TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase)
2011-06-01 Yury Shebzukhov , Sergei Nedospasov AffiliationGerman Rheumatism Research Center, a Leibniz Institute, Berlin, Germany (YS, SN); Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia (SN)
Identity
HGNC
LOCATION
8p23.1
LOCUSID
ALIAS
ARTD5,PARP-5a,PARP5A,PARPL,TIN1,TINF1,TNKS1,pART5
FUSION GENES
DNA/RNA
Description
Spans 226410 bp, 27 exons.
Transcription
9599 bp long mRNA, containing 3984 bp long ORF.
Proteins
TNKS protein. HPS: region containing homopolymeric runs of His, Pro, and Ser; ANK: ankyrin domain; SAM: multimerization domain homologous to the sterile alpha motif; PARP: PARP catalytic domain.
Description
Isoform 1 (1327 amino acids) contains region with homopolymeric runs of His, Pro, and Ser (HPS domain, aa 1-181), 15 ankyrin repeats (ANK 1 to 15, aa 215-934), multimerization domain homologous to the sterile alpha motif (SAM domain, aa 1030-1089) and PARP catalytic domain (aa 1112-1317). Isoform 2 (643 amino acids) contains only HPS domain and 9 ANK repeats.
Expression
Ubiquitous, high expression in brain and ganglions, skin and cardiac tissue.
Localisation
Nuclear and cytoplasmic.
Function
Poly(ADP-ribosyl)ation (PARsylation) of target proteins: TNKS itself, TNKS2/TNKL, TRF1, IRAP, TAB182/TNKS1BP1, EBNA-1, Mcl-1L, Mcl-1S, NuMA, AXIN1, AXIN2.
TNKS PARsylates TRF1 (telomeric repeat-binding factor 1), a negative regulator of telomere length maintenance. PARsylated TRF1 dissociates from telomeres, enhancing telomerase-mediated telomere elongation (Smith and de Lange, 2000; Cook et al., 2002).
PARsylation of NuMA (nuclear mitotic apparatus protein) by TNKS contributes to mitotic spindle pole assembly (Sbodio and Chi, 2002).
TNKS can PARsylate Mcl-1L and Mcl-1S and inhibit their anti- and pro-apoptotic function correspondingly (Bae et al., 2003).
TNKS inhibits Epstein-Barr virus OriP function by binding and modifying Epstein-Barr nuclear antigen 1 (EBNA1) (Deng et al., 2002; Deng et al., 2005).
PARsylation activity of TNKS increases after phosphorilation by mitogen-activated protein kinase (MAPK) upon insulin stimulation (Chi and Lodish, 2000).
TNKS together with its partner IRAP enhances insulin-stimulated exocytosis of GLUT4 (Yeh et al., 2007).
TNKS PARsylates AXIN1 and AXIN2 components of beta-catenin (the Wnt pathway transcription factor) destruction complex (Huang et al., 2009).
TNKS is a target of the FANCD2, the key protein involved in development of Fanconi anemia. FANCD binds tankyrase-1 and inhibits its PARsylation at telomeres (Lyakhovich et al., 2011).
TNKS PARsylates TRF1 (telomeric repeat-binding factor 1), a negative regulator of telomere length maintenance. PARsylated TRF1 dissociates from telomeres, enhancing telomerase-mediated telomere elongation (Smith and de Lange, 2000; Cook et al., 2002).
PARsylation of NuMA (nuclear mitotic apparatus protein) by TNKS contributes to mitotic spindle pole assembly (Sbodio and Chi, 2002).
TNKS can PARsylate Mcl-1L and Mcl-1S and inhibit their anti- and pro-apoptotic function correspondingly (Bae et al., 2003).
TNKS inhibits Epstein-Barr virus OriP function by binding and modifying Epstein-Barr nuclear antigen 1 (EBNA1) (Deng et al., 2002; Deng et al., 2005).
