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FLASH GENE

Symbol

PNKP

contributors: mct/npt/pgu - updated : 25-03-2016

HGNC name	polynucleotide kinase 3'-phosphatase
HGNC id	9154

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

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 Endocrine pancreas       highly Reproductive female system uterus cervix   highly   female system ovary     highly Urinary kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a putative ATP binding site
	a 3'phosphatase domain with similarity to L-2-haloacid dehalogenases
	a P-loop motif, and a second motif associated with several different phosphatases

HOMOLOGY

Homologene

FAMILY

DNA 3' phosphatase family (in the N-terminal section)

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,chromatin/chromosome
	intracellular,nucleus,nucleolus
text	presence of NEIL2 and PNKP in mitochondria

basic FUNCTION	5'-DNA kinase and 3'phosphatase facilitating DNA repair of DNA single strand breaks caused by ionizing radiation or oxidative damage
	direct, specific role in double-strand break repair
	bifunctional enzyme possessing a 5'-DNA kinase activity and a 3'-phosphatase activity
	required to process unligatable strand break termini generated directly by many genotoxic agents
	participates in repair of DNA double-strand breaks by nonhomologous end joining but not homologous recombination
	involved in multiple repair pathways (BER, SSBR, and double strand break repair), so its abundance may be a requirement for the cells
	involved in a poly(ADP-ribose) polymerase-1-dependent DNA double-strand breaks rejoining pathway
	may have a role in several DNA repair pathways
	implicated in repair of both double-strand breaks (DSBs) and single-strand breaks
	critical role of NEIL2 and PNKP in maintenance of the mammalian mitochondrial genome
	is a relatively abundant DNA repair protein in mitochondria
	plays a major role in repair of oxidized bases in the mitochondrial genome
	is a dual-function enzyme with a key role in different pathways of DNA damage repair. DNA repair disorders can result in accelerated cell death, leading to underdevelopment and neurodegeneration
	dual-function enzyme with a key role in different pathways of DNA-damage repair

CELLULAR PROCESS

nucleotide, repair

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	unphosphorylated XRCC4 interacts with PNKP through a lower affinity interaction site within the catalytic domain and this interaction stimulates the turnover of PNKP
	XRCC1 can interact with the catalytic domain of PNKP and stimulate PNKP activity
	interacting with XRCC1 (a major function of XRCC1 is to stimulate PNKP activity by displacing PNKP from the phosphorylated DNA product)
	binds to a phosphorylated segment of XRCC1 (between its two C-terminal BRCT domains) via its Forkhead-associated (FHA) domain
	PNKP is an ATM target
	co-association of NEIL2 and PNKP with POLG on the mitochondrial genome
	interact with DNA repair proteins involved in the onset of polyneuropathy and cerebellar degeneration
	DNA repair partners of TDP1 include PARP1, XRCC1, ligase III and PNKP from the base excision repair (BER) pathway
	overlapping roles for PARP1 and PARP2 in the recruitment of endogenous XRCC1 and PNKP into oxidized chromatin
	XRCC1 and PNKP interact via a high-affinity phosphorylation-dependent interaction site in XRCC1 and a forkhead-associated domain in PNKP
	repair function of PNKP is facilitated by its binding to the scaffold protein XRCC1, and phosphorylation of XRCC1 by CSNK2A2 at several consensus sites enables PNKP binding and recruitment to DNA damage

cell & other

REGULATION

activated by

XRCC1 at damaged DNA termini in order to accelerate DNA single strand break repair

Phosphorylated by

ATM (ATM-mediated phosphorylation of PNKP is required for effective DNA double-strand break repair)

ASSOCIATED DISORDERS

corresponding disease(s)

MCSZ , AOA4

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS