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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	10q23.32      Physical location : 93.558.150 - 93.625.231
Synonym name	tankyrase 2
	tankyrase-like protein
	poly [ADP-ribose] polymerase 5B
	ADP-ribosyltransferase diphtheria toxin-like 6
	TRF1-interacting ankyrin-related ADP-ribose polymerase 2
Synonym symbol(s)	TNKL, TANK2, PARP5B, PARP5C, PARP-5b, PARP-5c, ARTD6
EC.number	2.4.2.30

DNA

TYPE	functioning gene
STRUCTURE	67.08 kb     27 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence

Promoter

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_025235 27 - 6274 NP_079511 - 1166 - -

EXPRESSION

Type

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Digestive intestine large intestine colon   highly   intestine small intestine     highly   liver       highly Endocrine pancreas       highly Lymphoid/Immune lymph node       highly   spleen       highly   thymus       highly Nervous brain       highly   spinal cord       highly Reproductive female system breast mammary gland   highly   female system placenta     highly   female system ovary     highly   male system prostate     highly   male system testis     highly Respiratory lung       highly Mus musculus Fetal Urinary kidney       highly Mus musculus Fetal

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte

cell lineage
cell lines	breast carcinoma, meningioma
fluid/secretion

at STAGE

physiological period

fetal

Text	liver, heart, brain

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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