Details of Drug Off-Target (DOT)

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

DOT Name Serine/threonine-protein kinase MRCK alpha (CDC42BPA)
Synonyms EC 2.7.11.1; CDC42-binding protein kinase alpha; DMPK-like alpha; Myotonic dystrophy kinase-related CDC42-binding kinase alpha; MRCK alpha; Myotonic dystrophy protein kinase-like alpha
Gene Name CDC42BPA
UniProt ID
MRCKA_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.7.11.1
Pfam ID
PF00130 ; PF00780 ; PF08826 ; PF15796 ; PF00069 ; PF00433
Sequence
MSGEVRLRQLEQFILDGPAQTNGQCFSVETLLDILICLYDECNNSPLRREKNILEYLEWA
KPFTSKVKQMRLHREDFEILKVIGRGAFGEVAVVKLKNADKVFAMKILNKWEMLKRAETA
CFREERDVLVNGDNKWITTLHYAFQDDNNLYLVMDYYVGGDLLTLLSKFEDRLPEDMARF
YLAEMVIAIDSVHQLHYVHRDIKPDNILMDMNGHIRLADFGSCLKLMEDGTVQSSVAVGT
PDYISPEILQAMEDGKGRYGPECDWWSLGVCMYEMLYGETPFYAESLVETYGKIMNHKER
FQFPAQVTDVSENAKDLIRRLICSREHRLGQNGIEDFKKHPFFSGIDWDNIRNCEAPYIP
EVSSPTDTSNFDVDDDCLKNSETMPPPTHTAFSGHHLPFVGFTYTSSCVLSDRSCLRVTA
GPTSLDLDVNVQRTLDNNLATEAYERRIKRLEQEKLELSRKLQESTQTVQALQYSTVDGP
LTASKDLEIKNLKEEIEKLRKQVTESSHLEQQLEEANAVRQELDDAFRQIKAYEKQIKTL
QQEREDLNKELVQASERLKNQSKELKDAHCQRKLAMQEFMEINERLTELHTQKQKLARHV
RDKEEEVDLVMQKVESLRQELRRTERAKKELEVHTEALAAEASKDRKLREQSEHYSKQLE
NELEGLKQKQISYSPGVCSIEHQQEITKLKTDLEKKSIFYEEELSKREGIHANEIKNLKK
ELHDSEGQQLALNKEIMILKDKLEKTRRESQSEREEFESEFKQQYEREKVLLTEENKKLT
SELDKLTTLYENLSIHNQQLEEEVKDLADKKESVAHWEAQITEIIQWVSDEKDARGYLQA
LASKMTEELEALRNSSLGTRATDMPWKMRRFAKLDMSARLELQSALDAEIRAKQAIQEEL
NKVKASNIITECKLKDSEKKNLELLSEIEQLIKDTEELRSEKGIEHQDSQHSFLAFLNTP
TDALDQFERSPSCTPASKGRRTVDSTPLSVHTPTLRKKGCPGSTGFPPKRKTHQFFVKSF
TTPTKCHQCTSLMVGLIRQGCSCEVCGFSCHITCVNKAPTTCPVPPEQTKGPLGIDPQKG
IGTAYEGHVRIPKPAGVKKGWQRALAIVCDFKLFLYDIAEGKASQPSVVISQVIDMRDEE
FSVSSVLASDVIHASRKDIPCIFRVTASQLSASNNKCSILMLADTENEKNKWVGVLSELH
KILKKNKFRDRSVYVPKEAYDSTLPLIKTTQAAAIIDHERIALGNEEGLFVVHVTKDEII
RVGDNKKIHQIELIPNDQLVAVISGRNRHVRLFPMSALDGRETDFYKLSETKGCQTVTSG
KVRHGALTCLCVAMKRQVLCYELFQSKTRHRKFKEIQVPYNVQWMAIFSEQLCVGFQSGF
LRYPLNGEGNPYSMLHSNDHTLSFIAHQPMDAICAVEISSKEYLLCFNSIGIYTDCQGRR
SRQQELMWPANPSSCCYNAPYLSVYSENAVDIFDVNSMEWIQTLPLKKVRPLNNEGSLNL
LGLETIRLIYFKNKMAEGDELVVPETSDNSRKQMVRNINNKRRYSFRVPEEERMQQRREM
LRDPEMRNKLISNPTNFNHIAHMGPGDGIQILKDLPMNPRPQESRTVFSGSVSIPSITKS
RPEPGRSMSASSGLSARSSAQNGSALKREFSGGSYSAKRQPMPSPSEGSLSSGGMDQGSD
APARDFDGEDSDSPRHSTASNSSNLSSPPSPASPRKTKSLSLESTDRGSWDP
Function
Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. Regulates actin cytoskeletal reorganization via phosphorylation of PPP1R12C and MYL9/MLC2. In concert with MYO18A and LURAP1, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration. Phosphorylates: PPP1R12A, LIMK1 and LIMK2. May play a role in TFRC-mediated iron uptake. In concert with FAM89B/LRAP25 mediates the targeting of LIMK1 to the lamellipodium resulting in its activation and subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation. Triggers the formation of an extrusion apical actin ring required for epithelial extrusion of apoptotic cells.
Tissue Specificity Abundant in the heart, brain, skeletal muscle, kidney, and pancreas, with little or no expression in the lung and liver.
Reactome Pathway
RAC1 GTPase cycle (R-HSA-9013149 )
RHOQ GTPase cycle (R-HSA-9013406 )
RHOJ GTPase cycle (R-HSA-9013409 )
CDC42 GTPase cycle (R-HSA-9013148 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
15 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 Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [1]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [2]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [3]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [4]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [6]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [7]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [8]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [9]
Selenium DM25CGV Approved Selenium decreases the expression of Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [10]
Diethylstilbestrol DMN3UXQ Approved Diethylstilbestrol decreases the expression of Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [11]
Irinotecan DMP6SC2 Approved Irinotecan decreases the expression of Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [12]
Azacitidine DMTA5OE Approved Azacitidine decreases the expression of Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [13]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [14]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [10]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [16]
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⏷ Show the Full List of 15 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [5]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [15]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Serine/threonine-protein kinase MRCK alpha (CDC42BPA). [17]
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References

1 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
2 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.
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 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.
6 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
7 Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
8 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.
9 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
10 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.
11 Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
12 Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
13 The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
14 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
15 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.
16 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.
17 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.