Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOXWNV8)

• DOT Name: Nuclear respiratory factor 1 (NRF1)
• Synonyms: NRF-1; Alpha palindromic-binding protein; Alpha-pal
• Gene Name: NRF1
• Related Disease:
  Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia
  Invasive breast carcinoma
  Adult T-cell leukemia/lymphoma
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Autosomal dominant optic atrophy, classic form
  B-cell lymphoma
  B-cell neoplasm
  Brain cancer
  Brain disease
  Breast neoplasm
  Cardiac failure
  Chagas disease
  Congestive heart failure
  Corneal neovascularization
  Cytomegalovirus infection
  Fragile X syndrome
  Hepatitis B virus infection
  Her2-receptor negative breast cancer
  HER2/NEU overexpressing breast cancer
  Intervertebral disc degeneration
  Male infertility
  Melanocytic nevus
  Mitochondrial disease
  Nasopharyngeal carcinoma
  Neuroblastoma
  Non-alcoholic fatty liver disease
  Non-insulin dependent diabetes
  Obesity
  Parkinson disease
  Retinoblastoma
  T-cell leukaemia
  Triple negative breast cancer
  Type-1/2 diabetes
  Advanced cancer
  Amyotrophic lateral sclerosis
  Breast cancer
  Breast carcinoma
  Castration-resistant prostate carcinoma
  Epithelial ovarian cancer
  Glaucoma/ocular hypertension
  Hepatocellular carcinoma
  Kennedy disease
  Melanoma
  Neoplasm
  Nervous system inflammation
  Non-alcoholic steatohepatitis
  Van der Woude syndrome
• UniProt ID: NRF1_HUMAN
• PDB ID: 8K3D; 8K4L
• Pfam ID: PF10491
• Sequence:
  MEEHGVTQTEHMATIEAHAVAQQVQQVHVATYTEHSMLSADEDSPSSPEDTSYDDSDILN
  STAADEVTAHLAAAGPVGMAAAAAVATGKKRKRPHVFESNPSIRKRQQTRLLRKLRATLD
  EYTTRVGQQAIVLCISPSKPNPVFKVFGAAPLENVVRKYKSMILEDLESALAEHAPAPQE
  VNSELPPLTIDGIPVSVDKMTQAQLRAFIPEMLKYSTGRGKPGWGKESCKPIWWPEDIPW
  ANVRSDVRTEEQKQRVSWTQALRTIVKNCYKQHGREDLLYAFEDQQTQTQATATHSIAHL
  VPSQTVVQTFSNPDGTVSLIQVGTGATVATLADASELPTTVTVAQVNYSAVADGEVEQNW
  ATLQGGEMTIQTTQASEATQAVASLAEAAVAASQEMQQGATVTMALNSEAAAHAVATLAE
  ATLQGGGQIVLSGETAAAVGALTGVQDANGLVQIPVSMYQTVVTSLAQGNGPVQVAMAPV
  TTRISDSAVTMDGQAVEVVTLEQ
• Function: Transcription factor that activates the expression of the EIF2S1 (EIF2-alpha) gene. Links the transcriptional modulation of key metabolic genes to cellular growth and development. Implicated in the control of nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication.
• Tissue Specificity: Ubiquitously expressed with strongest expression in skeletal muscle.
• KEGG Pathway:
  Apelin sig.ling pathway (hsa04371)
  Huntington disease (hsa05016)
• Reactome Pathway:
  Transcriptional activation of mitochondrial biogenesis (R-HSA-2151201)
  PPARA activates gene expression (R-HSA-1989781)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia	DIS8CFD7	Definitive	Altered Expression	[1]
Invasive breast carcinoma	DISANYTW	Definitive	Biomarker	[2]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Altered Expression	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[5]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[5]
Autosomal dominant optic atrophy, classic form	DISXUAV9	Strong	Altered Expression	[6]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[7]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[8]
Brain cancer	DISBKFB7	Strong	Altered Expression	[9]
Brain disease	DIS6ZC3X	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[9]
Cardiac failure	DISDC067	Strong	Biomarker	[10]
Chagas disease	DIS8KNVF	Strong	Biomarker	[11]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[10]
Corneal neovascularization	DISKOGZP	Strong	Altered Expression	[12]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[13]
Fragile X syndrome	DISE8W3A	Strong	Biomarker	[14]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[15]
Her2-receptor negative breast cancer	DISS605N	Strong	Biomarker	[9]
HER2/NEU overexpressing breast cancer	DISYKID5	Strong	Biomarker	[9]
Intervertebral disc degeneration	DISG3AIM	Strong	Biomarker	[16]
Male infertility	DISY3YZZ	Strong	Altered Expression	[17]
Melanocytic nevus	DISYS32D	Strong	Altered Expression	[18]
Mitochondrial disease	DISKAHA3	Strong	Biomarker	[19]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Altered Expression	[20]
Neuroblastoma	DISVZBI4	Strong	Posttranslational Modification	[21]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[22]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[23]
Obesity	DIS47Y1K	Strong	Biomarker	[24]
Parkinson disease	DISQVHKL	Strong	Biomarker	[25]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[26]
T-cell leukaemia	DISJ6YIF	Strong	Altered Expression	[3]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[27]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[28]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[29]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Altered Expression	[30]
Breast cancer	DIS7DPX1	Limited	Biomarker	[31]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[31]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Biomarker	[32]
Epithelial ovarian cancer	DIS56MH2	Limited	Genetic Variation	[33]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Genetic Variation	[34]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[35]
Kennedy disease	DISXZVM1	Limited	Biomarker	[36]
Melanoma	DIS1RRCY	Limited	Altered Expression	[18]
Neoplasm	DISZKGEW	Limited	Biomarker	[29]
Nervous system inflammation	DISB3X5A	Limited	Altered Expression	[37]
Non-alcoholic steatohepatitis	DIST4788	Limited	Biomarker	[35]
Van der Woude syndrome	DISADZS1	Limited	Altered Expression	[38]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Zidovudine	DM4KI7O	Approved	Nuclear respiratory factor 1 (NRF1) increases the Mitochondrial toxicity ADR of Zidovudine.	[57]

