The ACHE gene spans about 6 kilobases on chromosome 7q22.

The gene gives rise to multiple alternatively spliced transcripts. These include AChE-Synaptic (AChE-S), AChE-Erythrocyte (AChE-E) and AChE-Read through (AChE-R). AChE-S is the major neuronal transcript. Alternative 3 splicing gives rise to AChE-E, a dimeric glycophosphatidylinositol (GPI)-anchored isoform expressed primarily in erythrocytes. The third variant AChE-R is produced by the inclusion of the normally spliced out intron 4 and is reported to be elevated during stress. In addition, the existence of multiple promoters leads to the production of several variants with extended N-terminal sequences which are transcribed from the alternative promoters although their expression patterns have not yet been well characterized (Soreq and Seidman, 2001; Meshorer and Soreq, 2006).

None.

Acetylcholinesterase (AChE) is a 57 kDa protein. AChE can be monomeric (AChE-R), dimeric (AChE-E) or tetrameric (AChE-S). Tetrameric AChE-S can further interact with collagen Q (ColQ), enabling anchorage to neuromuscular junctions (NMJs), and a proline-rich membrane anchor protein (PRiMA) is responsible for the synaptic docking of AChE-S in the brain. AChE-R is a soluble monomer with a unique naturally unfolded C-terminal peptide. Because AChE-E and AChE-R are incapable of anchorage to the NMJ or to synaptic membranes through ColQ or PRiMA, only the AChE-S form of the enzyme is regarded as truly "synaptic" (Massoulié et al., 1993; Taylor et al., 1993; Silman and Sussman, 2008).

Functional heterogeneity in AChE activity is regulated at the transcriptional, post-transcriptional and post-translational levels, leading to complex expression patterns that reflect tissue and cell-type specificity, differentiation state, physiological condition and response to external stimuli. Recent studies have also looked at regulation of AChE expression by microRNA (Hanin and Soreq, 2011).

Intracellular, extracellular, plasma, cerebrospinal fluid.

Acetylcholinesterase is a type B hydrolase that rapidly and selectively hydrolyzes the neurotransmitter acetylcholine (ACh) at cholinergic synapses, as well as at neuromuscular junctions (Soreq and Seidman, 2001). In addition to its catalytic function of the hydrolysis of acetylcholine, AChE has been shown to be involved in many non-cholinergic functions, such as cell growth, stem cell differentiation (Sperling et al., 2008; Falugi and Aluigi, 2012), neuritogenesis, cell adhesion (Paraoanu and Layer, 2008), synaptogenesis, activation of dopaminergic neurons, tumorigenesis, amyloid fibril assembly (Inestrosa et al., 1996; Alvarez et al., 1997), haematopoiesis and thrombopoiesis (Greenfield, 1996; Layer, 1996; Small et al., 1996). The role of acetylcholinesterase in modulating the regulation of cholinergic function is still being investigated (Shaked et al., 2009; Schliebs and Arendt, 2011). The role of AChE inhibitors in many neurodegenerative and neurodevelopmental pathologies is also being studied (Hargreaves, 2012; Li et al., 2012).

AChE is widely conserved in the animal kingdom and is found in mammals, Drosophila, C. elegans and Torpedo californica, among others.

No natural disease-causing mutations have been reported but a number of single nucleotide polymorphisms (SNPs) are known which may affect transcriptional activity and immune properties.