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Siglecs (sialic acid-binding Ig-like lectins) are members of the Ig superfamily expressed at the cell surface. Structurally, they have a characteristic N-terminal V-set Ig-like domain containing the sialic acid-binding site followed by varying numbers of C2-set domains. Most Siglecs have one or more immune receptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic tails implicated in negative regulatory signaling functions. The first Siglecs to be defined were sialoadhesin/Siglec-1, CD22/ Siglec-2, CD33/Siglec-3 and myelin-associated glycoprotein (MAG)/Siglec-4 expressed by macrophages, B-cells, myeloid cells and myelin-forming cells respectively. Each protein exhibits distinct sialic acid-binding properties and is expressed in a characteristic manner. Interestingly, the highest levels of expression of these proteins are found on effector cells of the innate immune system, including monocytes (Siglecs 3, 5, 7 and 9), neutrophils (Siglecs 5 and 9), eosinophils (Siglec-8) and natural killer cells (NK cells; Siglec-7). This observation, together with the common theme of sialic acid recognition and the presence of conserved, putative tyrosinebased inhibitory signaling motifs, has led to the suggestion that several of the CD33-related Siglecs might be involved in regulating activation of leucocytes via sialic acid recognition. In this paper researcher describe the properties of a new member of the Siglec family, Siglec-10. Amongst peripheral blood leucocytes Siglec-10 was found to be expressed on eosinophils, monocytes and B-cells. Higher levels of this novel Siglec were found on a minor subset of NK-like cells that express the CD16 low-affinity Fc receptor but lack the CD56 antigen. The molecular properties and expression pattern suggest that Siglec-10 may have evolved to function as an inhibitory receptor of the innate immune system.
Fig 1. Phylogenetic analysis of CD33-related Siglecs.
(Biochemical Journal, 2001.)
In a search for novel human Siglec cDNAs, 21 unique ESTs were identified in eight different cDNA libraries that encoded the same novel Siglec-like protein. A full-length clone encoding this novel Siglec was successfully isolated from a human spleen cDNA library. Based on sequence similarity with other Siglecs and its ability to bind sialic acid this protein has been designated Siglec-10. The extracellular region of Siglec-10 contains a hydrophobic signal peptide and five Ig-like domains that are made up of an N-terminal V-set domain and four C2-set domains. There are five potential Nlinked glycosylation sites. Following the transmembrane region, there is a cytoplasmic tail of 126 amino acids. Siglec-10 contains all of the characteristic features of the Siglec subgroup of Ig superfamily proteins. These include the critical arginine at position 120 that has been shown in the ligand-bound crystal structure of sialoadhesin to interact with the carboxy group of sialic acid. The other two tyrosine-based motifs in the cytoplasmic tail of Siglec-10 are more typical of the CD33-related Siglec subset.
Database searches showed that Siglec-10 shares the highest sequence similarity with the CD33-related Siglec subset, namely Siglecs 3, 5, 6, 7, 8 and 9. Within the first two Ig-like domains, Siglec-10 was found to be 40-48% identical to these proteins. The alignment also showed that domain 5 of Siglec-10 was highly related to domain 4 of Siglec-5. Siglec-10 also shared low, but significant similarity with MAG/Siglec-4 in all five Ig-like domains. To investigate further the possible evolutionary relationships between Siglec-10 and the other CD33-related Siglecs, unrooted phylogenetic trees were created using both the N-terminal regions and C-terminal regions. The N-terminal phylogenetic tree positioned Siglec-10 at an intermediate position between Siglecs 1, 2 and 4 and the other CD33-related Siglecs, which group together. A similar overall pattern was observed with the C-terminal phylogenetic tree.
Low levels of Siglec-10 on monocytes and on subsets of granulocytes and lymphocytes. Using anti-CD16 mAb to distinguish eosinophils from neutrophils, the CD16-negative eosinophils were found to stain specifically with 5G6. To date, Siglec-8 is the only other Siglec that has been shown to be expressed on eosinophils, although in this case its expression is highly restricted. It is evident that Siglec-8 is expressed at higher levels on eosinophils than Siglec-10. The dominant population expressing Siglec-10 was made up of CD19+ B-cells that were labelled weakly. Higher levels of Siglec-10 were seen on a very small subset (≈0.5%) of cells in the lymphocyte gate that expressed high levels of CD16 but no detectable CD56.
A single band of≈100-120 kDa was observed under both reducing and non-reducing conditions, demonstrating that Siglec-10 exists as a monomer in the plasma membrane. Since the observed molecular mass was considerably greater than that predicted from the amino acid sequence of the mature protein (74560 Da), it is likely that most or all of the five potential N-linked glycosylation sites are occupied by carbohydrate.
| Target | Cat. No. | Product Name | Host | Isotype | Application | |
| SIGLEC10 | DPAB-DC3694 | Anti-SIGLEC10 (aa 589-696) polyclonal antibody | Mouse | WB, ELISA | Inquiry | |
| SIGLEC10 | DCABY-663 | Anti-SIGLEC10 monoclonal antibody, clone 6H7 [R-PE] | Mouse | IgG1 | FC | Inquiry |
| SIGLEC10 | DCABY-661 | Anti-SIGLEC10 monoclonal antibody, clone 6H7 [FITC] | Mouse | IgG1 | FC | Inquiry |
| SIGLEC10 | DCABY-662 | Anti-SIGLEC10 monoclonal antibody, clone 6H7 | Mouse | IgG1 | FC | Inquiry |
| SIGLEC10 | CABT-Z893G | Goat Anti-Human SIGLEC10 Polyclonal Antibody [Functional Grade] | Goat | IgG | WB, FC, BL, Neut | Inquiry |
| Target | Cat. No. | Product Name | Size | Application | Detection Sample | |
| SIGLEC10 | DEIA-FN1378 | Human SIGLEC10 (Sialic acid-binding Ig-like lectin 10) ELISA Kit | 96T | Quantitative | serum, plasma, cell culture supernatants, tissue homogenate | Inquiry |
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