Details of Drug Off-Target (DOT)

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

• DOT Name: Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6)
• Synonyms: cAMP-dependent transcription factor ATF-6 alpha; Activating transcription factor 6 alpha; ATF6-alpha
• Gene Name: ATF6
• Related Disease:
  Achromatopsia 7
  ATF6-related retinopathy
  Retinitis pigmentosa
  Achromatopsia
  Acquired nystagmus
  Adenocarcinoma
  Amyotrophic lateral sclerosis
  Asbestosis
  B-cell neoplasm
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Cone-rod dystrophy 2
  Creutzfeldt Jacob disease
  Fatty liver disease
  Fetal growth restriction
  Glioma
  Huntington disease
  Inherited Creutzfeldt-Jakob disease
  Lung adenocarcinoma
  Myocardial infarction
  Narcolepsy
  Neoplasm
  Non-small-cell lung cancer
  Obesity
  Osteoarthritis
  Osteosarcoma
  Plasma cell myeloma
  Prostate cancer
  Prostate carcinoma
  Red color blindness
  Red-green color blindness
  Systemic lupus erythematosus
  Adult glioblastoma
  Asthma
  Chronic pancreatitis
  Glioblastoma multiforme
  Melanoma
  Cone-rod dystrophy
  Alzheimer disease
  Stroke
• UniProt ID: ATF6A_HUMAN
• Pfam ID: PF00170
• Sequence:
  MGEPAGVAGTMESPFSPGLFHRLDEDWDSALFAELGYFTDTDELQLEAANETYENNFDNL
  DFDLDLMPWESDIWDINNQICTVKDIKAEPQPLSPASSSYSVSSPRSVDSYSSTQHVPEE
  LDLSSSSQMSPLSLYGENSNSLSSAEPLKEDKPVTGPRNKTENGLTPKKKIQVNSKPSIQ
  PKPLLLPAAPKTQTNSSVPAKTIIIQTVPTLMPLAKQQPIISLQPAPTKGQTVLLSQPTV
  VQLQAPGVLPSAQPVLAVAGGVTQLPNHVVNVVPAPSANSPVNGKLSVTKPVLQSTMRNV
  GSDIAVLRRQQRMIKNRESACQSRKKKKEYMLGLEARLKAALSENEQLKKENGTLKRQLD
  EVVSENQRLKVPSPKRRVVCVMIVLAFIILNYGPMSMLEQDSRRMNPSVSPANQRRHLLG
  FSAKEAQDTSDGIIQKNSYRYDHSVSNDKALMVLTEEPLLYIPPPPCQPLINTTESLRLN
  HELRGWVHRHEVERTKSRRMTNNQQKTRILQGALEQGSNSQLMAVQYTETTSSISRNSGS
  ELQVYYASPRSYQDFFEAIRRRGDTFYVVSFRRDHLLLPATTHNKTTRPKMSIVLPAINI
  NENVINGQDYEVMMQIDCQVMDTRILHIKSSSVPPYLRDQQRNQTNTFFGSPPAATEATH
  VVSTIPESLQ
• Function: [Cyclic AMP-dependent transcription factor ATF-6 alpha]: Precursor of the transcription factor form (Processed cyclic AMP-dependent transcription factor ATF-6 alpha), which is embedded in the endoplasmic reticulum membrane. Endoplasmic reticulum stress promotes processing of this form, releasing the transcription factor form that translocates into the nucleus, where it activates transcription of genes involved in the unfolded protein response (UPR) ; [Processed cyclic AMP-dependent transcription factor ATF-6 alpha]: Transcription factor that initiates the unfolded protein response (UPR) during endoplasmic reticulum stress by activating transcription of genes involved in the UPR. Binds DNA on the 5'-CCAC[GA]-3'half of the ER stress response element (ERSE) (5'-CCAAT-N(9)-CCAC[GA]-3') and of ERSE II (5'-ATTGG-N-CCACG-3'). Binding to ERSE requires binding of NF-Y to ERSE. Could also be involved in activation of transcription by the serum response factor. May play a role in foveal development and cone function in the retina.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Protein processing in endoplasmic reticulum (hsa04141)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  ATF6 (ATF6-alpha) activates chaperones (R-HSA-381033)
  ATF6 (ATF6-alpha) activates chaperone genes (R-HSA-381183)
  ATF4 activates genes in response to endoplasmic reticulum stress (R-HSA-380994)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Achromatopsia 7	DISB3WKM	Definitive	Autosomal recessive	[1]
ATF6-related retinopathy	DIS9LAND	Definitive	Autosomal recessive	[2]
Retinitis pigmentosa	DISCGPY8	Definitive	Genetic Variation	[3]
Achromatopsia	DISKL51I	Strong	Autosomal recessive	[2]
Acquired nystagmus	DISMYF5H	Strong	Biomarker	[4]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[5]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Altered Expression	[6]
Asbestosis	DISO5XCZ	Strong	Biomarker	[7]
B-cell neoplasm	DISVY326	Strong	Biomarker	[8]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[9]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[10]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[11]
Colon cancer	DISVC52G	Strong	Altered Expression	[12]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[13]
Cone-rod dystrophy 2	DISX2RWY	Strong	GermlineCausalMutation	[14]
Creutzfeldt Jacob disease	DISCB6RX	Strong	Biomarker	[15]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[16]
Fetal growth restriction	DIS5WEJ5	Strong	Altered Expression	[17]
Glioma	DIS5RPEH	Strong	Biomarker	[18]
Huntington disease	DISQPLA4	Strong	Biomarker	[19]
Inherited Creutzfeldt-Jakob disease	DIS3TXG8	Strong	Biomarker	[15]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[20]
Myocardial infarction	DIS655KI	Strong	Biomarker	[21]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[22]
Neoplasm	DISZKGEW	Strong	Altered Expression	[23]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[24]
Obesity	DIS47Y1K	Strong	Biomarker	[25]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[26]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[9]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[27]
Prostate cancer	DISF190Y	Strong	Altered Expression	[28]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[28]
Red color blindness	DISQHW4Z	Strong	Biomarker	[4]
Red-green color blindness	DISV3ZVU	Strong	Biomarker	[4]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[29]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[30]
Asthma	DISW9QNS	moderate	Altered Expression	[31]
Chronic pancreatitis	DISBUOMJ	moderate	Altered Expression	[32]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[30]
Melanoma	DIS1RRCY	moderate	Biomarker	[33]
Cone-rod dystrophy	DISY9RWN	Supportive	Autosomal dominant	[14]
Alzheimer disease	DISF8S70	Limited	Altered Expression	[34]
Stroke	DISX6UHX	Limited	Biomarker	[35]

