Siglec-E Products

Description

Siglecs are sialic acid specific I‑type lectins that are characterized by an extracellular domain (ECD) with an N‑terminal Ig‑like V‑set domain followed by varying numbers of Ig‑like C2‑set domains (1, 2). Mouse Siglec‑E, also known as Myeloid Inhibitory Siglec (MIS), is an 80 ‑ 85 kDa member of the CD33‑related subfamily of Siglecs. It consists of a 335 amino acid (aa) ECD with one Ig‑like V‑set domain and two Ig‑like C2‑set domains, a 21 aa transmembrane segment, and a 93 aa cytoplasmic domain that contains two immunoreceptor tyrosine‑based inhibitory motifs (ITIM) (3, 4). Rodent and primate Siglec gene families have significantly diverged, and Siglec‑9 is the most likely human ortholog of mouse Siglec‑E (1). Within the ECD, mouse Siglec‑E shares 56% and 80% aa sequence identity with human Siglec‑9 and rat Siglec‑E, respectively. Siglec‑E is expressed as a heavily N‑glycosylated disulfide‑linked homodimer and shows binding preference for disialic acids in the alpha 2‑8 linkage (3, 5). It is expressed on the surface of several hematopoietic cell types including neutrophils, NK cells, monocytes, peritoneal macrophages and B1 cells, and splenic myeloid dendritic cells and marginal zone B cells (5). Tyrosine phosphorylation of the cytoplasmic ITIMs mediates the association of Siglec‑E with the phosphatases SHP‑1 and SHP‑2 (3, 4). Siglec‑E is up‑regulated and additionally phosphorylated following cellular stimulation by a variety of TLR agonists (6). Siglec‑E signaling negatively regulates the LPS‑induced production of TNF‑ alpha and IL‑6 by macrophages (4, 6). Its up‑regulation in macrophages parallels the development of endotoxin tolerance (6). Siglec‑E recognition of sialylated determinants on virulent T. cruzi contributes to the suppression of dendritic cell IL‑12 p40 production (7).

Bioinformatics

Uniprot	Q6PJ50
Product By Gene ID	8778
Alternate Names	CD170;CD33L2;OBBP2;OB-BP2;Sialic acid-binding Ig-like lectin 5;SIGLEC5;SIGLEC-5 SiglecE Siglec-E