Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF6TZ8E)

• DOT Name: Protein TANC1 (TANC1)
• Synonyms: Tetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing protein 1
• Gene Name: TANC1
• Related Disease:
  Cholelithiasis
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal adenoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Rhabdomyosarcoma
  Intellectual disability
  Neurodevelopmental disorder
  Prostate carcinoma
• UniProt ID: TANC1_HUMAN
• Pfam ID: PF00023 ; PF12796 ; PF13637
• Sequence:
  MLKAVLKKSREGGKGGKKEAGSDFGPETSPVLHLDHSADSPVSSLPTAEDTYRVSLAKGV
  SMSLPSSPLLPRQSHLVQSRVNKKSPGPVRKPKYVESPRVPGDAVIMPFREVAKPTEPDE
  HEAKADNEPSCSPAAQELLTRLGFLLGEGIPSATHITIEDKNETMCTALSQGISPCSTLT
  SSTASPSTDSPCSTLNSCVSKTAANKSPCETISSPSSTLESKDSGIIATITSSSENDDRS
  GSSLEWNKDGNLRLGVQKGVLHDRRADNCSPVAEEETTGSAESTLPKAESSAGDGPVPYS
  QGSSSLIMPRPNSVAATSSTKLEDLSYLDGQRNAPLRTSIRLPWHNTAGGRAQEVKARFA
  PYKPQDILLKPLLFEVPSITTDSVFVGRDWLFHQIEENLRNTELAENRGAVVVGNVGFGK
  TAIISKLVALSCHGSRMRQIASNSPGSSPKTSDPTQDLHFTPLLSPSSSTSASSTAKTPL
  GSISAENQRPREDAVKYLASKVVAYHYCQADNTYTCLVPEFVHSIAALLCRSHQLAAYRD
  LLIKEPQLQSMLSLRSCVQDPVAAFKRGVLEPLTNLRNEQKIPEEEYIILIDGLNEAEFH
  KPDYGDTLSSFITKIISKFPAWLKLIVTVRANFQEIISALPFVKLSLDDFPDNKDIHSDL
  HAYVQHRVHSSQDILSNISLNGKADATLIGKVSSHLVLRSLGSYLYLKLTLDLFQRGHLV
  IKSASYKVVPVSLSELYLLQCNMKFMTQSAFERALPILNVALASLHPMTDEQIFQAINAG
  HIQGEQGWEDFQQRMDALSCFLIKRRDKTRMFCHPSFREWLVWRADGENTAFLCEPRNGH
  ALLAFMFSRQEGKLNRQQTMELGHHILKAHIFKGLSKKTGISSSHLQALWIGYSTEGLSA
  ALASLRNLYTPNVKVSRLLILGGANVNYRTEVLNNAPILCVQSHLGHEEVVTLLLEFGAC
  LDGTSENGMTALCYAAAAGHMKLVCLLTKKGVRVDHLDKKGQCALVHSALRGHGDILQYL
  LTCEWSPGPPQPGTLRKSHALQQALTAAASMGHSSVVQCLLGMEKEHEVEVNGTDTLWGE
  TALTAAAGRGKLEVCELLLGHGAAVSRTNRRGVPPLFCAARQGHWQIVRLLLERGCDVNL
  SDKQGRTPLMVAACEGHLSTVEFLLSKGAALSSLDKEGLSALSWACLKGHRAVVQYLVEE
  GAAIDQTDKNGRTPLDLAAFYGDAETVLYLVEKGAVIEHVDHSGMRPLDRAIGCRNTSVV
  VALLRKGAKLGNAAWAMATSKPDILIILLQKLMEEGNVMYKKGKMKEAAQRYQYALRKFP
  REGFGEDMRPFNELRVSLYLNLSRCRRKTNDFGMAEEFASKALELKPKSYEAFYARARAK
  RNSRQFVAALADLQEAVKLCPTNQEVKRLLARVEEECKQLQRSQQQKQQGPLPAPLNDSE
  NEEDTPTPGLSDHFHSEETEEEETSPQEESVSPTPRSQPSSSVPSSYIRNLQEGLQSKGR
  PVSPQSRAGIGKSLREPVAQPGLLLQPSKQAQIVKTSQHLGSGQSAVRNGSMKVQISSQN
  PPPSPMPGRIAATPAGSRTQHLEGTGTFTTRAGCGHFGDRLGPSQNVRLQCGENGPAHPL
  PSKTKTTERLLSHSSVAVDAAPPNQGGLATCSDVRHPASLTSSGSSGSPSSSIKMSSSTS
  SLTSSSSFSDGFKVQGPDTRIKDKVVTHVQSGTAEHRPRNTPFMGIMDKTARFQQQSNPP
  SRSWHCPAPEGLLTNTSSAAGLQSANTEKPSLMQVGGYNNQAKTCSVSTLSASVHNGAQV
  KELEESKCQIPVHSQENRITKTVSHLYQESISKQQPHISNEAHRSHLTAAKPKRSFIESN
  V
• Function: May be a scaffold component in the postsynaptic density.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cholelithiasis	DISERLZB	Strong	Genetic Variation	[1]
Colon cancer	DISVC52G	Strong	Genetic Variation	[2]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[2]
Colorectal adenoma	DISTSVHM	Strong	Genetic Variation	[2]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[2]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[2]
Rhabdomyosarcoma	DISNR7MS	moderate	Altered Expression	[3]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[4]
Neurodevelopmental disorder	DIS372XH	Limited	Biomarker	[4]
Prostate carcinoma	DISMJPLE	Limited	Genetic Variation	[5]

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 Protein TANC1 (TANC1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein TANC1 (TANC1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein TANC1 (TANC1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein TANC1 (TANC1).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein TANC1 (TANC1).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Protein TANC1 (TANC1).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Protein TANC1 (TANC1).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein TANC1 (TANC1).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein TANC1 (TANC1).	[13]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Protein TANC1 (TANC1).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein TANC1 (TANC1).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein TANC1 (TANC1).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein TANC1 (TANC1).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein TANC1 (TANC1).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein TANC1 (TANC1).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein TANC1 (TANC1).	[21]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Protein TANC1 (TANC1).	[18]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Protein TANC1 (TANC1).	[18]

References

• [1] A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease.Nat Genet. 2007 Aug;39(8):995-9. doi: 10.1038/ng2101. Epub 2007 Jul 15.
• [2] Discovery of common and rare genetic risk variants for colorectal cancer.Nat Genet. 2019 Jan;51(1):76-87. doi: 10.1038/s41588-018-0286-6. Epub 2018 Dec 3.
• [3] Drosophila and mammalian models uncover a role for the myoblast fusion gene TANC1 in rhabdomyosarcoma.J Clin Invest. 2012 Jan;122(1):403-7. doi: 10.1172/JCI59877. Epub 2011 Dec 19.
• [4] Purification and mutagenesis studies of TANC1 ankyrin repeats domain provide clues to understand mis-sense variants from diseases.Biochem Biophys Res Commun. 2019 Jun 25;514(2):358-364. doi: 10.1016/j.bbrc.2019.04.151. Epub 2019 Apr 27.
• [5] A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1.Nat Genet. 2014 Aug;46(8):891-4. doi: 10.1038/ng.3020. Epub 2014 Jun 29.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] 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.
• [8] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [9] 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.
• [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] Arsenic targets Pin1 and cooperates with retinoic acid to inhibit cancer-driving pathways and tumor-initiating cells. Nat Commun. 2018 Aug 9;9(1):3069. doi: 10.1038/s41467-018-05402-2.
• [12] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [13] 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.
• [14] 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.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [20] 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.
• [21] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.