21 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 Nuclear respiratory factor 1 (NRF1).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Nuclear respiratory factor 1 (NRF1).	[41]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclear respiratory factor 1 (NRF1).	[42]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nuclear respiratory factor 1 (NRF1).	[43]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Nuclear respiratory factor 1 (NRF1).	[44]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Nuclear respiratory factor 1 (NRF1).	[45]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Nuclear respiratory factor 1 (NRF1).	[47]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Nuclear respiratory factor 1 (NRF1).	[48]
Isoniazid	DM5JVS3	Approved	Isoniazid decreases the expression of Nuclear respiratory factor 1 (NRF1).	[49]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Nuclear respiratory factor 1 (NRF1).	[50]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Nuclear respiratory factor 1 (NRF1).	[51]
Acadesine	DM1RMF5	Phase 3	Acadesine increases the expression of Nuclear respiratory factor 1 (NRF1).	[49]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Nuclear respiratory factor 1 (NRF1).	[51]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Nuclear respiratory factor 1 (NRF1).	[52]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Nuclear respiratory factor 1 (NRF1).	[53]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Nuclear respiratory factor 1 (NRF1).	[54]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Nuclear respiratory factor 1 (NRF1).	[55]
Erythropoietin	DM3R8YL	Investigative	Erythropoietin increases the expression of Nuclear respiratory factor 1 (NRF1).	[42]
propylpyrazoletriol	DMTCP8K	Investigative	propylpyrazoletriol increases the expression of Nuclear respiratory factor 1 (NRF1).	[51]
Ethidium	DMMEQUR	Investigative	Ethidium increases the expression of Nuclear respiratory factor 1 (NRF1).	[56]
diarylpropionitril	DM14X29	Investigative	diarylpropionitril increases the expression of Nuclear respiratory factor 1 (NRF1).	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Nuclear respiratory factor 1 (NRF1).	[40]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide affects the methylation of Nuclear respiratory factor 1 (NRF1).	[46]

References

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