Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK16BL9)

DOT Name Ankyrin repeat domain-containing protein 12 (ANKRD12)
Synonyms Ankyrin repeat-containing cofactor 2; GAC-1 protein
Gene Name ANKRD12
Related Disease
Bipolar disorder ( )
Breast cancer ( )
Breast carcinoma ( )
Colorectal carcinoma ( )
Schizophrenia ( )
Neoplasm ( )
UniProt ID
ANR12_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00023 ; PF12796
Sequence
MPKSGFTKPIQSENSDSDSNMVEKPYGRKSKDKIASYSKTPKIERSDVSKEMKEKSSMKR
KLPFTISPSRNEERDSDTDSDPGHTSENWGERLISSYRTYSEKEGPEKKKTKKEAGNKKS
TPVSILFGYPLSERKQMALLMQMTARDNSPDSTPNHPSQTTPAQKKTPSSSSRQKDKVNK
RNERGETPLHMAAIRGDVKQVKELISLGANVNVKDFAGWTPLHEACNVGYYDVAKILIAA
GADVNTQGLDDDTPLHDSASSGHRDIVKLLLRHGGNPFQANKHGERPVDVAETEELELLL
KREVPLSDDDESYTDSEEAQSVNPSSVDENIDSETEKDSLICESKQILPSKTPLPSALDE
YEFKDDDDEEINKMIDDRHILRKEQRKENEPEAEKTHLFAKQEKAFYPKSFKSKKQKPSR
VLYSSTESSDEEALQNKKISTSCSVIPETSNSDMQTKKEYVVSGEHKQKGKVKRKLKNQN
KNKENQELKQEKEGKENTRITNLTVNTGLDCSEKTREEGNFRKSFSPKDDTSLHLFHIST
GKSPKHSCGLSEKQSTPLKQEHTKTCLSPGSSEMSLQPDLVRYDNTESEFLPESSSVKSC
KHKEKSKHQKDFHLEFGEKSNAKIKDEDHSPTFENSDCTLKKMDKEGKTLKKHKLKHKER
EKEKHKKEIEGEKEKYKTKDSAKELQRSVEFDREFWKENFFKSDETEDLFLNMEHESLTL
EKKSKLEKNIKDDKSTKEKHVSKERNFKEERDKIKKESEKSFREEKIKDLKEERENIPTD
KDSEFTSLGMSAIEESIGLHLVEKEIDIEKQEKHIKESKEKPEKRSQIKEKDIEKMERKT
FEKEKKIKHEHKSEKDKLDLSECVDKIKEKDKLYSHHTEKCHKEGEKSKNTAAIKKTDDR
EKSREKMDRKHDKEKPEKERHLAESKEKHLMEKKNKQSDNSEYSKSEKGKNKEKDRELDK
KEKSRDKESINITNSKHIQEEKKSSIVDGNKAQHEKPLSLKEKTKDEPLKTPDGKEKDKK
DKDIDRYKERDKHKDKIQINSLLKLKSEADKPKPKSSPASKDTRPKEKRLVNDDLMQTSF
ERMLSLKDLEIEQWHKKHKEKIKQKEKERLRNRNCLELKIKDKEKTKHTPTESKNKELTR
SKSSEVTDAYTKEKQPKDAVSNRSQSVDTKNVMTLGKSSFVSDNSLNRSPRSENEKPGLS
SRSVSMISVASSEDSCHTTVTTPRPPVEYDSDFMLESSESQMSFSQSPFLSIAKSPALHE
RELDSLADLPERIKPPYANRLSTSHLRSSSVEDVKLIISEGRPTIEVRRCSMPSVICEHT
KQFQTISEESNQGSLLTVPGDTSPSPKPEVFSNVPERDLSNVSNIHSSFATSPTGASNSK
YVSADRNLIKNTAPVNTVMDSPVHLEPSSQVGVIQNKSWEMPVDRLETLSTRDFICPNSN
IPDQESSLQSFCNSENKVLKENADFLSLRQTELPGNSCAQDPASFMPPQQPCSFPSQSLS
DAESISKHMSLSYVANQEPGILQQKNAVQIISSALDTDNESTKDTENTFVLGDVQKTDAF
VPVYSDSTIQEASPNFEKAYTLPVLPSEKDFNGSDASTQLNTHYAFSKLTYKSSSGHEVE
NSTTDTQVISHEKENKLESLVLTHLSRCDSDLCEMNAGMPKGNLNEQDPKHCPESEKCLL
SIEDEESQQSILSSLENHSQQSTQPEMHKYGQLVKVELEENAEDDKTENQIPQRMTRNKA
NTMANQSKQILASCTLLSEKDSESSSPRGRIRLTEDDDPQIHHPRKRKVSRVPQPVQVSP
SLLQAKEKTQQSLAAIVDSLKLDEIQPYSSERANPYFEYLHIRKKIEEKRKLLCSVIPQA
PQYYDEYVTFNGSYLLDGNPLSKICIPTITPPPSLSDPLKELFRQQEVVRMKLRLQHSIE
REKLIVSNEQEVLRVHYRAARTLANQTLPFSACTVLLDAEVYNVPLDSQSDDSKTSVRDR
FNARQFMSWLQDVDDKFDKLKTCLLMRQQHEAAALNAVQRLEWQLKLQELDPATYKSISI
YEIQEFYVPLVDVNDDFELTPI
Function May recruit HDACs to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bipolar disorder DISAM7J2 Strong Biomarker [1]
Breast cancer DIS7DPX1 Strong Biomarker [2]
Breast carcinoma DIS2UE88 Strong Biomarker [2]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [3]
Schizophrenia DISSRV2N Strong Biomarker [1]
Neoplasm DISZKGEW moderate Biomarker [4]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Ankyrin repeat domain-containing protein 12 (ANKRD12). [5]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Ankyrin repeat domain-containing protein 12 (ANKRD12). [22]
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18 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 Ankyrin repeat domain-containing protein 12 (ANKRD12). [6]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Ankyrin repeat domain-containing protein 12 (ANKRD12). [7]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Ankyrin repeat domain-containing protein 12 (ANKRD12). [8]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Ankyrin repeat domain-containing protein 12 (ANKRD12). [9]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Ankyrin repeat domain-containing protein 12 (ANKRD12). [10]
