Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEUYTP1)

• DOT Name: Multiple epidermal growth factor-like domains protein 6 (MEGF6)
• Synonyms: Multiple EGF-like domains protein 6; Epidermal growth factor-like protein 3; EGF-like protein 3
• Gene Name: MEGF6
• Related Disease:
  Colorectal carcinoma
  Neoplasm
• UniProt ID: MEGF6_HUMAN
• Pfam ID: PF12662 ; PF07645 ; PF14670 ; PF00053
• Sequence:
  MSFLEEARAAGRAVVLALVLLLLPAVPVGASVPPRPLLPLQPGMPHVCAEQELTLVGRRQ
  PCVQALSHTVPVWKAGCGWQAWCVGHERRTVYYMGYRQVYTTEARTVLRCCRGWMQQPDE
  EGCLSAECSASLCFHGGRCVPGSAQPCHCPPGFQGPRCQYDVDECRTHNGGCQHRCVNTP
  GSYLCECKPGFRLHTDSRTCLAINSCALGNGGCQHHCVQLTITRHRCQCRPGFQLQEDGR
  HCVRRSPCANRNGSCMHRCQVVRGLARCECHVGYQLAADGKACEDVDECAAGLAQCAHGC
  LNTQGSFKCVCHAGYELGADGRQCYRIEMEIVNSCEANNGGCSHGCSHTSAGPLCTCPRG
  YELDTDQRTCIDVDDCADSPCCQQVCTNNPGGYECGCYAGYRLSADGCGCEDVDECASSR
  GGCEHHCTNLAGSFQCSCEAGYRLHEDRRGCSPLEEPMVDLDGELPFVRPLPHIAVLQDE
  LPQLFQDDDVGADEEEAELRGEHTLTEKFVCLDDSFGHDCSLTCDDCRNGGTCLLGLDGC
  DCPEGWTGLICNETCPPDTFGKNCSFSCSCQNGGTCDSVTGACRCPPGVSGTNCEDGCPK
  GYYGKHCRKKCNCANRGRCHRLYGACLCDPGLYGRFCHLTCPPWAFGPGCSEECQCVQPH
  TQSCDKRDGSCSCKAGFRGERCQAECELGYFGPGCWQACTCPVGVACDSVSGECGKRCPA
  GFQGEDCGQECPVGTFGVNCSSSCSCGGAPCHGVTGQCRCPPGRTGEDCEADCPEGRWGL
  GCQEICPACQHAARCDPETGACLCLPGFVGSRCQDVCPAGWYGPSCQTRCSCANDGHCHP
  ATGHCSCAPGWTGFSCQRACDTGHWGPDCSHPCNCSAGHGSCDAISGLCLCEAGYVGPRC
  EQQCPQGHFGPGCEQRCQCQHGAACDHVSGACTCPAGWRGTFCEHACPAGFFGLDCRSAC
  NCTAGAACDAVNGSCLCPAGRRGPRCAETCPAHTYGHNCSQACACFNGASCDPVHGQCHC
  APGWMGPSCLQACPAGLYGDNCRHSCLCQNGGTCDPVSGHCACPEGWAGLACEKECLPRD
  VRAGCRHSGGCLNGGLCDPHTGRCLCPAGWTGDKCQSPCLRGWFGEACAQRCSCPPGAAC
  HHVTGACRCPPGFTGSGCEQACPPGSFGEDCAQMCQCPGENPACHPATGTCSCAAGYHGP
  SCQQRCPPGRYGPGCEQLCGCLNGGSCDAATGACRCPTGFLGTDCNLTCPQGRFGPNCTH
  VCGCGQGAACDPVTGTCLCPPGRAGVRCERGCPQNRFGVGCEHTCSCRNGGLCHASNGSC
  SCGLGWTGRHCELACPPGRYGAACHLECSCHNNSTCEPATGTCRCGPGFYGQACEHPCPP
  GFHGAGCQGLCWCQHGAPCDPISGRCLCPAGFHGHFCERGCEPGSFGEGCHQRCDCDGGA
  PCDPVTGLCLCPPGRSGATCNLDCRRGQFGPSCTLHCDCGGGADCDPVSGQCHCVDGYMG
  PTCREGGPLRLPENPSLAQGSAGTLPASSRPTSRSGGPARH

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]

4 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 Multiple epidermal growth factor-like domains protein 6 (MEGF6).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Multiple epidermal growth factor-like domains protein 6 (MEGF6).	[8]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Multiple epidermal growth factor-like domains protein 6 (MEGF6).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Multiple epidermal growth factor-like domains protein 6 (MEGF6).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Multiple epidermal growth factor-like domains protein 6 (MEGF6).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Multiple epidermal growth factor-like domains protein 6 (MEGF6).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Multiple epidermal growth factor-like domains protein 6 (MEGF6).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Multiple epidermal growth factor-like domains protein 6 (MEGF6).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Multiple epidermal growth factor-like domains protein 6 (MEGF6).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Multiple epidermal growth factor-like domains protein 6 (MEGF6).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Multiple epidermal growth factor-like domains protein 6 (MEGF6).	[11]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Multiple epidermal growth factor-like domains protein 6 (MEGF6).	[11]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Multiple epidermal growth factor-like domains protein 6 (MEGF6).	[13]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Multiple epidermal growth factor-like domains protein 6 (MEGF6).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Multiple epidermal growth factor-like domains protein 6 (MEGF6).	[16]

References

• [1] MEGF6 Promotes the Epithelial-to-Mesenchymal Transition via the TGF/SMAD Signaling Pathway in Colorectal Cancer Metastasis.Cell Physiol Biochem. 2018;46(5):1895-1906. doi: 10.1159/000489374. Epub 2018 Apr 26.
• [2] Transcriptome profiling of caspase-2 deficient EMyc and Th-MYCN mouse tumors identifies distinct putative roles for caspase-2 in neuronal differentiation and immune signaling.Cell Death Dis. 2019 Jan 22;10(2):56. doi: 10.1038/s41419-018-1296-0.
• [3] 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.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] 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.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] 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.
• [11] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [12] 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.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [14] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [15] 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.
• [16] 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.