Syntaxin-binding protein 1 (also known as Munc18-1) is a protein that in humans is encoded by the STXBP1 gene. [5] 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 neurological disorders including epilepsy, intellectual disability, and movement disorders. [6] [7] [8] [9]
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. [6] The encoded protein is a peripheral membrane protein located in the cytosol. [10] [11] In the retina and cerebellum, an alternatively spliced transcript variant is expressed, containing an additional exon and totaling 603 amino acids. [5] Alternative splicing can produce an isoform with exon 19 and an isoform without. [12] [13]
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. [10] [11] 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. [14] This protein is essential for presynpatic vesicle release and is rapidly phosphorylated by protein kinase C upon neuronal depolarization. [15] The protein participates in the secretory pathway between the Golgi apparatus and cell membrane. [16] [13]
Mutations in the STXBP1 cause early infantile epileptic encephalopathy type 4 (EIEE4), 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 intellectual disability, and MRI evidence of brain hypomyelination. [6] [7] Inheritance of EIEE4 is autosomal dominant, but due to the severity of the condition most cases are de novo . [10] [11]
This gene was initially discovered in 2008 as cause for this severe form of epilepsy also called Ohtahara syndrome. Since then it has become one of the most prominent genes for epileptic encephalopathies, and is increasingly being associated with other forms of epilepsy. [8] [17]
STXBP1 variants are increasingly being identified in people with wider neurological problems, including intellectual disability or movement disorders without epilepsy. [8] [9]
In melanocytic cells STXBP1 gene expression may be regulated by MITF. [18]
The STXBP1 gene is expressed in the brain and spinal cord and highly enriched in axons. [10] [11] Expression of this protein is highest in the retina and cerebellum. [5] [13]
The encoded protein binds SYTL4. [10] [11] STXBP1 has been shown to interact with STX2, [19] [20] STX4 [19] [20] and STX1A. [20] [21] [22] [23] [24]
SNARE proteins – "SNAPREceptors" – are a large protein family consisting of at least 24 members in yeasts, more than 60 members in mammalian cells, and some numbers in plants. The primary role of SNARE proteins is to mediate the fusion of vesicles with the target membrane; this notably mediates exocytosis, but can also mediate the fusion of vesicles with membrane-bound compartments. The best studied SNAREs are those that mediate the release of synaptic vesicles containing neurotransmitters in neurons. These neuronal SNAREs are the targets of the neurotoxins responsible for botulism and tetanus produced by certain bacteria.
Synaptosomal-Associated Protein, 25kDa (SNAP-25) is a Target Soluble NSF (N-ethylmaleimide-sensitive factor) Attachment Protein Receptor (t-SNARE) protein encoded by the SNAP25 gene found on chromosome 20p12.2 in humans. SNAP-25 is a component of the trans-SNARE complex, which accounts for membrane fusion specificity and directly executes fusion by forming a tight complex that brings the synaptic vesicle and plasma membranes together.
Syntaxin-1A is a protein that in humans is encoded by the STX1A gene.
Synaptosomal-associated protein 23 is a protein that in humans is encoded by the SNAP23 gene. Two alternative transcript variants encoding different protein isoforms have been described for this gene.
Peripheral plasma membrane protein CASK is a protein that in humans is encoded by the CASK gene. This gene is also known by several other names: CMG 2, calcium/calmodulin-dependent serine protein kinase 3 and membrane-associated guanylate kinase 2. CASK gene mutations are the cause of XL-ID with or without nystagmus and MICPCH, an X-linked neurological disorder.
Syntaxin-4 is a protein that in humans is encoded by the STX4 gene.
Synaptotagmin-1 is a protein that in humans is encoded by the SYT1 gene.
Vesicle-associated membrane protein 2 (VAMP2) is a protein that in humans is encoded by the VAMP2 gene.
Syntaxin-6 is a protein that in humans is encoded by the STX6 gene.
Syntaxin-5 is a protein that in humans is encoded by the STX5 gene.
Syntaxin-2, also known as epimorphin, is a protein that in humans is encoded by the STX2 gene.
Regulating synaptic membrane exocytosis protein 1 is a protein that in humans is encoded by the RIMS1 gene.
Syntaxin-binding protein 2 is a protein that in humans is encoded by the STXBP2 gene.
Syntaxin-binding protein 3 is a protein that in humans is encoded by the STXBP3 gene.
Rab11 family-interacting protein 5 is a protein that in humans is encoded by the RAB11FIP5 gene.
Complexin-1 is a protein that in humans is encoded by the CPLX1 gene.
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.
Syntaxin 3, also known as STX3, is a protein which in humans is encoded by the STX3 gene.
Syntaxins are a family of membrane integrated Q-SNARE proteins participating in exocytosis.
Munc-18 proteins are the mammalian homologue of UNC-18 and are a member of the Sec1/Munc18-like (SM) protein family. Munc-18 proteins have been identified as essential components of the synaptic vesicle fusion protein complex and are crucial for the regulated exocytosis of neurons and neuroendocrine cells.
This article incorporates text from this source, which is in the public domain .
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.
