Members of the Fc receptor-like (FCRL1-6) gene family encode transmembrane glycoproteins that are preferentially expressed by B cells and generally repress responses via cytoplasmic tyrosine-based regulation. The FCRL gene family contained six members with FCRL1, FCRL2, FCRL3, FCRL4, FCRL5 and FCRL6. FCRL6 is located at a separate chromosomal position from the FCRL1-5 locus, has conserved synteny in mammals and is situated between the SLAMF8 and DUSP23 genes. FCRL6 gene representatives are widely present in all mammalian families, including basal mammals such as elephants, pangolins, and armadillos. It is reported that the extracellular part of FCRL molecules contains multiples numbers of Ig-like domains and their cytoplasmictail contains immunoreceptor tyrosine -based activation motifs (ITAMs) and immunoreceptor tyrosine-based inhibitory motifs (ITIMs). In humans, FCRL6 encodes a type I surface glycoprotein with three Ig-like domains, a hydrophobic transmembrane segment, and a cytoplasmic tail with two tyrosines that constitute a consensus ITIM or a non-canonical ITAM. In vitro, FcRL6 does not greatly influence NK-cell or CD8(+) T-cell-mediated cytotoxicity and has minimal impact on cytokine secretion. FCRL6 ability to recruit SHP-1, SHP-2, SHIP-1, and SHIP-2 phosphatases, and also adaptor protein Grb2 through phosphorylated cytoplasmic tyrosines.
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