Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOTX9VU)

DOT Name	Transcriptional regulator ERG (ERG)
Synonyms	Transforming protein ERG
Gene Name	ERG
Related Disease	Abdominal aortic aneurysm ( ) Acute myelogenous leukaemia ( ) Autism ( ) Carcinoma ( ) Hepatitis B virus infection ( ) Metastatic malignant neoplasm ( ) Small-cell lung cancer ( ) Acinar cell carcinoma ( ) Acute leukaemia ( ) Acute megakaryoblastic leukemia ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Benign prostatic hyperplasia ( ) Bone osteosarcoma ( ) Breast cancer ( ) Breast carcinoma ( ) Cardiovascular disease ( ) Childhood acute lymphoblastic leukemia ( ) CLN2 Batten disease ( ) Cone dystrophy ( ) Ductal breast carcinoma in situ ( ) Knee osteoarthritis ( ) Lymphoid leukemia ( ) Metastatic prostate carcinoma ( ) Multiple sclerosis ( ) Myeloid leukaemia ( ) Obesity ( ) Osteosarcoma ( ) Parkinson disease ( ) Promyelocytic leukaemia ( ) Prostate disease ( ) Retinitis pigmentosa ( ) Rheumatoid arthritis ( ) Severe early-childhood-onset retinal dystrophy ( ) Leukemia ( ) Retinopathy ( ) Adenocarcinoma ( ) Ewing sarcoma/peripheral primitive neuroectodermal tumor ( ) leukaemia ( ) Prostate adenocarcinoma ( )
UniProt ID	ERG_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1SXE; 4IRG; 4IRH; 4IRI; 5YBC; 5YBD; 6VGE; 6VGG
Pfam ID	PF00178 ; PF02198
Sequence	MASTIKEALSVVSEDQSLFECAYGTPHLAKTEMTASSSSDYGQTSKMSPRVPQQDWLSQP PARVTIKMECNPSQVNGSRNSPDECSVAKGGKMVGSPDTVGMNYGSYMEEKHMPPPNMTT NERRVIVPADPTLWSTDHVRQWLEWAVKEYGLPDVNILLFQNIDGKELCKMTKDDFQRLT PSYNADILLSHLHYLRETPLPHLTSDDVDKALQNSPRLMHARNTGGAAFIFPNTSVYPEA TQRITTRPDLPYEPPRRSAWTGHGHPTPQSKAAQPSPSTVPKTEDQRPQLDPYQILGPTS SRLANPGSGQIQLWQFLLELLSDSSNSSCITWEGTNGEFKMTDPDEVARRWGERKSKPNM NYDKLSRALRYYYDKNIMTKVHGKRYAYKFDFHGIAQALQPHPPESSLYKYPSDLPYMGS YHAHPQKMNFVAPHPPALPVTSSSFFAAPNPYWNSPTGGIYPNTRLPTSHMPSHLGTYY
Function	Transcriptional regulator. May participate in transcriptional regulation through the recruitment of SETDB1 histone methyltransferase and subsequent modification of local chromatin structure.
