Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZT6RAW)

• DOT Name: RNA exonuclease 1 homolog (REXO1)
• Synonyms: EC 3.1.-.-; Elongin-A-binding protein 1; EloA-BP1; Transcription elongation factor B polypeptide 3-binding protein 1
• Gene Name: REXO1
• Related Disease:
  Glioma
  Hepatocellular carcinoma
  Neoplasm
  Advanced cancer
  Cardiovascular disease
  Cervical cancer
  Cervical carcinoma
  Clear cell adenocarcinoma
  Kidney neoplasm
  Polycystic ovarian syndrome
  Pachyonychia congenita 3
  Rheumatoid arthritis
• UniProt ID: REXO1_HUMAN
• EC Number: 3.1.-.-
• Pfam ID: PF15870
• Sequence:
  MLRSTGFFRAIDCPYWSGAPGGPCRRPYCHFRHRGARGSGAPGDGGEAPPAAGLGYDPYN
  PELPKPPAQRENGTLGLGEEPRPDVLELELVNQAIEAVRSEVELEQRRYRELLETTREHR
  SAEAPALAPRGPNASPTVGPDEDAFPLAFDYSPGSHGLLSPDAGYQPTPLAAPAEPGSKY
  SLASLDRGQGRGGGGGGALEYVPKAVSQPRRHSRPVPSGKYVVDNSRPPTDLEYDPLSNY
  SARHLSRASSRDERAAKRPRGSRGSEPYTPAPKKLCDPFGSCDARFSDSEDEAATVPGNE
  PTTASTPKARADPEIKATGQPPSKEGLEAEGGGLRETKETAVQCDVGDLQPPPAKPASPA
  QVQSSQDGGCPKEGKPKKKKTGAPPAPSCKDGAQGKDKTKDKGRGRPVEKPRADKKGPQA
  SSPRRKAERPEGTKKKPSSATPVATSGKGRPDRPARRPSPTSGDSRPAAGRGPPRPLQLP
  DRKSTKAPSGKLVERKARSLDEGASQDAPKLKKRALSHADLFGDESEDEAAGPGVPSVWP
  SALPSLSSDSDSDSDSSLGFPEAQGPPKRLKASPPPSPAPSSSSSSSSSTSSAGADVDYS
  ALEKEVDFDSDPMEECLRIFNESTSVKTEDRGRLARQPPKEEKSEEKGLSGLTTLFPGQK
  RRISHLSKQGQEVEPPRRGPAVPPARPPTAQEVCYLRAQQAQRASASLLQAPARLAEKSP
  SVHISAPGEKRRIAHIPNPRLAAAPTGAKRTLAASGSQSSNGPEPGGQQLKTRTLSGMAS
  KTTTTIIPKRIAHSPSLQSLKKPIIPKEFGGKVPTVIRQRYLNLFIEECLKFCTSNQEAI
  EKALNEEKVAYDRSPSKNIYLNVAVNTLKKLRGLAPSAVPGLSKTSGRRVVSHEVVLGGR
  LAAKTSFSLSRPSSPRVEDLKGAALYSRLREYLLTQDQLKENGYPFPHPERPGGAIIFTA
  EEKRPKDSSCRTCCRCGTEYLVSSSGRCIRDEECYYHWGRLRRNRVAGGWETQYMCCSAA
  AGSVGCQVAKQHVQDGRKERLEGFVKTFEKELSGDTHPGIYALDCEMSYTTYGLELTRVT
  VVDTDVHVVYDTFVKPDNEIVDYNTRFSGVTEADLADTSVTLRDVQAVLLSMFSADTILI
  GHSLESDLLALKVIHSTVVDTSVLFPHRLGLPYKRSLRNLMADYLRQIIQDNVDGHSSSE
  DAGACMHLVIWKVREDAKTKR
• Function: Seems to have no detectable effect on transcription elongation in vitro.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway: Ribosome biogenesis in eukaryotes (hsa03008)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Definitive	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[2]
Neoplasm	DISZKGEW	Definitive	Posttranslational Modification	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[3]
Cervical cancer	DISFSHPF	Strong	Biomarker	[4]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[4]
Clear cell adenocarcinoma	DISYUGHZ	Strong	Altered Expression	[5]
Kidney neoplasm	DISBNZTN	Strong	Altered Expression	[5]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[6]
Pachyonychia congenita 3	DISZLC6C	Limited	Altered Expression	[7]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RNA exonuclease 1 homolog (REXO1).	[8]
Marinol	DM70IK5	Approved	Marinol increases the expression of RNA exonuclease 1 homolog (REXO1).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of RNA exonuclease 1 homolog (REXO1).	[10]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of RNA exonuclease 1 homolog (REXO1).	[11]

References

• [1] Knockdown of the potential cancer stem-like cell marker Rex-1 improves chemotherapeutic effects in gliomas.Hum Gene Ther. 2011 Dec;22(12):1551-62. doi: 10.1089/hum.2011.096. Epub 2011 Sep 29.
• [2] Deficiency in Embryonic Stem Cell Marker Reduced Expression 1 Activates Mitogen-Activated Protein Kinase Kinase 6-Dependent p38 Mitogen-Activated Protein Kinase Signaling to Drive Hepatocarcinogenesis.Hepatology. 2020 Jul;72(1):183-197. doi: 10.1002/hep.31020. Epub 2020 Apr 8.
• [3] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [4] REX1 promotes EMT-induced cell metastasis by activating the JAK2/STAT3-signaling pathway by targeting SOCS1 in cervical cancer.Oncogene. 2019 Oct;38(43):6940-6957. doi: 10.1038/s41388-019-0906-3. Epub 2019 Aug 13.
• [5] Decreased expression of the human stem cell marker, Rex-1 (zfp-42), in renal cell carcinoma.Carcinogenesis. 2006 Mar;27(3):499-507. doi: 10.1093/carcin/bgi299. Epub 2005 Dec 12.
• [6] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [7] Transcriptional regulation of Rex1 (zfp42) in normal prostate epithelial cells and prostate cancer cells.J Cell Physiol. 2010 Jul;224(1):17-27. doi: 10.1002/jcp.22071.
• [8] 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.
• [9] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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.