Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT331X59)

• DOT Name: Epidermal growth factor-like protein 6 (EGFL6)
• Synonyms: EGF-like protein 6; MAM and EGF domains-containing gene protein
• Gene Name: EGFL6
• UniProt ID: EGFL6_HUMAN
• Pfam ID: PF07645 ; PF00629
• Sequence:
  MPLPWSLALPLLLSWVAGGFGNAASARHHGLLASARQPGVCHYGTKLACCYGWRRNSKGV
  CEATCEPGCKFGECVGPNKCRCFPGYTGKTCSQDVNECGMKPRPCQHRCVNTHGSYKCFC
  LSGHMLMPDATCVNSRTCAMINCQYSCEDTEEGPQCLCPSSGLRLAPNGRDCLDIDECAS
  GKVICPYNRRCVNTFGSYYCKCHIGFELQYISGRYDCIDINECTMDSHTCSHHANCFNTQ
  GSFKCKCKQGYKGNGLRCSAIPENSVKEVLRAPGTIKDRIKKLLAHKNSMKKKAKIKNVT
  PEPTRTPTPKVNLQPFNYEEIVSRGGNSHGGKKGNEEKMKEGLEDEKREEKALKNDIEER
  SLRGDVFFPKVNEAGEFGLILVQRKALTSKLEHKDLNISVDCSFNHGICDWKQDREDDFD
  WNPADRDNAIGFYMAVPALAGHKKDIGRLKLLLPDLQPQSNFCLLFDYRLAGDKVGKLRV
  FVKNSNNALAWEKTTSEDEKWKTGKIQLYQGTDATKSIIFEAERGKGKTGEIAVDGVLLV
  SGLCPDSLLSVDD
• Function: May bind integrin alpha-8/beta-1 and play a role in hair follicle morphogenesis. Promotes matrix assembly.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Epidermal growth factor-like protein 6 (EGFL6) decreases the response to substance of Doxorubicin.	[11]
Cisplatin	DMRHGI9	Approved	Epidermal growth factor-like protein 6 (EGFL6) decreases the response to substance of Cisplatin.	[11]
Methotrexate	DM2TEOL	Approved	Epidermal growth factor-like protein 6 (EGFL6) decreases the response to substance of Methotrexate.	[11]
Paclitaxel	DMLB81S	Approved	Epidermal growth factor-like protein 6 (EGFL6) decreases the response to substance of Paclitaxel.	[11]
Topotecan	DMP6G8T	Approved	Epidermal growth factor-like protein 6 (EGFL6) decreases the response to substance of Topotecan.	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Epidermal growth factor-like protein 6 (EGFL6).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Epidermal growth factor-like protein 6 (EGFL6).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Epidermal growth factor-like protein 6 (EGFL6).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Epidermal growth factor-like protein 6 (EGFL6).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Epidermal growth factor-like protein 6 (EGFL6).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Epidermal growth factor-like protein 6 (EGFL6).	[5]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Epidermal growth factor-like protein 6 (EGFL6).	[6]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Epidermal growth factor-like protein 6 (EGFL6).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Epidermal growth factor-like protein 6 (EGFL6).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Epidermal growth factor-like protein 6 (EGFL6).	[10]

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] Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
• [3] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [4] 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.
• [5] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [6] 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.
• [7] Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205-18.
• [8] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [9] 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.
• [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] 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.