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Protein unc13 homolog A is a protein that in humans is encoded by the UNC13A gene.[1] An Error has occurred retrieving Wikidata item for infobox
Function
[edit]UNC13A plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. It is particularly important in most glutamatergic-mediated synapses but not GABA-mediated synapses.[2] 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. It plays a role in dendrite formation by melanocytes and in secretory granule priming in insulin secretion.[3]
Subcellular location
[edit]UNC13A is localized to the active zone of presynaptic density. It is translocated to the plasma membrane in response to phorbol ester binding.[3]
Protein structure
[edit]Several conserved domains have been found in UNC13A. These conserved domains including three C2 domains.[3][4] One C2 domain is centrally located, another is at the carboxyl end, and there is a third. In addition, there is one C1 domain, one MHD1, and one MHD2.[3][4]
Interaction
[edit]UNC13A has been shown to interact with:
Clinical significance
[edit]Single nucleotide polymorphisms in this gene may be associated with sporadic amyotrophic lateral sclerosis (ALS).[1] This single nucleotide polymorphisms has been discovered on chromosome 19.[5] This variation of the single nucleotide involving UNC13A has also been implicated in frontotemporal dementia (FTD).[5] Pathology involving TDP-43 is a result of the single nucleotide polymorphisms in both ALS and FTD.[5] This gene has also been associated with Alzheimer's Disease (AD).[6]
References
[edit]- ^ a b "UNC13A unc-13 homolog A (C. elegans) [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-04-10.
- ^ "http://www.genecards.org/cgi-bin/carddisp.pl?gene=UNC13A". www.genecards.org. Retrieved 2016-05-05.
{{cite web}}: External link in|title= - ^ a b c d e f g h i j k l "UNC13A - Protein unc-13 homolog A - Homo sapiens (Human) - UNC13A gene & protein". www.uniprot.org.
- ^ a b "Conserved domains on protein unc-13 homolog A". NCBI Conserved Domains. Retrieved 2 May 2016.
- ^ a b c Diekstra, Frank P.; Van Deerlin, Vivianna M.; van Swieten, John C.; Al-Chalabi, Ammar; Ludolph, Albert C.; Weishaupt, Jochen H.; Hardiman, Orla; Landers, John E.; Brown, Robert H. (2014-07-01). "C9orf72 and UNC13A are shared risk loci for amyotrophic lateral sclerosis and frontotemporal dementia: A genome-wide meta-analysis". Annals of Neurology. 76 (1): 120–133. doi:10.1002/ana.24198. ISSN 1531-8249. PMC 4137231. PMID 24931836.
- ^ Hartlage-Rübsamen, Maike; Waniek, Alexander; Roßner, Steffen (2013-02-01). "Munc13 genotype regulates secretory amyloid precursor protein processing via postsynaptic glutamate receptors". International Journal of Developmental Neuroscience. 31 (1): 36–45. doi:10.1016/j.ijdevneu.2012.10.001.
Further reading
[edit]- Augustin I, Rosenmund C, Sudhof TC, Brose N (1999). "Munc 13-1 is essential for fusion competence of glutamatergic synaptic vesicles". Nature. 400 (6743): 457–61. PMID 10440375.
- Betz A, Augustin I, Brose N, Ashery U, Neher E, Rettig J, Südhof T (1998). "Munc13-1 is a presynaptic phorbol ester receptor that enhances neurotransmitter release". Neuron. 21 (1): 123–36. PMID 9697857.
- Betz A, Thakur P, Junge HJ, Ashery U, Rhee J, Scheuss V, Brose N (2001). "Functional Interaction of the Active Zone Proteins Munc13-1 and RIM1 in Synaptic Vesicle Priming". Neuron. 30 (1): 183–96. PMID 11343654.
- Huang C, Yang D, Lin C, Kao L (2011). "Involvement of Rab3A in Vesicle Priming During Exocytosis: Interaction with Munc13-1 and Munc18-1". Traffic. 12 (10): 1356–70. doi:10.1111/j.1600-0854.2011.01237.x.
- Koch H, Brose N, Hofmann (2000). "Definition of Munc13-homology-domains and characterization of a novel ubiquitously expressed Munc13 isoform". Biochemical Journal. 349 (1): 247–53. doi:10.1042/0264-6021.
- Lavi A, Sheinin A, Shapira R, Zelmanoff D, Ashery U (2014). "DOC2B and Munc13-1 Differentially Regulate Neuronal Network Activity". Cerebral Cortex. 24 (9): 2309–23. doi:10.1093/cercor/bht081.
- Ohtsuka T, Takao-Rikitsu E, Inoue E, Inoue M, Takeuchi M, Matsubara K, Deguchi-Tawarada M, Satoh K, Morimoto K, Nakanishi H, Takai YJ (2002). "Cast: a novel protein of the cytomatrix at the active zone of synapses that forms a ternary complex with RIM1 and munc13-1". Journal of Cell Biology. 158 (3): 577–90. doi:10.1083/jcb.200202083.