STXB1_HUMAN
ID STXB1_HUMAN Reviewed; 594 AA.
AC P61764; B1AM97; Q28208; Q62759; Q64320; Q68CM6; Q96TG8;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Syntaxin-binding protein 1;
DE AltName: Full=MUNC18-1;
DE AltName: Full=N-Sec1;
DE AltName: Full=Protein unc-18 homolog 1;
DE Short=Unc18-1;
DE AltName: Full=Protein unc-18 homolog A;
DE Short=Unc-18A;
DE AltName: Full=p67;
GN Name=STXBP1; Synonyms=UNC18A;
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] (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=8824310; DOI=10.1523/jneurosci.16-21-06695.1996;
RA Gengyo-Ando K., Kitayama H., Mukaida M., Ikawa Y.;
RT "A murine neural-specific homolog corrects cholinergic defects in
RT Caenorhabditis elegans unc-18 mutants.";
RL J. Neurosci. 16:6695-6702(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=9545644; DOI=10.1006/geno.1997.5202;
RA Swanson D.A., Steel J.M., Valle D.;
RT "Identification and characterization of the human ortholog of rat STXBP1, a
RT protein implicated in vesicle trafficking and neurotransmitter release.";
RL Genomics 48:373-376(1998).
RN [3] {ECO:0000312|EMBL:CAA73255.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain {ECO:0000312|EMBL:CAA73255.1};
RA Franco B.;
RL Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 [7]
RP INTERACTION WITH STX1A.
RX PubMed=12730201; DOI=10.1074/jbc.m300492200;
RA Tian J.H., Das S., Sheng Z.H.;
RT "Ca2+-dependent phosphorylation of syntaxin-1A by the death-associated
RT protein (DAP) kinase regulates its interaction with Munc18.";
RL J. Biol. Chem. 278:26265-26274(2003).
RN [8]
RP INTERACTION WITH ALPHA-SYNUCLEIN/SNCA.
RX PubMed=27597756; DOI=10.1083/jcb.201512016;
RA Chai Y.J., Sierecki E., Tomatis V.M., Gormal R.S., Giles N., Morrow I.C.,
RA Xia D., Goetz J., Parton R.G., Collins B.M., Gambin Y., Meunier F.A.;
RT "Munc18-1 is a molecular chaperone for alpha-synuclein, controlling its
RT self-replicating aggregation.";
RL J. Cell Biol. 214:705-718(2016).
RN [9]
RP INVOLVEMENT IN DEE4, VARIANTS DEE4 ASP-84; TYR-180; ARG-443 AND ASP-544,
RP AND CHARACTERIZATION OF VARIANTS DEE4 ASP-84; TYR-180; ARG-443 AND ASP-544.
RX PubMed=18469812; DOI=10.1038/ng.150;
RA Saitsu H., Kato M., Mizuguchi T., Hamada K., Osaka H., Tohyama J.,
RA Uruno K., Kumada S., Nishiyama K., Nishimura A., Okada I., Yoshimura Y.,
RA Hirai S., Kumada T., Hayasaka K., Fukuda A., Ogata K., Matsumoto N.;
RT "De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early
RT infantile epileptic encephalopathy.";
RL Nat. Genet. 40:782-788(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP VARIANT DEE4 HIS-406, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF
RP VARIANTS ILE-84 AND LEU-431.
RX PubMed=20887364; DOI=10.1111/j.1528-1167.2010.02728.x;
RA Saitsu H., Kato M., Okada I., Orii K.E., Higuchi T., Hoshino H., Kubota M.,
RA Arai H., Tagawa T., Kimura S., Sudo A., Miyama S., Takami Y., Watanabe T.,
RA Nishimura A., Nishiyama K., Miyake N., Wada T., Osaka H., Kondo N.,
RA Hayasaka K., Matsumoto N.;
RT "STXBP1 mutations in early infantile epileptic encephalopathy with
RT suppression-burst pattern.";
RL Epilepsia 51:2397-2405(2010).
RN [14]
RP VARIANTS DEE4 ARG-183; LEU-480 AND PRO-574.
