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Literature summary for 3.6.5.1 extracted from
- Heterotrimeric G proteins: organizers of transmembrane signals (1995), Cell, 80, 249-257.
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| phosducin | inhibits betagamma function in vitro | Mammalia |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| GTP + H2O | Homo sapiens | - |
GDP + phosphate | - |
? |  |
| GTP + H2O | Mammalia | cycle of G protein activation and deactivation that transmits a signal from receptor to effector: when GDP is bound the alpha subunit associated with the betagamma subunit to form an inactive heterotrimer that binds to the receptor. Both alpha and betagamma subunits can bind to the receptor. When a chemical or physical signal stimulates the receptor, the receptor becomes activated and changes its conformation. The GDP-ligated alpha-subunit responds with a conformational change that decreases GDP affinity, so that GDP is released. Leaving GDP is replaced by GTP. Once ATP is bound, the alpha subunit assumes its activated conformation and dissociates both from the receptor and from betagamma. The activated state lasts until the GTP is hydrolyzed to GDP by the intrinsic GTPase activity of the alpha-subunit. Once GTP is cleaved to GDP, the alpha and betagamma subunits reassociate, become inactive, and return to the receptor. The free alpha and betagamma subunits each activate target effectors. Galphas and Galphaolf, stimulate adenylyl cyclase and regulate Ca2+ channels. Galphai-1, Galphai-2, Galphai-3, Galphao, Galphat-1, Galphat-2, Galphagust and Galphaz inhibit adenylyl cyclase, regulate K+ and Ca2+ channels, and activate cGMP phosphodiesterase. Galphaq, Galpha11, Galpha14, Galppha15 and Galpha16 activate phospholipase C. Galpha12 and Galpha13 regulate Na/K+ exchange. The betagamma subunit is a positive regulator of K+ channels, adenylyl cyclase, phospholipase Cbeta, phospholipase A2, phosphoinositide 3-kinase and beta-adrenergic receptor kinase | GDP + phosphate | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Mammalia | - |
- |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| lipoprotein | alpha subunits alphao, alphai and alphaz are myristoylated at the N-terminal Gly, alphas and alphaq are not myristoylated. Myristoylation is necessary for membrane attachment and facilitates binding of betagamma. It is an irreversible covalent modification and does not serve a regulatory role. Some alpha subunits are palmitoylated at Cys2. Palmitoylation is reversible. Activation of the beta-adrenergic receptor leads to rapid depalmitoylation of alphas, and depalmitoylated alphas does not activate adenylyl cyclase. Depalmitoylation might be a mechanism to turn off alphas and to sensitize the cell to beta-adrenergic stimulation | Mammalia |
| side-chain modification | betagamma subunit can be phosphorylated on His residues | Homo sapiens |
| side-chain modification | subunits alphai-2 and alphaz can be phosphorylated on Ser or Thr in vivo and in vitro. Several types of subunits can be phosphorylated in vitro on Tyr residues by pp60c-src or by insulin receptor, changes in activity upon phosphorylation are modest at best | Mammalia |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| leukemia cell | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| GTP + H2O | - |
Mammalia | GDP + phosphate | - |
? | |
| GTP + H2O | - |
Homo sapiens | GDP + phosphate | - |
? | |
| GTP + H2O | cycle of G protein activation and deactivation that transmits a signal from receptor to effector: when GDP is bound the alpha subunit associated with the betagamma subunit to form an inactive heterotrimer that binds to the receptor. Both alpha and betagamma subunits can bind to the receptor. When a chemical or physical signal stimulates the receptor, the receptor becomes activated and changes its conformation. The GDP-ligated alpha-subunit responds with a conformational change that decreases GDP affinity, so that GDP is released. Leaving GDP is replaced by GTP. Once ATP is bound, the alpha subunit assumes its activated conformation and dissociates both from the receptor and from betagamma. The activated state lasts until the GTP is hydrolyzed to GDP by the intrinsic GTPase activity of the alpha-subunit. Once GTP is cleaved to GDP, the alpha and betagamma subunits reassociate, become inactive, and return to the receptor. The free alpha and betagamma subunits each activate target effectors. Galphas and Galphaolf, stimulate adenylyl cyclase and regulate Ca2+ channels. Galphai-1, Galphai-2, Galphai-3, Galphao, Galphat-1, Galphat-2, Galphagust and Galphaz inhibit adenylyl cyclase, regulate K+ and Ca2+ channels, and activate cGMP phosphodiesterase. Galphaq, Galpha11, Galpha14, Galppha15 and Galpha16 activate phospholipase C. Galpha12 and Galpha13 regulate Na/K+ exchange. The betagamma subunit is a positive regulator of K+ channels, adenylyl cyclase, phospholipase Cbeta, phospholipase A2, phosphoinositide 3-kinase and beta-adrenergic receptor kinase | Mammalia | GDP + phosphate | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| More | - |
Homo sapiens |
| More | G proteins consist of three polypeptides: an alpha subunit that binds and hydrolyzes GTP, a beta subunit and a gamma subunit. The beta and gamma subunit form a dimer that only dissociates when it is denatured and is therefore a functional monomer. Structure of the subunits | Mammalia |
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