Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT03QCLM)

• DOT Name: Cyclic AMP-dependent transcription factor ATF-5 (ATF5)
• Synonyms: cAMP-dependent transcription factor ATF-5; Activating transcription factor 5; Transcription factor ATFx
• Gene Name: ATF5
• Related Disease:
  Hepatocellular carcinoma
  Acute myelogenous leukaemia
  Bipolar disorder
  Breast cancer
  Breast carcinoma
  Childhood acute lymphoblastic leukemia
  Epstein barr virus infection
  Glioma
  Hantavirus infection
  Hematologic disease
  Hemophagocytic syndrome
  Huntington disease
  Immune system disorder
  Mental disorder
  Prostate cancer
  Small lymphocytic lymphoma
  Status epilepticus seizure
  Adult glioblastoma
  Malignant glioma
  Medulloblastoma
  Neuroblastoma
  Advanced cancer
  Astrocytoma
• UniProt ID: ATF5_HUMAN
• Pfam ID: PF00170
• Sequence:
  MSLLATLGLELDRALLPASGLGWLVDYGKLPPAPAPLAPYEVLGGALEGGLPVGGEPLAG
  DGFSDWMTERVDFTALLPLEPPLPPGTLPQPSPTPPDLEAMASLLKKELEQMEDFFLDAP
  PLPPPSPPPLPPPPLPPAPSLPLSLPSFDLPQPPVLDTLDLLAIYCRNEAGQEEVGMPPL
  PPPQQPPPPSPPQPSRLAPYPHPATTRGDRKQKKRDQNKSAALRYRQRKRAEGEALEGEC
  QGLEARNRELKERAESVEREIQYVKDLLIEVYKARSQRTRSC
• Function: Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), ATF5-specific response element (ARE) (consensus: 5'-C[CT]TCT[CT]CCTT[AT]-3') but also the amino acid response element (AARE), present in many viral and cellular promoters. Critically involved, often in a cell type-dependent manner, in cell survival, proliferation, and differentiation. Its transcriptional activity is enhanced by CCND3 and slightly inhibited by CDK4. Important regulator of the cerebral cortex formation, functions in cerebral cortical neuroprogenitor cells to maintain proliferation and to block differentiation into neurons. Must be down-regulated in order for such cells to exit the cycle and differentiate. Participates in the pathways by which SHH promotes cerebellar granule neuron progenitor cells proliferation. Critical for survival of mature olfactory sensory neurons (OSN), directs expression of OSN-specific genes. May be involved in osteogenic differentiation. Promotes cell proliferation and survival by inducing the expression of EGR1 sinergistically with ELK1. Once acetylated by EP300, binds to ARE sequences on target genes promoters, such as BCL2 and EGR1. Plays an anti-apoptotic role through the transcriptional regulation of BCL2, this function seems to be cell type-dependent. Cooperates with NR1I3/CAR in the transcriptional activation of CYP2B6 in liver. In hepatic cells, represses CRE-dependent transcription and inhibits proliferation by blocking at G2/M phase. May act as a negative regulator of IL1B transduction pathway in liver. Upon IL1B stimulus, cooperates with NLK to activate the transactivation activity of C/EBP subfamily members. Besides its function of transcription factor, acts as a cofactor of CEBPB to activate CEBPA and promote adipocyte differentiation. Regulates centrosome dynamics in a cell-cycle- and centriole-age-dependent manner. Forms 9-foci symmetrical ring scaffold around the mother centriole to control centrosome function and the interaction between centrioles and pericentriolar material.
• Tissue Specificity: Widely expressed with higher expression levels in liver.
• Reactome Pathway: Response of EIF2AK1 (HRI) to heme deficiency (R-HSA-9648895)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Genetic Variation	[5]
Epstein barr virus infection	DISOO0WT	Strong	Biomarker	[6]
Glioma	DIS5RPEH	Strong	Biomarker	[7]
Hantavirus infection	DISZFTMH	Strong	Biomarker	[6]
Hematologic disease	DIS9XD9A	Strong	Biomarker	[8]
Hemophagocytic syndrome	DIS3TMN4	Strong	Altered Expression	[6]
Huntington disease	DISQPLA4	Strong	Biomarker	[9]
Immune system disorder	DISAEGPH	Strong	Biomarker	[6]
Mental disorder	DIS3J5R8	Strong	Biomarker	[10]
Prostate cancer	DISF190Y	Strong	Biomarker	[11]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[12]
Status epilepticus seizure	DISY3BIC	Strong	Altered Expression	[9]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[13]
Malignant glioma	DISFXKOV	moderate	Altered Expression	[7]
Medulloblastoma	DISZD2ZL	moderate	Altered Expression	[14]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[14]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[15]
Astrocytoma	DISL3V18	Limited	Altered Expression	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Cyclic AMP-dependent transcription factor ATF-5 (ATF5) affects the response to substance of Methotrexate.	[39]

24 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-5 (ATF5).	[16]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[18]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[19]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[20]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[21]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[22]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[23]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[19]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[24]
Selenium	DM25CGV	Approved	Selenium increases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[25]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[26]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[27]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[28]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[29]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[30]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[25]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[31]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[32]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[33]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[35]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[36]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid decreases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[37]
AM251	DMTAWHL	Investigative	AM251 increases the expression of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cyclic AMP-dependent transcription factor ATF-5 (ATF5).	[34]

References

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