Cloning, Characterization, and Phylogenetic Analysis of Siglec-9, a New Member of the CD33-related Group of Siglecs

The Siglecs are a subfamily of I-type lectins (immunoglobulin superfamily proteins that bind sugars) that specifically recognize sialic acids. We report the cloning and characterization of human Siglec-9. The cDNA encodes a type 1 transmembrane protein with three extracellular immunoglobulin-like domains and a cytosolic tail containing two tyrosines, one within a typical immunoreceptor tyrosine-based inhibitory motif (ITIM). The N-terminal V-set Ig domain has most amino acid residues typical of Siglecs. Siglec-9 is expressed on granulocytes and monocytes. Expression of the full-length cDNA in COS cells induces sialic-acid dependent erythrocyte binding. A recombinant soluble form of the extracellular domain binds to α2–3 and α2–6-linked sialic acids. Typical of Siglecs, the carboxyl group and side chain of sialic acid are essential for recognition, and mutation of a critical arginine residue in domain 1 abrogates binding. The underlying glycan structure also affects binding, with Galβ1–4Glc[NAc] being preferred. Siglec-9 shows closest homology to Siglec-7 and both belong to a Siglec-3/CD33-related subset of Siglecs (with Siglecs-5, -6, and -8). The Siglec-9 gene is on chromosome 19q13.3–13.4, in a cluster with all Siglec-3/CD33-related Siglec genes, suggesting their origin by gene duplications. A homology search of the Drosophila melanogaster and Caenorhabditis elegans genomes suggests that Siglec expression may be limited to animals of deuterostome lineage, coincident with the appearance of the genes of the sialic acid biosynthetic pathway. The Siglecs are a subfamily of I-type lectins (immunoglobulin superfamily proteins that bind sugars) that specifically recognize sialic acids. We report the cloning and characterization of human Siglec-9. The cDNA encodes a type 1 transmembrane protein with three extracellular immunoglobulin-like domains and a cytosolic tail containing two tyrosines, one within a typical immunoreceptor tyrosine-based inhibitory motif (ITIM). The N-terminal V-set Ig domain has most amino acid residues typical of Siglecs. Siglec-9 is expressed on granulocytes and monocytes. Expression of the full-length cDNA in COS cells induces sialic-acid dependent erythrocyte binding. A recombinant soluble form of the extracellular domain binds to α2–3 and α2–6-linked sialic acids. Typical of Siglecs, the carboxyl group and side chain of sialic acid are essential for recognition, and mutation of a critical arginine residue in domain 1 abrogates binding. The underlying glycan structure also affects binding, with Galβ1–4Glc[NAc] being preferred. Siglec-9 shows closest homology to Siglec-7 and both belong to a Siglec-3/CD33-related subset of Siglecs (with Siglecs-5, -6, and -8). The Siglec-9 gene is on chromosome 19q13.3–13.4, in a cluster with all Siglec-3/CD33-related Siglec genes, suggesting their origin by gene duplications. A homology search of the Drosophila melanogaster and Caenorhabditis elegans genomes suggests that Siglec expression may be limited to animals of deuterostome lineage, coincident with the appearance of the genes of the sialic acid biosynthetic pathway. biotinylated polyacrylamide signaling lymphocyte activation molecule SLAM-associated protein neural cell adhesion molecule bacterial artificial chromosome expressed sequence tag polymerase chain reaction enzyme-linked immunosorbent assay Sialic acids are a family of α-keto acids with 9-carbon backbones that are expressed abundantly in animals of the deuterostome lineage (1.Schauer R. Sialic Acids: Chemistry, Metabolism and Function, Cell Biology Monographs. Volume 10. Springer-Verlag, New York1982Crossref Google Scholar, 2.Varki A. Glycobiology. 1992; 2: 25-40Crossref PubMed Scopus (479) Google Scholar, 3.Kelm S. Schauer R. Int. Rev. Cytol. 