Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI618VF)

DOT Name PALM2-AKAP2 fusion protein (PALM2AKAP2)
Synonyms A-kinase anchor protein 2; AKAP-2; AKAP-KL; Paralemmin A kinase anchor protein; Paralemmin-2; Protein kinase A-anchoring protein 2; PRKA2
Gene Name PALM2AKAP2
Related Disease
Advanced cancer ( )
Alzheimer disease ( )
Androgen insensitivity syndrome ( )
Cardiovascular disease ( )
Epithelial ovarian cancer ( )
Kallmann syndrome ( )
Metastatic prostate carcinoma ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Acute myelogenous leukaemia ( )
UniProt ID
PLAK2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF03285
Sequence
MAEAELHKERLQAIAEKRKRQTEIEGKRQQLDEQILLLQHSKSKVLREKWLLQGIPAGTA
EEEEARRRQSEEDEFRVKQLEDNIQRLEQEIQTLESEESQISAKEQIILEKLKETEKSFK
DFQKGFSSTDGDAVNYISSQLPDLPILCSRTAEPSPGQDGTSRAAGVGWENVLLKEGESA
SNATETSGPDMTIKKPPQLSEDDIWLKSEGDNYSATLLEPAASSLSPDHKNMEIEVSVAE
CKSVPGITSTPHPMDHPSAFYSPPHNGLLTDHHESLDNDVAREIRYLDEVLEANCCDSAV
DGTYNGTSSPEPGAVVLVGGLSPPVHEATQPEPTERTASRQAPPHIELSNSSPDPMAEAE
RTNGHSPSQPRDALGDSLQVPVSPSSTTSSRCSSRDGEFTLTTLKKEAKFELRAFHEDKK
PSKLFEDDEHEKEQYCIRKVRPSEEMLELEKERRELIRSQAVKKNPGIAAKWWNPPQEKT
IEEQLDEEHLESHKKYKERKERRAQQEQLLLQKQLQQQQQQPPSQLCTAPASSHERASMI
DKAKEDIVTEQIDFSAARKQFQLMENSRQAVAKGQSTPRLFSIKPFYRPLGSVNSDKPLT
NPRPPSVGGPPEDSGASAAKGQKSPGALETPSAAGSQGNTASQGKEGPYSEPSKRGPLSK
LWAEDGEFTSARAVLTVVKDDDHGILDQFSRSVNVSLTQEELDSGLDELSVRSQDTTVLE
TLSNDFSMDNISDSGASNETTNALQENSLADFSLPQTPQTDNPSEGRGEGVSKSFSDHGF
YSPSSTLGDSPLVDDPLEYQAGLLVQNAIQQAIAEQVDKAVSKTSRDGAEQQGPEATVEE
AEAAAFGSEKPQSMFEPPQVSSPVQEKRDVLPKILPAEDRALRERGPPQPLPAVQPSGPI
NMEETRPEGSYFSKYSEAAELRSTASLLATQESDVMVGPFKLRSRKQRTLSMIEEEIRAA
QEREEELKRQRQVLQSTQSPRTKNAPSLPSRTCYKTAPGKIEKVKPPPSPTTEGPSLQPD
LAPEEAAGTQRPKNLMQTLMEDYETHKSKRRERMDDSSYTSKLLSCKVTSEVLEATRVNR
RKSALALRWEAGIYANQEEEDNE
Function
Binds to regulatory subunit (RII) of protein kinase A. May be involved in establishing polarity in signaling systems or in integrating PKA-RII isoforms with downstream effectors to capture, amplify and focus diffuse, trans-cellular signals carried by cAMP. Binds to and modulates the structure of the actin cytoskeleton.
Tissue Specificity .Expressed in infantile heart and muscle, and fibroblasts.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Altered Expression [1]
Alzheimer disease DISF8S70 Strong Genetic Variation [2]
Androgen insensitivity syndrome DISUZBBO Strong Genetic Variation [3]
Cardiovascular disease DIS2IQDX Strong Genetic Variation [4]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [1]
Kallmann syndrome DISO3HDG Strong Biomarker [5]
Metastatic prostate carcinoma DISVBEZ9 Strong Altered Expression [6]
Ovarian cancer DISZJHAP Strong Altered Expression [1]
Ovarian neoplasm DISEAFTY Strong Altered Expression [1]
Acute myelogenous leukaemia DISCSPTN moderate Genetic Variation [7]
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⏷ Show the Full List of 10 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of PALM2-AKAP2 fusion protein (PALM2AKAP2). [8]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of PALM2-AKAP2 fusion protein (PALM2AKAP2). [13]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of PALM2-AKAP2 fusion protein (PALM2AKAP2). [21]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of PALM2-AKAP2 fusion protein (PALM2AKAP2). [23]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of PALM2-AKAP2 fusion protein (PALM2AKAP2). [23]
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16 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 PALM2-AKAP2 fusion protein (PALM2AKAP2). [9]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of PALM2-AKAP2 fusion protein (PALM2AKAP2). [10]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of PALM2-AKAP2 fusion protein (PALM2AKAP2). [11]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of PALM2-AKAP2 fusion protein (PALM2AKAP2). [12]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of PALM2-AKAP2 fusion protein (PALM2AKAP2). [14]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of PALM2-AKAP2 fusion protein (PALM2AKAP2). [15]
Triclosan DMZUR4N Approved Triclosan decreases the expression of PALM2-AKAP2 fusion protein (PALM2AKAP2). [16]
Selenium DM25CGV Approved Selenium increases the expression of PALM2-AKAP2 fusion protein (PALM2AKAP2). [17]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of PALM2-AKAP2 fusion protein (PALM2AKAP2). [18]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of PALM2-AKAP2 fusion protein (PALM2AKAP2). [19]
Cyclophosphamide DM4O2Z7 Approved Cyclophosphamide increases the expression of PALM2-AKAP2 fusion protein (PALM2AKAP2). [20]
Tamibarotene DM3G74J Phase 3 Tamibarotene affects the expression of PALM2-AKAP2 fusion protein (PALM2AKAP2). [10]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of PALM2-AKAP2 fusion protein (PALM2AKAP2). [17]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of PALM2-AKAP2 fusion protein (PALM2AKAP2). [22]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of PALM2-AKAP2 fusion protein (PALM2AKAP2). [24]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of PALM2-AKAP2 fusion protein (PALM2AKAP2). [25]
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⏷ Show the Full List of 16 Drug(s)

