Characterization of siglec-5, a novel glycoprotein expressed on myeloid cells related to CD33.
We describe the characterization of siglec-5 (sialic acid-binding Ig-like lectin-5), a novel transmembrane member of the immunoglobulin superfamily, highly related to the myeloid antigen, CD33. A full-length cDNA encoding siglec-5 was isolated from a human activated monocyte cDNA library. Sequencing predicted that siglec-5 contains four extracellular immunoglobulin-like domains, the N-terminal two of which are 57% identical to the corresponding region of CD33. The cytoplasmic tail is also related to that of CD33, containing two tyrosine residues embodied in immunoreceptor tyrosine-based inhibitory motif-like motifs. The siglec-5 gene was shown to map to chromosome 19q13.41-43, closely linked to the CD33 gene. When siglec-5 was expressed on COS cells or as a recombinant protein fused to the Fc region of human IgG1, it was able to mediate sialic acid-dependent binding to human erythrocytes and soluble glycoconjugates, suggesting that it may be involved in cell-cell interactions. By using specific antibodies, siglec-5 was found to have an expression pattern distinct from that of CD33, being present at relatively high levels on neutrophils but absent from leukemic cell lines representing early stages of myelomonocytic differentiation. Western blot analysis of neutrophil lysates indicated that siglec-5 exists as a disulfide-linked dimer of approximately 140 kD.
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The Wellcome Trust Building, Department of Biochemistry, University of Dundee, Dundee, Scotland, UK; the Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK; and Human Genome Sciences Inc, Rockville, MD, USA.
Freeman
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S
Forbes
G
G
Ni
J
J
Zhang
M
M
Cepeda
M
M
Gentz
R
R
Augustus
M
M
Carter
K C
KC
Crocker
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PR
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D002236:Carbohydrate Conformation; D002460:Cell Line; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000097:blood; D007951:Leukemia, Myeloid / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000097:blood; D009504:Neutrophils / Q000737:chemistry; D012397:Rosette Formation; D017386:Sequence Homology, Amino Acid; D063268:Sialic Acid Binding Ig-like Lectin 3; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D037102:Lectins; D008562:Membrane Glycoproteins; C114531:SIGLEC5 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3; D019158:N-Acetylneuraminic Acid