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Literature summary for 2.7.1.23 extracted from
- Structure and function of NAD kinase and NADP phosphatase: key enzymes that regulate the intracellular balance of NAD(H) and NADP(H) (2008), Biosci. Biotechnol. Biochem., 72, 919-930.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| Calmodulin | Ca2+/calmodulin regulates NAD kinase activity. Ca2+/calmodulin has no detectable effect on recombinant human NAD kinase | Homo sapiens |  |
| H2O2 | upregulates NADK1 by 3fold after treatment of plant cells with 5 mM | Arabidopsis thaliana | |
| additional information | irradiation upregulates NADK1 by 8fold. NADK1 is Ca2+/calmodulin-independent, and not activated by Ca2+/calmodulin | Arabidopsis thaliana | |
| additional information | is not regulated by NADH | Micrococcus luteus | |
| additional information | NADK2 is Ca2+/calmodulin-independent, and not activated by Ca2+/calmodulin, although recombinant NADK2, which has a calmodulin-binding motif in its N-terminal, is able to bind to calmodulin | Arabidopsis thaliana | |
| additional information | NADK3 is Ca2+/calmodulin-independent, and not activated by Ca2+/calmodulin | Arabidopsis thaliana |
Application
| Application | Comment | Organism |
|---|---|---|
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Cyberlindnera jadinii |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Glycine max |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Dictyostelium discoideum |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Triticum sp. |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Schizosaccharomyces pombe |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Candida albicans |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Lactuca sativa |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Oryza sativa |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Salmonella enterica |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Sorghum sp. |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Columba livia |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Archaeoglobus fulgidus |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Thermotoga maritima |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Listeria monocytogenes |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Homo sapiens |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Synechococcus elongatus PCC 6301 |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Mycobacterium tuberculosis |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Arabidopsis thaliana |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Saccharomyces cerevisiae |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Methanocaldococcus jannaschii |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Pyrococcus horikoshii |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Bacillus subtilis |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Escherichia coli |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Sphingomonas sp. A1 |
| additional information | one of the key enzymes regulating the balance of NAD(H) and NADP(H) | Micrococcus luteus |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
- |
Homo sapiens |
- |
Arabidopsis thaliana |
- |
Methanocaldococcus jannaschii |
| overexpression of UTR1 via a high-copy plasmid | Saccharomyces cerevisiae |
| overexpression of YEF1 via a high-copy plasmid | Saccharomyces cerevisiae |
| Ppnk overexpressed | Mycobacterium tuberculosis |
