Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDXY7PX)

DOT Name Protein TANC2 (TANC2)
Synonyms Tetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing protein 2
Gene Name TANC2
Related Disease
Intellectual developmental disorder with autistic features and language delay, with or without seizures ( )
Narcolepsy ( )
Mental disorder ( )
Epilepsy ( )
Intellectual disability ( )
Neurodevelopmental disorder ( )
Syndromic intellectual disability ( )
Breast cancer ( )
Breast carcinoma ( )
UniProt ID
TANC2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF12796 ; PF13637 ; PF13181
Sequence
MFRNSLKMLLTGGKSSRKNRSSDGGSEEPPDRRQSSVDSRQSRSGQGGISTESDCAFEPD
YAVPPLPVSEGDAEQELGPPPSVDEAANTLMTRLGFLLGEKVTEVQPGDQYSMEVQDENQ
TSAITQRISPCSTLTSSTASPPASSPCSTLPPISTNATAKDCSYGAVTSPTSTLESRDSG
IIATLTSYSENVERTKYAGESSKELGSGGNIKPWQSQKSSMDSCLYRVDENMTASTYSLN
KIPERNLETVLSQSVQSIPLYLMPRPNSVAATSSAHLEDLAYLDEQRHTPLRTSLRMPRQ
SMGGARTQQDLRVRFAPYRPPDISLKPLLFEVPSITTESVFVGRDWVFHEIDAQLQSSNA
SVNQGVVIVGNIGFGKTAIISRLVALSCHGTRMRQIASDSPHASPKHVDANRELPLTQPP
SAHSSITSGSCPGTPEMRRRQEEAMRRLASQVVAYHYCQADNAYTCLVPEFVHNVAALLC
RSPQLTAYREQLLREPHLQSMLSLRSCVQDPMASFRRGVLEPLENLHKERKIPDEDFIIL
IDGLNEAEFHKPDYGDTIVSFLSKMIGKFPSWLKLIVTVRTSLQEITKLLPFHRIFLDRL
EENEAIDQDLQAYILHRIHSSSEIQNNISLNGKMDNTTFGKLSSHLKTLSQGSYLYLKLT
FDLIEKGYLVLKSSSYKVVPVSLSEVYLLQCNMKFPTQSSFDRVMPLLNVAVASLHPLTD
EHIFQAINAGSIEGTLEWEDFQQRMENLSMFLIKRRDMTRMFVHPSFREWLIWREEGEKT
KFLCDPRSGHTLLAFWFSRQEGKLNRQQTIELGHHILKAHIFKGLSKKVGVSSSILQGLW
ISYSTEGLSMALASLRNLYTPNIKVSRLLILGGANINYRTEVLNNAPILCVQSHLGYTEM
VALLLEFGANVDASSESGLTPLGYAAAAGYLSIVVLLCKKRAKVDHLDKNGQCALVHAAL
RGHLEVVKFLIQCDWTMAGQQQGVFKKSHAIQQALIAAASMGYTEIVSYLLDLPEKDEEE
VERAQINSFDSLWGETALTAAAGRGKLEVCRLLLEQGAAVAQPNRRGAVPLFSTVRQGHW
QIVDLLLTHGADVNMADKQGRTPLMMAASEGHLGTVDFLLAQGASIALMDKEGLTALSWA
CLKGHLSVVRSLVDNGAATDHADKNGRTPLDLAAFYGDAEVVQFLVDHGAMIEHVDYSGM
RPLDRAVGCRNTSVVVTLLKKGAKIGPATWAMATSKPDIMIILLSKLMEEGDMFYKKGKV
KEAAQRYQYALKKFPREGFGEDLKTFRELKVSLLLNLSRCRRKMNDFGMAEEFATKALEL
KPKSYEAYYARARAKRSSRQFAAALEDLNEAIKLCPNNREIQRLLLRVEEECRQMQQPQQ
PPPPPQPQQQLPEEAEPEPQHEDIYSVQDIFEEEYLEQDVENVSIGLQTEARPSQGLPVI
QSPPSSPPHRDSAYISSSPLGSHQVFDFRSSSSVGSPTRQTYQSTSPALSPTHQNSHYRP
SPPHTSPAHQGGSYRFSPPPVGGQGKEYPSPPPSPLRRGPQYRASPPAESMSVYRSQSGS
PVRYQQETSVSQLPGRPKSPLSKMAQRPYQMPQLPVAVPQQGLRLQPAKAQIVRSNQPSP
AVHSSTVIPTGAYGQVAHSMASKYQSSQGDIGVSQSRLVYQGSIGGIVGDGRPVQHVQAS
LSAGAICQHGGLTKEDLPQRPSSAYRGGVRYSQTPQIGRSQSASYYPVCHSKLDLERSSS
QLGSPDVSHLIRRPISVNPNEIKPHPPTPRPLLHSQSVGLRFSPSSNSISSTSNLTPTFR
PSSSIQQMEIPLKPAYERSCDELSPVSPTQGGYPSEPTRSRTTPFMGIIDKTARTQQYPH
LHQQNRTWAVSSVDTVLSPTSPGNLPQPESFSPPSSISNIAFYNKTNNAQNGHLLEDDYY
SPHGMLANGSRGDLLERVSQASSYPDVKVARTLPVAQAYQDNLYRQLSRDSRQGQTSPIK
PKRPFVESNV
Function Scaffolding protein in the dendritic spines which acts as immobile postsynaptic posts able to recruit KIF1A-driven dense core vesicles to dendritic spines.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Intellectual developmental disorder with autistic features and language delay, with or without seizures DIS25TU4 Definitive Autosomal dominant [1]
Narcolepsy DISLCNLI Definitive Genetic Variation [2]
Mental disorder DIS3J5R8 Strong Genetic Variation [3]
Epilepsy DISBB28L moderate Biomarker [3]
Intellectual disability DISMBNXP moderate Biomarker [3]
Neurodevelopmental disorder DIS372XH moderate Biomarker [3]
