Target Information
| Target General Information | Top | |||||
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| Target ID |
T38087
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| Target Name |
Tankyrase-2 (TNKS-2)
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| Synonyms |
Tankyrase-related protein; Tankyrase-like protein; Tankyrase II; TRF1-interacting ankyrin-related ADP-ribose polymerase 2; TNKL; TANK2; Protein poly-ADP-ribosyltransferase tankyrase-2; Poly [ADP-ribose] polymerase tankyrase-2; Poly [ADP-ribose] polymerase 5B; PARP5B; ARTD6; ADP-ribosyltransferase diphtheria toxin-like 6
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| Gene Name |
TNKS2
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Ovarian cancer [ICD-11: 2C73] | |||||
| Function |
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. Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking.
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| BioChemical Class |
Glycosyltransferases
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| UniProt ID | ||||||
| EC Number |
EC 2.4.2.30
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| Sequence |
MSGRRCAGGGAACASAAAEAVEPAARELFEACRNGDVERVKRLVTPEKVNSRDTAGRKST
PLHFAAGFGRKDVVEYLLQNGANVQARDDGGLIPLHNACSFGHAEVVNLLLRHGADPNAR DNWNYTPLHEAAIKGKIDVCIVLLQHGAEPTIRNTDGRTALDLADPSAKAVLTGEYKKDE LLESARSGNEEKMMALLTPLNVNCHASDGRKSTPLHLAAGYNRVKIVQLLLQHGADVHAK DKGDLVPLHNACSYGHYEVTELLVKHGACVNAMDLWQFTPLHEAASKNRVEVCSLLLSYG ADPTLLNCHNKSAIDLAPTPQLKERLAYEFKGHSLLQAAREADVTRIKKHLSLEMVNFKH PQTHETALHCAAASPYPKRKQICELLLRKGANINEKTKEFLTPLHVASEKAHNDVVEVVV KHEAKVNALDNLGQTSLHRAAYCGHLQTCRLLLSYGCDPNIISLQGFTALQMGNENVQQL LQEGISLGNSEADRQLLEAAKAGDVETVKKLCTVQSVNCRDIEGRQSTPLHFAAGYNRVS VVEYLLQHGADVHAKDKGGLVPLHNACSYGHYEVAELLVKHGAVVNVADLWKFTPLHEAA AKGKYEICKLLLQHGADPTKKNRDGNTPLDLVKDGDTDIQDLLRGDAALLDAAKKGCLAR VKKLSSPDNVNCRDTQGRHSTPLHLAAGYNNLEVAEYLLQHGADVNAQDKGGLIPLHNAA SYGHVDVAALLIKYNACVNATDKWAFTPLHEAAQKGRTQLCALLLAHGADPTLKNQEGQT PLDLVSADDVSALLTAAMPPSALPSCYKPQVLNGVRSPGATADALSSGPSSPSSLSAASS LDNLSGSFSELSSVVSSSGTEGASSLEKKEVPGVDFSITQFVRNLGLEHLMDIFEREQIT LDVLVEMGHKELKEIGINAYGHRHKLIKGVERLISGQQGLNPYLTLNTSGSGTILIDLSP DDKEFQSVEEEMQSTVREHRDGGHAGGIFNRYNILKIQKVCNKKLWERYTHRRKEVSEEN HNHANERMLFHGSPFVNAIIHKGFDERHAYIGGMFGAGIYFAENSSKSNQYVYGIGGGTG CPVHKDRSCYICHRQLLFCRVTLGKSFLQFSAMKMAHSPPGHHSVTGRPSVNGLALAEYV IYRGEQAYPEYLITYQIMRPEGMVDG Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | PMID27841036-Compound-37 | Drug Info | Phase 2 | Ovarian cancer | [2] | |
| 2 | Stenoparib | Drug Info | Phase 2 | Ovarian cancer | [3] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 2 Inhibitor drugs | + | ||||
| 1 | PMID27841036-Compound-37 | Drug Info | [1] | |||
| 2 | Stenoparib | Drug Info | [3] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Nicotinamide | Ligand Info | |||||
| Structure Description | Complex structure of human tankyrase 2 with nicotinamide | PDB:3U9H | ||||
| Method | X-ray diffraction | Resolution | 1.75 Å | Mutation | No | [4] |
| PDB Sequence |
GTILIDLSPD
961 DKEFQSVEEE971 MQSTVREHRD981 GGHAGGIFNR991 YNILKIQKVC1001 NKKLWERYTH 1011 RRKEVSEENH1021 NHANERMLFH1031 GSPFVNAIIH1041 KGFDERHAYI1051 GGMFGAGIYF 1061 AENSSKSNQY1071 VYGIGGGTGC1081 PVHKDRSCYI1091 CHRQLLFCRV1101 TLGKSFLQFS 1111 AMAHSPPGHH1123 SVTGRPSVNG1133 LALAEYVIYR1143 GEQAYPEYLI1153 TYQIMRPE |
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Rucaparib | Ligand Info | |||||
| Structure Description | Crystal structure of human tankyrase 2 in complex with Rucaparib | PDB:4BJC | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [5] |
| PDB Sequence |
GTILIDLSPD
961 DKEFQSVEEE971 MQSTVREHRD981 GGHAGGIFNR991 YNILKIQKVC1001 NKKLWERYTH 1011 RRKEVSEENH1021 NHANERMLFH1031 GSPFVNAIIH1041 KGFDERHAGI1059 YFAENSSKSN 1069 QYVYGIGGGT1079 GCPVHKDRSC1089 YICHRQLLFC1099 RVTLGKSFLQ1109 FSHSPPGHHS 1124 VTGRPSVNGL1134 ALAEYVIYRG1144 EQAYPEYLIT1154 YQIMRPE
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Biological Network Descriptors
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| Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 8.75E-05 |
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| Closeness centrality | 2.17E-01 | Radiality | 1.38E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 2.54E+01 | Topological coefficient | 2.09E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | PARP inhibitors as antitumor agents: a patent update (2013-2015).Expert Opin Ther Pat. 2017 Mar;27(3):363-382. | |||||
| REF 2 | ClinicalTrials.gov (NCT03878849) Investigation of 2X-121 in Patients With Advanced Ovarian Cancer Selected by the 2X-121 DRP (PREDICT 2X-121). U.S. National Institutes of Health. | |||||
| REF 3 | Clinical pipeline report, company report or official report of Allarity Therapeutics. | |||||
| REF 4 | Structural basis of selective inhibition of human tankyrases. J Med Chem. 2012 Feb 9;55(3):1360-7. | |||||
| REF 5 | Evaluation and Structural Basis for the Inhibition of Tankyrases by PARP Inhibitors. ACS Med Chem Lett. 2013 Nov 20;5(1):18-22. | |||||
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