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FLASH GENE
Symbol TNKS contributors: mct/pgu - updated : 27-08-2017
HGNC name tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase
HGNC id 11941
Location 8p23.1      Physical location : 9.413.444 - 9.639.855
Synonym name tankyrase 1
Synonym symbol(s) TIN1, TINF1, TNKS1, PARP-5a, PARP5A, PARPL
EC.number 2.4.2.30
DNA
TYPE functioning gene
STRUCTURE 226.41 kb     27 Exon(s)    1 Copie(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked Y status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
27 - 9599 - 1327 - 2007 17561506
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrineneuroendocrinepituitary  highly
 neuroendocrinepituitary  highly
Reproductivemale systemtestis  highly
Respiratorylung   highly Mus musculusFetal
Urinarykidney   highly Mus musculusFetal
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal region with HPS (His, Pro, Ser) runs
  • five domains called ankyrin repeat cluster (ARC) I to V, binding to various partners, including TERF1 and LNPEP
  • a sterile alpha motif (SAM), which contributes to protein multimerization
  • C motif of homology to the PARP catalytic domain
  • HOMOLOGY
    interspecies homolog to murine Tnks (97.9pc)
    homolog to rattus Tnks (97.9pc)
    Homologene
    FAMILY PARP family
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,chromatin/chromosome,telomere
    intracellular,nuclear envelope,pore
    text
  • localizes to centrosomes exclusively in G1, coinciding with CENPJ degradation
  • basic FUNCTION
  • promoting telomere elongation by down-regulation of TERF1, a negative regulator of telomere extension
  • could be auto-regulated by forming dormant protein complexes
  • multifunctional poly(ADP-ribose) polymerase
  • containing epitopes that induce humoral and cellular immune responses in cancer patients
  • TNKS and TNKS2 are critical regulators of canonical Wnt signaling in some cellular contexts
  • TNKS and TNKS2 are core components of the canonical Wnt pathway and their inhibitors should enjoy broad usage as antagonists of Wnt signaling
  • poly(ADP-ribosyl)ates the telomere-binding protein TERF1
  • tankyrase-1 assembly to large protein complexes masks its telomeric function
  • TNKS multimerization and subsequent larger protein complex formation block its telomeric function
  • component of a regulatory pathway controlling bone homeostasis and inflammatory cytokine production
  • TNKS/TNKS2) catalyze the covalent linkage of ADP-ribose polymer chains onto target proteins, regulating their ubiquitylation, stability, and function
  • play pharmaceutically important roles, at least in telomere homeostasis and Wnt signaling, by covalently ADP-ribosylating target proteins and consequently regulating their functions
  • critical role for TNKS and the canonical Wnt pathway in maintaining lung cancer cells during EGFR inhibition
  • CELLULAR PROCESS nucleotide, replication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • TNKS-RNF146-AMOT axis is an upstream pathway regulating YAP1
  • a component
  • complexing with tankyrase 2 (TNKS2) and TNKS1BP1
  • RNF146, tankyrase, and Axin form a protein complex, and RNF146 mediates ubiquitylation of all three proteins to target them for proteasomal degradation
  • GMDS forms stable 1:1 complexes with the TNKS ankyrin repeat domain
  • INTERACTION
    DNA
    RNA
    small molecule metal binding, cofactor,
  • zinc ion binding
  • protein
  • interacting with MCL1 and inhibiting its regulation of apoptosis protein
  • NUMA1 is a major eacceptor of poly(ADP ribosyl)ation by TNKS in mitosis
  • binding to FBNP1
  • overexpression of TNKS reduces genotoxic-induced cell deathby inhibiing PARP1
  • NUMA1 interacting with TNKS (interaction contributing to colocalization of tankyrase and NUMA1 at mitotic spindle poles)
  • RNF146 destabilizes tankyrases TNKS and TNKS2 proteins and, in a reciprocal relationship, tankyrase activity reduces RNF146 protein levels
  • regulates SH3BP2 stability through ADP-ribosylation and subsequent ubiquitylation by the E3-ubiquitin ligase RNF146 in osteoclasts
  • bivalent binding of AXIN1 to TNKS is required for AXIN1 turnover, since mutations in either gate-binding glycine residue in AXIN1 lead to its stabilization in the cell
  • CENPJ degradation and function is controlled by the poly(ADP-ribose) polymerase TNKS
  • PARsylation of HEPACAM2 by TNKS is a key initial event promoting prometaphase
  • USP25 directly interacted with TNKS, TNKS2 to promote their deubiquitination and stabilization
  • cell & other
    REGULATION
    inhibited by XAV939 and thus stabilizes axin and antagonizes Wnt signalling
    Other regulated by TINF2 (TRF1) interacting nuclear factor
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast cancer
    tumoral        
    aberrantly expressed in colon tumors
    Susceptibility
    Variant & Polymorphism SNP polymorphisms contribute to genetic susceptibility to lung cancer
    Candidate gene for CDLS3
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    could be a molecular target for cancer therapy
    ANIMAL & CELL MODELS