1997; 175: 137-240Crossref PubMed Google Scholar). They are found mostly at distal positions of oligosaccharide chains of glycoproteins and glycolipids and are thus exposed to the extracellular environment, allowing them to be recognized during the initial contact of cells with various pathogenic agents such as viruses, bacteria, protozoa, and toxins (4.Varki A. FASEB J. 1997; 11: 248-255Crossref PubMed Scopus (488) Google Scholar, 5.Karlsson K.A. Mol. Microbiol. 1998; 29: 1-11Crossref PubMed Scopus (147) Google Scholar). The marked structural complexity of sialic acids can thus be interpreted as a result of evolutionary arms race between the hosts and the pathogens (6.Gagneux P. Varki A. Glycobiology. 1999; 9: 747-755Crossref PubMed Scopus (421) Google Scholar). Recent studies have revealed another prominent role of sialic acids, namely their functions in generating ligands for endogenous lectins (4.Varki A. FASEB J. 1997; 11: 248-255Crossref PubMed Scopus (488) Google Scholar). Siglecs (sialic acid-binding Igsuperfamily lectins) are a family of such sialic acid-recognizing lectins that have been recently defined (7.Crocker S. S. J. Schauer R. Varki A. Glycobiology. 1998; PubMed Google Scholar). proteins are all type 1 transmembrane with N-terminal Ig V-set by of Ig a transmembrane and a The V-set domain is the most in recognition, and the domain may also to the A. K.A. J. Google Scholar, S. P. J. PubMed Scopus Google Scholar, S. A. J. PubMed Scopus Google Scholar, Schauer R. S. J. PubMed Scopus Google Scholar). of the family have been in and shows cell on S. A. S. S. P. J. PubMed Scopus Google Varki A. S. J. PubMed Google and S. PubMed Google and S. A. Schauer R. S. A. P. PubMed Scopus Google and S. J. R. 1998; PubMed Google and S. Varki A. J. 1999; PubMed Scopus Google cells and R. S. R. A. J. 1999; PubMed Scopus Google Scholar, J. P. J. S. J. 1999; PubMed Scopus Google Scholar, Varki A. Glycobiology. PubMed Scopus Google and J. J. J. PubMed Scopus Google of the Siglecs have in the of immunoreceptor tyrosine-based inhibitory motif in their suggesting their in signaling and have been to be of by R. S. R. A. J. 1999; PubMed Scopus Google Scholar, J. 1999; PubMed Scopus Google Scholar, J. J. 1999; 29: PubMed Scopus Google Scholar). of a role by the studies PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, S. PubMed Scopus Google Scholar, R. 1997; PubMed Scopus Google Scholar). the the of sialic acid-binding of Siglecs is the between and S. A. 1998; PubMed Scopus Google suggests that sialic acid the signaling of of sialic acids is in animals of the deuterostome lineage in and their expression in another group of the and is (1.Schauer R. Sialic Acids: Chemistry, Metabolism and Function, Cell Biology Monographs. Volume 10. Springer-Verlag, New York1982Crossref Google A. Glycobiology. 1992; 2: 25-40Crossref PubMed Scopus (479) Google Scholar). evolutionary of is also are Siglec in the of sialic acids in J. A. Schauer R. 1992; PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, R. R. J. 1999; is that the expression of sialic acids and sialic acid lectins is that has for cDNA cloning of the report the cloning and characterization of a of Siglec family in and that is to a Siglec-3/CD33-related that have by gene duplications. We the expression and glycan of the The of sialic acids and Siglecs is also and of the of the of a PubMed Scopus Google and a elegans 1998; PubMed Scopus Google Siglec-9 cDNA encodes a protein with typical of Siglecs. The domain two amino acid residues critical in sialic acid Mol. 1998; PubMed Scopus Google arginine in in and amino acid in of that residues are with the carboxyl group and side chain of sialic Mol. 1998; PubMed Scopus Google Scholar). A in Siglec-9 the of amino acid the in is in contact with sialic acid The that Siglec-9 shows to mutation of residue in the of sialic acid in Mol. 1998; PubMed Scopus Google shows that the of side chain in is Siglecs. the of in that the