KEGG Pathway	Transcriptio.l misregulation in cancer (hsa05202 ) Prostate cancer (hsa05215 )

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Abdominal aortic aneurysm	DISD06OF	Definitive	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	Definitive	Altered Expression	[2]
Autism	DISV4V1Z	Definitive	Genetic Variation	[3]
Carcinoma	DISH9F1N	Definitive	Altered Expression	[4]
Hepatitis B virus infection	DISLQ2XY	Definitive	Genetic Variation	[5]
Metastatic malignant neoplasm	DIS86UK6	Definitive	Biomarker	[4]
Small-cell lung cancer	DISK3LZD	Definitive	Genetic Variation	[6]
Acinar cell carcinoma	DIS37Y0J	Strong	Altered Expression	[7]
Acute leukaemia	DISDQFDI	Strong	Biomarker	[8]
Acute megakaryoblastic leukemia	DIS0JX3M	Strong	Biomarker	[9]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[10]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[10]
Benign prostatic hyperplasia	DISI3CW2	Strong	Biomarker	[11]
Bone osteosarcoma	DIST1004	Strong	Genetic Variation	[12]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[13]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[13]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[14]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[15]
CLN2 Batten disease	DISZC5YB	Strong	Biomarker	[16]
Cone dystrophy	DIS7SAZZ	Strong	Biomarker	[17]
Ductal breast carcinoma in situ	DISLCJY7	Strong	Altered Expression	[18]
Knee osteoarthritis	DISLSNBJ	Strong	Genetic Variation	[19]
Lymphoid leukemia	DIS65TYQ	Strong	Biomarker	[20]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Altered Expression	[21]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[22]
Myeloid leukaemia	DISMN944	Strong	Altered Expression	[23]
Obesity	DIS47Y1K	Strong	Biomarker	[24]
Osteosarcoma	DISLQ7E2	Strong	Genetic Variation	[12]
Parkinson disease	DISQVHKL	Strong	Biomarker	[25]
Promyelocytic leukaemia	DISYGG13	Strong	Altered Expression	[26]
Prostate disease	DISFVG19	Strong	Biomarker	[27]
Retinitis pigmentosa	DISCGPY8	Strong	Biomarker	[28]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[29]
Severe early-childhood-onset retinal dystrophy	DISFDRFO	Strong	Biomarker	[30]
Leukemia	DISNAKFL	moderate	Biomarker	[31]
Retinopathy	DISB4B0F	moderate	Altered Expression	[32]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[33]
Ewing sarcoma/peripheral primitive neuroectodermal tumor	DISD4VQC	Limited	Biomarker	[34]
leukaemia	DISS7D1V	Limited	Biomarker	[31]
Prostate adenocarcinoma	DISBZYU8	Limited	Biomarker	[35]
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⏷ Show the Full List of 40 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

10 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 Transcriptional regulator ERG (ERG).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcriptional regulator ERG (ERG).	[37]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcriptional regulator ERG (ERG).	[38]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Transcriptional regulator ERG (ERG).	[39]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Transcriptional regulator ERG (ERG).	[40]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Transcriptional regulator ERG (ERG).	[41]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transcriptional regulator ERG (ERG).	[41]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transcriptional regulator ERG (ERG).	[38]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transcriptional regulator ERG (ERG).	[43]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Transcriptional regulator ERG (ERG).	[43]
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⏷ Show the Full List of 10 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transcriptional regulator ERG (ERG).	[42]
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References

1	Replication of Newly Identified Genetic Associations Between Abdominal Aortic Aneurysm and SMYD2, LINC00540, PCIF1/MMP9/ZNF335, and ERG.Eur J Vasc Endovasc Surg. 2020 Jan;59(1):92-97. doi: 10.1016/j.ejvs.2019.02.017. Epub 2019 Nov 1.
2	High IL2RA mRNA expression is an independent adverse prognostic biomarker in core binding factor and intermediate-risk acute myeloid leukemia.J Transl Med. 2019 Jun 6;17(1):191. doi: 10.1186/s12967-019-1926-z.
3	Individual common variants exert weak effects on the risk for autism spectrum disorders.Hum Mol Genet. 2012 Nov 1;21(21):4781-92. doi: 10.1093/hmg/dds301. Epub 2012 Jul 26.
4	Prostatic adenocarcinoma CNS parenchymal and dural metastases: alterations in ERG, CHD1 and MAP3K7 expression.J Neurooncol. 2019 Apr;142(2):319-325. doi: 10.1007/s11060-019-03099-x. Epub 2019 Jan 17.
5	A genome-wide association study of chronic hepatitis B identified novel risk locus in a Japanese population.Hum Mol Genet. 2011 Oct 1;20(19):3884-92. doi: 10.1093/hmg/ddr301. Epub 2011 Jul 12.
6	Increased androgen receptor gene copy number is associated with TMPRSS2-ERG rearrangement in prostatic small cell carcinoma.Mol Carcinog. 2015 Sep;54(9):900-7. doi: 10.1002/mc.22162. Epub 2014 Apr 29.
7	Evaluation of ERG and PTEN protein expression in cribriform architecture prostate carcinomas.Pathol Res Pract. 2017 Jan;213(1):34-38. doi: 10.1016/j.prp.2016.10.007. Epub 2016 Oct 26.
8	Molecular characteristic of acute leukemias with t(16;21)/FUS-ERG.Ann Hematol. 2018 Jun;97(6):977-988. doi: 10.1007/s00277-018-3267-z. Epub 2018 Feb 9.
9	Early lineage priming by trisomy of Erg leads to myeloproliferation in a Down syndrome model.PLoS Genet. 2015 May 14;11(5):e1005211. doi: 10.1371/journal.pgen.1005211. eCollection 2015 May.
10	A non-coding genetic variant associated with abdominal aortic aneurysm alters ERG gene regulation.Hum Mol Genet. 2020 Mar 13;29(4):554-565. doi: 10.1093/hmg/ddz256.
11	Detection of TMPRSS2-ERG fusion gene in benign prostatic hyperplasia.Tumour Biol. 2014 Oct;35(10):9597-602. doi: 10.1007/s13277-014-2250-0. Epub 2014 Jun 25.
12	The Evolutionarily Conserved Cassette Exon 7b Drives ERG's Oncogenic Properties.Transl Oncol. 2019 Jan;12(1):134-142. doi: 10.1016/j.tranon.2018.09.001. Epub 2018 Oct 5.
13	The PEA3 group of ETS-related transcription factors. Role in breast cancer metastasis.Adv Exp Med Biol. 2000;480:107-16. doi: 10.1007/0-306-46832-8_13.
14	The Transcription Factor ERG Regulates Super-Enhancers Associated With an Endothelial-Specific Gene Expression Program.Circ Res. 2019 Apr 26;124(9):1337-1349. doi: 10.1161/CIRCRESAHA.118.313788.
15	Deregulation of DUX4 and ERG in acute lymphoblastic leukemia.Nat Genet. 2016 Dec;48(12):1481-1489. doi: 10.1038/ng.3691. Epub 2016 Oct 24.
16	Ocular morphology and function in juvenile neuronal ceroid lipofuscinosis (CLN3) in the first decade of life.Ophthalmic Genet. 2017 May-Jun;38(3):252-259. doi: 10.1080/13816810.2016.1210651. Epub 2016 Aug 2.
17	Cone dystrophy with "supernormal" rod ERG: psychophysical testing shows comparable rod and cone temporal sensitivity losses with no gain in rod function.Invest Ophthalmol Vis Sci. 2014 Feb 10;55(2):832-40. doi: 10.1167/iovs.13-12919.
18	The expression profile and heterogeneity analysis of ERG in 633 consecutive prostate cancers from a single center.Prostate. 2019 Jun;79(8):819-825. doi: 10.1002/pros.23785. Epub 2019 Mar 22.
19	Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data. Nat Genet. 2019 Feb;51(2):230-236.
20	ERG induces a mesenchymal-like state associated with chemoresistance in leukemia cells.Oncotarget. 2014 Jan 30;5(2):351-62. doi: 10.18632/oncotarget.1449.
21	Comparison of ERG and SPINK1 expression among incidental and metastatic prostate cancer in Japanese men.Prostate. 2019 Jan;79(1):3-8. doi: 10.1002/pros.23705. Epub 2018 Jul 26.
22	Association of SHMT1, MAZ, ERG, and L3MBTL3 Gene Polymorphisms with Susceptibility to Multiple Sclerosis.Biochem Genet. 2019 Jun;57(3):355-370. doi: 10.1007/s10528-018-9894-1. Epub 2018 Nov 19.
23	Genome-scale expression and transcription factor binding profiles reveal therapeutic targets in transgenic ERG myeloid leukemia.Blood. 2013 Oct 10;122(15):2694-703. doi: 10.1182/blood-2013-01-477133. Epub 2013 Aug 23.
