:0007829|PDB:1XTG" FT STRAND 191..193 FT /evidence="ECO:0007829|PDB:1XTG" SQ SEQUENCE 206 AA; 23315 MW; FBED2B082A4CB6A6 CRC64; MAEDADMRNE LEEMQRRADQ LADESLESTR RMLQLVEESK DAGIRTLVML DEQGEQLERI EEGMDQINKD MKEAEKNLTD LGKFCGLCVC PCNKLKSSDA YKKAWGNNQD GVVASQPARV VDEREQMAIS GGFIRRVTND ARENEMDENL EQVSGIIGNL RHMALDMGNE IDTQNRQIDR IMEKADSNKT RIDEANQRAT KMLGSG //