STXBP1

STXBP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3PUJ
Identifiers
Aliases	STXBP1, MUNC18-1, NSEC1, P67, RBSEC1, UNC18, syntaxin binding protein 1
External IDs	OMIM: 602926 MGI: 107363 HomoloGene: 2382 GeneCards: STXBP1
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q34.11 Start 127,579,370 bp[1] End 127,696,027 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 B|2 22.09 cM Start 32,677,614 bp[2] End 32,737,257 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in middle temporal gyrus Brodmann area 23 pons superior frontal gyrus postcentral gyrus frontal pole Brodmann area 10 orbitofrontal cortex Brodmann area 46 entorhinal cortex Top expressed in pontine nuclei inferior colliculus superior colliculus piriform cortex medulla oblongata cerebellar cortex medial vestibular nucleus dorsomedial hypothalamic nucleus primary motor cortex entorhinal cortex More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein domain specific binding protein N-terminus binding syntaxin-1 binding protein binding identical protein binding syntaxin binding protein kinase binding SNARE binding RNA binding phospholipase binding Cellular component platelet alpha granule membrane myelin sheath plasma membrane nucleoplasm terminal bouton mitochondrion extracellular exosome cytoplasm cytosol presynaptic active zone membrane nucleus cytoskeleton axon perinuclear region of cytoplasm presynapse postsynapse protein-containing complex phagocytic vesicle glutamatergic synapse Biological process negative regulation of neuron apoptotic process exocytosis axon target recognition protein stabilization platelet degranulation positive regulation of calcium ion-dependent exocytosis glutamate secretion regulation of synaptic vesicle fusion to presynaptic active zone membrane neuromuscular synaptic transmission negative regulation of synaptic transmission, GABAergic long-term depression protein transport positive regulation of exocytosis protein localization to plasma membrane platelet aggregation regulation of SNARE complex assembly synaptic vesicle maturation vesicle-mediated transport neurotransmitter secretion regulation of synaptic vesicle priming vesicle docking involved in exocytosis negative regulation of protein-containing complex assembly presynaptic dense core vesicle exocytosis developmental process involved in reproduction regulation of vesicle fusion response to estradiol positive regulation of mast cell degranulation positive regulation of vesicle docking positive regulation of glutamate secretion, neurotransmission transport synaptic vesicle priming cellular response to interferon-gamma SNARE complex assembly regulation of acrosomal vesicle exocytosis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6812 20910 Ensembl ENSG00000136854 ENSMUSG00000026797 UniProt P61764 O08599 RefSeq (mRNA) NM_003165 NM_001032221 NM_001113569 NM_009295 RefSeq (protein) NP_001027392 NP_003156 NP_001361235 NP_001361236 NP_001361237 NP_001361238 NP_001361239 NP_001361240 NP_001361241 NP_001361242 NP_001361243 NP_001361244 NP_001107041 NP_033321 Location (UCSC) Chr 9: 127.58 – 127.7 Mb Chr 2: 32.68 – 32.74 Mb PubMed search [3] [4]
Wikidata
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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]

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.^[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]

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.^[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]

Clinical significance

Epilepsy

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]

Intellectual disability and movement disorders

STXBP1 variants are increasingly being identified in people with wider neurological problems, including intellectual disability or movement disorders without epilepsy.^[8][9]

Expression

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]

Interactions

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]}

References

External links

• Overview of all the structural information available in the PDB for UniProt: P61765 (Rat Syntaxin-binding protein 1) at the PDBe-KB.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.