Schematic representation of the two main RAGE isoforms, full-length RAGE and RAGE_v1. Full-length RAGE is an immunoglobulin like receptor with one variable-like domain (V) and two constant-like domains (C) comprising residues. A short transmembrane domain anchors RAGE to the cell surface. A 41 residues intracellular tail is critical for signal transduction. RAGE_v1 does not possess the transmembrane domain and the intracellular tail. It is soluble in the circulation and plays the role of decoy to antagonize the activation of full-length RAGE by its ligands. A soluble form of RAGE can also be generated by proteolysis. S100B, AGEs A oligomers, and TTR bind to RAGE V domain. A aggregates binds to RAGE C1 domain. S100A6 binds both to the V and C2 domain but exerts its cellular effects preferentially through the C2 domain. The exact oligomerization states of full-length RAGE and RAGE_v1 are currently unknown. RAGE is arbitrarily represented as a dimer.
