Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCRY2AN)

• DOT Name: Ras-interacting protein 1 (RASIP1)
• Synonyms: Rain
• Gene Name: RASIP1
• Related Disease:
  Sotos syndrome
  Advanced cancer
  Neoplasm
  Non-small-cell lung cancer
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Bacterial infection
  Bipolar disorder
  Atopic dermatitis
  Psoriasis
• UniProt ID: RAIN_HUMAN
• PDB ID: 5KHO; 5KHQ
• Pfam ID: PF01843 ; PF00788
• Sequence:
  MLSGERKEGGSPRFGKLHLPVGLWINSPRKQLAKLGRRWPSAASVKSSSSDTGSRSSEPL
  PPPPPHVELRRVGAVKAAGGASGSRAKRISQLFRGSGTGTTGSSGAGGPGTPGGAQRWAS
  EKKLPELAAGVAPEPPLATRATAPPGVLKIFGAGLASGANYKSVLATARSTARELVAEAL
  ERYGLAGSPGGGPGESSCVDAFALCDALGRPAAAGVGSGEWRAEHLRVLGDSERPLLVQE
  LWRARPGWARRFELRGREEARRLEQEAFGAADSEGTGAPSWRPQKNRSRAASGGAALASP
  GPGTGSGAPAGSGGKERSENLSLRRSVSELSLQGRRRRQQERRQQALSMAPGAADAQIGT
  ADPGDFDQLTQCLIQAPSNRPYFLLLQGYQDAQDFVVYVMTREQHVFGRGGNSSGRGGSP
  APYVDTFLNAPDILPRHCTVRAGPEHPAMVRPSRGAPVTHNGCLLLREAELHPGDLLGLG
  EHFLFMYKDPRTGGSGPARPPWLPARPGATPPGPGWAFSCRLCGRGLQERGEALAAYLDG
  REPVLRFRPREEEALLGEIVRAAAAGSGDLPPLGPATLLALCVQHSARELELGHLPRLLG
  RLARLIKEAVWEKIKEIGDRQPENHPEGVPEVPLTPEAVSVELRPLMLWMANTTELLSFV
  QEKVLEMEKEADQEDPQLCNDLELCDEAMALLDEVIMCTFQQSVYYLTKTLYSTLPALLD
  SNPFTAGAELPGPGAELGAMPPGLRPTLGVFQAALELTSQCELHPDLVSQTFGYLFFFSN
  ASLLNSLMERGQGRPFYQWSRAVQIRTNLDLVLDWLQGAGLGDIATEFFRKLSMAVNLLC
  VPRTSLLKASWSSLRTDHPTLTPAQLHHLLSHYQLGPGRGPPAAWDPPPAEREAVDTGDI
  FESFSSHPPLILPLGSSRLRLTGPVTDDALHRELRRLRRLLWDLEQQELPANYRHGPPVA
  TSP
• Function: Required for the proper formation of vascular structures that develop via both vasculogenesis and angiogenesis. Acts as a critical and vascular-specific regulator of GTPase signaling, cell architecture, and adhesion, which is essential for endothelial cell morphogenesis and blood vessel tubulogenesis. Regulates the activity of Rho GTPases in part by recruiting ARHGAP29 and suppressing RhoA signaling and dampening ROCK and MYH9 activities in endothelial cells. May act as effector for Golgi-bound HRAS and other Ras-like proteins. May promote HRAS-mediated transformation. Negative regulator of amino acid starvation-induced autophagy.
• Tissue Specificity: Highly expressed in heart. Detected at lower levels in placenta and pancreas.
• KEGG Pathway: Adherens junction (hsa04520)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Sotos syndrome	DISN4U1D	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[4]
Thyroid cancer	DIS3VLDH	Strong	Altered Expression	[2]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[2]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[2]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[5]
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[6]
Atopic dermatitis	DISTCP41	Limited	Genetic Variation	[7]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[7]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Ras-interacting protein 1 (RASIP1) affects the response to substance of Etoposide.	[14]

2 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 Ras-interacting protein 1 (RASIP1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ras-interacting protein 1 (RASIP1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ras-interacting protein 1 (RASIP1).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Ras-interacting protein 1 (RASIP1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ras-interacting protein 1 (RASIP1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ras-interacting protein 1 (RASIP1).	[13]

References

• [1] Sotos syndrome is associated with deregulation of the MAPK/ERK-signaling pathway.PLoS One. 2012;7(11):e49229. doi: 10.1371/journal.pone.0049229. Epub 2012 Nov 14.
• [2] RAIN Is a Novel Enhancer-Associated lncRNA That Controls RUNX2 Expression and Promotes Breast and Thyroid Cancer.Mol Cancer Res. 2020 Jan;18(1):140-152. doi: 10.1158/1541-7786.MCR-19-0564. Epub 2019 Oct 17.
• [3] Triple-layer dissection of the lung adenocarcinoma transcriptome: regulation at the gene, transcript, and exon levels.Oncotarget. 2015 Oct 6;6(30):28755-73. doi: 10.18632/oncotarget.4810.
• [4] Rasip1 is a RUNX1 target gene and promotes migration of NSCLC cells.Cancer Manag Res. 2018 Oct 12;10:4537-4552. doi: 10.2147/CMAR.S168438. eCollection 2018.
• [5] RAIN study: a protocol for a randomised controlled trial evaluating efficacy, safety and cost-effectiveness of intravenous-to-oral antibiotic switch therapy in neonates with a probable bacterial infection.BMJ Open. 2019 Jul 9;9(7):e026688. doi: 10.1136/bmjopen-2018-026688.
• [6] Replication of bipolar disorder susceptibility alleles and identification of two novel genome-wide significant associations in a new bipolar disorder case-control sample.Mol Psychiatry. 2013 Dec;18(12):1302-7. doi: 10.1038/mp.2012.142. Epub 2012 Oct 16.
• [7] Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms.Am J Hum Genet. 2015 Jan 8;96(1):104-20. doi: 10.1016/j.ajhg.2014.12.004.
• [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] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [14] 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.