Alternative titles; symbols
HGNC Approved Gene Symbol: UCN2
Cytogenetic location: 3p21.31 Genomic coordinates (GRCh38) : 3:48,561,718-48,563,781 (from NCBI)
The stresscopin (SCP; 605901) and stresscopin-related peptide (SRP) genes encode specific ligands for the type-2 corticotropin-releasing hormone receptor (CRHR2; 602034), which mediates stress coping responses during the recovery phase of stress (Hsu and Hsueh, 2001).
Hsu and Hsueh (2001) identified human SCP and SRP as CRH/urocortin (600945) family members. The 112-amino acid human SRP open reading frame contains a signal peptide for secretion, and the region containing the 43-amino acid mature peptide is flanked by potential proteolytic cleavage sites and an alpha-amidation donor residue. A stretch of 30 residues at the respective C termini of human and pufferfish SRP has an extended alpha-helical structure shared by all CRH family peptides. SRP is expressed in diverse peripheral tissues as well as in the central nervous system.
Reyes et al. (2001) cloned mouse urocortin II, a homolog of human SRP, and a partial cDNA encoding human SRP, which they termed urocortin-related peptide (URP). The mouse and human proteins share 76% amino acid identity. Hybridization histochemistry showed expression in cell groups involved in stress-related physiologic and behavioral functions.
Hsu and Hsueh (2001) found that treatment with SCP or SRP suppressed food intake and delayed gastric emptying in mice and decreased heat-induced edema in rats. They 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.
Hao et al. (2008) stated that genetic deletion of the Ucn2 receptor Crfr2 (CRHR2) in mice results in profound postnatal hypervascularization characterized by both increased total vessel number and increased vessel diameter. They found that viral-mediated expression of Ucn2 inhibited growth and vascularization of mouse Lewis lung carcinoma cell (LLCC) tumors in vivo, independent of whether exposure to Ucn2 occurred before or after establishment of measurable tumors. In vitro, Ucn2 directly inhibited proliferation of LLCCs, suggesting that the tumor-suppressing effects of Crfr2 activation involve both direct inhibition of tumor cell cycling and suppression of tumor vascularization.
By analysis of a BAC clone, Reyes et al. (2001) mapped the SRP gene to chromosome 3p21.3.
Using glucose-tolerance and insulin-tolerance tests and hyperinsulinemic euglycemic glucose clamp studies, Chen et al. (2006) demonstrated that mice lacking Ucn2 exhibited increased insulin sensitivity and were protected against fat-induced insulin resistance. Administration of synthetic Ucn2 to mutant mice restored blood glucose to wildtype levels. Administration of a Crfr2-selective antagonist to wildtype mice resulted in a glucose-tolerance test profile that mirrored that of Ucn2-null mice. Ucn2-null mice fed a high fat diet had less fat and more lean tissue compared with wildtype mice. In primary mouse skeletal muscle cells and a mouse myoblast cell line, Ucn2 inhibited insulin-induced Akt (164730) and Erk1 (MAPK3; 601795)/Erk2 (MAPK1; 176948) phosphorylation. Chen et al. (2006) concluded that UCN2 negatively regulates glucose uptake in skeletal muscle by inhibiting insulin signaling.
Chen, A., Brar, B., Choi, C. S., Rousso, D., Vaughan, J., Kuperman, Y., Kim, S. N., Donaldson, C., Smith, S. M., Jamieson, P., Li, C., Nagy, T. R., Shulman, G. I., Lee, K.-F., Vale, W. Urocortin 2 modulates glucose utilization and insulin sensitivity in skeletal muscle. Proc. Nat. Acad. Sci. 103: 16580-16585, 2006. [PubMed: 17050686] [Full Text: https://doi.org/10.1073/pnas.0607337103]
Hao, Z., Huang, Y., Cleman, J., Jovin, I. S., Vale, W. W., Bale, T. L., Giordano, F. J. Urocortin2 inhibits tumor growth via effects on vascularization and cell proliferation. Proc. Nat. Acad. Sci. 105: 3939-3944, 2008. [PubMed: 18308934] [Full Text: https://doi.org/10.1073/pnas.0712366105]
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]
Reyes, T. M., Lewis, K., Perrin, M. H., Kunitake, K. S., Vaughan, J., Arias, C. A., Hogenesch, J. B., Gulyas, J., Rivier, J., Vale, W. W., Sawchenko, P. E. Urocortin II: a member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors. Proc. Nat. Acad. Sci. 98: 2843-2848, 2001. [PubMed: 11226328] [Full Text: https://doi.org/10.1073/pnas.051626398]