Poly [ADP-ribose] polymerase tankyrase-1
Also known as: PARP5A, PARPL, TIN1, TINF1, TNKS, TNKS1
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 (PARsylation) 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 PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1. Stimulates 26S proteasome activity.
Classification
- Family (Pfam)
- PF00023 Ank, PF12796 Ank_2, 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 · 42
- 2RF5 X-ray 2.30A
- 3UDD X-ray 1.95A
- 3UH2 X-ray 2.00A
- 3UH4 X-ray 2.00A
- 4DVI X-ray 1.90A
- 4I9I X-ray 2.40A
- 4K4E X-ray 2.30A
- 4K4F X-ray 2.90A
- 4KRS X-ray 2.29A
- 4LI6 X-ray 2.05A
- 4LI7 X-ray 2.20A
- 4LI8 X-ray 2.52A
- … and 30 more
A predicted model is available from AlphaFold.
Gene Ontology · 38
- GO:0000781 chromosome, telomeric region
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0005794 Golgi apparatus
- GO:0000139 Golgi membrane
- GO:0097431 mitotic spindle pole
- GO:0031965 nuclear membrane
- GO:0005643 nuclear pore
- GO:0005634 nucleus
- GO:0000242 pericentriolar material
- GO:0042393 histone 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:0010521 telomerase inhibitor activity
- GO:0008270 zinc ion binding
- GO:0051301 cell division
- GO:0007052 mitotic spindle organization
- GO:0051028 mRNA transport
- GO:1904908 negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric
- GO:1904357 negative regulation of telomere maintenance via telomere lengthening
- GO:0018105 peptidyl-serine phosphorylation
- GO:0018107 peptidyl-threonine phosphorylation
- 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:1904358 positive regulation of telomere maintenance via telomere lengthening
- GO:0045944 positive regulation of transcription by RNA polymerase II
- 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:0015031 protein transport
- GO:0032210 regulation of telomere maintenance via telomerase
- GO:0051225 spindle assembly
- GO:0016055 Wnt signaling pathway
Drugs targeting this protein · 1
- 2X-121 inhibitor
Related proteins · sequence + function similarity
- Poly [ADP-ribose] polymerase tankyrase-1 0.99
- Poly [ADP-ribose] polymerase tankyrase-2 0.94
- Poly [ADP-ribose] polymerase tankyrase-2 0.94
- Poly [ADP-ribose] polymerase tankyrase 0.92
- Ankyrin-3 0.81
- Ankyrin-2 0.81
- Ankyrin-2 0.81
- Ankyrin-3 0.78
- Ankyrin-3 0.78
- Ankyrin-1 0.77
- Ankyrin-1 0.76
- Ankyrin repeat domain-containing protein 17 0.72
Co-cited proteins · studied together in the literature
- HEPACAM family member 2 1 shared papers
- Poly [ADP-ribose] polymerase tankyrase-2 9 shared papers
- Nuclear mitotic apparatus protein 1 2 shared papers
- Ubiquitin carboxyl-terminal hydrolase 25 1 shared papers
- Axin-2 2 shared papers
- Telomeric repeat-binding factor 1 2 shared papers
- E3 ubiquitin-protein ligase RNF146 2 shared papers
- Axin-1 3 shared papers
- TERF1-interacting nuclear factor 2 1 shared papers
- Golgin-45 1 shared papers
- Protection of telomeres protein 1 1 shared papers
- Poly [ADP-ribose] polymerase 1 4 shared papers
Literature · 19 cited papers
- Dissecting the molecular determinants of clinical PARP1 inhibitor selectivity for tankyrase1. J. Biol. Chem. · 2021
- USP25 regulates Wnt signaling by controlling the stability of tankyrases. Genes Dev. · 2017
- Family-wide analysis of poly(ADP-ribose) polymerase activity. Nat. Commun. · 2014
- Proteasome regulation by ADP-ribosylation. Cell · 2013
- Poly-ADP ribosylation of Miki by tankyrase-1 promotes centrosome maturation. Mol. Cell · 2012
- 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
- Toward a unified nomenclature for mammalian ADP-ribosyltransferases. Trends Biochem. Sci. · 2010
- Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature · 2009
- Zinc binding catalytic domain of human tankyrase 1. J. Mol. Biol. · 2008
- DNA sequence and analysis of human chromosome 8. Nature · 2006
- NuMA is a major acceptor of poly(ADP-ribosyl)ation by tankyrase 1 in mitosis. Biochem. J. · 2005
- … and 7 more in the literature graph
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