Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2CEJW4)

• DOT Name: A-kinase anchor protein 17A (AKAP17A)
• Synonyms: AKAP-17A; 721P; B-lymphocyte antigen; Protein XE7; Protein kinase A-anchoring protein 17A; PRKA17A; Splicing factor, arginine/serine-rich 17A
• Gene Name: AKAP17A
• Related Disease:
  Bruton-type agammaglobulinemia
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
• UniProt ID: AK17A_HUMAN
• Sequence:
  MAAATIVHDTSEAVELCPAYGLYLKPITKMTISVALPQLKQPGKSISNWEVMERLKGMVQ
  NHQFSTLRISKSTMDFIRFEGEVENKSLVKSFLACLDGKTIKLSGFSDILKVRAAEFKID
  FPTRHDWDSFFRDAKDMNETLPGERPDTIHLEGLPCKWFALKESGSEKPSEDVLVKVFEK
  FGEIRNVDIPMLDPYREEMTGRNFHTFSFGGHLNFEAYVQYREYMGFIQAMSALRGMKLM
  YKGEDGKAVACNIKVSFDSTKHLSDASIKKRQLERQKLQELEQQREEQKRREKEAEERQR
  AEERKQKELEELERERKREEKLRKREQKQRDRELRRNQKKLEKLQAEEQKQLQEKIKLEE
  RKLLLAQRNLQSIRLIAELLSRAKAVKLREQEQKEEKLRLQQQEERRRLQEAELRRVEEE
  KERALGLQRKERELRERLLSILLSKKPDDSHTHDELGVAHADLLQPVLDILQTVSSGCVS
  ATTLHPLGGQPPAGAPKESPAHPEADGAPKSVNGSVAEEAPCKEVQSSCRVVPEDGSPEK
  RCPGGVLSCIPDNNQQPKGIPACEQNVSRKDTRSEQDKCNREPSKGRGRATGDGLADRHK
  RERSRARRASSREDGRPRKERRPHKKHAYKDDSPRRRSTSPDHTRSRRSHSKDRHRRERS
  RERRGSASRKHSRHRRRSERSRSRSPSRHRSTWNR
• Function: Splice factor regulating alternative splice site selection for certain mRNA precursors. Mediates regulation of pre-mRNA splicing in a PKA-dependent manner.
• Tissue Specificity: Widely expressed. Found in heart, brain, lung, liver, skeletal muscle, kidney and pancreas. Expressed in activated B-cells and placenta. Expressed in all cell lines tested including Jurkat-TAg, U-937 and HEK293 cells.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bruton-type agammaglobulinemia	DISQ5ZYP	Strong	Genetic Variation	[1]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[2]
Liver cancer	DISDE4BI	Limited	Biomarker	[2]

3 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 A-kinase anchor protein 17A (AKAP17A).	[3]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of A-kinase anchor protein 17A (AKAP17A).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of A-kinase anchor protein 17A (AKAP17A).	[10]

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of A-kinase anchor protein 17A (AKAP17A).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of A-kinase anchor protein 17A (AKAP17A).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of A-kinase anchor protein 17A (AKAP17A).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of A-kinase anchor protein 17A (AKAP17A).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of A-kinase anchor protein 17A (AKAP17A).	[9]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of A-kinase anchor protein 17A (AKAP17A).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of A-kinase anchor protein 17A (AKAP17A).	[12]

References

• [1] Atypical X-linked agammaglobulinaemia caused by a novel BTK mutation in a selective immunoglobulin M deficiency patient.BMC Pediatr. 2013 Sep 27;13:150. doi: 10.1186/1471-2431-13-150.
• [2] Design Graph Theoretical Analysis and In Silico Modeling of Dunaliella Bardawil Biomass Encapsulated N-Succinyl Chitosan Nanoparticles for Enhanced Anticancer Activity.Anticancer Agents Med Chem. 2018;18(13):1900-1918. doi: 10.2174/1871520618666180628155223.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [7] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [8] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [12] Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S. Toxicol In Vitro. 2015 Aug;29(5):1060-9.