Fig. 1

Gene organization and transcript variants of human MAPs with tau-like microtubule binding domains. a Chromosomal loci and genetic linkage maps of human MAPT, MAP2 and MAP4, including MAPT-IT1 and STH within the MAPT gene. There is also evidence that segmental chromosome duplications 17 ↔ 2 and 17 ↔ 3 formed the paralogous gene pairs MAPT-KANSL1 and MAP2-KANSL1L (see text). b Official gene names and sizes identify the graphic outlines of their respective exon distributions. MAPT intron 1 contains MAPT-IT1 (intronic transcript 1, long non-coding RNA), intron 11 contains the saitohin gene (STH) encoding a single open reading frame and peptide, while numerous remaining non-coding regulatory RNAs and repetitive elements in other introns are not annotated here. c Alternatively spliced transcripts of 8 human MAPT isoforms are identified by formal and familiar terminology showing size distributions of untranslated and coding (grey-filled) exons. The descriptive summary of protein products corresponds to different alternatively spliced exons produced by skipping of one or more exons 3, 4, 6, 8, 10 and 12 in different cell types and conditions; note that a previous, non-standard nomenclature restricted to the 6 brain isoforms started numbering at 1 for the first “coding” exon 2 while exon 4A was designated for exon 6 leading to an apparent maximum exon number of 13 instead of the true 15 [12]. The 4 MTBDs are marked at the top, the second one in color to denote the possible splicing out of exon 12. Known and predicted phosphorylation sites are identified by the ball and stick symbol above MAPT isoform 1. Note that the underlined 6 protein isoforms (v2, v3, v4, v5, v7, v8) are expressed in the central nervous system. Experimental evidence for the expression of exon 10 in humans is still lacking (NCBI BLASTN human RefSeq transcripts). A schematic representation showing the functional organization of tau is displayed on top. d Human MAP2 and MAP4 coding (grey-filled), non-coding and alternatively spliced exons (red numbers) are shown to characterize protein isoforms and localize MAP domains, including the exon splicing affecting the second MTBD