Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ5TRRV)

DOT Name Sialic acid-binding Ig-like lectin 8 (SIGLEC8)
Synonyms Siglec-8; Sialoadhesin family member 2; SAF-2
Gene Name SIGLEC8
Related Disease
Allergic asthma ( )
Asthma ( )
Chronic eosinophilic leukemia ( )
Chronic obstructive pulmonary disease ( )
Clear cell renal carcinoma ( )
Eosinophilic esophagitis ( )
Mast cell leukaemia ( )
Neoplasm ( )
Pneumonia ( )
Pneumonitis ( )
Hirschsprung disease ( )
Chronic urticaria ( )
Eosinophilic gastroenteritis ( )
Gastritis ( )
Gastroenteritis ( )
UniProt ID
SIGL8_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2N7A; 2N7B; 7QU6; 7QUH; 7QUI
Pfam ID
PF00047 ; PF13927 ; PF07686
Sequence
MLLLLLLLPLLWGTKGMEGDRQYGDGYLLQVQELVTVQEGLCVHVPCSFSYPQDGWTDSD
PVHGYWFRAGDRPYQDAPVATNNPDREVQAETQGRFQLLGDIWSNDCSLSIRDARKRDKG
SYFFRLERGSMKWSYKSQLNYKTKQLSVFVTALTHRPDILILGTLESGHSRNLTCSVPWA
CKQGTPPMISWIGASVSSPGPTTARSSVLTLTPKPQDHGTSLTCQVTLPGTGVTTTSTVR
LDVSYPPWNLTMTVFQGDATASTALGNGSSLSVLEGQSLRLVCAVNSNPPARLSWTRGSL
TLCPSRSSNPGLLELPRVHVRDEGEFTCRAQNAQGSQHISLSLSLQNEGTGTSRPVSQVT
LAAVGGAGATALAFLSFCIIFIIVRSCRKKSARPAAGVGDTGMEDAKAIRGSASQGPLTE
SWKDGNPLKKPPPAVAPSSGEEGELHYATLSFHKVKPQDPQGQEATDSEYSEIKIHKRET
AETQACLRNHNPSSKEVRG
Function
Putative adhesion molecule that mediates sialic-acid dependent binding to red blood cells. Preferentially binds to alpha-2,3-linked sialic acid. Also binds to alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. Recognizes simultaneously epitopes having a terminal N-acetylneuraminic acid (sialic acid) and an underlying 6-O-sulfated galactose. Preferentially binds to Gal-6-sulfated sialyl-Lewis X glycan epitopes.
Tissue Specificity Expressed specifically on red blood cells namely basophil, mast cells and eosinophils.
Reactome Pathway
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933 )

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Allergic asthma DISHF0H3 Strong Biomarker [1]
Asthma DISW9QNS Strong Genetic Variation [2]
Chronic eosinophilic leukemia DISAJOUO Strong Biomarker [3]
Chronic obstructive pulmonary disease DISQCIRF Strong Genetic Variation [2]
Clear cell renal carcinoma DISBXRFJ Strong Altered Expression [4]
Eosinophilic esophagitis DISR8WSB Strong Biomarker [5]
Mast cell leukaemia DIS7VQW9 Strong Biomarker [6]
Neoplasm DISZKGEW Strong Biomarker [4]
Pneumonia DIS8EF3M Strong Altered Expression [1]
Pneumonitis DIS88E0K Strong Altered Expression [1]
Hirschsprung disease DISUUSM1 moderate Altered Expression [7]
Chronic urticaria DISMBYB0 Limited Biomarker [8]
Eosinophilic gastroenteritis DISYIW4H Limited Biomarker [5]
Gastritis DIS8G07K Limited Biomarker [5]
Gastroenteritis DISXQCG5 Limited Biomarker [5]
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⏷ Show the Full List of 15 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Sialic acid-binding Ig-like lectin 8 (SIGLEC8). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Sialic acid-binding Ig-like lectin 8 (SIGLEC8). [10]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Sialic acid-binding Ig-like lectin 8 (SIGLEC8). [11]
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References

1 Characterization of Siglec-8 Expression on Lavage Cells after Segmental Lung Allergen Challenge.Int Arch Allergy Immunol. 2018;177(1):16-28. doi: 10.1159/000488951. Epub 2018 Jun 7.
2 Associations of genetic polymorphisms of Siglecs with human diseases.Glycobiology. 2014 Sep;24(9):785-93. doi: 10.1093/glycob/cwu043. Epub 2014 May 19.
3 Developmental, malignancy-related, and cross-species analysis of eosinophil, mast cell, and basophil siglec-8 expression.J Clin Immunol. 2011 Dec;31(6):1045-53. doi: 10.1007/s10875-011-9589-4. Epub 2011 Sep 22.
4 Enhancement of Siglec-8 expression predicts adverse prognosis in patients with clear cell renal cell carcinoma.Urol Oncol. 2017 Oct;35(10):607.e1-607.e8. doi: 10.1016/j.urolonc.2017.05.016. Epub 2017 Jun 12.
5 Siglec-8 antibody reduces eosinophils and mast cells in a transgenic mouse model of eosinophilic gastroenteritis.JCI Insight. 2019 Oct 3;4(19):e126219. doi: 10.1172/jci.insight.126219.
6 Leveraging Siglec-8 endocytic mechanisms to kill human eosinophils and malignant mast cells.J Allergy Clin Immunol. 2018 May;141(5):1774-1785.e7. doi: 10.1016/j.jaci.2017.06.028. Epub 2017 Jul 20.
7 Role of MiR-215 in Hirschsprung's Disease Pathogenesis by Targeting SIGLEC-8.Cell Physiol Biochem. 2016;40(6):1646-1655. doi: 10.1159/000453214. Epub 2016 Dec 23.
8 New treatments for chronic urticaria.Ann Allergy Asthma Immunol. 2020 Jan;124(1):2-12. doi: 10.1016/j.anai.2019.08.014. Epub 2019 Aug 23.
9 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
10 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
11 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.