TNKS tankyrase [Homo sapiens (human)] - Gene

Summary

Official Symbol: TNKSprovided by HGNC
Official Full Name: tankyraseprovided by HGNC
Primary source: HGNC:HGNC:11941
See related: Ensembl:ENSG00000173273 MIM:603303; Vega:OTTHUMG00000090481
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TIN1; ARTD5; PARPL; TINF1; TNKS1; pART5; PARP5A; PARP-5a
Expression: Ubiquitous expression in testis (RPKM 8.6), brain (RPKM 7.0) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 8p23.1

Exon count:: 29

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	8	NC_000008.11 (9555230..9782346)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (9412756..9639856)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Either tankyrase 1 or 2 is sufficient to maintain telomere length, but both are required to resolve telomere cohesion and maintain mitotic spindle integrity. Tankyrases are required for Notch2 to exit the plasma membrane and enter the nucleus to activate transcription.
Title: Whole proteome analysis of human tankyrase knockout cells reveals targets of tankyrase-mediated degradation.
Finally, through functional validation, we uncovered a role for TNKS/2 in peroxisome homeostasis and determined that this function is independent of TNKS enzyme activities.
Title: Proteomic Analysis of the Human Tankyrase Protein Interaction Network Reveals Its Role in Pexophagy.
The data indicate that the sterile alpha motif domain polymerization is critical for TNKS1 catalytic activity and allows TNKS1 to efficiently access cytoplasmic signaling complexes.
Title: Tankyrase Sterile α Motif Domain Polymerization Is Required for Its Role in Wnt Signaling.
Polymerization is required for Tankyrase to drive beta-catenin-dependent transcription. The polymeric state supports PARP activity and allows Tankyrase to effectively access destruction complexes through enabling avidity-dependent AXIN binding.
Title: Tankyrase Requires SAM Domain-Dependent Polymerization to Support Wnt-β-Catenin Signaling.
In late S/G2 phase, the DNA damage-responsive E3 ligase RNF8 conjugates K63-linked ubiquitin chains to tankyrase 1, while in G1 phase such ubiquitin chains are removed by BRISC, an ABRO1/BRCC36-containing deubiquitinase complex.
Title: Cell cycle-regulated ubiquitination of tankyrase 1 by RNF8 and ABRO1/BRCC36 controls the timing of sister telomere resolution.
These structural insights will be invaluable for the functional and biophysical characterization of TNKS1/2, including the role of TNKS oligomerization in protein poly(ADP-ribosyl)ation (PARylation) and PARylation-dependent ubiquitylation.
Title: Structural insights into SAM domain-mediated tankyrase oligomerization.
Results describe the structure of three consecutive TNKS- ankyrin repeat clusters (ARCs). Binding analysis indicates specific ARC pairs engage bivalent binding partner Axin1, and that both rigid and flexible ARC connections form an adaptable TNKS binding platform.
Title: Tankyrase-1 Ankyrin Repeats Form an Adaptable Binding Platform for Targets of ADP-Ribose Modification.
we show for the first time that Tankyrase 1 inhibitior XAV939 was able to significantly increase the apoptosis induced by 5-FU/DDP, accompanied by the protein expression level alternation of b-catenin, Axin and CSC markers in colon cancer cells.
Title: Tankyrase 1 inhibitior XAV939 increases chemosensitivity in colon cancer cell lines via inhibition of the Wnt signaling pathway.
Data show that poly(ADP-ribose) polymerase (PARP) enzyme Tankyrase (TNKS) inhibition in colon cancer cells decreases beta-catenin signaling at the level of both Axin and APC2.
Title: The Poly(ADP-ribose) Polymerase Enzyme Tankyrase Antagonizes Activity of the β-Catenin Destruction Complex through ADP-ribosylation of Axin and APC2.
HCMV modulates the activity of TNKS to induce Axin1, resulting in inhibition of the beta-catenin pathway.
Title: Human Cytomegalovirus Inhibits the PARsylation Activity of Tankyrase--A Potential Strategy for Suppression of the Wnt Pathway.

