Proteopedia

1mr0

SOLUTION NMR STRUCTURE OF AGRP(87-120; C105A)SOLUTION NMR STRUCTURE OF AGRP(87-120; C105A)

Structural highlights

1mr0 is a 1 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 1mc6. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

AGRP_HUMAN Genetic variations in AGRP may be a cause of obesity (OBESITY) [MIM:601665. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.[1]

Function

AGRP_HUMAN 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.[2] [3] [4] [5] [6]

Evolutionary Conservation

 

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

  1. ↑ Argyropoulos G, Rankinen T, Neufeld DR, Rice T, Province MA, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C. A polymorphism in the human agouti-related protein is associated with late-onset obesity. J Clin Endocrinol Metab. 2002 Sep;87(9):4198-202. PMID:12213871
  2. ↑ Yang YK, Thompson DA, Dickinson CJ, Wilken J, Barsh GS, Kent SB, Gantz I. Characterization of Agouti-related protein binding to melanocortin receptors. Mol Endocrinol. 1999 Jan;13(1):148-55. PMID:9892020
  3. ↑ Nijenhuis WA, Oosterom J, Adan RA. AgRP(83-132) acts as an inverse agonist on the human-melanocortin-4 receptor. Mol Endocrinol. 2001 Jan;15(1):164-71. PMID:11145747
  4. ↑ Breit A, Wolff K, Kalwa H, Jarry H, Buch T, Gudermann T. 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. Epub 2006 Oct 14. PMID:17041250 doi:10.1074/jbc.M605982200
  5. ↑ Bolin KA, Anderson DJ, Trulson JA, Thompson DA, Wilken J, Kent SB, Gantz I, Millhauser GL. NMR structure of a minimized human agouti related protein prepared by total chemical synthesis. FEBS Lett. 1999 May 21;451(2):125-31. PMID:10371151
  6. ↑ de Rijke CE, Jackson PJ, Garner KM, van Rozen RJ, Douglas NR, Kas MJ, Millhauser GL, Adan RA. 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. PMID:15927146 doi:10.1016/j.bcp.2005.04.033
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