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Gene Review

ASIP  -  agouti signaling protein

Homo sapiens

Synonyms: AGSW, AGTI, AGTIL, ASP, Agouti switch protein, ...
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Disease relevance of ASIP


High impact information on ASIP

  • We created a comprehensive web-interfaced database to compile and visualize the evidence for alternative splicing in plants (Alternative Splicing in Plants, available at [5].
  • Unexpectedly, we found that the whole coding region of ASIP was missing only from the gibbon genome; gibbons constitute a large group of hominoid species in Southeast Asia. Our analyses revealed that unequal homologous recombination mediated by two AluSx elements erased a approximately 100-kb region including ASIP from the gibbon genome [6].
  • In this study, we have tried to determine DNA sequences of the ASIP gene (ASIP) of various simian species to find molecular evolutionary aspects of ASIP [6].
  • Ubiquitous ASIP expression in mice gives rise to a pleiotropic phenotype characterized by a uniform yellow coat color, obesity, overgrowth, and metabolic derangements similar to type II diabetes in humans [7].
  • In the models of the ASIP fragment complexed with both receptors, the core ligand tripeptide, Arg-Phe-Phe, positioned between TMHs 3 and 6, is shifted toward TMHs 2 and 7 relative to its position in the AGRP-hMC4R model, while the N-terminal loop and two central disulfides of the antagonists interact with EL2 of the receptors [8].

Biological context of ASIP

  • Subsequent analyses revealed a strong effect on M index from ASIP genotypes in African American females (P<0.001) [9].
  • Studies have shown that a single-nucleotide polymorphism (SNP) in the 3'UTR of the ASIP gene is associated with dark hair and eyes; however, little is known about its role in inter-individual variation in skin color [9].
  • MC1R was sequenced, ASIP was genotyped, and DNA repair capacity was measured by the host-cell reactivation assay [2].
  • BMI and ASIP gene expression were negatively correlated in men (rho = -0.70; p < 0.05), whereas a positive relationship was observed in women (rho = 0.48; p < 0.05) [4].
  • If ASIP is involved in appetite regulation or energy homeostasis in humans, this observation may contribute to the recognized differences in these parameters between men and women [4].

Anatomical context of ASIP

  • DISCUSSION: These results show that men and women of similar age and BMI present similar ASIP mRNA levels in omental and subcutaneous abdominal adipocytes [4].
  • To test this hypothesis, ASIP mRNA levels were quantified in melanocytes carrying the variant and non-variant alleles [10].
  • To determine whether ASIP regulates known melanogenic genes in humans, ASIP was over-expressed in a human melanoma cell line [11].
  • However it is known that human ASIP is expressed at highest levels in adipose tissue where it may antagonize one of the melanocortin receptors [12].
  • At passage I, the tumor-cell line (AGTI) showed 15% of the metaphases with a translocation involving chromosomes 5 and 14 [13].

Associations of ASIP with chemical compounds

  • The amino acid sequence of human hepatic peroxisomal L-alanine: glyoxylate aminotransferase 1 (AGTI) deduced from cDNA shows 78% sequence identity with that of rat mitochondrial AGTI, but lacks the N-terminal 22 amino acids (the putative mitochondrial targeting signal) [14].

Other interactions of ASIP

  • However, ASIP-[90-132 (L89Y)] was found to be less potent than full-length recombinant ASIP and, surprisingly, only exhibited weak inhibitory activity at the hMC2R [15].
  • This study demonstrates the smaller analogs AgRP (87-120) and ASIP [90-132 (L89Y)], and short peptides Yc[CRFFNAFC]Y and Qc[CRFFRSAC]S are also MC4R inverse agonists [16].
  • ASIP mRNA levels in isolated omental and subcutaneous abdominal adipocytes were measured by quantitative reverse transcription polymerase chain reaction [4].
  • The frequency of the G allele of 3'UTR in ASIP was 17% in vitiligo and 12% in controls [P = 0.14, OR (95% CI) = 1.49 (0.87-2.54)] [17].