PARsylation activity of TNKS increases after phosphorilation by mitogen-activated protein kinase (MAPK) upon insulin stimulation (Chi and Lodish, 2000).
TNKS together with its partner IRAP enhances insulin-stimulated exocytosis of GLUT4 (Yeh et al., 2007).
TNKS PARsylates AXIN1 and AXIN2 components of beta-catenin (the Wnt pathway transcription factor) destruction complex (Huang et al., 2009).
TNKS is a target of the FANCD2, the key protein involved in development of Fanconi anemia. FANCD binds tankyrase-1 and inhibits its PARsylation at telomeres (Lyakhovich et al., 2011).
Homology
With TNKS2/TNKL.
Mutations
Somatic
Frameshift mutations are found in exons 9 and 10 in gastric and colorectal malignant tumors (Kim et al., 2011).
Implicated in
Entity name
Cancer
Note
TNKS is considered as a potential target for anticancer treatment.
Inhibition of PARP activities of TNKS blocks Wnt/beta-catenin pathway and increases efficiency of telomerase inhibitors (Seimiya et al., 2005; Huang et al., 2009; Zhang et al., 2010).
Inhibition of PARP activities of TNKS blocks Wnt/beta-catenin pathway and increases efficiency of telomerase inhibitors (Seimiya et al., 2005; Huang et al., 2009; Zhang et al., 2010).
Disease
TNKS expression increased in some tumors (compared to adjacent normal tissues), including breast, bladder and gastric cancer (Gelmini et al., 2004; Gelmini et al., 2007; Poonepalli et al., 2008; Gao et al., 2011), but in other tumors, e.g. malignant glioma and colorectal cancer TNKS expression might be downregulated (Shervington et al., 2007; Shebzukhov et al., 2008), Fanconi anemia (Lyakhovich et al., 2011).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 12475993 | 2003 | Tankyrase 1 interacts with Mcl-1 proteins and inhibits their regulation of apoptosis. | Bae J et al |
| 10988299 | 2000 | Tankyrase is a golgi-associated mitogen-activated protein kinase substrate that interacts with IRAP in GLUT4 vesicles. | Chi NW et al |
| 11739745 | 2002 | Role for the related poly(ADP-Ribose) polymerases tankyrase 1 and 2 at human telomeres. | Cook BD et al |
| 15795250 | 2005 | Inhibition of Epstein-Barr virus OriP function by tankyrase, a telomere-associated poly-ADP ribose polymerase that binds and modifies EBNA1. | Deng Z et al |
| 11931758 | 2002 | Telomeric proteins regulate episomal maintenance of Epstein-Barr virus origin of plasmid replication. | Deng Z et al |
| 21455637 | 2011 | Expression of tankyrase 1 in gastric cancer and its correlation with telomerase activity. | Gao J et al |
| 15500951 | 2004 | Tankyrase, a positive regulator of telomere elongation, is over expressed in human breast cancer. | Gelmini S et al |
| 17617028 | 2007 | Tankyrase-1 mRNA expression in bladder cancer and paired urine sediment: preliminary experience. | Gelmini S et al |
| 19759537 | 2009 | Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. | Huang SM et al |
| 21333322 | 2011 | Frameshift mutations of poly(adenosine diphosphate-ribose) polymerase genes in gastric and colorectal cancers with microsatellite instability. | Kim MS et al |
| 21314979 | 2011 | Fanconi anemia protein FANCD2 inhibits TRF1 polyADP-ribosylation through tankyrase1-dependent manner. | Lyakhovich A et al |
| 18720522 | 2008 | Telomere-mediated genomic instability and the clinico-pathological parameters in breast cancer. | Poonepalli A et al |
| 12080061 | 2002 | 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. | Sbodio JI et al |
