• Purity

  >95%, by SDS-PAGE under reducing conditions and visualized by silver stain

• Endotoxin Level

  <0.01 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by its ability to antagonize alpha -MSH-induced cAMP accumulation in HEK293 human embryonic kidney cells transfected with human Melanocortin-4 Receptor. Ollmann, M.M.     et al. (1997) Science     278:135. The ED    ₅₀ for this effect is typically 0.025-0.15 μg/mL in the presence of 10 ng/mL of alpha -MSH.

• Source

  E. coli-derived Ser82-Thr131

• Accession #

• N-terminal Sequence    
  Analysis

  Ser82

• Predicted Molecular Mass

  5.7 kDa

Background: AgRP/ART

Agouti-Related Protein (AgRP), the protein product of the Agouti-Related Transcript (ART), is a neuroprotein that regulates energy metabolism and the development of obesity by antagonizing alpha -melanocyte stimulating hormone ( alpha -MSH) action on MC-3 and MC-4 receptors (1-4). AgRP is predominantly expressed in the hypothalamus and adrenal medulla (5). Mature mouse AgRP is a 111 amino acid (aa) polypeptide; its C-terminal portion contains ten conserved cysteines that form five disulfide bonds (5, 6). Within the C-terminal region, mouse AgRP shares 80% and 90% aa sequence identity with human and rat AgRP, respectively. It also shares 44% aa sequence identity with Agouti. As with Agouti, the C-terminal cysteine-rich region is sufficient for biological activity (7). AgRP, however, is 100 times more potent than Agouti in antagonizing MC-3 and MC-4 receptors (8). AgRP also induces the beta -arrestin dependent endocytosis of MC-3 and MC-4 (9). Hypothalamic expression of AgRP is up-regulated 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 via a mechanism that does not involve melanocortin receptors (14).

• References:

1. Martin, N.M. et al. (2006) Peptides 27:333.

2. Fan, W. et al. (1997) Nature 385:165.

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 Dev. 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.

• Long Name:

  Agouti-related Protein

• Entrez Gene IDs:

  181 (Human); 11604 (Mouse)

• Alternate Names:

  agouti related protein homolog (mouse); agouti-related protein; AgRP; Agrt; AGRTMGC118963; ART; ARTagouti (mouse) related protein; ASIP2