STXBP5

Protein-coding gene in the species Homo sapiens

STXBP5

Identifiers

Aliases

STXBP5, Tomosyn, LGL3, LLGL3, Nbla04300, syntaxin binding protein 5

External IDs

OMIM: 604586; MGI: 1926058; HomoloGene: 16402; GeneCards: STXBP5; OMA:STXBP5 - orthologs

Gene location (Human)

Chr.	Chromosome 6 (human)^[1]

Band	6q24.3	Start	147,204,417 bp^[1]
Band	6q24.3	End	147,390,476 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 10 (mouse)^[2]

Band	10\|10 A1	Start	9,755,547 bp^[2]
Band	10\|10 A1	End	9,901,079 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

Brodmann area 23

Achilles tendon

cerebellar hemisphere

endothelial cell

Brodmann area 9

sperm

right hemisphere of cerebellum

superior frontal gyrus

primary visual cortex

Brodmann area 46

Top expressed in

zygote

secondary oocyte

granulocyte

mammillary body

paraventricular nucleus of hypothalamus

supraoptic nucleus

inferior colliculus

neural layer of retina

habenula

dentate gyrus

More reference expression data

BioGPS

n/a

Gene ontology
Molecular function	GTPase activator activity syntaxin-1 binding syntaxin binding myosin II binding
Cellular component	integral component of membrane acetylcholine-gated channel complex membrane synaptic vesicle plasma membrane synapse cell junction cytoplasmic vesicle membrane cytoplasmic vesicle cytosol cytoplasm neuromuscular junction Schaffer collateral - CA1 synapse extrinsic component of presynaptic membrane presynaptic cytosol SNARE complex
Biological process	regulation of exocytosis protein transport positive regulation of exocytosis vesicle-mediated transport exocytosis regulation of protein secretion positive regulation of GTPase activity synaptic vesicle cycle
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


134957


78808

Ensembl


ENSG00000164506


ENSMUSG00000019790

UniProt


Q5T5C0


Q8K400

RefSeq (mRNA)


NM_001127715 NM_139244 NM_001394409


NM_001081344 NM_030191

RefSeq (protein)


NP_001121187 NP_640337


NP_001074813 NP_001394992 NP_001394993 NP_001394994

Location (UCSC)

Chr 6: 147.2 – 147.39 Mb

Chr 10: 9.76 – 9.9 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Syntaxin-binding protein 5 is a protein that in humans is encoded by the STXBP5 gene. It is also known as tomosyn, after 友, "friend" in Japanese, for its role as a binding protein.^[5]^[6]^[7]

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.^[7]

Positional cloning suggested that tomosyn might inhibit neurotransmitter secretion in Caenorhabditis elegans neurons.]^[8] This hypothesis was tested and confirmed, showing that tomosyn specifically inhibits synaptic vesicle priming—the biochemical step immediately preceding vesicle fusion and neurotransmitter release.^[9]

Structure

Two functional domains 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 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.^[10] 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.^[11]

Interactions

STXBP5 has been shown to interact with STX4^[12] and STX1A.^[5]^[12]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000164506 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000019790 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b Fujita Y, Shirataki H, Sakisaka T, Asakura T, Ohya T, Kotani H, Yokoyama S, Nishioka H, Matsuura Y, Mizoguchi A, Scheller RH, Takai Y (Jun 1998). "Tomosyn: a syntaxin-1-binding protein that forms a novel complex in the neurotransmitter release process". Neuron. 20 (5): 905–15. doi:10.1016/S0896-6273(00)80472-9. PMID 9620695. S2CID 12597505.
^ Katoh M, Katoh M (Feb 2004). "Identification and characterization of human LLGL4 gene and mouse Llgl4 gene in silico". Int. J. Oncol. 24 (3): 737–42. doi:10.3892/ijo.24.3.737. PMID 14767561.
^ ^a ^b "Entrez Gene: STXBP5 syntaxin binding protein 5 (tomosyn)".
^ Dybbs M, Ngai J, Kaplan JM (July 2005). "Using microarrays to facilitate positional cloning: identification of tomosyn as an inhibitor of neurosecretion". PLOS Genet. 1 (1): 6–16. doi:10.1371/journal.pgen.0010002. PMC 1183521. PMID 16103915.
^ Gracheva EO, Burdina AO, Holgado AM, et al. (July 2006). "Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans". PLOS Biol. 4 (8): e261. doi:10.1371/journal.pbio.0040261. PMC 1514790. PMID 16895441.
^ Hattendorf DA, Andreeva A, Gangar A, Brennwald PJ, Weis WI (March 2007). "Structure of the yeast polarity protein Sro7 reveals a SNARE regulatory mechanism". Nature. 446 (7135): 567–71. Bibcode:2007Natur.446..567H. doi:10.1038/nature05635. PMID 17392788. S2CID 4399611.
^ "Q5T5C0". SWISS-MODEL Repository.
^ ^a ^b Widberg CH, Bryant NJ, Girotti M, Rea S, James DE (Sep 2003). "Tomosyn interacts with the t-SNAREs syntaxin4 and SNAP23 and plays a role in insulin-stimulated GLUT4 translocation". J. Biol. Chem. 278 (37): 35093–101. doi:10.1074/jbc.M304261200. PMID 12832401.