| Protein-carbohydrate interactions serve multiple functions in the immune system. Many animal lectins mediate both pathogen recognition and cell-cell interactions using structurally related Ca+-dependent carbohydrate-recognition domains (C-type CRDs). To identify new adhesion molecules related to C-type lectins in human fetal liver ESTs libraries, the C-type lectins, CD23, DC-SIGN and DC-SIGNR, all of which were known to be typical adhesion molecules, were selected as baits. Based on large-scale sequencing of human fetal liver cDNA libraries, following routine bioinformatic strategies and RACE (rapid amplification of cDNA ends) technique, we have obtained a new CD23-like gene, termed CD23L. CD23L gene spans 3295bp, consists of 9 exons which encode an open reading frame of 293 amino acids, and maps to chromosome 19p13.3 adjacent to the previously described C-type lectins, CD23, DC-SIGN and DC-SIGNR. CD23L gene was situated just between CD23 gene and DC-SIGN gene, which was followed by DC-SIGNR gene. The four genes form a tight cluster in an insert size of 105 kb. From centeromere to telomere, there are DC-SIGNR, DC-SIGN, CD23L and CD23 in turn. DC-SIGN, CD23L and CD23 were arranged in the same orientation but DC-SIGNR in opposition to them. The genomic structure comparison of the four C-type lectin genes showed that they had analogous genomic organization except for the difference in the neck region. As is characteristic of type II C-type lectins , the region corresponding to their CRDs are encoded by three exons at 3′-terminal, and their amino-terminal cytoplasmic tails and anchor sequences are encoded by two exons. In the neck region, the number and the length of exons are different among them. The exons arrangement of CD23L in the neck region is more similar to that of CD23 than those of DC-SIGN and DC-SIGNR, because there are 5 exons (333bp) in CD23 neck region containing three homologous exons, each 63bp long, which result in three leucine-rich repeats, and 4 exons (312bp) in CD23L that include exon 5 of 105bp encoding three leucine-rich repeats corresponding to exon 6 and 7 of CD23, and exon 3, exon 4 and exon 6 corresponding to exon 4, exon5 and exon 8 of CD23 in size, respectively. In contrast to CD23 and CD23L, there is only one large exon (570bp) containing seven 69 bp repeats in the neck regions of both DC-SIGN and DC-SIGNR. The close linkage and similar genomic structures suggest that these fourgenes may have arisen via duplication of an ancestral gene.CD23L is one of type II C-type lectin family members, consisting of a short, NH2-terminal cytoplasmic tail of 31 amino acids preceding a transmembrane domain (23 amino acids) and a COOH-terminal extracellular region. The extracellular part is composed of a stalk region of 110 amino acids that connects the transmembrane domain to a single CTLD (C-type lectin-like domain) in the C-terminal that spans at least 129 amino acids. CD23L shows 32%, 31% and 31% identity to DC-SIGNR, DC-SIGN and CD23 at amino acid levels, repectively. Moreover, using CRD domain of CD23L peptide searching protein database, showed that 70% identity to the mouse unnamed protein, 39% to DC-SIGNR, 38% to DC-SIGN and 37% to CD23. CD23L, DC-SIGNR, DC-SIGN and CD23 all belong to type II integral membrane protein, and display similar protein domain organization. Most notably, in the CTLD, it has a complete Ca2+-binding site 2, which is largely responsible for sugar binding in a Ca2+-dependent manner in other C-type lectin family members, and in this site, contains a EPN sequence characteristic of mannose-, N-acetylglucosamine- and fucose-binding C-type lectins. In contrast to DC-SIGN and DC-SIGNR, the Ca2+-binding site 1 of CD23L is partly conserved in a manner analogous to CD23. Northern blot showed that CD23 was only expressed in liver and lymph node of 15 human tissues tested. RT-PCR analysis indicated that CD23L was neither expressed on hematopoietic cells nor on DCs and liver cancer cell lines such as HepG2 and BEL-7402 either. To further id...
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