Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMA4YA4)

• DOT Name: Protein RUFY3 (RUFY3)
• Synonyms: RUN and FYVE domain-containing protein 3; Rap2-interacting protein x; RIPx; Single axon-regulated protein; Singar
• Gene Name: RUFY3
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Skin disease
  Gastric cancer
  Stomach cancer
• UniProt ID: RUFY3_HUMAN
• Pfam ID: PF02759
• Sequence:
  MSALTPPTDMPTPTTDKITQAAMETIYLCKFRVSMDGEWLCLRELDDISLTPDPEPTHED
  PNYLMANERMNLMNMAKLSIKGLIESALNLGRTLDSDYAPLQQFFVVMEHCLKHGLKAKK
  TFLGQNKSFWGPLELVEKLVPEAAEITASVKDLPGLKTPVGRGRAWLRLALMQKKLSEYM
  KALINKKELLSEFYEPNALMMEEEGAIIAGLLVGLNVIDANFCMKGEDLDSQVGVIDFSM
  YLKDGNSSKGTEGDGQITAILDQKNYVEELNRHLNATVNNLQAKVDALEKSNTKLTEELA
  VANNRIITLQEEMERVKEESSYILESNRKGPKQDRTAEGQALSEARKHLKEETQLRLDVE
  KELEMQISMRQEMELAMKMLEKDVCEKQDALVSLRQQLDDLRALKHELAFKLQSSDLGVK
  QKSELNSRLEEKTNQMAATIKQLEQSEKDLVKQAKTLNSAANKLIPKHH
• Function: Plays a role in the generation of neuronal polarity formation and axon growth. Implicated in the formation of a single axon by developing neurons. May inhibit the formation of additional axons by inhibition of PI3K in minor neuronal processes. Plays a role in the formation of F-actin-enriched protrusive structures at the cell periphery. Plays a role in cytoskeletal organization by regulating the subcellular localization of FSCN1 and DBN1 at axonal growth cones. Promotes gastric cancer cell migration and invasion in a PAK1-dependent manner.
• Tissue Specificity: Overexpressed in gastric cancer cells and tissues (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[2]
Lung cancer	DISCM4YA	Strong	Altered Expression	[2]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[2]
Skin disease	DISDW8R6	Strong	Biomarker	[3]
Gastric cancer	DISXGOUK	Limited	Biomarker	[4]
Stomach cancer	DISKIJSX	Limited	Biomarker	[4]

15 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 Protein RUFY3 (RUFY3).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein RUFY3 (RUFY3).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein RUFY3 (RUFY3).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein RUFY3 (RUFY3).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein RUFY3 (RUFY3).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein RUFY3 (RUFY3).	[10]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Protein RUFY3 (RUFY3).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein RUFY3 (RUFY3).	[12]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Protein RUFY3 (RUFY3).	[13]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Protein RUFY3 (RUFY3).	[14]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Protein RUFY3 (RUFY3).	[15]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Protein RUFY3 (RUFY3).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein RUFY3 (RUFY3).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein RUFY3 (RUFY3).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein RUFY3 (RUFY3).	[18]

References

• [1] Rufy3 promotes metastasis through epithelial-mesenchymal transition in colorectal cancer.Cancer Lett. 2017 Apr 1;390:30-38. doi: 10.1016/j.canlet.2017.01.001. Epub 2017 Jan 13.
• [2] RUFY3 Predicts Poor Prognosis and Promotes Metastasis through Epithelial-mesenchymal Transition in Lung Adenocarcinoma.J Cancer. 2019 Oct 17;10(25):6278-6285. doi: 10.7150/jca.35072. eCollection 2019.
• [3] Gene expression profiles in peripheral lymphocytes by arsenic exposure and skin lesion status in a Bangladeshi population. Cancer Epidemiol Biomarkers Prev. 2006 Jul;15(7):1367-75. doi: 10.1158/1055-9965.EPI-06-0106.
• [4] HOXD9 promotes the growth, invasion and metastasis of gastric cancer cells by transcriptional activation of RUFY3.J Exp Clin Cancer Res. 2019 Sep 23;38(1):412. doi: 10.1186/s13046-019-1399-1.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [9] 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.
• [10] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [11] Gene expression profiles in peripheral lymphocytes by arsenic exposure and skin lesion status in a Bangladeshi population. Cancer Epidemiol Biomarkers Prev. 2006 Jul;15(7):1367-75. doi: 10.1158/1055-9965.EPI-06-0106.
• [12] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [13] 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.
• [14] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [15] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [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.
• [17] 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.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.