Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2008) Nucleic Acids Res , doi:10.1093/nar/gkn808

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The domain within your query sequence starts at position 1 and ends at position 109; the E-value for the Agouti domain shown below is 53111.44114.

MNTFLLSALCLLGAWATLTGGVIVQDGDFSFSLESVKKLKDLQELQEPRIPRNPVGPITS
NLCSLPTFPEELKPLCKEPNAQEILDRLGAIAADPSTCEICAYAACAGC

Agouti Agouti protein

There are 110 Agouti domains in 110 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a Agouti domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with Agouti domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Homo sapiens, Mus musculus, Rattus norvegicus, Takifugu rubripes

• Cellular role (predicted cellular role)

• Cellular role: metabolism
  

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Kanetsky PA, Swoyer J, Panossian S, Holmes R, Guerry D, Rebbeck TR
  • A polymorphism in the agouti signaling protein gene is associated with human pigmentation.
  • Am J Hum Genet. 2002; 70: 770-5
  • Display abstract

  • In mice and humans, binding of alpha-melanocyte--stimulating hormone to the melanocyte-stimulating--hormone receptor (MSHR), the protein product of melanocortin-1 receptor (MC1R) gene, leads to the synthesis of eumelanin. In the mouse, ligation of MSHR by agouti signaling protein (ASP) results in the production of pheomelanin. The role of ASP in humans is unclear. We sought to characterize the agouti signaling protein gene (ASIP) in a group of white subjects, to assess whether ASIP was a determinant of human pigmentation and whether this gene may be associated with increased melanoma risk. We found no evidence of coding-region sequence variation in ASIP, but detected a g.8818A-->G polymorphism in the 3' untranslated region. We genotyped 746 participants in a study of melanoma susceptibility for g.8818A-->G, by means of polymerase chain reaction and restriction fragment--length polymorphism analysis. Among the 147 healthy controls, the frequency of the G allele was.12. Carriage of the G allele was significantly associated with dark hair (odds ratio 1.8; 95% confidence interval [CI] 1.2--2.8) and brown eyes (odds ratio 1.9; 95% CI 1.3--2.8) after adjusting for age, gender, and disease status. ASIP g.8818A-->G was not associated independently with disease status. This is the first report of an association of ASIP with specific human pigmentation characteristics. It remains to be investigated whether the interaction of MC1R and ASIP can enhance prediction of human pigmentation and melanoma risk.

  • Voisey J, van Daal A
  • Agouti: from mouse to man, from skin to fat.
  • Pigment Cell Res. 2002; 15: 10-8
  • Display abstract

  • The agouti protein regulates pigmentation in the mouse hair follicle producing a black hair with a subapical yellow band. Its effect on pigmentation is achieved by antagonizing 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). Dominant mutations in the non-coding region of mouse agouti cause yellow coat colour and ectopic expression also results in obesity, type 11 diabetes, increased somatic growth and tumourigenesis. At least some of these pleiotropic effects can be explained by antagonism of other members of the melanocortin receptor family by agouti protein. The yellow coat colour is the result of agouti chronically antagonizing the binding of alpha-MSH to Mc1r and the obese phenotype results from agouti protein antagonizing the binding of alpha-MSH to Mc3r and/or Mc4r. Despite the existence of a highly homologous agouti protein in humans, agouti signal protein (ASIP), its role has yet to be defined. However it is known that human ASIP is expressed at highest levels in adipose tissue where it may antagonize one of the melanocortin receptors. The conserved nature of the agouti protein combined with the diverse phenotypic effects of agouti mutations in mouse and the different expression patterns of human and mouse agouti, suggest ASIP may play a role in human energy homeostasis and possibly human pigmentation.

• Metabolism (metabolic pathways involving proteins which contain this domain)

• % proteins involved KEGG pathway ID Description 37.50 map04916 Melanogenesis 31.25 map04920 Adipocytokine signaling pathway 31.25 map04080 Neuroactive ligand-receptor interaction This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with Agouti domain which could be assigned to a KEGG orthologous group, and not all proteins containing Agouti domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of Agouti domains in PDB

  PDB code	Main view	Title
  1y7j		Nmr structure family of human agouti signalling protein (80- 132: q115y, s124y)
  1y7k		Nmr structure family of human agouti signalling protein (80- 132: q115y, s124y)

• Links (links to other resources describing this domain)

• PFAM	Agouti
  INTERPRO	IPR007733