Description
Sialic acid-binding immunoglobulin-like lectin 2 (Siglec-2), also known as B-cell receptor CD22 or B-lymphocyte cell adhesion molecule (BL-CAM), is a I-type (Ig-type) lectin belonging to the sialoadhesin subclass of the immunoglobulin superfamily (1). Fourteen human and nine mouse Siglecs have been characterized and are divided into 2 families: CD33 related and evolutionarily conserved (2, 3). The extracellular domain (ECD) of Siglecs are characterized by an N-terminal Ig-like V-type domain, which mediates sialic acid binding, followed by varying numbers of Ig-like C2-type domains (1 -3). The predominant form of human Siglec-2 contains a N-terminal Ig-like V-type domain, six Ig-like C2-type domains, a transmembrane region and a cytoplasmic tail with six tyrosine residues and four immunoreceptor tyrosine-based inhibition motifs (ITIMs) (1 - 3). A variant form of Siglec-2 missing two Ig-like C2-type domains along with a truncated cytoplasmic tail has also been identified (4). The mature ECD of human Siglec-2 shares 59% and 58% amino acid sequence identity with mouse and rat Siglec-2, respectively. Siglec-2 is an adhesion molecule that preferentially binds alpha 2,6- linked sialic acid on the same (cis) or adjacent (trans) cells (5). Besides its role as an adhesion molecule, Siglec-2 is a coreceptor that physically interacts with B-cell receptor (BCR), negatively regulating BCR signals by recruiting tyrosine phosphatase SHP-1 to its ITIMs. Phosphorylated Siglec-2 can also interact with other intracellular effector proteins such as Syk, PLC gamma, PI3 kinase and Grb-2, suggesting it may play a role in positive signaling (2). Another function of Siglec-2 is that it mediates the anti-phagocytic effect of alpha 2,6-linked sialic acid, and inhibition of Siglec-2 promotes the clearance of myelin debris, amyloid-beta oligomers and alpha -synuclein fibrils in vivo (6). Siglec-2 also plays a role in autoimmunity and has great potential for Siglec-2-based immunotherapeutics for the treatment of autoimmune diseases such as systemic lupus erythematosus (SLE) (7). Our Avi-tag Biotinylated Recombinant Human Siglec-2 features biotinylation at a single site contained within the Avi-tag, a unique 15 amino acid peptide. Protein orientation will be uniform when bound to streptavidin-coated surface due to the precise control of biotinylation and the rest of the protein is unchanged so there is no interference in the protein's bioactivity