Details of Drug Off-Target (DOT)

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

• DOT Name: Testican-2 (SPOCK2)
• Synonyms: SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 2
• Gene Name: SPOCK2
• Related Disease:
  Advanced cancer
  Endometrial cancer
  Endometrial carcinoma
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Influenza
  Ankylosing spondylitis
  Bronchopulmonary dysplasia
  Glioma
• UniProt ID: TICN2_HUMAN
• Pfam ID: PF07648 ; PF10591 ; PF00086
• Sequence:
  MRAPGCGRLVLPLLLLAAAALAEGDAKGLKEGETPGNFMEDEQWLSSISQYSGKIKHWNR
  FRDEVEDDYIKSWEDNQQGDEALDTTKDPCQKVKCSRHKVCIAQGYQRAMCISRKKLEHR
  IKQPTVKLHGNKDSICKPCHMAQLASVCGSDGHTYSSVCKLEQQACLSSKQLAVRCEGPC
  PCPTEQAATSTADGKPETCTGQDLADLGDRLRDWFQLLHENSKQNGSASSVAGPASGLDK
  SLGASCKDSIGWMFSKLDTSADLFLDQTELAAINLDKYEVCIRPFFNSCDTYKDGRVSTA
  EWCFCFWREKPPCLAELERIQIQEAAKKKPGIFIPSCDEDGYYRKMQCDQSSGDCWCVDQ
  LGLELTGTRTHGSPDCDDIVGFSGDFGSGVGWEDEEEKETEEAGEEAEEEEGEAGEADDG
  GYIW
• Function: May participate in diverse steps of neurogenesis. Binds calcium.
• Tissue Specificity: Highly expressed in brain. Also found in lung and testis.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Posttranslational Modification	[1]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[2]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[3]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[3]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[3]
Prostate cancer	DISF190Y	Strong	Biomarker	[4]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[4]
Influenza	DIS3PNU3	moderate	Biomarker	[5]
Ankylosing spondylitis	DISRC6IR	Limited	Biomarker	[6]
Bronchopulmonary dysplasia	DISO0BY5	Limited	Biomarker	[7]
Glioma	DIS5RPEH	Limited	Biomarker	[8]

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 Testican-2 (SPOCK2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Testican-2 (SPOCK2).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Testican-2 (SPOCK2).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Testican-2 (SPOCK2).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Testican-2 (SPOCK2).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Testican-2 (SPOCK2).	[12]

References

• [1] Identification of novel tumor markers in prostate, colon and breast cancer by unbiased methylation profiling.PLoS One. 2008 Apr 30;3(4):e2079. doi: 10.1371/journal.pone.0002079.
• [2] SPOCK2 Affects the Biological Behavior of Endometrial Cancer Cells by Regulation of MT1-MMP and MMP2.Reprod Sci. 2019 Mar 4:1933719119834341. doi: 10.1177/1933719119834341. Online ahead of print.
• [3] Dysregulation of pseudogene/lncRNA-hsa-miR-363-3p-SPOCK2 pathway fuels stage progression of ovarian cancer.Aging (Albany NY). 2019 Dec 3;11(23):11416-11439. doi: 10.18632/aging.102538. Epub 2019 Dec 3.
• [4] Upregulation of SPOCK2 inhibits the invasion and migration of prostate cancer cells by regulating the MT1-MMP/MMP2 pathway.PeerJ. 2019 Jul 12;7:e7163. doi: 10.7717/peerj.7163. eCollection 2019.
• [5] The Interferon-Inducible Proteoglycan Testican-2/SPOCK2 Functions as a Protective Barrier against Virus Infection of Lung Epithelial Cells.J Virol. 2019 Sep 30;93(20):e00662-19. doi: 10.1128/JVI.00662-19. Print 2019 Oct 15.
• [6] Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects.Arthritis Res Ther. 2011 Apr 7;13(2):R57. doi: 10.1186/ar3309.
• [7] Angiogenesis-related genes may be a more important factor than matrix metalloproteinases in bronchopulmonary dysplasia development.Oncotarget. 2017 Mar 21;8(12):18670-18679. doi: 10.18632/oncotarget.14722.
• [8] Testican 2 abrogates inhibition of membrane-type matrix metalloproteinases by other testican family proteins.Cancer Res. 2003 Jun 15;63(12):3364-9.
• [9] 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.
• [10] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [11] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [12] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [13] 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.
• [14] 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.