Syndromic intellectual disability DISH7SDF Supportive Autosomal dominant [3]
Breast cancer DIS7DPX1 Limited Biomarker [4]
Breast carcinoma DIS2UE88 Limited Biomarker [4]
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⏷ Show the Full List of 9 Disease(s)
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 Protein TANC2 (TANC2). [5]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Protein TANC2 (TANC2). [6]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Protein TANC2 (TANC2). [7]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Protein TANC2 (TANC2). [8]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Protein TANC2 (TANC2). [9]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Protein TANC2 (TANC2). [11]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Protein TANC2 (TANC2). [12]
Marinol DM70IK5 Approved Marinol increases the expression of Protein TANC2 (TANC2). [13]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Protein TANC2 (TANC2). [14]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate increases the expression of Protein TANC2 (TANC2). [15]
OTX-015 DMI8RG1 Phase 1/2 OTX-015 increases the expression of Protein TANC2 (TANC2). [16]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Protein TANC2 (TANC2). [18]
Mivebresib DMCPF90 Phase 1 Mivebresib increases the expression of Protein TANC2 (TANC2). [16]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Protein TANC2 (TANC2). [19]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Protein TANC2 (TANC2). [21]
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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 Protein TANC2 (TANC2). [10]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Protein TANC2 (TANC2). [17]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Protein TANC2 (TANC2). [20]
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References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
3 Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders. Nat Commun. 2019 Oct 15;10(1):4679. doi: 10.1038/s41467-019-12435-8.
4 A siRNA screen identifies RAD21, EIF3H, CHRAC1 and TANC2 as driver genes within the 8q23, 8q24.3 and 17q23 amplicons in breast cancer with effects on cell growth, survival and transformation.Carcinogenesis. 2014 Mar;35(3):670-82. doi: 10.1093/carcin/bgt351. Epub 2013 Oct 22.
5 Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
6 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.
7 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
8 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.
9 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
10 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.
11 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
12 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.
13 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.
14 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
15 Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
16 Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
17 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.
18 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
19 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.
20 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.
21 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.