Search
tankyrase-1; TANK1; poly [ADP-ribose] polymerase 5A; TNKS-1; TRF1-interacting ankyrin-related ADP-ribose polymerase (TNKS, PARP5A, PARPL, TIN1, TINF1, TNKS1)
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
- 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
Structure:
- contains 15 ANK repeats
- contains 1 PARP catalytic domain
- contains 1 SAM (sterile alpha motif) domain
Compartment:
- 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
Alternative splicing: named isoforms=2
Expression:
- ubiquitous
- highest levels in testis
Related
182 kD tankyrase-1-binding protein (TNKS1BP1, KIAA1741, TAB182)
ankyrin
NAD+ ADP-ribosyltransferase or poly ADP-ribose polymerase
telomeric repeat binding factor
General
ankyrin repeat domain protein (ANKRD)
phosphoprotein
tankyrase
Properties
SIZE: entity length = 1327 aa
MW = 142 kD
COMPARTMENT: cytoplasm
cell nucleus
golgi
MOTIF: histidine-rich region {9-14}
MOTIF: histidine residue (SEVERAL)
proline-rich region
SITE: 27-34
MOTIF: proline residue (SEVERAL)
serine-rich region {128-134}
MOTIF: serine residue (SEVERAL)
serine-rich region {137-145}
MOTIF: serine residue (SEVERAL)
ankyrin repeat
NAME: ankyrin repeat
SITE: 215-247
ankyrin repeat
NAME: ankyrin repeat
SITE: 248-280
ankyrin repeat
NAME: ankyrin repeat
SITE: 281-313
Ser phosphorylation site {S365}
ankyrin repeat
NAME: ankyrin repeat
SITE: 368-400
ankyrin repeat
NAME: ankyrin repeat
SITE: 401-433
ankyrin repeat
NAME: ankyrin repeat
SITE: 434-466
ankyrin repeat
NAME: ankyrin repeat
SITE: 521-556
ankyrin repeat
NAME: ankyrin repeat
SITE: 557-589
ankyrin repeat
NAME: ankyrin repeat
SITE: 590-622
ankyrin repeat
NAME: ankyrin repeat
SITE: 683-715
ankyrin repeat
NAME: ankyrin repeat
SITE: 716-748
ankyrin repeat
NAME: ankyrin repeat
SITE: 749-781
ankyrin repeat
NAME: ankyrin repeat
SITE: 836-868
ankyrin repeat
NAME: ankyrin repeat
SITE: 869-901
ankyrin repeat
NAME: ankyrin repeat
SITE: 902-934
sterile alpha motif
NAME: sterile alpha motif
SITE: 1030-1089
catalytic domain
SITE: 1112-1317
Database Correlations
OMIM 603303
UniProt O95271
PFAM correlations
Entrez Gene 8658
Kegg hsa:8658
ENZYME 2.4.2.30
References
UniProt :accession O95271