between the arginine and carboxyl group of sialic acid is in of as is the with all Siglecs S. A. J. PubMed Scopus Google Scholar, Schauer R. S. J. PubMed Scopus Google Scholar, Varki A. Glycobiology. PubMed Scopus Google Scholar, J. 1999; PubMed Scopus Google Scholar, S. J. Cell 1997; PubMed Scopus Google cytosolic tail of Siglec-9 two The amino acid sequence the is found in the of immunoreceptor tyrosine-based inhibitory motif is the for the and J. 1997; Google Scholar, J. 1999; PubMed Scopus Google Scholar). The of motif in Siglec-9 to be motif is to be in the the sequence of the motif with in and have been to with R. S. R. A. J. 1999; PubMed Scopus Google Scholar, J. 1999; PubMed Scopus Google Scholar, J. J. 1999; 29: PubMed Scopus Google Scholar). the sequence the with is to the on J. Mol. 1999; PubMed Scopus Google Scholar). is that with motif in and superfamily expressed on and to of J. S. R. 1998; PubMed Scopus Google Scholar, S. J. 1999; Google Scholar). A mutation in human J. S. R. 1998; PubMed Scopus Google Scholar). motif in Siglec-9 with and the protein J. Mol. 1999; PubMed Scopus Google to be the of in as by revealed that Siglec-9 is expressed on granulocytes and monocytes. of expression of Siglec-9 on the expression found in the and may be to cells and to be by a The of Siglec-9 cells that can be in the with as of the Siglec-9 functions as of to role of as as that of another and is in both and α2–6-linked sialic acids. of sialic acid is Siglecs expressed on and and granulocytes and S. J. R. 1998; PubMed Google Scholar, J. P. J. S. J. 1999; PubMed Scopus Google Scholar, J. J. J. PubMed Scopus Google Scholar, Varki A. J. PubMed Scopus Google Scholar). and -6, S. A. S. S. P. J. PubMed Scopus Google Scholar, Varki A. S. J. PubMed Google Scholar, S. A. Schauer R. S. A. P. PubMed Scopus Google Scholar, S. Varki A. J. 1999; PubMed Scopus Google Scholar, Varki A. J. PubMed Scopus Google Scholar, S. Varki A. J. PubMed Scopus Google Scholar, A. J. 1997; PubMed Scopus Google Scholar). of by Siglec-9 is also of the for the underlying glycan as Siglec-9 is the Siglec that can recognize the structure is by the residue on the as is with to Siglec-9 between found in and found in and The of and with to Siglec functions is to that of the Siglecs by ligands may be to thus the cells that are Siglecs may be in a to that of cell expressed on by expressed on result in of on cell thus the cell to by cells Rev. 1999; PubMed Scopus Google Scholar). in in sialic acid expression with by may activation of the cells in the cell inhibitory genes are on chromosome Rev. 1999; PubMed Scopus Google the of the Siglecs -6, and are to both in sequence and S. J. R. 1998; PubMed Google Scholar, J. P. J. S. J. 1999; PubMed Scopus Google Scholar, Varki A. Glycobiology. PubMed Scopus Google Scholar, J. J. J. PubMed Scopus Google Scholar, PubMed Google Scholar, S. Cell 1997; PubMed Scopus Google and are as The genes for are all on chromosome The of cluster suggests that genes by gene at during We that the a to the human is that the has been is that of the gene in cluster of the of and are gene in of the such as P. R. S. A. R. Cell PubMed Scopus Google the gene cluster 1999; Google and the cell family suggesting that have been gene in is that are in J. PubMed Google that have of genes by of in S. A. PubMed Scopus Google Scholar). of the in of the Siglec-3/CD33-related is that is expressed in of cell type and shows of sialic acid the gene may have been for by functions in cell of the may their cloning also the of their expression in cell Ig superfamily genes are to and to be Siglec in elegans two of the most lineage result is with the that lineage is also to expression of sialic acids. the of homology search on the also the that lineage animals sialic acids. We found that both Drosophila genomes the genes for sialic acid genes in are and the of cells to sialic acids J. A. Schauer R. 1992; PubMed