Poly [ADP-ribose] polymerase tankyrase-2

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.

Classification

Family (Pfam)

PF00023 Ank, PF12796 Ank_2, PF13637 Ank_4, PF00644 PARP, PF07647 SAM_2

InterPro

Ankyrin_rpt, Ankyrin_rpt-contain_sf, Poly(ADP-ribose)pol_cat_dom, SAM, SAM/pointed_sf

Functional cluster

C2H2 Zinc-Finger Transcription Factors

Experimental structures · PDB · 195

• 2Y0I X-ray 2.28A
• 3KR7 X-ray 1.95A
• 3KR8 X-ray 2.10A
• 3MHJ X-ray 1.80A
• 3MHK X-ray 2.30A
• 3P0N X-ray 1.90A
• 3P0P X-ray 2.49A
• 3P0Q X-ray 1.90A
• 3TWQ X-ray 2.15A
• 3TWR X-ray 1.55A
• 3TWS X-ray 1.70A
• 3TWT X-ray 1.85A
• … and 183 more

A predicted model is available from AlphaFold.

Gene Ontology · 24

• GO:0000781 chromosome, telomeric region
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0000139 Golgi membrane
• GO:0005635 nuclear envelope
• GO:0005634 nucleus
• GO:0000242 pericentriolar material
• GO:0048471 perinuclear region of cytoplasm
• GO:0019899 enzyme binding
• GO:0046872 metal ion binding
• GO:0003950 NAD+ poly-ADP-ribosyltransferase activity
• GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity
• GO:0140806 NAD+-protein-aspartate ADP-ribosyltransferase activity
• GO:0140807 NAD+-protein-glutamate ADP-ribosyltransferase activity
• GO:0016779 nucleotidyltransferase activity
• GO:1904357 negative regulation of telomere maintenance via telomere lengthening
• GO:0090263 positive regulation of canonical Wnt signaling pathway
• GO:1904355 positive regulation of telomere capping
• GO:0032212 positive regulation of telomere maintenance via telomerase
• GO:0070213 protein auto-ADP-ribosylation
• GO:0070198 protein localization to chromosome, telomeric region
• GO:0070212 protein poly-ADP-ribosylation
• GO:0000209 protein polyubiquitination
• GO:0016055 Wnt signaling pathway

Drugs targeting this protein · 1

• 2X-121 inhibitor

Related proteins · sequence + function similarity

• Poly [ADP-ribose] polymerase tankyrase-2 1.00
• Poly [ADP-ribose] polymerase tankyrase 0.94
• Poly [ADP-ribose] polymerase tankyrase-1 0.94
• Poly [ADP-ribose] polymerase tankyrase-1 0.94
• Ankyrin-2 0.82
• Ankyrin-3 0.82
• Ankyrin-2 0.82
• Ankyrin-3 0.79
• Ankyrin-1 0.79
• Ankyrin-3 0.79
• Ankyrin-1 0.78
• CARD- and ANK-domain containing inflammasome adapter protein 0.76

Co-cited proteins · studied together in the literature

• Poly [ADP-ribose] polymerase tankyrase-1 9 shared papers
• Hypoxia-inducible factor 1-alpha inhibitor 1 shared papers
• Axin-2 2 shared papers
• E3 ubiquitin-protein ligase RNF146 2 shared papers
• Axin-1 3 shared papers
• Telomeric repeat-binding factor 1 1 shared papers
• Nuclear mitotic apparatus protein 1 1 shared papers
• Golgin-45 1 shared papers
• Poly [ADP-ribose] polymerase 1 4 shared papers
• Proteasome subunit alpha type-6 1 shared papers
• 26S proteasome non-ATPase regulatory subunit 9 1 shared papers
• 26S proteasome non-ATPase regulatory subunit 5 1 shared papers

Literature · 18 cited papers

• Dissecting the molecular determinants of clinical PARP1 inhibitor selectivity for tankyrase1. J. Biol. Chem. · 2021
• Family-wide analysis of poly(ADP-ribose) polymerase activity. Nat. Commun. · 2014
• Proteasome regulation by ADP-ribosylation. Cell · 2013
• Ubiquitin ligase RNF146 regulates tankyrase and Axin to promote Wnt signaling. PLoS ONE · 2011
• RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. Nat. Cell Biol. · 2011
• Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post-translational hydroxylation of histidinyl residues within ankyrin repeat domains. FEBS J. · 2011
• Toward a unified nomenclature for mammalian ADP-ribosyltransferases. Trends Biochem. Sci. · 2010
• Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature · 2009
• Proteomics-based identification of novel factor inhibiting hypoxia-inducible factor (FIH) substrates indicates widespread asparaginyl hydroxylation of ankyrin repeat domain-containing proteins. Mol. Cell. Proteomics · 2009
• The DNA sequence and comparative analysis of human chromosome 10. Nature · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• Identification of a tankyrase-binding motif shared by IRAP, TAB182, and human TRF1 but not mouse TRF1. NuMA contains this RXXPDG motif and is a novel tankyrase partner. J. Biol. Chem. · 2002
• … and 6 more in the literature graph