Background: | 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 MRVI1/IRAG 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. |
Synonyms: | cGMP-dependent protein kinase 1 (cGK 1) (cGK1) (EC 2.7.11.12) (cGMP-dependent protein kinase I) (cGKI), PRKG1, PRKG1B PRKGR1A PRKGR1B |
UniProt Protein Function: | PKG1: an AGC kinase of the PKG family. Type I cGMP-dependent protein kinase; relaxes vascular smooth muscle and inhibits platelet aggregation. Binding of cGMP results in enzyme activation. Two splice variant isoforms have been described. |
UniProt Protein Details: | Protein type:AGC group; EC 2.7.11.12; Kinase, protein; PKG family; Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor) Chromosomal Location of Human Ortholog: 10q11.23-q21.1 Cellular Component: cytoplasm; cytosol; plasma membrane Molecular Function:calcium channel regulator activity; cGMP-dependent protein kinase activity; protein binding; protein serine/threonine kinase activity Biological Process: actin cytoskeleton organization and biogenesis; regulation of GTPase activity; signal transduction |
NCBI Summary: | Mammals have three different isoforms of cyclic GMP-dependent protein kinase (Ialpha, Ibeta, and II). These PRKG isoforms act as key mediators of the nitric oxide/cGMP signaling pathway and are important components of many signal transduction processes in diverse cell types. This PRKG1 gene on human chromosome 10 encodes the soluble Ialpha and Ibeta isoforms of PRKG by alternative transcript splicing. A separate gene on human chromosome 4, PRKG2, encodes the membrane-bound PRKG isoform II. The PRKG1 proteins play a central role in regulating cardiovascular and neuronal functions in addition to relaxing smooth muscle tone, preventing platelet aggregation, and modulating cell growth. This gene is most strongly expressed in all types of smooth muscle, platelets, cerebellar Purkinje cells, hippocampal neurons, and the lateral amygdala. Isoforms Ialpha and Ibeta have identical cGMP-binding and catalytic domains but differ in their leucine/isoleucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity. [provided by RefSeq, Sep 2011] |
UniProt Code: | Q13976 |
NCBI GenInfo Identifier: | 6225588 |
NCBI Gene ID: | 5592 |
NCBI Accession: | Q13976.3 |
UniProt Secondary Accession: | Q13976,P14619, Q5JP05, Q5JSJ6, Q6P5T7, A5YM56, B3KSF3 E2PU10, |
UniProt Related Accession: | Q13976 |
Molecular Weight: | |
NCBI Full Name: | cGMP-dependent protein kinase 1 |
NCBI Synonym Full Names: | protein kinase, cGMP-dependent, type I |
NCBI Official Symbol: | PRKG1 |
NCBI Official Synonym Symbols: | PKG; cGK; AAT8; cGK1; cGKI; cGK 1; PRKG1B; PRKGR1B; cGKI-BETA; cGKI-alpha |
NCBI Protein Information: | cGMP-dependent protein kinase 1 |
UniProt Protein Name: | cGMP-dependent protein kinase 1 |
UniProt Synonym Protein Names: | cGMP-dependent protein kinase I; cGKI |
UniProt Gene Name: | PRKG1 |