ID:TNKS2_HUMAN DESCRIPTION: RecName: Full=Tankyrase-2; Short=TANK2; EC=2.4.2.30; AltName: Full=ADP-ribosyltransferase diphtheria toxin-like 6; Short=ARTD6; AltName: Full=Poly [ADP-ribose] polymerase 5B; AltName: Full=TNKS-2; AltName: Full=TRF1-interacting ankyrin-related ADP-ribose polymerase 2; AltName: Full=Tankyrase II; AltName: Full=Tankyrase-like protein; AltName: Full=Tankyrase-related protein; 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. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. 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 TNKS. Interacts with the cytoplasmic domain of LNPEP/Otase in SLC2A4/GLUT4-vesicles. Binds to the N-terminus of Grb14 and TRF1 with its ankyrin repeat region. Interacts with HIF1AN. Interacts with RNF146; this interaction leads to ubiquitination and proteasomal degradation. INTERACTION: O15084:ANKRD28; NbExp=3; IntAct=EBI-4398527, EBI-359567; O15169:AXIN1; NbExp=2; IntAct=EBI-4398527, EBI-710484; Q9NWV8:BABAM1; NbExp=4; IntAct=EBI-4398527, EBI-745725; P11274:BCR; NbExp=3; IntAct=EBI-4398527, EBI-712838; Q6V0I7:FAT4; NbExp=2; IntAct=EBI-4398527, EBI-948985; Q92698:RAD54L; NbExp=3; IntAct=EBI-4398527, EBI-5333483; P78314:SH3BP2; NbExp=5; IntAct=EBI-4398527, EBI-727062; Q06649:Sh3bp2 (xeno); NbExp=6; IntAct=EBI-4398527, EBI-5323518; O43815:STRN; NbExp=2; IntAct=EBI-4398527, EBI-1046642; P54274:TERF1; NbExp=2; IntAct=EBI-4398527, EBI-710997; SUBCELLULAR LOCATION: Cytoplasm. Golgi apparatus membrane; Peripheral membrane protein. Nucleus. Chromosome, telomere (Potential). Note=Associated with the Golgi and with juxtanuclear SLC2A4/GLUT4-vesicles. Also found around the pericentriolar matrix of mitotic centromeres. During interphase, a small fraction of TNKS2 is found in the nucleus, associated with TRF1. TISSUE SPECIFICITY: Highly expressed in placenta, skeletal muscle, liver, brain, kidney, heart, thymus, spinal cord, lung, peripheral blood leukocytes, pancreas, lymph nodes, spleen, prostate, testis, ovary, small intestine, colon, mammary gland, breast and breast carcinoma, and in common-type meningioma. Highly expressed in fetal liver, heart and brain. PTM: Ubiquitinated at 'Lys-48' and 'Lys-63' by RNF146 when auto- poly-ADP-ribosylated; this leads to degradation. PTM: ADP-ribosylated (-auto). Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination. PTM: The crystallographic evidence suggests that the 3- hydroxyhistidine may be the (3S) stereoisomer. SIMILARITY: Contains 15 ANK repeats. SIMILARITY: Contains 1 PARP catalytic domain. SIMILARITY: Contains 1 SAM (sterile alpha motif) domain. SEQUENCE CAUTION: Sequence=AAG25674.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=BAB14665.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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 Q9H2K2
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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.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0003950 NAD+ ADP-ribosyltransferase activity GO:0005515 protein binding GO:0016740 transferase activity GO:0016757 transferase activity, transferring glycosyl groups GO:0019899 enzyme binding GO:0046872 metal ion binding
Biological Process: GO:0000209 protein polyubiquitination GO:0006471 protein ADP-ribosylation GO:0016055 Wnt signaling pathway GO:0032212 positive regulation of telomere maintenance via telomerase GO:0035264 multicellular organism growth GO:0040014 regulation of multicellular organism growth GO:0070198 protein localization to chromosome, telomeric region 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
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
