Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXXV5V7)

• DOT Name: Transcription factor A, mitochondrial (TFAM)
• Synonyms: mtTFA; Mitochondrial transcription factor 1; MtTF1; Transcription factor 6; TCF-6; Transcription factor 6-like 2
• Gene Name: TFAM
• Related Disease:
  Cholestasis
  Hyperglycemia
  Lactic acidosis
  Adult glioblastoma
  Advanced cancer
  Amyotrophic lateral sclerosis
  Arteriosclerosis
  Atherosclerosis
  Brain neoplasm
  Cardiac failure
  Cardiomyopathy
  Chronic obstructive pulmonary disease
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Congestive heart failure
  Epithelial ovarian cancer
  Familial Alzheimer disease
  Glioblastoma multiforme
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Mitochondrial DNA depletion syndrome
  Mitochondrial myopathy
  Myopathy
  Neoplasm
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Obesity
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Squamous cell carcinoma
  Breast cancer
  Breast carcinoma
  Hypoglycemia
  Idiopathic parkinson disease
  Liver failure
  Myocardial infarction
  Osteoarthritis
  Melanoma
  Lymphoma
  Mitochondrial DNA depletion syndrome 15 (hepatocerebral type)
  Status epilepticus seizure
  Type-1/2 diabetes
• UniProt ID: TFAM_HUMAN
• PDB ID: 3FGH; 3TMM; 3TQ6; 4NNU; 4NOD; 6ERP; 6ERQ; 6HB4; 6HC3; 7LBW; 7LBX
• Pfam ID: PF00505 ; PF09011
• Sequence:
  MAFLRSMWGVLSALGRSGAELCTGCGSRLRSPFSFVYLPRWFSSVLASCPKKPVSSYLRF
  SKEQLPIFKAQNPDAKTTELIRRIAQRWRELPDSKKKIYQDAYRAEWQVYKEEISRFKEQ
  LTPSQIMSLEKEIMDKHLKRKAMTKKKELTLLGKPKRPRSAYNVYVAERFQEAKGDSPQE
  KLKTVKENWKNLSDSEKELYIQHAKEDETRYHNEMKSWEEQMIEVGRKDLLRRTIKKQRK
  YGAEEC
• Function: Binds to the mitochondrial light strand promoter and functions in mitochondrial transcription regulation. Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT that is required for basal transcription of mitochondrial DNA. In this complex, TFAM recruits POLRMT to a specific promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand. Required for accurate and efficient promoter recognition by the mitochondrial RNA polymerase. Promotes transcription initiation from the HSP1 and the light strand promoter by binding immediately upstream of transcriptional start sites. Is able to unwind DNA. Bends the mitochondrial light strand promoter DNA into a U-turn shape via its HMG boxes. Required for maintenance of normal levels of mitochondrial DNA. May play a role in organizing and compacting mitochondrial DNA.
• KEGG Pathway:
  Apelin sig.ling pathway (hsa04371)
  Huntington disease (hsa05016)
• Reactome Pathway:
  Transcriptional activation of mitochondrial biogenesis (R-HSA-2151201)
  Mitochondrial transcription initiation (R-HSA-163282)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cholestasis	DISDJJWE	Definitive	Altered Expression	[1]
Hyperglycemia	DIS0BZB5	Definitive	Altered Expression	[2]
Lactic acidosis	DISZI1ZK	Definitive	Altered Expression	[3]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Biomarker	[6]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[7]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[7]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[4]
Cardiac failure	DISDC067	Strong	Biomarker	[8]
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[9]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Posttranslational Modification	[10]
Colon cancer	DISVC52G	Strong	Biomarker	[11]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[12]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[8]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[13]
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[14]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[4]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[16]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[17]
Lung cancer	DISCM4YA	Strong	Altered Expression	[18]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[18]
Mitochondrial DNA depletion syndrome	DISIGZSM	Strong	Genetic Variation	[19]
Mitochondrial myopathy	DIS9SA7V	Strong	Biomarker	[20]
Myopathy	DISOWG27	Strong	Biomarker	[21]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[22]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[23]
Obesity	DIS47Y1K	Strong	Biomarker	[24]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[13]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[13]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[25]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[25]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[26]
Breast cancer	DIS7DPX1	moderate	Biomarker	[27]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[27]
Hypoglycemia	DISRCKR7	moderate	Genetic Variation	[28]
Idiopathic parkinson disease	DIS18PD0	moderate	Biomarker	[29]
Liver failure	DISLGEL6	moderate	Genetic Variation	[28]
Myocardial infarction	DIS655KI	moderate	Altered Expression	[30]
Osteoarthritis	DIS05URM	moderate	Biomarker	[31]
Melanoma	DIS1RRCY	Disputed	Biomarker	[32]
Lymphoma	DISN6V4S	Limited	Biomarker	[33]
Mitochondrial DNA depletion syndrome 15 (hepatocerebral type)	DISBLB7M	Limited	Autosomal recessive	[34]
Status epilepticus seizure	DISY3BIC	Limited	Biomarker	[35]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[9]

