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Updated: Jul 15, 2026
09:37
An Integrated Approach for Microprotein Identification and Sequence Analysis
Published on: July 12, 2022
Siglec-15: an immune system Siglec conserved throughout vertebrate evolution
Takashi Angata1, Yukako Tabuchi, Kazunori Nakamura
1Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan. takashi-angata@aist.go.jp
Glycobiology
|May 8, 2007
Summary
Researchers discovered Siglec-15, a novel vertebrate immune receptor recognizing specific sialylated glycans. This activating receptor, found on immune cells, plays a conserved role in vertebrate immunity.
Area of Science:
- Immunology
- Glycobiology
- Molecular Biology
Background:
- Sialic acid-binding immunoglobulin-like lectins (Siglecs) are cell-surface receptors crucial for recognizing sialylated glycans in vertebrates.
- The functional diversity and evolutionary conservation of Siglecs are key areas of investigation in immune system regulation.
Purpose of the Study:
- To identify and characterize a novel Siglec, designated Siglec-15.
- To elucidate the molecular structure, ligand specificity, and signaling potential of Siglec-15.
- To investigate the evolutionary conservation and potential immune regulatory role of Siglec-15 across vertebrate species.
Main Methods:
- Protein characterization of Siglec-15, including its domain structure (immunoglobulin-like domains, transmembrane domain with lysine, cytoplasmic tail).
- Expression analysis of Siglec-15 in human immune cells (macrophages, dendritic cells) from spleen and lymph nodes.
- Ligand binding assays to determine the preferred glycan structure recognized by Siglec-15 (Neu5Acalpha2-6GalNAcalpha-).
- Co-immunoprecipitation and signaling pathway analysis to identify associated adaptor proteins (DAP12, DAP10) and confirm activating function.
Main Results:
- Siglec-15 is a type-I transmembrane protein expressed on human macrophages and dendritic cells.
- Siglec-15 specifically binds to Neu5Acalpha2-6GalNAcalpha- structures.
- Siglec-15 associates with DAP12 and DAP10 via a transmembrane lysine residue, functioning as an activating signaling molecule.
- Siglec-15 is the second activating human Siglec identified and lacks an inhibitory counterpart.
- Orthologs of Siglec-15 are broadly conserved across vertebrates, unlike other immune system Siglecs.
Conclusions:
- Siglec-15 represents a novel, broadly conserved activating receptor within the vertebrate immune system.
- Its unique evolutionary conservation suggests a fundamental regulatory role in innate and adaptive immunity across diverse vertebrate species.
- Siglec-15's activating nature, distinct from inhibitory Siglecs, highlights its specific contribution to immune cell function.
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