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{{Infobox_gene}}
{{Infobox_gene}}
'''Syntaxin-binding protein 1''' (also known as [[Munc18|Munc18-1]]) is a [[protein]] that in humans is encoded by the ''STXBP1'' [[gene]].<ref name="pmid9545644">{{cite journal | vauthors = Swanson DA, Steel JM, Valle D | title = Identification and characterization of the human ortholog of rat STXBP1, a protein implicated in vesicle trafficking and neurotransmitter release | journal = Genomics | volume = 48 | issue = 3 | pages = 373–6 | date = Jun 1998 | pmid = 9545644 | pmc =  | doi = 10.1006/geno.1997.5202 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: STXBP1 syntaxin binding protein 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6812| accessdate = }}</ref>
'''Syntaxin-binding protein 1''' (also known as [[Munc18|Munc18-1]]) is a [[protein]] that in humans is encoded by the ''STXBP1'' [[gene]].<ref name="pmid9545644">{{cite journal | vauthors = Swanson DA, Steel JM, Valle D | title = Identification and characterization of the human ortholog of rat STXBP1, a protein implicated in vesicle trafficking and neurotransmitter release | journal = Genomics | volume = 48 | issue = 3 | pages = 373–6 | date = March 1998 | pmid = 9545644 | pmc =  | doi = 10.1006/geno.1997.5202 }}</ref> This gene encodes a [[Syntaxin#Binding|syntaxin-binding]] protein. The encoded protein appears to play a role in release of [[neurotransmitter]]s via regulation of syntaxin, a transmembrane attachment protein receptor. [[Mutation]]s in this gene have been associated with [[Ohtahara syndrome|infantile epileptic encephalopathy-4]].<ref name="entrez">{{cite web | title = Entrez Gene: STXBP1 syntaxin binding protein 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6812| access-date = 2018-08-29}}{{PD-notice}}</ref>


In melanocytic cells STXBP1 gene expression may be regulated by [[Microphthalmia-associated transcription factor|MITF]].<ref name="pmid19067971">{{cite journal | vauthors = Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E | title = Novel MITF targets identified using a two-step DNA microarray strategy | journal = Pigment Cell Melanoma Res | volume = 21 | issue = 6 | pages = 665–76 | year = 2008 | pmid = 19067971 | doi = 10.1111/j.1755-148X.2008.00505.x }}</ref>
== Structure ==
The ''STXBP1'' gene is located on the q arm of [[chromosome 9]] in position 34.11 and has 20 [[exon]]s spanning 80,510 base pairs.<ref name = "entrez"/> The encoded protein is a [[peripheral membrane protein]] located in the [[cytosol]].<ref name=":0">{{Cite web|url=https://www.uniprot.org/uniprot/P61764|title= STXBP1 -Syntaxin-binding protein 1 - Homo sapiens (Human) - STXBP1 gene & protein|website=www.uniprot.org|language=en|access-date=2018-08-29}}{{CC-notice|cc=by4}}</ref><ref name=":3">{{cite journal | vauthors =  | title = UniProt: the universal protein knowledgebase | journal = Nucleic Acids Research | volume = 45 | issue = D1 | pages = D158-D169 | date = January 2017 | pmid = 27899622 | pmc = 5210571 | doi = 10.1093/nar/gkw1099 | url = https://doi.org/10.1093/nar/gkw1099 }}</ref> In the [[retina]] and [[cerebellum]], an [[Alternative splicing|alternatively spliced]] transcript variant is expressed, containing an additional exon and totaling 603 [[amino acid]]s.<ref name=":1">{{cite journal | vauthors = Swanson DA, Steel JM, Valle D | title = Identification and characterization of the human ortholog of rat STXBP1, a protein implicated in vesicle trafficking and neurotransmitter release | journal = Genomics | volume = 48 | issue = 3 | pages = 373–6 | date = March 1998 | pmid = 9545644 | doi = 10.1006/geno.1997.5202 }}</ref> Alternative splicing can produce an [[protein isoform|isoform]] with exon 19 and an isoform without.<ref>{{cite journal | vauthors = Hamdan FF, Piton A, Gauthier J, Lortie A, Dubeau F, Dobrzeniecka S, Spiegelman D, Noreau A, Pellerin S, Côté M, Henrion E, Fombonne E, Mottron L, Marineau C, Drapeau P, Lafrenière RG, Lacaille JC, Rouleau GA, Michaud JL | title = De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy | journal = Annals of Neurology | volume = 65 | issue = 6 | pages = 748–53 | date = June 2009 | pmid = 19557857 | doi = 10.1002/ana.21625 }}</ref><ref name=":2">Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: {602926}: {04/22/2014}: . World Wide Web URL: https://omim.org/</ref>
 
