Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0L3PZ6)

• DOT Name: A-kinase anchor protein 7 isoforms alpha and beta (AKAP7)
• Synonyms: AKAP-7 isoforms alpha and beta; A-kinase anchor protein 18 kDa; AKAP 18; Protein kinase A-anchoring protein 7 isoforms alpha/beta; PRKA7 isoforms alpha/beta
• Gene Name: AKAP7
• Related Disease:
  Drug dependence
  Substance abuse
  Substance dependence
• UniProt ID: AKA7A_HUMAN
• Pfam ID: PF10470
• Sequence:
  MGQLCCFPFSRDEGKISELESSSSAVLQRYSKDIPSWSSGEKNGGEPDDAELVRLSKRLV
  ENAVLKAVQQYLEETQNKNKPGEGSSVKTEAADQNGNDNENNRK
• Function: Targets the cAMP-dependent protein kinase (PKA) to the plasma membrane, and permits functional coupling to the L-type calcium channel. The membrane-associated form reduces epithelial sodium channel (ENaC) activity, whereas the free cytoplasmic form may negatively regulate ENaC channel feedback inhibition by intracellular sodium.
• Tissue Specificity: Expressed in brain, heart, lung, pancreas and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Drug dependence	DIS9IXRC	Strong	Biomarker	[1]
Substance abuse	DIS327VW	Strong	Biomarker	[1]
Substance dependence	DISDRAAR	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Lovastatin	DM9OZWQ	Approved	A-kinase anchor protein 7 isoforms alpha and beta (AKAP7) decreases the response to substance of Lovastatin.	[14]

11 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 A-kinase anchor protein 7 isoforms alpha and beta (AKAP7).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of A-kinase anchor protein 7 isoforms alpha and beta (AKAP7).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of A-kinase anchor protein 7 isoforms alpha and beta (AKAP7).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of A-kinase anchor protein 7 isoforms alpha and beta (AKAP7).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of A-kinase anchor protein 7 isoforms alpha and beta (AKAP7).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of A-kinase anchor protein 7 isoforms alpha and beta (AKAP7).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of A-kinase anchor protein 7 isoforms alpha and beta (AKAP7).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of A-kinase anchor protein 7 isoforms alpha and beta (AKAP7).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of A-kinase anchor protein 7 isoforms alpha and beta (AKAP7).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of A-kinase anchor protein 7 isoforms alpha and beta (AKAP7).	[11]
Manganese	DMKT129	Investigative	Manganese decreases the expression of A-kinase anchor protein 7 isoforms alpha and beta (AKAP7).	[13]

2 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 A-kinase anchor protein 7 isoforms alpha and beta (AKAP7).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of A-kinase anchor protein 7 isoforms alpha and beta (AKAP7).	[12]

References

• [1] Genome wide association for addiction: replicated results and comparisons of two analytic approaches.PLoS One. 2010 Jan 21;5(1):e8832. doi: 10.1371/journal.pone.0008832.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [7] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [11] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [12] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [13] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.
• [14] NCI60 cancer cell line panel data and RNAi analysis help identify EAF2 as a modulator of simvastatin and lovastatin response in HCT-116 cells. PLoS One. 2011 Apr 4;6(4):e18306. doi: 10.1371/journal.pone.0018306.