The gene structure and minimal promoter of the human agouti related protein.
The murine agouti related protein (mAGRP) is upregulated in obese and diabetic mice and stimulates hyperphagia when administered intracerebroventricularly (i.c.v.) or when overexpressed in transgenic mice. The human ortholog, hAGRP, has been isolated and has similar molecular and physiological properties. Here, we report the complete gene structure of the human AGRP gene and upstream regions with differential promoter activity. A polymorphism, A67T, in the third exon was identified but was not associated with obesity- or type 2 diabetes-related phenotypes. Putative binding sites for transcription factors were identified in the promoter of the gene including recognition sites for the signal transducers and activators of transcription (STATs) that may potentially mediate leptin's action in the hypothalamus. The upstream non-coding exon had significant promoter activity in a periphery- but not so in a hypothalamus-derived cell line, suggesting that it might contain the minimal promoter required for expression of the short transcript of hAGRP in the periphery.
Brown
A M
AM
Department of Medicine, Medical University of South Carolina, Strom Thurmond Biomedical Research Center Room 528, 114 Doughty Street, Charleston, SC 29403, USA.
Mayfield
D K
DK
Volaufova
J
J
Argyropoulos
G
G
D054369:Agouti-Related Protein; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005091:Exons; D005787:Gene Frequency; D005796:Genes / Q000235:genetics*; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007438:Introns; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014162:Transfection
C515198:AGRP protein, human; D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D004247:DNA; D008156:Luciferases