Submit: New GeneRIF Correction See all GeneRIFs (59)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Description
Genome-wide association study identifies ALLC polymorphisms correlated with FEV&#x02081; change by corticosteroid. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
The CCND1 c.870G&gt;A polymorphism is a risk factor for t(11;14)(q13;q32) multiple myeloma. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Two new Loci for body-weight regulation identified in a joint analysis of genome-wide association studies for early-onset extreme obesity in French and german study groups. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Degradation of AXIN, organism-specific biosystem (from REACTOME)
Degradation of AXIN, organism-specific biosystemAXIN is present in low concentrations in the cell and is considered to be the limiting component of the beta-catenin destruction complex in Xenopus; this may not be the case in mammalian cells, howev...
Deubiquitination, organism-specific biosystem (from REACTOME)
Deubiquitination, organism-specific biosystemUbiquitination, the modification of proteins by the covalent attachment of ubiquitin (Ub), is a key regulatory mechanism for many many cellular processes, including protein degradation by the 26S pro...
Disease, organism-specific biosystem (from REACTOME)
Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
Diseases of signal transduction, organism-specific biosystem (from REACTOME)
Diseases of signal transduction, organism-specific biosystemSignaling processes are central to human physiology (e.g., Pires-da Silva & Sommer 2003), and their disruption by either germ-line and somatic mutation can lead to serious disease. Here, the molecula...
Metabolism of proteins, organism-specific biosystem (from REACTOME)
Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
NAD+ biosynthetic pathways, organism-specific biosystem (from WikiPathways)
NAD+ biosynthetic pathways, organism-specific biosystemNAD+ biosynthetic pathways. NAD+ levels are maintained by three independent pathways. First, the Preiss-Handler pathway uses dietary nicotinic acid and the enzyme nicotinic acid phosphoribosyltransfe...
Post-translational protein modification, organism-specific biosystem (from REACTOME)
Post-translational protein modification, organism-specific biosystemAfter translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the...
Regulation of Telomerase, organism-specific biosystem (from Pathway Interaction Database)
Regulation of Telomerase, organism-specific biosystem
Regulation of Telomerase
Regulation of Wnt/B-catenin Signaling by Small Molecule Compounds, organism-specific biosystem (from WikiPathways)
Regulation of Wnt/B-catenin Signaling by Small Molecule Compounds, organism-specific biosystemThe Wnt/B-catenin pathway begins with Wnt family activation by MBOAT that allows Wnt proteins to translocate out of a cell and bind to FZD and LRP to form a complex. This complex stimulates B-catenin...
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by WNT in cancer, organism-specific biosystem (from REACTOME)
Signaling by WNT in cancer, organism-specific biosystemThe WNT signaling pathway has been linked with cancer ever since the identification of the first WNT as a gene activated by integration of mouse mammary tumor virus proviral DNA in virally-induced br...
Signaling by Wnt, organism-specific biosystem (from REACTOME)
Signaling by Wnt, organism-specific biosystemWNT signaling pathways control a wide range of developmental and adult process in metozoans including cell proliferation, cell fate decisions, cell polarity and stem cell maintenance (reviewed in Sai...
TCF dependent signaling in response to WNT, organism-specific biosystem (from REACTOME)
TCF dependent signaling in response to WNT, organism-specific biosystem19 WNT ligands and 10 FZD receptors have been identified in human cells; interactions amongst these ligands and receptors vary in a developmental and tissue-specific manner and lead to activation of ...
Ub-specific processing proteases, organism-specific biosystem (from REACTOME)
Ub-specific processing proteases, organism-specific biosystemUb-specific processing proteases (USPs) are the largest of the DUB families with more than 50 members in humans. The USP catalytic domain varies considerably in size and consists of six conserved mo...
XAV939 inhibits tankyrase, stabilizing AXIN, organism-specific biosystem (from REACTOME)
XAV939 inhibits tankyrase, stabilizing AXIN, organism-specific biosystemXAV939 binds to the catalytic sites of tankyrase 1 and 2 and inhibits the ADP-ribosylation of AXIN1 and 2. Treatment of cells with XAV939 significantly increases the protein, but not the mRNA levels ...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-24414 (e-PCR)
- UniSTS:81158

