This gene encodes a member of the adhesion-GPCR receptor family  expressed predominantly by cells of the immune system. Family members are characterized by an extended extracellular region with a variable number of N-terminal protein modules coupled to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain. In the case of EMR2 the N-terminal domains consist of alternatively spliced epidermal growth factor (EGF)-like domains.
This gene is closely linked to the gene encoding egf-like molecule containing mucin-like hormone receptor 3 on chromosome 19 EMR3. This protein does not interact with the complement regulatory protein, decay accelerating factor CD55, unlike the related CD97 antigen, and indicates that these very closely related proteins likely have nonredundant functions.
EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2) is an adhesion GPCR that undergoes GPS autoproteolysis before being trafficked to the plasma membrane. Mutations in the GPS have shown that EMR2 does not need to undergo autoproteolysis to be trafficked, but loses function. EMR2 has been shown to be necessary for in vitro cell migration.
Upon cleavage the N-terminus has been shown to associate with the 7TM, but to also dissociate, giving two possible functions. When the N-terminus dissociates it can be found in lipid rafts. Additionally, the cleaved EMR2 protein 7TM has been found to associate with EMR4 N-terminus.
^Huang, Y. S., N. Y. Chiang, C. H. Hu, C. C. Hsiao, K. F. Cheng, W. P. Tsai, S. Yona, M. Stacey, S. Gordon, G. W. Chang, H. H. Lin. 2012. Activation of myeloid cell-specific adhesion class G protein-coupled receptor EMR2 via ligation-induced translocation and interaction of receptor subunits in lipid raft microdomains" Mol. Cell. Biol 32: 1408–1420.
Lin HH, Stacey M, Hamann J, et al. (2000). "Human EMR2, a novel EGF-TM7 molecule on chromosome 19p13.1, is closely related to CD97". Genomics67 (2): 188–200. doi:10.1006/geno.2000.6238. PMID10903844.
Lin HH, Stacey M, Saxby C, et al. (2001). "Molecular analysis of the epidermal growth factor-like short consensus repeat domain-mediated protein-protein interactions: dissection of the CD97-CD55 complex". J. Biol. Chem.276 (26): 24160–9. doi:10.1074/jbc.M101770200. PMID11297558.
Kwakkenbos MJ, Chang GW, Lin HH, et al. (2002). "The human EGF-TM7 family member EMR2 is a heterodimeric receptor expressed on myeloid cells". J. Leukoc. Biol.71 (5): 854–62. PMID11994511.
Stacey M, Chang GW, Davies JQ, et al. (2003). "The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans". Blood102 (8): 2916–24. doi:10.1182/blood-2002-11-3540. PMID12829604.
Chang GW, Stacey M, Kwakkenbos MJ, et al. (2003). "Proteolytic cleavage of the EMR2 receptor requires both the extracellular stalk and the GPS motif". FEBS Lett.547 (1–3): 145–50. doi:10.1016/S0014-5793(03)00695-1. PMID12860403.
Lin HH, Chang GW, Davies JQ, et al. (2004). "Autocatalytic cleavage of the EMR2 receptor occurs at a conserved G protein-coupled receptor proteolytic site motif". J. Biol. Chem.279 (30): 31823–32. doi:10.1074/jbc.M402974200. PMID15150276.
Bjarnadóttir TK, Fredriksson R, Höglund PJ, et al. (2005). "The human and mouse repertoire of the adhesion family of G-protein-coupled receptors". Genomics84 (1): 23–33. doi:10.1016/j.ygeno.2003.12.004. PMID15203201.
Chang GW, Davies JQ, Stacey M, et al. (2007). "CD312, the human adhesion-GPCR EMR2, is differentially expressed during differentiation, maturation, and activation of myeloid cells". Biochem. Biophys. Res. Commun.353 (1): 133–8. doi:10.1016/j.bbrc.2006.11.148. PMID17174274.