Enzymes
UniProtKB help_outline | 1,886 proteins |
Reaction participants Show >> << Hide
- Name help_outline 2-hydroxyisobutanoyl-CoA Identifier CHEBI:131780 Charge -4 Formula C25H38N7O18P3S InChIKeyhelp_outline FFVUICCDNWZCRC-ZSJPKINUSA-J SMILEShelp_outline [C@@H]1(N2C3=C(C(=NC=N3)N)N=C2)O[C@H](COP(OP(OCC(C)([C@H](C(NCCC(NCCSC(=O)C(C)(C)O)=O)=O)O)C)(=O)[O-])(=O)[O-])[C@H]([C@H]1O)OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
L-lysyl-[protein]
Identifier
RHEA-COMP:9752
Reactive part
help_outline
- Name help_outline L-lysine residue Identifier CHEBI:29969 Charge 1 Formula C6H13N2O SMILEShelp_outline C([C@@H](C(*)=O)N*)CCC[NH3+] 2D coordinates Mol file for the small molecule Search links Involved in 137 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
N6-(2-hydroxyisobutanoyl)-L-lysyl-[protein]
Identifier
RHEA-COMP:15921
Reactive part
help_outline
- Name help_outline N6-(2-hydroxyisobutanoyl)-L-lysine residue Identifier CHEBI:144968 Charge 0 Formula C10H18N2O3 SMILEShelp_outline C(*)([C@@H](N*)CCCCNC(C(O)(C)C)=O)=O 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline CoA Identifier CHEBI:57287 (Beilstein: 11604429) help_outline Charge -4 Formula C21H32N7O16P3S InChIKeyhelp_outline RGJOEKWQDUBAIZ-IBOSZNHHSA-J SMILEShelp_outline CC(C)(COP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP([O-])([O-])=O)n1cnc2c(N)ncnc12)[C@@H](O)C(=O)NCCC(=O)NCCS 2D coordinates Mol file for the small molecule Search links Involved in 1,511 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,521 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:24180 | RHEA:24181 | RHEA:24182 | RHEA:24183 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Gene Ontology help_outline |
Publications
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Landscape of the regulatory elements for lysine 2-hydroxyisobutyrylation pathway.
Huang H., Luo Z., Qi S., Huang J., Xu P., Wang X., Gao L., Li F., Wang J., Zhao W., Gu W., Chen Z., Dai L., Dai J., Zhao Y.
Short-chain fatty acids and their corresponding acyl-CoAs sit at the crossroads of metabolic pathways and play important roles in diverse cellular processes. They are also precursors for protein post-translational lysine acylation modifications. A noteworthy example is the newly identified lysine ... >> More
Short-chain fatty acids and their corresponding acyl-CoAs sit at the crossroads of metabolic pathways and play important roles in diverse cellular processes. They are also precursors for protein post-translational lysine acylation modifications. A noteworthy example is the newly identified lysine 2-hydroxyisobutyrylation (K<sub>hib</sub>) that is derived from 2-hydroxyisobutyrate and 2-hydroxyisobutyryl-CoA. Histone K<sub>hib</sub> has been shown to be associated with active gene expression in spermatogenic cells. However, the key elements that regulate this post-translational lysine acylation pathway remain unknown. This has hindered characterization of the mechanisms by which this modification exerts its biological functions. Here we show that Esa1p in budding yeast and its homologue Tip60 in human could add K<sub>hib</sub> to substrate proteins both in vitro and in vivo. In addition, we have identified HDAC2 and HDAC3 as the major enzymes to remove K<sub>hib</sub>. Moreover, we report the first global profiling of K<sub>hib</sub> proteome in mammalian cells, identifying 6 548 K<sub>hib</sub> sites on 1 725 substrate proteins. Our study has thus discovered both the "writers" and "erasers" for histone K<sub>hib</sub> marks, and major K<sub>hib</sub> protein substrates. These results not only illustrate the landscape of this new lysine acylation pathway, but also open new avenues for studying diverse functions of cellular metabolites associated with this pathway. << Less
Cell Res. 28:111-125(2018) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.
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p300-mediated lysine 2-hydroxyisobutyrylation regulates glycolysis.
Huang H., Tang S., Ji M., Tang Z., Shimada M., Liu X., Qi S., Locasale J.W., Roeder R.G., Zhao Y., Li X.
Lysine 2-hydroxyisobutyrylation (Khib) is an evolutionarily conserved and widespread histone mark like lysine acetylation (Kac). Here we report that p300 functions as a lysine 2-hyroxyisobutyryltransferase to regulate glycolysis in response to nutritional cues. We discovered that p300 differential ... >> More
Lysine 2-hydroxyisobutyrylation (Khib) is an evolutionarily conserved and widespread histone mark like lysine acetylation (Kac). Here we report that p300 functions as a lysine 2-hyroxyisobutyryltransferase to regulate glycolysis in response to nutritional cues. We discovered that p300 differentially regulates Khib and Kac on distinct lysine sites, with only 6 of the 149 p300-targeted Khib sites overlapping with the 693 p300-targeted Kac sites. We demonstrate that diverse cellular proteins, particularly glycolytic enzymes, are targeted by p300 for Khib, but not for Kac. Specifically, deletion of p300 significantly reduces Khib levels on several p300-dependent, Khib-specific sites on key glycolytic enzymes including ENO1, decreasing their catalytic activities. Consequently, p300-deficient cells have impaired glycolysis and are hypersensitive to glucose-depletion-induced cell death. Our study reveals an p300-catalyzed, Khib-specific molecular mechanism that regulates cellular glucose metabolism and further indicate that p300 has an intrinsic ability to select short-chain acyl-CoA-dependent protein substrates. << Less