Agouti-signaling protein (ASIP)

Agouti-signaling protein (ASIP) is a small, secreted, paracrine signaling protein encoded by the ASIP gene in humans and other mammals. It acts as a competitive antagonist or inverse agonist at certain melanocortin receptors, primarily melanocortin 1 receptor (MC1R), where it blocks the action of α-melanocyte-stimulating hormone (α-MSH), switching melanin synthesis from eumelanin (dark pigment) to pheomelanin (red/yellow)[4]. The structure comprises a C-terminal cysteine-rich domain that adopts an inhibitor cystine knot fold, critical for high affinity binding and functional antagonism at MC1R[1][2][3]. In animal models, aberrant expression of ASIP is linked to yellow coat color and obesity, highlighting a role in energy homeostasis and metabolic regulation as well as pigmentation[1][4]. ASIP is not currently a common drug target nor routinely used as a therapeutic biomarker in clinical practice.

Other names

Agouti-signaling proteinASIPAGTIAGTILASPAgouti switch proteinnonagouti homolog (mouse)AGSWSHEP9nonagouti homologagouti switch protein

Competitive antagonist or inverse agonist at melanocortin receptors (especially MC1R) Inhibits α-melanocyte-stimulating hormone (α-MSH)-induced activity to shift melanin production from eumelanin (dark) to pheomelanin (red/yellow)[1][2][4]