Human EMR2 Alexa Fluor® 488-conjugated Antibody

EMR2 (EGF-like Module-containing Mucin-like Hormone Receptor 2), designated CD312, is a 90-100 kDa glycoprotein belonging to the EGF-TM7 family of adhesion-type class B 7‑transmembrane (TM) receptors. EGF-like sequences within long extracellular N-termini, and a GPS (G-protein proteolytic site) domain are characteristic of this family, which is mainly expressed on cells of the immune system (1-3). The human EMR2 cDNA encodes an 823 amino acid (aa) protein with five EGF-like domains within the first 250 aa, followed by a mucin-like stalk, a GPS domain (aa 479‑530) and a 7‑TM sequence (aa 531‑785). The GPS domain is the site of autocatalytic cleavage, forming a 70 kDa N-terminal, and a 30 kDa C-terminal portion that remains non-covalently attached as a heterodimer (2, 4). Of the first 290 aa of human EMR2, 284 aa (97%) are identical with family member CD97, likely due to gene duplication (3). The portion of human EMR2 N-terminal to the GPS domain (aa 1‑478) shares 64%, 59%, 48% and 45% aa identity with corresponding regions of canine EMR2, equine EMR2, mouse CD97 and rat CD97, respectively. There is no mouse ortholog for human EMR2. Alternate splicing of EMR2 creates isoforms that contain 2‑5 EGF-like domains. Only the 5-EGF form contains EGF4, which is necessary for calcium-dependent binding of the EMR2/CD97 ligand, chondroitin sulfate (CS) (3, 5‑7). None of the isoforms engage the CD97 ligand, CD55 (DAF). Notably, alternative trans-splicing produces a EMR2:CD97 hybrid where the third EGF-likek motif of CD97 is substituted for the third EGF-like motif of EMR2 (8). EMR2 is restricted to myeloid cells (2, 3). EMR2 expression increases as monocytes differentiate into macrophages, and decreases with differentiation into dendritic cells (6). Activation increases neutrophil EMR2 expression (6). EMR2 localizes to the leading edge of migrating neutrophils and plays an important role in migration, adhesion and superoxide production (9). It is also thought to facilitate specific interaction of myeloid cells with peripheral B lymphocytes which express CS (7).