Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRHPFO2)

• DOT Name: Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A)
• Synonyms: Acidic nuclear phosphoprotein pp32; pp32; Leucine-rich acidic nuclear protein; LANP; Mapmodulin; Potent heat-stable protein phosphatase 2A inhibitor I1PP2A; Putative HLA-DR-associated protein I; PHAPI
• Gene Name: ANP32A
• Related Disease:
  Cognitive impairment
  Colorectal neoplasm
  Acute myelogenous leukaemia
  Adenocarcinoma
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Carcinoma
  Colorectal carcinoma
  Glioma
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Lung neoplasm
  Oral cancer
  Osteoarthritis
  Pancreatic cancer
  Prostate adenocarcinoma
  Prostate cancer
  Prostate carcinoma
  Spinocerebellar ataxia type 1
  Squamous cell carcinoma
  Influenza
  Advanced cancer
  Neoplasm
• UniProt ID: AN32A_HUMAN
• PDB ID: 2JE0; 2JE1; 4XOS; 6XZQ
• Pfam ID: PF14580
• Sequence:
  MEMGRRIHLELRNRTPSDVKELVLDNSRSNEGKLEGLTDEFEELEFLSTINVGLTSIANL
  PKLNKLKKLELSDNRVSGGLEVLAEKCPNLTHLNLSGNKIKDLSTIEPLKKLENLKSLDL
  FNCEVTNLNDYRENVFKLLPQLTYLDGYDRDDKEAPDSDAEGYVEGLDDEEEDEDEEEYD
  EDAQVVEDEEDEDEEEEGEEEDVSGEEEEDEEGYNDGEVDDEEDEEELGEEERGQKRKRE
  PEDEGEDDD
• Function: Multifunctional protein that is involved in the regulation of many processes including tumor suppression, apoptosis, cell cycle progression or transcription. Promotes apoptosis by favouring the activation of caspase-9/CASP9 and allowing apoptosome formation. In addition, plays a role in the modulation of histone acetylation and transcription as part of the INHAT (inhibitor of histone acetyltransferases) complex. Inhibits the histone-acetyltranferase activity of EP300/CREBBP (CREB-binding protein) and EP300/CREBBP-associated factor by histone masking. Preferentially binds to unmodified histone H3 and sterically inhibiting its acetylation and phosphorylation leading to cell growth inhibition. Participates in other biochemical processes such as regulation of mRNA nuclear-to-cytoplasmic translocation and stability by its association with ELAVL1 (Hu-antigen R). Plays a role in E4F1-mediated transcriptional repression as well as inhibition of protein phosphatase 2A ; (Microbial infection) Plays an essential role in influenza A, B and C viral genome replication. Mechanistically, mediates the assembly of the viral replicase asymmetric dimers composed of PB1, PB2 and PA via its N-terminal region. Also plays an essential role in foamy virus mRNA export from the nucleus.
• Tissue Specificity: Expressed in all tissues tested. Highly expressed in kidney and skeletal muscle, moderate levels of expression in brain, placenta and pancreas, and weakly expressed in lung. Found in all regions of the brain examined (amygdala, caudate nucleus, corpus callosum, hippocampus and thalamus), with highest levels in amygdala.
• Reactome Pathway: HuR (ELAVL1) binds and stabilizes mRNA (R-HSA-450520)

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cognitive impairment	DISH2ERD	Definitive	Genetic Variation	[1]
Colorectal neoplasm	DISR1UCN	Definitive	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Carcinoma	DISH9F1N	Strong	Altered Expression	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[8]
Glioma	DIS5RPEH	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[7]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[10]
Lung neoplasm	DISVARNB	Strong	Biomarker	[11]
Oral cancer	DISLD42D	Strong	Biomarker	[12]
Osteoarthritis	DIS05URM	Strong	Biomarker	[13]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[14]
Prostate adenocarcinoma	DISBZYU8	Strong	Altered Expression	[15]
Prostate cancer	DISF190Y	Strong	Biomarker	[15]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[15]
Spinocerebellar ataxia type 1	DISF7BO2	Strong	Biomarker	[16]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[12]
Influenza	DIS3PNU3	moderate	Biomarker	[17]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[8]
Neoplasm	DISZKGEW	Limited	Biomarker	[18]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A) affects the response to substance of Paclitaxel.	[41]
Topotecan	DMP6G8T	Approved	Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A) affects the response to substance of Topotecan.	[41]

1 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 Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[19]

20 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 Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[23]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[25]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[27]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[28]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[29]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[30]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[31]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[32]
Isoflavone	DM7U58J	Phase 4	Isoflavone affects the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[33]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[34]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[35]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[36]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[38]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[39]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol affects the localization of Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A).	[26]

References

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