== Function ==
The encoded protein may participate in the regulation of [[synaptic vesicle]] docking and [[Vesicle fusion|fusion]], possibly through [[protein-protein interaction|interaction]] with [[G protein|GTP-binding proteins]]. It is essential for [[neurotransmission]] and binds [[syntaxin]], a component of the synaptic vesicle fusion machinery probably in a 1:1 ratio. It can interact with syntaxins 1, 2, and 3 but not syntaxin 4 and may play a role in determining the specificity of intracellular fusion reactions.<ref name=":0" /><ref name=":3" /> This protein functions in a late stage of the intracellular membrane fusion process of [[exocytosis]]. Dissociation of this protein from syntaxin determines the [[Chemical kinetics|kinetics]] of postfusion events.<ref>{{cite journal | vauthors = Fisher RJ, Pevsner J, Burgoyne RD | title = Control of fusion pore dynamics during exocytosis by Munc18 | journal = Science | volume = 291 | issue = 5505 | pages = 875–8 | date = February 2001 | pmid = 11157167 | doi = 10.1126/science.291.5505.875 }}</ref> This protein is essential for presynpatic [[Synaptic vesicle|vesicle]] release and is rapidly [[Protein phosphorylation|phosphorylated]] by [[protein kinase C]] upon neuronal [[Depolarization#Neurons|depolarization]].<ref>{{cite journal | vauthors = Wierda KD, Toonen RF, de Wit H, Brussaard AB, Verhage M | title = Interdependence of PKC-dependent and PKC-independent pathways for presynaptic plasticity | journal = Neuron | volume = 54 | issue = 2 | pages = 275–90 | date = April 2007 | pmid = 17442248 | doi = 10.1016/j.neuron.2007.04.001 }}</ref> The protein participates in the [[Secretion|secretory pathway]] between the [[Golgi apparatus]] and [[cell membrane]].<ref>{{cite journal | vauthors = Pevsner J, Hsu SC, Scheller RH | title = n-Sec1: a neural-specific syntaxin-binding protein | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 91 | issue = 4 | pages = 1445–9 | date = February 1994 | pmid = 8108429 | pmc = 43176 }}</ref><ref name=":2" />
 
== Clinical Significance ==
=== Epileptic Encephalopathy ===
Mutations in the ''STXBP1'' cause [[Ohtahara Syndrome|Early Infantile Epileptic Encephalopathy Type 4 (EIEE4)]], a severe form of [[epilepsy]] characterized by frequent tonic seizures or spasms beginning in infancy with a specific [[Electroencephalography|EEG]] finding of [[Burst suppression|suppression-burst]] patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Affected individuals have [[Neonatology|neonatal]] or infantile onset of [[Epileptic seizure|seizures]], profound [[Intellectual disability|mental retardation]], and [[Magnetic resonance imaging|MRI]] evidence of brain [[myelin|hypomyelination]]. Inheritance of EIEE4 is [[Genetic disorder#Autosomal dominant|autosomal dominant]].<ref name=":0" /><ref name=":3" />


This gene was initially discovered in 2008 as cause for [[Ohtahara Syndrome]]. Ever since, it has become one of the most prominent genes for epileptic encephalopathies so far.<ref>[http://epilepsygenetics.net/2015/08/04/stxbp1-this-is-what-you-need-to-know-in-2015/ STXBP1 – this is what you need to know in 2015]</ref>
This gene was initially discovered in 2008 as cause for [[Ohtahara Syndrome]]. Ever since, it has become one of the most prominent genes for epileptic encephalopathies so far.<ref>[http://epilepsygenetics.net/2015/08/04/stxbp1-this-is-what-you-need-to-know-in-2015/ STXBP1 – this is what you need to know in 2015]</ref>
=== Expression ===
In [[melanocyte|melanocytic cells]] STXBP1 [[gene expression]] may be [[Regulation of gene expression|regulated]] by [[Microphthalmia-associated transcription factor|MITF]].<ref name="pmid19067971">{{cite journal | vauthors = Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E | title = Novel MITF targets identified using a two-step DNA microarray strategy | journal = Pigment Cell & Melanoma Research | volume = 21 | issue = 6 | pages = 665–76 | date = December 2008 | pmid = 19067971 | doi = 10.1111/j.1755-148X.2008.00505.x }}</ref>
The ''STXBP1'' gene is expressed in the [[brain]] and [[spinal cord]] and highly enriched in [[axon]]s.<ref name=":0" /><ref name=":3" /> Expression of this protein is highest in the retina and cerebellum.<ref name=":1" /><ref name=":2" />


