Cloned (Comment) | Organism |
---|---|
gene PANK1, PANK1alpha and PANK1beta are splice variants of the PANK1 gene | Mus musculus |
gene PANK1, PANK1alpha and PANK1beta are splice variants of the PANK1 gene | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
G19V | site-directed mutagenesis, PANK3(G19V) cannot bind ATP, and biochemical analyses of an engineered PANK3/PANK3(G19V) heterodimer confirmed that the two active sites are functionally coupled. Analysis of PANK3/PANK3(G19V) heterodimers, overview | Homo sapiens |
additional information | generation of unction Pank1-/-Pank2-/-, Pank1-/-Pank3-/-, and Pank2-/- Pank-/-double knock-out mice | Mus musculus |
additional information | generation of unction Pank1-/-Pank2-/-, Pank1-/-Pank3-/-, and Pank2-/-Pank-/-3 double knock-out mice | Mus musculus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
acetyl-CoA | feedback inhibition, competitive versus ATP, but acetyl-CoA binds far more tightly than ATP. The 1alpha and 1beta isoforms are least sensitive to inhibition, whereas isoforms 2 and 3 are more potently inhibited by acetyl-CoA; feedback inhibition, competitive versus ATP, but acetyl-CoA binds far more tightly than ATP. The 1alpha and 1beta isoforms are least sensitive to inhibition, whereas isoforms 2 and 3 are more potently inhibited by acetyl-CoA; feedback inhibition, competitive versus ATP, but acetyl-CoA binds far more tightly than ATP. The 1alpha and 1beta isoforms are least sensitive to inhibition, whereas isoforms 2 and 3 are more potently inhibited by acetyl-CoA | Homo sapiens | |
acetyl-CoA | feedback inhibition, competitive versus ATP, but acetyl-CoA binds far more tightly than ATP. The 1alpha and 1beta isoforms are least sensitive to inhibition, whereas isoforms 2 and 3 are more potently inhibited by acetyl-CoA; feedback inhibition, competitive versus ATP, but acetyl-CoA binds far more tightly than ATP. The 1alpha and 1beta isoforms are least sensitive to inhibition, whereas isoforms 2 and 3 are more potently inhibited by acetyl-CoA; feedback inhibition, competitive versus ATP, but acetyl-CoA binds far more tightly than ATP. The 1alpha and 1beta isoforms are least sensitive to inhibition, whereas isoforms 2 and 3 are more potently inhibited by acetyl-CoA. Comparison of the overall structures of the actyl-CoA-bound inactive and the active PANK3 conformations, overview | Mus musculus |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | allosteric regulation of mammalian pantothenate kinase | Mus musculus | |
additional information | - |
additional information | allosteric regulation of mammalian pantothenate kinase | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytosol | human isozyme 3 is cytosolic | Homo sapiens | 5829 | - |
cytosol | isozyme 2 of mice is cytosolic | Mus musculus | 5829 | - |
cytosol | isozyme 3 of mice is cytosolic | Mus musculus | 5829 | - |
endosome | isozyme 1beta | Mus musculus | 5768 | - |
endosome | isozyme 1beta | Homo sapiens | 5768 | - |
mitochondrion | - |
Homo sapiens | 5739 | - |
additional information | isoform 1alpha is targeted to the nucleus, whereas isoform 1beta is associated with endosomes | Mus musculus | - |
- |
additional information | isoform 1alpha is targeted to the nucleus, whereas isoform 1beta is associated with endosomes | Homo sapiens | - |
- |
additional information | the PANK2 gene in humans encodes a protein with both nuclear localization and mitochondrial targeting sequences. Human PANK2 accumulates in the intra-membrane space in mitochondria | Homo sapiens | - |
- |
nucleus | - |
Homo sapiens | 5634 | - |
nucleus | isozyme 1alpha | Mus musculus | 5634 | - |
nucleus | isozyme 1alpha | Homo sapiens | 5634 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Mus musculus | |
Mg2+ | required | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + (R)-pantothenate | Mus musculus | - |
ADP + (R)-4'-phosphopantothenate | - |
? | |
ATP + (R)-pantothenate | Homo sapiens | - |
ADP + (R)-4'-phosphopantothenate | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q8TE04 | - |
- |
Homo sapiens | Q9BZ23 | - |
- |
Homo sapiens | Q9H999 | - |
- |
Mus musculus | - |
- |
- |
Mus musculus | Q8K4K6 | - |
- |
Mus musculus | Q8R2W9 | - |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + (R)-pantothenate | - |
Mus musculus | ADP + (R)-4'-phosphopantothenate | - |
? | |
ATP + (R)-pantothenate | - |
Homo sapiens | ADP + (R)-4'-phosphopantothenate | - |
? |
Subunits | Comment | Organism |
---|---|---|