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| apo form of Ppnk at 2.8 A resolution. Crystals belong to space group C2 (a=140.2, b=69.4, c=106.4 A, and beta=130°). Holo form of Ppnk complexed with NAD+ at 2.6 A resolution. Crystals belong space group to P62 (a=b=110.5 and c=108.9 A). Overall structures of apo-Ppnk and Ppnk-NAD consist of an N-domain (residues 1-138 and 279-283), a C-domain (residues 139-278), and a C-terminal tail (residues 284-307) | Mycobacterium tuberculosis |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | mutant for NadF is lethal | Bacillus subtilis |
| additional information | mutants of the NAD kinase gene are lethal | Salmonella enterica |
| additional information | mutants of the NAD kinase gene are lethal | Mycobacterium tuberculosis |
| additional information | NADK1-deficient mutant exhibits sensitivity to gamma irradiation and paraquat-induced oxidative stress | Arabidopsis thaliana |
| additional information | NADK2-deficient mutant grows slowly, is sensitive to environmental stress, which leads to oxidative stress, and shows reduced chlorophyll content. NADK1-deficient mutant exhibits sensitivity to gamma irradiation and paraquat-induced oxidative stress | Arabidopsis thaliana |
| additional information | sensitivity of NADK(-) cells to oxidative stress is the same as that of the control cells | Homo sapiens |
| additional information | triple mutant utr1yef1pos5 is lethal | Saccharomyces cerevisiae |
| additional information | triple mutant utr1yef1pos5 is lethal. Double mutant utr1pos5 is lethal against the SEY6210.5 and S288c backgrounds | Saccharomyces cerevisiae |
| additional information | triple mutant utr1yef1pos5 is lethal. Double mutant utr1pos5 is lethal against the SEY6210.5 and S288c backgrounds. Mutant for POS5 shows several phenotypes related to decreased NADPH concentration in the mitochondria, and consequently, decreased mitochondrial function | Saccharomyces cerevisiae |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| additional information | utr1 shows slow growth in a low-iron medium | Saccharomyces cerevisiae | |
| NADH | - |
Escherichia coli | |
| NADH | - |
Salmonella enterica | |
| NADPH | - |
Escherichia coli | |
| NADPH | - |
Homo sapiens | |
| NADPH | - |
Salmonella enterica | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.18 | - |
NADP+ | - |
Methanocaldococcus jannaschii | |
| 0.3 | - |
NADPH | - |
Methanocaldococcus jannaschii | |
| 0.43 | - |
fructose-1,6-bisphosphate | - |
Methanocaldococcus jannaschii | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| chloroplast | - |
Arabidopsis thaliana | 9507 | - |
| chloroplast | isoform NADK2 | Arabidopsis thaliana | 9507 | - |
| cytoplasm | - |
Homo sapiens | 5737 | - |
| cytosol | - |
Saccharomyces cerevisiae | 5829 | - |
| mitochondrion | - |
Saccharomyces cerevisiae | 5739 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Ca2+ | Ca2+/calmodulin regulates NAD kinase activity. Ca2+/calmodulin has no detectable effect on recombinant human NAD kinase | Homo sapiens | |
| Ca2+ | Ca2+/calmodulin-binding domain | Glycine max | |
| Ca2+ | Ca2+/calmodulin-binding domain | Triticum sp. | |
| Ca2+ | Ca2+/calmodulin-binding domain | Lactuca sativa | |
| Ca2+ | Ca2+/calmodulin-binding domain | Oryza sativa | |
| Ca2+ | Ca2+/calmodulin-binding domain | Sorghum sp. | |
| Cu2+ | POS5 is upregulated 3.4fold after treatment for 10 to 12 min with 2.5 mM | Saccharomyces cerevisiae | |
| additional information | NADK1 is Ca2+/calmodulin-independent, and not activated by Ca2+/calmodulin | Arabidopsis thaliana | |
| additional information | NADK2 is Ca2+/calmodulin-independent, and not activated by Ca2+/calmodulin | Arabidopsis thaliana | |
| additional information | NADK3 is Ca2+/calmodulin-independent, and not activated by Ca2+/calmodulin | Arabidopsis thaliana |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 30000 | - |
2 * 30000 | Bacillus subtilis |
| 32000 | - |
