Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1P0LJM)

• DOT Name: Syndecan-3 (SDC3)
• Synonyms: SYND3
• Gene Name: SDC3
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Clear cell renal carcinoma
  Duchenne muscular dystrophy
  Familial Alzheimer disease
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Pancreatic cancer
  Renal cell carcinoma
  Rheumatoid arthritis
  Breast carcinoma
  Breast fibrocystic disease
  Inflammation
  Periodontitis
• UniProt ID: SDC3_HUMAN
• Pfam ID: PF01034
• Sequence:
  MKPGPPHRAGAAHGAGAGAGAAAGPGARGLLLPPLLLLLLAGRAAGAQRWRSENFERPVD
  LEGSGDDDSFPDDELDDLYSGSGSGYFEQESGIETAMRFSPDVALAVSTTPAVLPTTNIQ
  PVGTPFEELPSERPTLEPATSPLVVTEVPEEPSQRATTVSTTMATTAATSTGDPTVATVP
  ATVATATPSTPAAPPFTATTAVIRTTGVRRLLPLPLTTVATARATTPEAPSPPTTAAVLD
  TEAPTPRLVSTATSRPRALPRPATTQEPDIPERSTLPLGTTAPGPTEVAQTPTPETFLTT
  IRDEPEVPVSGGPSGDFELPEEETTQPDTANEVVAVGGAAAKASSPPGTLPKGARPGPGL
  LDNAIDSGSSAAQLPQKSILERKEVLVAVIVGGVVGALFAAFLVTLLIYRMKKKDEGSYT
  LEEPKQASVTYQKPDKQEEFYA
• Function: Cell surface proteoglycan that may bear heparan sulfate. May have a role in the organization of cell shape by affecting the actin cytoskeleton, possibly by transferring signals from the cell surface in a sugar-dependent mechanism.
• Tissue Specificity: Expressed in the nervous system, the adrenal gland, and the spleen.
• KEGG Pathway:
  Cell adhesion molecules (hsa04514)
  Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway:
  HS-GAG biosynthesis (R-HSA-2022928)
  HS-GAG degradation (R-HSA-2024096)
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Syndecan interactions (R-HSA-3000170)
  Defective B4GALT7 causes EDS, progeroid type (R-HSA-3560783)
  Defective B3GAT3 causes JDSSDHD (R-HSA-3560801)
  Defective EXT2 causes exostoses 2 (R-HSA-3656237)
  Defective EXT1 causes exostoses 1, TRPS2 and CHDS (R-HSA-3656253)
  Defective B3GALT6 causes EDSP2 and SEMDJL1 (R-HSA-4420332)
  Attachment and Entry (R-HSA-9694614)
  Retinoid metabolism and transport (R-HSA-975634)
  A tetrasaccharide linker sequence is required for GAG synthesis (R-HSA-1971475)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[1]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[3]
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[4]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[6]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[9]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[1]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[10]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[8]
Breast fibrocystic disease	DISUM7ID	Limited	Biomarker	[8]
Inflammation	DISJUQ5T	Limited	Biomarker	[10]
Periodontitis	DISI9JOI	Limited	Altered Expression	[10]

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 Syndecan-3 (SDC3).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Syndecan-3 (SDC3).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Syndecan-3 (SDC3).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Syndecan-3 (SDC3).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Syndecan-3 (SDC3).	[15]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Syndecan-3 (SDC3).	[16]
Marinol	DM70IK5	Approved	Marinol increases the expression of Syndecan-3 (SDC3).	[17]
Selenium	DM25CGV	Approved	Selenium increases the expression of Syndecan-3 (SDC3).	[18]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Syndecan-3 (SDC3).	[19]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Syndecan-3 (SDC3).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Syndecan-3 (SDC3).	[20]

References

• [1] Regulation of antitumor miR-144-5p targets oncogenes: Direct regulation of syndecan-3 and its clinical significance.Cancer Sci. 2018 Sep;109(9):2919-2936. doi: 10.1111/cas.13722. Epub 2018 Jul 28.
• [2] Contribution of syndecans to cellular internalization and fibrillation of amyloid-(1-42).Sci Rep. 2019 Feb 4;9(1):1393. doi: 10.1038/s41598-018-37476-9.
• [3] Augmented synthesis and differential localization of heparan sulfate proteoglycans in Duchenne muscular dystrophy.J Cell Biochem. 2002;85(4):703-13. doi: 10.1002/jcb.10184.
• [4] In silico Analysis of Gamma-Secretase-Complex Mutations in Hidradenitis Suppurativa Demonstrates Disease-Specific Substrate Recognition and Cleavage Alterations.Front Med (Lausanne). 2019 Sep 19;6:206. doi: 10.3389/fmed.2019.00206. eCollection 2019.
• [5] Attachment and Postattachment Receptors Important for Hepatitis C Virus Infection and Cell-to-Cell Transmission.J Virol. 2017 Jun 9;91(13):e00280-17. doi: 10.1128/JVI.00280-17. Print 2017 Jul 1.
• [6] Pleiotrophin, a target of miR-384, promotes proliferation, metastasis and lipogenesis in HBV-related hepatocellular carcinoma.J Cell Mol Med. 2017 Nov;21(11):3023-3043. doi: 10.1111/jcmm.13213. Epub 2017 May 30.
• [7] Loss of receptor protein tyrosine phosphatase / (RPTP/) promotes prostate cancer metastasis.J Biol Chem. 2012 Nov 23;287(48):40339-49. doi: 10.1074/jbc.M112.405852. Epub 2012 Oct 11.
• [8] Prognostic significance of the expression of GFR1, GFR3 and syndecan-3, proteins binding ARTEMIN, in mammary carcinoma.BMC Cancer. 2013 Jan 26;13:34. doi: 10.1186/1471-2407-13-34.
• [9] Pleiotrophin and N-syndecan promote perineural invasion and tumor progression in an orthotopic mouse model of pancreatic cancer.World J Gastroenterol. 2017 Jun 7;23(21):3907-3914. doi: 10.3748/wjg.v23.i21.3907.
• [10] Soluble syndecan-3 binds chemokines, reduces leukocyte migration in vitro and ameliorates disease severity in models of rheumatoid arthritis.Arthritis Res Ther. 2019 Jul 12;21(1):172. doi: 10.1186/s13075-019-1939-2.
• [11] 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.
• [12] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [13] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [16] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [17] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [18] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [19] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [20] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.