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Cyclo-oxygenase (Cox), a rate-limiting enzyme in the synthesis of prostanoids, is encoded by two genes, Cox-1 and Cox-2, which are differentially expressed and regulated. Human Cox-1 and -2 polypeptides share 61% primary sequence identity. While the expression of Cox-1 is maximal in quiescent cells. Cox-2 expression is induced by growth factors and cytokines. We have screened a human genomic library with a probe from the 5′-untranslated region (UTR) of the human Cox-2 (hCox-2) cDNA and isolated two overlapping genomic clones. We have determined the DNA sequence of 0.8 kb upstream of the transcription start site, 6 kb of protein coding region, which includes 10 exons and 9 introns, as well as 2.5 kb of the 3′-UTR. The structures of the hCox-1 and hCox-2 and the murine TIS10 (Cox-2) genes are highly conserved, with a few exceptions. The 3′-UTRs of the Cox-1 and -2 genes are distinct; for …