RX PubMed=21770924; DOI=10.1111/j.1528-1167.2011.03181.x;
RA Milh M., Villeneuve N., Chouchane M., Kaminska A., Laroche C.,
RA Barthez M.A., Gitiaux C., Bartoli C., Borges-Correia A., Cacciagli P.,
RA Mignon-Ravix C., Cuberos H., Chabrol B., Villard L.;
RT "Epileptic and nonepileptic features in patients with early onset epileptic
RT encephalopathy and STXBP1 mutations.";
RL Epilepsia 52:1828-1834(2011).
RN [15]
RP INVOLVEMENT IN DEE4.
RX PubMed=23662938; DOI=10.1111/epi.12203;
RA Kodera H., Kato M., Nord A.S., Walsh T., Lee M., Yamanaka G., Tohyama J.,
RA Nakamura K., Nakagawa E., Ikeda T., Ben-Zeev B., Lev D., Lerman-Sagie T.,
RA Straussberg R., Tanabe S., Ueda K., Amamoto M., Ohta S., Nonoda Y.,
RA Nishiyama K., Tsurusaki Y., Nakashima M., Miyake N., Hayasaka K.,
RA King M.C., Matsumoto N., Saitsu H.;
RT "Targeted capture and sequencing for detection of mutations causing early
RT onset epileptic encephalopathy.";
RL Epilepsia 54:1262-1269(2013).
RN [16]
RP VARIANTS DEE4 PHE-42; TRP-190 AND ARG-354, AND VARIANTS PRO-80; CYS-544 AND
RP ALA-570.
RX PubMed=23708187; DOI=10.1038/ng.2646;
RA Carvill G.L., Heavin S.B., Yendle S.C., McMahon J.M., O'Roak B.J., Cook J.,
RA Khan A., Dorschner M.O., Weaver M., Calvert S., Malone S., Wallace G.,
RA Stanley T., Bye A.M., Bleasel A., Howell K.B., Kivity S., Mackay M.T.,
RA Rodriguez-Casero V., Webster R., Korczyn A., Afawi Z., Zelnick N.,
RA Lerman-Sagie T., Lev D., Moeller R.S., Gill D., Andrade D.M., Freeman J.L.,
RA Sadleir L.G., Shendure J., Berkovic S.F., Scheffer I.E., Mefford H.C.;
RT "Targeted resequencing in epileptic encephalopathies identifies de novo
RT mutations in CHD2 and SYNGAP1.";
RL Nat. Genet. 45:825-830(2013).
RN [17]
RP VARIANT DEE4 THR-251.
RX PubMed=24170257; DOI=10.1177/0883073813506936;
RA Romaniello R., Zucca C., Tenderini E., Arrigoni F., Ragona F., Zorzi G.,
RA Bassi M.T., Borgatti R.;
RT "A novel mutation in STXBP1 gene in a child with epileptic encephalopathy
RT and an atypical electroclinical pattern.";
RL J. Child Neurol. 29:249-253(2014).
RN [18]
RP VARIANTS DEE4 LYS-283; TYR-285 AND PRO-445.
RX PubMed=24623842; DOI=10.1212/wnl.0000000000000291;
RA Carvill G.L., Weckhuysen S., McMahon J.M., Hartmann C., Moller R.S.,
RA Hjalgrim H., Cook J., Geraghty E., O'Roak B.J., Petrou S., Clarke A.,
RA Gill D., Sadleir L.G., Muhle H., von Spiczak S., Nikanorova M.,
RA Hodgson B.L., Gazina E.V., Suls A., Shendure J., Dibbens L.M.,
RA De Jonghe P., Helbig I., Berkovic S.F., Scheffer I.E., Mefford H.C.;
RT "GABRA1 and STXBP1: novel genetic causes of Dravet syndrome.";
RL Neurology 82:1245-1253(2014).
RN [19]
RP VARIANT DEE4 122-ARG--SER-594 DEL.
RX PubMed=25818041; DOI=10.1111/epi.12954;
RA Mercimek-Mahmutoglu S., Patel J., Cordeiro D., Hewson S., Callen D.,
RA Donner E.J., Hahn C.D., Kannu P., Kobayashi J., Minassian B.A., Moharir M.,
RA Siriwardena K., Weiss S.K., Weksberg R., Snead O.C. III;
RT "Diagnostic yield of genetic testing in epileptic encephalopathy in
RT childhood.";
RL Epilepsia 56:707-716(2015).
