Tchem TNKS2 Tankyrase-2

Protein Summary

Description

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. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. Stimulates 26S proteasome activity.

Uniprot Accession IDs

• Q9H2K2
• B2RBD3
• Q9H8F2
• Q9HAS4
• TANK2

Gene Name

• TNKS2

Ensembl ID

• ENST00000371627
• ENSP00000360689
• ENSG00000107854

Symbol

• PARP5B
• TANK2
• TNKL
• TNKL
• ARTD6
• TANK2
• pART6
• PARP5B
• PARP5C
• PARP-5b
• PARP-5c

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
histone modification site profile	0.91
protein domain	0.85
cellular component	0.77
transcription factor perturbation	0.74
transcription factor binding site profile	0.73

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 83.23   (req: < 5)

Gene RIFs: 24   (req: <= 3)

Antibodies: 209   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 83.23   (req: >= 5)

Gene RIFs: 24   (req: > 3)

Antibodies: 209   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 14

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 339

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 3

Approved Drugs (3)

Explore Approved Drugs

1 – 3 of 3

midostaurin

TNKS2Tchem Enzyme

Kd : 6.92

rucaparib

TNKS2Tchem Enzyme

INHIBITOR IC50 : 6.05000019

olaparib

TNKS2Tchem Enzyme

IC50 : 8.28

Active Ligands (339)

Explore Active Ligands

1 – 10 of 339

CHEMBL603469

TNKS2Tchem Enzyme

Kd : 8.18

CHEMBL1086580

TNKS2Tchem Enzyme

Kd : 8

CHEMBL3740104

TNKS2Tchem Enzyme

IC50 : 6.8

CHEMBL275638

TNKS2Tchem Enzyme

IC50 : 6.85

CHEMBL3907010

TNKS2Tchem Enzyme

IC50 : 6.03

CHEMBL3919533

TNKS2Tchem Enzyme

IC50 : 6.12

CHEMBL372303

TNKS2Tchem Enzyme

IC50 : 6.66

CHEMBL3891329

TNKS2Tchem Enzyme

IC50 : 6.85

CHEMBL45245

TNKS2Tchem Enzyme

IC50 : 7.86

CHEMBL2419698

TNKS2Tchem Enzyme

IC50 : 8.12

GWAS Traits (6)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
sex hormone-binding globulin measurement	EFO_0004696	6	3	6		99.1
testosterone measurement	EFO_0004908	2	2	2		83.8
type II diabetes mellitus	EFO_0001360	1	1	0	1.3	72.8
neutrophil count	EFO_0004833	2	2	2		57.6
myeloid white cell count	EFO_0007988	1	1	1		6.7

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
sex hormone-binding globulin measurement	EFO_0004696	6		99.1
testosterone measurement	EFO_0004908	2		83.8
type II diabetes mellitus	EFO_0001360	0	1.3	72.8
neutrophil count	EFO_0004833	2		57.6
myeloid white cell count	EFO_0007988	1		6.7

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Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	tankyrase 2	VGNC:8886	100609110
Macaque	tankyrase 2		698050
Mouse	tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase 2	MGI:1921743	74493
Rat	tankyrase-2-like	RGD:6496922	100910717
Dog	tankyrase 2	VGNC:47683	100855568

Species	Name	OMA	EggNOG	Inparanoid
Chimp	tankyrase 2
Macaque	tankyrase 2
Mouse	tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase 2
Rat	tankyrase-2-like
Dog	tankyrase 2

Protein Structure (146 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-Q9H2K2-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 146

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (23)

Reactome (16)

WikiPathways (7)

Degradation of AXIN (R-HSA-4641257)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Degradation of AXIN	56 targets	R-HSA-4641257
Reactome	Deubiquitination	278 targets	R-HSA-5688426
Reactome	Disease	1105 targets	R-HSA-1643685
Reactome	Diseases of signal transduction	387 targets	R-HSA-5663202
Reactome	Intracellular signaling by second messengers	305 targets	R-HSA-9006925

Name	Explore in Pharos	Explore in Source
Degradation of AXIN	56 targets	R-HSA-4641257
Deubiquitination	278 targets	R-HSA-5688426
Disease	1105 targets	R-HSA-1643685
Diseases of signal transduction	387 targets	R-HSA-5663202
Intracellular signaling by second messengers	305 targets	R-HSA-9006925

Gene Ontology Terms (22)

Functions (3)

Components (8)

Processes (11)

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1 – 3 of 3

GO Term	Evidence	Assigned by
NAD+ ADP-ribosyltransferase activity	Inferred from Direct Assay (IDA)	UniProtKB
enzyme binding	Inferred from Physical Interaction (IPI)	UniProtKB
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (115)

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1 – 10 of 115

• See Interactions on String-DB

PAGE4

Tbio

Novelty: 0.05404149

p_int: 0.999999971

p_ni: 2.9e-8

Data Source: BioPlex

HIF1AN

Tbio

Novelty: 0.00861018

p_int: 0.999999935

p_ni: 6.5e-8

Score: 0.908

Data Source: BioPlex,STRINGDB

BABAM1

Tbio

Novelty: 0.03812501

p_int: 0.999999654

p_ni: 3.46e-7

Score: 0.341

Data Source: BioPlex,STRINGDB

GMDS

Tbio

Family: Enzyme

Novelty: 0.00622275

p_int: 0.99999891

p_ni: 0.00000109

Score: 0.827

Data Source: BioPlex,STRINGDB

SSSCA1

Tdark

Novelty: 0.53523038

p_int: 0.999998775

p_ni: 0.000001223

p_wrong: 1e-9

Data Source: BioPlex

FAM117B

Tdark

Novelty: 1.06316483

p_int: 0.999998536

p_ni: 0.000001464

Data Source: BioPlex

RNF166

Tdark

Novelty: 0.71460884

p_int: 0.999997572

p_ni: 0.000002428

Data Source: BioPlex

PPP1R12B

Tbio

Family: Enzyme

Novelty: 0.0424259

p_int: 0.999997458

p_ni: 0.000002541

Data Source: BioPlex

SH3BP5L

Tdark

Novelty: 1.7921497

p_int: 0.999996413

p_ni: 0.000003587

Data Source: BioPlex

EPN3

Tbio

Novelty: 0.12685855

p_int: 0.999980638

p_ni: 0.000019362

Score: 0.159

Data Source: BioPlex,STRINGDB

Publication Statistics

PubMed Score  83.23

PubMed score by year

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PubTator Score  443.51

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

3D-structure
ADP-ribosylation
ANK repeat
Chromosome
Complete proteome
Cytoplasm
Glycosyltransferase
Golgi apparatus
Hydroxylation
Membrane

GWAS Trait Find Similar Targets

leukocyte count
myeloid white cell count
neutrophil count
sex hormone-binding globulin measurement
testosterone measurement
type II diabetes mellitus

MGI Phenotype Find Similar Targets

adipose tissue phenotype
behavior/neurological phenotype
cellular phenotype
growth/size/body region phenotype
mortality/aging
skeleton phenotype