| 15652747 | 2005 | Tankyrase 1 as a target for telomere-directed molecular cancer therapeutics. | Seimiya H et al |
| 18026951 | 2008 | Human tankyrases are aberrantly expressed in colon tumors and contain multiple epitopes that induce humoral and cellular immune responses in cancer patients. | Shebzukhov YV et al |
| 17196947 | 2007 | Telomerase subunits expression variation between biopsy samples and cell lines derived from malignant glioma. | Shervington A et al |
| 11069113 | 2000 | Tankyrase promotes telomere elongation in human cells. | Smith S et al |
| 17059388 | 2007 | Insulin-stimulated exocytosis of GLUT4 is enhanced by IRAP and its partner tankyrase. | Yeh TY et al |
| 20811689 | 2010 | Inhibition of tankyrase 1 in human gastric cancer cells enhances telomere shortening by telomerase inhibitors. | Zhang H et al |
Other Information
Locus ID:
NCBI: 8658
MIM: 603303
HGNC: 11941
Ensembl: ENSG00000173273
Variants:
dbSNP: 8658
ClinVar: 8658
TCGA: ENSG00000173273
COSMIC: TNKS
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37741944 | 2024 | Tankyrase inhibition interferes with junction remodeling, induces leakiness, and disturbs YAP1/TAZ signaling in the endothelium. | 0 |
| 38216082 | 2024 | BET protein-dependent E2F pathway activity confers bell-shaped type resistance to tankyrase inhibitors in APC-mutated colorectal cancer. | 0 |
| 37741944 | 2024 | Tankyrase inhibition interferes with junction remodeling, induces leakiness, and disturbs YAP1/TAZ signaling in the endothelium. | 0 |
| 38216082 | 2024 | BET protein-dependent E2F pathway activity confers bell-shaped type resistance to tankyrase inhibitors in APC-mutated colorectal cancer. | 0 |
| 36603485 | 2023 | Effect and interaction of TNKS genetic polymorphisms and environmental factors on telomere damage in COEs-exposure workers. | 0 |
| 36603485 | 2023 | Effect and interaction of TNKS genetic polymorphisms and environmental factors on telomere damage in COEs-exposure workers. | 0 |
| 35450028 | 2022 | Deubiquitination of TNKS1 Regulates Wnt/β-Catenin to Affect the Expression of USP25 to Promote the Progression of Glioma. | 3 |
| 35733260 | 2022 | Tankyrases inhibit innate antiviral response by PARylating VISA/MAVS and priming it for RNF146-mediated ubiquitination and degradation. | 12 |
| 35450028 | 2022 | Deubiquitination of TNKS1 Regulates Wnt/β-Catenin to Affect the Expression of USP25 to Promote the Progression of Glioma. | 3 |
| 35733260 | 2022 | Tankyrases inhibit innate antiviral response by PARylating VISA/MAVS and priming it for RNF146-mediated ubiquitination and degradation. | 12 |
| 33361107 | 2021 | Dissecting the molecular determinants of clinical PARP1 inhibitor selectivity for tankyrase1. | 18 |
| 33811251 | 2021 | Evaluation of AXIN1 and AXIN2 as targets of tankyrase inhibition in hepatocellular carcinoma cell lines. | 12 |
| 33923443 | 2021 | Arpin Regulates Migration Persistence by Interacting with Both Tankyrases and the Arp2/3 Complex. | 5 |
| 34298950 | 2021 | Discovery of a Novel Triazolopyridine Derivative as a Tankyrase Inhibitor. | 2 |
| 34876695 | 2021 | Tankyrase-1-mediated degradation of Golgin45 regulates glycosyltransferase trafficking and protein glycosylation in Rab2-GTP-dependent manner. | 8 |
Citation
Yury Shebzukhov ; Sergei Nedospasov
TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase)
Atlas Genet Cytogenet Oncol Haematol. 2011-06-01
Online version: http://atlasgeneticsoncology.org/gene/43534/tnks-(tankyrase-trf1-interacting-ankyrin-related-adp-ribose-polymerase)
