General Information of Drug Off-Target (DOT) (ID: OTVVM637)

DOT Name Inactive tyrosine-protein kinase PEAK1 (PEAK1)
Synonyms Pseudopodium-enriched atypical kinase 1; Sugen kinase 269; Tyrosine-protein kinase SgK269
Gene Name PEAK1
Related Disease
Parkinson disease ( )
Advanced cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Neoplasm ( )
Pancreatic cancer ( )
Metastatic malignant neoplasm ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Matthew-Wood syndrome ( )
Pancreatic ductal carcinoma ( )
Rectal carcinoma ( )
UniProt ID
PEAK1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6BHC; 8DGM
Pfam ID
PF00069
Sequence
MSACNTFTEHVWKPGECKNCFKPKSLHQLPPDPEKAPITHGNVKTNANHSNNHRIRNTGN
FRPPVAKKPTIAVKPTMIVADGQSICGELSIQEHCENKPVIIGWNRNRAALSQKPLNNNN
EDDEGISHVPKPYGNNDSAKKMSDNNNGLTEVLKEIAGLDTAPQIRGNETNSRETFLGRI
NDCYKRSLERKLPPSCMIGGIKETQGKHVILSGSTEVISNEGGRFCYPEFSSGEESEEDV
LFSNMEEEHESWDESDEELLAMEIRMRGQPRFANFRANTLSPVRFFVDKKWNTIPLRNKS
LQRICAVDYDDSYDEILNGYEENSVVSYGQGSIQSMVSSDSTSPDSSLTEESRSETASSL
SQKICNGGLSPGNPGDSKDMKEIEPNYESPSSNNQDKDSSQASKSSIKVPETHKAVLALR
LEEKDGKIAVQTEKEESKASTDVAGQAVTINLVPTEEQAKPYRVVNLEQPLCKPYTVVDV
SAAMASEHLEGPVNSPKTKSSSSTPNSPVTSSSLTPGQISAHFQKSSAIRYQEVWTSSTS
PRQKIPKVELITSGTGPNVPPRKNCHKSAPTSPTATNISSKTIPVKSPNLSEIKFNSYNN
AGMPPFPIIIHDEPTYARSSKNAIKVPIVINPNAYDNLAIYKSFLGTSGELSVKEKTTSV
ISHTYEEIETESKVPDNTTSKTTDCLQTKGFSNSTEHKRGSVAQKVQEFNNCLNRGQSSP
QRSYSSSHSSPAKIQRATQEPVAKIEGTQESQMVGSSSTREKASTVLSQIVASIQPPQSP
PETPQSGPKACSVEELYAIPPDADVAKSTPKSTPVRPKSLFTSQPSGEAEAPQTTDSPTT
KVQKDPSIKPVTPSPSKLVTSPQSEPPAPFPPPRSTSSPYHAGNLLQRHFTNWTKPTSPT
RSTEAESVLHSEGSRRAADAKPKRWISFKSFFRRRKTDEEDDKEKEREKGKLVGLDGTVI
HMLPPPPVQRHHWFTEAKGESSEKPAIVFMYRCDPAQGQLSVDQSKARTDQAAVMEKGRA
ENALLQDSEKKRSHSSPSQIPKKILSHMTHEVTEDFSPRDPRTVVGKQDGRGCTSVTTAL
SLPELEREDGKEDISDPMDPNPCSATYSNLGQSRAAMIPPKQPRQPKGAVDDAIAFGGKT
DQEAPNASQPTPPPLPKKMIIRANTEPISKDLQKSMESSLCVMANPTYDIDPNWDASSAG
SSISYELKGLDIESYDSLERPLRKERPVPSAANSISSLTTLSIKDRFSNSMESLSSRRGP
SCRQGRGIQKPQRQALYRGLENREEVVGKIRSLHTDALKKLAVKCEDLFMAGQKDQLRFG
VDSWSDFRLTSDKPCCEAGDAVYYTASYAKDPLNNYAVKICKSKAKESQQYYHSLAVRQS
LAVHFNIQQDCGHFLAEVPNRLLPWEDPDDPEKDEDDMEETEEDAKGETDGKNPKPCSEA
ASSQKENQGVMSKKQRSHVVVITREVPCLTVADFVRDSLAQHGKSPDLYERQVCLLLLQL
CSGLEHLKPYHVTHCDLRLENLLLVHYQPGGTAQGFGPAEPSPTSSYPTRLIVSNFSQAK
QKSHLVDPEILRDQSRLAPEIITATQYKKCDEFQTGILIYEMLHLPNPFDENPELKEREY
TRADLPRIPFRSPYSRGLQQLASCLLNPNPSERILISDAKGILQCLLWGPREDLFQTFTA
CPSLVQRNTLLQNWLDIKRTLLMIKFAEKSLDREGGISLEDWLCAQYLAFATTDSLSCIV
KILQHR
Function
Probable catalytically inactive kinase. Scaffolding protein that regulates the cytoskeleton to control cell spreading and migration by modulating focal adhesion dynamics. Acts as a scaffold for mediating EGFR signaling.
Reactome Pathway
RHOV GTPase cycle (R-HSA-9013424 )
RHOU GTPase cycle (R-HSA-9013420 )

