PNKP
Domain
The FHA domain binds threonine-phosphorylated peptides from XRCC1/4, and is responsible for the recruitment of PNKP to the sites of DNA repair. The affinity is ten times greater if peptides are also phosphorylated on the serine preceeding the phosphothreonine.
Function
Plays a key role in the repair of DNA damage, functioning as part of both the non-homologous end-joining (NHEJ) and base excision repair (BER) pathways (PubMed:10446192, PubMed:10446193, PubMed:15385968, PubMed:20852255, PubMed:28453785). Through its two catalytic activities, PNK ensures that DNA termini are compatible with extension and ligation by either removing 3'-phosphates from, or by phosphorylating 5'-hydroxyl groups on, the ribose sugar of the DNA backbone (PubMed:10446192, PubMed:10446193).
Involvement in disease
Microcephaly, seizures, and developmental delay
MCSZ
An autosomal recessive neurodevelopmental disorder characterized by infantile-onset seizures, microcephaly, severe intellectual disability and delayed motor milestones with absent speech or only achieving a few words. Most patients also have behavioral problems with hyperactivity. Microcephaly is progressive and without neuronal migration or structural abnormalities, consistent with primary microcephaly.
None
The disease is caused by variants affecting the gene represented in this entry.
Ataxia-oculomotor apraxia 4
AOA4
An autosomal recessive disease characterized by cerebellar ataxia, oculomotor apraxia, areflexia and peripheral neuropathy.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
In the N-terminal section; belongs to the DNA 3' phosphatase family.
Tissue Specificity
Expressed in many tissues with highest expression in spleen and testis, and lowest expression in small intestine (PubMed:10446192). Expressed in higher amount in pancreas, heart and kidney and at lower levels in brain, lung and liver (PubMed:10446193).
Cellular localization
- Nucleus
- Chromosome
- Localizes to site of double-strand breaks.
Alternative names
Bifunctional polynucleotide phosphatase/kinase, DNA 5'-kinase/3'-phosphatase, Polynucleotide kinase-3'-phosphatase, PNKP