RN [20]
RP VARIANT DEE4 HIS-406.
RX PubMed=25714420; DOI=10.1097/wnr.0000000000000337;
RA Romaniello R., Saettini F., Panzeri E., Arrigoni F., Bassi M.T.,
RA Borgatti R.;
RT "A de-novo STXBP1 gene mutation in a patient showing the Rett syndrome
RT phenotype.";
RL NeuroReport 26:254-257(2015).
RN [21]
RP VARIANTS DEE4 PRO-281 AND HIS-292.
RX PubMed=26993267; DOI=10.1136/jmedgenet-2015-103263;
RA Trump N., McTague A., Brittain H., Papandreou A., Meyer E., Ngoh A.,
RA Palmer R., Morrogh D., Boustred C., Hurst J.A., Jenkins L., Kurian M.A.,
RA Scott R.H.;
RT "Improving diagnosis and broadening the phenotypes in early-onset seizure
RT and severe developmental delay disorders through gene panel analysis.";
RL J. Med. Genet. 53:310-317(2016).
RN [22]
RP VARIANT DEE4 CYS-406.
RX PubMed=27864847; DOI=10.1002/humu.23149;
RG Clinical Study Group;
RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D.,
RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S.,
RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.;
RT "Diagnostic targeted resequencing in 349 patients with drug-resistant
RT pediatric epilepsies identifies causative mutations in 30 different
RT genes.";
RL Hum. Mutat. 38:216-225(2017).
CC -!- FUNCTION: Participates in the regulation of synaptic vesicle docking
CC and fusion through interaction with GTP-binding proteins (By
CC similarity). Essential for neurotransmission and binds syntaxin, a
CC component of the synaptic vesicle fusion machinery probably in a 1:1
CC ratio. Can interact with syntaxins 1, 2, and 3 but not syntaxin 4. May
CC play a role in determining the specificity of intracellular fusion
CC reactions. {ECO:0000250|UniProtKB:P61765}.
CC -!- SUBUNIT: Interacts with SYTL4 (By similarity). Interacts with STX1A
CC (PubMed:12730201). Interacts with alpha-synuclein/SNCA; this
CC interaction controls SNCA self-replicating aggregation
CC (PubMed:27597756). Interacts with RAB3A; this interaction promotes
CC RAB3A dissociation from the vesicle membrane (By similarity). Interacts
CC with CABP5 (By similarity). {ECO:0000250|UniProtKB:P61763,
CC ECO:0000250|UniProtKB:P61765, ECO:0000269|PubMed:12730201,
CC ECO:0000269|PubMed:27597756}.
CC -!- INTERACTION:
CC P61764; P05067: APP; NbExp=7; IntAct=EBI-960169, EBI-77613;
CC P61764; Q0VDD7: BRME1; NbExp=3; IntAct=EBI-960169, EBI-741210;
CC P61764; Q6IPU0: CENPP; NbExp=3; IntAct=EBI-960169, EBI-10250303;
CC P61764; P21917: DRD4; NbExp=3; IntAct=EBI-960169, EBI-8592297;
CC P61764; P11142: HSPA8; NbExp=2; IntAct=EBI-960169, EBI-351896;
CC P61764; P42858: HTT; NbExp=7; IntAct=EBI-960169, EBI-466029;
CC P61764; O14901: KLF11; NbExp=3; IntAct=EBI-960169, EBI-948266;
CC P61764; P28482: MAPK1; NbExp=3; IntAct=EBI-960169, EBI-959949;
CC P61764; P50222: MEOX2; NbExp=3; IntAct=EBI-960169, EBI-748397;
CC P61764; O75376: NCOR1; NbExp=3; IntAct=EBI-960169, EBI-347233;
CC P61764; Q8N0Z3: SPICE1; NbExp=3; IntAct=EBI-960169, EBI-2361917;
CC P61764; O75558: STX11; NbExp=6; IntAct=EBI-960169, EBI-714135;
CC P61764; Q8N4C7: STX19; NbExp=9; IntAct=EBI-960169, EBI-8484990;
CC P61764; Q13190: STX5; NbExp=6; IntAct=EBI-960169, EBI-714206;
CC P61764; Q96C24: SYTL4; NbExp=3; IntAct=EBI-960169, EBI-747142;
CC P61764; O00635: TRIM38; NbExp=9; IntAct=EBI-960169, EBI-2130415;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:20887364}.
CC Membrane; Peripheral membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=A;
CC IsoId=P61764-1, Q64320-1;
CC Sequence=Displayed;
CC Name=2; Synonyms=BE, HUNC18b;
CC IsoId=P61764-2, Q64320-2;
CC Sequence=VSP_006713;
CC -!- TISSUE SPECIFICITY: Brain and spinal cord. Highly enriched in axons.
CC -!- DISEASE: Developmental and epileptic encephalopathy 4 (DEE4)
CC [MIM:612164]: A severe form of epilepsy characterized by frequent tonic
CC seizures or spasms beginning in infancy with a specific EEG finding of
CC suppression-burst patterns, characterized by high-voltage bursts
CC alternating with almost flat suppression phases. Affected individuals
CC have neonatal or infantile onset of seizures, profound intellectual
CC disability, and MRI evidence of brain hypomyelination.
CC {ECO:0000269|PubMed:18469812, ECO:0000269|PubMed:20887364,
CC ECO:0000269|PubMed:21770924, ECO:0000269|PubMed:23662938,
CC ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:24170257,
CC ECO:0000269|PubMed:24623842, ECO:0000269|PubMed:25714420,
CC ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26993267,
CC ECO:0000269|PubMed:27864847}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the STXBP/unc-18/SEC1 family. {ECO:0000305}.
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DR EMBL; D63851; BAA19483.1; -; mRNA.
DR EMBL; AF004562; AAC39688.1; -; mRNA.
DR EMBL; AF004563; AAC39689.1; -; mRNA.
DR EMBL; Y12723; CAA73255.1; -; mRNA.
DR EMBL; AL162426; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471090; EAW87679.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW87681.1; -; Genomic_DNA.
DR EMBL; BC015749; AAH15749.1; -; mRNA.
DR CCDS; CCDS35146.1; -.
DR CCDS; CCDS6874.1; -. [P61764-2]
DR RefSeq; NP_001027392.1; NM_001032221.3. [P61764-1]
DR RefSeq; NP_003156.1; NM_003165.3. [P61764-2]
DR PDB; 6L03; X-ray; 2.08 A; F=141-149.
DR PDBsum; 6L03; -.
DR AlphaFoldDB; P61764; -.
DR SMR; P61764; -.
DR BioGRID; 112681; 107.
DR IntAct; P61764; 75.
DR MINT; P61764; -.
DR STRING; 9606.ENSP00000362399; -.
DR TCDB; 1.F.1.1.3; the synaptosomal vesicle fusion pore (svf-pore) family.
DR iPTMnet; P61764; -.
DR MetOSite; P61764; -.
DR PhosphoSitePlus; P61764; -.
DR BioMuta; STXBP1; -.
DR DMDM; 50403646; -.
DR EPD; P61764; -.
DR jPOST; P61764; -.
DR MassIVE; P61764; -.
DR MaxQB; P61764; -.
DR PaxDb; P61764; -.
DR PeptideAtlas; P61764; -.
DR PRIDE; P61764; -.
DR ProteomicsDB; 57331; -.
DR ProteomicsDB; 57332; -. [P61764-2]
DR Antibodypedia; 2191; 517 antibodies from 41 providers.
DR DNASU; 6812; -.
DR Ensembl; ENST00000373299.5; ENSP00000362396.2; ENSG00000136854.24. [P61764-1]
DR Ensembl; ENST00000373302.8; ENSP00000362399.3; ENSG00000136854.24. [P61764-2]
DR GeneID; 6812; -.
DR KEGG; hsa:6812; -.
DR MANE-Select; ENST00000373299.5; ENSP00000362396.2; NM_001032221.6; NP_001027392.1.
DR UCSC; uc004brk.2; human.
DR UCSC; uc004brl.3; human.
DR CTD; 6812; -.
DR DisGeNET; 6812; -.
DR GeneCards; STXBP1; -.
DR GeneReviews; STXBP1; -.
DR HGNC; HGNC:11444; STXBP1.
DR HPA; ENSG00000136854; Group enriched (brain, pituitary gland, retina).
DR MalaCards; STXBP1; -.
DR MIM; 602926; gene.
DR MIM; 612164; phenotype.
DR neXtProt; NX_P61764; -.
DR OpenTargets; ENSG00000136854; -.
DR Orphanet; 495818; 9q33.3q34.11 microdeletion syndrome.
DR Orphanet; 599373; STXBP1-related encephalopathy.
DR PharmGKB; PA36241; -.
DR VEuPathDB; HostDB:ENSG00000136854; -.
DR eggNOG; KOG1300; Eukaryota.
DR GeneTree; ENSGT00940000155127; -.
DR HOGENOM; CLU_009210_2_0_1; -.
DR InParanoid; P61764; -.
DR OMA; ITDRTMD; -.
DR OrthoDB; 725424at2759; -.
DR PhylomeDB; P61764; -.
DR TreeFam; TF313242; -.
DR PathwayCommons; P61764; -.
DR Reactome; R-HSA-181429; Serotonin Neurotransmitter Release Cycle. [P61764-1]
DR Reactome; R-HSA-181430; Norepinephrine Neurotransmitter Release Cycle. [P61764-1]
DR Reactome; R-HSA-210500; Glutamate Neurotransmitter Release Cycle. [P61764-1]
DR Reactome; R-HSA-212676; Dopamine Neurotransmitter Release Cycle. [P61764-1]
DR Reactome; R-HSA-264642; Acetylcholine Neurotransmitter Release Cycle. [P61764-1]
DR Reactome; R-HSA-422356; Regulation of insulin secretion.
DR Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR Reactome; R-HSA-888590; GABA synthesis, release, reuptake and degradation. [P61764-1]
DR SignaLink; P61764; -.
DR SIGNOR; P61764; -.
DR BioGRID-ORCS; 6812; 46 hits in 1077 CRISPR screens.
DR ChiTaRS; STXBP1; human.
DR GeneWiki; STXBP1; -.
DR GenomeRNAi; 6812; -.
DR Pharos; P61764; Tbio.
DR PRO; PR:P61764; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P61764; protein.
DR Bgee; ENSG00000136854; Expressed in middle temporal gyrus and 194 other tissues.
DR ExpressionAtlas; P61764; baseline and differential.
DR Genevisible; P61764; HS.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0045335; C:phagocytic vesicle; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0031091; C:platelet alpha granule; IDA:UniProtKB.
DR GO; GO:0098794; C:postsynapse; IEA:Ensembl.
DR GO; GO:0048787; C:presynaptic active zone membrane; IEA:Ensembl.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0030141; C:secretory granule; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0043274; F:phospholipase binding; IEA:Ensembl.
DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0047485; F:protein N-terminus binding; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0000149; F:SNARE binding; ISS:UniProtKB.
DR GO; GO:0019905; F:syntaxin binding; IPI:UniProtKB.
DR GO; GO:0017075; F:syntaxin-1 binding; IPI:UniProtKB.
DR GO; GO:0007412; P:axon target recognition; ISS:UniProtKB.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEA:Ensembl.
DR GO; GO:0003006; P:developmental process involved in reproduction; IEA:Ensembl.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0060292; P:long-term synaptic depression; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IEA:Ensembl.
DR GO; GO:0032229; P:negative regulation of synaptic transmission, GABAergic; ISS:UniProtKB.
DR GO; GO:0007274; P:neuromuscular synaptic transmission; IEA:Ensembl.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0007269; P:neurotransmitter secretion; IBA:GO_Central.
DR GO; GO:0070527; P:platelet aggregation; IMP:UniProtKB.
DR GO; GO:0002576; P:platelet degranulation; IMP:UniProtKB.
DR GO; GO:0045956; P:positive regulation of calcium ion-dependent exocytosis; IEA:Ensembl.
DR GO; GO:1903296; P:positive regulation of glutamate secretion, neurotransmission; IEA:Ensembl.
DR GO; GO:0043306; P:positive regulation of mast cell degranulation; IEA:Ensembl.
DR GO; GO:0106022; P:positive regulation of vesicle docking; IEA:Ensembl.
DR GO; GO:0099525; P:presynaptic dense core vesicle exocytosis; IEA:Ensembl.
DR GO; GO:0072659; P:protein localization to plasma membrane; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IEA:Ensembl.
