|CD169||SIGLEC-1 (sialic acid-binding Ig-like lectin 1, sialoadhesin), SN (sialoadhesin)|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Lineage Restricted Molecule|
Type 1 glycoprotein
|180 / 180|
200 / 200
|CD169 sialoadhesin (SN) is expressed by macrophages with a strong expression by perifollicular macrophages in the spleen, sinsusoidal and subcapsular macrophages in lymph nodes, stromal macrophages in bone marrow and inflammatory macrophages associated with rheumatoid arthritis and atherosclerosis. Expression is on tissue macrophages and secondary lymphoid organs. Macrophages of the liver, gut and lung display moderate expression but there is no expression on microgial cells in the brain. Expression is induced on monocytes in vitro by IFN-g, TNF-a or autologous serum. |
|MOLECULAR FAMILY NAME: Belong to the immunoglobulin gene superfamily.|
CD169 is a single-pass type-1 709 aa glycoprotein. It contains a leader peptide, a large extracellular domain which contains 16 Ig-like C2-type domains, 1 Ig-like N-terminal V-type domain which mediates binding to conserved sialic acid and 14 potential N-glycosylation sites , a transmembrane domain and a poorly conserved 47 residue cytoplasmic tail with 2 potential phosphorylation sites but lacks ITIM motifs. The short cytoplasmic domain contains a PKC motif and CK2 phosphorylation sites and is poorly conserved between man and mouse, suggesting primarily an extracellular role, namely cell-cell or cell-matrix interactions. It is the member of a structurally related group of IgSF domain-containing sialic acid binding proteins called sialoadhesin (SN) family, which includes CD22, CD33 and myelin-associated glycoprotein (MAG). Members of this family share ~35% identity between their 2-4 membrane-distal IgSF domains. Like other members of the SN family, SN is predicted to have an unusual disulfide bond between b strands B and E in domain 1 and a disulfide bond between domains 1 and 2. The CD169 gene is the only known siglec not found on human chromosome 19.
Alternative splicing yields 3 different isoforms in human. There is 1 mRNA transcript of 7.5 kb in man and 2 of 6.5 kb and ~8 kb in the mouse, resulting from an alternative stop codon which gives rise to a shortened 3"UTR. Mouse CD169 has 2 alternatively spliced forms were characterized. There is 1 which predicts a soluble secreted 3-domain form and the other a soluble secreted 16-domain form. Identification of 2 splice isoforms have been made which encode soluble proteins truncated after the 3rd and 16th IgSF domain, respectively. Domains 4-17 of SN are made up of 7 homologous tandem repeats consisting of a short and a long IgSF domain.
Alternative splicing of CD169 produces an isoform encoding a protein isoform that is soluble rather than membrane-bound, however, the full length nature of this variant has not been determined. CD169 has 14 potential N-glycosylation sites in the extracellular domain but little glycosylation is predicted because the actual Mr is similar to the predicted Mr. Cell-specific glycoforms, bearing SO4-4-GalNAc, bind to the cysteine-rich domain of the mannose receptor CD206. There is 1 potential PKC and CK2 phosphorylation site in the cytoplasmic tail.
|CD169 binds to sialoglycoconjugates NeuAca2 ->3Galb1 -3(4)GlcAc and NeuAca2 -3Galb1 ->3GalNAc which are present on glycoproteins and glycolipids. The sialic acid binding site has been localized to the GFCC'C'' b sheet of the membrane-distal IgSF domain and includes a conserved arginine of a 97 residue. CD169 has two known counter-receptors, mucin CD227 on breast cancer cells and erythroid cells and CD43 (leukosialin) on T cells.|
LIGANDS AND MOLECULES ASSOCIATED WITH CD169
|CD169 is an adhesion and a macrophage-restricted cellular interaction molecule that binds glycolipids and glycoproteins with sialylated ligands specifically sialic acid in the a-2,3-glycosidic lineage. The extension of CD169 from the macrophage cell surface enables it to interact with sialic acids with interference from sialic acid expressed by the same cell. High level expression of CD169 by stromal macrophages interacting with developing myeloid cells, particularly erythroid cells in bone marrow, suggests a role in myeloid cell development. The binding is on hemopoietic cells, particularly neutrophils, but also on monocytes, NK and B cells, and a subset of CD8+ T lymphocytes. CD169 can mediate adhesion to lymphocytes in the spleen section overlay assays. The encoded protein in SIGLEC1 is a lectin-like adhesion molecule that binds glycoconjugate ligands on cell surfaces in terminal sialic acid residues carried on as yet unidentified glycoprotein counter-receptors. CD169 mediates cell-cell and cell-matrix interactions such as stromal macrophage-myeloid cell contacts in the bone marrow. It may function as a pattern of self/non-self recognition receptor and mediate negative signals into the cell. CD169 is a non-phagocytic receptor, but may facilitate phagocytosis. CD169 is one of the prototypic members of the Siglec family of cellular interaction molecules and has been designated Siglec-1. Murine studies of allogenic tumor rejection indicate that CD169 may play a role in leukocyte trafficking and in T-cell effector functions.|
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD169 IN INTACT ANIMAL
CD169 is highly expressed on macrophages and is involved in mediating cell-cell interactions. The is expression in chronically inflamed tissues, such as rheumatoid synovium and atherosclerotic plaques suggesting a role in inflammation. There is a striking difference in the ligand density between human and chimpanzee cells, associated with a difference in the distribution of siglec-1 itself in the spleen. CD169 binds to MUC-1, CD227 on breast epithelial cells and may have a role in macrophage-tumor cell interactions in breast cancer. CD169+ macrophage-T cell interactions play a role in allogeneic tumor rejection in mice. CD169 may also play a role in hemopoiesis. CD169 recognizes sialic acids expressed by some microbial pathogens such as Neisseria sp. CD169 deficient macrophages have a capacity to bind Neisseria.
|MOLECULAR INTERACTIONS -|
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD169: No information.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD169: No information.
Database accession numbers
Revised June 25, 2008