======= PRKG1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: PRKG1
  * **<color #00a2e8>Official Name</color>**: protein kinase cGMP-dependent 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5592|5592]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q13976|Q13976]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=PRKG1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PRKG1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/176894|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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. {ECO:0000269|PubMed:10567269, ECO:0000269|PubMed:11162591, ECO:0000269|PubMed:11723116, ECO:0000269|PubMed:12082086, ECO:0000269|PubMed:14608379, ECO:0000269|PubMed:15194681, ECO:0000269|PubMed:16990611, ECO:0000269|PubMed:8182057}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|cNMP binding|
|Pkinase|
|Pkinase Tyr|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|cGMP-dependent protein kinase activity|
|negative regulation of vascular associated smooth muscle cell migration|
|relaxation of vascular smooth muscle|
|relaxation of smooth muscle|
|cAMP-dependent protein kinase activity|
|negative regulation of platelet aggregation|
|cAMP-dependent protein kinase complex|
|negative regulation of smooth muscle contraction|
|negative regulation of homotypic cell-cell adhesion|
|cGMP binding|
|regulation of platelet aggregation|
|negative regulation of vascular smooth muscle cell proliferation|
|negative regulation of platelet activation|
|relaxation of muscle|
|regulation of vascular associated smooth muscle cell migration|
|negative regulation of smooth muscle cell migration|
|negative regulation of muscle contraction|
|regulation of homotypic cell-cell adhesion|
|cGMP-mediated signaling|
|vasodilation|
|regulation of platelet activation|
|calcium channel regulator activity|
|negative regulation of smooth muscle cell proliferation|
|regulation of vascular smooth muscle cell proliferation|
|negative regulation of blood coagulation|
|negative regulation of hemostasis|
|negative regulation of coagulation|
|positive regulation of blood vessel diameter|
|regulation of smooth muscle cell migration|
|regulation of smooth muscle contraction|
|negative regulation of wound healing|
|regulation of blood coagulation|
|regulation of hemostasis|
|regulation of coagulation|
|negative regulation of response to wounding|
|dendrite development|
|neuron migration|
|regulation of smooth muscle cell proliferation|
|regulation of wound healing|
|regulation of tube diameter|
|regulation of blood vessel diameter|
|regulation of tube size|
|regulation of muscle contraction|
|regulation of response to wounding|
|vascular process in circulatory system|
|cyclic-nucleotide-mediated signaling|
|negative regulation of cell-cell adhesion|
|peptidyl-serine phosphorylation|
|negative regulation of cell activation|
|peptidyl-serine modification|
|regulation of muscle system process|
|protein kinase activity|
|negative regulation of cell migration|
|negative regulation of cell adhesion|
|negative regulation of cell motility|
|muscle system process|
|negative regulation of cellular component movement|
|negative regulation of locomotion|
|second-messenger-mediated signaling|
|negative regulation of response to external stimulus|
|forebrain development|
|blood circulation|
|circulatory system process|
|regulation of cell-cell adhesion|
|regulation of GTPase activity|
|actin cytoskeleton organization|
|regulation of body fluid levels|
|regulation of anatomical structure size|
|actin filament-based process|
|regulation of system process|
|regulation of cell activation|
|neuron projection development|
|negative regulation of cell population proliferation|
|regulation of cell adhesion|
|brain development|
|head development|
|neuron development|
|regulation of cell migration|
|peptidyl-amino acid modification|
|regulation of cell motility|
|cell migration|
|protein phosphorylation|
|central nervous system development|
|regulation of locomotion|
|Golgi apparatus|
|regulation of cellular component movement|
|neuron differentiation|
|localization of cell|
|cell motility|
|regulation of response to external stimulus|
|cytoskeleton organization|
|plasma membrane bounded cell projection organization|
|cell projection organization|
|negative regulation of multicellular organismal process|
|regulation of hydrolase activity|
|phosphorylation|
|locomotion|
|regulation of response to stress|
|ATP binding|
|generation of neurons|
|movement of cell or subcellular component|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|neurogenesis|
|cell development|
|intracellular signal transduction|
|system process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp410|THZ531 0.11 to 0.125μM on day4 R07 exp410]]|-2.18|
|[[:results:exp165|RO-3306 3 to 4μM on day4 R04 exp165]]|-1.74|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 11919
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 4.18 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='PRKG1 Expression in NALM6 Cells: 4.18'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>