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Literature summary for 2.3.1.48 extracted from
- Lysine acetyltransferase NuA4 and acetyl-CoA regulate glucose-deprived stress granule formation in Saccharomyces cerevisiae (2017), PLoS Genet., 13, e1006626 .
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | wild-type, mutants of core stress-granule (SG) subunits pbp1DELTA and pub1DELTA, along with NuA4 non-essential mutants eaf1DELTA and eaf7DELTA, are transformed with a Pab1-GFP expressing plasmid. None of the mutants examined display a significant increase or constitutive formation of SGs under glucose conditions compared to wild-type. Upon glucose deprivation (GD), Pab1-GFP SGs are induced in wild-type cells but the induction is significantly reduced in pub1DELTA and pbp1DELTA cells. Upon glucose deprivation eaf1DELTA and eaf7DELTA cells show a decrease in Pab1-GFP SGs to a similar extent as pbp1DELTA and pub1DELTA cells. Decreases in GD-SG formation are seen for NuA4 mutants' eaf3DELTA and eaf5DELTA. Furthermore, while the temperature-sensitive allele of ESA1, esa1-L254P (esa1-ts) form GD-SGs at the permissive temperature (25°C), when pre-incubated at the non-permissive temperature (37°C) prior to 10 minutes of glucose deprivation, there is a significant decrease in Pab1-GFP foci formation, indicating that the catalytic activity of NuA4 is required for Pab1-GFP SG formation. While gcn5DELTA cells do not display a significant reduction in GD-SG assembly compared to wild-type cells using the endogenously integrated Pab1-GFP, eaf7DELTAgcn5DELTA cells display a significant reduction in GD-SG formation at 10 minutes compared to both wild-type and single KAT mutants | Saccharomyces cerevisiae |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| NU9056 | causes decreased acetylation level of histone H4 in mammalian cells | Homo sapiens |  |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| acetyl-CoA + [histone H4]-L-lysine | Saccharomyces cerevisiae | - |
CoA + [histone H4]-N6-acetyl-L-lysine | - |
? | |
| acetyl-CoA + [histone H4]-L-lysine | Saccharomyces cerevisiae BY4741 | - |
CoA + [histone H4]-N6-acetyl-L-lysine | - |
? | |
| acetyl-CoA + [protein]-L-lysine | Saccharomyces cerevisiae | - |
CoA + [protein]-N6-acetyl-L-lysine | - |
? | |
| acetyl-CoA + [protein]-L-lysine | Homo sapiens | - |
CoA + [protein]-N6-acetyl-L-lysine | - |
? | |
| acetyl-CoA + [protein]-L-lysine | Saccharomyces cerevisiae BY4741 | - |
CoA + [protein]-N6-acetyl-L-lysine | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q92993 | - |
- |
| Saccharomyces cerevisiae | Q08649 | NuA4 is a 13-subunit KAT complex containing the essential catalytic domain Esa1 | - |
| Saccharomyces cerevisiae BY4741 | Q08649 | NuA4 is a 13-subunit KAT complex containing the essential catalytic domain Esa1 | - |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| breast cancer cell | - |
Homo sapiens | - |
| HeLa cell | - |
Homo sapiens | - |
| MCF-7 cell | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| acetyl-CoA + [histone H4]-L-lysine | - |
Saccharomyces cerevisiae | CoA + [histone H4]-N6-acetyl-L-lysine | - |
? | |
| acetyl-CoA + [histone H4]-L-lysine | - |
Saccharomyces cerevisiae BY4741 | CoA + [histone H4]-N6-acetyl-L-lysine | - |
? | |
| acetyl-CoA + [protein]-L-lysine | - |
Saccharomyces cerevisiae | CoA + [protein]-N6-acetyl-L-lysine | - |
? | |
| acetyl-CoA + [protein]-L-lysine | - |
Homo sapiens | CoA + [protein]-N6-acetyl-L-lysine | - |
? | |
| acetyl-CoA + [protein]-L-lysine | - |
Saccharomyces cerevisiae BY4741 | CoA + [protein]-N6-acetyl-L-lysine | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| More | NuA4 is a multi-subunit complex, composed of the essential catalytic subunit Esa1, five other essential subunits Act1, Arp4, Epl1, Swc4, Tra1, and seven non-essential subunits Eaf1, Eaf3, Eaf5, Eaf6, Eaf7, Yaf9, and Yng2. Molecular and structural dissection has revealed NuA4 to be modular in nature, assembly of its multiple sub-complexes depends on the Eaf1 subunit | Saccharomyces cerevisiae |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| KAT5 | - |
Homo sapiens |
| lysine acetyltransferase | - |
Saccharomyces cerevisiae |
| lysine acetyltransferase | - |
Homo sapiens |
| NuA4 | - |
Saccharomyces cerevisiae |
| NuA4 | the NuA4 histone acetyltransferase complex is composed of at least ACT1, ARP4, EAF3, EAF5, EAF6, EAF7, EPL1, ESA1, SWC4, TRA1, VID21, YAF9 and YNG2 subunits | Saccharomyces cerevisiae |
| Tip60 | - |
Homo sapiens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | acetyl-CoA levels are elevated in NuA4 mutants | Saccharomyces cerevisiae |
| metabolism | exogenous acetate and reduced expression of ACC1 decreases glucose-deprived stress granule formation | Saccharomyces cerevisiae |
| metabolism | exogenous acetate and reduced expression of ACC1 decreases glucose-deprived stress granule formation | Homo sapiens |
| metabolism | stress granule formation is a conserved cellular stress response. Elevated acetyl-CoA levels suppress the formation of glucose-deprived stress granules, decreased acetyl-CoA levels enhance stress granule formation upon glucose deprivation. NuA4 mutant cells exhibit reduced Pab1-GFP cytoplasmic foci upon glucose deprivation. Suppression of glucose-deprived stress granule formation by eaf7DELTA mutants is mediated by increased acetyl-CoA. Acc1 activity is reduced in eaf1DELTA cells | Saccharomyces cerevisiae |
| physiological function | conserved role for Tip60, the mammalian homologue of Saccharomyces cerevisiae Esa1, in the regulation of stress granules in human breast cancer cells. Stress granule formation is a conserved cellular stress response. Tip60 affects stress granule levels in mammalian cells | Homo sapiens |
| physiological function | the Saccharomyces cerevisiae lysine acetyltransferase complex NuA4 is required for stress granule (SG) formation upon glucose deprivation but not heat stress. The impact of NuA4 on glucose-deprived stress granule formation is partially mediated through regulation of acetyl-CoA levels via the acetyl-CoA carboxylase Acc1. Both NuA4 and the metabolite acetyl-CoA are critical signaling pathways regulating the formation of glucose-deprived stress granules. Functionally redundant roles for Eaf7 and Gcn5 in SG formation upon glucose deprivation, overview. NuA4 is required for glucose deprivation stress granule formation but does not impact processing bodies. NuA4 does not regulate the formation of stress granules through the inhibition of translation initiation or the Snf1 pathway. Eaf1 and Eaf7 are not required for the inhibition of translation initiation upon 10 minutes glucose deprivation | Saccharomyces cerevisiae |
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