PRKG1 - cGMP-dependent protein kinase 1 - human protein (Function)
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PRKG1 »  cGMP-dependent protein kinase 1   [ EC ]  (cGK1)
Protein also known as:  cGMP-dependent protein kinase I (cGKI).
Gene name:  PRKG1
Entry whose protein(s) existence is based on evidence at protein level
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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 Ca(2+) release from intracellular stores, phosphorylation of KCNMA1 (BKCa) channels decreases intracellular Ca(2+) 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.  
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Calcium channel regulator activitydefinition[GO:0005246]  
  • IDAUniProtKB
cGMP bindingdefinition[GO:0030553] silver  
  • IEAOrtholog Compara
cGMP-dependent protein kinase activitydefinition[GO:0004692]  
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
  • IPIUniProtKB
  • IPIIntAct
GO biological process 
Actin cytoskeleton organizationdefinition[GO:0030036]  
Dendrite developmentdefinition[GO:0016358] silver  
  • IEAOrtholog Compara
Forebrain developmentdefinition[GO:0030900] silver  
  • IEAOrtholog Compara
Negative regulation of platelet aggregationdefinition[GO:0090331]  
  • IMPUniProtKB
Neuron migrationdefinition[GO:0001764] silver  
  • IEAOrtholog Compara
Protein phosphorylationdefinition[GO:0006468] silver  
  • IEAOrtholog Compara
Regulation of GTPase activitydefinition[GO:0043087]  
  • IMPUniProtKB
Signal transductiondefinition[GO:0007165] silver  
  • IEAOrtholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It is regulated in the following manner
In the absence of cGMP, PRKG1 activity is suppressed by autoinhibitory contacts.  
  • CuratedUniProtKB
More information is available from:
According to KEGG, this protein belongs to the following pathways:
Gap junction  hsa04540+5592  
Long-term depression  hsa04730+5592  
Olfactory transduction  hsa04740+5592  
Salivary secretion  hsa04970+5592  
Vascular smooth muscle contraction  hsa04270+5592  
According to Reactome, this protein belongs to the following pathways:
Ca2+ pathway  REACT_172761  
cGMP effects  REACT_23767  
Rap1 signalling  REACT_23898  


Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Allosteric enzyme  definition   [KW-0021]
Reference proteome  definition   [KW-1185]

Further external links

GeneWiki: PRKG1
GenomeRNAi: 5592
PRO: PR:Q13976