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FLASH GENE
Symbol TNKS2 contributors: mct/pgu - updated : 28-08-2013
HGNC name tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase 2
HGNC id 15677
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • repeating unit of the Tankyrase N terminus, the ARC, consists of five stacked ankyrin repeats forming a modular unit and occurs five times within the Tankyrase N terminus
  • 15 ank repeats
  • one sterile alpha motif (SAM) domain
  • one PARP catalytic domain
    • mono polymer oligo
    HOMOLOGY
    interspecies homolog to murine Tnks2 (96.9pc)
    homolog to rattus Tnks2 (97.3pc)
    Homologene
    FAMILY
  • PARP family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus,chromatin/chromosome,telomere
    intracellular,nuclear envelope
    text
  • peripheral membrane
  • pericentriolar matrix of mitotic centromeres
  • AXIN1, TNKS2 and KIF3A are co-localized with SLC2A4 on the trans-Golgi network
    • basic FUNCTION
  • having PARP activity and may be modifying TERF1, and thereby contributing to the regulation of telomere length
  • may regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles
  • 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
  • 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
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component RNF146, tankyrase, and Axin form a protein complex, and RNF146 mediates ubiquitylation of all three proteins to target them for proteasomal degradation
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • complexing with TNKS
  • interacting with LNPEP/Otase in the SLC2A4/GLUT4-vesicles
  • binding to the N-terminus of GRB14 and TERF1
  • RNF146 destabilizes tankyrases TNKS and TNKS2 proteins and, in a reciprocal relationship, tankyrase activity reduces RNF146 protein levels
  • ability of TNKS2 to perturb SH3BP2 protein levels is not a result of binding alone but requires the intact TNKS2 catalytic domain
  • Axin interacts with TNKS2 and the kinesin motor protein KIF3A, forming a ternary complex crucial for SLC2A4 translocation in response to insulin
  • 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 auto ADP-ribosylated
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    pathological overexpression in some tumors
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    Tnks2(-/-) mice exhibit reduced insulin sensitivity and higher blood glucose levels when re-fed after fasting