Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW4M7HI)

DOT Name Transforming acidic coiled-coil-containing protein 2 (TACC2)
Synonyms Anti-Zuai-1; AZU-1
Gene Name TACC2
Related Disease
Advanced cancer ( )
Breast carcinoma ( )
Neoplasm ( )
Psoriasis ( )
Castration-resistant prostate carcinoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Acute myelogenous leukaemia ( )
Breast cancer ( )
Breast neoplasm ( )
Hepatocellular carcinoma ( )
Invasive ductal breast carcinoma ( )
UniProt ID
TACC2_HUMAN
Pfam ID
PF05010
Sequence
MGNENSTSDNQRTLSAQTPRSAQPPGNSQNIKRKQQDTPGSPDHRDASSIGSVGLGGFCT
ASESSASLDPCLVSPEVTEPRKDPQGARGPEGSLLPSPPPSQEREHPSSSMPFAECPPEG
CLASPAAAPEDGPQTQSPRREPAPNAPGDIAAAFPAERDSSTPYQEIAAVPSAGRERQPK
EEGQKSSFSFSSGIDQSPGMSPVPLREPMKAPLCGEGDQPGGFESQEKEAAGGFPPAESR
QGVASVQVTPEAPAAAQQGTESSAVLEKSPLKPMAPIPQDPAPRASDRERGQGEAPPQYL
TDDLEFLRACHLPRSNSGAAPEAEVNAASQESCQQPVGAYLPHAELPWGLPSPALVPEAG
GSGKEALDTIDVQGHPQTGMRGTKPNQVVCVAAGGQPEGGLPVSPEPSLLTPTEEAHPAS
SLASFPAAQIPIAVEEPGSSSRESVSKAGMPVSADAAKEVVDAGLVGLERQVSDLGSKGE
HPEGDPGEVPAPSPQERGEHLNTEQSHEVQPGVPPPPLPKEQSHEVQPGAPPPPLPKAPS
ESARGPPGPTDGAKVHEDSTSPAVAKEGSRSPGDSPGGKEEAPEPPDGGDPGNLQGEDSQ
AFSSKRDPEVGKDELSKPSSDAESRDHPSSHSAQPPRKGGAGHTDGPHSQTAEADASGLP
HKLGEEDPVLPPVPDGAGEPTVPEGAIWEGSGLQPKCPDTLQSREGLGRMESFLTLESEK
SDFPPTPVAEVAPKAQEGESTLEIRKMGSCDGEGLLTSPDQPRGPACDASRQEFHAGVPH
PPQGENLAADLGLTALILDQDQQGIPSCPGEGWIRGAASEWPLLSSEKHLQPSQAQPETS
IFDVLKEQAQPPENGKETSPSHPGFKDQGADSSQIHVPVEPQEDNNLPTHGGQEQALGSE
LQSQLPKGTLSDTPTSSPTDMVWESSLTEESELSAPTRQKLPALGEKRPEGACGDGQSSR
VSPPAADVLKDFSLAGNFSRKETCCTGQGPNKSQQALADALEEGSQHEEACQRHPGASEA
ADGCSPLWGLSKREMASGNTGEAPPCQPDSVALLDAVPCLPALAPASPGVTPTQDAPETE
ACDETQEGRQQPVPAPQQKMECWATSDAESPKLLASFPSAGEQGGEAGAAETGGSAGAGD
PGKQQAPEKPGEATLSCGLLQTEHCLTSGEEASTSALRESCQAEHPMASCQDALLPAREL
GGIPRSTMDFSTHQAVPDPKELLLSGPPEVAAPDTPYLHVDSAAQRGAEDSGVKAVSSAD
PRAPGESPCPVGEPPLALENAASLKLFAGSLAPLLQPGAAGGEIPAVQASSGSPKARTTE