== Interactions ==
== Interactions ==
 
The encoded protein binds [[SYTL4]].<ref name=":0" /><ref name=":3" /> STXBP1 has been shown to [[Protein-protein interaction|interact]] with [[STX2]],<ref name="pmid12773094">{{cite journal | vauthors = Schraw TD, Lemons PP, Dean WL, Whiteheart SW | title = A role for Sec1/Munc18 proteins in platelet exocytosis | journal = The Biochemical Journal | volume = 374 | issue = Pt 1 | pages = 207–17 | date = August 2003 | pmid = 12773094 | pmc = 1223584 | doi = 10.1042/BJ20030610 }}</ref><ref name="pmid7768895">{{cite journal | vauthors = Hata Y, Südhof TC | title = A novel ubiquitous form of Munc-18 interacts with multiple syntaxins. Use of the yeast two-hybrid system to study interactions between proteins involved in membrane traffic | journal = The Journal of Biological Chemistry | volume = 270 | issue = 22 | pages = 13022–8 | date = June 1995 | pmid = 7768895 | doi = 10.1074/jbc.270.22.13022 }}</ref> [[STX4]]<ref name="pmid12773094" /><ref name="pmid7768895" /> and [[STX1A]].<ref name=pmid7768895/><ref name=pmid12963086>{{cite journal | vauthors = Bhaskar K, Shareef MM, Sharma VM, Shetty AP, Ramamohan Y, Pant HC, Raju TR, Shetty KT | title = Co-purification and localization of Munc18-1 (p67) and Cdk5 with neuronal cytoskeletal proteins | journal = Neurochemistry International | volume = 44 | issue = 1 | pages = 35–44 | date = January 2004 | pmid = 12963086 | doi = 10.1016/S0197-0186(03)00099-8 }}</ref><ref name=pmid10449403>{{cite journal | vauthors = Dulubova I, Sugita S, Hill S, Hosaka M, Fernandez I, Südhof TC, Rizo J | title = A conformational switch in syntaxin during exocytosis: role of munc18 | journal = The EMBO Journal | volume = 18 | issue = 16 | pages = 4372–82 | date = August 1999 | pmid = 10449403 | pmc = 1171512 | doi = 10.1093/emboj/18.16.4372 }}</ref><ref name=pmid7553862>{{cite journal | vauthors = McMahon HT, Missler M, Li C, Südhof TC | title = Complexins: cytosolic proteins that regulate SNAP receptor function | journal = Cell | volume = 83 | issue = 1 | pages = 111–9 | date = October 1995 | pmid = 7553862 | doi = 10.1016/0092-8674(95)90239-2 }}</ref><ref name=pmid12093152>{{cite journal | vauthors = Pérez-Brangulí F, Muhaisen A, Blasi J | title = Munc 18a binding to syntaxin 1A and 1B isoforms defines its localization at the plasma membrane and blocks SNARE assembly in a three-hybrid system assay | journal = Molecular and Cellular Neurosciences | volume = 20 | issue = 2 | pages = 169–80 | date = June 2002 | pmid = 12093152 | doi = 10.1006/mcne.2002.1122 }}</ref>{{clear}}
STXBP1 has been shown to [[Protein-protein interaction|interact]] with [[STX2]],<ref name=pmid12773094>{{cite journal | vauthors = Schraw TD, Lemons PP, Dean WL, Whiteheart SW | title = A role for Sec1/Munc18 proteins in platelet exocytosis | journal = Biochem. J. | volume = 374 | issue = Pt 1 | pages = 207–17 | date = Aug 2003 | pmid = 12773094 | pmc = 1223584 | doi = 10.1042/BJ20030610 }}</ref><ref name=pmid7768895>{{cite journal | vauthors = Hata Y, Südhof TC | title = A novel ubiquitous form of Munc-18 interacts with multiple syntaxins. Use of the yeast two-hybrid system to study interactions between proteins involved in membrane traffic | journal = J. Biol. Chem. | volume = 270 | issue = 22 | pages = 13022–8 | date = Jun 1995 | pmid = 7768895 | doi = 10.1074/jbc.270.22.13022 }}</ref> [[STX4]]<ref name=pmid12773094/><ref name=pmid7768895/> and [[STX1A]].<ref name=pmid7768895/><ref name=pmid12963086>{{cite journal | vauthors = Bhaskar K, Shareef MM, Sharma VM, Shetty AP, Ramamohan Y, Pant HC, Raju TR, Shetty KT | title = Co-purification and localization of Munc18-1 (p67) and Cdk5 with neuronal cytoskeletal proteins | journal = Neurochem. Int. | volume = 44 | issue = 1 | pages = 35–44 | date = Jan 2004 | pmid = 12963086 | doi = 10.1016/S0197-0186(03)00099-8 }}</ref><ref name=pmid10449403>{{cite journal | vauthors = Dulubova I, Sugita S, Hill S, Hosaka M, Fernandez I, Südhof TC, Rizo J | title = A conformational switch in syntaxin during exocytosis: role of munc18 | journal = EMBO J. | volume = 18 | issue = 16 | pages = 4372–82 | date = Aug 1999 | pmid = 10449403 | pmc = 1171512 | doi = 10.1093/emboj/18.16.4372 }}</ref><ref name=pmid7553862>{{cite journal | vauthors = McMahon HT, Missler M, Li C, Südhof TC | title = Complexins: cytosolic proteins that regulate SNAP receptor function | journal = Cell | volume = 83 | issue = 1 | pages = 111–9 | date = Oct 1995 | pmid = 7553862 | doi = 10.1016/0092-8674(95)90239-2 }}</ref><ref name=pmid12093152>{{cite journal | vauthors = Pérez-Brangulí F, Muhaisen A, Blasi J | title = Munc 18a binding to syntaxin 1A and 1B isoforms defines its localization at the plasma membrane and blocks SNARE assembly in a three-hybrid system assay | journal = Mol. Cell. Neurosci. | volume = 20 | issue = 2 | pages = 169–80 | date = Jun 2002 | pmid = 12093152 | doi = 10.1006/mcne.2002.1122 }}</ref>


