sialic acid binding Ig like lectin 8
Target has curated data in GtoImmuPdb
Target id: 3012
Nomenclature: sialic acid binding Ig like lectin 8
Abbreviated Name: SIGLEC8
Family: CD33-related SIGLECs
Contents:
Gene and Protein Information  |
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| 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 |
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| 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 [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 ClinicalTrials.gov's full list of AK002 trials. |
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| Immuno Process Associations | ||
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| General Comments |
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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. |
References
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, https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=628417
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 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=3012.
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