  1. A polymorphism in the agouti signaling protein gene is associated with human pigmentation. Kanetsky, P.A., Swoyer, J., Panossian, S., Holmes, R., Guerry, D., Rebbeck, T.R. Am. J. Hum. Genet. (2002) [Pubmed]
  2. MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population. Landi, M.T., Kanetsky, P.A., Tsang, S., Gold, B., Munroe, D., Rebbeck, T., Swoyer, J., Ter-Minassian, M., Hedayati, M., Grossman, L., Goldstein, A.M., Calista, D., Pfeiffer, R.M. J. Natl. Cancer Inst. (2005) [Pubmed]
  3. The effect of isoforms of the cell polarity protein, human ASIP, on the cell cycle and Fas/FasL-mediated apoptosis in human hepatoma cells. Hu, Y., Fang, C., Xu, Y. Cell. Mol. Life Sci. (2005) [Pubmed]
  4. Body mass index-related human adipocyte agouti expression is sex-specific but not depot-specific. Voisey, J., Imbeault, P., Hutley, L., Prins, J.B., van Daal, A. Obes. Res. (2002) [Pubmed]
  5. Genomewide comparative analysis of alternative splicing in plants. Wang, B.B., Brendel, V. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. Alu-mediated 100-kb deletion in the primate genome: the loss of the agouti signaling protein gene in the lesser apes. Nakayama, K., Ishida, T. Genome Res. (2006) [Pubmed]
  7. Structures of the agouti signaling protein. McNulty, J.C., Jackson, P.J., Thompson, D.A., Chai, B., Gantz, I., Barsh, G.S., Dawson, P.E., Millhauser, G.L. J. Mol. Biol. (2005) [Pubmed]
  8. Receptor-antagonist interactions in the complexes of agouti and agouti-related protein with human melanocortin 1 and 4 receptors. Chai, B.X., Pogozheva, I.D., Lai, Y.M., Li, J.Y., Neubig, R.R., Mosberg, H.I., Gantz, I. Biochemistry (2005) [Pubmed]
  9. The 8818G allele of the agouti signaling protein (ASIP) gene is ancestral and is associated with darker skin color in African Americans. Bonilla, C., Boxill, L.A., Donald, S.A., Williams, T., Sylvester, N., Parra, E.J., Dios, S., Norton, H.L., Shriver, M.D., Kittles, R.A. Hum. Genet. (2005) [Pubmed]
  10. A polymorphism in the agouti signalling protein (ASIP) is associated with decreased levels of mRNA. Voisey, J., Gomez-Cabrera, M.d.e.l. .C., Smit, D.J., Leonard, J.H., Sturm, R.A., van Daal, A. Pigment Cell Res. (2006) [Pubmed]
  11. Agouti signal protein regulation in human melanoma cells. Voisey, J., Kelly, G., Van Daal, A. Pigment Cell Res. (2003) [Pubmed]
  12. Agouti: from mouse to man, from skin to fat. Voisey, J., van Daal, A. Pigment Cell Res. (2002) [Pubmed]
  13. Spontaneous development of a chromosomal translocation 5;14 in an Epstein-Barr-virus-associated B-cell lymphoma in a SCID mouse. Glaser, R., Theil, K.S., Bonneau, R.H., Sheridan, J.F., Vasquez, M., Allen, C.M. Int. J. Cancer (1993) [Pubmed]
  14. Human peroxisomal L-alanine: glyoxylate aminotransferase. Evolutionary loss of a mitochondrial targeting signal by point mutation of the initiation codon. Takada, Y., Kaneko, N., Esumi, H., Purdue, P.E., Danpure, C.J. Biochem. J. (1990) [Pubmed]
  15. Functional properties of an agouti signaling protein variant and characteristics of its cognate radioligand. Yang, Y.K., Dickinson, C., Lai, Y.M., Li, J.Y., Gantz, I. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2001) [Pubmed]
  16. Inverse agonist activity of agouti and agouti-related protein. Chai, B.X., Neubig, R.R., Millhauser, G.L., Thompson, D.A., Jackson, P.J., Barsh, G.S., Dickinson, C.J., Li, J.Y., Lai, Y.M., Gantz, I. Peptides (2003) [Pubmed]
  17. Polymorphisms in the melanocortin-1 receptor (MC1R) and agouti signaling protein (ASIP) genes in Korean vitiligo patients. Na, G.Y., Lee, K.H., Kim, M.K., Lee, S.J., Kim, d.o. .W., Kim, J.C. Pigment Cell Res. (2003) [Pubmed]
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