Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2VUR7L)

• DOT Name: Cytoplasmic aconitate hydratase (ACO1)
• Synonyms: Aconitase; EC 4.2.1.3; Citrate hydro-lyase; Ferritin repressor protein; Iron regulatory protein 1; IRP1; Iron-responsive element-binding protein 1; IRE-BP 1
• Gene Name: ACO1
• Related Disease:
  Alzheimer disease
  Anemia
  Duodenal ulcer
  Hepatocellular carcinoma
  Hereditary hemochromatosis
  Hereditary hyperferritinemia with congenital cataracts
  Huntington disease
  Neoplasm
  Neuroblastoma
  Pancreatic cancer
  Pheochromocytoma
  Polycythemia
  Polycythemia vera
  Prostate cancer
  Secondary polycythemia
  Age-related macular degeneration
  High blood pressure
  Non-alcoholic steatohepatitis
  Advanced cancer
  Cutaneous melanoma
  IRIDA syndrome
  Iron-deficiency anemia
  Osteoarthritis
  Parkinson disease
  Psoriasis
  Toxoplasmosis
• UniProt ID: ACOHC_HUMAN
• PDB ID: 2B3X; 2B3Y
• EC Number: 4.2.1.3
• Pfam ID: PF00330 ; PF00694
• Sequence:
  MSNPFAHLAEPLDPVQPGKKFFNLNKLEDSRYGRLPFSIRVLLEAAIRNCDEFLVKKQDI
  ENILHWNVTQHKNIEVPFKPARVILQDFTGVPAVVDFAAMRDAVKKLGGDPEKINPVCPA
  DLVIDHSIQVDFNRRADSLQKNQDLEFERNRERFEFLKWGSQAFHNMRIIPPGSGIIHQV
  NLEYLARVVFDQDGYYYPDSLVGTDSHTTMIDGLGILGWGVGGIEAEAVMLGQPISMVLP
  QVIGYRLMGKPHPLVTSTDIVLTITKHLRQVGVVGKFVEFFGPGVAQLSIADRATIANMC
  PEYGATAAFFPVDEVSITYLVQTGRDEEKLKYIKKYLQAVGMFRDFNDPSQDPDFTQVVE
  LDLKTVVPCCSGPKRPQDKVAVSDMKKDFESCLGAKQGFKGFQVAPEHHNDHKTFIYDNT
  EFTLAHGSVVIAAITSCTNTSNPSVMLGAGLLAKKAVDAGLNVMPYIKTSLSPGSGVVTY
  YLQESGVMPYLSQLGFDVVGYGCMTCIGNSGPLPEPVVEAITQGDLVAVGVLSGNRNFEG
  RVHPNTRANYLASPPLVIAYAIAGTIRIDFEKEPLGVNAKGQQVFLKDIWPTRDEIQAVE
  RQYVIPGMFKEVYQKIETVNESWNALATPSDKLFFWNSKSTYIKSPPFFENLTLDLQPPK
  SIVDAYVLLNLGDSVTTDHISPAGNIARNSPAARYLTNRGLTPREFNSYGSRRGNDAVMA
  RGTFANIRLLNRFLNKQAPQTIHLPSGEILDVFDAAERYQQAGLPLIVLAGKEYGAGSSR
  DWAAKGPFLLGIKAVLAESYERIHRSNLVGMGVIPLEYLPGENADALGLTGQERYTIIIP
  ENLKPQMKVQVKLDTGKTFQAVMRFDTDVELTYFLNGGILNYMIRKMAK
• Function: Bifunctional iron sensor that switches between 2 activities depending on iron availability. Iron deprivation, promotes its mRNA binding activity through which it regulates the expression of genes involved in iron uptake, sequestration and utilization. Binds to iron-responsive elements (IRES) in the untranslated region of target mRNAs preventing for instance the translation of ferritin and aminolevulinic acid synthase and stabilizing the transferrin receptor mRNA ; Conversely, when cellular iron levels are high, binds a 4Fe-4S cluster which precludes RNA binding activity and promotes the aconitase activity, the isomerization of citrate to isocitrate via cis-aconitate.
• KEGG Pathway:
  Citrate cycle (TCA cycle) (hsa00020)
  Glyoxylate and dicarboxylate metabolism (hsa00630)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  2-Oxocarboxylic acid metabolism (hsa01210)
  Biosynthesis of amino acids (hsa01230)
• Reactome Pathway: Iron uptake and transport (R-HSA-917937)
• BioCyc Pathway: MetaCyc:HS04597-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Anemia	DISTVL0C	Strong	Genetic Variation	[2]
Duodenal ulcer	DISNHHCN	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[4]
Hereditary hemochromatosis	DISVG5MT	Strong	Biomarker	[5]
Hereditary hyperferritinemia with congenital cataracts	DISGL689	Strong	Genetic Variation	[6]
Huntington disease	DISQPLA4	Strong	Altered Expression	[7]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[8]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[9]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[10]