== References ==
== References ==
{{reflist}}
{{reflist|32em}}


== Further reading ==
== Further reading ==
{{refbegin | 2}}
{{refbegin|32em}}
* {{cite journal | vauthors = Garcia EP, McPherson PS, Chilcote TJ, Takei K, De Camilli P | title = rbSec1A and B colocalize with syntaxin 1 and SNAP-25 throughout the axon, but are not in a stable complex with syntaxin | journal = J. Cell Biol. | volume = 129 | issue = 1 | pages = 105–20 | year = 1995 | pmid = 7698978 | pmc = 2120371 | doi = 10.1083/jcb.129.1.105 }}
* {{cite journal | vauthors = Barcia G, Barnerias C, Rio M, Siquier-Pernet K, Desguerre I, Colleaux L, Munnich A, Rotig A, Nabbout R | title = A novel mutation in STXBP1 causing epileptic encephalopathy (late onset infantile spasms) with partial respiratory chain complex IV deficiency | journal = European Journal of Medical Genetics | volume = 56 | issue = 12 | pages = 683–5 | date = December 2013 | pmid = 24095819 | doi = 10.1016/j.ejmg.2013.09.013 }}
* {{cite journal | vauthors = Pevsner J, Hsu SC, Scheller RH | title = n-Sec1: a neural-specific syntaxin-binding protein | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 91 | issue = 4 | pages = 1445–9 | year = 1994 | pmid = 8108429 | pmc = 43176 | doi = 10.1073/pnas.91.4.1445 }}
* {{cite journal | vauthors = Garcia EP, McPherson PS, Chilcote TJ, Takei K, De Camilli P | title = rbSec1A and B colocalize with syntaxin 1 and SNAP-25 throughout the axon, but are not in a stable complex with syntaxin | journal = The Journal of Cell Biology | volume = 129 | issue = 1 | pages = 105–20 | date = April 1995 | pmid = 7698978 | pmc = 2120371 | doi = 10.1083/jcb.129.1.105 }}
* {{cite journal | vauthors = Fujita Y, Sasaki T, Fukui K, Kotani H, Kimura T, Hata Y, Südhof TC, Scheller RH, Takai Y | title = Phosphorylation of Munc-18/n-Sec1/rbSec1 by protein kinase C: its implication in regulating the interaction of Munc-18/n-Sec1/rbSec1 with syntaxin | journal = J. Biol. Chem. | volume = 271 | issue = 13 | pages = 7265–8 | year = 1996 | pmid = 8631738 | doi = 10.1074/jbc.271.13.7265 }}
* {{cite journal | vauthors = Pevsner J, Hsu SC, Scheller RH | title = n-Sec1: a neural-specific syntaxin-binding protein | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 91 | issue = 4 | pages = 1445–9 | date = February 1994 | pmid = 8108429 | pmc = 43176 | doi = 10.1073/pnas.91.4.1445 }}
* {{cite journal | vauthors = Gengyo-Ando K, Kitayama H, Mukaida M, Ikawa Y | title = A murine neural-specific homolog corrects cholinergic defects in Caenorhabditis elegans unc-18 mutants | journal = J. Neurosci. | volume = 16 | issue = 21 | pages = 6695–702 | year = 1996 | pmid = 8824310 | doi = }}
* {{cite journal | vauthors = Fujita Y, Sasaki T, Fukui K, Kotani H, Kimura T, Hata Y, Südhof TC, Scheller RH, Takai Y | title = Phosphorylation of Munc-18/n-Sec1/rbSec1 by protein kinase C: its implication in regulating the interaction of Munc-18/n-Sec1/rbSec1 with syntaxin | journal = The Journal of Biological Chemistry | volume = 271 | issue = 13 | pages = 7265–8 | date = March 1996 | pmid = 8631738 | doi = 10.1074/jbc.271.13.7265 }}
* {{cite journal | vauthors = Tellam JT, Macaulay SL, McIntosh S, Hewish DR, Ward CW, James DE | title = Characterization of Munc-18c and syntaxin-4 in 3T3-L1 adipocytes. Putative role in insulin-dependent movement of GLUT-4 | journal = J. Biol. Chem. | volume = 272 | issue = 10 | pages = 6179–86 | year = 1997 | pmid = 9045631 | doi = 10.1074/jbc.272.10.6179 }}
* {{cite journal | vauthors = Gengyo-Ando K, Kitayama H, Mukaida M, Ikawa Y | title = A murine neural-specific homolog corrects cholinergic defects in Caenorhabditis elegans unc-18 mutants | journal = The Journal of Neuroscience | volume = 16 | issue = 21 | pages = 6695–702 | date = November 1996 | pmid = 8824310 | doi = }}
* {{cite journal | vauthors = Verhage M, de Vries KJ, Røshol H, Burbach JP, Gispen WH, Südhof TC | title = DOC2 proteins in rat brain: complementary distribution and proposed function as vesicular adapter proteins in early stages of secretion | journal = Neuron | volume = 18 | issue = 3 | pages = 453–61 | year = 1997 | pmid = 9115738 | doi = 10.1016/S0896-6273(00)81245-3 }}
* {{cite journal | vauthors = Tellam JT, Macaulay SL, McIntosh S, Hewish DR, Ward CW, James DE | title = Characterization of Munc-18c and syntaxin-4 in 3T3-L1 adipocytes. Putative role in insulin-dependent movement of GLUT-4 | journal = The Journal of Biological Chemistry | volume = 272 | issue = 10 | pages = 6179–86 | date = March 1997 | pmid = 9045631 | doi = 10.1074/jbc.272.10.6179 }}
* {{cite journal | vauthors = Okamoto M, Südhof TC | title = Mints, Munc18-interacting proteins in synaptic vesicle exocytosis | journal = J. Biol. Chem. | volume = 272 | issue = 50 | pages = 31459–64 | year = 1997 | pmid = 9395480 | doi = 10.1074/jbc.272.50.31459 }}
* {{cite journal | vauthors = Verhage M, de Vries KJ, Røshol H, Burbach JP, Gispen WH, Südhof TC | title = DOC2 proteins in rat brain: complementary distribution and proposed function as vesicular adapter proteins in early stages of secretion | journal = Neuron | volume = 18 | issue = 3 | pages = 453–61 | date = March 1997 | pmid = 9115738 | doi = 10.1016/S0896-6273(00)81245-3 }}
* {{cite journal | vauthors = Fletcher AI, Shuang R, Giovannucci DR, Zhang L, Bittner MA, Stuenkel EL | title = Regulation of exocytosis by cyclin-dependent kinase 5 via phosphorylation of Munc18 | journal = J. Biol. Chem. | volume = 274 | issue = 7 | pages = 4027–35 | year = 1999 | pmid = 9933594 | doi = 10.1074/jbc.274.7.4027 }}
* {{cite journal | vauthors = Okamoto M, Südhof TC | title = Mints, Munc18-interacting proteins in synaptic vesicle exocytosis | journal = The Journal of Biological Chemistry | volume = 272 | issue = 50 | pages = 31459–64 | date = December 1997 | pmid = 9395480 | doi = 10.1074/jbc.272.50.31459 }}
* {{cite journal | vauthors = Reed GL, Houng AK, Fitzgerald ML | title = Human platelets contain SNARE proteins and a Sec1p homologue that interacts with syntaxin 4 and is phosphorylated after thrombin activation: implications for platelet secretion | journal = Blood | volume = 93 | issue = 8 | pages = 2617–26 | year = 1999 | pmid = 10194441 | doi = }}
* {{cite journal | vauthors = Fletcher AI, Shuang R, Giovannucci DR, Zhang L, Bittner MA, Stuenkel EL | title = Regulation of exocytosis by cyclin-dependent kinase 5 via phosphorylation of Munc18 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 7 | pages = 4027–35 | date = February 1999 | pmid = 9933594 | doi = 10.1074/jbc.274.7.4027 }}
* {{cite journal | vauthors = Dulubova I, Sugita S, Hill S, Hosaka M, Fernandez I, Südhof TC, Rizo J | title = A conformational switch in syntaxin during exocytosis: role of munc18 | journal = EMBO J. | volume = 18 | issue = 16 | pages = 4372–82 | year = 1999 | pmid = 10449403 | pmc = 1171512 | doi = 10.1093/emboj/18.16.4372 }}
* {{cite journal | vauthors = Reed GL, Houng AK, Fitzgerald ML | title = Human platelets contain SNARE proteins and a Sec1p homologue that interacts with syntaxin 4 and is phosphorylated after thrombin activation: implications for platelet secretion | journal = Blood | volume = 93 | issue = 8 | pages = 2617–26 | date = April 1999 | pmid = 10194441 | doi = }}
* {{cite journal | vauthors = Misura KM, Scheller RH, Weis WI | title = Three-dimensional structure of the neuronal-Sec1-syntaxin 1a complex | journal = Nature | volume = 404 | issue = 6776 | pages = 355–62 | year = 2000 | pmid = 10746715 | doi = 10.1038/35006120 }}
* {{cite journal | vauthors = Dulubova I, Sugita S, Hill S, Hosaka M, Fernandez I, Südhof TC, Rizo J | title = A conformational switch in syntaxin during exocytosis: role of munc18 | journal = The EMBO Journal | volume = 18 | issue = 16 | pages = 4372–82 | date = August 1999 | pmid = 10449403 | pmc = 1171512 | doi = 10.1093/emboj/18.16.4372 }}
* {{cite journal | vauthors = Allan BB, Moyer BD, Balch WE | title = Rab1 recruitment of p115 into a cis-SNARE complex: programming budding COPII vesicles for fusion | journal = Science | volume = 289 | issue = 5478 | pages = 444–8 | year = 2000 | pmid = 10903204 | doi = 10.1126/science.289.5478.444 }}
* {{cite journal | vauthors = Misura KM, Scheller RH, Weis WI | title = Three-dimensional structure of the neuronal-Sec1-syntaxin 1a complex | journal = Nature | volume = 404 | issue = 6776 | pages = 355–62 | date = March 2000 | pmid = 10746715 | doi = 10.1038/35006120 }}
* {{cite journal | vauthors = Shorter J, Beard MB, Seemann J, Dirac-Svejstrup AB, Warren G | title = Sequential tethering of Golgins and catalysis of SNAREpin assembly by the vesicle-tethering protein p115 | journal = J. Cell Biol. | volume = 157 | issue = 1 | pages = 45–62 | year = 2002 | pmid = 11927603 | pmc = 2173270 | doi = 10.1083/jcb.200112127 }}
* {{cite journal | vauthors = Allan BB, Moyer BD, Balch WE | title = Rab1 recruitment of p115 into a cis-SNARE complex: programming budding COPII vesicles for fusion | journal = Science | volume = 289 | issue = 5478 | pages = 444–8 | date = July 2000 | pmid = 10903204 | doi = 10.1126/science.289.5478.444 }}
* {{cite journal | vauthors = Ho CS, Marinescu V, Steinhilb ML, Gaut JR, Turner RS, Stuenkel EL | title = Synergistic effects of Munc18a and X11 proteins on amyloid precursor protein metabolism | journal = J. Biol. Chem. | volume = 277 | issue = 30 | pages = 27021–8 | year = 2002 | pmid = 12016213 | doi = 10.1074/jbc.M201823200 }}
* {{cite journal | vauthors = Shorter J, Beard MB, Seemann J, Dirac-Svejstrup AB, Warren G | title = Sequential tethering of Golgins and catalysis of SNAREpin assembly by the vesicle-tethering protein p115 | journal = The Journal of Cell Biology | volume = 157 | issue = 1 | pages = 45–62 | date = April 2002 | pmid = 11927603 | pmc = 2173270 | doi = 10.1083/jcb.200112127 }}
* {{cite journal | vauthors = Pérez-Brangulí F, Muhaisen A, Blasi J | title = Munc 18a binding to syntaxin 1A and 1B isoforms defines its localization at the plasma membrane and blocks SNARE assembly in a three-hybrid system assay | journal = Mol. Cell. Neurosci. | volume = 20 | issue = 2 | pages = 169–80 | year = 2002 | pmid = 12093152 | doi = 10.1006/mcne.2002.1122 }}
* {{cite journal | vauthors = Ho CS, Marinescu V, Steinhilb ML, Gaut JR, Turner RS, Stuenkel EL | title = Synergistic effects of Munc18a and X11 proteins on amyloid precursor protein metabolism | journal = The Journal of Biological Chemistry | volume = 277 | issue = 30 | pages = 27021–8 | date = July 2002 | pmid = 12016213 | doi = 10.1074/jbc.M201823200 }}
* {{cite journal | vauthors = Barclay JW, Craig TJ, Fisher RJ, Ciufo LF, Evans GJ, Morgan A, Burgoyne RD | title = Phosphorylation of Munc18 by protein kinase C regulates the kinetics of exocytosis | journal = J. Biol. Chem. | volume = 278 | issue = 12 | pages = 10538–45 | year = 2003 | pmid = 12519779 | doi = 10.1074/jbc.M211114200 }}
* {{cite journal | vauthors = Pérez-Brangulí F, Muhaisen A, Blasi J | title = Munc 18a binding to syntaxin 1A and 1B isoforms defines its localization at the plasma membrane and blocks SNARE assembly in a three-hybrid system assay | journal = Molecular and Cellular Neurosciences | volume = 20 | issue = 2 | pages = 169–80 | date = June 2002 | pmid = 12093152 | doi = 10.1006/mcne.2002.1122 }}
* {{cite journal | vauthors = Fukuda M | title = Slp4-a/granuphilin-a inhibits dense-core vesicle exocytosis through interaction with the GDP-bound form of Rab27A in PC12 cells | journal = J. Biol. Chem. | volume = 278 | issue = 17 | pages = 15390–6 | year = 2003 | pmid = 12590134 | doi = 10.1074/jbc.M213090200 }}
* {{cite journal | vauthors = Barclay JW, Craig TJ, Fisher RJ, Ciufo LF, Evans GJ, Morgan A, Burgoyne RD | title = Phosphorylation of Munc18 by protein kinase C regulates the kinetics of exocytosis | journal = The Journal of Biological Chemistry | volume = 278 | issue = 12 | pages = 10538–45 | date = March 2003 | pmid = 12519779 | doi = 10.1074/jbc.M211114200 }}
* {{cite journal | vauthors = Craig TJ, Evans GJ, Morgan A | title = Physiological regulation of Munc18/nSec1 phosphorylation on serine-313 | journal = J. Neurochem. | volume = 86 | issue = 6 | pages = 1450–7 | year = 2003 | pmid = 12950453 | doi = 10.1046/j.1471-4159.2003.01955.x }}
* {{cite journal | vauthors = Fukuda M | title = Slp4-a/granuphilin-a inhibits dense-core vesicle exocytosis through interaction with the GDP-bound form of Rab27A in PC12 cells | journal = The Journal of Biological Chemistry | volume = 278 | issue = 17 | pages = 15390–6 | date = April 2003 | pmid = 12590134 | doi = 10.1074/jbc.M213090200 }}
* {{cite journal | vauthors = Craig TJ, Evans GJ, Morgan A | title = Physiological regulation of Munc18/nSec1 phosphorylation on serine-313 | journal = Journal of Neurochemistry | volume = 86 | issue = 6 | pages = 1450–7 | date = September 2003 | pmid = 12950453 | doi = 10.1046/j.1471-4159.2003.01955.x }}
{{refend}}
{{refend}}