Quercetin DM3NC4M Approved Quercetin increases the expression of Ankyrin repeat domain-containing protein 12 (ANKRD12). [11]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Ankyrin repeat domain-containing protein 12 (ANKRD12). [12]
Marinol DM70IK5 Approved Marinol increases the expression of Ankyrin repeat domain-containing protein 12 (ANKRD12). [13]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Ankyrin repeat domain-containing protein 12 (ANKRD12). [14]
Niclosamide DMJAGXQ Approved Niclosamide increases the expression of Ankyrin repeat domain-containing protein 12 (ANKRD12). [15]
Clorgyline DMCEUJD Approved Clorgyline increases the expression of Ankyrin repeat domain-containing protein 12 (ANKRD12). [16]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Ankyrin repeat domain-containing protein 12 (ANKRD12). [17]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Ankyrin repeat domain-containing protein 12 (ANKRD12). [18]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Ankyrin repeat domain-containing protein 12 (ANKRD12). [20]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Ankyrin repeat domain-containing protein 12 (ANKRD12). [21]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Ankyrin repeat domain-containing protein 12 (ANKRD12). [23]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Ankyrin repeat domain-containing protein 12 (ANKRD12). [24]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Ankyrin repeat domain-containing protein 12 (ANKRD12). [25]
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⏷ Show the Full List of 18 Drug(s)
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 Ankyrin repeat domain-containing protein 12 (ANKRD12). [19]
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References

1 The difference in serum proteomes in schizophrenia and bipolar disorder.BMC Genomics. 2019 Jul 11;20(Suppl 7):535. doi: 10.1186/s12864-019-5848-1.
2 Loss of ANCO1 repression at AIB1/YAP targets drives breast cancer progression.EMBO Rep. 2020 Jan 7;21(1):e48741. doi: 10.15252/embr.201948741. Epub 2019 Dec 2.
3 Clinical significance of Ankyrin repeat domain 12 expression in colorectal cancer.J Exp Clin Cancer Res. 2013 May 29;32(1):35. doi: 10.1186/1756-9966-32-35.
4 One repressor to rule them all: ANCO1 links YAP and AIB1.EMBO Rep. 2020 Jan 7;21(1):e49647. doi: 10.15252/embr.201949647. Epub 2019 Dec 2.
5 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.
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 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.
8 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.
9 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
10 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
11 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.
12 Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
13 Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
14 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
15 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.
16 Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
17 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
18 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
19 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.
20 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
21 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
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 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.
24 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
25 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.