Figure 2: NOS3 transcript isoforms. Depicted at the top is the NOS3 protein (NOS3 protein) with its functional domains (OXY: oxygenase domain; CaM: calmodulin-binding site; FMN: FMN recognition site; AE: autoinhibitory element; FAD: FAD recognition site; NADPH: NADPH recognition site). The corresponding full-length transcript (NOS3 fl mRNA) annotated in Ensembl (v.93) with numbered exons is shown in the green dotted box. The coding region (wide boxes) extends from exon 2 into exon 27. Nonfunctional transcripts, i.e., transcripts not coding for functional NOS3, are shown in the red box below. Skipping of exon 20 (NOS3 Δ20), 21 (NOS3 Δ21), or both (NOS3 Δ20/21) leads to nonfunctional proteins due to frame shifts (dotted boxes) [31]. The variants NOS3 14A/B/C (previously described as NOS3 13A/B/C [32]) originate from splicing events from exon 14 into exons located in the intron of the full-length NOS3 transcript (black boxes). These transcripts terminate in a common polyadenylation signal and encode C-terminally truncated proteins only containing the OXY and CaM domains. The transcript starting at exon 18 (NOS3 E18-23A) lacks the 5-portion and shows a similar splicing phenomenon as NOS3 14A/B/C at its 3-end. Thus, it codes for an N- and C-terminally truncated protein.