DR GO; GO:2000367; P:regulation of acrosomal vesicle exocytosis; IMP:UniProtKB.
DR GO; GO:0035542; P:regulation of SNARE complex assembly; TAS:ParkinsonsUK-UCL.
DR GO; GO:0031630; P:regulation of synaptic vesicle fusion to presynaptic active zone membrane; TAS:ParkinsonsUK-UCL.
DR GO; GO:0010807; P:regulation of synaptic vesicle priming; ISS:UniProtKB.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:0035493; P:SNARE complex assembly; IMP:UniProtKB.
DR GO; GO:0016188; P:synaptic vesicle maturation; ISS:UniProtKB.
DR GO; GO:0016082; P:synaptic vesicle priming; IEA:Ensembl.
DR GO; GO:0006904; P:vesicle docking involved in exocytosis; ISS:ParkinsonsUK-UCL.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR Gene3D; 3.40.50.1910; -; 1.
DR Gene3D; 3.40.50.2060; -; 1.
DR Gene3D; 3.90.830.10; -; 1.
DR InterPro; IPR043154; Sec-1-like_dom1.
DR InterPro; IPR043127; Sec-1-like_dom3a.
DR InterPro; IPR001619; Sec1-like.
DR InterPro; IPR027482; Sec1-like_dom2.
DR InterPro; IPR036045; Sec1-like_sf.
DR PANTHER; PTHR11679; PTHR11679; 1.
DR Pfam; PF00995; Sec1; 1.
DR PIRSF; PIRSF005715; VPS45_Sec1; 1.
DR SUPFAM; SSF56815; SSF56815; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant; Epilepsy;
KW Intellectual disability; Membrane; Phosphoprotein; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1..594
FT /note="Syntaxin-binding protein 1"
FT /id="PRO_0000206277"
FT MOD_RES 476
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P61765"
FT MOD_RES 509
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08599"
FT MOD_RES 511
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08599"
FT MOD_RES 516
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08599"
FT MOD_RES 593
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P61765"
FT VAR_SEQ 576..594
FT /note="QKLLDTLKKLNKTDEEISS -> TKFLMDLRHPDFRESSRVSFEDQAPTME
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9545644"
FT /id="VSP_006713"
FT VARIANT 42
FT /note="S -> F (in DEE4)"
FT /evidence="ECO:0000269|PubMed:23708187"
FT /id="VAR_078631"
FT VARIANT 80
FT /note="S -> P (probable disease-associated variant found in
FT a patient with epileptic encephalopathy)"
FT /evidence="ECO:0000269|PubMed:23708187"
FT /id="VAR_078632"
FT VARIANT 84
FT /note="V -> D (in DEE4; may alter protein structure;
FT dbSNP:rs121918320)"
FT /evidence="ECO:0000269|PubMed:18469812"
FT /id="VAR_046205"
FT VARIANT 84
FT /note="V -> I (no effect on subcellular location;
FT dbSNP:rs34830702)"
FT /evidence="ECO:0000269|PubMed:20887364"
FT /id="VAR_073148"
FT VARIANT 122..594
FT /note="Missing (in DEE4)"
FT /evidence="ECO:0000269|PubMed:25818041"
FT /id="VAR_078757"
FT VARIANT 180
FT /note="C -> Y (in DEE4; reduced thermostability; decreased
FT binding to STX1A; dbSNP:rs121918318)"
FT /evidence="ECO:0000269|PubMed:18469812"
FT /id="VAR_046206"
FT VARIANT 183
FT /note="L -> R (in DEE4)"
FT /evidence="ECO:0000269|PubMed:21770924"
FT /id="VAR_073149"
FT VARIANT 190
FT /note="R -> W (in DEE4; dbSNP:rs796053355)"