Scopus Google Scholar, R. R. J. 1999; Scholar, J. PubMed Scopus Google be in such as the of of of sialic acids the biosynthetic the that the of Siglecs during dependent on the expression of sialic acids in deuterostome lineage is to are Siglec in such as and are to of sialic acids. be that full-length amino acid of Siglecs in the homology search of Drosophila gene that homology and such as and the homology between gene and human Siglec proteins limited to the Ig domains and Siglecs are defined by sialic acid binding, homology in the Ig domain as Siglec The is as of 1997; PubMed Google shows to in the a of between two genes of of deuterostome and of sialic The that shows homology with proteins also that may be the closest to the of Siglec is that by gene another Siglec gene and to to proteins of the Siglec family in animals be to as as the of the of Siglec-9 and the Siglec-3/CD33-related in are in with another on Siglec-9 by J. and P. R. J. in of the Sialic acids are a family of α-keto acids with 9-carbon backbones that are expressed abundantly in animals of the deuterostome lineage (1.Schauer R. Sialic Acids: Chemistry, Metabolism and Function, Cell Biology Monographs. Volume 10. Springer-Verlag, New York1982Crossref Google Scholar, 2.Varki A. Glycobiology. 1992; 2: 25-40Crossref PubMed Scopus (479) Google Scholar, 3.Kelm S. Schauer R. Int. Rev. Cytol. 1997; 175: 137-240Crossref PubMed Google Scholar). They are found mostly at distal positions of oligosaccharide chains of glycoproteins and glycolipids and are thus exposed to the extracellular environment, allowing them to be recognized during the initial contact of cells with various pathogenic agents such as viruses, bacteria, protozoa, and toxins (4.Varki A. FASEB J. 1997; 11: 248-255Crossref PubMed Scopus (488) Google Scholar, 5.Karlsson K.A. Mol. Microbiol. 1998; 29: 1-11Crossref PubMed Scopus (147) Google Scholar). The marked structural complexity of sialic acids can thus be interpreted as a result of evolutionary arms race between the hosts and the pathogens (6.Gagneux P. Varki A. Glycobiology. 1999; 9: 747-755Crossref PubMed Scopus (421) Google Scholar). Recent studies have revealed another prominent role of sialic acids, namely their functions in generating ligands for endogenous lectins (4.Varki A. FASEB J. 1997; 11: 248-255Crossref PubMed Scopus (488) Google Scholar). Siglecs (sialic acid-binding Igsuperfamily lectins) are a family of such sialic acid-recognizing lectins that have been recently defined (7.Crocker S. S. J. Schauer R. Varki A. Glycobiology. 1998; PubMed Google Scholar). proteins are all type 1 transmembrane with N-terminal Ig V-set by of Ig a transmembrane and a The V-set domain is the most in recognition, and the domain may also to the A. K.A. J. Google Scholar, S. P. J. PubMed Scopus Google Scholar, S. A. J. PubMed Scopus Google Scholar, Schauer R. S. J. PubMed Scopus Google Scholar). of the family have been in and shows cell on S. A. S. S. P. J. PubMed Scopus Google Varki A. S. J. PubMed Google and S. PubMed Google and S. A. Schauer R. S. A. P. PubMed Scopus Google and S. J. R. 1998; PubMed Google and S. Varki A. J. 1999; PubMed Scopus Google cells and R. S. R. A. J. 1999; PubMed Scopus Google Scholar, J. P. J. S. J. 1999; PubMed Scopus Google Scholar, Varki A. Glycobiology. PubMed Scopus Google and J. J. J. PubMed Scopus Google Scholar). of the Siglecs have in the of immunoreceptor tyrosine-based inhibitory motif in their suggesting their in signaling and have been to be of by R. S. R. A. J. 1999; PubMed Scopus Google Scholar, J. 1999; PubMed Scopus Google Scholar, J. J. 1999; 29: PubMed Scopus Google Scholar). of a role by the studies PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, S. PubMed Scopus Google Scholar, R. 1997; PubMed Scopus Google Scholar). the the of sialic acid-binding of Siglecs is the between and S. A. 1998; PubMed Scopus Google suggests that sialic acid the signaling of Expression of sialic acids is in animals of the deuterostome lineage in and their expression in another group of the and is (1.Schauer R. Sialic Acids: Chemistry, Metabolism and Function, Cell Biology Monographs. Volume 10. Springer-Verlag, New York1982Crossref Google A. Glycobiology. 