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. 2023 Sep 19;15(18):4629. doi: 10.3390/cancers15184629

Figure 4.

Figure 4

Structure and expression of the human acetylcholinesterase gene, molecular forms of the AChE protein originated by oligomerizing the various subunits, and quaternary associations of other proteins. (A) From 5′ to 3′, the ACHE gene has three exon 1 variants (E1e, E1c, and E1a, each with a distinct promoter), three common exons (E2, E3, and E4, shown in gray) with all the information necessary to produce catalytically active proteins, a pseudo intron (I4′, shown in yellow), and two exons (5 and 6, shown in black and green, respectively). Introns are shown as bold solid lines, and light lines connecting exons mean constitutive and alternative splicing. PolyA sites (blue and red circles), initiation (ATG), and STOP codons (yellow hexagons) are also highlighted. Via transcription, three different 5′ ends can be produced by activating different E1 promoters (alternative 5′ splicing), and three other 3′ ends can be generated by alternative splicing of I4′, E5, and E6. Therefore, nine types of mature mRNAs can be produced from AChE. For the six AChE mRNAs with exons E1c or E1a that lack an initiation codon, translation begins at E2 and generates the identical isoforms of AChE regardless of the E1 used. Therefore, three isoforms of AChE may differ at the C-terminal end (the classical isoforms AChE-T, AChE-H, and AChE-R). The translation begins in this exon for the three AChE mRNAs with exon E1e, which has an initiation codon. The three isoforms generated will contain an extension N-terminal (the N-extended isoforms N-AChE-T, N-AChE-H, and N-AChE-R). (B) AChE-R consists of monomeric variants. AChE-H or AChE-E (hydrophobic or erythrocytic AChE) produces amphiphilic membrane-anchored monomers and dimers via GPI. AChE-T or AChE-S (synaptic AChE) generates globular components that may or may not have the PRiMA membrane-binding protein or the collagen-type Q tail (ColQ) (asymmetric form). The N-AChE variants are anchored to the membrane through the N-terminal generated by exon 1Ee, N-AChE-T (green), N-AChE-R (yellow), and N-AChE-H (gray). Adapted from [62,63]. Created with Biorender.com (accessed on 12 June 2023).