40 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 Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[36]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[39]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[40]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[41]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[42]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[43]
Marinol	DM70IK5	Approved	Marinol increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[44]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[45]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[46]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[47]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[48]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[47]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[47]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[47]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate decreases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[50]
Nefazodone	DM4ZS8M	Approved	Nefazodone increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[51]
Glucosamine	DM4ZLFD	Approved	Glucosamine increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[52]
Atazanavir	DMSYRBX	Approved	Atazanavir increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[51]
Nilotinib	DM7HXWT	Approved	Nilotinib decreases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[54]
Allopurinol	DMLPAOB	Approved	Allopurinol increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[47]
Riluzole	DMECBWN	Approved	Riluzole increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[56]
Pyrazinamide	DM4IF32	Approved	Pyrazinamide increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[57]
Saquinavir	DMG814N	Approved	Saquinavir increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[58]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[59]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[60]
Psoralen	DMIZJ8M	Phase 3	Psoralen increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[61]
Thymoquinone	DMVDTR2	Phase 2/3	Thymoquinone increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[62]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[41]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[65]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[67]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[68]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[69]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[70]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[71]
Manganese	DMKT129	Investigative	Manganese decreases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[72]
Bilirubin	DMI0V4O	Investigative	Bilirubin increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[73]
3,7,3',4'-TETRAHYDROXYFLAVONE	DMES906	Investigative	3,7,3',4'-TETRAHYDROXYFLAVONE increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[75]
L-Serine	DM6WPIS	Investigative	L-Serine increases the expression of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[76]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methamphetamine	DMPM4SK	Approved	Methamphetamine increases the cleavage of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[49]
Cantharidin	DMBP5N3	Approved	Cantharidin increases the cleavage of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[53]
Nelfinavir mesylate	DMFX6G8	Approved	Nelfinavir mesylate decreases the cleavage of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[55]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the cleavage of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[74]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[63]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[64]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6).	[66]

References

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