Reaction participants Show >> << Hide
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Namehelp_outline
L-glutaminyl-[protein]
Identifier
RHEA-COMP:10207
Reactive part
help_outline
- Name help_outline L-glutamine residue Identifier CHEBI:30011 Charge 0 Formula C5H8N2O2 SMILEShelp_outline O=C(*)[C@@H](N*)CCC(=O)N 2D coordinates Mol file for the small molecule Search links Involved in 12 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline serotonin Identifier CHEBI:350546 Charge 1 Formula C10H13N2O InChIKeyhelp_outline QZAYGJVTTNCVMB-UHFFFAOYSA-O SMILEShelp_outline [NH3+]CCc1c[nH]c2ccc(O)cc12 2D coordinates Mol file for the small molecule Search links Involved in 17 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
5-serotonyl-L-glutamyl-[protein]
Identifier
RHEA-COMP:17052
Reactive part
help_outline
- Name help_outline 5-glutamyl serotonin residue Identifier CHEBI:167174 Charge 0 Formula C15H17N3O3 SMILEShelp_outline O=C(*)[C@@H](N*)CCC(=O)NCCC=1C2=CC(=CC=C2NC1)O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NH4+ Identifier CHEBI:28938 (CAS: 14798-03-9) help_outline Charge 1 Formula H4N InChIKeyhelp_outline QGZKDVFQNNGYKY-UHFFFAOYSA-O SMILEShelp_outline [H][N+]([H])([H])[H] 2D coordinates Mol file for the small molecule Search links Involved in 518 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:66552 | RHEA:66553 | RHEA:66554 | RHEA:66555 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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MetaCyc help_outline |
Publications
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Transglutaminase 2-mediated serotonylation in pulmonary hypertension.
Penumatsa K.C., Fanburg B.L.
The monoamine serotonin (5-HT) has been previously implicated in pulmonary arterial remodeling and is considered a potential therapeutic target for the disease pulmonary arterial hypertension (PAH). More recently, it has been recognized that the enzyme tissue transglutaminase (TG2) mediates cross- ... >> More
The monoamine serotonin (5-HT) has been previously implicated in pulmonary arterial remodeling and is considered a potential therapeutic target for the disease pulmonary arterial hypertension (PAH). More recently, it has been recognized that the enzyme tissue transglutaminase (TG2) mediates cross-linking of proteins with 5-HT, a posttranslational process of monoaminylation known as "serotonylation." TG2 activity and serotonylation of protein participate in both smooth muscle proliferation and contraction produced by 5-HT. Indeed, markedly increased TG2 activity has now been identified in lung tissue of an experimental rodent model of pulmonary hypertension, and elevated serotonylation of fibronectin and the signaling molecule Rho, downstream products of transglutamidation, have been found in blood of patients with PAH. The basic mechanism by which TG2 is activated and the potential role(s) of serotonylated proteins in pulmonary hypertension remain a mystery. In the present review we have tried to address the current understanding of 5-HT metabolism in pulmonary hypertension and relate it to what is currently known about the evolving cellular process of serotonylation. << Less
Am J Physiol Lung Cell Mol Physiol 306:L309-15(2014) [PubMed] [EuropePMC]
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Role of protein transamidation in serotonin-induced proliferation and migration of pulmonary artery smooth muscle cells.
Liu Y., Wei L., Laskin D.L., Fanburg B.L.
Pulmonary hypertension is characterized by elevated pulmonary artery pressure and pulmonary artery smooth muscle cell (SMC) proliferation and migration. Clinical and experimental evidence suggests that serotonin (5-HT) is important in these responses. We previously demonstrated the participation o ... >> More
Pulmonary hypertension is characterized by elevated pulmonary artery pressure and pulmonary artery smooth muscle cell (SMC) proliferation and migration. Clinical and experimental evidence suggests that serotonin (5-HT) is important in these responses. We previously demonstrated the participation of the 5-HT transporter and intracellular 5-HT (5-HTi) in the pulmonary vascular SMC-proliferative response to 5-HT. However, the mechanism underlying the intracellular actions of 5-HT is unknown. We speculated that 5-HTi activates SMC growth by post-translational transamidation of proteins via transglutaminase (TGase) activity, a process referred to as serotonylation. To test this hypothesis, serotonylation of pulmonary artery SMC proteins, and their role in 5-HT-induced proliferative and migratory responses, were assessed. 5-HT caused dose- and time-dependent increase in serotonylation of multiple proteins in both bovine and rat pulmonary artery SMCs. Inhibition of TGase with dansylcadaverin blocked this activity, as well as SMC-proliferative and migratory responses to 5-HT. Serotonylation of proteins also was blocked by 5-HT transporter inhibitors, and was enhanced by inhibition of monoamine oxidase, an enzyme known to degrade 5-HTi, indicating that 5-HTi levels regulate serotonylation. Immunoprecipitation assays and HPLC-mass spectral peptide sequencing revealed that a major protein serotonylated by TGase was fibronectin (FN). 5-HT-stimulated SMC serotonylation and proliferation were blocked by FN small interfering (si) RNA. These findings, together with previous observations that FN expression in the lung strongly correlates with the progression of pulmonary hypertension in both experimental animals and humans, suggest an important role of FN serotonylation in the pathogenesis of this disease. << Less
Am J Respir Cell Mol Biol 44:548-555(2011) [PubMed] [EuropePMC]
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Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3.
