Recombinant Human Stabilin-2 (aa 2198-2295) Protein

Stabilin-2, also known as HARE (hyaluronan receptor for endocytosis) and FEEL-2 (fasciclin, EGF-like, laminin type EGF-like, and link domain containing scavenger receptor 2), is a type I transmembrane multi-domain protein that is the closest homolog of stabilin-1 (1, 2). It is a scavenger receptor that is expressed on sinusoidal endothelial cells of liver, spleen, and lymph node (1, 2). Its 2439 amino acid (aa) extracellular domain contains seven fasciclin domains, multiple EGF-like and laminin type EGF-like domains, and a link domain related to molecules of the TSG-6 superfamily (3). The 72 aa cytoplasmic tail of Stabilin-2 contains a motif that allows the AP2 classical cargo adaptor to direct cargo into clathrin-coated pits (4). As a recycling receptor, stabilin-2 cycles from the membrane to clathrin-coated pits each 10 - 15 minutes, with about two thirds of the protein found within the endocytic system at any one time (4). The link domain binds and mediates the systemic clearance of hyaluronan (HA) (2 - 6). Within the link domain (aa 2198 - 2295), human stabilin-2 shares 86% and 89% aa identity with mouse and rat stabilin-2, respectively. Total human HA is about 15 grams, of which about 5 grams are cleared each day (5). Stabilin-2 also mediates the endocytosis of chondroitin and chondroitin sulfate, advanced glycosylation end-product (AGE), collagen N-terminal propeptides and acetylated LDL (4 - 7). Human stabilin-2 mRNA encodes a 2251 aa, 315 kDa protein that produces an isoform of 190 kDa through proteolytic cleavage (2, 6). The 190 kDa form lacks some N-terminal fasciclin and EGF-like domains, but shows similar activities when compared with the 315 kDa form (2, 6).