Activating Compound | Comment | Organism | Structure |
---|---|---|---|
XRCC1 | mechanism underlying XRCC1-induced stimulation of PNKP, XRCC1 displaces PNKP from the reaction product, and addition of XRCC1 increases PNKP enzymatic turnover | Homo sapiens | |
XRCC1 | mechanism underlying XRCC1-induced stimulation of PNKP, XRCC1 displaces PNKP from the reaction product, and addition of XRCC1 increases PNKP enzymatic turnover. Phosphorylation of XRCC1 by CK2 stimulates the kinase and phosphatase activities of PNKP | Mus musculus | |
XRCC4 | - |
Mus musculus | |
XRCC4 | - |
Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
crystal structure determination and analysis | Mus musculus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Mus musculus | PNKP function is modulated by interaction with the DNA repair scaffold proteins XRCC1 and XRCC4, which is mediated by binding of the PNKP forkhead-associated domain to phosphorylated motifs on XRCC1 and XRCC4, overview | ? | - |
? | |
additional information | Homo sapiens | PNKP function is modulated by interaction with the DNA repair scaffold proteins XRCC1 and XRCC4, which is mediated by binding of the PNKP forkhead-associated domain to phosphorylated motifs on XRCC1 and XRCC4, overview. Phosphorylation-independent interaction between PNKP and XRCC1 in human cells, since a non-phosphorylated XRCC1S518A/T519A/T523A triple mutant is also bound | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Mus musculus | - |
- |
- |
Schizosaccharomyces pombe | - |
- |
- |
Tequatrovirus T4 | - |
- |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | PNKP function is modulated by interaction with the DNA repair scaffold proteins XRCC1 and XRCC4, which is mediated by binding of the PNKP forkhead-associated domain to phosphorylated motifs on XRCC1 and XRCC4, overview | Mus musculus | ? | - |
? | |
additional information | PNKP function is modulated by interaction with the DNA repair scaffold proteins XRCC1 and XRCC4, which is mediated by binding of the PNKP forkhead-associated domain to phosphorylated motifs on XRCC1 and XRCC4, overview. Phosphorylation-independent interaction between PNKP and XRCC1 in human cells, since a non-phosphorylated XRCC1S518A/T519A/T523A triple mutant is also bound | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | PNKP is a multi-domain enzyme that consists of an N-terminal forkhead-associated domain and a C-terminal catalytic domain composed of fused phosphatase and kinase subdomains | Homo sapiens |
More | PNKP is a multi-domain enzyme that consists of an N-terminal forkhead-associated domain and a C-terminal catalytic domain composed of fused phosphatase and kinase subdomains. The forkhead-associated domain is linked to the catalytic domain through a flexible polypeptide segment and acts to selectively bind acidic casein kinase 2-phosphorylated regions in XRCC1 and XRCC4, which are key scaffolding proteins in the repair of DNA single and double strand breaks, respectively. Two catalytic active sites are positioned on the same side of the protein | Mus musculus |
More | PNKP is a multi-domain enzyme that consists of an N-terminal forkhead-associated domain and a C-terminal catalytic domain composed of fused phosphatase and kinase subdomains. The forkhead-associated domain is linked to the catalytic domain through a flexible polypeptide segment and acts to selectively bind acidic casein kinase 2-phosphorylated regions in XRCC1 and XRCC4, which are key scaffolding proteins in the repair of DNA single and double strand breaks, respectively. Two catalytic active sites are positioned on the same side of the protein | Tequatrovirus T4 |
Synonyms | Comment | Organism |
---|---|---|
Pnk1 | - |
Schizosaccharomyces pombe |
PNKP | - |
Mus musculus |
PNKP | - |
Homo sapiens |
PNKP | - |
Tequatrovirus T4 |
polynucleotide kinase/phosphatase | - |
Mus musculus |
polynucleotide kinase/phosphatase | - |
Homo sapiens |
polynucleotide kinase/phosphatase | - |
Schizosaccharomyces pombe |
polynucleotide kinase/phosphatase | - |
Tequatrovirus T4 |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Schizosaccharomyces pombe | |
ATP | the ATP binding site is defined by the Walker A (P-loop) and B motifs conserved in various kinases, as well as an Asp residue that activates the 5'-OH for attack on the ATP gamma-phosphate | Tequatrovirus T4 | |
ATP | the ATP binding site is defined by the Walker A (P-loop) and B motifs conserved in various kinases, as well as an Asp396 that activates the 5'-OH for attack on the ATP gamma-phosphate | Mus musculus | |
ATP | the ATP binding site is defined by the Walker A (P-loop) and B motifs conserved in various kinases, as well as an Asp396 that activates the 5'-OH for attack on the ATP gamma-phosphate | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | Pnk1 deletion in fission yeast renders cells sensitive to camptothecin | Schizosaccharomyces pombe |
malfunction | PNKP depletion in human cells renders cells sensitive to camptothecin. A small molecule inhibitor of PNKP phosphatase activity enhances the sensitivity of cells to IR and camptothecin. Enzyme mutational defects can cause neurological disorders with various symptoms, e.g. a severe neurological autosomal recessive disease characterized by microcephaly, intractable seizures and developmental delay | Homo sapiens |
additional information | molecular architecture of the enzyme, overview. The mammalian enzyme preferentially phosphorylates 5'-hydroxyl termini within nicked, gapped or double-strand breaks with single-stranded 3'-overhanging ends, whereas single-stranded 5'-termini or blunt double-stranded ends are phosphorylated less efficiently. The selective recognition of the larger, double-stranded DNA substrates is effected by a broad DNA recognition groove composed of two distinct positively charged surfaces. Mechanisms of single-strand break and double-strand break repairs, and of base excision repair, overview | Homo sapiens |
additional information | molecular architecture of the enzyme, overview. The mammalian enzyme preferentially phosphorylates 5'-hydroxyl termini within nicked, gapped or DSBs with single-stranded 3' overhanging ends, whereas single-stranded 5'-termini or blunt double-stranded ends are phosphorylated less efficiently. The selective recognition of the larger, double-stranded DNA substrates is effected by a broad DNA recognition groove composed of two distinct positively charged surfaces. Mechanisms of single-strand break and double-strand break repairs, and base excision repair, overview | Mus musculus |
additional information | molecular architecture of the enzyme, overview. The phage PNK DNA binding cleft forms a narrow channel leading to the conserved catalytic aspartic acid residue that accommodates single-stranded, but not double-stranded, substrates. Mechanisms of single-strand break and double-strand break repairs, overview | Tequatrovirus T4 |
physiological function | polynucleotide kinase/phosphatase is an essential enzyme for the repair of damaged DNA termini. PNKP possesses both 5'-kinase and 3'-phosphatase activities that are frequently required for processing of single- and double-strand break termini | Mus musculus |
physiological function | polynucleotide kinase/phosphatase is an essential enzyme for the repair of damaged DNA termini. PNKP possesses both 5'-kinase and 3'-phosphatase activities that are frequently required for processing of single- and double-strand break termini | Homo sapiens |
physiological function | polynucleotide kinase/phosphatase is an essential enzyme for the repair of damaged DNA termini. PNKP possesses both 5'-kinase and 3'-phosphatase activities that are frequently required for processing of single- and double-strand break termini | Schizosaccharomyces pombe |
physiological function | polynucleotide kinase/phosphatase is an essential enzyme for the repair of damaged DNA termini. PNKP possesses both 5'-kinase and 3'-phosphatase activities that are frequently required for processing of single- and double-strand break termini | Tequatrovirus T4 |