2 * 32000 | Sphingomonas sp. A1 |
| 37000 | - |
4 * 37000 | Pyrococcus horikoshii |
| 46000 | - |
x * 46000 | Saccharomyces cerevisiae |
| 49000 | - |
4 * 49000 | Homo sapiens |
| 60000 | - |
6 * 60000 | Saccharomyces cerevisiae |
| 60000 | - |
8 * 60000 | Saccharomyces cerevisiae |
| 60000 | - |
6 * 60000, Utr1p | Saccharomyces cerevisiae |
| 60000 | - |
6 * 60000, Yef1p | Saccharomyces cerevisiae |
| 110000 | - |
isoform NADK2 | Arabidopsis thaliana |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Arabidopsis thaliana | - |
- |
- |
| Arabidopsis thaliana | Q500Y9 | - |
- |
| Arabidopsis thaliana | Q56YN3 | - |
- |
| Arabidopsis thaliana | Q9C5W3 | - |
- |
| Archaeoglobus fulgidus | - |
- |
- |
| Bacillus subtilis | O31612 | - |
- |
| Bacillus subtilis | O34934 | - |
- |
| Candida albicans | - |
- |
- |
| Columba livia | - |
- |
- |
| Cyberlindnera jadinii | - |
- |
- |
| Dictyostelium discoideum | - |
- |
- |
| Escherichia coli | P0A7B3 | - |
- |
| Glycine max | - |
- |
- |
| Homo sapiens | - |
- |
- |
| Homo sapiens | O95544 | - |
- |
| Lactuca sativa | - |
- |
- |
| Listeria monocytogenes | - |
- |
- |
| Methanocaldococcus jannaschii | Q58327 | - |
- |
| Micrococcus luteus | Q8VUL9 | - |
- |
| Mycobacterium tuberculosis | P9WHV7 | - |
- |
| Mycobacterium tuberculosis H37Rv | P9WHV7 | - |
- |
| Oryza sativa | - |
- |
- |
| Pyrococcus horikoshii | O58801 | - |
- |
| Saccharomyces cerevisiae | C7GKE4 | - |
- |
| Saccharomyces cerevisiae | P21373 | - |
- |
| Saccharomyces cerevisiae | P32622 | - |
- |
| Saccharomyces cerevisiae | Q06892 | - |
- |
| Salmonella enterica | - |
- |
- |
| Schizosaccharomyces pombe | - |
- |
- |
| Sorghum sp. | - |
- |
- |
| Sphingomonas sp. A1 | Q6L7J5 | - |
- |
| Synechococcus elongatus PCC 6301 | - |
- |
- |
| Thermotoga maritima | - |
- |
- |
| Triticum sp. | - |
- |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
- |
Cyberlindnera jadinii |
- |
Columba livia |
- |
Homo sapiens |
- |
Methanocaldococcus jannaschii |
| partially purified | Arabidopsis thaliana |
| partially purified | Saccharomyces cerevisiae |
| Rv1695 protein | Mycobacterium tuberculosis |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| heart | - |
Columba livia | - |
| liver | - |
Columba livia | - |
| neutrophil | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + NAD+ | - |
Homo sapiens | ADP + NADP+ | - |
? | |
| ATP + NAD+ | - |
Salmonella enterica | ADP + NADP+ | - |
? | |
| ATP + NAD+ | - |
Mycobacterium tuberculosis | ADP + NADP+ | - |
? | |
| ATP + NAD+ | - |
Arabidopsis thaliana | ADP + NADP+ | - |
? | |
| ATP + NAD+ | - |
Saccharomyces cerevisiae | ADP + NADP+ | - |
? | |
| ATP + NAD+ | - |
Methanocaldococcus jannaschii | ADP + NADP+ | - |
? | |
| ATP + NAD+ | - |
Pyrococcus horikoshii | ADP + NADP+ | - |
? | |
| ATP + NAD+ | - |
Bacillus subtilis | ADP + NADP+ | - |
? | |
| ATP + NAD+ | - |
Escherichia coli | ADP + NADP+ | - |
? | |
| ATP + NAD+ | - |
Sphingomonas sp. A1 | ADP + NADP+ | - |
? | |
| ATP + NAD+ | - |
Micrococcus luteus | ADP + NADP+ | - |
? | |
| ATP + NAD+ | 100% activity | Arabidopsis thaliana | ADP + NADP+ | - |
? | |
| ATP + NAD+ | - |
Mycobacterium tuberculosis H37Rv | ADP + NADP+ | - |
? | |
| ATP + NADH | - |
Homo sapiens | ADP + NADPH | - |
? | |
| ATP + NADH | - |
Arabidopsis thaliana | ADP + NADPH | - |
? | |
| ATP + NADH | - |
Methanocaldococcus jannaschii | ADP + NADPH | - |
? | |
| ATP + NADH | - |
Pyrococcus horikoshii | ADP + NADPH | - |
? | |
| ATP + NADH | - |
Micrococcus luteus | ADP + NADPH | - |
? | |
| ATP + NADH | low activity | Mycobacterium tuberculosis | ADP + NADPH | - |
? | |
| ATP + NADH | higher activity with NADH than with NAD+ | Saccharomyces cerevisiae | ADP + NADPH | - |
? | |
