Agouti signalling peptide

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agouti signalling protein, nonagouti homolog (mouse)
File:1y7k.png
NMR structure family of Agouti Signalling Protein, C-terminal knotting domain. PDB entry 1y7k[1]
Identifiers
SymbolASIP
Alt. symbolsAGTIL
Entrez434
HUGO745
OMIM600201
RefSeqNM_001672
UniProtP42127
Other data
LocusChr. 20 q11.2-q12

Agouti signalling peptide, a product of the Agouti gene, is a peptide consisting of 131 amino acids. Its discovery was published in 1994 in the scientific journal Nature where its functional properties were described. It acts as an inverse agonist at melanocortin receptors, to be specific MC1.[2] It is produced by the Agouti gene ASIP.[3][4]

Function

In mice, the agouti gene encodes a paracrine signalling molecule that causes hair follicle melanocytes to synthesize the yellow pigment pheomelanin instead of the black or brown pigment eumelanin. Pleiotropic effects of constitutive expression of the mouse gene include adult-onset obesity, increased tumor susceptibility, and premature infertility. This gene is highly similar to the mouse gene and encodes a secreted protein that may (1) affect the quality of hair pigmentation, (2) act as an inverse agonist of alpha-melanocyte-stimulating hormone, (3) play a role in neuroendocrine aspects of melanocortin action, and (4) have a functional role in regulating lipid metabolism in adipocytes.[5]

Structure

Agouti signalling peptide adopts an inhibitor cystine knot motif. [1] Along with the homologous Agouti-related peptide, these are the only known mammalian proteins to adopt this fold.

See also

References

  1. 1.0 1.1 McNulty, J. C.; Jackson, P. J.; Thompson, D. A.; Chai, B.; Gantz, I.; Barsh, G. S.; Dawson, P. E.; Millhauser, G. L. (2005). "Structures of the Agouti Signaling Protein". Journal of Molecular Biology. 346 (4): 1059–1070. doi:10.1016/j.jmb.2004.12.030. PMID 15701517.
  2. Lu D, Willard D, Patel IR, Kadwell S, Overton L, Kost T, Luther M, Chen W, Woychik RP, Wilkison WO, et al. (October 1994). "Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor". Nature. 371 (6500): 709–802. doi:10.1038/371799a0. PMID 7935841.
  3. Kwon HY, Bultman SJ, Löffler C, Chen WJ, Furdon PJ, Powell JG, Usala AL, Wilkison W, Hansmann I, Woychik RP (October 1994). "Molecular structure and chromosomal mapping of the human homolog of the agouti gene". Proc. Natl. Acad. Sci. U.S.A. 91 (21): 9760–4. doi:10.1073/pnas.91.21.9760. PMC 44896. PMID 7937887.
  4. Wilson BD, Ollmann MM, Kang L, Stoffel M, Bell GI, Barsh GS (February 1995). "Structure and function of ASP, the human homolog of the mouse agouti gene". Hum. Mol. Genet. 4 (2): 223–30. doi:10.1093/hmg/4.2.223. PMID 7757071.
  5. "Entrez Gene: ASIP".

Further reading

External links


This article incorporates text from the United States National Library of Medicine, which is in the public domain.