PRKG1

PRKG1 (Protein Kinase CGMP-Dependent 1) is a Protein Coding gene. Diseases associated with PRKG1 include Aortic Aneurysm, Familial Thoracic 8 and Phosphoglycerate Kinase Deficiency. Among its related pathways are Cytoskeletal Signaling and Gap junction. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is PRKG2.

protein kinase, cGMP-dependent, type I

Serine/threonine protein kinase that acts as key mediator of the nitric oxide (NO)/cGMP signaling pathway. GMP binding activates PRKG1, which phosphorylates serines and threonines on many cellular proteins. Numerous protein targets for PRKG1 phosphorylation are implicated in modulating cellular calcium, but the contribution of each of these targets may vary substantially among cell types. Proteins that are phosphorylated by PRKG1 regulate platelet activation and adhesion, smooth muscle contraction, cardiac function, gene expression, feedback of the NO-signaling pathway, and other processes involved in several aspects of the CNS like axon guidance, hippocampal and cerebellar learning, circadian rhythm and nociception. Smooth muscle relaxation is mediated through lowering of intracellular free calcium, by desensitization of contractile proteins to calcium, and by decrease in the contractile state of smooth muscle or in platelet activation. Regulates intracellular calcium levels via several pathways: phosphorylates IRAG1 and inhibits IP3-induced Ca2+ release from intracellular stores, phosphorylation of KCNMA1 (BKCa) channels decreases intracellular Ca2+ levels, which leads to increased opening of this channel. PRKG1 phosphorylates the canonical transient receptor potential channel (TRPC) family which inactivates the associated inward calcium current. Another mode of action of NO/cGMP/PKGI signaling involves PKGI-mediated inactivation of the Ras homolog gene family member A (RhoA). Phosphorylation of RHOA by PRKG1 blocks the action of this protein in myriad processes: regulation of RHOA translocation; decreasing contraction; controlling vesicle trafficking, reduction of myosin light chain phosphorylation resulting in vasorelaxation. Activation of PRKG1 by NO signaling alters also gene expression in a number of tissues. In smooth muscle cells, increased cGMP and PRKG1 activity influence expression of smooth muscle-specific contractile proteins, levels of proteins in the NO/cGMP signaling pathway, down-regulation of the matrix proteins osteopontin and thrombospondin-1 to limit smooth muscle cell migration and phenotype. Regulates vasodilator-stimulated phosphoprotein (VASP) functions in platelets and smooth muscle.

Actin cytoskeleton organizationManual Assertion Based On ExperimentTAS:ProtInc
cGMP-mediated signalingIEA:Ensembl
Dendrite developmentIEA:Ensembl
Forebrain developmentIEA:Ensembl
Negative regulation of platelet aggregationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of vascular associated smooth muscle cell migrationManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of vascular associated smooth muscle cell proliferationManual Assertion Based On ExperimentIDA:BHF-UCL
Neuron migrationIEA:Ensembl
Protein phosphorylationManual Assertion Based On ExperimentTAS:ProtInc
Regulation of GTPase activityManual Assertion Based On ExperimentIMP:UniProtKB
Relaxation of vascular associated smooth muscleIEA:Ensembl
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc

Cytoplasm
Colocalized with TRPC7 in the plasma membrane.

Aortic aneurysm, familial thoracic 8 (AAT8):
A disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance.

Autophosphorylation increases kinase activity.
65 kDa monomer is produced by proteolytic cleavage.