Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBTL3PN)

• DOT Name: Tyrosine-protein kinase receptor Tie-1 (TIE1)
• Synonyms: EC 2.7.10.1
• Gene Name: TIE1
• Related Disease: Lymphatic malformation 11
• UniProt ID: TIE1_HUMAN
• PDB ID: 5N06
• EC Number: 2.7.10.1
• Pfam ID: PF00041 ; PF00047 ; PF07714
• Sequence:
  MVWRVPPFLLPILFLASHVGAAVDLTLLANLRLTDPQRFFLTCVSGEAGAGRGSDAWGPP
  LLLEKDDRIVRTPPGPPLRLARNGSHQVTLRGFSKPSDLVGVFSCVGGAGARRTRVIYVH
  NSPGAHLLPDKVTHTVNKGDTAVLSARVHKEKQTDVIWKSNGSYFYTLDWHEAQDGRFLL
  QLPNVQPPSSGIYSATYLEASPLGSAFFRLIVRGCGAGRWGPGCTKECPGCLHGGVCHDH
  DGECVCPPGFTGTRCEQACREGRFGQSCQEQCPGISGCRGLTFCLPDPYGCSCGSGWRGS
  QCQEACAPGHFGADCRLQCQCQNGGTCDRFSGCVCPSGWHGVHCEKSDRIPQILNMASEL
  EFNLETMPRINCAAAGNPFPVRGSIELRKPDGTVLLSTKAIVEPEKTTAEFEVPRLVLAD
  SGFWECRVSTSGGQDSRRFKVNVKVPPVPLAAPRLLTKQSRQLVVSPLVSFSGDGPISTV
  RLHYRPQDSTMDWSTIVVDPSENVTLMNLRPKTGYSVRVQLSRPGEGGEGAWGPPTLMTT
  DCPEPLLQPWLEGWHVEGTDRLRVSWSLPLVPGPLVGDGFLLRLWDGTRGQERRENVSSP
  QARTALLTGLTPGTHYQLDVQLYHCTLLGPASPPAHVLLPPSGPPAPRHLHAQALSDSEI
  QLTWKHPEALPGPISKYVVEVQVAGGAGDPLWIDVDRPEETSTIIRGLNASTRYLFRMRA
  SIQGLGDWSNTVEESTLGNGLQAEGPVQESRAAEEGLDQQLILAVVGSVSATCLTILAAL
  LTLVCIRRSCLHRRRTFTYQSGSGEETILQFSSGTLTLTRRPKLQPEPLSYPVLEWEDIT
  FEDLIGEGNFGQVIRAMIKKDGLKMNAAIKMLKEYASENDHRDFAGELEVLCKLGHHPNI
  INLLGACKNRGYLYIAIEYAPYGNLLDFLRKSRVLETDPAFAREHGTASTLSSRQLLRFA
  SDAANGMQYLSEKQFIHRDLAARNVLVGENLASKIADFGLSRGEEVYVKKTMGRLPVRWM
  AIESLNYSVYTTKSDVWSFGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRMEQPRNCDD
  EVYELMRQCWRDRPYERPPFAQIALQLGRMLEARKAYVNMSLFENFTYAGIDATAEEA
• Function: Transmembrane tyrosine-protein kinase that may modulate TEK/TIE2 activity and contribute to the regulation of angiogenesis.
• Tissue Specificity: Specifically expressed in developing vascular endothelial cells.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lymphatic malformation 11	DISY7N3M	Limited	Autosomal dominant	[1]

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 Tyrosine-protein kinase receptor Tie-1 (TIE1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Tyrosine-protein kinase receptor Tie-1 (TIE1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tyrosine-protein kinase receptor Tie-1 (TIE1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tyrosine-protein kinase receptor Tie-1 (TIE1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tyrosine-protein kinase receptor Tie-1 (TIE1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Tyrosine-protein kinase receptor Tie-1 (TIE1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Tyrosine-protein kinase receptor Tie-1 (TIE1).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Tyrosine-protein kinase receptor Tie-1 (TIE1).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Tyrosine-protein kinase receptor Tie-1 (TIE1).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Tyrosine-protein kinase receptor Tie-1 (TIE1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Tyrosine-protein kinase receptor Tie-1 (TIE1).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Tyrosine-protein kinase receptor Tie-1 (TIE1).	[11]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [7] Gene alterations of ovarian cancer cells expressing estrogen receptors by estrogen and bisphenol a using microarray analysis. Lab Anim Res. 2011 Jun;27(2):99-107. doi: 10.5625/lar.2011.27.2.99. Epub 2011 Jun 22.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] 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.
• [10] 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.
• [11] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.