24	Height, Obesity, and the Risk of TMPRSS2:ERG-Defined Prostate Cancer.Cancer Epidemiol Biomarkers Prev. 2018 Feb;27(2):193-200. doi: 10.1158/1055-9965.EPI-17-0547. Epub 2017 Nov 22.
25	Combination of Multifocal Electroretinogram and Spectral-Domain OCT Can Increase Diagnostic Efficacy of Parkinson's Disease.Parkinsons Dis. 2018 Mar 1;2018:4163239. doi: 10.1155/2018/4163239. eCollection 2018.
26	High expression of the Ets-related gene (ERG) is an independent prognostic marker for relapse-free survival in patients with acute promyelocytic leukemia.Ann Hematol. 2013 Apr;92(4):443-9. doi: 10.1007/s00277-012-1648-2. Epub 2012 Dec 19.
27	Circulating Antioxidant Levels and Risk of Prostate Cancer by TMPRSS2:ERG.Prostate. 2017 May;77(6):647-653. doi: 10.1002/pros.23312. Epub 2017 Jan 19.
28	Time and frequency components of ERG responses in retinitis pigmentosa.Int Ophthalmol. 2018 Dec;38(6):2435-2444. doi: 10.1007/s10792-017-0748-3. Epub 2017 Nov 30.
29	Local production of complement proteins in rheumatoid arthritis synovium.Arthritis Rheum. 2002 Apr;46(4):934-45. doi: 10.1002/art.10183.
30	CFH Y402H polymorphism in Italian patients with age-related macular degeneration, retinitis pigmentosa, and Stargardt disease.Ophthalmic Genet. 2018 Dec;39(6):699-705. doi: 10.1080/13816810.2018.1525753. Epub 2018 Oct 4.
31	An ERG Enhancer-Based Reporter Identifies Leukemia Cells with Elevated Leukemogenic Potential Driven by ERG-USP9X Feed-Forward Regulation.Cancer Res. 2019 Aug 1;79(15):3862-3876. doi: 10.1158/0008-5472.CAN-18-3215. Epub 2019 Jun 7.
32	Cone Photoreceptor Dysfunction in Early-Stage Diabetic Retinopathy: Association Between the Activation Phase of Cone Phototransduction and the Flicker Electroretinogram.Invest Ophthalmol Vis Sci. 2019 Jan 2;60(1):64-72. doi: 10.1167/iovs.18-25946.
33	Molecular evidence that invasive adenocarcinoma can mimic prostatic intraepithelial neoplasia (PIN) and intraductal carcinoma through retrograde glandular colonization.J Pathol. 2016 Jan;238(1):31-41. doi: 10.1002/path.4628. Epub 2015 Oct 14.
34	Clinicopathological and molecular spectrum of ewing sarcomas/PNETs, including validation of EWSR1 rearrangement by conventional and array FISH technique in certain cases.Pathol Oncol Res. 2014 Jul;20(3):503-16. doi: 10.1007/s12253-013-9721-2. Epub 2013 Nov 30.
35	Integrative clinical transcriptome analysis reveals TMPRSS2-ERG dependency of prognostic biomarkers in prostate adenocarcinoma.Int J Cancer. 2020 Apr 1;146(7):2036-2046. doi: 10.1002/ijc.32792. Epub 2019 Nov 29.
36	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
37	Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
38	Comparative Analysis of Transcriptomic Changes including mRNA and microRNA Expression Induced by the Xenoestrogens Zearalenone and Bisphenol A in Human Ovarian Cells. Toxins (Basel). 2023 Feb 9;15(2):140. doi: 10.3390/toxins15020140.
39	The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
40	Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
41	Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer. Nature. 2014 Jun 12;510(7504):278-82. doi: 10.1038/nature13229. Epub 2014 Apr 23.
42	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.
43	Sulforaphane destabilizes the androgen receptor in prostate cancer cells by inactivating histone deacetylase 6. Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16663-8. doi: 10.1073/pnas.0908908106. Epub 2009 Sep 15.