RH11883 (e-PCR)
- UniSTS:25352

RH18302 (e-PCR)
- UniSTS:28435

NoName (e-PCR)
- UniSTS:45338

RH104269 (e-PCR)
- UniSTS:98594

PMC156606P2 (e-PCR)
- UniSTS:271409

D8S2278 (e-PCR)
- UniSTS:473906

D8S2279 (e-PCR)
- UniSTS:473907

G20573 (e-PCR)
- UniSTS:4932

A005X23 (e-PCR)
- UniSTS:4933

SHGC-132382 (e-PCR)
- UniSTS:184694

HSC2QE062 (e-PCR)
- UniSTS:13182

G59681 (e-PCR)
- UniSTS:136835

SHGC-63000 (e-PCR)
- UniSTS:95383

RH120367 (e-PCR)
- UniSTS:132508

RH103385 (e-PCR)
- UniSTS:97711

RH44938 (e-PCR)
- UniSTS:45547

Homology

Homologs of the TNKS gene: The TNKS gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and frog.
Orthologs from Annotation Pipeline: 182 organisms have orthologs with human gene TNKS
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
NAD+ ADP-ribosyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
NAD+ ADP-ribosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
NAD+ ADP-ribosyltransferase activity	TAS Traceable Author Statement more info
histone binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
cell division	IEA Inferred from Electronic Annotation more info
cellular response to nutrient	IEA Inferred from Electronic Annotation more info
mRNA transport	IEA Inferred from Electronic Annotation more info
mitotic spindle organization	TAS Traceable Author Statement more info	PubMed
negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of telomere maintenance via telomere lengthening	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of telomeric DNA binding	IDA Inferred from Direct Assay more info	PubMed
negative regulation of telomeric DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
peptidyl-serine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
peptidyl-threonine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of canonical Wnt signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of canonical Wnt signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of canonical Wnt signaling pathway	TAS Traceable Author Statement more info
positive regulation of telomerase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of telomere capping	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of telomere capping	IDA Inferred from Direct Assay more info	PubMed
positive regulation of telomere capping	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of telomere maintenance via telomerase	IDA Inferred from Direct Assay more info	PubMed
positive regulation of telomere maintenance via telomerase	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
protein ADP-ribosylation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein ADP-ribosylation	IDA Inferred from Direct Assay more info	PubMed
protein auto-ADP-ribosylation	IDA Inferred from Direct Assay more info	PubMed
protein localization to chromosome, telomeric region	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein localization to chromosome, telomeric region	IMP Inferred from Mutant Phenotype more info	PubMed
protein poly-ADP-ribosylation	IDA Inferred from Direct Assay more info	PubMed
protein poly-ADP-ribosylation	IMP Inferred from Mutant Phenotype more info	PubMed
protein polyubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein transport	IEA Inferred from Electronic Annotation more info
regulation of telomere maintenance via telomerase	IC Inferred by Curator more info	PubMed
spindle assembly	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
Golgi membrane	IEA Inferred from Electronic Annotation more info
chromosome, centromeric region	IEA Inferred from Electronic Annotation more info
chromosome, telomeric region	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytosol	TAS Traceable Author Statement more info
mitotic spindle pole	IDA Inferred from Direct Assay more info	PubMed
nuclear body	IDA Inferred from Direct Assay more info
nuclear chromosome, telomeric region	IDA Inferred from Direct Assay more info	PubMed
nuclear membrane	IDA Inferred from Direct Assay more info
nuclear membrane	TAS Traceable Author Statement more info	PubMed
nuclear pore	TAS Traceable Author Statement more info	PubMed
nucleoplasm	IDA Inferred from Direct Assay more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
pericentriolar material	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: tankyrase-1

Names: ADP-ribosyltransferase diphtheria toxin-like 5; TANK1; TNKS-1; TRF1-interacting ankyrin-related ADP-ribose polymerase 1; poly [ADP-ribose] polymerase 5A; tankyrase I; tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase

NP_003738.2

EC 2.4.2.30

XP_006716326.1

EC 2.4.2.30

XP_011542147.1

EC 2.4.2.30

XP_011542148.1

EC 2.4.2.30

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_003747.2 → NP_003738.2 tankyrase-1

See identical proteins and their annotated locations for NP_003738.2

Status: VALIDATED

Source sequence(s)

