Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI3MBLV)

DOT Name Dedicator of cytokinesis protein 10 (DOCK10)
Synonyms Zizimin-3
Gene Name DOCK10
Related Disease
Melanoma ( )
Acute myelogenous leukaemia ( )
Small lymphocytic lymphoma ( )
UniProt ID
DOC10_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
6TKY; 6TKZ; 6TM1; 7Q43
Pfam ID
PF06920 ; PF20422 ; PF20421 ; PF14429 ; PF11878 ; PF00169
Sequence
MAGERTRRFTRSLLRPGQAAELRHSAASAAAVAVSSRQQQRQEKPRLLEPLDYETVIEEL
EKTYRNDPLQDLLFFPSDDFSAATVSWDIRTLYSTVPEDAEHKAENLLVKEACKFYSSQW
HVVNYKYEQYSGDIRQLPRAEYKPEKLPSHSFEIDHEDADKDEDTTSHSSSKGGGGAGGT
GVFKSGWLYKGNFNSTVNNTVTVRSFKKRYFQLTQLPDNSYIMNFYKDEKISKEPKGCIF
LDSCTGVVQNNRLRKYAFELKMNDLTYFVLAAETESDMDEWIHTLNRILQISPEGPLQGR
RSTELTDLGLDSLDNSVTCECTPEETDSSENNLHADFAKYLTETEDTVKTTRNMERLNLF
SLDPDIDTLKLQKKDLLEPESVIKPFEEKAAKRIMIICKALNSNLQGCVTENENDPITNI
EPFFVSVALYDLRDSRKISADFHVDLNHAAVRQMLLGASVALENGNIDTITPRQSEEPHI
KGLPEEWLKFPKQAVFSVSNPHSEIVLVAKIEKVLMGNIASGAEPYIKNPDSNKYAQKIL
KSNRQFCSKLGKYRMPFAWAVRSVFKDNQGNVDRDSRFSPLFRQESSKISTEDLVKLVSD
YRRADRISKMQTIPGSLDIAVDNVPLEHPNCVTSSFIPVKPFNMMAQTEPTVEVEEFVYD
STKYCRPYRVYKNQIYIYPKHLKYDSQKCFNKARNITVCIEFKNSDEESAKPLKCIYGKP
GGPLFTSAAYTAVLHHSQNPDFSDEVKIELPTQLHEKHHILFSFYHVTCDINAKANAKKK
EALETSVGYAWLPLMKHDQIASQEYNIPIATSLPPNYLSFQDSASGKHGGSDIKWVDGGK
PLFKVSTFVVSTVNTQDPHVNAFFQECQKREKDMSQSPTSNFIRSCKNLLNVEKIHAIMS
FLPIILNQLFKVLVQNEEDEITTTVTRVLTDIVAKCHEEQLDHSVQSYIKFVFKTRACKE
RTVHEELAKNVTGLLKSNDSTTVKHVLKHSWFFFAIILKSMAQHLIDTNKIQLPRPQRFP
ESYQNELDNLVMVLSDHVIWKYKDALEETRRANHSVARFLKRCFTFMDRGYVFKMVNNYI
SMFSSGDLKTLCQYKFDFLQEVCQHEHFIPLCLPIRSANIPDPLTPSESTQELHASDMPE
YSVTNEFCRKHFLIGILLREVGFALQEDQDVRHLALAVLKNLMAKHSFDDRYREPRKQAQ
IASLYMPLYGMLLDNMPRIYLKDLYPFTVNTSNQGSRDDLSTNGGFQSQTAIKHANSVDT
SFSKDVLNSIAAFSSIAISTVNHADSRASLASLDSNPSTNEKSSEKTDNCEKIPRPLSLI
GSTLRFDKLDQAETRSLLMCFLHIMKTISYETLIAYWQRAPSPEVSDFFSILDVCLQNFR
YLGKRNIIRKIAAAFKFVQSTQNNGTLKGSNPSCQTSGLLSQWMHSTSSHEGHKQHRSQT
LPIIRGKNALSNPKLLQMLDNTMTSNSNEIDIVHHVDTEANIATEVCLTILDLLSLFTQT
HQRQLQQCDCQNSLMKRVFDTYMLFFQVNQSATALKHVFASLRLFVCKFPSAFFQGPADL
CGSFCYEVLKCCNHRSRSTQTEASALLYFFMRKNFEFNKQKSIVRSHLQLIKAVSQLIAD
AGIGGSRFQHSLAITNNFANGDKQMKNSNFPAEVKDLTKRIRTVLMATAQMKEHEKDPEM
LVDLQYSLANSYASTPELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGYW
KVEKICTASLLSEDTHPCDSNSLLTTPSGGSMFSMGWPAFLSITPNIKEEGAMKEDSGMQ
DTPYNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYDIHRSY
LKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADK
FGADNVKIIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFE
TPFTLSGKKHGGVAEQCKRRTILTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSKKV
SELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKLLKEI
FRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSELSTVMNEQITGRDDLSKRGV
DQTCTRVISKATPALPTVSISSSAEV
Function
Guanine nucleotide-exchange factor (GEF) that activates CDC42 and RAC1 by exchanging bound GDP for free GTP. Essential for dendritic spine morphogenesis in Purkinje cells and in hippocampal neurons, via a CDC42-mediated pathway. Sustains B-cell lymphopoiesis in secondary lymphoid tissues and regulates FCER2/CD23 expression.
Tissue Specificity Expressed at low level in brain and lung. Isoform 1 is enriched in normal T-cells, isoform 3 is enriched in normal B-cells and chronic lymphocytic leukemia (CLL) B-cells.
Reactome Pathway
RAC1 GTPase cycle (R-HSA-9013149 )
RAC2 GTPase cycle (R-HSA-9013404 )
RAC3 GTPase cycle (R-HSA-9013423 )
Factors involved in megakaryocyte development and platelet production (R-HSA-983231 )
CDC42 GTPase cycle (R-HSA-9013148 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Melanoma DIS1RRCY Strong Altered Expression [1]
