UNC13A

UNC13A
Identifiers
Aliases	UNC13A, Munc13-1, unc-13 homolog A (C. elegans), unc-13 homolog A
External IDs	OMIM: 609894; MGI: 3051532; HomoloGene: 11279; GeneCards: UNC13A; OMA:UNC13A - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.11 Start 17,601,336 bp[1] End 17,688,365 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 B3.3 Start 72,077,061 bp[2] End 72,124,401 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right hemisphere of cerebellum beta cell olfactory bulb right frontal lobe prefrontal cortex superior frontal gyrus middle temporal gyrus dorsolateral prefrontal cortex Brodmann area 9 pituitary gland Top expressed in superior frontal gyrus dentate gyrus of hippocampal formation granule cell primary visual cortex primary motor cortex neural layer of retina cerebellar cortex piriform cortex prefrontal cortex hippocampus proper subiculum More reference expression data BioGPS n/a
Gene ontology Molecular function syntaxin-1 binding metal ion binding diacylglycerol binding calmodulin binding calcium ion binding phospholipid binding Cellular component cytoplasm membrane neuromuscular junction plasma membrane synapse axon cell junction neuron projection presynaptic membrane presynapse terminal bouton calyx of Held presynaptic active zone glutamatergic synapse synaptic vesicle membrane presynaptic active zone cytoplasmic component Biological process cell differentiation intracellular signal transduction synaptic vesicle docking synaptic transmission, glutamatergic regulation of short-term neuronal synaptic plasticity positive regulation of neurotransmitter secretion amyloid-beta metabolic process neuromuscular junction development positive regulation of dendrite extension regulation of synaptic transmission, glutamatergic innervation synaptic vesicle maturation neurotransmitter secretion exocytosis chemical synaptic transmission synaptic vesicle exocytosis synaptic vesicle priming positive regulation of synaptic plasticity positive regulation of glutamate receptor signaling pathway regulation of amyloid precursor protein catabolic process presynaptic dense core vesicle exocytosis dense core granule priming Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 23025 382018 Ensembl ENSG00000130477 ENSMUSG00000034799 UniProt Q9UPW8 Q4KUS2 RefSeq (mRNA) NM_001080421 NM_001387021 NM_001387022 NM_001387023 NM_001029873 RefSeq (protein) NP_001073890 NP_001025044 Location (UCSC) Chr 19: 17.6 – 17.69 Mb Chr 8: 72.08 – 72.12 Mb PubMed search [3] [4]
Wikidata
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Unc-13 homolog A (C. elegans) is a protein that in humans is encoded by the UNC13A gene.^[5]

Function

This gene encodes a member of the UNC13 family.^[5] UNC13A plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. It is involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool. In Drosophila melanogaster, the protein has been shown to define the vesicle release site by regulating the coupling distance between synaptic vesicles and calcium channels in cooperation with another isoform, UNC13B.^[6] It is particularly important in most glutamatergic-mediated synapses as well as GABA-mediated synapses. It plays a role in dendrite formation by melanocytes and in secretory granule priming in insulin secretion.^[7]

Protein structure

Several conserved domains have been found in UNC13A. These conserved domains include three C2 domains. One C2 domain is centrally located, another is at the carboxyl end, and there is a third. In addition, there is one C1 domain, as well as Munc13 homology domains 1 (MHD1) and 2 (MHD2).^[7][8]

Subcellular location

UNC13A is localized to the active zone of presynaptic density. It is translocated to the plasma membrane in response to phorbol ester binding.^[7]

Interaction

UNC13A has been shown to interact with:

• STX1A,^[7]
• STX1B1,^[7]
• DOC2A,^[7]
• BSN,^[7]
• RIMS1,^[7]
• RIMS2,^[7]
• ERC2,^[7] and
• RAB3A.^[7]

Clinical significance

Single nucleotide polymorphisms in this gene may be associated with sporadic amyotrophic lateral sclerosis.^{[9][10][11][12]} This single nucleotide polymorphism has been discovered on chromosome 19. This variation of the single nucleotide involving UNC13A has also been implicated in frontotemporal dementia (FTD). Pathology of TDP-43 in both ALS and FTD results in a cryptic exon being expressed in UNC13A, which is exercerbated by the single nucleotide polymorphisms associated with ALS and FTD risk.^[13][14][15] This gene has also been associated with Alzheimer's disease (AD).^[16]

References

Further reading

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