ID:TNKS1_HUMAN DESCRIPTION: RecName: Full=Tankyrase-1; Short=TANK1; EC=2.4.2.30; AltName: Full=ADP-ribosyltransferase diphtheria toxin-like 5; Short=ARTD5; AltName: Full=Poly [ADP-ribose] polymerase 5A; AltName: Full=TNKS-1; AltName: Full=TRF1-interacting ankyrin-related ADP-ribose polymerase; AltName: Full=Tankyrase I; 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. CATALYTIC ACTIVITY: NAD(+) + (ADP-D-ribosyl)(n)-acceptor = nicotinamide + (ADP-D-ribosyl)(n+1)-acceptor. ENZYME REGULATION: Specifically inhibited by XAV939, a small molecule, leading to inhibit the Wnt signaling pathway by stabilizing AXIN1 and AXIN2. SUBUNIT: Oligomerizes and associates with TNKS2. Interacts with the cytoplasmic domain of LNPEP/Otase in SLC2A4/GLUT4-vesicles. Binds to the N-terminus of telomeric TERF1 via the ANK repeats. Found in a complex with POT1; TERF1 and TINF2. Interacts with AXIN1, AXIN2, BLZF1 and CASC3. INTERACTION: O35625:Axin1 (xeno); NbExp=4; IntAct=EBI-1105254, EBI-2365912; Q96RU3:FNBP1; NbExp=4; IntAct=EBI-1105254, EBI-1111248; SUBCELLULAR LOCATION: Cytoplasm. Golgi apparatus membrane; Peripheral membrane protein. Chromosome, centromere. Nucleus, nuclear pore complex. Chromosome, telomere (Potential). Cytoplasm, cytoskeleton, spindle pole. Note=Associated with the Golgi and with juxtanuclear SLC2A4/GLUT4-vesicles. A minor proportion is also found at nuclear pore complexes and around the pericentriolar matrix of mitotic centromeres. During interphase, a small fraction of TNKS is found in the nucleus, associated with TERF1. Localizes to spindle poles at mitosis onset via interaction with NUMA1. TISSUE SPECIFICITY: Ubiquitous; highest levels in testis. PTM: Phosphorylated on serine residues by MAPK kinases upon insulin stimulation. Phosphorylated during mitosis. PTM: Ubiquitinated by RNF146 when auto-poly-ADP-ribosylated, leading to its degradation. PTM: ADP-ribosylated (-auto). Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination. SIMILARITY: Contains 15 ANK repeats. SIMILARITY: Contains 1 PARP catalytic domain. SIMILARITY: Contains 1 SAM (sterile alpha motif) domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O95271
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000209 protein polyubiquitination GO:0006471 protein ADP-ribosylation GO:0007049 cell cycle GO:0007052 mitotic spindle organization GO:0015031 protein transport GO:0016055 Wnt signaling pathway GO:0018105 peptidyl-serine phosphorylation GO:0018107 peptidyl-threonine phosphorylation GO:0032210 regulation of telomere maintenance via telomerase GO:0032212 positive regulation of telomere maintenance via telomerase GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0051028 mRNA transport GO:0051225 spindle assembly GO:0051301 cell division GO:0051973 positive regulation of telomerase activity GO:0070198 protein localization to chromosome, telomeric region GO:0070212 protein poly-ADP-ribosylation GO:0070213 protein auto-ADP-ribosylation GO:0090263 positive regulation of canonical Wnt signaling pathway GO:1904355 positive regulation of telomere capping GO:1904357 negative regulation of telomere maintenance via telomere lengthening GO:1904743 negative regulation of telomeric DNA binding GO:1904908 negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric