View source for STXBP5

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''Syntaxin-binding protein 5''' is a [[protein]] that in humans is encoded by the ''STXBP5'' [[gene]]. It is also known as '''tomosyn''', after {{lang|ja|[[wikt:友#Japanese|友]]}}, "friend" in [[Japanese language|Japanese]], for its role as a binding protein.<ref name="pmid9620695">{{cite journal | vauthors = Fujita Y, Shirataki H, Sakisaka T, Asakura T, Ohya T, Kotani H, Yokoyama S, Nishioka H, Matsuura Y, Mizoguchi A, Scheller RH, Takai Y | title = Tomosyn: a syntaxin-1-binding protein that forms a novel complex in the neurotransmitter release process | journal = Neuron | volume = 20 | issue = 5 | pages = 905–15  | date = Jun 1998 | pmid = 9620695 | doi = 10.1016/S0896-6273(00)80472-9 | s2cid = 12597505 | doi-access = free }}</ref><ref name="pmid14767561">{{cite journal | vauthors = Katoh M, Katoh M | title = Identification and characterization of human LLGL4 gene and mouse Llgl4 gene in silico | journal = Int. J. Oncol. | volume = 24 | issue = 3 | pages = 737–42  | date = Feb 2004 | pmid = 14767561 | doi = 10.3892/ijo.24.3.737 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: STXBP5 syntaxin binding protein 5 (tomosyn)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=134957}}</ref>
== Function ==
Syntaxin 1 is a component of the 7S and 20S SNARE complexes which are involved in docking and fusion of synaptic vesicles with the presynaptic plasma membrane. This gene encodes a syntaxin 1 binding protein. In rat, a similar protein dissociates syntaxin 1 from the Munc18/n-Sec1/rbSec1 complex to form a 10S complex, an intermediate which can be converted to the 7S SNARE complex. Thus this protein is thought to be involved in neurotransmitter release by stimulating SNARE complex formation. Alternatively spliced variants have been identified, but their biological validity has not been determined.<ref name="entrez"/>
[[Positional cloning]] suggested that tomosyn might inhibit [[neurotransmitter]] secretion in ''[[Caenorhabditis elegans]]'' [[neuron]]s.]<ref>{{cite journal |vauthors=Dybbs M, Ngai J, Kaplan JM |title=Using microarrays to facilitate positional cloning: identification of tomosyn as an inhibitor of neurosecretion |journal=PLOS Genet. |volume=1 |issue=1 |pages=6–16 |date=July 2005 |pmid=16103915 |pmc=1183521 |doi=10.1371/journal.pgen.0010002 |doi-access=free }} {{open access}}</ref> This hypothesis was tested and confirmed, showing that tomosyn specifically inhibits synaptic vesicle priming—the biochemical step immediately preceding vesicle fusion and neurotransmitter release.<ref>{{cite journal  |vauthors=Gracheva EO, Burdina AO, Holgado AM, etal |title=Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans |journal=PLOS Biol. |volume=4 |issue=8 |pages=e261 |date=July 2006 |pmid=16895441 |pmc=1514790 |doi=10.1371/journal.pbio.0040261 |doi-access=free }} {{open access}}</ref>
== Structure ==
Two [[functional domain]]s were originally identified, including one which binds to [[syntaxin]], but recent crystallization of the yeast homolog Sro7 revealed that tomosyn likely has three functional domains: one [[WD40 repeat|WD40 domain]] and one syntaxin-binding domain, as previously recognized, but also another WD40 domain. The study also suggested that tomosyn's 'syntaxin binding domain' is not the reason tomosyn is inhibitory for neurotransmitter release, as originally proposed.<ref name="Hattendorf">{{cite journal |vauthors=Hattendorf DA, Andreeva A, Gangar A, Brennwald PJ, Weis WI |title=Structure of the yeast polarity protein Sro7 reveals a SNARE regulatory mechanism |journal=Nature |volume=446 |issue=7135 |pages=567–71 |date=March 2007 |pmid=17392788 |doi=10.1038/nature05635 |bibcode=2007Natur.446..567H |s2cid=4399611 }}</ref> The Sro7-based structure is currently given on SWISS-MODEL, which includes the WD40 domains but not most of the [[coiled coil]] syntaxin-binding domain seen in the infobox.<ref>{{cite web |title=Q5T5C0 |url=https://swissmodel.expasy.org/repository/uniprot/Q5T5C0 |website=SWISS-MODEL Repository}}</ref>
== Interactions ==
STXBP5 has been shown to [[Protein-protein interaction|interact]] with [[STX4]]<ref name=pmid12832401>{{cite journal | vauthors = Widberg CH, Bryant NJ, Girotti M, Rea S, James DE | title = Tomosyn interacts with the t-SNAREs syntaxin4 and SNAP23 and plays a role in insulin-stimulated GLUT4 translocation | journal = J. Biol. Chem. | volume = 278 | issue = 37 | pages = 35093–101  | date = Sep 2003 | pmid = 12832401 | doi = 10.1074/jbc.M304261200 | doi-access = free }}</ref> and [[STX1A]].<ref name=pmid9620695 /><ref name=pmid12832401/>
== References ==
{{reflist}}
== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–48 | year = 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 | s2cid = 7827573 | doi-access = free }}
* {{cite journal | vauthors = Widberg CH, Bryant NJ, Girotti M, Rea S, James DE | title = Tomosyn interacts with the t-SNAREs syntaxin4 and SNAP23 and plays a role in insulin-stimulated GLUT4 translocation | journal = J. Biol. Chem. | volume = 278 | issue = 37 | pages = 35093–101 | year = 2003 | pmid = 12832401 | doi = 10.1074/jbc.M304261200 | doi-access = free }}
* {{cite journal | vauthors = Yokoyama S, Shirataki H, Sakisaka T, Takai Y | title = Three splicing variants of tomosyn and identification of their syntaxin-binding region | journal = Biochem. Biophys. Res. Commun. | volume = 256 | issue = 1 | pages = 218–22 | year = 1999 | pmid = 10066450 | doi = 10.1006/bbrc.1999.0300 }}
{{refend}}
{{PDB Gallery|geneid=134957}}
[[Category:Proteins]]
{{gene-6-stub}}