1992; 2: 25-40Crossref PubMed Scopus (479) Google Scholar). evolutionary of is also are Siglec in the of sialic acids in J. A. Schauer R. 1992; PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, R. R. J. 1999; is that the expression of sialic acids and sialic acid lectins is that has for cDNA cloning of the report the cloning and characterization of a of Siglec family in and that is to a Siglec-3/CD33-related that have by gene duplications. We the expression and glycan of the The of sialic acids and Siglecs is also and of the of the of a PubMed Scopus Google and a elegans 1998; PubMed Scopus Google Scholar). Siglec-9 cDNA encodes a protein with typical of Siglecs. The domain two amino acid residues critical in sialic acid Mol. 1998; PubMed Scopus Google arginine in in and amino acid in of that residues are with the carboxyl group and side chain of sialic Mol. 1998; PubMed Scopus Google Scholar). A in Siglec-9 the of amino acid the in is in contact with sialic acid The that Siglec-9 shows to mutation of residue in the of sialic acid in Mol. 1998; PubMed Scopus Google shows that the of side chain in is Siglecs. the of in that the between the arginine and carboxyl group of sialic acid is in of as is the with all Siglecs S. A. J. PubMed Scopus Google Scholar, Schauer R. S. J. PubMed Scopus Google Scholar, Varki A. Glycobiology. PubMed Scopus Google Scholar, J. 1999; PubMed Scopus Google Scholar, S. J. Cell 1997; PubMed Scopus Google cytosolic tail of Siglec-9 two The amino acid sequence the is found in the of immunoreceptor tyrosine-based inhibitory motif is the for the and J. 1997; Google Scholar, J. 1999; PubMed Scopus Google Scholar). The of motif in Siglec-9 to be motif is to be in the the sequence of the motif with in and have been to with R. S. R. A. J. 1999; PubMed Scopus Google Scholar, J. 1999; PubMed Scopus Google Scholar, J. J. 1999; 29: PubMed Scopus Google Scholar). the sequence the with is to the on J. Mol. 1999; PubMed Scopus Google Scholar). is that with motif in and superfamily expressed on and to of J. S. R. 1998; PubMed Scopus Google Scholar, S. J. 1999; Google Scholar). A mutation in human J. S. R. 1998; PubMed Scopus Google Scholar). motif in Siglec-9 with and the protein J. Mol. 1999; PubMed Scopus Google to be the of in as by revealed that Siglec-9 is expressed on granulocytes and monocytes. of expression of Siglec-9 on the expression found in the and may be to cells and to be by a The of Siglec-9 cells that can be in the with as of the Siglec-9 functions as of to role of as as that of another and is in both and α2–6-linked sialic acids. of sialic acid is Siglecs expressed on and and granulocytes and S. J. R. 1998; PubMed Google Scholar, J. P. J. S. J. 1999; PubMed Scopus Google Scholar, J. J. J. PubMed Scopus Google Scholar, Varki A. J. PubMed Scopus Google Scholar). and -6, S. A. S. S. P. J. PubMed Scopus Google Scholar, Varki A. S. J. PubMed Google Scholar, S. A. Schauer R. S. A. P. PubMed Scopus Google Scholar, S. Varki A. J. 1999; PubMed Scopus Google Scholar, Varki A. J. PubMed Scopus Google Scholar, S. Varki A. J. PubMed Scopus Google Scholar, A. J. 1997; PubMed Scopus Google Scholar). of by Siglec-9 is also of the for the underlying glycan as Siglec-9 is the Siglec that can recognize the structure is by the residue on the as is with to Siglec-9 between found in and found in and The of and with to Siglec functions is to that of the Siglecs by ligands may be to thus the cells that are Siglecs may be in a to that of cell expressed on by expressed on result in of on cell thus the cell to by cells Rev. 1999; PubMed Scopus Google Scholar). in in sialic