ASIP
Domain
The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.
Function
Involved in the regulation of melanogenesis. The binding of ASP to MC1R precludes alpha-MSH initiated signaling and thus blocks production of cAMP, leading to a down-regulation of eumelanogenesis (brown/black pigment) and thus increasing synthesis of pheomelanin (yellow/red pigment). In higher primates, agouti may affect the quality of hair pigmentation rather than its pattern of deposition. Could well play a role in neuroendocrine aspects of melanocortin action. May have some functional role in regulating the lipid metabolism with adipocytes.
Involvement in disease
Obesity and hypopigmentation
OBHP
An autosomal dominant disorder characterized by early-onset obesity, overgrowth, hyperinsulinemia, and hypopigmentation of the skin. Some affected individuals experience hyperphagia and exhibit reduced energy expenditure.
None
The gene represented in this entry is involved in disease pathogenesis. A tandem duplication on chromosome 20 encompassing the neighboring genes ASIP and ITCH creates an ITCH-ASIP transcript consisting of the first two non-coding ITCH exons fused to the ASIP coding exons. This results in ASIP ectopic overexpression controlled by the ubiquitously active ITCH promoter. Ectopically expressed ASIP may antagonize MC4R signaling in the hypothalamus and may affect processes related to eating behavior and energy expenditure.
Tissue Specificity
Widely expressed at low levels. Highly expressed in the skin. Expressed in adipose tissue.
Cellular localization
- Secreted
Alternative names
AGTI, AGTIL, ASP, ASIP, Agouti-signaling protein, Agouti switch protein