Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2JGGXD)

• DOT Name: Sialic acid-binding Ig-like lectin 14 (SIGLEC14)
• Synonyms: Siglec-14
• Gene Name: SIGLEC14
• Related Disease:
  Meningeal tuberculosis
  Tuberculosis
  Arthropathy
  Chronic obstructive pulmonary disease
  Lupus
  Skin disease
  Systemic lupus erythematosus
  Asthma
  Streptococcal B infection
• UniProt ID: SIG14_HUMAN
• Pfam ID: PF08205 ; PF13895 ; PF07686
• Sequence:
  MLPLLLLPLLWGGSLQEKPVYELQVQKSVTVQEGLCVLVPCSFSYPWRSWYSSPPLYVYW
  FRDGEIPYYAEVVATNNPDRRVKPETQGRFRLLGDVQKKNCSLSIGDARMEDTGSYFFRV
  ERGRDVKYSYQQNKLNLEVTALIEKPDIHFLEPLESGRPTRLSCSLPGSCEAGPPLTFSW
  TGNALSPLDPETTRSSELTLTPRPEDHGTNLTCQVKRQGAQVTTERTVQLNVSYAPQNLA
  ISIFFRNGTGTALRILSNGMSVPIQEGQSLFLACTVDSNPPASLSWFREGKALNPSQTSM
  SGTLELPNIGAREGGEFTCRVQHPLGSQHLSFILSVQRSSSSCICVTEKQQGSWPLVLTL
  IRGALMGAGFLLTYGLTWIYYTRCGGPQQSRAERPG
• Function: Putative adhesion molecule. Sialic acid-binding paired receptor which may activate associated receptors.
• Tissue Specificity: Mainly expressed in hematopoietic tissues including bone marrow, spleen and fetal liver. Also detected in lung and testis.
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  DAP12 interactions (R-HSA-2172127)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Meningeal tuberculosis	DIS8KHDE	Definitive	Genetic Variation	[1]
Tuberculosis	DIS2YIMD	Definitive	Genetic Variation	[1]
Arthropathy	DISVEERK	Strong	Biomarker	[2]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[3]
Lupus	DISOKJWA	Strong	Altered Expression	[4]
Skin disease	DISDW8R6	Strong	Genetic Variation	[2]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[4]
Asthma	DISW9QNS	moderate	Biomarker	[5]
Streptococcal B infection	DISN80QT	Limited	Biomarker	[6]

2 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 14 (SIGLEC14).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sialic acid-binding Ig-like lectin 14 (SIGLEC14).	[9]

1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Sialic acid-binding Ig-like lectin 14 (SIGLEC14).	[8]

References

• [1] The SIGLEC14 null allele is associated with Mycobacterium tuberculosis- and BCG-induced clinical and immunologic outcomes.Tuberculosis (Edinb). 2017 May;104:38-45. doi: 10.1016/j.tube.2017.02.005. Epub 2017 Feb 21.
• [2] Epigenome-wide analysis of sperm cells identifies IL22 as a possible germ line risk locus for psoriatic arthritis.PLoS One. 2019 Feb 19;14(2):e0212043. doi: 10.1371/journal.pone.0212043. eCollection 2019.
• [3] 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.
• [4] Monocyte Siglec-14 expression is upregulated in patients with systemic lupus erythematosus and correlates with lupus disease activity.Rheumatology (Oxford). 2017 Jun 1;56(6):1025-1030. doi: 10.1093/rheumatology/kew498.
• [5] Inhaled corticosteroids increase siglec-5/14 expression in sputum cells of COPD patients.Adv Exp Med Biol. 2015;839:1-5. doi: 10.1007/5584_2014_51.
• [6] Siglec-14 Enhances NLRP3-Inflammasome Activation in Macrophages.J Innate Immun. 2020;12(4):333-343. doi: 10.1159/000504323. Epub 2019 Dec 5.
• [7] 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.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 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.