Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVDR68G)

• DOT Name: Matrilin-2 (MATN2)
• Gene Name: MATN2
• Related Disease:
  Neoplasm
  Allergic rhinitis
  Aortic valve disorder
  Erectile dysfunction
  Hepatocellular carcinoma
  Liver cirrhosis
  Astrocytoma
  Neurofibromatosis type 1
  Stroke
• UniProt ID: MATN2_HUMAN
• Pfam ID: PF12662 ; PF07645 ; PF14670 ; PF10393 ; PF00092
• Sequence:
  MEKMLAGCFLLILGQIVLLPAEARERSRGRSISRGRHARTHPQTALLESSCENKRADLVF
  IIDSSRSVNTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFKRKSEV
  ERAVKRMRHLSTGTMTGLAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQDSVAEV
  AAKARDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQIETLTSVFQKKLCTAH
  MCSTLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCVNVPGS
  FVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPDKKTCT
  KIDYCASSNHGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEHECVNM
  EESYYCRCHRGYTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFLINEDLK
  TCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDHGCEHSC
  VSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECLEGFRLAE
  DGKRCRRKDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCTEGPIDLVFVI
  DGSKSLGEENFEVVKQFVTGIIDSLTISPKAARVGLLQYSTQVHTEFTLRNFNSAKDMKK
  AVAHMKYMGKGSMTGLALKHMFERSFTQGEGARPLSTRVPRAAIVFTDGRAQDDVSEWAS
  KAKANGITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEISEKLKKGICEALED
  SDGRQDSPAGELPKTVQQPTESEPVTINIQDLLSCSNFAVQHRYLFEEDNLLRSTQKLSH
  STKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTQRMEALENRLRYR
• Function: Involved in matrix assembly.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Allergic rhinitis	DIS3U9HN	Strong	Biomarker	[2]
Aortic valve disorder	DISKLYD7	Strong	Biomarker	[3]
Erectile dysfunction	DISD8MTH	Strong	Genetic Variation	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[5]
Astrocytoma	DISL3V18	moderate	Biomarker	[6]
Neurofibromatosis type 1	DIS53JH9	moderate	Biomarker	[6]
Stroke	DISX6UHX	Limited	Biomarker	[7]

This DOT Affected the Drug Response of 8 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Matrilin-2 (MATN2) decreases the response to substance of Doxorubicin.	[25]
Cisplatin	DMRHGI9	Approved	Matrilin-2 (MATN2) decreases the response to substance of Cisplatin.	[25]
Methotrexate	DM2TEOL	Approved	Matrilin-2 (MATN2) decreases the response to substance of Methotrexate.	[25]
Etoposide	DMNH3PG	Approved	Matrilin-2 (MATN2) affects the response to substance of Etoposide.	[26]
Paclitaxel	DMLB81S	Approved	Matrilin-2 (MATN2) decreases the response to substance of Paclitaxel.	[25]
Mitomycin	DMH0ZJE	Approved	Matrilin-2 (MATN2) affects the response to substance of Mitomycin.	[26]
Topotecan	DMP6G8T	Approved	Matrilin-2 (MATN2) decreases the response to substance of Topotecan.	[25]
Chlorothiazide	DMLHESP	Approved	Matrilin-2 (MATN2) increases the Neutropenia ADR of Chlorothiazide.	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Matrilin-2 (MATN2).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Matrilin-2 (MATN2).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Matrilin-2 (MATN2).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Matrilin-2 (MATN2).	[11]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Matrilin-2 (MATN2).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Matrilin-2 (MATN2).	[14]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Matrilin-2 (MATN2).	[15]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Matrilin-2 (MATN2).	[16]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Matrilin-2 (MATN2).	[17]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Matrilin-2 (MATN2).	[18]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Matrilin-2 (MATN2).	[19]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Matrilin-2 (MATN2).	[20]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Matrilin-2 (MATN2).	[21]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Matrilin-2 (MATN2).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Matrilin-2 (MATN2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Matrilin-2 (MATN2).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Matrilin-2 (MATN2).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Matrilin-2 (MATN2).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Matrilin-2 (MATN2).	[13]

References

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• [2] MiR-202-5p Promotes M2 Polarization in Allergic Rhinitis by Targeting MATN2.Int Arch Allergy Immunol. 2019;178(2):119-127. doi: 10.1159/000493803. Epub 2018 Nov 8.
• [3] ADAMTS5 Deficiency in Calcified Aortic Valves Is Associated With Elevated Pro-Osteogenic Activity in Valvular Interstitial Cells.Arterioscler Thromb Vasc Biol. 2017 Jul;37(7):1339-1351. doi: 10.1161/ATVBAHA.117.309021. Epub 2017 May 25.
• [4] GWAS Identifies Risk Locus for Erectile Dysfunction and Implicates Hypothalamic Neurobiology and Diabetes in Etiology.Am J Hum Genet. 2019 Jan 3;104(1):157-163. doi: 10.1016/j.ajhg.2018.11.004. Epub 2018 Dec 21.
• [5] Expression of matrilin-2 in liver cirrhosis and hepatocellular carcinoma.Pathol Oncol Res. 2008 Mar;14(1):15-22. doi: 10.1007/s12253-008-9005-4. Epub 2008 Apr 2.
• [6] Matrilin-2 expression distinguishes clinically relevant subsets of pilocytic astrocytoma.Neurology. 2006 Jan 10;66(1):127-30. doi: 10.1212/01.wnl.0000188667.66646.1c.
• [7] White Matter Stroke Induces a Unique Oligo-Astrocyte Niche That Inhibits Recovery.J Neurosci. 2019 Nov 20;39(47):9343-9359. doi: 10.1523/JNEUROSCI.0103-19.2019. Epub 2019 Oct 7.
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• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
• [11] 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.
• [12] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [13] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [14] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
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• [16] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [17] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [18] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [19] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [20] Steroid and xenobiotic receptor-mediated effects of bisphenol A on human osteoblasts. Life Sci. 2016 Jun 15;155:29-35.
• [21] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [22] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [23] 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.
• [24] 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.
• [25] Microarray-based detection and expression analysis of extracellular matrix proteins in drug?resistant ovarian cancer cell lines. Oncol Rep. 2014 Nov;32(5):1981-90. doi: 10.3892/or.2014.3468. Epub 2014 Sep 9.
• [26] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [27] Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan. Cancer Sci. 2013 Aug;104(8):1074-82. doi: 10.1111/cas.12186. Epub 2013 Jun 10.