Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRW8XQO)

DOT Name Poly polymerase tankyrase-2 (TNKS2)
Synonyms
EC 2.4.2.30; ADP-ribosyltransferase diphtheria toxin-like 6; ARTD6; Poly polymerase 5B; Protein poly-ADP-ribosyltransferase tankyrase-2; EC 2.4.2.-; TNKS-2; TRF1-interacting ankyrin-related ADP-ribose polymerase 2; Tankyrase II; Tankyrase-2; TANK2; Tankyrase-like protein; Tankyrase-related protein
Gene Name TNKS2
UniProt ID
TNKS2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2Y0I ; 3KR7 ; 3KR8 ; 3MHJ ; 3MHK ; 3P0N ; 3P0P ; 3P0Q ; 3TWQ ; 3TWR ; 3TWS ; 3TWT ; 3TWU ; 3TWV ; 3TWW ; 3TWX ; 3U9H ; 3U9Y ; 3UA9 ; 3W51 ; 4AVU ; 4AVW ; 4BFP ; 4BJ9 ; 4BJB ; 4BJC ; 4BS4 ; 4BU3 ; 4BU5 ; 4BU6 ; 4BU7 ; 4BU8 ; 4BU9 ; 4BUA ; 4BUD ; 4BUE ; 4BUF ; 4BUI ; 4BUS ; 4BUT ; 4BUU ; 4BUV ; 4BUW ; 4BUX ; 4BUY ; 4HKI ; 4HKK ; 4HKN ; 4HL5 ; 4HLF ; 4HLG ; 4HLH ; 4HLK ; 4HLM ; 4HMH ; 4HYF ; 4IUE ; 4J1Z ; 4J21 ; 4J22 ; 4J3L ; 4J3M ; 4KZL ; 4KZQ ; 4KZU ; 4L09 ; 4L0B ; 4L0I ; 4L0S ; 4L0T ; 4L0V ; 4L10 ; 4L2F ; 4L2G ; 4L2K ; 4L31 ; 4L32 ; 4L33 ; 4L34 ; 4M7B ; 4PML ; 4PNL ; 4PNM ; 4PNN ; 4PNQ ; 4PNR ; 4PNS ; 4PNT ; 4TJU ; 4TJW ; 4TJY ; 4TK0 ; 4TK5 ; 4TKF ; 4TKG ; 4TKI ; 4UFU ; 4UFY ; 4UHG ; 4UI3 ; 4UI4 ; 4UI5 ; 4UI6 ; 4UI7 ; 4UI8 ; 4UVL ; 4UVN ; 4UVO ; 4UVP ; 4UVS ; 4UVT ; 4UVU ; 4UVV ; 4UVW ; 4UVX ; 4UVY ; 4UVZ ; 4UX4 ; 4W5I ; 4Z68 ; 5ADQ ; 5ADR ; 5ADS ; 5ADT ; 5AEH ; 5AKU ; 5AKW ; 5AL1 ; 5AL2 ; 5AL3 ; 5AL4 ; 5AL5 ; 5BXO ; 5BXU ; 5C5P ; 5C5Q ; 5C5R ; 5DCZ ; 5FPF ; 5FPG ; 5JRT ; 5NOB ; 5NSP ; 5NUT ; 5OWS ; 5OWT ; 6TG4 ; 6TKM ; 6TKN ; 6TKP ; 6TKQ ; 6TKR ; 6TKS ; 7A1S ; 7O6X ; 7POX ; 7R3Z ; 8ALY
EC Number
2.4.2.-; 2.4.2.30
Pfam ID
PF00023 ; PF12796 ; PF13606 ; PF13637 ; PF00644 ; PF07647
Sequence
MSGRRCAGGGAACASAAAEAVEPAARELFEACRNGDVERVKRLVTPEKVNSRDTAGRKST
PLHFAAGFGRKDVVEYLLQNGANVQARDDGGLIPLHNACSFGHAEVVNLLLRHGADPNAR
DNWNYTPLHEAAIKGKIDVCIVLLQHGAEPTIRNTDGRTALDLADPSAKAVLTGEYKKDE
LLESARSGNEEKMMALLTPLNVNCHASDGRKSTPLHLAAGYNRVKIVQLLLQHGADVHAK
DKGDLVPLHNACSYGHYEVTELLVKHGACVNAMDLWQFTPLHEAASKNRVEVCSLLLSYG
ADPTLLNCHNKSAIDLAPTPQLKERLAYEFKGHSLLQAAREADVTRIKKHLSLEMVNFKH
PQTHETALHCAAASPYPKRKQICELLLRKGANINEKTKEFLTPLHVASEKAHNDVVEVVV
KHEAKVNALDNLGQTSLHRAAYCGHLQTCRLLLSYGCDPNIISLQGFTALQMGNENVQQL
LQEGISLGNSEADRQLLEAAKAGDVETVKKLCTVQSVNCRDIEGRQSTPLHFAAGYNRVS
VVEYLLQHGADVHAKDKGGLVPLHNACSYGHYEVAELLVKHGAVVNVADLWKFTPLHEAA
AKGKYEICKLLLQHGADPTKKNRDGNTPLDLVKDGDTDIQDLLRGDAALLDAAKKGCLAR
VKKLSSPDNVNCRDTQGRHSTPLHLAAGYNNLEVAEYLLQHGADVNAQDKGGLIPLHNAA
SYGHVDVAALLIKYNACVNATDKWAFTPLHEAAQKGRTQLCALLLAHGADPTLKNQEGQT
PLDLVSADDVSALLTAAMPPSALPSCYKPQVLNGVRSPGATADALSSGPSSPSSLSAASS
