Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUN4V3N)

• DOT Name: Elongation factor G, mitochondrial (GFM1)
• Synonyms: EF-Gmt; Elongation factor G 1, mitochondrial; mEF-G 1; Elongation factor G1; hEFG1
• Gene Name: GFM1
• Related Disease:
  Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1
  Arteriosclerosis
  Atherosclerosis
  Biliary tract cancer
  Breast cancer
  Breast carcinoma
  Cataract 3 multiple types
  Chondrosarcoma
  Chronic myelomonocytic leukemia
  Craniosynostosis
  Liver failure
  Mitochondrial disease
  Myelodysplastic syndrome
  Neoplasm
  Adenovirus infection
  Cervical carcinoma
  Leigh syndrome
  Brooke-Spiegler syndrome
  Lung cancer
  Lung carcinoma
• UniProt ID: EFGM_HUMAN
• PDB ID: 6VLZ; 6VMI; 6YDP; 6YDW; 7A5K
• Pfam ID: PF00679 ; PF14492 ; PF03764 ; PF00009 ; PF03144
• Sequence:
  MRLLGAAAVAALGRGRAPASLGWQRKQVNWKACRWSSSGVIPNEKIRNIGISAHIDSGKT
  TLTERVLYYTGRIAKMHEVKGKDGVGAVMDSMELERQRGITIQSAATYTMWKDVNINIID
  TPGHVDFTIEVERALRVLDGAVLVLCAVGGVQCQTMTVNRQMKRYNVPFLTFINKLDRMG
  SNPARALQQMRSKLNHNAAFMQIPMGLEGNFKGIVDLIEERAIYFDGDFGQIVRYGEIPA
  ELRAAATDHRQELIECVANSDEQLGEMFLEEKIPSISDLKLAIRRATLKRSFTPVFLGSA
  LKNKGVQPLLDAVLEYLPNPSEVQNYAILNKEDDSKEKTKILMNSSRDNSHPFVGLAFKL
  EVGRFGQLTYVRSYQGELKKGDTIYNTRTRKKVRLQRLARMHADMMEDVEEVYAGDICAL
  FGIDCASGDTFTDKANSGLSMESIHVPDPVISIAMKPSNKNDLEKFSKGIGRFTREDPTF
  KVYFDTENKETVISGMGELHLEIYAQRLEREYGCPCITGKPKVAFRETITAPVPFDFTHK
  KQSGGAGQYGKVIGVLEPLDPEDYTKLEFSDETFGSNIPKQFVPAVEKGFLDACEKGPLS
  GHKLSGLRFVLQDGAHHMVDSNEISFIRAGEGALKQALANATLCILEPIMAVEVVAPNEF
  QGQVIAGINRRHGVITGQDGVEDYFTLYADVPLNDMFGYSTELRSCTEGKGEYTMEYSRY
  QPCLPSTQEDVINKYLEATGQLPVKKGKAKN
• Function: Mitochondrial GTPase that catalyzes the GTP-dependent ribosomal translocation step during translation elongation. During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively. Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome. Does not mediate the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis.
• Reactome Pathway: Mitochondrial translation elongation (R-HSA-5389840)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1	DISKWI67	Definitive	Autosomal recessive	[1]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[2]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[2]
Biliary tract cancer	DISBNYQL	Strong	Genetic Variation	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Cataract 3 multiple types	DIS6WOLW	Strong	Altered Expression	[5]
Chondrosarcoma	DIS4I7JB	Strong	Altered Expression	[6]
Chronic myelomonocytic leukemia	DISIL8UR	Strong	Biomarker	[7]
Craniosynostosis	DIS6J405	Strong	Biomarker	[8]
Liver failure	DISLGEL6	Strong	Genetic Variation	[9]
Mitochondrial disease	DISKAHA3	Strong	Genetic Variation	[10]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[11]
Neoplasm	DISZKGEW	Strong	Biomarker	[12]
Adenovirus infection	DISUYSBZ	moderate	Altered Expression	[13]
Cervical carcinoma	DIST4S00	moderate	Biomarker	[14]
Leigh syndrome	DISWQU45	Moderate	Autosomal recessive	[15]
Brooke-Spiegler syndrome	DIS36OT6	Limited	Genetic Variation	[16]
Lung cancer	DISCM4YA	Limited	Biomarker	[17]
Lung carcinoma	DISTR26C	Limited	Biomarker	[17]

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 Elongation factor G, mitochondrial (GFM1).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Elongation factor G, mitochondrial (GFM1).	[26]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Elongation factor G, mitochondrial (GFM1).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Elongation factor G, mitochondrial (GFM1).	[19]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Elongation factor G, mitochondrial (GFM1).	[20]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Elongation factor G, mitochondrial (GFM1).	[21]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Elongation factor G, mitochondrial (GFM1).	[22]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Elongation factor G, mitochondrial (GFM1).	[23]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Elongation factor G, mitochondrial (GFM1).	[24]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Elongation factor G, mitochondrial (GFM1).	[25]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Elongation factor G, mitochondrial (GFM1).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Elongation factor G, mitochondrial (GFM1).	[29]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Elongation factor G, mitochondrial (GFM1).	[30]

References

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• [23] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
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