LRPAP: Proteins and Enzymes

LRPAP (LDL receptor-related protein-associated protein 1; also named RAP) is a ubiquitously expressed 39 kDa molecular chaperone for LDL receptor family proteins. Mature mouse LRPAP is 332 amino acids (aa) in length and secreted into the ER/Golgi of the cell. It shares 77% and 97% aa sequence identity with human and rat LRPAP, respectively. LRPAP contains three approximately 100 aa alpha-helical domains (D1 - D3). The D1 domain contains a low affinity binding site for LRP, and the associated D2 and D3 domains bind LRP with high affinity. Domains D2 and D3 interact with each other, while D1 is independent. The majority of LRPAP is localized in the endoplasmic reticulum and Golgi. LRPAP prevents the premature interaction of LRP, LRP2/megalin, and VLDLR with their co-expressed ligands, thereby promoting proper receptor folding and export from the ER.