D
IPR027300

Agouti domain

InterPro entry
Short nameAgouti_dom
Overlapping
homologous
superfamilies
 

Description

The agouti signaling protein (ASIP or the agouti protein) and its neuropeptide homologue the agouti-related protein (AgRP) are paracrine signaling molecules that act as inverse agonists at distinct subsets of melanocortin receptors. ASIP antagonizes the binding of alpha-melanocyte stimulating hormone (alpha-MSH) to melanocortin 1 receptor (MC1R), switching melanin synthesis from eumelanin (black/brown) to phaeomelanin (red/yellow). The effect of ASIP on pigment type-switching is responsible for a variety of coat color patterns accross a broad range of mammalian species. AgRP is involved in energy balance and acts normally at the MC3R and MC4R to control body weight regulation and metabolism
[1, 2]
.

Sequence similarity between ASIP and AgRP is confined to their Cys-rich C-terminal domains, which are also responsible for melanocortin receptor binding activity in vitro. Approximately 40 residues in length, there are ten cysteine residues in the C-terminal domain that form a network of five disulfide bonds. The agouti C-terminal domain contains a three-stranded antiparallel β sheet, where the last two strands form a β hairpin. The hairpin's turn region presents a triplet of residues (Arg-Phe-Phe) known to be essential for melanocortin receptor binding. The agouti C-terminal domain adopts the inhibitor cystine knot (ICK) or knottin fold identified in numerous invertebrate toxins
[2, 3]
.

This entry represents the agouti domain which covers the 10 cysteines involved in disulfide bonds.

References

1.Agouti signal protein regulation in human melanoma cells. Voisey J, Kelly G, Van Daal A. Pigment Cell Res. 16, 65-71, (2003). View articlePMID: 12519127

2.Structures of the agouti signaling protein. McNulty JC, Jackson PJ, Thompson DA, Chai B, Gantz I, Barsh GS, Dawson PE, Millhauser GL. J. Mol. Biol. 346, 1059-70, (2005). View articlePMID: 15701517

3.High-resolution NMR structure of the chemically-synthesized melanocortin receptor binding domain AGRP(87-132) of the agouti-related protein. McNulty JC, Thompson DA, Bolin KA, Wilken J, Barsh GS, Millhauser GL. Biochemistry 40, 15520-7, (2001). View articlePMID: 11747427

GO terms

biological process

  • None

cellular component

  • None
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