Siglec-7: a sialic acid-binding lectin of the immunoglobulin superfamily.
The Siglecs are a recently discovered family of sialic acid-binding lectins of the immunoglobulin (Ig) superfamily. We report a molecule showing homology to the six first reported Siglecs, with the closest relationship to Siglec-3(CD33), Siglec-5, and Siglec-6(OBBP-1). The extracellular portion has two Ig-like domains, with the amino-terminal V-set Ig domain including amino acid residues known to be involved in sialic acid recognition by other Siglecs. The cytoplasmic domain has putative sites of tyrosine phosphorylation shared with some Siglecs, including an Immuno-receptor Tyrosine-based Inhibitory Motif (ITIM). Expression of the full-length cDNA induces sialic acid-dependent binding to human erythrocytes. A recombinant chimeric form containing the extracellular Ig domains selectively recognizes the sequence Neu5Acalpha2-6Galbeta1-4Glc, and binding requires the side chain of sialic acid. Mutation of an arginine residue predicted to be critical for sialic acid binding abolishes both interactions. Taken together, our findings justify designation of the molecule as Siglec-7. Analysis of bacterial artificial chromosome (BAC) clones spanning the known human genomic location of Siglec-3 indicates that the Siglec-7 gene is also located on chromosome 19q13.3-13.4. Human tissues show strong expression of Siglec-7 mRNA in spleen, peripheral blood leukocytes, and liver. The combination of an extracellular sialic acid binding site and an intracellular ITIM motif suggests that this molecule is involved in trans-membrane regulatory signaling reactions.
Angata
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Glycobiology Research and Training Center, Department of Medicine and Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
Varki
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D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D019556:COS Cells; D002888:Chromosomes, Human, Pair 19; D018076:DNA, Complementary / Q000737:chemistry; D004912:Erythrocytes / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D037102:Lectins; D007962:Leukocytes / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D017385:Sequence Homology; D013154:Spleen / Q000737:chemistry; D014162:Transfection
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018076:DNA, Complementary; D037102:Lectins; D012333:RNA, Messenger; C402206:SIGLEC7 protein, human; D019158:N-Acetylneuraminic Acid