Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT63I0CL)

DOT Name Dedicator of cytokinesis protein 5 (DOCK5)
Gene Name DOCK5
Related Disease
Acute myelogenous leukaemia ( )
Advanced cancer ( )
Asthma ( )
Obesity ( )
Osteoporosis ( )
Head-neck squamous cell carcinoma ( )
Neoplasm ( )
UniProt ID
DOCK5_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7DPA
Pfam ID
PF06920 ; PF20422 ; PF20421 ; PF14429 ; PF16172 ; PF00018
Sequence
MARWIPTKRQKYGVAIYNYNASQDVELSLQIGDTVHILEMYEGWYRGYTLQNKSKKGIFP
ETYIHLKEATVEDLGQHETVIPGELPLVQELTSTLREWAVIWRKLYVNNKLTLFRQLQQM
TYSLIEWRSQILSGTLPKDELAELKKKVTAKIDHGNRMLGLDLVVRDDNGNILDPDETST
IALFKAHEVASKRIEEKIQEEKSILQNLDLRGQSIFSTIHTYGLYVNFKNFVCNIGEDAE
LFMALYDPDQSTFISENYLIRWGSNGMPKEIEKLNNLQAVFTDLSSMDLIRPRVSLVCQI
VRVGHMELKEGKKHTCGLRRPFGVAVMDITDIIHGKVDDEEKQHFIPFQQIAMETYIRQR
QLIMSPLITSHVIGENEPLTSVLNKVIAAKEVNHKGQGLWVSLKLLPGDLTQVQKNFSHL
VDRSTAIARKMGFPEIILPGDVRNDIYVTLIHGEFDKGKKKTPKNVEVTMSVHDEEGKLL
EKAIHPGAGYEGISEYKSVVYYQVKQPCWYETVKVSIAIEEVTRCHIRFTFRHRSSQETR
DKSERAFGVAFVKLMNPDGTTLQDGRHDLVVYKGDNKKMEDAKFYLTLPGTKMEMEEKEL
QASKNLVTFTPSKDSTKDSFQIATLICSTKLTQNVDLLGLLNWRSNSQNIKHNLKKLMEV
DGGEIVKFLQDTLDALFNIMMEMSDSETYDFLVFDALVFIISLIGDIKFQHFNPVLETYI
YKHFSATLAYVKLSKVLNFYVANADDSSKTELLFAALKALKYLFRFIIQSRVLYLRFYGQ
SKDGDEFNNSIRQLFLAFNMLMDRPLEEAVKIKGAALKYLPSIINDVKLVFDPVELSVLF
CKFIQSIPDNQLVRQKLNCMTKIVESTLFRQSECREVLLPLLTDQLSGQLDDNSNKPDHE
ASSQLLSNILEVLDRKDVGATAVHIQLIMERLLRRINRTVIGMNRQSPHIGSFVACMIAL
LQQMDDSHYSHYISTFKTRQDIIDFLMETFIMFKDLIGKNVYAKDWMVMNMTQNRVFLRA
INQFAEVLTRFFMDQASFELQLWNNYFHLAVAFLTHESLQLETFSQAKRNKIVKKYGDMR
KEIGFRIRDMWYNLGPHKIKFIPSMVGPILEVTLTPEVELRKATIPIFFDMMQCEFNFSG
NGNFHMFENELITKLDQEVEGGRGDEQYKVLLEKLLLEHCRKHKYLSSSGEVFALLVSSL
LENLLDYRTIIMQDESKENRMSCTVNVLNFYKEKKREDIYIRYLYKLRDLHRDCENYTEA
AYTLLLHAELLQWSDKPCVPHLLQKDSYYVYTQQELKEKLYQEIISYFDKGKMWEKAIKL
SKELAETYESKVFDYEGLGNLLKKRASFYENIIKAMRPQPEYFAVGYYGQGFPSFLRNKI
FIYRGKEYERREDFSLRLLTQFPNAEKMTSTTPPGEDIKSSPKQYMQCFTVKPVMSLPPS
YKDKPVPEQILNYYRANEVQQFRYSRPFRKGEKDPDNEFATMWIERTTYTTAYTFPGILK
WFEVKQISTEEISPLENAIETMELTNERISNCVQQHAWDRSLSVHPLSMLLSGIVDPAVM
GGFSNYEKAFFTEKYLQEHPEDQEKVELLKRLIALQMPLLTEGIRIHGEKLTEQLKPLHE
RLSSCFRELKEKVEKHYGVITLPPNLTERKQSRTGSIVLPYIMSSTLRRLSITSVTSSVV
STSSNSSDNAPSRPGSDGSILEPLLERRASSGARVEDLSLREENSENRISKFKRKDWSLS
KSQVIAEKAPEPDLMSPTRKAQRPKSLQLMDNRLSPFHGSSPPQSTPLSPPPLTPKATRT
LSSPSLQTDGIAATPVPPPPPPKSKPYEGSQRNSTELAPPLPVRREAKAPPPPPPKARKS
GIPTSEPGSQ
Function
Guanine nucleotide exchange factor (GEF) for Rho and Rac. GEF proteins activate small GTPases by exchanging bound GDP for free GTP. Along with DOCK1, mediates CRK/CRKL regulation of epithelial and endothelial cell spreading and migration on type IV collagen.
Reactome Pathway
RHOG GTPase cycle (R-HSA-9013408 )
Factors involved in megakaryocyte development and platelet production (R-HSA-983231 )
RAC1 GTPase cycle (R-HSA-9013149 )