References

1 AKAP2 is upregulated in ovarian cancer, and promotes growth and migration of cancer cells.Mol Med Rep. 2017 Oct;16(4):5151-5156. doi: 10.3892/mmr.2017.7286. Epub 2017 Aug 18.
2 SORL1 is genetically associated with late-onset Alzheimer's disease in Japanese, Koreans and Caucasians.PLoS One. 2013;8(4):e58618. doi: 10.1371/journal.pone.0058618. Epub 2013 Apr 2.
3 Lack of association between AKAP2 and the susceptibility of adolescent idiopathic scoliosis in the Chinese population.BMC Musculoskelet Disord. 2017 Aug 24;18(1):368. doi: 10.1186/s12891-017-1731-x.
4 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
5 The breakpoint identified in a balanced de novo translocation t(7;9)(p14.1;q31.3) disrupts the A-kinase (PRKA) anchor protein 2 gene (AKAP2) on chromosome 9 in a patient with Kallmann syndrome and bone anomalies.Int J Mol Med. 2007 Mar;19(3):429-35.
6 A-kinase anchoring protein 2 is required for calcitonin-mediated invasion of cancer cells.Endocr Relat Cancer. 2016 Jan;23(1):1-14. doi: 10.1530/ERC-15-0425. Epub 2015 Oct 2.
7 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
8 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.
9 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
10 Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
11 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
12 The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
13 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
14 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
15 Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 2008 Oct;7(10):1607-18.
16 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
17 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
18 Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics. 2003 Jun;81(6):543-55.
19 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
20 Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
21 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.
22 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
23 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.
24 Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
25 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.