GPVDSMPCLDRMPLLAKGKQATGEEKAATAPGAGAKASGEGMAGDAAGETEGSMERMGEP
SQDPKQGTSGGVDTSSEQIATLTGFPDFREHIAKIFEKPVLGALATPGEKAGAGRSAVGK
DLTRPLGPEKLLDGPPGVDVTLLPAPPARLQVEKKQQLAGEAEISHLALQDPASDKLLGP
AGLTWERNLPGAGVGKEMAGVPPTLREDERPEGPGAAWPGLEGQAYSQLERSRQELASGL
PSPAATQELPVERAAAFQVAPHSHGEEAVAQDRIPSGKQHQETSACDSPHGEDGPGDFAH
TGVPGHVPRSTCAPSPQREVLTVPEANSEPWTLDTLGGERRPGVTAGILEMRNALGNQST
PAPPTGEVADTPLEPGKVAGAAGEAEGDITLSTAETQACASGDLPEAGTTRTFSVVAGDL
VLPGSCQDPACSDKAPGMEGTAALHGDSPARPQQAKEQPGPERPIPAGDGKVCVSSPPEP
DETHDPKLQHLAPEELHTDRESPRPGPSMLPSVPKKDAPRVMDKVTSDETRGAEGTESSP
VADDIIQPAAPADLESPTLAASSYHGDVVGQVSTDLIAQSISPAAAHAGLPPSAAEHIVS
PSAPAGDRVEASTPSCPDPAKDLSRSSDSEEAFETPESTTPVKAPPAPPPPPPEVIPEPE
VSTQPPPEEPGCGSETVPVPDGPRSDSVEGSPFRPPSHSFSAVFDEDKPIASSGTYNLDF
DNIELVDTFQTLEPRASDAKNQEGKVNTRRKSTDSVPISKSTLSRSLSLQASDFDGASSS
GNPEAVALAPDAYSTGSSSASSTLKRTKKPRPPSLKKKQTTKKPTETPPVKETQQEPDEE
SLVPSGENLASETKTESAKTEGPSPALLEETPLEPAVGPKAACPLDSESAEGVVPPASGG
GRVQNSPPVGRKTLPLTTAPEAGEVTPSDSGGQEDSPAKGLSVRLEFDYSEDKSSWDNQQ
ENPPPTKKIGKKPVAKMPLRRPKMKKTPEKLDNTPASPPRSPAEPNDIPIAKGTYTFDID
KWDDPNFNPFSSTSKMQESPKLPQQSYNFDPDTCDESVDPFKTSSKTPSSPSKSPASFEI
PASAMEANGVDGDGLNKPAKKKKTPLKTDTFRVKKSPKRSPLSDPPSQDPTPAATPETPP
VISAVVHATDEEKLAVTNQKWTCMTVDLEADKQDYPQPSDLSTFVNETKFSSPTEELDYR
NSYEIEYMEKIGSSLPQDDDAPKKQALYLMFDTSQESPVKSSPVRMSESPTPCSGSSFEE
TEALVNTAAKNQHPVPRGLAPNQESHLQVPEKSSQKELEAMGLGTPSEAIEITAPEGSFA
SADALLSRLAHPVSLCGALDYLEPDLAEKNPPLFAQKLQEELEFAIMRIEALKLARQIAL
ASRSHQDAKREAAHPTDVSISKTALYSRIGTAEVEKPAGLLFQQPDLDSALQIARAEIIT
KEREVSEWKDKYEESRREVMEMRKIVAEYEKTIAQMIEDEQREKSVSHQTVQQLVLEKEQ
ALADLNSVEKSLADLFRRYEKMKEVLEGFRKNEEVLKRCAQEYLSRVKKEEQRYQALKVH
AEEKLDRANAEIAQVRGKAQQEQAAHQASLRKEQLRVDALERTLEQKNKEIEELTKICDE
LIAKMGKS
Function
Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors. May play a role in organizing centrosomal microtubules. May act as a tumor suppressor protein. May represent a tumor progression marker.
