Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | asymmetric dimethylarginine, ADMA, decreases GCH1 protein, but not mRNA concentrations, in pulmonary arterial endothelial cells because of the ubiquitination and proteasome-dependent degradation of GCH1. Overexpression of CHIP potentiates, whereas a CHIP U-box domain mutant attenuates, ADMA-induced GCH1 degradation and reductions in cellular BH4 concentrations. L-Arginine acts antagonistic and restores the activities | Ovis aries |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Ovis aries | - |
lambs | - |
Posttranslational Modification | Comment | Organism |
---|---|---|
additional information | ubiquitination and proteasome-dependent degradation of GCH1. The CHIP-ubiquitin pathway modifies GCH1 in a lamb model of pulmonary hypertension secondary to increased pulmonary blood flow | Ovis aries |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
lung | - |
Ovis aries | - |
pulmonary artery endothelial cell | - |
Ovis aries | - |
Synonyms | Comment | Organism |
---|---|---|
GCH1 | - |
Ovis aries |
guanosine-5'-triphosphate cyclohydrolase 1 | - |
Ovis aries |
General Information | Comment | Organism |
---|---|---|
metabolism | GCH1 is the rate-limiting enzyme in the generation of BH4 | Ovis aries |
additional information | asymmetric dimethylarginine, ADMA, decreases GCH1 protein, but not mRNA concentrations, in pulmonary arterial endothelial cells because of the ubiquitination and proteasome-dependent degradation of GCH1. Hsp90-GCH1 interactions are reduced, whereas the association of GCH1 with Hsp70 and the C-terminus of Hsp70-interacting protein, i.e. CHIP, increases in the cells. In vivo Hsp90/GCH1 interactions are decreased, whereas GCH1-Hsp70 and GCH1-CHIP interactions and GCH1 ubiquitination are increased. L-Arginine acts antagonistic and restores the activities | Ovis aries |
physiological function | GTP cyclohydrolase I interaction is required for degradation of the C-terminus of heat shock protein 70-interacting protein. GCH1 is a client protein for Hsp90. The U-box domain of CHIP is essential for ADMA-mediated GCH1 degradation in pulmonary arterial endothelial cells | Ovis aries |