The Ly9 glycoprotein is a member of the immunoglobulin (Ig) superfamily, which is expressed on the cell surface of thymocytes, and mature T and B lymphocytes. With two alleles (Ly9.1 and Ly9.2), it was first described as an alloantigenic marker of lymphocyte differentiation. Ly9 consists of four Ig-like domains with the structural features of the CD2 subfamily, which includes CD2, CD48, CD58, 2B4, CD84, and CDw150 (SLAM) .
The Ly9 gene, which encompasses at least 19 kb and contains ten separated exons, with sizes ranging from 54 to 355 bp. Each Ig-like domain is encoded by an individual exon. Sequence analysis of a 1.5-kb fragment upstream from the start translational codon revealed the absence of appropriately located TATA and CAAT boxes. However, potential binding sites for the transcription factors PU.1, Ikaros, AP-1, GATA-2, NF-GMa, NFAT-1 and Oct-2, which are involved in the early development and maturation of lymphocytes, were found.
Ly9.1 is found in most mouse strains, whereas Ly9.2 is specifically found in C57BL/6 and related strains (C57BR, C57L, and C58).
The extracellular structure of these glycoproteins comprises one distal-membrane nondisulfide-bounded V-set domain and a proximal-membrane truncated C2-set domain with two disulfide bonds. In contrast to other members of the subfamily, Ly9 contains a tandem repeat of two V-C2-set domains. Ly9 shares its highest sequence similarity with the cell surface molecules CD84 and CD48. The Ly9 locus lies close to the CD48 and CD84 genes on both mouse and human Chromosome 1. Analysis of the amino acid sequences and chromosomal localization suggest that Ly9, CD84, CD48 arose by gene duplication from a common ancestor and that a second duplication lead to the four-domain structure of Ly9.
Cytoplasmic tail reveals the presence of six potential SH2 binding motifs identical to those found in several receptors involved in leukocyte activation. The tyrosine phosphatase SHP-2 and the signaling adaptor molecule SAP have been reported to bind to a tyrosine-based motif in the cytoplasmic tail of SLAM and 2B4, two members of the CD2 subfamily.