AgRP, Recombinant, Human (Agouti Related Protein, ART, AGRT, ASIP2, Agouti-related transcript)

Agouti-related protein is an endogenous antagonist of hypothalamic alpha-melanocortin receptors MC3R and MC4R with potent orexigenic activity. Although a complete deletion of the AGRP gene does not produce any significant metabolic phenotypes, reduction in AGRP expression by RNA interference is associated with increased metabolic rate along with reduced weight gain. In hypothalamus, it is produced by neurons in the medial portion of arcuate nucleus, which produce also the potent orexigenic peptide Neuropeptide Y (NP-Y). Another site of central AGRP production is the hypothalamic nucleus. AGRP encompasses 132 amino acid residues and its alpha-melanocortin inhibiting activity results in a 34 amino acid cystine knot domain within the C-terminal (87-132) portion of the protein. Both AGRP and NP-Y expression was shown to be supressed by leptin. Central administration of AGRP induces hyperphagia and increased gain in body weight in rodents, but may also exert metabolic effects even when hyperphagia is prevented. In the absence of hyperphagia, intracerebralventricular administration of AGRP caused significant increases in plasma leptin and insulin concentrations (twofold and 1.5-fold, respectively) and fat pad mass. In the perifery, AGRP mRNA was found in adrenal glands, lung, testis, ovary, skeletal muscle and adipose tissue in humans or rodents. In the adrenals, it was shown that AGRP antagonizes glucosteroid production mediated by MC4R. AGRP could then modulate locally the functions of some peripheral tissues such as adrenals. In human and rat serum, detectable levels of AGRP-like activity were reported in the lower picogram range. The serum AGRP levels were elevated in obese humans compared to lean controls and increased with fasting in rats.\n\nDescription: \nThe Human Agouti-related protein is created as a recombinant protein with N-terminal fusion of HisTag. The Human Agouti-related protein His-Tagged Fusion Protein, produced in E. coli, is 14.4kD protein containing 112 amino acid residues of the human AGRP and 16 additional amino acid residues-HisTag, thrombin cleavage site (underlined). MKHHHHHHHM LVPRGSAQMG LAPMEGIRRP DQALLPELPG LGLRAPLKKT TAEQAEEDLL QEAQALAEVL DLQDREPRSS RRCVRLHESC LGQQVPCCDP CATCYCRFFN AFCYCRKLGT AMNPCSRT\n\nSpecificity: \nThe amino acid sequence of the recombinant human Agouti

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SPECIFICATIONS

Catalog Number

A1059-62H

Size

2ug

Form

Supplied as a lyophilized powder in 5mM Tris, 25mM sodium chloride, pH 7.5.

Purity

(same/more than) 95% (SDS-PAGE analyzed); Three-step procedure using affinity Ni-NTA chromatography and size exclusion chromatography before and after refolding.

References

1. Pharmacological characterization of 40 human melanocortin-4 receptor polymorphisms with the endogenous proopiomelanocortin-derived agonists and the agouti-related protein (AGRP) antagonist. Biochemistry 2006 Jun 13;45(23):7277-88 2. Stat binding sites but not Stat3 are required for fasting-induced transcription of Agouti-related protein mRNA. Mol Endocrinol 2006 May 18; 3. Agouti-related protein is posttranslationally cleaved by proprotein convertase 1 to generate agouti-related protein (AGRP)83-132: interaction between AGRP83-132 and melanocortin receptors cannot be influenced by syndecan-3. Endocrinology 2006 Apr;147(4):1621-31 4. Agouti-related protein-deficient mice display an age-related lean phenotype. Cell Metab 2005 Dec;2(6):421-7 5. Agouti related protein (AgRP) is upregulated in Cushing's syndrome. Exp Clin Endocrinol Diabetes 2005 Dec;113(10):602-6 6. Mutation analysis of the agouti related protein promoter region and the melanocortin-3 receptor in anorexia nervosa patients. Psychiatr Genet 2005 Dec;15(4):237