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Parkinson disease DISQVHKL Definitive Biomarker [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Breast cancer DIS7DPX1 Strong Biomarker [3]
Breast carcinoma DIS2UE88 Strong Biomarker [3]
Neoplasm DISZKGEW Strong Biomarker [2]
Pancreatic cancer DISJC981 Strong Biomarker [4]
Metastatic malignant neoplasm DIS86UK6 moderate Altered Expression [5]
Colon cancer DISVC52G Limited Altered Expression [6]
Colon carcinoma DISJYKUO Limited Altered Expression [6]
Colorectal carcinoma DIS5PYL0 Limited Altered Expression [2]
Lung cancer DISCM4YA Limited Altered Expression [5]
Lung carcinoma DISTR26C Limited Altered Expression [5]
Matthew-Wood syndrome DISA7HR7 Limited Biomarker [4]
Pancreatic ductal carcinoma DIS26F9Q Limited Biomarker [4]
Rectal carcinoma DIS8FRR7 Limited Altered Expression [6]
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⏷ Show the Full List of 15 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Inactive tyrosine-protein kinase PEAK1 (PEAK1). [7]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Inactive tyrosine-protein kinase PEAK1 (PEAK1). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Inactive tyrosine-protein kinase PEAK1 (PEAK1). [9]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Inactive tyrosine-protein kinase PEAK1 (PEAK1). [10]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Inactive tyrosine-protein kinase PEAK1 (PEAK1). [11]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Inactive tyrosine-protein kinase PEAK1 (PEAK1). [12]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate increases the expression of Inactive tyrosine-protein kinase PEAK1 (PEAK1). [13]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Inactive tyrosine-protein kinase PEAK1 (PEAK1). [15]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Inactive tyrosine-protein kinase PEAK1 (PEAK1). [17]
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⏷ Show the Full List of 9 Drug(s)
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 increases the methylation of Inactive tyrosine-protein kinase PEAK1 (PEAK1). [14]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Inactive tyrosine-protein kinase PEAK1 (PEAK1). [16]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Inactive tyrosine-protein kinase PEAK1 (PEAK1). [16]
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References

1 The crystal structure of pseudokinase PEAK1 (Sugen kinase 269) reveals an unusual catalytic cleft and a novel mode of kinase fold dimerization.J Biol Chem. 2018 Feb 2;293(5):1642-1650. doi: 10.1074/jbc.RA117.000751. Epub 2017 Dec 6.
2 The PEAK1-PPP1R12B axis inhibits tumor growth and metastasis by regulating Grb2/PI3K/Akt signalling in colorectal cancer.Cancer Lett. 2019 Feb 1;442:383-395. doi: 10.1016/j.canlet.2018.11.014. Epub 2018 Nov 22.
3 DHPS-dependent hypusination of eIF5A1/2 is necessary for TGF/fibronectin-induced breast cancer metastasis and associates with prognostically unfavorable genomic alterations in TP53.Biochem Biophys Res Commun. 2019 Nov 19;519(4):838-845. doi: 10.1016/j.bbrc.2019.09.075. Epub 2019 Sep 24.
4 eIF5A-PEAK1 Signaling Regulates YAP1/TAZ Protein Expression and Pancreatic Cancer Cell Growth.Cancer Res. 2017 Apr 15;77(8):1997-2007. doi: 10.1158/0008-5472.CAN-16-2594. Epub 2017 Apr 5.
5 Overexpression of PEAK1 contributes to epithelial-mesenchymal transition and tumor metastasis in lung cancer through modulating ERK1/2 and JAK2 signaling.Cell Death Dis. 2018 Jul 23;9(8):802. doi: 10.1038/s41419-018-0817-1.
6 PEAK1, acting as a tumor promoter in colorectal cancer, is regulated by the EGFR/KRas signaling axis and miR-181d.Cell Death Dis. 2018 Feb 15;9(3):271. doi: 10.1038/s41419-018-0320-8.
7 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
8 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
9 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.
10 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.
11 Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
12 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
13 Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
14 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.
15 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.
16 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.
17 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.