Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMW1B47)

DOT Name Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1)
Synonyms B-cell adapter for phosphoinositide 3-kinase; B-cell phosphoinositide 3-kinase adapter protein 1
Gene Name PIK3AP1
Related Disease
Allergic rhinitis ( )
Burkitt lymphoma ( )
Malignant soft tissue neoplasm ( )
Narcolepsy ( )
Neurodevelopmental disorder ( )
Sarcoma ( )
Gastric cancer ( )
Neoplasm ( )
Stomach cancer ( )
Nervous system inflammation ( )
UniProt ID
BCAP_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
5FOR; 6SWS
Pfam ID
PF14545 ; PF18567
Sequence
MAASGVPRGCDILIVYSPDAEEWCQYLQTLFLSSRQVRSQKILTHRLGPEASFSAEDLSL
FLSTRCVVVLLSAELVQHFHKPALLPLLQRAFHPPHRVVRLLCGVRDSEEFLDFFPDWAH
WQELTCDDEPETYVAAVKKAISEDSGCDSVTDTEPEDEKVVSYSKQQNLPTVTSPGNLMV
VQPDRIRCGAETTVYVIVRCKLDDRVATEAEFSPEDSPSVRMEAKVENEYTISVKAPNLS
SGNVSLKIYSGDLVVCETVISYYTDMEEIGNLLSNAANPVEFMCQAFKIVPYNTETLDKL
LTESLKNNIPASGLHLFGINQLEEEDMMTNQRDEELPTLLHFAAKYGLKNLTALLLTCPG
ALQAYSVANKHGHYPNTIAEKHGFRDLRQFIDEYVETVDMLKSHIKEELMHGEEADAVYE
SMAHLSTDLLMKCSLNPGCDEDLYESMAAFVPAATEDLYVEMLQASTSNPIPGDGFSRAT
KDSMIRKFLEGNSMGMTNLERDQCHLGQEEDVYHTVDDDEAFSVDLASRPPVPVPRPETT
APGAHQLPDNEPYIFKVFAEKSQERPGNFYVSSESIRKGPPVRPWRDRPQSSIYDPFAGM
KTPGQRQLITLQEQVKLGIVNVDEAVLHFKEWQLNQKKRSESFRFQQENLKRLRDSITRR
QREKQKSGKQTDLEITVPIRHSQHLPAKVEFGVYESGPRKSVIPPRTELRRGDWKTDSTS
STASSTSNRSSTRSLLSVSSGMEGDNEDNEVPEVTRSRSPGPPQVDGTPTMSLERPPRVP
PRAASQRPPTRETFHPPPPVPPRGR
Function
Signaling adapter that contributes to B-cell development by linking B-cell receptor (BCR) signaling to the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. Has a complementary role to the BCR coreceptor CD19, coupling BCR and PI3K activation by providing a docking site for the PI3K subunit PIK3R1. Alternatively, links Toll-like receptor (TLR) signaling to PI3K activation, a process preventing excessive inflammatory cytokine production. Also involved in the activation of PI3K in natural killer cells. May be involved in the survival of mature B-cells via activation of REL.
Tissue Specificity Expressed in natural killer (NK) cells.
KEGG Pathway
PI3K-Akt sig.ling pathway (hsa04151 )
B cell receptor sig.ling pathway (hsa04662 )
Reactome Pathway
Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530 )
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558 )
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers (R-HSA-983695 )
PIP3 activates AKT signaling (R-HSA-1257604 )

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Allergic rhinitis DIS3U9HN Strong Biomarker [1]
Burkitt lymphoma DIS9D5XU Strong Altered Expression [2]
Malignant soft tissue neoplasm DISTC6NO Strong Biomarker [3]
Narcolepsy DISLCNLI Strong Genetic Variation [4]
Neurodevelopmental disorder DIS372XH Strong Biomarker [5]
Sarcoma DISZDG3U Strong Biomarker [3]
Gastric cancer DISXGOUK Disputed Biomarker [6]
Neoplasm DISZKGEW Disputed Biomarker [6]
Stomach cancer DISKIJSX Disputed Biomarker [6]
Nervous system inflammation DISB3X5A Limited Biomarker [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
12 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 Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1). [8]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1). [9]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1). [10]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1). [11]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1). [12]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1). [13]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1). [15]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1). [16]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1). [17]
Fenfluramine DM0762O Phase 3 Fenfluramine increases the expression of Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1). [18]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1). [20]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1). [21]
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⏷ Show the Full List of 12 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1). [14]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1). [14]
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References

1 Genome-wide association study for atopy and allergic rhinitis in a Singapore Chinese population.PLoS One. 2011;6(5):e19719. doi: 10.1371/journal.pone.0019719. Epub 2011 May 20.
2 Proteomics and Transcriptomics of BJAB Cells Expressing the Epstein-Barr Virus Noncoding RNAs EBER1 and EBER2.PLoS One. 2015 Jun 29;10(6):e0124638. doi: 10.1371/journal.pone.0124638. eCollection 2015.
3 Anti-tumor and immunomodulatory activities induced by an alkali-extracted polysaccharide BCAP-1 from Bupleurum chinense via NF-B signaling pathway.Int J Biol Macromol. 2017 Feb;95:357-362. doi: 10.1016/j.ijbiomac.2016.10.112. Epub 2016 Nov 22.
4 Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
5 The role of recessive inheritance in early-onset epileptic encephalopathies: a combined whole-exome sequencing and copy number study. Eur J Hum Genet. 2019 Mar;27(3):408-421. doi: 10.1038/s41431-018-0299-8. Epub 2018 Dec 14.
6 A miR-567-PIK3AP1-PI3K/AKT-c-Myc feedback loop regulates tumour growth and chemoresistance in gastric cancer.EBioMedicine. 2019 Jun;44:311-321. doi: 10.1016/j.ebiom.2019.05.003. Epub 2019 May 9.
7 BCAP links IL-1R to the PI3K-mTOR pathway and regulates pathogenic Th17 cell differentiation.J Exp Med. 2018 Sep 3;215(9):2413-2428. doi: 10.1084/jem.20171810. Epub 2018 Aug 9.
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 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
11 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
12 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
13 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
14 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.
15 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
16 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
17 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
18 Fenfluramine-induced gene dysregulation in human pulmonary artery smooth muscle and endothelial cells. Pulm Circ. 2011 Jul-Sep;1(3):405-18. doi: 10.4103/2045-8932.87310.
19 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.
20 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.
21 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.