Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSH78HD)

• DOT Name: GTPase Era, mitochondrial (ERAL1)
• Synonyms: H-ERA; hERA; Conserved ERA-like GTPase; CEGA; ERA-W; ERA-like protein 1
• Gene Name: ERAL1
• Related Disease:
  Chorea-acanthocytosis
  Chronic kidney disease
  Neuroblastoma
  Rabies
  Renal osteodystrophy
  Arthritis
  Breast cancer
  Breast carcinoma
  Chronic renal failure
  End-stage renal disease
  Familial Mediterranean fever
  High blood pressure
  Juvenile idiopathic arthritis
  Myocardial infarction
  Nephropathy
  Psoriatic arthritis
  Scleroderma
  Systemic lupus erythematosus
  Systemic sclerosis
  Perrault syndrome 6
  Perrault syndrome
  Autoimmune disease
  Autosomal dominant polycystic kidney disease
  Castration-resistant prostate carcinoma
  Post-traumatic stress disorder
• UniProt ID: ERAL1_HUMAN
• PDB ID: 8CSP; 8CSQ
• Pfam ID: PF01926
• Sequence:
  MAAPSWRGARLVQSVLRVWQVGPHVARERVIPFSSLLGFQRRCVSCVAGSAFSGPRLASA
  SRSNGQGSALDHFLGFSQPDSSVTPCVPAVSMNRDEQDVLLVHHPDMPENSRVLRVVLLG
  APNAGKSTLSNQLLGRKVFPVSRKVHTTRCQALGVITEKETQVILLDTPGIISPGKQKRH
  HLELSLLEDPWKSMESADLVVVLVDVSDKWTRNQLSPQLLRCLTKYSQIPSVLVMNKVDC
  LKQKSVLLELTAALTEGVVNGKKLKMRQAFHSHPGTHCPSPAVKDPNTQSVGNPQRIGWP
  HFKEIFMLSALSQEDVKTLKQYLLTQAQPGPWEYHSAVLTSQTPEEICANIIREKLLEHL
  PQEVPYNVQQKTAVWEEGPGGELVIQQKLLVPKESYVKLLIGPKGHVISQIAQEAGHDLM
  DIFLCDVDIRLSVKLLK
• Function: Probable GTPase that plays a role in the mitochondrial ribosomal small subunit assembly. Specifically binds the 12S mitochondrial rRNA (12S mt-rRNA) to a 33 nucleotide section delineating the 3' terminal stem-loop region. May act as a chaperone that protects the 12S mt-rRNA on the 28S mitoribosomal subunit during ribosomal small subunit assembly.
• Reactome Pathway:
  Mitochondrial translation elongation (R-HSA-5389840)
  Mitochondrial translation termination (R-HSA-5419276)
  Mitochondrial translation initiation (R-HSA-5368286)

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chorea-acanthocytosis	DISW1V6N	Definitive	Biomarker	[1]
Chronic kidney disease	DISW82R7	Definitive	Biomarker	[2]
Neuroblastoma	DISVZBI4	Definitive	Biomarker	[3]
Rabies	DISSC4V5	Definitive	Biomarker	[3]
Renal osteodystrophy	DISN2OO5	Definitive	Biomarker	[2]
Arthritis	DIST1YEL	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Chronic renal failure	DISGG7K6	Strong	Genetic Variation	[6]
End-stage renal disease	DISXA7GG	Strong	Genetic Variation	[6]
Familial Mediterranean fever	DISVP5WP	Strong	Genetic Variation	[7]
High blood pressure	DISY2OHH	Strong	Biomarker	[8]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Altered Expression	[4]
Myocardial infarction	DIS655KI	Strong	Biomarker	[9]
Nephropathy	DISXWP4P	Strong	Genetic Variation	[10]
Psoriatic arthritis	DISLWTG2	Strong	Biomarker	[11]
Scleroderma	DISVQ342	Strong	Genetic Variation	[12]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[13]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[12]
Perrault syndrome 6	DISLMXA5	Moderate	Autosomal recessive	[14]
Perrault syndrome	DISG2YOV	Supportive	Autosomal recessive	[14]
Autoimmune disease	DISORMTM	Limited	Genetic Variation	[5]
Autosomal dominant polycystic kidney disease	DISBHWUI	Limited	Biomarker	[15]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Biomarker	[16]
Post-traumatic stress disorder	DISHL1EY	Limited	Biomarker	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of GTPase Era, mitochondrial (ERAL1).	[18]

