Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYC440J)

• DOT Name: Sialic acid-binding Ig-like lectin 5 (SIGLEC5)
• Synonyms: Siglec-5; CD33 antigen-like 2; Obesity-binding protein 2; OB-BP2; OB-binding protein 2; CD antigen CD170
• Gene Name: SIGLEC5
• Related Disease:
  Acute myelogenous leukaemia
  Neoplasm
  Periodontitis
  Systemic lupus erythematosus
  Leprosy
  Non-insulin dependent diabetes
  Type-1/2 diabetes
• UniProt ID: SIGL5_HUMAN
• PDB ID: 2ZG1; 2ZG2; 2ZG3
• Pfam ID: PF13927 ; PF07686
• Sequence:
  MLPLLLLPLLWGGSLQEKPVYELQVQKSVTVQEGLCVLVPCSFSYPWRSWYSSPPLYVYW
  FRDGEIPYYAEVVATNNPDRRVKPETQGRFRLLGDVQKKNCSLSIGDARMEDTGSYFFRV
  ERGRDVKYSYQQNKLNLEVTALIEKPDIHFLEPLESGRPTRLSCSLPGSCEAGPPLTFSW
  TGNALSPLDPETTRSSELTLTPRPEDHGTNLTCQMKRQGAQVTTERTVQLNVSYAPQTIT
  IFRNGIALEILQNTSYLPVLEGQALRLLCDAPSNPPAHLSWFQGSPALNATPISNTGILE
  LRRVRSAEEGGFTCRAQHPLGFLQIFLNLSVYSLPQLLGPSCSWEAEGLHCRCSFRARPA
  PSLCWRLEEKPLEGNSSQGSFKVNSSSAGPWANSSLILHGGLSSDLKVSCKAWNIYGSQS
  GSVLLLQGRSNLGTGVVPAALGGAGVMALLCICLCLIFFLIVKARRKQAAGRPEKMDDED
  PIMGTITSGSRKKPWPDSPGDQASPPGDAPPLEEQKELHYASLSFSEMKSREPKDQEAPS
  TTEYSEIKTSK
• Function: Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Binds equally to alpha-2,3-linked and 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.
• Tissue Specificity: Expressed by monocytic/myeloid lineage cells. Found at high levels in peripheral blood leukocytes, spleen, bone marrow and at lower levels in lymph node, lung, appendix, placenta, pancreas and thymus. Expressed by monocytes and neutrophils but absent from leukemic cell lines representing early stages of myelomonocytic differentiation.
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[2]
Periodontitis	DISI9JOI	Strong	Genetic Variation	[3]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[4]
Leprosy	DISAA4UI	moderate	Genetic Variation	[5]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[6]
Type-1/2 diabetes	DISIUHAP	Limited	Genetic Variation	[6]

1 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 5 (SIGLEC5).	[7]

4 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 5 (SIGLEC5).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Sialic acid-binding Ig-like lectin 5 (SIGLEC5).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Sialic acid-binding Ig-like lectin 5 (SIGLEC5).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Sialic acid-binding Ig-like lectin 5 (SIGLEC5).	[11]

References

• [1] Developing aptamer probes for acute myelogenous leukemia detection and surface protein biomarker discovery.J Hematol Oncol. 2014 Jan 9;7:5. doi: 10.1186/1756-8722-7-5.
• [2] Lectin galactoside-binding soluble 3 binding protein (LGALS3BP) is a tumor-associated immunomodulatory ligand for CD33-related Siglecs.J Biol Chem. 2014 Nov 28;289(48):33481-91. doi: 10.1074/jbc.M114.593129. Epub 2014 Oct 15.
• [3] Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci.Eur J Hum Genet. 2019 Jan;27(1):102-113. doi: 10.1038/s41431-018-0265-5. Epub 2018 Sep 14.
• [4] Soluble siglec-5 is a novel salivary biomarker for primary Sjogren's syndrome.J Autoimmun. 2019 Jun;100:114-119. doi: 10.1016/j.jaut.2019.03.008. Epub 2019 Mar 25.
• [5] Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy.Nat Genet. 2015 Mar;47(3):267-71. doi: 10.1038/ng.3212. Epub 2015 Feb 2.
• [6] Siglec-5 is a novel marker of critical limb ischemia in patients with diabetes.Sci Rep. 2017 Sep 12;7(1):11272. doi: 10.1038/s41598-017-11820-x.
• [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] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [9] Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells. Environ Toxicol. 2016 Mar;31(3):314-28.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.