Syntaxin-binding protein 1 (STXBP1)
The protein contains 594 amino acids for an estimated molecular weight of 67569 Da.
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)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
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.
This protein is annotated as membranous in Gene Ontology.
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Biological Process
Axon target recognition
Cellular response to interferon-gamma
Chemical synaptic transmission
Developmental process involved in reproduction
Energy reserve metabolic process
Glutamate secretion
Intracellular protein transport
Long-term synaptic depression
Negative regulation of neuron apoptotic process
Negative regulation of protein-containing complex assembly
Negative regulation of synaptic transmission, GABAergic
Neuromuscular synaptic transmission
Neurotransmitter secretion
Neurotransmitter transport
Platelet aggregation
Platelet degranulation
Positive regulation of calcium ion-dependent exocytosis
Positive regulation of glutamate secretion, neurotransmission
Positive regulation of mast cell degranulation
Positive regulation of vesicle docking
Presynaptic dense core vesicle exocytosis
Protein localization to plasma membrane
Protein stabilization
Protein transport
Regulation of acrosomal vesicle exocytosis
Regulation of insulin secretion
Regulation of SNARE complex assembly
Regulation of synaptic vesicle fusion to presynaptic active zone membrane
Regulation of synaptic vesicle priming
Response to estradiol
Small molecule metabolic process
SNARE complex assembly
Synaptic vesicle maturation
Synaptic vesicle priming
Vesicle docking involved in exocytosis
Vesicle-mediated transport
Cellular Component
Axon
Cytoplasm
Cytoskeleton
Cytosol
Extracellular exosome
Glutamatergic synapse
Mitochondrion
Myelin sheath
Nucleoplasm
Perinuclear region of cytoplasm
Phagocytic vesicle
Plasma membrane
Platelet alpha granule
Postsynapse
Presynaptic active zone membrane
Protein complex
Protein-containing complex
Secretory granule
Terminal bouton
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 ... More on the omim web site
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.