Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYSOOO7)

• DOT Name: Testican-3 (SPOCK3)
• Synonyms: SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 3
• Gene Name: SPOCK3
• Related Disease:
  Adult T-cell leukemia/lymphoma
  Attention deficit hyperactivity disorder
  T-cell leukaemia
• UniProt ID: TICN3_HUMAN
• Pfam ID: PF07648 ; PF10591 ; PF00086
• Sequence:
  MLKVSAVLCVCAAAWCSQSLAAAAAVAAAGGRSDGGNFLDDKQWLTTISQYDKEVGQWNK
  FRDEVEDDYFRTWSPGKPFDQALDPAKDPCLKMKCSRHKVCIAQDSQTAVCISHRRLTHR
  MKEAGVDHRQWRGPILSTCKQCPVVYPSPVCGSDGHTYSFQCKLEYQACVLGKQISVKCE
  GHCPCPSDKPTSTSRNVKRACSDLEFREVANRLRDWFKALHESGSQNKKTKTLLRPERSR
  FDTSILPICKDSLGWMFNRLDTNYDLLLDQSELRSIYLDKNEQCTKAFFNSCDTYKDSLI
  SNNEWCYCFQRQQDPPCQTELSNIQKRQGVKKLLGQYIPLCDEDGYYKPTQCHGSVGQCW
  CVDRYGNEVMGSRINGVADCAIDFEISGDFASGDFHEWTDDEDDEDDIMNDEDEIEDDDE
  DEGDDDDGGDDHDVYI
• Function: May participate in diverse steps of neurogenesis. Inhibits the processing of pro-matrix metalloproteinase 2 (MMP-2) by MT1-MMP and MT3-MMP. May interfere with tumor invasion.
• Tissue Specificity: Expressed in brain.
• Reactome Pathway: Activation of Matrix Metalloproteinases (R-HSA-1592389)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Altered Expression	[1]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[2]
T-cell leukaemia	DISJ6YIF	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Testican-3 (SPOCK3).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Testican-3 (SPOCK3).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Testican-3 (SPOCK3).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Testican-3 (SPOCK3).	[6]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Testican-3 (SPOCK3).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Testican-3 (SPOCK3).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Testican-3 (SPOCK3).	[10]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of Testican-3 (SPOCK3).	[11]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Testican-3 (SPOCK3).	[7]

References

• [1] Testican 3 expression in adult T-cell leukemia.Leuk Res. 2009 Jul;33(7):913-8. doi: 10.1016/j.leukres.2008.11.006. Epub 2009 Jan 13.
• [2] SPOCK3, a risk gene for adult ADHD and personality disorders.Eur Arch Psychiatry Clin Neurosci. 2014 Aug;264(5):409-21. doi: 10.1007/s00406-013-0476-2. Epub 2013 Nov 29.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Comparative effects of raloxifene, tamoxifen and estradiol on human osteoblasts in vitro: estrogen receptor dependent or independent pathways of raloxifene. J Steroid Biochem Mol Biol. 2009 Feb;113(3-5):281-9.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [11] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.