AC104052, AF082556, AL706619, BC098394

Consensus CDS

CCDS5974.1

UniProtKB/Swiss-Prot

O95271

Related

ENSP00000311579.6, OTTHUMP00000115550, ENST00000310430.10, OTTHUMT00000206935

Conserved Domains (8) summary

cd09524
Location:1024 → 1089

SAM_tankyrase1,2; SAM domain of tankyrase1,2 subfamily

smart00454
Location:1030 → 1087

SAM; Sterile alpha motif

cd00204
Location:676 → 801

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

cd01438
Location:1091 → 1313

tankyrase_like; Tankyrases interact with the telomere reverse transcriptase complex (TERT). Tankyrase 1 poly-ADP-ribosylates Telomere Repeat Binding Factor 1 (TRF1) while Tankyrase 2 can poly-ADP-ribosylate itself or TRF1. The tankyrases also contain multiple ankyrin ...

pfam00644
Location:1105 → 1308

PARP; Poly(ADP-ribose) polymerase catalytic domain

pfam12796
Location:688 → 780

Ank_2; Ankyrin repeats (3 copies)

pfam13637
Location:803 → 857

Ank_4; Ankyrin repeats (many copies)

sd00045
Location:371 → 399

ANK; ANK repeat [structural motif]

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p12 Primary Assembly

Range

9555230..9782346

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006716263.4 → XP_006716326.1 tankyrase-1 isoform X1

See identical proteins and their annotated locations for XP_006716326.1

Conserved Domains (8) summary

cd09524
Location:1024 → 1089

SAM_tankyrase1,2; SAM domain of tankyrase1,2 subfamily

smart00454
Location:1030 → 1087

SAM; Sterile alpha motif

cd00204
Location:676 → 801

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

cd01438
Location:1091 → 1299

tankyrase_like; Tankyrases interact with the telomere reverse transcriptase complex (TERT). Tankyrase 1 poly-ADP-ribosylates Telomere Repeat Binding Factor 1 (TRF1) while Tankyrase 2 can poly-ADP-ribosylate itself or TRF1. The tankyrases also contain multiple ankyrin ...

pfam00644
Location:1105 → 1300

PARP; Poly(ADP-ribose) polymerase catalytic domain

pfam12796
Location:688 → 780

Ank_2; Ankyrin repeats (3 copies)

pfam13637
Location:803 → 857

Ank_4; Ankyrin repeats (many copies)

sd00045
Location:371 → 399

ANK; ANK repeat [structural motif]
XM_011543845.3 → XP_011542147.1 tankyrase-1 isoform X1

See identical proteins and their annotated locations for XP_011542147.1

Conserved Domains (8) summary

cd09524
Location:1024 → 1089

SAM_tankyrase1,2; SAM domain of tankyrase1,2 subfamily

smart00454
Location:1030 → 1087

SAM; Sterile alpha motif

cd00204
Location:676 → 801

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

cd01438
Location:1091 → 1299

tankyrase_like; Tankyrases interact with the telomere reverse transcriptase complex (TERT). Tankyrase 1 poly-ADP-ribosylates Telomere Repeat Binding Factor 1 (TRF1) while Tankyrase 2 can poly-ADP-ribosylate itself or TRF1. The tankyrases also contain multiple ankyrin ...

pfam00644
Location:1105 → 1300

PARP; Poly(ADP-ribose) polymerase catalytic domain

pfam12796
Location:688 → 780

Ank_2; Ankyrin repeats (3 copies)

pfam13637
Location:803 → 857

Ank_4; Ankyrin repeats (many copies)

sd00045
Location:371 → 399

ANK; ANK repeat [structural motif]
XM_011543846.3 → XP_011542148.1 tankyrase-1 isoform X2

Conserved Domains (8) summary

cd09524
Location:1024 → 1089

SAM_tankyrase1,2; SAM domain of tankyrase1,2 subfamily

smart00454
Location:1030 → 1087

SAM; Sterile alpha motif

cd00204
Location:676 → 801

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

cd01438
Location:1091 → 1299

tankyrase_like; Tankyrases interact with the telomere reverse transcriptase complex (TERT). Tankyrase 1 poly-ADP-ribosylates Telomere Repeat Binding Factor 1 (TRF1) while Tankyrase 2 can poly-ADP-ribosylate itself or TRF1. The tankyrases also contain multiple ankyrin ...

pfam00644
Location:1105 → 1300

PARP; Poly(ADP-ribose) polymerase catalytic domain

pfam12796
Location:688 → 780

Ank_2; Ankyrin repeats (3 copies)

pfam13637
Location:803 → 857

Ank_4; Ankyrin repeats (many copies)

sd00045
Location:371 → 399

ANK; ANK repeat [structural motif]