SIGLEC10
Description
The SIGLEC10 (sialic acid binding Ig like lectin 10) is a protein-coding gene located on chromosome 19.
Sialic acid-binding Ig-like lectin 10 is a protein that in humans is encoded by the SIGLEC10 gene. Siglec-G is often referred to as the murine paralog of human Siglec-10. Like most but not all other Siglecs, Siglec-10 bears an ITIM (Immunoreceptor tyrosine-based inhibitory motif) within its cytoplasmic domain. Siglec-10 is a ligand for CD52, the target of the therapeutic monoclonal antibody Alemtuzumab. It is also reported to bind to Vascular adhesion protein 1 (VAP-1) and to the co-stimulatory molecule CD24 also known as HSA (Heat-stable antigen). SIGLECs are members of the immunoglobulin superfamily that are expressed on the cell surface. Most SIGLECs have 1 or more cytoplasmic immune receptor tyrosine-based inhibitory motifs, or ITIMs.
Siglec-10 is a putative adhesion molecule that binds to cells in a sialic acid-dependent manner, preferentially recognizing alpha-2,3- or alpha-2,6-linked sialic acid. Its sialic acid recognition site can be masked by interactions with sialic acids on the same cell surface. In immune responses, Siglec-10 acts as an inhibitory receptor, blocking signal transduction through dephosphorylation of signaling molecules. This inhibition is achieved by recruiting cytoplasmic phosphatases via their SH2 domains upon ligand-induced tyrosine phosphorylation. Siglec-10 plays a role in negatively regulating B-cell antigen receptor signaling, where its inhibition of B cell activation depends on PTPN6/SHP-1. In association with CD24, Siglec-10 may selectively suppress immune responses to danger-associated molecular patterns (DAMPs) like HMGB1, HSP70, and HSP90. This association may also regulate the immune responses of natural killer (NK) cells. Siglec-10 contributes to the control of autoimmunity. During initiation of adaptive immune responses by CD8-alpha(+) dendritic cells, Siglec-10 inhibits cross-presentation by hindering the formation of MHC class I-peptide complexes. This function appears to involve the recruitment of PTPN6/SHP-1, which dephosphorylates NCF1 of the NADPH oxidase complex, promoting phagosomal acidification.
SIGLEC10 is also known as PRO940, SIGLEC-10, SLG2.
Associated Diseases
- COVID-19
- common variable immunodeficiency
- combined immunodeficiency with skin granulomas
- BENTA disease
- classic Hodgkin lymphoma
- immunodeficiency 18
- isolated agammaglobulinemia
- immunodeficiency 62
- severe combined immunodeficiency due to CTPS1 deficiency
- immunodeficiency, common variable, 14
- severe combined immunodeficiency due to CARD11 deficiency
- immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia
- agammaglobulinemia 10, autosomal dominant
- immunodeficiency 105
- neutropenia, severe congenital, 2, autosomal dominant
- hyper-IgM syndrome type 3
- inborn error of immunity
- immunodeficiency, common variable, 4
- immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias
