Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

TNKS2 (Q9H2K2) - Overview - Molecular Target Synopsis

Protein


TNKS2, Poly [ADP-ribose] polymerase tankyrase-2
Enzyme Classification 2.4.2.30
UniProt Q9H2K2

Also Known as TNKS2_HUMAN, TNKS2, PARP5B, TANK2, TNKL

Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking (PubMed:11739745, PubMed:11802774, PubMed:19759537, PubMed:21478859, PubMed:23622245, PubMed:25043379). 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 (PubMed:19759537, PubMed:21478859). Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination (PubMed:21478859). Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length (PubMed:11739745). Stimulates 26S proteasome activity (PubMed:23622245). Oligomerizes and associates with TNKS. Interacts with the cytoplasmic domain of LNPEP/Otase in SLC2A4/GLUT4-vesicles (PubMed:11802774). Binds to the N-terminus of Grb14 and TRF1 with its ankyrin repeat region (PubMed:11802774). Interacts with HIF1AN (PubMed:18936059, PubMed:21251231). Interacts with RNF146; this interaction leads to ubiquitination and proteasomal degradation (PubMed:21799911). Interacts with NUMA1 (PubMed:12080061).

5NWB
CRYSTAL STRUCTURE OF TNKS2 IN COMPLEX WITH 2-{4-[(2-HYDROXYETHYL) (METHYL)AMINO]PHENYL}-3,4-DIHYDROQUINAZOLIN-4-ONE
RCSB/PDB
Inspect Structure
See all 3D Structures for TNKS2

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
1166ENSG00000107854ENST00000371627ENSP00000360689Q9H2K2-1

Sub-cellular localization


UniProt: TNKS2 is active in the following subcellular-locations: chromosome, cytoplasm, golgi apparatus membrane, nucleus, telomere.
GO terms: TNKS2 is active in the following subcellular-locations: cytoplasm, cytosol, Golgi membrane, nuclear chromosome, nuclear envelope, nucleus, pericentriolar material, perinuclear region of cytoplasm.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project TNKS2 has gain in 1 cell-lines, loss in 1 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SR, T47D, MDA_N

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Hs 746T, WSU-FSCCL, SU-DHL-1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, HSMM, AG445

(see details)

RNA Interference


TNKS2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: . (see details)

3D Structures


For TNKS2 there are:
158 structures (439 chains) solved
148 are solved in complex with at least one small molecule ligand
5 are solved with an approved drug

TNKS2 is solved in complex with the approved drug(s):

09L/OLAPARIB (3U9Y_A, 4TKG_A, 4TKG_B, 4TKG_C, 4TKG_D),
NCA/NIACINAMIDE (3U9H_A, 3U9H_B, 4HYF_A, 4HYF_B, 4HYF_C),
RPB/RUCAPARIB (4BJC_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


TNKS2 has been screened with 566 compounds (1119 bioactivities), 293 compounds have bioactivities that show binding affinity of <= 500nM (393 bioactivities). (see details)