tankyrase-1; TANK1; poly [ADP-ribose] polymerase 5A; TNKS-1; TRF1-interacting ankyrin-related ADP-ribose polymerase (TNKS, PARP5A, PARPL, TIN1, TINF1, TNKS1)

^[1]

Function

poly-ADP-ribosyltransferase
role in various processes
- Wnt signaling pathway
- telomere length
- vesicle trafficking
acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 & AXIN2, 2 key components of the beta-catenin destruction complex:
- poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination & subsequent degradation
mediates poly-ADP-ribosylation of BLZF1 & CASC3, followed by recruitment of RNF146 & subsequent ubiquitination
mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length
may also regulate vesicle trafficking & modulate subcellular distribution of SLC2A4/GLUT4-vesicles
phosphorylated on Ser by MAPK kinases upon insulin stimulation
ADP-ribosylated (-auto)
ubiquitinated by RNF146 when auto-poly-ADP-ribosylated, leading to its degradation
oligomerizes & associates with TNKS2
interacts with the cytoplasmic domain of LNPEP/Otase in SLC2A4/GLUT4-vesicles
binds to the N-terminus of telomeric TERF1 via the ANK repeats
found in a complex with POT1; TERF1 & TINF2
interacts with AXIN1, AXIN2, BLZF1 & CASC3

NAD+ + (ADP-D-ribosyl)(n)-acceptor = nicotinamide + (ADP-D-ribosyl)(n+1)-acceptor

Inhibition:

specifically inhibited by XAV939, a small molecule, leading to inhibit the Wnt signaling pathway by stabilizing AXIN1 & AXIN2

cytoplasm, Golgi membrane, peripheral membrane
nucleus, nuclear pore complex
chromosome, centromere,telomere (putative)
associated with the Golgi & with juxtanuclear SLC2A4/GLUT4-vesicles
a minor proportion is also found at nuclear pore complexes & around the pericentriolar matrix of mitotic centromeres
during interphase, a small fraction of TNKS is found in the nucleus, associated with TERF1