Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1AT2OL)

• DOT Name: Syntenin-2 (SDCBP2)
• Synonyms: Similar to TACIP18; SITAC; Syndecan-binding protein 2
• Gene Name: SDCBP2
• Related Disease:
  Alzheimer disease
  Congestive heart failure
  Neoplasm
  Epidermodysplasia verruciformis
• UniProt ID: SDCB2_HUMAN
• Pfam ID: PF00595
• Sequence:
  MSSLYPSLEDLKVDQAIQAQVRASPKMPALPVQATAISPPPVLYPNLAELENYMGLSLSS
  QEVQESLLQIPEGDSTAVSGPGPGQMVAPVTGYSLGVRRAEIKPGVREIHLCKDERGKTG
  LRLRKVDQGLFVQLVQANTPASLVGLRFGDQLLQIDGRDCAGWSSHKAHQVVKKASGDKI
  VVVVRDRPFQRTVTMHKDSMGHVGFVIKKGKIVSLVKGSSAARNGLLTNHYVCEVDGQNV
  IGLKDKKIMEILATAGNVVTLTIIPSVIYEHMVKKLPPVLLHHTMDHSIPDA
• Function: Binds phosphatidylinositol 4,5-bisphosphate (PIP2). May play a role in the organization of nuclear PIP2, cell division and cell survival.
• Tissue Specificity: Preferentially expressed in cells of the digestive tract . Low expression in skeletal muscle and kidney . Detected in differentiated keratinocytes of normal and malignant epithelium . In healthy skin, expression is localized in suprabasal epidermal layers .

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Altered Expression	[1]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Epidermodysplasia verruciformis	DIS54WBS	moderate	Altered Expression	[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 Syntenin-2 (SDCBP2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Syntenin-2 (SDCBP2).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Syntenin-2 (SDCBP2).	[11]

8 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 Syntenin-2 (SDCBP2).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Syntenin-2 (SDCBP2).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Syntenin-2 (SDCBP2).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Syntenin-2 (SDCBP2).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Syntenin-2 (SDCBP2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Syntenin-2 (SDCBP2).	[10]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Syntenin-2 (SDCBP2).	[12]
Manganese	DMKT129	Investigative	Manganese decreases the expression of Syntenin-2 (SDCBP2).	[13]

References

• [1] Ganglioside-Dependent Neural Stem Cell Proliferation in Alzheimer's Disease Model Mice.ASN Neuro. 2015 Dec 23;7(6):1759091415618916. doi: 10.1177/1759091415618916. Print 2015 Nov-Dec.
• [2] Soluble ST2 protein and hospitalizations due to worsening chronic heart failure during a one-year follow-up in a population with reduced ejection fraction.Adv Clin Exp Med. 2017 Sep;26(6):931-938. doi: 10.17219/acem/63005.
• [3] HPV8-E6 Interferes with Syntenin-2 Expression through Deregulation of Differentiation, Methylation and Phosphatidylinositide-Kinase Dependent Mechanisms.Front Microbiol. 2017 Sep 8;8:1724. doi: 10.3389/fmicb.2017.01724. eCollection 2017.
• [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] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [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.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [12] In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.
• [13] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.