Agouti-Related Protein (AgRP), the protein product of the Agouti-Related Transcript (ART), is a neuropeptide that regulates energy metabolism and the development of obesity by antagonizing α-melanocyte stimulating hormone (α-MSH) on MC-3 and MC-4 receptors (1 - 4). AgRP is predominantly expressed in the hypothalamus and adrenal medulla (5). Mature human AgRP is a 112 aa peptide; its C-terminal portion contains ten conserved cysteines that form five disulfide bonds (5, 6). Human AgRP shares 82% and 72% aa sequence identity with mouse and rat AgRP, respectively. It shares 32% aa sequence identity with Agouti. As in the case of Agouti, the C-terminal cysteine-rich region is sufficient for biological activity (7). AgRP is 100 times more potent than Agouti in antagonizing MC-3 and MC-4 receptors (8). AgRP also induces induces the β-arrestin dependent endocytosis of MC-3 and MC-4 (9). Hypothalamic expression of AgRP is upregulated in obesity and diabetes (5, 10), and chronic AgRP administration increases food intake and weight gain in rats (11). Genetically-linked polymorphisms of AgRP in humans are associated with susceptibility to anorexia nervosa (12, 13). In addition, AgRP inhibits the ACTH-induced synthesis of steroid hormones in a mechanism that does not involve melanocortin receptors (14).
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3. Ollmann, M.M. et al., 1997, Science 278:135.
4. Arora, S. and Anubhuti, 2006, Neuropeptides 40:375.
5. Shutter, J.R. et al., 1997, Genes Develop. 11:593.
6. Kiefer, L.L. et al., 1998, Biochemistry 37:991.
7. Jackson, P.J. et al., 2002, Biochemistry 41:7565.
8. Fong, T.M. et al., 1997, Biochem. Biophys. Res. Commun. 237:629.
9. Breit, A. et al., 2006, J. Biol. Chem. 281:37447.
10. Katsuki, A. et al., 2001, J. Clin. Endocrinol. Metab. 86:1921.
11. Small, C.K. et al., 2001, Diabetes 50:248.
12. Vink, T. et al., 2001, Mol. Psychiatry 6:325.
13. Dardennes, R.M. et al., 2007, Psychoneuroendocrinology 32:106.
14. Doghman, M. et al., 2007, Mol. Cell. Endocrinol. 265 - 266:108.
Note: This protein is designed for use as an ELISA control.
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