Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO4F5C9)

• DOT Name: Sialic acid-binding Ig-like lectin 6 (SIGLEC6)
• Synonyms: Siglec-6; CD33 antigen-like 1; CDw327; Obesity-binding protein 1; OB-BP1; CD antigen CD327
• Gene Name: SIGLEC6
• Related Disease:
  Colorectal carcinoma
  Small lymphocytic lymphoma
  Systemic lupus erythematosus
• UniProt ID: SIGL6_HUMAN
• Pfam ID: PF07679 ; PF00047 ; PF07686
• Sequence:
  MQGAQEASASEMLPLLLPLLWAGALAQERRFQLEGPESLTVQEGLCVLVPCRLPTTLPAS
  YYGYGYWFLEGADVPVATNDPDEEVQEETRGRFHLLWDPRRKNCSLSIRDARRRDNAAYF
  FRLKSKWMKYGYTSSKLSVRVMALTHRPNISIPGTLESGHPSNLTCSVPWVCEQGTPPIF
  SWMSAAPTSLGPRTTQSSVLTITPRPQDHSTNLTCQVTFPGAGVTMERTIQLNVSYAPQK
  VAISIFQGNSAAFKILQNTSSLPVLEGQALRLLCDADGNPPAHLSWFQGFPALNATPISN
  TGVLELPQVGSAEEGDFTCRAQHPLGSLQISLSLFVHWKPEGRAGGVLGAVWGASITTLV
  FLCVCFIFRVKTRRKKAAQPVQNTDDVNPVMVSGSRGHQHQFQTGIVSDHPAEAGPISED
  EQELHYAVLHFHKVQPQEPKVTDTEYSEIKIHK
• Function: Putative adhesion molecule that mediates sialic-acid dependent binding to cells. 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.
• Tissue Specificity: Expressed at high levels in placenta (cyto- and syncytiotrophoblastic cells) and at lower levels in spleen, peripheral blood leukocytes (predominantly B-cells) and small intestine.
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Small lymphocytic lymphoma	DIS30POX	Limited	Altered Expression	[2]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[3]

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 6 (SIGLEC6).	[4]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Sialic acid-binding Ig-like lectin 6 (SIGLEC6).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Sialic acid-binding Ig-like lectin 6 (SIGLEC6).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Sialic acid-binding Ig-like lectin 6 (SIGLEC6).	[5]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Sialic acid-binding Ig-like lectin 6 (SIGLEC6).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Sialic acid-binding Ig-like lectin 6 (SIGLEC6).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Sialic acid-binding Ig-like lectin 6 (SIGLEC6).	[10]

References

• [1] Functional Inhibitory Siglec-6 Is Upregulated in Human Colorectal Cancer-Associated Mast Cells.Front Immunol. 2018 Sep 20;9:2138. doi: 10.3389/fimmu.2018.02138. eCollection 2018.
• [2] Siglec-6 on Chronic Lymphocytic Leukemia Cells Is a Target for Post-Allogeneic Hematopoietic Stem Cell Transplantation Antibodies.Cancer Immunol Res. 2018 Sep;6(9):1008-1013. doi: 10.1158/2326-6066.CIR-18-0102. Epub 2018 Jul 6.
• [3] Siglec genes confer resistance to systemic lupus erythematosus in humans and mice.Cell Mol Immunol. 2019 Feb;16(2):154-164. doi: 10.1038/cmi.2017.160. Epub 2018 Mar 5.
• [4] 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.
• [5] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [6] 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.
• [7] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [8] 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.
• [9] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [10] 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.