1. COX-1 and known variants.
COX-1 and known variants. A, structure of the COX-1 gene (length of introns not drawn to scale). Retention of intron-1 or parts thereof (denoted by one asterisk) gives rise to canine COX-3 and is found in some canine PCOXs. Retention of part of intron-2 is found in some human COX-1 transcripts (unpublished data). This intron is analogous to intron-1 in COX-2 transcripts that can be retained in a signal transduction-responsive fashion in chicken embryo fibroblasts (Xie et al., 1991). Skipping of exons 3–8 (denoted by 2 asterisks) can produce a PCOX protein. Use of a cryptic splice site in exon 9 (denoted by three asterisks) produces an inactive COX variant in humans (Diaz et al., 1992). Cryptic splicing has been detected in exon 10 (denoted by four asterisks; unpublished data) in humans resulting in a truncated open reading frame. Alternative polyadenylation (denoted by five asterisks) produces COX-1 transcript ranging from 2 to 6 through >7 kb in size. In humans and rodents, retention of intron-1 is frequently coupled to alternative polyadenylation. Alternative polyadenylation is also observed in COX-2 transcripts. B, diagram of the functional domains of COX-1 and COX-2 and the effects of alternative splicing in the insertion of intron-1 in canine COX-3 and PCOX-1b and deletion of 5 to 8 in canine PCOX-1a.
Daniel L. Simmons et al. Pharmacol Rev 2004;56:
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