User:SabatinoAL/sandbox

Protein unc13 homolog A is a protein that in humans is encoded by the UNC13A gene.

Function
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. 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.

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.

Protein structure
Several conserved domains have been found in UNC13A. These conserved domains including 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, one MHD1, and one MHD2.

Interaction
UNC13A has been shown to interact with:


 * STX1A
 * STX1B1
 * DOC2A
 * BSN
 * RIMS1
 * RIMS2
 * ERC2, and
 * RAB3A

Clinical significance
Single nucleotide polymorphisms in this gene may be associated with sporadic amyotrophic lateral sclerosis (ALS). This single nucleotide polymorphisms has been discovered on chromosome 19. This variation of the single nucleotide involving UNC13A has also been implicated in frontotemporal dementia (FTD). Pathology involving TDP-43 is a result of the single nucleotide polymorphisms in both ALS and FTD. This gene has also been associated with Alzheimer's Disease (AD).