Agouti-related protein

Definition:

Plays a role in weight homeostasis. Involved in the control of feeding behavior through the central melanocortin system. Acts as alpha melanocyte-stimulating hormone antagonist by inhibiting cAMP production mediated by stimulation of melanocortin receptors within the hypothalamus and adrenal gland. Has very low activity with MC5R (By similarity). Is an inverse agonist for MC3R and MC4R being able to suppress their constitutive activity. It promotes MC3R and MC4R endocytosis in an arrestin-dependent manner.

References:

[1]. Y K Yang, et al. Characterization of Agouti-related protein binding to melanocortin receptors. Mol Endocrinol. 1999 Jan;13(1):148-55. [Content Brief]

[2]. W A Nijenhuis, et al. AgRP(83-132) acts as an inverse agonist on the human-melanocortin-4 receptor. Mol Endocrinol. 2001 Jan;15(1):164-71. [Content Brief]

[3]. K A Bolin, et al. NMR structure of a minimized human agouti related protein prepared by total chemical synthesis. FEBS Lett. 1999 May 21;451(2):125-31. [Content Brief]

[4]. Andreas Breit, et al. The natural inverse agonist agouti-related protein induces arrestin-mediated endocytosis of melanocortin-3 and -4 receptors. J Biol Chem. 2006 Dec 8;281(49):37447-56. [Content Brief]

[5]. Corine E de Rijke, et al. Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness. Biochem Pharmacol. 2005 Jul 15;70(2):308-16. [Content Brief]

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