Conserved Siglecs

What Is Conserved Siglecs?

Siglecs can be classified into many groups using various categorization criteria. For example, Siglecs can be divided into two groups CD33-Related Siglecs and conserved Siglecs, depending on how much of their sequence is conserved. The word "conserved" actually refers to the fact that conserved Siglecs have been maintained throughout evolution and are constant in rodents and humans. CD BioGlyco has established a Microarray Platform and offers Sialic Acid Microarray and Lectin Microarray Assay for customers to study conversed Siglecs.

Fig.1 Presence of Siglec family members in selected mammalian species. (Bornhöfft, et al., 2018)

Conversed Siglecs Family

There are four members of the Conserved family, Siglec-1 (Sialoadhesin/ CD169), Siglec-2 (CD22), Siglec-4 (myelin-associated glycoprotein/MAG), and Siglec-15, The sequence identity between them is low. but they have clear orthologues in all mammalian species examined. Due to these Siglecs all binding to sialic acid, CD BioGlyco provides Sialic Acid Analysis Service for customers to study the ability of Siglecs to bind to sialic acid.

Siglec-1 (Sialoadhesin/ CD169)

Only mature dendritic cells, monocyte progenitors, and macrophages contain Siglec-1, sometimes referred to as Sialoadhesin. Through the high-affinity ligand NeuAc2-3Gal on N- and O-linked sugars and glycolipids, it primarily functions in cell adhesion. Siglec-1 has 16 C2-set domains that isolate its binding site from the cell surface and 16 V-set domains that bind ligands.

Siglec-2 (CD22)

With an immunoreceptor tyrosine-based inhibition motif (ITIM) that conveys immunosuppressive signals, Siglec-2 is a member of the immunosuppressive siglecs family. It can lessen phagocytosis, lessen inflammation, and suppress both the pathogen- and danger-associated molecular patterns (DAMP and PAM).

Siglec-4 (MAG)

The most conserved protein in all vertebrates, Siglec-4, preferentially binds to sialic acid that has been related to D-galactose (2-3). MAG, also known as native Siglec-4, is solely expressed by oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system. It has five Ig-like domains: an N-terminal group V domain and four group C2 domains.

Siglec-15

Siglec-15 lacks a cytoplasmic tail and possesses an extracellular domain with two Ig-like domains. Siglec-15 activates signaling by attaching to the adaptor proteins DAP10 and DAP12 via transmembrane Lys residues, in contrast to most inhibitory receptors.

Roles in Biology

When Siglec-2 interacts with BCR, BCR signaling is suppressed. Additionally, Siglec-2 has been linked to toll-like receptor signaling, which connects innate and adaptive immune responses. Notably, Siglec-2 is a prime target for B-cell malignancies due to its restricted expression on B cells and its function in preventing BCR activation. B-cell cancers are treated with CD22-targeting CAR-T cells or CAR-T cells that simultaneously target CD19 and CD22.
Siglec-4 is a cell adhesion molecule that transports the carbohydrates of the human natural killer 1 (HNK-1). The anticancer efficacy of a Siglec-4-derived long spacer for CAR-T therapy is comparable to that of a CD8 spacer, but it is suggested to target membrane-proximal epitopes more effectively with reduced CNS toxicity.
To the sialyl-Tn structure seen in malignancies, Siglec-15 can bind. This is linked to 2,3-linked sialic acid as well as a bad prognosis in patients with ovarian, colorectal, or stomach cancer. For patients with anti-PD-1 / PD-L1 resistance, Siglec-15 is now emerging as a novel immunosuppressant because it is mutually exclusive with PD-L1.

CD BioGlyco provides excellent microarray analysis services and can customize microarrays to meet various research needs. We want to be your assistant in the field of Siglecs research, so please contact us if you are interested in our services.

References:

Bornhöfft, K.F.; et al. Siglecs: A journey through the evolution of sialic acid-binding immunoglobulin-type lectins. Developmental & Comparative Immunology. 2018, 86: 219–231.
Jiang, K.Y.; et al. The intriguing roles of SIGLEC family members in the tumor microenvironment. Biomarker Research. 2022, 10(1).

This service is for Research Use Only, not intended for any clinical use.