Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5IM7B3)

• DOT Name: Endonuclease G, mitochondrial (ENDOG)
• Synonyms: Endo G; EC 3.1.30.-
• Gene Name: ENDOG
• Related Disease:
  Cardiac failure
  Congestive heart failure
  Gastric neoplasm
  Adult glioblastoma
  B-cell neoplasm
  Bone osteosarcoma
  Breast neoplasm
  Colon carcinoma
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Leber hereditary optic neuropathy
  Osteosarcoma
  Plasma cell myeloma
  Prostate cancer
  Prostate carcinoma
  Retinoblastoma
  Coronary atherosclerosis
  Myocardial ischemia
  Acute myelogenous leukaemia
  Myelodysplastic syndrome
  Neoplasm
  Neuroblastoma
  Parkinson disease
• UniProt ID: NUCG_HUMAN
• EC Number: 3.1.30.-
• Pfam ID: PF01223
• Sequence:
  MRALRAGLTLASGAGLGAVVEGWRRRREDARAAPGLLGRLPVLPVAAAAELPPVPGGPRG
  PGELAKYGLPGLAQLKSRESYVLCYDPRTRGALWVVEQLRPERLRGDGDRRECDFREDDS
  VHAYHRATNADYRGSGFDRGHLAAAANHRWSQKAMDDTFYLSNVAPQVPHLNQNAWNNLE
  KYSRSLTRSYQNVYVCTGPLFLPRTEADGKSYVKYQVIGKNHVAVPTHFFKVLILEAAGG
  QIELRTYVMPNAPVDEAIPLERFLVPIESIERASGLLFVPNILARAGSLKAITAGSK
• Function: Endonuclease that preferentially catalyzes the cleavage of double-stranded 5-hydroxymethylcytosine (5hmC)-modified DNA. The 5hmC-modified nucleotide does not increase the binding affinity, but instead increases the efficiency of cutting and specifies the site of cleavage for the modified DNAs. Shows significantly higher affinity for four-stranded Holliday junction over duplex and single-stranded DNAs. Promotes conservative recombination when the DNA is 5hmC-modified. Promotes autophagy through the suppression of mTOR by its phosphorylation-mediated interaction with YWHAG and its endonuclease activity-mediated DNA damage response. GSK3-beta mediated phosphorylation of ENDOG enhances its interaction with YWHAG, leading to the release of TSC2 and PIK3C3 from YWHAG resulting in mTOR pathway suppression and autophagy initiation. Promotes cleavage of mtDNA in response to oxidative and nitrosative stress, in turn inducing compensatory mtDNA replication.
• KEGG Pathway: Apoptosis (hsa04210)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac failure	DISDC067	Definitive	Biomarker	[1]
Congestive heart failure	DIS32MEA	Definitive	Biomarker	[1]
Gastric neoplasm	DISOKN4Y	Definitive	Altered Expression	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
B-cell neoplasm	DISVY326	Strong	Biomarker	[4]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[7]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[8]
Leber hereditary optic neuropathy	DIS7Y2EE	Strong	Biomarker	[9]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[5]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[10]
Prostate cancer	DISF190Y	Strong	Biomarker	[11]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[11]
Retinoblastoma	DISVPNPB	Strong	Genetic Variation	[5]
Coronary atherosclerosis	DISKNDYU	moderate	Biomarker	[12]
Myocardial ischemia	DISFTVXF	moderate	Biomarker	[12]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[13]
Myelodysplastic syndrome	DISYHNUI	Limited	Biomarker	[13]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[14]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[15]
Parkinson disease	DISQVHKL	Limited	Biomarker	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Endonuclease G, mitochondrial (ENDOG).	[16]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Endonuclease G, mitochondrial (ENDOG).	[22]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Endonuclease G, mitochondrial (ENDOG).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Endonuclease G, mitochondrial (ENDOG).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Endonuclease G, mitochondrial (ENDOG).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Endonuclease G, mitochondrial (ENDOG).	[19]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Endonuclease G, mitochondrial (ENDOG).	[20]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Endonuclease G, mitochondrial (ENDOG).	[21]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Endonuclease G, mitochondrial (ENDOG).	[23]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Endonuclease G, mitochondrial (ENDOG).	[24]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Endonuclease G, mitochondrial (ENDOG).	[25]
Selenium	DM25CGV	Approved	Selenium increases the expression of Endonuclease G, mitochondrial (ENDOG).	[26]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Endonuclease G, mitochondrial (ENDOG).	[25]
Acocantherin	DM7JT24	Approved	Acocantherin increases the expression of Endonuclease G, mitochondrial (ENDOG).	[28]
Cantharidin	DMBP5N3	Approved	Cantharidin increases the expression of Endonuclease G, mitochondrial (ENDOG).	[29]
Isoflavone	DM7U58J	Phase 4	Isoflavone decreases the expression of Endonuclease G, mitochondrial (ENDOG).	[30]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Endonuclease G, mitochondrial (ENDOG).	[26]
Tetrandrine	DMAOJBX	Phase 1	Tetrandrine decreases the expression of Endonuclease G, mitochondrial (ENDOG).	[33]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Endonuclease G, mitochondrial (ENDOG).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Endonuclease G, mitochondrial (ENDOG).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Endonuclease G, mitochondrial (ENDOG).	[36]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Endonuclease G, mitochondrial (ENDOG).	[37]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Endonuclease G, mitochondrial (ENDOG).	[38]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID increases the expression of Endonuclease G, mitochondrial (ENDOG).	[39]

3 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Sulindac	DM2QHZU	Approved	Sulindac affects the localization of Endonuclease G, mitochondrial (ENDOG).	[27]
Resveratrol	DM3RWXL	Phase 3	Resveratrol affects the localization of Endonuclease G, mitochondrial (ENDOG).	[31]
3,7,3',4'-TETRAHYDROXYFLAVONE	DMES906	Investigative	3,7,3',4'-TETRAHYDROXYFLAVONE increases the localization of Endonuclease G, mitochondrial (ENDOG).	[40]

References

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