Tissue Specificity Strongly expressed in heart, skeletal muscle, brain, prostate, thyroid and trachea.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Breast carcinoma DIS2UE88 Strong Genetic Variation [2]
Neoplasm DISZKGEW Strong Biomarker [3]
Psoriasis DIS59VMN Strong Biomarker [4]
Castration-resistant prostate carcinoma DISVGAE6 moderate Altered Expression [3]
Prostate cancer DISF190Y moderate Biomarker [3]
Prostate carcinoma DISMJPLE moderate Biomarker [3]
Acute myelogenous leukaemia DISCSPTN Limited Genetic Variation [5]
Breast cancer DIS7DPX1 Limited Biomarker [6]
Breast neoplasm DISNGJLM Limited Altered Expression [7]
Hepatocellular carcinoma DIS0J828 Limited Biomarker [8]
Invasive ductal breast carcinoma DIS43J58 Limited Biomarker [6]
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⏷ Show the Full List of 12 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Transforming acidic coiled-coil-containing protein 2 (TACC2). [9]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Transforming acidic coiled-coil-containing protein 2 (TACC2). [15]
Quercetin DM3NC4M Approved Quercetin decreases the phosphorylation of Transforming acidic coiled-coil-containing protein 2 (TACC2). [16]
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of Transforming acidic coiled-coil-containing protein 2 (TACC2). [23]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Transforming acidic coiled-coil-containing protein 2 (TACC2). [26]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Transforming acidic coiled-coil-containing protein 2 (TACC2). [16]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the methylation of Transforming acidic coiled-coil-containing protein 2 (TACC2). [23]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Transforming acidic coiled-coil-containing protein 2 (TACC2). [16]
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⏷ Show the Full List of 8 Drug(s)
15 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 Transforming acidic coiled-coil-containing protein 2 (TACC2). [10]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Transforming acidic coiled-coil-containing protein 2 (TACC2). [11]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Transforming acidic coiled-coil-containing protein 2 (TACC2). [12]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Transforming acidic coiled-coil-containing protein 2 (TACC2). [13]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Transforming acidic coiled-coil-containing protein 2 (TACC2). [14]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Transforming acidic coiled-coil-containing protein 2 (TACC2). [17]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Transforming acidic coiled-coil-containing protein 2 (TACC2). [18]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Transforming acidic coiled-coil-containing protein 2 (TACC2). [19]
Marinol DM70IK5 Approved Marinol increases the expression of Transforming acidic coiled-coil-containing protein 2 (TACC2). [20]
Progesterone DMUY35B Approved Progesterone increases the expression of Transforming acidic coiled-coil-containing protein 2 (TACC2). [21]
Menadione DMSJDTY Approved Menadione affects the expression of Transforming acidic coiled-coil-containing protein 2 (TACC2). [22]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of Transforming acidic coiled-coil-containing protein 2 (TACC2). [24]
Melphalan DMOLNHF Approved Melphalan decreases the expression of Transforming acidic coiled-coil-containing protein 2 (TACC2). [25]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Transforming acidic coiled-coil-containing protein 2 (TACC2). [27]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Transforming acidic coiled-coil-containing protein 2 (TACC2). [28]
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⏷ Show the Full List of 15 Drug(s)

References

1 Transforming acidic coiled-coil-containing protein 2 (TACC2) in human breast cancer, expression pattern and clinical/prognostic relevance.Cancer Genomics Proteomics. 2010 Mar-Apr;7(2):67-73.
2 Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
3 TACC2 is an androgen-responsive cell cycle regulator promoting androgen-mediated and castration-resistant growth of prostate cancer.Mol Endocrinol. 2012 May;26(5):748-61. doi: 10.1210/me.2011-1242. Epub 2012 Mar 28.
4 Levels of miR-31 and its target genes in dermal mesenchymal cells of patients with psoriasis.Int J Dermatol. 2019 Feb;58(2):198-204. doi: 10.1111/ijd.14197. Epub 2018 Sep 9.
5 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.
6 TACC2 (transforming acidic coiled-coil protein 2) in breast carcinoma as a potent prognostic predictor associated with cell proliferation.Cancer Med. 2016 Aug;5(8):1973-82. doi: 10.1002/cam4.736. Epub 2016 Jun 22.
7 Molecular cloning, genomic structure and interactions of the putative breast tumor suppressor TACC2.Genomics. 2003 Feb;81(2):192-201. doi: 10.1016/s0888-7543(02)00039-3.
8 High expression of TACC2 in hepatocellular carcinoma is associated with poor prognosis.Cancer Biomark. 2018;22(4):611-619. doi: 10.3233/CBM-170091.
9 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
10 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.
11 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.
12 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.
13 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.
14 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
15 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.
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 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
18 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.
19 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
20 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.
21 Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
22 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
23 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.
24 Identification of novel human CTL epitopes and their agonist epitopes of mesothelin. Clin Cancer Res. 2005 Sep 1;11(17):6342-51. doi: 10.1158/1078-0432.CCR-05-0596.
25 Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
26 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.
27 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.
28 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.