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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
a) Wnt signaling pathway
b) telomere length
c) 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
Related
ankyrin
NAD+ ADP-ribosyltransferase or poly ADP-ribose polymerase
telomeric repeat binding factor
General
ankyrin repeat domain protein (ANKRD)
tankyrase
Properties
SIZE: entity length = 1166 aa
MW = 127 kD
COMPARTMENT: cytoplasm
cell nucleus
golgi
MOTIF: ankyrin repeat
NAME: ankyrin repeat
SITE: 57-89
ankyrin repeat
NAME: ankyrin repeat
SITE: 90-122
ankyrin repeat
NAME: ankyrin repeat
SITE: 123-155
ankyrin repeat
NAME: ankyrin repeat
SITE: 210-242
ankyrin repeat
NAME: ankyrin repeat
SITE: 243-275
ankyrin repeat
NAME: ankyrin repeat
SITE: 276-308
ankyrin repeat
NAME: ankyrin repeat
SITE: 363-398
ankyrin repeat
NAME: ankyrin repeat
SITE: 399-431
ankyrin repeat
NAME: ankyrin repeat
SITE: 432-464
ankyrin repeat
NAME: ankyrin repeat
SITE: 525-557
ankyrin repeat
NAME: ankyrin repeat
SITE: 558-590
ankyrin repeat
NAME: ankyrin repeat
SITE: 591-623
ankyrin repeat
NAME: ankyrin repeat
SITE: 678-710
ankyrin repeat
NAME: ankyrin repeat
SITE: 711-743
ankyrin repeat
NAME: ankyrin repeat
SITE: 744-776
sterile alpha motif
NAME: sterile alpha motif
SITE: 873-936
catalytic domain
SITE: 959-1164
Database Correlations
OMIM 607128
UniProt Q9H2K2
PFAM correlations
Entrez Gene 80351
Kegg hsa:80351
ENZYME 2.4.2.30
References
UniProt :accession Q9H2K2