Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOQTF5K)

• DOT Name: Elongin-A (ELOA)
• Synonyms: EloA; Elongin 110 kDa subunit; RNA polymerase II transcription factor SIII subunit A1; SIII p110; Transcription elongation factor B polypeptide 3
• Gene Name: ELOA
• Related Disease:
  Asthma
  Brugada syndrome
  Clear cell renal carcinoma
  Hemangioblastoma
  Pheochromocytoma
  Ventricular tachycardia
  Von hippel-lindau disease
  Cutaneous mastocytosis
  Psoriasis
• UniProt ID: ELOA1_HUMAN
• PDB ID: 4HFX; 6ZUZ; 8OEV; 8OEW; 8OF0
• Pfam ID: PF06881 ; PF08711
• Sequence:
  MAAESALQVVEKLQARLAANPDPKKLLKYLKKLSTLPITVDILAETGVGKTVNSLRKHEH
  VGSFARDLVAQWKKLVPVERNAEPDEQDFEKSNSRKRPRDALQKEEEMEGDYQETWKATG
  SRSYSPDHRQKKHRKLSELERPHKVSHGHERRDERKRCHRMSPTYSSDPESSDYGHVQSP
  PSCTSPHQMYVDHYRSLEEDQEPIVSHQKPGKGHSNAFQDRLGASQERHLGEPHGKGVVS
  QNKEHKSSHKDKRPVDAKSDEKASVVSREKSHKALSKEENRRPPSGDNAREKPPSSGVKK
  EKDREGSSLKKKCLPPSEAASDNHLKKPKHRDPEKAKLDKSKQGLDSFDTGKGAGDLLPK
  VKEKGSNNLKTPEGKVKTNLDRKSLGSLPKVEETDMEDEFEQPTMSFESYLSYDQPRKKK
  KKIVKTSATALGDKGLKKNDSKSTGKNLDSVQKLPKVNKTKSEKPAGADLAKLRKVPDVL
  PVLPDLPLPAIQANYRPLPSLELISSFQPKRKAFSSPQEEEEAGFTGRRMNSKMQVYSGS
  KCAYLPKMMTLHQQCIRVLKNNIDSIFEVGGVPYSVLEPVLERCTPDQLYRIEEYNHVLI
  EETDQLWKVHCHRDFKEERPEEYESWREMYLRLQDAREQRLRVLTKNIQFAHANKPKGRQ
  AKMAFVNSVAKPPRDVRRRQEKFGTGGAAVPEKIKIKPAPYPMGSSHASASSISFNPSPE
  EPAYDGPSTSSAHLAPVVSSTVSYDPRKPTVKKIAPMMAKTIKAFKNRFSRR
• Function: SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex); As part of a multisubunit complex composed of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5; polyubiquitinates monoubiquitinated POLR2A.
• Reactome Pathway:
  Formation of HIV elongation complex in the absence of HIV Tat (R-HSA-167152)
  Formation of HIV-1 elongation complex containing HIV-1 Tat (R-HSA-167200)
  Pausing and recovery of Tat-mediated HIV elongation (R-HSA-167238)
  Tat-mediated HIV elongation arrest and recovery (R-HSA-167243)
  Tat-mediated elongation of the HIV-1 transcript (R-HSA-167246)
  HIV elongation arrest and recovery (R-HSA-167287)
  Pausing and recovery of HIV elongation (R-HSA-167290)
  RNA Polymerase II Pre-transcription Events (R-HSA-674695)
  TP53 Regulates Transcription of DNA Repair Genes (R-HSA-6796648)
  RNA Polymerase II Transcription Elongation (R-HSA-75955)
  Formation of RNA Pol II elongation complex (R-HSA-112382)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Definitive	Biomarker	[1]
Brugada syndrome	DISSGN0E	Strong	Biomarker	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Genetic Variation	[3]
Hemangioblastoma	DIS1EAZC	Strong	Genetic Variation	[3]
Pheochromocytoma	DIS56IFV	Strong	Genetic Variation	[3]
Ventricular tachycardia	DISIBXJ3	Strong	Biomarker	[2]
Von hippel-lindau disease	DIS6ZFQQ	Strong	Altered Expression	[3]
Cutaneous mastocytosis	DISLBZEF	Limited	Biomarker	[4]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[5]

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 Elongin-A (ELOA).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Elongin-A (ELOA).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Elongin-A (ELOA).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Elongin-A (ELOA).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat affects the expression of Elongin-A (ELOA).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Elongin-A (ELOA).	[11]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Elongin-A (ELOA).	[12]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Elongin-A (ELOA).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Elongin-A (ELOA).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Elongin-A (ELOA).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Elongin-A (ELOA).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Elongin-A (ELOA).	[16]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Elongin-A (ELOA).	[16]

References

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• [2] Prediction of ventricular tachyarrhythmia in Brugada syndrome by right ventricular outflow tract conduction delay signs.J Cardiovasc Electrophysiol. 2018 Jul;29(7):998-1003. doi: 10.1111/jce.13496. Epub 2018 Apr 20.
• [3] Expression of the von Hippel-Lindau-binding protein-1 (Vbp1) in fetal and adult mouse tissues.Hum Mol Genet. 1999 Feb;8(2):229-36. doi: 10.1093/hmg/8.2.229.
• [4] Radiofrequency ablation versus laparoscopic hepatectomy for hepatocellular carcinoma: A real world single center study.Eur J Surg Oncol. 2020 Apr;46(4 Pt A):548-559. doi: 10.1016/j.ejso.2019.10.026. Epub 2019 Oct 24.
• [5] Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms.Am J Hum Genet. 2015 Jan 8;96(1):104-20. doi: 10.1016/j.ajhg.2014.12.004.
• [6] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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.
• [10] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [11] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [12] Cell-type-specific responses to chemotherapeutics in breast cancer. Cancer Res. 2004 Jun 15;64(12):4218-26.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.