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myelogenous leukaemia DISCSPTN Strong Altered Expression [1]
Advanced cancer DISAT1Z9 Strong Altered Expression [1]
Asthma DISW9QNS Strong Biomarker [2]
Obesity DIS47Y1K Strong Biomarker [3]
Osteoporosis DISF2JE0 Strong Biomarker [4]
Head-neck squamous cell carcinoma DISF7P24 moderate Altered Expression [5]
Neoplasm DISZKGEW moderate Genetic Variation [5]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
16 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 Dedicator of cytokinesis protein 5 (DOCK5). [6]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Dedicator of cytokinesis protein 5 (DOCK5). [7]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Dedicator of cytokinesis protein 5 (DOCK5). [8]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Dedicator of cytokinesis protein 5 (DOCK5). [9]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Dedicator of cytokinesis protein 5 (DOCK5). [10]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Dedicator of cytokinesis protein 5 (DOCK5). [11]
Quercetin DM3NC4M Approved Quercetin increases the expression of Dedicator of cytokinesis protein 5 (DOCK5). [13]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Dedicator of cytokinesis protein 5 (DOCK5). [14]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Dedicator of cytokinesis protein 5 (DOCK5). [15]
Niclosamide DMJAGXQ Approved Niclosamide decreases the expression of Dedicator of cytokinesis protein 5 (DOCK5). [16]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Dedicator of cytokinesis protein 5 (DOCK5). [15]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Dedicator of cytokinesis protein 5 (DOCK5). [17]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Dedicator of cytokinesis protein 5 (DOCK5). [19]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Dedicator of cytokinesis protein 5 (DOCK5). [21]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Dedicator of cytokinesis protein 5 (DOCK5). [23]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Dedicator of cytokinesis protein 5 (DOCK5). [24]
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⏷ Show the Full List of 16 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 Dedicator of cytokinesis protein 5 (DOCK5). [12]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Dedicator of cytokinesis protein 5 (DOCK5). [20]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Dedicator of cytokinesis protein 5 (DOCK5). [22]
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1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
DNCB DMDTVYC Phase 2 DNCB affects the binding of Dedicator of cytokinesis protein 5 (DOCK5). [18]
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References

1 MBD3/NuRD loss participates with KDM6A program to promote DOCK5/8 expression and Rac GTPase activation in human acute myeloid leukemia.FASEB J. 2019 Apr;33(4):5268-5286. doi: 10.1096/fj.201801035R. Epub 2019 Jan 22.
2 CDC42-related genes are upregulated in helper Tcells from obese asthmatic children.J Allergy Clin Immunol. 2018 Feb;141(2):539-548.e7. doi: 10.1016/j.jaci.2017.04.016. Epub 2017 May 4.
3 Novel association approach for variable number tandem repeats (VNTRs) identifies DOCK5 as a susceptibility gene for severe obesity.Hum Mol Genet. 2012 Aug 15;21(16):3727-38. doi: 10.1093/hmg/dds187. Epub 2012 May 16.
4 Allosteric inhibition of the guanine nucleotide exchange factor DOCK5 by a small molecule.Sci Rep. 2017 Oct 31;7(1):14409. doi: 10.1038/s41598-017-13619-2.
5 Characterization of Alternative Splicing Events in HPV-Negative Head and Neck Squamous Cell Carcinoma Identifies an Oncogenic DOCK5 Variant.Clin Cancer Res. 2018 Oct 15;24(20):5123-5132. doi: 10.1158/1078-0432.CCR-18-0752. Epub 2018 Jun 26.
6 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
7 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
8 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
9 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.
10 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.
11 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.
12 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.
13 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.
14 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
15 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
16 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
17 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
18 Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
19 Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.
20 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
21 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.
22 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.
23 Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
24 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.