Farrelly L.A., Thompson R.E., Zhao S., Lepack A.E., Lyu Y., Bhanu N.V., Zhang B., Loh Y.E., Ramakrishnan A., Vadodaria K.C., Heard K.J., Erikson G., Nakadai T., Bastle R.M., Lukasak B.J., Zebroski H. III, Alenina N., Bader M., Berton O., Roeder R.G., Molina H., Gage F.H., Shen L., Garcia B.A., Li H., Muir T.W., Maze I.
Chemical modifications of histones can mediate diverse DNA-templated processes, including gene transcription<sup>1-3</sup>. Here we provide evidence for a class of histone post-translational modification, serotonylation of glutamine, which occurs at position 5 (Q5ser) on histone H3 in organisms th ... >> More
Chemical modifications of histones can mediate diverse DNA-templated processes, including gene transcription<sup>1-3</sup>. Here we provide evidence for a class of histone post-translational modification, serotonylation of glutamine, which occurs at position 5 (Q5ser) on histone H3 in organisms that produce serotonin (also known as 5-hydroxytryptamine (5-HT)). We demonstrate that tissue transglutaminase 2 can serotonylate histone H3 tri-methylated lysine 4 (H3K4me3)-marked nucleosomes, resulting in the presence of combinatorial H3K4me3Q5ser in vivo. H3K4me3Q5ser displays a ubiquitous pattern of tissue expression in mammals, with enrichment observed in brain and gut, two organ systems responsible for the bulk of 5-HT production. Genome-wide analyses of human serotonergic neurons, developing mouse brain and cultured serotonergic cells indicate that H3K4me3Q5ser nucleosomes are enriched in euchromatin, are sensitive to cellular differentiation and correlate with permissive gene expression, phenomena that are linked to the potentiation of TFIID<sup>4-6</sup> interactions with H3K4me3. Cells that ectopically express a H3 mutant that cannot be serotonylated display significantly altered expression of H3K4me3Q5ser-target loci, which leads to deficits in differentiation. Taken together, these data identify a direct role for 5-HT, independent from its contributions to neurotransmission and cellular signalling, in the mediation of permissive gene expression. << Less
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Transglutaminase-mediated transamidation of serotonin, dopamine and noradrenaline to fibronectin: evidence for a general mechanism of monoaminylation.
Hummerich R., Thumfart J.O., Findeisen P., Bartsch D., Schloss P.
The activity of some small GTPases is regulated by covalent transamidation of serotonin (5-hydropxytryptamien) to glutamine residues of the enzymes. This process is mediated by transglutaminase (TGase) and is termed "serotonylation". In addition, serotonylation of neural proteins and proteins of t ... >> More
The activity of some small GTPases is regulated by covalent transamidation of serotonin (5-hydropxytryptamien) to glutamine residues of the enzymes. This process is mediated by transglutaminase (TGase) and is termed "serotonylation". In addition, serotonylation of neural proteins and proteins of the extracellular matrix such as fibronectin has been demonstrated. Here we show that the catecholamines dopamine (DA) and noradrenaline (NA) inhibit serotonylation of fibronectin and that DA and NA themselves can be selectively transamidated into fibronectin by TGase. All three biogenic monoamines also block TGase-mediated transamidation of another monoamine, monodansylacadaverine, into fibronectin, suggesting a general mechanism of TGase-mediated "monoaminylation". << Less
FEBS Lett. 586:3421-3428(2012) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.