Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC36XP9)

• DOT Name: Sialic acid-binding Ig-like lectin 12 (SIGLEC12)
• Synonyms: Siglec-12; Sialic acid-binding Ig-like lectin-like 1; Siglec-L1
• Gene Name: SIGLEC12
• Related Disease:
  Carcinoma
  Chronic fatigue syndrome
  Cytomegalovirus infection
  Metabolic disorder
  Obesity
  Systemic lupus erythematosus
• UniProt ID: SIG12_HUMAN
• Pfam ID: PF13927 ; PF07686
• Sequence:
  MLLLLLLLPPLLCGRVGAKEQKDYLLTMQKSVTVQEGLCVSVLCSFSYPQNGWTASDPVH
  GYWFRAGDHVSRNIPVATNNPARAVQEETRDRFHLLGDPQNKDCTLSIRDTRESDAGTYV
  FCVERGNMKWNYKYDQLSVNVTASQDLLSRYRLEVPESVTVQEGLCVSVPCSVLYPHYNW
  TASSPVYGSWFKEGADIPWDIPVATNTPSGKVQEDTHGRFLLLGDPQTNNCSLSIRDARK
  GDSGKYYFQVERGSRKWNYIYDKLSVHVTALTHMPTFSIPGTLESGHPRNLTCSVPWACE
  QGTPPTITWMGASVSSLDPTITRSSMLSLIPQPQDHGTSLTCQVTLPGAGVTMTRAVRLN
  ISYPPQNLTMTVFQGDGTASTTLRNGSALSVLEGQSLHLVCAVDSNPPARLSWTWGSLTL
  SPSQSSNLGVLELPRVHVKDEGEFTCRAQNPLGSQHISLSLSLQNEYTGKMRPISGVTLG
  AFGGAGATALVFLYFCIIFVVVRSCRKKSARPAVGVGDTGMEDANAVRGSASQGPLIESP
  ADDSPPHHAPPALATPSPEEGEIQYASLSFHKARPQYPQEQEAIGYEYSEINIPK
• Function: Putative adhesion molecule that mediates sialic-acid dependent binding to cells. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface.
• Tissue Specificity: Isoform Short is highly expressed in spleen, small intestine and adrenal gland; it is lower expressed in thyroid, placenta, brain, stomach, bone marrow, spinal cord and breast. Isoform Long is highly expressed in spleen, small intestine and bone marrow; it is lower expressed in thyroid, placenta, thymus, trachea, stomach, lung, adrenal gland, fetal brain and testis.
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Strong	Altered Expression	[1]
Chronic fatigue syndrome	DIS34WJ5	Strong	Genetic Variation	[2]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[3]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[4]
Obesity	DIS47Y1K	Strong	Biomarker	[4]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[5]

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 12 (SIGLEC12).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sialic acid-binding Ig-like lectin 12 (SIGLEC12).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sialic acid-binding Ig-like lectin 12 (SIGLEC12).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Sialic acid-binding Ig-like lectin 12 (SIGLEC12).	[8]

References

• [1] SIGLEC12, a human-specific segregating (pseudo)gene, encodes a signaling molecule expressed in prostate carcinomas.J Biol Chem. 2011 Jul 1;286(26):23003-11. doi: 10.1074/jbc.M111.244152. Epub 2011 May 9.
• [2] Maintenance of Chronic Fatigue Syndrome (CFS) in Young CFS Patients Is Associated with the 5-HTTLPR and SNP rs25531 A > G Genotype.PLoS One. 2015 Oct 16;10(10):e0140883. doi: 10.1371/journal.pone.0140883. eCollection 2015.
• [3] Early detection of cytomegalovirus (CMV) infection in bone marrow transplant patients by reverse transcription-PCR for CMV spliced late gene UL21.5: a two site evaluation.J Clin Virol. 2002 Feb;24(1-2):13-23. doi: 10.1016/s1386-6532(01)00209-8.
• [4] Seabuckthorn Leaves Extract and Flavonoid Glycosides Extract from Seabuckthorn Leaves Ameliorates Adiposity, Hepatic Steatosis, Insulin Resistance, and Inflammation in Diet-Induced Obesity.Nutrients. 2017 Jun 2;9(6):569. doi: 10.3390/nu9060569.
• [5] 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.
• [6] 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.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [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] 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.