Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS8F4GD)

DOT Name Tyrosine-protein kinase ABL2 (ABL2)
Synonyms EC 2.7.10.2; Abelson murine leukemia viral oncogene homolog 2; Abelson tyrosine-protein kinase 2; Abelson-related gene protein; Tyrosine-protein kinase ARG
Gene Name ABL2
UniProt ID
ABL2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2ECD; 2KK1; 2XYN; 3GVU; 3HMI; 3ULR; 4EIH; 5NP3; 5NP5
EC Number
2.7.10.2
Pfam ID
PF08919 ; PF07714 ; PF00017 ; PF00018
Sequence
MGQQVGRVGEAPGLQQPQPRGIRGSSAARPSGRRRDPAGRTTETGFNIFTQHDHFASCVE
DGFEGDKTGGSSPEALHRPYGCDVEPQALNEAIRWSSKENLLGATESDPNLFVALYDFVA
SGDNTLSITKGEKLRVLGYNQNGEWSEVRSKNGQGWVPSNYITPVNSLEKHSWYHGPVSR
SAAEYLLSSLINGSFLVRESESSPGQLSISLRYEGRVYHYRINTTADGKVYVTAESRFST
LAELVHHHSTVADGLVTTLHYPAPKCNKPTVYGVSPIHDKWEMERTDITMKHKLGGGQYG
EVYVGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTLEPPFYIV
TEYMPYGNLLDYLRECNREEVTAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGEN
HVVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPESLAYNTFSIKSDVWAFGVLLWEIAT
YGMSPYPGIDLSQVYDLLEKGYRMEQPEGCPPKVYELMRACWKWSPADRPSFAETHQAFE
TMFHDSSISEEVAEELGRAASSSSVVPYLPRLPILPSKTRTLKKQVENKENIEGAQDATE
NSASSLAPGFIRGAQASSGSPALPRKQRDKSPSSLLEDAKETCFTRDRKGGFFSSFMKKR
NAPTPPKRSSSFREMENQPHKKYELTGNFSSVASLQHADGFSFTPAQQEANLVPPKCYGG
SFAQRNLCNDDGGGGGGSGTAGGGWSGITGFFTPRLIKKTLGLRAGKPTASDDTSKPFPR
SNSTSSMSSGLPEQDRMAMTLPRNCQRSKLQLERTVSTSSQPEENVDRANDMLPKKSEES
AAPSRERPKAKLLPRGATALPLRTPSGDLAITEKDPPGVGVAGVAAAPKGKEKNGGARLG
MAGVPEDGEQPGWPSPAKAAPVLPTTHNHKVPVLISPTLKHTPADVQLIGTDSQGNKFKL
LSEHQVTSSGDKDRPRRVKPKCAPPPPPVMRLLQHPSICSDPTEEPTALTAGQSTSETQE
GGKKAALGAVPISGKAGRPVMPPPQVPLPTSSISPAKMANGTAGTKVALRKTKQAAEKIS
ADKISKEALLECADLLSSALTEPVPNSQLVDTGHQLLDYCSGYVDCIPQTRNKFAFREAV
SKLELSLQELQVSSAAAGVPGTNPVLNNLLSCVQEISDVVQR
Function
Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 acts also as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1.
Tissue Specificity Widely expressed.
KEGG Pathway
ErbB sig.ling pathway (hsa04012 )
Ras sig.ling pathway (hsa04014 )
Chemical carcinogenesis - reactive oxygen species (hsa05208 )
Viral myocarditis (hsa05416 )
Reactome Pathway
RAC1 GTPase cycle (R-HSA-9013149 )
RAC3 GTPase cycle (R-HSA-9013423 )
Negative regulation of FLT3 (R-HSA-9706369 )
Role of ABL in ROBO-SLIT signaling (R-HSA-428890 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
13 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 Tyrosine-protein kinase ABL2 (ABL2). [1]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Tyrosine-protein kinase ABL2 (ABL2). [2]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Tyrosine-protein kinase ABL2 (ABL2). [3]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Tyrosine-protein kinase ABL2 (ABL2). [4]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Tyrosine-protein kinase ABL2 (ABL2). [5]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Tyrosine-protein kinase ABL2 (ABL2). [6]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Tyrosine-protein kinase ABL2 (ABL2). [7]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Tyrosine-protein kinase ABL2 (ABL2). [8]
Diclofenac DMPIHLS Approved Diclofenac affects the expression of Tyrosine-protein kinase ABL2 (ABL2). [7]
PMID28870136-Compound-48 DMPIM9L Patented PMID28870136-Compound-48 decreases the expression of Tyrosine-protein kinase ABL2 (ABL2). [12]
PMID25656651-Compound-5 DMAI95U Patented PMID25656651-Compound-5 decreases the activity of Tyrosine-protein kinase ABL2 (ABL2). [13]
Milchsaure DM462BT Investigative Milchsaure increases the expression of Tyrosine-protein kinase ABL2 (ABL2). [14]
Taurine DMVW7N3 Investigative Taurine increases the expression of Tyrosine-protein kinase ABL2 (ABL2). [15]
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⏷ Show the Full List of 13 Drug(s)
1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Dasatinib DMJV2EK Approved Dasatinib affects the binding of Tyrosine-protein kinase ABL2 (ABL2). [9]
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3 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 Tyrosine-protein kinase ABL2 (ABL2). [10]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Tyrosine-protein kinase ABL2 (ABL2). [11]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Tyrosine-protein kinase ABL2 (ABL2). [11]
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References

1 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.
2 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
3 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
4 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
5 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
6 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
7 Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
8 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.
9 The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib. Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13283-8. doi: 10.1073/pnas.0702654104. Epub 2007 Aug 7.
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 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.
12 Global expression profiling of theophylline response genes in macrophages: evidence of airway anti-inflammatory regulation. Respir Res. 2005 Aug 8;6(1):89. doi: 10.1186/1465-9921-6-89.
13 AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009 Nov 6;16(5):401-12. doi: 10.1016/j.ccr.2009.09.028.
14 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
15 Taurine-responsive genes related to signal transduction as identified by cDNA microarray analyses of HepG2 cells. J Med Food. 2006 Spring;9(1):33-41. doi: 10.1089/jmf.2006.9.33.