acid expression with by may activation of the cells in the cell inhibitory genes are on chromosome Rev. 1999; PubMed Scopus Google the of the Siglecs -6, and are to both in sequence and S. J. R. 1998; PubMed Google Scholar, J. P. J. S. J. 1999; PubMed Scopus Google Scholar, Varki A. Glycobiology. PubMed Scopus Google Scholar, J. J. J. PubMed Scopus Google Scholar, PubMed Google Scholar, S. Cell 1997; PubMed Scopus Google and are as The genes for are all on chromosome The of cluster suggests that genes by gene at during We that the a to the human is that the has been is that of the gene in cluster of the of and are gene in of the such as P. R. S. A. R. Cell PubMed Scopus Google the gene cluster 1999; Google and the cell family suggesting that have been gene in is that are in J. PubMed Google that have of genes by of in S. A. PubMed Scopus Google Scholar). of the in of the Siglec-3/CD33-related is that is expressed in of cell type and shows of sialic acid the gene may have been for by functions in cell of the may their cloning also the of their expression in cell Ig superfamily genes are to and to be Siglec in elegans two of the most lineage result is with the that lineage is also to expression of sialic acids. the of homology search on the also the that lineage animals sialic acids. We found that both Drosophila genomes the genes for sialic acid genes in are and the of cells to sialic acids J. A. Schauer R. 1992; PubMed Scopus Google Scholar, R. R. J. 1999; Scholar, J. PubMed Scopus Google be in such as the of of of sialic acids the biosynthetic the that the of Siglecs during dependent on the expression of sialic acids in deuterostome lineage is to are Siglec in such as and are to of sialic acids. be that full-length amino acid of Siglecs in the homology search of Drosophila gene that homology and such as and the homology between gene and human Siglec proteins limited to the Ig domains and Siglecs are defined by sialic acid binding, homology in the Ig domain as Siglec The is as of 1997; PubMed Google shows to in the a of between two genes of of deuterostome and of sialic The that shows homology with proteins also that may be the closest to the of Siglec is that by gene another Siglec gene and to to proteins of the Siglec family in animals be to as as the of the of Siglec-9 and the Siglec-3/CD33-related The Siglec-9 cDNA encodes a protein with typical of Siglecs. The domain two amino acid residues critical in sialic acid Mol. 1998; PubMed Scopus Google arginine in in and amino acid in of that residues are with the carboxyl group and side chain of sialic Mol. 1998; PubMed Scopus Google Scholar). A in Siglec-9 the of amino acid the in is in contact with sialic acid The that Siglec-9 shows to mutation of residue in the of sialic acid in Mol. 1998; PubMed Scopus Google shows that the of side chain in is Siglecs. the of in that the between the arginine and carboxyl group of sialic acid is in of as is the with all Siglecs S. A. J. PubMed Scopus Google Scholar, Schauer R. S. J. PubMed Scopus Google Scholar, Varki A. Glycobiology. PubMed Scopus Google Scholar, J. 1999; PubMed Scopus Google Scholar, S. J. Cell 1997; PubMed Scopus Google Scholar). The cytosolic tail of Siglec-9 two The amino acid sequence the is found in the of immunoreceptor tyrosine-based inhibitory motif is the for the and J. 1997; Google Scholar, J. 1999; PubMed Scopus Google Scholar). The of motif in Siglec-9 to be motif is to be in the the sequence of the motif with in and have been to with R. S. R. A. J. 1999; PubMed Scopus Google Scholar, J. 1999; PubMed Scopus Google Scholar, J. J. 1999; 29: PubMed Scopus Google Scholar). the sequence the with is to the on J. Mol. 1999; PubMed Scopus Google Scholar). is that with motif in and superfamily expressed on and to of J. S. R. 1998; PubMed Scopus Google Scholar, S. J. 1999; Google Scholar). A mutation in human J. S. R. 1998; PubMed Scopus Google Scholar). motif