p16 is a peptide derived from the C-terminal domain sequence at the GPCR proteolysis cleavage site of GPR126. p16 specifically activates both wild type GPR126 and generated chimeric P2Y12-iGPS-CTF(GPR126) receptors. In vivo p16 serves as an agonist for endogenous Gpr126 using zebrafish posterior lateral line nerve (PLLn) myelin basic protein expression as an assay. p16 is highly selective for GPR126, and is a short tethered sequence (the Stachel sequence) within the ectodomain of GPR126, demonstating that tethered peptide activation is a common signaling mechanism for adhesion GPCRs.
