Disease relevance of ASIP

• It remains to be investigated whether the interaction of MC1R and ASIP can enhance prediction of human pigmentation and melanoma risk [1].
• We examined MC1R and ASIP genotypes in relation to phenotypic characteristics, sporadic and familial melanoma risk, and melanoma thickness as an indicator of disease progression in a Mediterranean population [2].
• The effect of isoforms of the cell polarity protein, human ASIP, on the cell cycle and Fas/FasL-mediated apoptosis in human hepatoma cells [3].
• OBJECTIVE: To determine if human adipocyte agouti signal protein (ASIP) mRNA expression is associated with obesity and is gender and/or depot specific [4].

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 www.plantgdb.org/ASIP) [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].

References