Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIXX2TR)

• DOT Name: RUN and FYVE domain-containing protein 1 (RUFY1)
• Synonyms: FYVE-finger protein EIP1; La-binding protein 1; Rab4-interacting protein; Zinc finger FYVE domain-containing protein 12
• Gene Name: RUFY1
• Related Disease:
  Advanced cancer
  Gastric cancer
  Stomach cancer
• UniProt ID: RUFY1_HUMAN
• PDB ID: 2YQM; 2YW8
• Pfam ID: PF01363 ; PF02759
• Sequence:
  MADREGGCAAGRGRELEPELEPGPGPGSALEPGEEFEIVDRSQLPGPGDLRSATRPRAAE
  GWSAPILTLARRATGNLSASCGSALRAAAGLGGGDSGDGTARAASKCQMMEERANLMHMM
  KLSIKVLLQSALSLGRSLDADHAPLQQFFVVMEHCLKHGLKVKKSFIGQNKSFFGPLELV
  EKLCPEASDIATSVRNLPELKTAVGRGRAWLYLALMQKKLADYLKVLIDNKHLLSEFYEP
  EALMMEEEGMVIVGLLVGLNVLDANLCLKGEDLDSQVGVIDFSLYLKDVQDLDGGKEHER
  ITDVLDQKNYVEELNRHLSCTVGDLQTKIDGLEKTNSKLQEELSAATDRICSLQEEQQQL
  REQNELIRERSEKSVEITKQDTKVELETYKQTRQGLDEMYSDVWKQLKEEKKVRLELEKE
  LELQIGMKTEMEIAMKLLEKDTHEKQDTLVALRQQLEEVKAINLQMFHKAQNAESSLQQK
  NEAITSFEGKTNQVMSSMKQMEERLQHSERARQGAEERSHKLQQELGGRIGALQLQLSQL
  HEQCSSLEKELKSEKEQRQALQRELQHEKDTSSLLRMELQQVEGLKKELRELQDEKAELQ
  KICEEQEQALQEMGLHLSQSKLKMEDIKEVNQALKGHAWLKDDEATHCRQCEKEFSISRR
  KHHCRNCGHIFCNTCSSNELALPSYPKPVRVCDSCHTLLLQRCSSTAS
• Function: Binds phospholipid vesicles containing phosphatidylinositol 3-phosphate and participates in early endosomal trafficking.
• Tissue Specificity: Broadly expressed, with highest levels in lung, testis, kidney and brain.
• KEGG Pathway: Endocytosis (hsa04144)
• Reactome Pathway: Synthesis of PIPs at the plasma membrane (R-HSA-1660499)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	Strong	Biomarker	[1]
Stomach cancer	DISKIJSX	Strong	Biomarker	[1]

8 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 RUN and FYVE domain-containing protein 1 (RUFY1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RUN and FYVE domain-containing protein 1 (RUFY1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of RUN and FYVE domain-containing protein 1 (RUFY1).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RUN and FYVE domain-containing protein 1 (RUFY1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of RUN and FYVE domain-containing protein 1 (RUFY1).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of RUN and FYVE domain-containing protein 1 (RUFY1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of RUN and FYVE domain-containing protein 1 (RUFY1).	[10]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of RUN and FYVE domain-containing protein 1 (RUFY1).	[13]

4 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 RUN and FYVE domain-containing protein 1 (RUFY1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of RUN and FYVE domain-containing protein 1 (RUFY1).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of RUN and FYVE domain-containing protein 1 (RUFY1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of RUN and FYVE domain-containing protein 1 (RUFY1).	[12]

References

• [1] Podocalyxin-like protein promotes gastric cancer progression through interacting with RUN and FYVE domain containing 1 protein.Cancer Sci. 2019 Jan;110(1):118-134. doi: 10.1111/cas.13864. Epub 2018 Dec 15.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] 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.
• [7] 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.
• [8] 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.
• [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] 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.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [12] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [13] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.