HGNC Approved Gene Symbol: UTS2
Cytogenetic location: 1p36.23 Genomic coordinates (GRCh38) : 1:7,847,612-7,913,249 (from NCBI)
Urotensin II is a cyclic peptide with several cardiovascular actions, including potent vasoactive and cardiac inotropic and hypertropic properties (summary by Douglas et al., 2002).
Coulouarn et al. (1998) clearly established the existence of urotensin II in mammals by characterizing cDNAs encoding the urotensin II precursors not only in frog but also in human. In both species, the UTS2 sequence is located at the C-terminal position of the precursor. Human UTS2 is composed of only 11 amino acid residues, while fish and frog UTS2 possess 12 and 13 amino acid residues, respectively. The cyclic region of UTS2, which is responsible for the biologic activity of the peptide, has been fully conserved from fish to human. Northern blot and dot blot analysis showed that UTS2 precursor mRNAs are found predominantly in the frog and human spinal cord. In situ hybridization studies showed that the UTS2 precursor gene is actively expressed in motoneurons. The fact that evolutionary pressure has acted to conserve fully the biologically active sequence of UTS2 suggests that the peptide may exert important physiologic functions in humans.
Gross (2014) mapped the UTS2 gene to chromosome 1p36.23 based on an alignment of the UTS2 sequence (GenBank AF104118) with the genomic sequence (GRCh37).
Ames et al. (1999) identified a human G protein-coupled receptor, GPR14 (600896), which functions as a urotensin II receptor. Human urotensin II binds to recombinant human GPR14 with high affinity, and the binding is functionally coupled to calcium mobilization. Human urotensin II is found within both vascular and cardiac tissue, including coronary atheroma, and effectively constricts isolated arteries from nonhuman primates. The potency of vasoconstriction of urotensin II was an order of magnitude greater than that of endothelin-1 (131240), making human urotensin II the most potent mammalian vasoconstrictor identified to that time. In vivo, human urotensin II markedly increased total peripheral resistance in anesthetized nonhuman primates, a response associated with profound cardiac contractile dysfunction. Furthermore, urotensin II immunoreactivity was found within the central nervous system and endocrine tissues, suggesting that it may have additional activities.
Douglas et al. (2002) investigated the degree of expression of UTS2 and its receptor GPR14 in the myocardium of patients with congestive heart failure. They obtained specimens of myocardium from the hearts of 19 patients with end-stage congestive heart failure, 5 patients with early-stage congestive heart failure, and 8 healthy controls. They found strong expression of UTS2 in the cardiomyocytes, and to a lesser extent in the vascular smooth muscle cells, endothelial cells, and inflammatory cells of patients with end-stage congestive heart failure. There was significantly less UTS2 expression in the myocardium of patients with early-stage congestive heart failure, and little or no UTS2 expression in the myocardium of healthy controls. RT-PCR showed increased concentrations of UTS2 and the presence of urotensin receptor mRNA in the myocardium of patients with congestive heart failure. Confocal microscopy showed a significant increase in the binding sites for urotensin in the myocardium of patients with end-stage congestive heart failure.
The caudal neurosecretory system of teleost fish, which terminates in the urophysis, exhibits morphofunctional similarities to the hypothalamoneurohypophyseal complex (Bern et al., 1985). Two major regulatory peptides have been isolated from urophysial extracts and chemically characterized. Urotensin I, a 41-amino acid peptide, is structurally similar to mammalian corticotropin-releasing factor (CRF; 122560) and to the frog skin peptide sauvagine; urotensin II (UTS2) is a cyclic 12-amino acid peptide that has some sequence similarity, but is not homologous, to somatostatin-14 (see 182450). The characterization of UTS2 from the urophysis of various teleost species has shown that the structure of the C-terminal cyclic hexapeptide has been fully conserved, while several substitutions have occurred in the N-terminal region of the molecule. Subsequently it was found that urotensin II-like molecules are present in distant taxa, from mollusks to amphibians, suggesting that urotensin-related peptides may also occur in mammals. In support of this hypothesis, a peptide with a high degree of sequence similarity with UTS1, called urocortin (UCN; 600945), was characterized in the rat and human brain. In addition, specific binding sites for urotensin II were demonstrated in rat blood vessels, and fish urotensin II was found to exert cardiovascular effects in rat and rabbit. It was also found that the mouse anococcygeus muscle has special sensitivity to urotensin II (summary by Coulouarn et al., 1998).
Ames, R. S., Sarau, H. M., Chambers, J. K., Willette, R. N., Aiyar, N. V., Romanic, A. M., Louden, C. S., Foley, J. J., Sauermelch, C. F., Coatney, R. W., Ao, Z., Disa, J., and 15 others. Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature 401: 282-286, 1999. Note: Erratum: Nature 402: 898 only, 1999. [PubMed: 10499587] [Full Text: https://doi.org/10.1038/45809]
Bern, H. A., Pearson, D., Larson, B. A., Nishioka, R. S. Complete amino acid sequence of urotensin I, a hypotensive and corticotropin-releasing neuropeptide from Catostomus. Recent Prog. Horm. Res. 41: 533-552, 1985. [PubMed: 2864726] [Full Text: https://doi.org/10.1016/b978-0-12-571141-8.50016-0]
Coulouarn, Y., Lihrmann, I., Jegou, S., Anouar, Y., Tostivint, H., Beauvillain, J. C., Conlon, J. M., Bern, H. A., Vaudry, H. Cloning of the cDNA encoding the urotensin II precursor in frog and human reveals intense expression of the urotensin II gene in motoneurons of the spinal cord. Proc. Nat. Acad. Sci. 95: 15803-15808, 1998. [PubMed: 9861051] [Full Text: https://doi.org/10.1073/pnas.95.26.15803]
Douglas, S. A., Tayara, L., Ohlstein, E. H., Halawa, N., Giaid, A. Congestive heart failure and expression of myocardial urotensin II. Lancet 359: 1990-1997, 2002. [PubMed: 12076554] [Full Text: https://doi.org/10.1016/S0140-6736(02)08831-1]
Gross, M. B. Personal Communication. Baltimore, Md. 6/25/2014.