sialic acid binding Ig like lectin 8 | Sialic acid binding Ig like lectins | IUPHAR Guide to IMMUNOPHARMACOLOGY

Top ▲

sialic acid binding Ig like lectin 8

Target id: 3012

Nomenclature: sialic acid binding Ig like lectin 8

Abbreviated Name: SIGLEC8

Family: Sialic acid binding Ig like lectins

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: ON :     sialic acid binding Ig like lectin 8 has curated data in GtoImmuPdb

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
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
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) [1,6-7]. For example, Allakos have an anti-SIGLEC8 monoclonal antibody named AK002 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.
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
General Comments
SSIGLEC8 is an I-type lectin that is expressed only on human eosinophils, basophils, mast cells [5]. It is an inhibitory receptor that engages sialoglycan ligands to diminish ongoing inflammation.

References

Show »

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. 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]

How to cite this page

Sialic acid binding Ig like lectins: sialic acid binding Ig like lectin 8. Last modified on 02/07/2018. Accessed on 15/12/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=3012.