SIGLEC1
Description
The SIGLEC1 (sialic acid binding Ig like lectin 1) is a protein-coding gene located on chromosome 20.
Sialoadhesin (SIGLEC-1) is a cell adhesion molecule found on the surface of macrophages. It is found in especially high amounts on macrophages of the spleen, liver, lymph node, bone marrow, colon, and lungs. Soluble SIGLEC-1 is a biomarker of monocyte-macrophage activation in systemic lupus erythematosus (SLE) and other autoimmune disorders. In patients with rheumatoid arthritis, the protein has been found in great amounts on macrophages of the affected tissues. It is defined as an I-type lectin, since it contains 17 immunoglobulin (Ig) domains (one variable domain and 16 constant domains), and thus also belongs to the immunoglobulin superfamily (IgSF). Sialoadhesin binds to certain molecules called sialic acids. During this binding process a salt bridge (protein) is formed between a highly conserved arginine residue (from the v-set domain to the 3'-sialyllactose) and the carboxylate group of the sialic acid. Since sialoadhesin binds sialic acids with its N-terminal IgV-domain, it is also a member of the SIGLEC family. Alternate names for sialoadhesin include siglec-1 and CD169 (cluster of differentiation 169). Sialoadhesin predominantly binds neutrophils, but can also bind monocytes, natural killer cells, B cells and a subset of cytotoxic T cells by interacting with sialic acid molecules in the ligands on their surfaces.
SIGLEC1 is a macrophage-restricted adhesion molecule that binds to lymphocytes, including granulocytes, monocytes, natural killer cells, B-cells and CD8 T-cells in a sialic acid dependent manner. It plays a crucial role in limiting bacterial dissemination by engaging sialylated bacteria to promote effective phagocytosis and antigen presentation for the adaptive immune response (PubMed:12940982, PubMed:33489013). SIGLEC1 mediates the uptake of various enveloped viruses via sialic acid recognition and subsequently induces the formation of intracellular compartments filled with virions (VCCs) (PubMed:28129379). In turn, it enhances macrophage-to-T-cell transmission of several viruses including HIV-1 or SARS-CoV-2 (PubMed:28129379, PubMed:34782760). SIGLEC1 acts as an endocytic receptor mediating clathrin dependent endocytosis. It preferentially binds to alpha-2,3-linked sialic acid (PubMed:12940982). SIGLEC1 binds to SPN/CD43 on T-cells (By similarity). SIGLEC1 may play a role in hemopoiesis. SIGLEC1 plays a role in the inhibition of antiviral innate immune by promoting TBK1 degradation via TYROBP and TRIM27-mediated ubiquitination (PubMed:26358190).
SIGLEC1 is also known as CD169, SIGLEC-1, SN.
