SNP25_HUMAN
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 03-AUG-2022, entry version 184.
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 binds CPLX1 (PubMed:11832227). Found in a complex
CC containing SYT1, SV2B and syntaxin-1 (By similarity). Found in a
CC ternary complex with STX1A and VAMP8 (By similarity). Interacts with
CC HSC70 and with SYT9, forming a complex with DNAJC5 (By similarity). The
CC interaction with SYT9 is inhibited in presence of calcium (By
CC similarity). Isoform 1 and isoform 2 interact with BLOC1S6
CC (PubMed:19546860). Interacts with CENPF (By similarity). Interacts with
CC EQTN (By similarity). Interacts with HGS (By similarity). Interacts
CC with KCNB1 (via N-terminus); reduces the voltage-dependent potassium
CC channel KCNB1 activity in pancreatic beta cells (By similarity).
CC Interacts with OTOF (By similarity). Interacts with RIMS1 (By
CC similarity). Interacts with SNAPIN (By similarity). Interacts with
CC STXBP6 (By similarity). Interacts with TRIM9 (By similarity). Interacts
CC with ZDHHC13 (via ANK repeats) (By similarity). Interacts with ZDHHC17
CC (via ANK repeats) (PubMed:28882895, PubMed:28757145). Associates with
CC the BLOC-1 complex (PubMed:19546860). Interacts with PLCL1 (via C2
CC domain) (By similarity). Interacts with PRRT2; this interaction may
CC impair the formation of the SNARE complex (PubMed:22832103,
CC 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;
CC Sequence=Displayed;
CC Name=2; Synonyms=SNAP-25a;
CC IsoId=P60880-2, P13795-2;
CC 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}.
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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. [P60880-1]
DR RefSeq; XP_016883510.1; XM_017028021.1. [P60880-2]
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; 53.
DR CORUM; P60880; -.
DR DIP; DIP-34554N; -.
DR IntAct; P60880; 62.
DR MINT; P60880; -.
DR STRING; 9606.ENSP00000254976; -.
DR ChEMBL; CHEMBL2364159; -.
DR DrugBank; DB00083; Botulinum toxin type A.
DR DrugCentral; P60880; -.
DR TCDB; 1.F.1.1.1; the synaptosomal vesicle fusion pore (svf-pore) family.
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; P60880; -.
DR PeptideAtlas; P60880; -.
DR PRIDE; P60880; -.
DR ProteomicsDB; 57231; -.
DR ProteomicsDB; 57232; -. [P60880-2]
DR Antibodypedia; 713; 1205 antibodies from 48 providers.
DR DNASU; 6616; -.
DR Ensembl; ENST00000254976.7; ENSP00000254976.3; ENSG00000132639.14. [P60880-1]
DR Ensembl; ENST00000304886.6; ENSP00000307341.2; ENSG00000132639.14. [P60880-2]
DR Ensembl; ENST00000685131.1; ENSP00000508837.1; ENSG00000132639.14. [P60880-1]
DR Ensembl; ENST00000687785.1; ENSP00000510219.1; ENSG00000132639.14. [P60880-1]
DR Ensembl; ENST00000689757.1; ENSP00000509312.1; ENSG00000132639.14. [P60880-1]
DR Ensembl; ENST00000689858.1; ENSP00000510663.1; ENSG00000132639.14. [P60880-1]
DR Ensembl; ENST00000690812.1; ENSP00000509287.1; ENSG00000132639.14. [P60880-1]
DR Ensembl; ENST00000691161.1; ENSP00000510109.1; ENSG00000132639.14. [P60880-1]
DR Ensembl; ENST00000691353.1; ENSP00000509759.1; ENSG00000132639.14. [P60880-1]
DR Ensembl; ENST00000691665.1; ENSP00000508541.1; ENSG00000132639.14. [P60880-1]
DR Ensembl; ENST00000692411.1; ENSP00000508939.1; ENSG00000132639.14. [P60880-1]
DR Ensembl; ENST00000693325.1; ENSP00000510558.1; ENSG00000132639.14. [P60880-1]
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 CTD; 6616; -.
DR DisGeNET; 6616; -.
DR GeneCards; SNAP25; -.
DR HGNC; HGNC:11132; SNAP25.
DR HPA; ENSG00000132639; Group enriched (brain, retina).
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; WKASEDG; -.
DR OrthoDB; 1197028at2759; -.
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; 6 hits in 1068 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 147 other tissues.
DR ExpressionAtlas; P60880; baseline and differential.
DR Genevisible; P60880; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0030426; C:growth cone; ISS:HGNC-UCL.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISS:HGNC-UCL.
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: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:0036477; C:somatodendritic compartment; IEA:Ensembl.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0008021; C:synaptic vesicle; IEA:Ensembl.
DR GO; GO:0070032; C:synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex; IBA:GO_Central.
DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome.
DR GO; GO:0005802; C:trans-Golgi network; IEA:Ensembl.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0005484; F:SNAP receptor activity; IBA:GO_Central.
DR GO; GO:0019905; F:syntaxin binding; IBA:GO_Central.
DR GO; GO:0017075; F:syntaxin-1 binding; IPI:UniProtKB.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IEA:InterPro.
DR GO; GO:0008306; P:associative learning; IEA:Ensembl.
DR GO; GO:0007268; P:chemical synaptic transmission; NAS:UniProtKB.
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: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:0050796; P:regulation of insulin secretion; TAS:UniProtKB.
DR GO; GO:0010975; P:regulation of neuron projection development; 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 GO; GO:0006906; P:vesicle fusion; IBA:GO_Central.
DR DisProt; DP02561; -.
DR InterPro; IPR039077; SNAP-25.
DR InterPro; IPR000928; SNAP-25_dom.
DR InterPro; IPR000727; T_SNARE_dom.
DR PANTHER; PTHR19305:SF5; PTHR19305:SF5; 1.
DR Pfam; PF00835; SNAP-25; 1.
DR SMART; SM00397; t_SNARE; 2.
DR PROSITE; PS50192; T_SNARE; 2.
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; interfers 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