3 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 GTPase Era, mitochondrial (ERAL1).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of GTPase Era, mitochondrial (ERAL1).	[20]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of GTPase Era, mitochondrial (ERAL1).	[21]

References

• [1] Current state of knowledge in Chorea-Acanthocytosis as core Neuroacanthocytosis syndrome.Eur J Med Genet. 2018 Nov;61(11):699-705. doi: 10.1016/j.ejmg.2017.12.007. Epub 2017 Dec 16.
• [2] Bone biopsy practice patterns across Europe: the European renal osteodystrophy initiative-a position paper.Nephrol Dial Transplant. 2017 Oct 1;32(10):1608-1613. doi: 10.1093/ndt/gfw468.
• [3] Generation of a novel live rabies vaccine strain with a high level of safety by introducing attenuating mutations in the nucleoprotein and glycoprotein.Vaccine. 2017 Oct 9;35(42):5622-5628. doi: 10.1016/j.vaccine.2017.08.050. Epub 2017 Sep 4.
• [4] Long-Term Outcomes in Juvenile Idiopathic Arthritis: Eighteen Years of Follow-Up in the Population-Based Nordic Juvenile Idiopathic Arthritis Cohort.Arthritis Care Res (Hoboken). 2020 Apr;72(4):507-516. doi: 10.1002/acr.23853.
• [5] Autoimmunity and Benefit from Trastuzumab Treatment in Breast Cancer: Results from the HERA Trial.Anticancer Res. 2019 Feb;39(2):797-802. doi: 10.21873/anticanres.13177.
• [6] The European Renal Association?European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report 2016: a summary.Clin Kidney J. 2019 Feb 26;12(5):702-720. doi: 10.1093/ckj/sfz011. eCollection 2019 Oct.
• [7] MEFV gene mutations in Turkish children with juvenile idiopathic arthritis.Eur J Pediatr. 2013 Aug;172(8):1061-7. doi: 10.1007/s00431-013-2003-x. Epub 2013 Apr 16.
• [8] Hypertension in dialysis patients: a consensus document by the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) and the Hypertension and the Kidney working group of the European Society of Hypertension (ESH).J Hypertens. 2017 Apr;35(4):657-676. doi: 10.1097/HJH.0000000000001283.
• [9] Thrombolytic Therapy in the Current ERA: Myocardial Infarction and Beyond.Curr Pharm Des. 2018;24(4):414-426. doi: 10.2174/1381612824666171227211623.
• [10] The nephrology crystal ball: the medium-term future.Nephrol Dial Transplant. 2020 Feb 1;35(2):222-226. doi: 10.1093/ndt/gfz199.
• [11] Leflunomide treatment in juvenile idiopathic arthritis.Rheumatol Int. 2019 Sep;39(9):1615-1619. doi: 10.1007/s00296-019-04385-7. Epub 2019 Jul 20.
• [12] Characteristics and Outcomes of Patients With Systemic Sclerosis (Scleroderma) Requiring Renal Replacement Therapy in Europe: Results From the ERA-EDTA Registry.Am J Kidney Dis. 2019 Feb;73(2):184-193. doi: 10.1053/j.ajkd.2018.05.016. Epub 2018 Aug 16.
• [13] Molecular analysis of estrogen receptor alpha and beta in lupus patients.Eur J Clin Invest. 2001 Jan;31(1):86-93. doi: 10.1046/j.1365-2362.2001.00762.x.
• [14] A homozygous missense mutation in ERAL1, encoding a mitochondrial rRNA chaperone, causes Perrault syndrome. Hum Mol Genet. 2017 Jul 1;26(13):2541-2550. doi: 10.1093/hmg/ddx152.
• [15] Prevalence of autosomal dominant polycystic kidney disease in the European Union.Nephrol Dial Transplant. 2017 Aug 1;32(8):1356-1363. doi: 10.1093/ndt/gfw240.
• [16] Higher Risk of Fragility Fractures in Prostate Cancer Patients Treated with Combined Radium-223 and Abiraterone: Prednisone May Be the Culprit.Eur Urol. 2019 Jun;75(6):894-895. doi: 10.1016/j.eururo.2019.01.026. Epub 2019 Jan 31.
• [17] EFFECT OF THE APOE 4 ALLELE AND COMBAT EXPOSURE ON PTSD AMONG IRAQ/AFGHANISTAN-ERA VETERANS.Depress Anxiety. 2015 May;32(5):307-15. doi: 10.1002/da.22348. Epub 2015 Feb 24.
• [18] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [19] 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.
• [20] 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.
• [21] 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.