sialic acid binding Ig like lectin 8
Target id: 3012
Nomenclature: sialic acid binding Ig like lectin 8
Abbreviated Name: SIGLEC8
Family: CD33-related SIGLECs
Contents:
Gene and Protein Information  |
||||||
| 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 |
| SAF2 | SIGLEC-8 | SIGLEC8L |
| Database Links |
|
| Alphafold | Q9NYZ4 (Hs), Q920G3 (Mm) |
| ChEMBL Target | CHEMBL4630877 (Hs) |
| Ensembl Gene | ENSG00000105366 (Hs), ENSMUSG00000039013 (Mm), ENSRNOG00000022640 (Rn) |
| Entrez Gene | 27181 (Hs), 233186 (Mm), 292846 (Rn) |
| Human Protein Atlas | ENSG00000105366 (Hs) |
| KEGG Gene | hsa:27181 (Hs), mmu:233186 (Mm), rno:292846 (Rn) |
| OMIM | 605639 (Hs) |
| Pharos | Q9NYZ4 (Hs) |
| RefSeq Nucleotide | NM_014442 (Hs), NM_145581 (Mm) |
| RefSeq Protein | NP_055257 (Hs), NP_663556 (Mm) |
| UniProtKB | Q9NYZ4 (Hs), Q920G3 (Mm) |
| Wikipedia | SIGLEC8 (Hs) |
| 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 [4,6]. Endogenous ligands for SIGLEC8 are sialoglycan ligands that are upregulated on the surfaces of inflamed cells and tissues [5]. 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) [1,7-10]. Allakos progressed their anti-SIGLEC8 monoclonal antibody lirentelimab (formerly antolimab; AK002) [11] to early stage clinical trials for various eosinophilic diseases [2] and mastocytosis. Lirentelimab was granted FDA orphan drug designation for the treatment of eosinophilic gastritis (in January 2018) [3], but development was discontinued at phase 2. |
| Cell Type Associations | ||||||
|
||||||
|
| Immuno Process Associations | ||
|
| General Comments |
|
SIGLEC8 is an I-type lectin that is expressed only on human eosinophils, basophils and mast cells [6]. 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. |
References
1. Bochner BS. (2016) "Siglec"ting the allergic response for therapeutic targeting. Glycobiology, 26 (6): 546-52. [PMID:26911285]
2. Dellon ES, Peterson KA, Murray JA, Falk GW, Gonsalves N, Chehade M, Genta RM, Leung J, Khoury P, Klion AD et al.. (2020) Anti-Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis. N Engl J Med, 383 (17): 1624-1634. [PMID:33085861]
3. 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, https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=628417
4. 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]
5. 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]
6. 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]
7. 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]
8. 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]
9. 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]
10. 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]
11. 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 28/01/2025. Accessed on 25/04/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3012.
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License