40 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 Transcription factor A, mitochondrial (TFAM).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor A, mitochondrial (TFAM).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcription factor A, mitochondrial (TFAM).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription factor A, mitochondrial (TFAM).	[39]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transcription factor A, mitochondrial (TFAM).	[40]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcription factor A, mitochondrial (TFAM).	[41]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Transcription factor A, mitochondrial (TFAM).	[42]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Transcription factor A, mitochondrial (TFAM).	[43]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Transcription factor A, mitochondrial (TFAM).	[44]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transcription factor A, mitochondrial (TFAM).	[45]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Transcription factor A, mitochondrial (TFAM).	[46]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Transcription factor A, mitochondrial (TFAM).	[47]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Transcription factor A, mitochondrial (TFAM).	[48]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Transcription factor A, mitochondrial (TFAM).	[49]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Transcription factor A, mitochondrial (TFAM).	[46]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Transcription factor A, mitochondrial (TFAM).	[50]
Melatonin	DMKWFBT	Approved	Melatonin increases the expression of Transcription factor A, mitochondrial (TFAM).	[51]
Zalcitabine	DMH7MUV	Approved	Zalcitabine affects the expression of Transcription factor A, mitochondrial (TFAM).	[52]
Chloramphenicol	DMFXEWT	Approved	Chloramphenicol increases the expression of Transcription factor A, mitochondrial (TFAM).	[53]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Transcription factor A, mitochondrial (TFAM).	[54]
Fenretinide	DMRD5SP	Phase 3	Fenretinide affects the expression of Transcription factor A, mitochondrial (TFAM).	[55]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Transcription factor A, mitochondrial (TFAM).	[56]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Transcription factor A, mitochondrial (TFAM).	[41]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transcription factor A, mitochondrial (TFAM).	[57]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transcription factor A, mitochondrial (TFAM).	[58]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Transcription factor A, mitochondrial (TFAM).	[60]
Baicalin	DMY1TLZ	Terminated	Baicalin decreases the expression of Transcription factor A, mitochondrial (TFAM).	[61]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transcription factor A, mitochondrial (TFAM).	[62]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transcription factor A, mitochondrial (TFAM).	[63]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Transcription factor A, mitochondrial (TFAM).	[64]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Transcription factor A, mitochondrial (TFAM).	[65]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Transcription factor A, mitochondrial (TFAM).	[66]
acrolein	DMAMCSR	Investigative	acrolein decreases the expression of Transcription factor A, mitochondrial (TFAM).	[67]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID decreases the expression of Transcription factor A, mitochondrial (TFAM).	[54]
Kaempferol	DMHEMUB	Investigative	Kaempferol increases the expression of Transcription factor A, mitochondrial (TFAM).	[68]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Transcription factor A, mitochondrial (TFAM).	[69]
Propanoic Acid	DM9TN2W	Investigative	Propanoic Acid decreases the expression of Transcription factor A, mitochondrial (TFAM).	[70]
aconitine	DMFOZ60	Investigative	aconitine increases the expression of Transcription factor A, mitochondrial (TFAM).	[71]
Ethidium	DMMEQUR	Investigative	Ethidium increases the expression of Transcription factor A, mitochondrial (TFAM).	[53]
Oxalacetic acid	DMPZSV1	Investigative	Oxalacetic acid increases the expression of Transcription factor A, mitochondrial (TFAM).	[66]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Transcription factor A, mitochondrial (TFAM).	[59]

References

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