Alternative titles; symbols
HGNC Approved Gene Symbol: ADGRE3
Cytogenetic location: 19p13.12 Genomic coordinates (GRCh38) : 19:14,600,117-14,674,844 (from NCBI)
Epidermal growth factor (EGF; 131530)-7-transmembrane (TM7) proteins are G protein-coupled receptors (GPCRs) found on monocytes and neutrophils. They include mouse F4/80, mouse and human CD97 (601211), and EMR1 (600493), the likely human homolog of F4/80. EGF-TM7 glycoproteins have variable numbers of N-terminal EGF-like repeats coupled to a family-B GPCR-related moiety via a mucin-like stalk (summary by Stacey et al., 2001). By searching DNA databases, using 5-prime and 3-prime RACE, and screening a spleen cDNA library, Stacey et al. (2001) identified cDNAs encoding EMR2 (606100), EMR3, and splice variants of each. The deduced 652-amino acid EMR3 protein contains an N-terminal signal peptide, 2 EGF-like domains, the first of which does not contain a calcium-binding sequence, a mucin-like spacer region with several N- and O-linked glycosylation sites, a putative GPCR proteolytic site, a TM7 region, and a 51-residue cytoplasmic tail. A truncated EMR3 splice variant containing only the 2 EGF-like domains and no transmembrane domain was predicted to be a soluble protein. Northern blot analysis of tissues and RT-PCR analysis of cell lines revealed that expression of 2.4- and 4.0-kb EMR3 transcripts was restricted to leukocytes. Flow cytometric screening demonstrated that EMR3, but not EMR2, interacts with monocyte-derived macrophages and neutrophils activated with fMLP but not with CD55 (125240), the CD97 ligand. Stacey et al. (2001) noted that EMR3 and EMR2 share a high degree of sequence identity in the TM domains but not in the extracellular domains, whereas EMR2 and CD97 are highly homologous in the EGF-like domains but not in the transmembrane domains, suggesting different ligand-binding and intracellular signaling activities.
By genomic sequence analysis, Stacey et al. (2001) mapped the EMR3 gene to 19p13.1, close to the other EGF-TM7 genes.
Stacey, M., Lin, H.-H., Hilyard, K. L., Gordon, S., McKnight, A. J. Human epidermal growth factor (EGF) module-containing mucin-like hormone receptor 3 is a new member of the EGF-TM7 family that recognizes a ligand on human macrophages and activated neutrophils. J. Biol. Chem. 276: 18863-18870, 2001. [PubMed: 11279179] [Full Text: https://doi.org/10.1074/jbc.M101147200]