in Siglec-9 with and the protein J. Mol. 1999; PubMed Scopus Google to be the of in as by revealed that Siglec-9 is expressed on granulocytes and monocytes. of expression of Siglec-9 on the expression found in the and may be to cells and to be by a The of Siglec-9 cells that can be in the with as of the Siglec-9 functions as of to role of as as that of another and is in Siglec-9 both and α2–6-linked sialic acids. of sialic acid is Siglecs expressed on and and granulocytes and S. J. R. 1998; PubMed Google Scholar, J. P. J. S. J. 1999; PubMed Scopus Google Scholar, J. J. J. PubMed Scopus Google Scholar, Varki A. J. PubMed Scopus Google Scholar). and -6, S. A. S. S. P. J. PubMed Scopus Google Scholar, Varki A. S. J. PubMed Google Scholar, S. A. Schauer R. S. A. P. PubMed Scopus Google Scholar, S. Varki A. J. 1999; PubMed Scopus Google Scholar, Varki A. J. PubMed Scopus Google Scholar, S. Varki A. J. PubMed Scopus Google Scholar, A. J. 1997; PubMed Scopus Google Scholar). of by Siglec-9 is also of the for the underlying glycan as Siglec-9 is the Siglec that can recognize the structure is by the residue on the as is with to Siglec-9 between found in and found in and The of and with to Siglec functions is to that of the Siglecs by ligands may be to thus the cells that are Siglecs may be in a to that of cell expressed on by expressed on result in of on cell thus the cell to by cells Rev. 1999; PubMed Scopus Google Scholar). in in sialic acid expression with by may activation of the cells in the cell inhibitory genes are on chromosome Rev. 1999; PubMed Scopus Google the of the Siglecs -6, and are to both in sequence and S. J. R. 1998; PubMed Google Scholar, J. P. J. S. J. 1999; PubMed Scopus Google Scholar, Varki A. Glycobiology. PubMed Scopus Google Scholar, J. J. J. PubMed Scopus Google Scholar, PubMed Google Scholar, S. Cell 1997; PubMed Scopus Google and are as The genes for are all on chromosome The of cluster suggests that genes by gene at during We that the a to the human is that the has been is that of the gene in cluster of the of and are gene in of the such as P. R. S. A. R. Cell PubMed Scopus Google the gene cluster 1999; Google and the cell family suggesting that have been gene in is that are in J. PubMed Google that have of genes by of in S. A. PubMed Scopus Google Scholar). of the in of the Siglec-3/CD33-related is that is expressed in of cell type and shows of sialic acid the gene may have been for by functions in cell of the may their cloning also the of their expression in cell Ig superfamily genes are to and to be Siglec in elegans two of the most lineage result is with the that lineage is also to expression of sialic acids. the of homology search on the also the that lineage animals sialic acids. We found that both Drosophila genomes the genes for sialic acid genes in are and the of cells to sialic acids J. A. Schauer R. 1992; PubMed Scopus Google Scholar, R. R. J. 1999; Scholar, J. PubMed Scopus Google be in such as the of of of sialic acids the biosynthetic the that the of Siglecs during dependent on the expression of sialic acids in deuterostome lineage is to are Siglec in such as and are to of sialic acids. be that full-length amino acid of Siglecs in the homology search of Drosophila gene that homology and such as and the homology between gene and human Siglec proteins limited to the Ig domains and Siglecs are defined by sialic acid binding, homology in the Ig domain as Siglec The is as of 1997; PubMed Google shows to in the a of between two genes of of deuterostome and of sialic The that shows homology with proteins also that may be the closest to the of Siglec is that by gene another Siglec gene and to to proteins of the Siglec family in animals be to as as the of the of Siglec-9 and the Siglec-3/CD33-related in are in with another on Siglec-9 by J. and P. R. J. in of the The are in with another on Siglec-9 by J. and P. R. J. in of the We and for and