Acute myelogenous leukaemia DISCSPTN Limited Genetic Variation [2]
Small lymphocytic lymphoma DIS30POX Limited Altered Expression [3]
------------------------------------------------------------------------------------
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
Valproate DMCFE9I Approved Valproate increases the expression of Dedicator of cytokinesis protein 10 (DOCK10). [4]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Dedicator of cytokinesis protein 10 (DOCK10). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Dedicator of cytokinesis protein 10 (DOCK10). [6]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Dedicator of cytokinesis protein 10 (DOCK10). [7]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Dedicator of cytokinesis protein 10 (DOCK10). [8]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Dedicator of cytokinesis protein 10 (DOCK10). [9]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Dedicator of cytokinesis protein 10 (DOCK10). [10]
Marinol DM70IK5 Approved Marinol increases the expression of Dedicator of cytokinesis protein 10 (DOCK10). [11]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Dedicator of cytokinesis protein 10 (DOCK10). [12]
Ethinyl estradiol DMODJ40 Approved Ethinyl estradiol decreases the expression of Dedicator of cytokinesis protein 10 (DOCK10). [14]
Belinostat DM6OC53 Phase 2 Belinostat decreases the expression of Dedicator of cytokinesis protein 10 (DOCK10). [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Dedicator of cytokinesis protein 10 (DOCK10). [16]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Dedicator of cytokinesis protein 10 (DOCK10). [17]
------------------------------------------------------------------------------------
⏷ Show the Full List of 13 Drug(s)
2 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 Dedicator of cytokinesis protein 10 (DOCK10). [13]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Dedicator of cytokinesis protein 10 (DOCK10). [13]
------------------------------------------------------------------------------------

References

1 DOCK10-mediated Cdc42 activation is necessary for amoeboid invasion of melanoma cells.Curr Biol. 2008 Oct 14;18(19):1456-65. doi: 10.1016/j.cub.2008.08.053. Epub 2008 Oct 2.
2 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
3 Dock10, a novel CZH protein selectively induced by interleukin-4 in human B lymphocytes.Mol Immunol. 2008 Jul;45(12):3411-8. doi: 10.1016/j.molimm.2008.04.003. Epub 2008 May 21.
4 Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
5 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.
6 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.
7 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
8 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
9 Quantitative proteomic analysis of HepG2 cells treated with quercetin suggests IQGAP1 involved in quercetin-induced regulation of cell proliferation and migration. OMICS. 2009 Apr;13(2):93-103. doi: 10.1089/omi.2008.0075.
10 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.
11 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
12 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
13 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.
14 The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
15 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.
16 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
17 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.