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sialic acid binding Ig like lectin 8

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 3012

Nomenclature: sialic acid binding Ig like lectin 8

Abbreviated Name: SIGLEC8

Family: CD33-related SIGLECs

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 499 19q13.33-q13.41 SIGLEC8 sialic acid binding Ig like lectin 8
Mouse 1 569 7 B3 Siglecf sialic acid binding Ig-like lectin F
Rat 1 - 1q22 Siglec8 sialic acid binding Ig-like lectin 8
Previous and Unofficial Names Click here for help
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Immunopharmacology Comments
SIGLEC8 is a single-pass type I membrane protein. It is a member of the CD33-like subgroup of SIGLECs, and like the other members of this subgroup it carries a conserved cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM) which facilitates its role as an inhibitory receptor on the surface of mast cells and eosinophils [3,5]. Endogenous ligands for SIGLEC8 are sialoglycan ligands that are upregulated on the surfaces of inflamed cells and tissues [4]. Receptor-ligand engagement down-regulates onging inflammation.

Blocking SIGLEC8 is being investigated as a novel mechanism to reduce pathological symptoms in diseases that are driven by aberrant eosinophil and/or mast cell activation (e.g. eosinophilic gastritis, mastocytosis, urticaria and severe allergic conjunctivitis) [1,6-9]. For example, Allakos have an anti-SIGLEC8 monoclonal antibody named antolimab (AK002) [10] that is in early stage clinical trials for various eosinophilic diseases and mastocytosis, and which has been granted FDA orphan drug designation for the treatment of eosinophilic gastritis (in January 2018) [2]. Click here to link to's full list of AK002 trials.
Cell Type Associations
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   mature eosinophil (CL:0000041)
basophil (CL:0000767)
References:  5
Immuno Cell Type:  Mast cells
Cell Ontology Term:   mast cell (CL:0000097)
References:  5
Immuno Process Associations
Immuno Process:  Antigen presentation
General Comments
SIGLEC8 is an I-type lectin that is expressed only on human eosinophils, basophils and mast cells [5]. It is an inhibitory receptor that engages sialoglycan ligands to diminish ongoing inflammation.
This protein contains an immunoglobulin (Ig)-like domain that resembles the antibody variable domain, that has been coined the 'V-set domain'. The genes for all human V-set domain containing proteins are listed in HGNC gene group 590.


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1. Bochner BS. (2016) "Siglec"ting the allergic response for therapeutic targeting. Glycobiology, 26 (6): 546-52. [PMID:26911285]

2. FDA. humanized non-fucosylated anti-siglec-8 monoclonal antibody (IgG1). Accessed on 02/07/2018. Modified on 02/07/2018. US FDA Orphan Drug Designations and Approvals,

3. Floyd H, Ni J, Cornish AL, Zeng Z, Liu D, Carter KC, Steel J, Crocker PR. (2000) Siglec-8. A novel eosinophil-specific member of the immunoglobulin superfamily. J Biol Chem, 275 (2): 861-6. [PMID:10625619]

4. Jia Y, Yu H, Fernandes SM, Wei Y, Gonzalez-Gil A, Motari MG, Vajn K, Stevens WW, Peters AT, Bochner BS et al.. (2015) Expression of ligands for Siglec-8 and Siglec-9 in human airways and airway cells. J Allergy Clin Immunol, 135 (3): 799-810.e7. [PMID:25747723]

5. Kikly KK, Bochner BS, Freeman SD, Tan KB, Gallagher KT, D'alessio KJ, Holmes SD, Abrahamson JA, Erickson-Miller CL, Murdock PR et al.. (2000) Identification of SAF-2, a novel siglec expressed on eosinophils, mast cells, and basophils. J Allergy Clin Immunol, 105 (6 Pt 1): 1093-100. [PMID:10856141]

6. Kiwamoto T, Kawasaki N, Paulson JC, Bochner BS. (2012) Siglec-8 as a drugable target to treat eosinophil and mast cell-associated conditions. Pharmacol Ther, 135 (3): 327-36. [PMID:22749793]

7. O'Sullivan JA, Chang AT, Youngblood BA, Bochner BS. (2020) Eosinophil and mast cell Siglecs: From biology to drug target. J Leukoc Biol, 108 (1): 73-81. [PMID:31965606]

8. Schanin J, Gebremeskel S, Korver W, Falahati R, Butuci M, Haw TJ, Nair PM, Liu G, Hansbro NG, Hansbro PM et al.. (2021) A monoclonal antibody to Siglec-8 suppresses non-allergic airway inflammation and inhibits IgE-independent mast cell activation. Mucosal Immunol, 14 (2): 366-376. [PMID:32814824]

9. Schleimer RP, Schnaar RL, Bochner BS. (2016) Regulation of airway inflammation by Siglec-8 and Siglec-9 sialoglycan ligand expression. Curr Opin Allergy Clin Immunol, 16 (1): 24-30. [PMID:26694037]

10. Youngblood BA, Brock EC, Leung J, Falahati R, Bryce PJ, Bright J, Williams J, Shultz LD, Greiner DL, Brehm MA et al.. (2019) AK002, a Humanized Sialic Acid-Binding Immunoglobulin-Like Lectin-8 Antibody that Induces Antibody-Dependent Cell-Mediated Cytotoxicity against Human Eosinophils and Inhibits Mast Cell-Mediated Anaphylaxis in Mice. Int Arch Allergy Immunol, 180 (2): 91-102. [PMID:31401630]

How to cite this page

CD33-related SIGLECs: sialic acid binding Ig like lectin 8. Last modified on 28/01/2021. Accessed on 23/06/2024. IUPHAR/BPS Guide to PHARMACOLOGY,