homodimer | - |
Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
hPanK1 | - |
Homo sapiens |
hPANK2 | - |
Homo sapiens |
hPanK3 | - |
Homo sapiens |
mPank1 | - |
Mus musculus |
mPanK2 | - |
Mus musculus |
mPanK3 | - |
Mus musculus |
PanK | - |
Mus musculus |
PanK | - |
Homo sapiens |
PanK1 | - |
Mus musculus |
PanK1 | - |
Homo sapiens |
PanK2 | - |
Mus musculus |
PanK2 | - |
Homo sapiens |
PanK3 | - |
Homo sapiens |
PanK3 | - |
Mus musculus |
pantothenate kinase 1 | - |
Mus musculus |
pantothenate kinase 1 | - |
Homo sapiens |
pantothenate kinase 2 | - |
Mus musculus |
pantothenate kinase 2 | - |
Homo sapiens |
pantothenate kinase 3 | - |
Homo sapiens |
pantothenate kinase 3 | - |
Mus musculus |
General Information | Comment | Organism |
---|---|---|
evolution | isozyme PANK3 belongs to the ASKHA kinase superfamily, which typically uses either an Asp or Glu residue as the catalytic base to activate the substrate hydroxyl for attack on the gamma-phosphate of ATP | Mus musculus |
evolution | isozyme PANK3 belongs to the ASKHA kinase superfamily, which typically uses either an Asp or Glu residue as the catalytic base to activate the substrate hydroxyl for attack on the gamma-phosphate of ATP. Glu138 appears to be the logical candidate for the catalytic base | Homo sapiens |
malfunction | mutant Pank1-/-Pank2-/- double knock-out mice are unable to metabolize fats and ketones resulting in early postnatal death, and Pank1-/-Pank3-/- and Pank2-/- Pank-/- double knock-out mice are both embryonic lethal. A chemical knockout of all pantothenate kinases in adult mice results in an 80% reduction in hepatic CoA levels and death within days | Mus musculus |
malfunction | mutant Pank1-/-Pank2-/- double knock-out mice are unable to metabolize fats and ketones resulting in early postnatal death, and Pank1-/-Pank3-/- and Pank2-/- Pank-/-x03 double knock-out mice are both embryonic lethal. A chemical knockout of all pantothenate kinases in adult mice results in an 80% reduction in hepatic CoA levels and death within days | Mus musculus |
malfunction | mutant Pank1-/-Pank2-/- double knock-out mice are unable to metabolize fats and ketones resulting in early postnatal death, and Pank1-/-Pank3-/- and Pank2-/-Pank3-/- double knock-out mice are both embryonic lethal. A chemical knockout of all pantothenate kinases in adult mice results in an 80% reduction in hepatic CoA levels and death within days | Mus musculus |
additional information | comparison of the human PANK3x02acetyl-CoA complex to the structures of PANK3 in four catalytically relevant complexes, 5'-adenylyl-beta,gamma-imidodiphosphate (AMPPNP)x02Mg2+, MPPNP-Mg2+-pantothenate, ADP-Mg2+-phosphopantothenate, and AMP phosphoramidate (AMPPN)-Mg2+, all reveal a large conformational change in the dimeric enzyme. The amino-terminal nucleotide binding domain rotates to close the active site, and this allows the P-loop to engage ATP and facilitates required substrate/product interactions at the active site. The transition between the inactive and active conformations, as assessed by the binding of either ATP-Mg2+ or acyl-CoA to PANK3, is highly cooperative indicating that both protomers move in concert. The communication between the two protomers is mediated by an alpha-helix that interacts with the ATP-binding site at its amino terminus and with the substrate/inhibitor-binding site of the opposite protomer at its carboxyl terminus. The two alpha-helices within the dimer together with the bound ligands create a ring that stabilizes the assembly in either the active closed conformation or the inactive open conformation. Thus, both active sites of the dimeric mammalian pantothenate kinases coordinately switch between the on and off states in response to intracellular concentrations of ATP and its key negative regulators, acetyl(acyl)-CoA. Analysis of PANK3 catalytic intermediates. Glu138 appears to be the logical candidate for the catalytic base, binding structure, and substrate/product interactions within the active site during the PANK3 catalytic cycle, detailed overview | Homo sapiens |
physiological function | allosteric regulation of mammalian pantothenate kinase. Pantothenate kinase is the master regulator of CoA biosynthesis and is feedback-inhibited by acetyl-CoA | Mus musculus |
physiological function | allosteric regulation of mammalian pantothenate kinase. Pantothenate kinase is the master regulator of CoA biosynthesis and is feedback-inhibited by acetyl-CoA | Homo sapiens |