LDNLSGSFSELSSVVSSSGTEGASSLEKKEVPGVDFSITQFVRNLGLEHLMDIFEREQIT
LDVLVEMGHKELKEIGINAYGHRHKLIKGVERLISGQQGLNPYLTLNTSGSGTILIDLSP
DDKEFQSVEEEMQSTVREHRDGGHAGGIFNRYNILKIQKVCNKKLWERYTHRRKEVSEEN
HNHANERMLFHGSPFVNAIIHKGFDERHAYIGGMFGAGIYFAENSSKSNQYVYGIGGGTG
CPVHKDRSCYICHRQLLFCRVTLGKSFLQFSAMKMAHSPPGHHSVTGRPSVNGLALAEYV
IYRGEQAYPEYLITYQIMRPEGMVDG
Function
Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. Stimulates 26S proteasome activity.
Tissue Specificity
Highly expressed in placenta, skeletal muscle, liver, brain, kidney, heart, thymus, spinal cord, lung, peripheral blood leukocytes, pancreas, lymph nodes, spleen, prostate, testis, ovary, small intestine, colon, mammary gland, breast and breast carcinoma, and in common-type meningioma. Highly expressed in fetal liver, heart and brain.
Reactome Pathway
Degradation of AXIN (R-HSA-4641257 )
XAV939 stabilizes AXIN (R-HSA-5545619 )
Ub-specific processing proteases (R-HSA-5689880 )
Regulation of PTEN stability and activity (R-HSA-8948751 )
TCF dependent signaling in response to WNT (R-HSA-201681 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 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 Poly polymerase tankyrase-2 (TNKS2). [1]
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5 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 Poly polymerase tankyrase-2 (TNKS2). [2]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the mutagenesis of Poly polymerase tankyrase-2 (TNKS2). [3]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Poly polymerase tankyrase-2 (TNKS2). [4]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin increases the expression of Poly polymerase tankyrase-2 (TNKS2). [5]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Poly polymerase tankyrase-2 (TNKS2). [7]
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1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
PJ34 DMXO6YH Preclinical PJ34 affects the binding of Poly polymerase tankyrase-2 (TNKS2). [6]
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References

1 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.
2 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.
3 Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
4 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.
5 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
6 Identification of pim kinases as novel targets for PJ34 with confounding effects in PARP biology. ACS Chem Biol. 2012 Dec 21;7(12):1962-7. doi: 10.1021/cb300317y. Epub 2012 Oct 8.
7 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.