STXBP1


Syntaxin-binding protein 1 is a protein that in humans is encoded by the STXBP1 gene. 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.

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. The encoded protein is a peripheral membrane protein located in the cytosol. In the retina and cerebellum, an alternatively spliced transcript variant is expressed, containing an additional exon and totaling 603 amino acids. Alternative splicing can produce an isoform with exon 19 and an isoform without.

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. 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. This protein is essential for presynpatic vesicle release and is rapidly phosphorylated by protein kinase C upon neuronal depolarization. The protein participates in the secretory pathway between the Golgi apparatus and cell membrane.

Clinical Significance

Epileptic Encephalopathy

Mutations in the STXBP1 cause Early Infantile Epileptic Encephalopathy Type 4, 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.
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.

Expression

In melanocytic cells STXBP1 gene expression may be regulated by MITF.
The STXBP1 gene is expressed in the brain and spinal cord and highly enriched in axons. Expression of this protein is highest in the retina and cerebellum.

Interactions

The encoded protein binds SYTL4. STXBP1 has been shown to interact with STX2, STX4 and STX1A.