Urotensin receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The urotensin-II (U-II) receptor (UT, nomenclature as agreed by the NC-IUPHAR Subcommittee on the Urotensin receptor [26, 36, 89]) is activated by the endogenous dodecapeptide urotensin-II, originally isolated from the urophysis, the endocrine organ of the caudal neurosecretory system of teleost fish [7, 88]. Several structural forms of U-II exist in fish and amphibians. The goby orthologue was used to identify U-II as the cognate ligand for the predicted receptor encoded by the rat gene gpr14 [20, 62, 68, 70]. Human urotensin-II, an 11-amino-acid peptide [20], retains the cyclohexapeptide sequence of goby U-II that is thought to be important in ligand binding [53, 11]. This sequence is also conserved in the deduced amino-acid sequence of rat urotensin-II (14 amino-acids) and mouse urotensin-II (14 amino-acids), although the N-terminal is more divergent from the human sequence [19]. A second endogenous ligand for the UT has been discovered in rat [83]. This is the urotensin II-related peptide, an octapeptide that is derived from a different gene, but shares the C-terminal sequence (CFWKYCV) common to U-II from other species. Identical sequences to rat urotensin II-related peptide are predicted for the mature mouse and human peptides [32]. UT exhibits relatively high sequence identity with somatostatin, opioid and galanin receptors [89].