FT /evidence="ECO:0000269|PubMed:23708187"
FT /id="VAR_078633"
FT VARIANT 251
FT /note="A -> T (in DEE4)"
FT /evidence="ECO:0000269|PubMed:24170257"
FT /id="VAR_073150"
FT VARIANT 281
FT /note="L -> P (in DEE4)"
FT /evidence="ECO:0000269|PubMed:26993267"
FT /id="VAR_078758"
FT VARIANT 283
FT /note="E -> K (in DEE4; dbSNP:rs587777310)"
FT /evidence="ECO:0000269|PubMed:24623842"
FT /id="VAR_071814"
FT VARIANT 285
FT /note="D -> Y (in DEE4)"
FT /evidence="ECO:0000269|PubMed:24623842"
FT /id="VAR_071815"
FT VARIANT 292
FT /note="R -> H (in DEE4; dbSNP:rs796053361)"
FT /evidence="ECO:0000269|PubMed:26993267"
FT /id="VAR_078759"
FT VARIANT 354
FT /note="C -> R (in DEE4; dbSNP:rs886041337)"
FT /evidence="ECO:0000269|PubMed:23708187"
FT /id="VAR_078634"
FT VARIANT 406
FT /note="R -> C (in DEE4; dbSNP:rs796053367)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078218"
FT VARIANT 406
FT /note="R -> H (in DEE4; dbSNP:rs886041246)"
FT /evidence="ECO:0000269|PubMed:20887364,
FT ECO:0000269|PubMed:25714420"
FT /id="VAR_073151"
FT VARIANT 431
FT /note="Q -> L (variant of uncertain significance; expressed
FT at low levels compared with wild-type; no effect on
FT subcellular location)"
FT /evidence="ECO:0000269|PubMed:20887364"
FT /id="VAR_073152"
FT VARIANT 443
FT /note="M -> R (in DEE4; may alter protein structure;
FT dbSNP:rs121918319)"
FT /evidence="ECO:0000269|PubMed:18469812"
FT /id="VAR_046207"
FT VARIANT 445
FT /note="H -> P (in DEE4)"
FT /evidence="ECO:0000269|PubMed:24623842"
FT /id="VAR_071816"
FT VARIANT 480
FT /note="P -> L (in DEE4; dbSNP:rs796053368)"
FT /evidence="ECO:0000269|PubMed:21770924"
FT /id="VAR_073153"
FT VARIANT 544
FT /note="G -> C (found in a patient with Lennox-Gastaut
FT syndrome; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:23708187"
FT /id="VAR_078635"
FT VARIANT 544
FT /note="G -> D (in DEE4; may alter protein structure;
FT dbSNP:rs121918317)"
FT /evidence="ECO:0000269|PubMed:18469812"
FT /id="VAR_046208"
FT VARIANT 570
FT /note="T -> A (probable disease-associated variant found in
FT a patient with epileptic encephalopathy)"
FT /evidence="ECO:0000269|PubMed:23708187"
FT /id="VAR_078636"
FT VARIANT 574
FT /note="T -> P (in DEE4)"
FT /evidence="ECO:0000269|PubMed:21770924"
FT /id="VAR_073154"
SQ SEQUENCE 594 AA; 67569 MW; 2DD0715F875CE0F3 CRC64;
MAPIGLKAVV GEKIMHDVIK KVKKKGEWKV LVVDQLSMRM LSSCCKMTDI MTEGITIVED
INKRREPLPS LEAVYLITPS EKSVHSLISD FKDPPTAKYR AAHVFFTDSC PDALFNELVK
SRAAKVIKTL TEINIAFLPY ESQVYSLDSA DSFQSFYSPH KAQMKNPILE RLAEQIATLC
ATLKEYPAVR YRGEYKDNAL LAQLIQDKLD AYKADDPTMG EGPDKARSQL LILDRGFDPS
SPVLHELTFQ AMSYDLLPIE NDVYKYETSG IGEARVKEVL LDEDDDLWIA LRHKHIAEVS
QEVTRSLKDF SSSKRMNTGE KTTMRDLSQM LKKMPQYQKE LSKYSTHLHL AEDCMKHYQG
TVDKLCRVEQ DLAMGTDAEG EKIKDPMRAI VPILLDANVS TYDKIRIILL YIFLKNGITE
ENLNKLIQHA QIPPEDSEII TNMAHLGVPI VTDSTLRRRS KPERKERISE QTYQLSRWTP
IIKDIMEDTI EDKLDTKHYP YISTRSSASF STTAVSARYG HWHKNKAPGE YRSGPRLIIF
ILGGVSLNEM RCAYEVTQAN GKWEVLIGST HILTPQKLLD TLKKLNKTDE EISS