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Latest revision as of 07:33, 10 January 2019

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Syntaxin-binding protein 1 (also known as Munc18-1) is a protein that in humans is encoded by the STXBP1 gene.[1] This gene encodes a syntaxin-binding protein. The encoded protein appears to play a role in release of neurotransmitters via regulation of syntaxin, a transmembrane attachment protein receptor. Mutations in this gene have been associated with infantile epileptic encephalopathy-4.[2]

Structure

The STXBP1 gene is located on the q arm of chromosome 9 in position 34.11 and has 20 exons spanning 80,510 base pairs.[2] The encoded protein is a peripheral membrane protein located in the cytosol.[3][4] In the retina and cerebellum, an alternatively spliced transcript variant is expressed, containing an additional exon and totaling 603 amino acids.[5] Alternative splicing can produce an isoform with exon 19 and an isoform without.[6][7]

Function

The encoded protein may participate in the regulation of synaptic vesicle docking and fusion, possibly through interaction with GTP-binding proteins. It is essential for neurotransmission and binds syntaxin, a component of the synaptic vesicle fusion machinery probably in a 1:1 ratio. It can interact with syntaxins 1, 2, and 3 but not syntaxin 4 and may play a role in determining the specificity of intracellular fusion reactions.[3][4] This protein functions in a late stage of the intracellular membrane fusion process of exocytosis. Dissociation of this protein from syntaxin determines the kinetics of postfusion events.[8] This protein is essential for presynpatic vesicle release and is rapidly phosphorylated by protein kinase C upon neuronal depolarization.[9] The protein participates in the secretory pathway between the Golgi apparatus and cell membrane.[10][7]

Clinical Significance

Epileptic Encephalopathy

Mutations in the STXBP1 cause Early Infantile Epileptic Encephalopathy Type 4 (EIEE4), a severe form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Affected individuals have neonatal or infantile onset of seizures, profound mental retardation, and MRI evidence of brain hypomyelination. Inheritance of EIEE4 is autosomal dominant.[3][4]

This gene was initially discovered in 2008 as cause for Ohtahara Syndrome. Ever since, it has become one of the most prominent genes for epileptic encephalopathies so far.[11]

Expression

In melanocytic cells STXBP1 gene expression may be regulated by MITF.[12]

The STXBP1 gene is expressed in the brain and spinal cord and highly enriched in axons.[3][4] Expression of this protein is highest in the retina and cerebellum.[5][7]

Interactions

The encoded protein binds SYTL4.[3][4] STXBP1 has been shown to interact with STX2,[13][14] STX4[13][14] and STX1A.[14][15][16][17][18]

