tankyrase-2; poly [ADP-ribose] polymerase 5B; TNKS-2; TRF1-interacting ankyrin-related ADP-ribose polymerase 2; tankyrase-like protein; tankyrase-related protein (TNKS2, PARP5B, TANK2, TNKL)

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
• also mediates poly-ADP-ribosylation of BLZF1 & CASC3, followed by recruitment of RNF146 & subsequent ubiquitination
• mediates poly-ADP-ribosylation of TERF1, thus contributing to the regulation of telomere length
• may also regulate vesicle trafficking & modulate the subcellular distribution of SLC2A4/GLUT4-vesicles
• ADP-ribosylated (-auto)
• ubiquitinated by RNF146 when auto-poly-ADP-ribosylated, leading to its degradation
• oligomerizes & associates with TNKS
• interacts with the cytoplasmic domain of LNPEP/Otase in SLC2A4/GLUT4-vesicles
• binds to the N-terminus of Grb14 & TRF1 with its ankyrin repeat region

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

Structure

• contains 15 ANK repeats
• contains 1 PARP catalytic domain
• contains 1 SAM (sterile alpha motif) domain

Compartment

• cytoplasm. Golgi membrane, peripheral membrane
• nucleus, chromosome, telomere (putative)
• associated with the Golgi & with juxtanuclear SLC2A4/GLUT4-vesicles
• also found around the pericentriolar matrix of mitotic centromeres
• during interphase, a small fraction of TNKS2 is found in the nucleus, associated with TRF1

Expression

• highly expressed in placenta, skeletal muscle, liver, brain, kidney, heart, thymus, spinal cord, lung, peripheral blood leukocytes, pancreas, lymph nodes, spleen, prostate, testis, ovary, small intestine, colon, mammary gland, breast & breast carcinoma, & in common-type meningioma
• highly expressed in fetal liver, heart & brain

More general terms

• tankyrase
• ankyrin repeat domain protein (ANKRD)

Additional terms

• ankyrin
• NAD+ ADP-ribosyltransferase or poly ADP-ribose polymerase
• telomeric repeat binding factor

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=80351
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:80351
• OMIM: https://mirror.omim.org/entry/607128
• UniProt: http://www.uniprot.org/uniprot/Q9H2K2.html