Details of Drug Off-Target (DOT)

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

• DOT Name: Extracellular matrix protein 2 (ECM2)
• Synonyms: Matrix glycoprotein SC1/ECM2
• Gene Name: ECM2
• UniProt ID: ECM2_HUMAN
• Pfam ID: PF12799 ; PF13855 ; PF00093
• Sequence:
  MKIAVLFCFFLLIIFQTDFGKNEEIPRKQRRKIYHRRLRKSSTSHKHRSNRQLGIQQTTV
  FTPVARLPIVNFDYSMEEKFESFSSFPGVESSYNVLPGKKGHCLVKGITMYNKAVWSPEP
  CTTCLCSDGRVLCDETMCHPQRCPQTVIPEGECCPVCSATVSYSLLSGIALNDRNEFSGD
  SSEQREPTNLLHKQLPPPQVGMDRIVRKEALQSEEDEEVKEEDTEQKRETPESRNQGQLY
  SEGDSRGGDRKQRPGEERRLAHQQQRQGREEEEDEEEEGEEGEEDEEDEEDPVRGDMFRM
  PSRSPLPAPPRGTLRLPSGCSLSYRTISCINAMLTQIPPLTAPQITSLELTGNSIASIPD
  EAFNGLPNLERLDLSKNNITSSGIGPKAFKLLKKLMRLNMDGNNLIQIPSQLPSTLEELK
  VNENNLQAIDEESLSDLNQLVTLELEGNNLSEANVNPLAFKPLKSLAYLRLGKNKFRIIP
  QGLPGSIEELYLENNQIEEITEICFNHTRKINVIVLRYNKIEENRIAPLAWINQENLESI
  DLSYNKLYHVPSYLPKSLLHLVLLGNQIERIPGYVFGHMEPGLEYLYLSFNKLADDGMDR
  VSFYGAYHSLRELFLDHNDLKSIPPGIQEMKALHFLRLNNNKIRNILPEEICNAEEDDDS
  NLEHLHLENNYIKIREIPSYTFSCIRSYSSIVLKPQNIK
• Function: Promotes matrix assembly and cell adhesiveness.
• Tissue Specificity: Expressed predominantly in adipose tissue as well as female-specific organs such as mammary gland, ovary, and uterus.

Molecular Interaction Atlas (MIA) of This DOT

11 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 Extracellular matrix protein 2 (ECM2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Extracellular matrix protein 2 (ECM2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Extracellular matrix protein 2 (ECM2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Extracellular matrix protein 2 (ECM2).	[4]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Extracellular matrix protein 2 (ECM2).	[5]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Extracellular matrix protein 2 (ECM2).	[6]
DTI-015	DMXZRW0	Approved	DTI-015 increases the expression of Extracellular matrix protein 2 (ECM2).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Extracellular matrix protein 2 (ECM2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Extracellular matrix protein 2 (ECM2).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Extracellular matrix protein 2 (ECM2).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Extracellular matrix protein 2 (ECM2).	[11]

References

• [1] 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.
• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] 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.
• [6] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [7] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [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] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.