Pheochromocytoma	DIS56IFV	Strong	Genetic Variation	[8]
Polycythemia	DIS8B6VW	Strong	Biomarker	[11]
Polycythemia vera	DISB5FPO	Strong	Genetic Variation	[8]
Prostate cancer	DISF190Y	Strong	Altered Expression	[12]
Secondary polycythemia	DISKEVNK	Strong	Genetic Variation	[8]
Age-related macular degeneration	DIS0XS2C	moderate	Genetic Variation	[13]
High blood pressure	DISY2OHH	moderate	Biomarker	[14]
Non-alcoholic steatohepatitis	DIST4788	moderate	Altered Expression	[15]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[16]
Cutaneous melanoma	DIS3MMH9	Limited	Genetic Variation	[17]
IRIDA syndrome	DISPN8YW	Limited	Biomarker	[18]
Iron-deficiency anemia	DIS0VQYF	Limited	Altered Expression	[5]
Osteoarthritis	DIS05URM	Limited	Biomarker	[19]
Parkinson disease	DISQVHKL	Limited	Altered Expression	[20]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[21]
Toxoplasmosis	DISYP8FH	Limited	Altered Expression	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitomycin	DMH0ZJE	Approved	Cytoplasmic aconitate hydratase (ACO1) affects the response to substance of Mitomycin.	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Cytoplasmic aconitate hydratase (ACO1).	[23]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cytoplasmic aconitate hydratase (ACO1).	[24]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cytoplasmic aconitate hydratase (ACO1).	[25]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cytoplasmic aconitate hydratase (ACO1).	[26]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cytoplasmic aconitate hydratase (ACO1).	[27]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cytoplasmic aconitate hydratase (ACO1).	[28]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cytoplasmic aconitate hydratase (ACO1).	[29]
Arsenic	DMTL2Y1	Approved	Arsenic increases the activity of Cytoplasmic aconitate hydratase (ACO1).	[30]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cytoplasmic aconitate hydratase (ACO1).	[31]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Cytoplasmic aconitate hydratase (ACO1).	[32]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cytoplasmic aconitate hydratase (ACO1).	[33]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Cytoplasmic aconitate hydratase (ACO1).	[34]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Cytoplasmic aconitate hydratase (ACO1).	[36]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Cytoplasmic aconitate hydratase (ACO1).	[37]
Gallium nitrate	DMF9O6B	Approved	Gallium nitrate increases the expression of Cytoplasmic aconitate hydratase (ACO1).	[38]
Trabectedin	DMG3Y89	Approved	Trabectedin increases the expression of Cytoplasmic aconitate hydratase (ACO1).	[39]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Cytoplasmic aconitate hydratase (ACO1).	[40]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the activity of Cytoplasmic aconitate hydratase (ACO1).	[41]
Manganese	DMKT129	Investigative	Manganese increases the activity of Cytoplasmic aconitate hydratase (ACO1).	[30]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Cytoplasmic aconitate hydratase (ACO1).	[42]
PD98059	DMZC90M	Investigative	PD98059 increases the expression of Cytoplasmic aconitate hydratase (ACO1).	[43]

2 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 Cytoplasmic aconitate hydratase (ACO1).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cytoplasmic aconitate hydratase (ACO1).	[35]

References

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