| ATP + NADH | low activity with NADH | Saccharomyces cerevisiae | ADP + NADPH | - |
? | |
| ATP + NADH | isoform Utr1p displays 15% activity with NADH compared to NAD+ | Saccharomyces cerevisiae | ADP + NADPH | - |
? | |
| ATP + NADH | while isoform Yef1p displays 15% activity with NADH compared to NAD+ | Saccharomyces cerevisiae | ADP + NADPH | - |
? | |
| ATP + NADH | low activity | Mycobacterium tuberculosis H37Rv | ADP + NADPH | - |
? | |
| fructose-1,6-bisphosphate + ? | - |
Methanocaldococcus jannaschii | ? | - |
? | |
| additional information | absence of any NADH-phosphorylating (NADH kinase) activity of NAD kinase | Salmonella enterica | ? | - |
? | |
| additional information | no activity with poly(P) | Saccharomyces cerevisiae | ? | - |
? | |
| additional information | does not accept poly(P) as phosphoryl donor | Arabidopsis thaliana | ? | - |
? | |
| additional information | does not accept poly(P) as phosphoryl donor | Saccharomyces cerevisiae | ? | - |
? | |
| NADH + poly(P)4 | - |
Mycobacterium tuberculosis | NADPH + poly(P)3 | - |
? | |
| NADH + poly(P)4 | - |
Methanocaldococcus jannaschii | NADPH + poly(P)3 | - |
? | |
| NADH + poly(P)4 | - |
Pyrococcus horikoshii | NADPH + poly(P)3 | - |
? | |
| NADH + poly(P)4 | - |
Bacillus subtilis | NADPH + poly(P)3 | - |
? | |
| NADH + poly(P)4 | - |
Micrococcus luteus | NADPH + poly(P)3 | - |
? | |
| NADH + poly(P)4 | - |
Mycobacterium tuberculosis H37Rv | NADPH + poly(P)3 | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| ? | x * 46000 | Saccharomyces cerevisiae |
| ? | ? x 110000 | Arabidopsis thaliana |
| ? | ? x 58000 | Arabidopsis thaliana |
| homodimer | 2 * 32000 | Sphingomonas sp. A1 |
| homodimer | 2 * 30000 | Bacillus subtilis |
| homodimer | 2 x 34000 | Micrococcus luteus |
| homodimer | 2 x 38000 | Arabidopsis thaliana |
| homohexamer | 6 * 60000 | Saccharomyces cerevisiae |
| homohexamer | 6 x 30000 | Escherichia coli |
| homohexamer | 6 * 60000, Utr1p | Saccharomyces cerevisiae |
| homooctamer | 8 * 60000 | Saccharomyces cerevisiae |
| homooctamer | 6 * 60000, Yef1p | Saccharomyces cerevisiae |
| homotetramer | 4 * 37000 | Pyrococcus horikoshii |
| homotetramer | 4 x 35000 | Mycobacterium tuberculosis |
| homotetramer | 4 x 49000 | Homo sapiens |
| homotetramer | 4 x 64000 | Methanocaldococcus jannaschii |
| homotetramer | 4 * 49000 | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| NadF | - |
Bacillus subtilis |
| NADK | - |
Sphingomonas sp. A1 |
| NADK1 | - |
Listeria monocytogenes |
| NADK1 | - |
Arabidopsis thaliana |
| NADK2 | - |
Arabidopsis thaliana |
| NADK2 | isoform | Arabidopsis thaliana |
| NADK3 | - |
Arabidopsis thaliana |
| poly(P)/ATP-NAD kinase | - |
Mycobacterium tuberculosis |
| Pos5 | - |
Saccharomyces cerevisiae |
| Ppnk | - |
Mycobacterium tuberculosis |
| styNadK | - |
Salmonella enterica |
| Utr1 | - |
Saccharomyces cerevisiae |
| Utr1p | - |
Saccharomyces cerevisiae |
| Yef1p | - |
Saccharomyces cerevisiae |
| YfjB | - |
Escherichia coli |
| YjbN | - |
Bacillus subtilis |
| YtdI | - |
Bacillus subtilis |
Turnover Number [1/s]
| Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 212 | - |
NADP+ | - |
Methanocaldococcus jannaschii | |
| 212 | - |
fructose-1,6-bisphosphate | - |
Methanocaldococcus jannaschii | |
| 236 | - |
NADPH | - |
Methanocaldococcus jannaschii | |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| NAD+ | - |
Homo sapiens | |
| NAD+ | - |
Arabidopsis thaliana | |
| NAD+ | - |
Saccharomyces cerevisiae | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| physiological function | chloroplast NAD kinase 2 has an important role in chlorophyll biosynthesis and protects chloroplasts from oxidative stress | Arabidopsis thaliana |
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