Urotensin-II (U-II) is synthesised from a larger precursor molecule, known as Prepro-urotensin-II, two isoforms have been identified in man of lengths 124 and 139 residues. Cleavage of either of these precursors produces identical, eleven residue, mature U-II peptides. The cyclic, C-terminal hexapeptide sequence((-CYS*-TRY-LYS-TRP-PHE-CYS*-), (*bridged CYS residues)), has been conserved through evolution from lamprey to human, species which diverged some 560 million years ago. The fact that such a strong evolutionary pressure has acted to conserve this sequence, highlights its physiological importance, indeed this hexapeptide sequence confers biological activity.

Urotensin-II (U-II) is a peptide ligand, initially isolated from the neurosecretory system of the Goby fish (Gillichthys mirabilis) Bern et al. 1969. For many years it was thought that U-II does not exhibit significant effects in mammalian systems; a view quickly overturned when it was demonstrated that Goby U-II produces slow relaxation of mouse annococygeus muscle, in addition to contraction of rat artery segments. In 1998, the cDNA encoding a U-II precursor was cloned in man, unequivocally demonstrating its existence in mammalian species.