Alternative titles; symbols
HGNC Approved Gene Symbol: UCN3
Cytogenetic location: 10p15.1 Genomic coordinates (GRCh38) : 10:5,364,966-5,374,692 (from NCBI)
The stresscopin (SCP) and stresscopin-related peptide (SRP; 605902) genes are expressed in diverse peripheral tissues as well as in the central nervous system and encode specific ligands for CRHR2 (602034) (Hsu and Hsueh, 2001).
Adaptive stress responses mediated by the endocrine, autonomic, cardiovascular, and immune systems are essential for the survival of the individual. Initial stress-induced responses provide a vital short-term metabolic lift, but prolonged or inappropriate exposure to stress can compromise homeostasis, thereby leading to disease. This 'fight or flight' response is characterized by the activation of the corticotropin-releasing hormone (CRH)-adrenocorticotropin-glucocorticoid axis, mediated by the type 1 CRH receptor (122561). In contrast, the type 2 CRH receptor (CRHR2) mediates the stress coping responses during the recovery phase of stress. Hsu and Hsueh (2001) identified human stresscopin (SCP) and stresscopin-related peptide (SRP) as specific ligands for CRHR2. The human SCP gene encodes a preproprotein of 161 amino acids and a putative mature protein of 40 amino acids. The open reading frame contains a signal peptide for secretion, and the predicted mature region is flanked by potential proteolytic cleavage sites and an alpha-amidation donor residue. The mature human SCP peptide sequence shares 72% identity with that of Takifugu rubripes and 57% identity with that of Tetraodon nigroviridis, a freshwater pufferfish. In human and fish, a stretch of 30 residues at the respective carboxy termini has an extended alpha-helical structure shared by all CRH family peptides. The genes encoding SCP and SRP are expressed in diverse peripheral tissues as well as in the central nervous system. Treatment with SCP or SRP suppressed food intake and delayed gastric emptying in mice and decreased heat-induced edema in rats. Thus, Hsu and Hsueh (2001) concluded that SCP and SRP might represent endogenous ligands for maintaining homeostasis after stress, and could allow the design of drugs to ameliorate stress-related diseases.
By EST database searching with a pufferfish sequence related to urocortin and use of a nested PCR strategy, Lewis et al. (2001) independently identified a full-length stresscopin cDNA, which they designated urocortin III (UCN3). They also cloned the mouse ortholog. In the mouse, urocortin III mRNA expression was found in areas of the brain including the hypothalamus, amygdala, and brainstem, but was not evident in the cerebellum, pituitary, or cerebral cortex; it was also expressed peripherally in small intestine and skin.
Hsu, S. Y., Hsueh, A. J. W. Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor. Nature Med. 7: 605-611, 2001. [PubMed: 11329063] [Full Text: https://doi.org/10.1038/87936]
Lewis, K., Li, C., Perrin, M. H., Blount, A., Kunitake, K., Donaldson, C., Vaughan, J., Reyes, T. M., Gulyas, J., Fischer, W., Bilezikjian, L., Rivier, J., Sawchenko, P. E., Vale, W. W. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc. Nat. Acad. Sci. 98: 7570-7575, 2001. [PubMed: 11416224] [Full Text: https://doi.org/10.1073/pnas.121165198]