Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT9C6SM)

• DOT Name: RUN and FYVE domain-containing protein 2 (RUFY2)
• Synonyms: Rab4-interacting protein related
• Gene Name: RUFY2
• Related Disease: Thyroid gland papillary carcinoma
• UniProt ID: RUFY2_HUMAN
• Pfam ID: PF01363 ; PF02759
• Sequence:
  MATKDPTAVERANLLNMAKLSIKGLIESALSFGRTLDSDYPPLQQFFVVMEHCLKHGLKV
  RKSFLSYNKTIWGPLELVEKLYPEAEEIGASVRDLPGLKTPLGRARAWLRLALMQKKMAD
  YLRCLIIQRDLLSEFYEYHALMMEEEGAVIVGLLVGLNVIDANLCVKGEDLDSQVGVIDF
  SMYLKNEEDIGNKERNVQIAAILDQKNYVEELNRQLNSTVSSLHSRVDSLEKSNTKLIEE
  LAIAKNNIIKLQEENHQLRSENKLILMKTQQHLEVTKVDVETELQTYKHSRQGLDEMYNE
  ARRQLRDESQLRQDVENELAVQVSMKHEIELAMKLLEKDIHEKQDTLIGLRQQLEEVKAI
  NIEMYQKLQGSEDGLKEKNEIIARLEEKTNKITAAMRQLEQRLQQAEKAQMEAEDEDEKY
  LQECLSKSDSLQKQISQKEKQLVQLETDLKIEKEWRQTLQEDLQKEKDALSHLRNETQQI
  ISLKKEFLNLQDENQQLKKIYHEQEQALQELGNKLSESKLKIEDIKEANKALQGLVWLKD
  KEATHCKLCEKEFSLSKRKHHCRNCGEIFCNACSDNELPLPSSPKPVRVCDSCHALLIQR
  CSSNLP
• Tissue Specificity: Expressed in brain, lung and testis.
• KEGG Pathway: Endocytosis (hsa04144)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Biomarker	[1]

12 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 2 (RUFY2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of RUN and FYVE domain-containing protein 2 (RUFY2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of RUN and FYVE domain-containing protein 2 (RUFY2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RUN and FYVE domain-containing protein 2 (RUFY2).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of RUN and FYVE domain-containing protein 2 (RUFY2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of RUN and FYVE domain-containing protein 2 (RUFY2).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of RUN and FYVE domain-containing protein 2 (RUFY2).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of RUN and FYVE domain-containing protein 2 (RUFY2).	[10]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of RUN and FYVE domain-containing protein 2 (RUFY2).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of RUN and FYVE domain-containing protein 2 (RUFY2).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of RUN and FYVE domain-containing protein 2 (RUFY2).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of RUN and FYVE domain-containing protein 2 (RUFY2).	[15]

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 RUN and FYVE domain-containing protein 2 (RUFY2).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of RUN and FYVE domain-containing protein 2 (RUFY2).	[12]

References

• [1] Novel rearrangements involving the RET gene in papillary thyroid carcinoma.Cancer Genet. 2019 Jan;230:13-20. doi: 10.1016/j.cancergen.2018.11.002. Epub 2018 Nov 13.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] 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.
• [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] 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] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] 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.
• [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] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.