References

  1. ↑ Swanson DA, Steel JM, Valle D (March 1998). "Identification and characterization of the human ortholog of rat STXBP1, a protein implicated in vesicle trafficking and neurotransmitter release". Genomics. 48 (3): 373–6. doi:10.1006/geno.1997.5202. PMID 9545644.
  2. ↑ 2.0 2.1 "Entrez Gene: STXBP1 syntaxin binding protein 1". Retrieved 2018-08-29. This article incorporates text from this source, which is in the public domain.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 "STXBP1 -Syntaxin-binding protein 1 - Homo sapiens (Human) - STXBP1 gene & protein". www.uniprot.org. Retrieved 2018-08-29.File:CC-BY-icon-80x15.png This article incorporates text available under the CC BY 4.0 license.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  5. ↑ 5.0 5.1 Swanson DA, Steel JM, Valle D (March 1998). "Identification and characterization of the human ortholog of rat STXBP1, a protein implicated in vesicle trafficking and neurotransmitter release". Genomics. 48 (3): 373–6. doi:10.1006/geno.1997.5202. PMID 9545644.
  6. ↑ Hamdan FF, Piton A, Gauthier J, Lortie A, Dubeau F, Dobrzeniecka S, Spiegelman D, Noreau A, Pellerin S, Côté M, Henrion E, Fombonne E, Mottron L, Marineau C, Drapeau P, Lafrenière RG, Lacaille JC, Rouleau GA, Michaud JL (June 2009). "De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy". Annals of Neurology. 65 (6): 748–53. doi:10.1002/ana.21625. PMID 19557857.
  7. ↑ 7.0 7.1 7.2 Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: {602926}: {04/22/2014}: . World Wide Web URL: https://omim.org/
  8. ↑ Fisher RJ, Pevsner J, Burgoyne RD (February 2001). "Control of fusion pore dynamics during exocytosis by Munc18". Science. 291 (5505): 875–8. doi:10.1126/science.291.5505.875. PMID 11157167.
  9. ↑ Wierda KD, Toonen RF, de Wit H, Brussaard AB, Verhage M (April 2007). "Interdependence of PKC-dependent and PKC-independent pathways for presynaptic plasticity". Neuron. 54 (2): 275–90. doi:10.1016/j.neuron.2007.04.001. PMID 17442248.
  10. ↑ Pevsner J, Hsu SC, Scheller RH (February 1994). "n-Sec1: a neural-specific syntaxin-binding protein". Proceedings of the National Academy of Sciences of the United States of America. 91 (4): 1445–9. PMC 43176. PMID 8108429.
  11. ↑ STXBP1 – this is what you need to know in 2015
  12. ↑ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (December 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
  13. ↑ 13.0 13.1 Schraw TD, Lemons PP, Dean WL, Whiteheart SW (August 2003). "A role for Sec1/Munc18 proteins in platelet exocytosis". The Biochemical Journal. 374 (Pt 1): 207–17. doi:10.1042/BJ20030610. PMC 1223584. PMID 12773094.
  14. ↑ 14.0 14.1 14.2 Hata Y, Südhof TC (June 1995). "A novel ubiquitous form of Munc-18 interacts with multiple syntaxins. Use of the yeast two-hybrid system to study interactions between proteins involved in membrane traffic". The Journal of Biological Chemistry. 270 (22): 13022–8. doi:10.1074/jbc.270.22.13022. PMID 7768895.
  15. ↑ Bhaskar K, Shareef MM, Sharma VM, Shetty AP, Ramamohan Y, Pant HC, Raju TR, Shetty KT (January 2004). "Co-purification and localization of Munc18-1 (p67) and Cdk5 with neuronal cytoskeletal proteins". Neurochemistry International. 44 (1): 35–44. doi:10.1016/S0197-0186(03)00099-8. PMID 12963086.
  16. ↑ Dulubova I, Sugita S, Hill S, Hosaka M, Fernandez I, Südhof TC, Rizo J (August 1999). "A conformational switch in syntaxin during exocytosis: role of munc18". The EMBO Journal. 18 (16): 4372–82. doi:10.1093/emboj/18.16.4372. PMC 1171512. PMID 10449403.
  17. ↑ McMahon HT, Missler M, Li C, Südhof TC (October 1995). "Complexins: cytosolic proteins that regulate SNAP receptor function". Cell. 83 (1): 111–9. doi:10.1016/0092-8674(95)90239-2. PMID 7553862.
  18. ↑ Pérez-Brangulí F, Muhaisen A, Blasi J (June 2002). "Munc 18a binding to syntaxin 1A and 1B isoforms defines its localization at the plasma membrane and blocks SNARE assembly in a three-hybrid system assay". Molecular and Cellular Neurosciences. 20 (2): 169–80. doi:10.1006/mcne.2002.1122. PMID 12093152.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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