Participates in the regulation of synaptic vesicle docking and fusion through interaction with GTP-binding proteins (By similarity). Essential for neurotransmission and binds syntaxin, a component of the synaptic vesicle fusion machinery probably in a 1:1 ratio. Can interact with syntaxins 1, 2, and 3 but not syntaxin 4. May play a role in determining the specificity of intracellular fusion reactions. (updated: May 8, 2019)
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
No sequence conservation computed yet.
This protein is annotated as membranous in Gene Ontology.
Total structural coverage: 100%
No model available.
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The reference OMIM entry for this protein is 602926
Syntaxin-binding protein 1; stxbp1
Unc18, c. elegans, homolog of, 1
Munc18-1
CLONING
Within the secretory pathway, proteins and other cargo are transferred from one compartment to another by vesicular traffic. Transport vesicles bud from donor membranes and dock to specific acceptor compartments. The S. cerevisiae protein Sec1 participates in the constitutive secretory pathway between the Golgi apparatus and the plasma membrane. Pevsner et al. (1994) identified rat Stxbp1, which they called n-Sec1. The predicted 68-kD n-Sec1 protein shares 27% identity with S. cerevisiae Sec1 and 59% identity with C. elegans Unc18. RNA blot analysis showed that n-Sec1 mRNA expression was neural-specific. Since Unc18 mutation leads to severe paralysis and presynaptic acetylcholine accumulation, Unc18 has been implicated in neurotransmitter release. Gengyo-Ando et al. (1996) identified cDNAs encoding 2 mouse Unc18 homologs, a neural-specific protein called Munc18-1 and a ubiquitous protein called Munc18-3. They used the murine cDNAs to isolate human Munc18-1 cDNAs from a fetal brain cDNA library. The sequences of the predicted 594-amino acid mouse and human Munc18-1 proteins are identical. Gengyo-Ando et al. (1996) found that Munc18-1 complemented the locomotion and cholinergic defects in Unc18 mutant animals. By Northern blot analysis of human tissues, Swanson et al. (1998) determined that STXBP1 is expressed as a 4-kb transcript in various tissues. The highest levels of expression were observed in retina and cerebellum. RT-PCR analysis revealed an additional, alternatively spliced form of STXBP1 in retina and cerebellum. This mRNA contains an additional exon and encodes a predicted 603-amino acid protein. Two alternatively spliced forms of STXBP1 are also found in rat, and the predicted proteins are identical to their human counterparts.
GENE STRUCTURE
Hamdan et al. (2009) stated that the STXBP1 gene contains 20 exons and that alternative splicing results in 2 isoforms with and without exon 19.
MAPPING
By fluorescence in situ hybridization, Swanson et al. (1998) mapped the STXBP1 gene to chromosome 9q34.1.
GENE FUNCTION
Pevsner et al. (1994) found that rat n-Sec1 is a neural-specific, syntaxin (see
186590)-binding protein that may participate in the regulation of synaptic vesicle docking and fusion. Yang et al. (2000) identified high titer autoantibodies against Munc18 in the serum and CSF of a single patient with Rasmussen encephalitis, a rare disorder characterized by progressive degeneration of a single cerebral hemisphere and intractable seizures. The patient had previously been reported by Rogers et al. (1994) who identified autoantibodies against GLUR3 (GRIA3;
305915) in serum and CSF. Weak immunoreactivity to Munc18 was found in 3 of 14 additional patients with Rasmussen encephalitis, but often only on prolonged exposure or multiple experiments. As Munc18 is a cytosolic protein, Yang et al. (2000) hypothesized that humoral attack on GluR3 would first damage neurons, thus exposing Munc18 and leading to expanded immune attack. Both proteins are involved in synaptic transmission; immune attack on these proteins may have acted synergistically to produce a severe neurologic phenotype. In adrenal chromaffin cells, Fisher et al. (2001) expressed a Munc18 mutant with reduced affinity for syntaxin, which specifically modified the kinetics of single-granule exocytotic release events, consistent with an acceleration of fusion pore expansion. This observation demonstrated that Munc18 functi ...
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May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602926 was added.