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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]
PRKG1 (Protein Kinase CGMP-Dependent 1) is a Protein Coding gene. Diseases associated with PRKG1 include Aortic Aneurysm, Familial Thoracic 8 and Familial Thoracic Aortic Aneurysm And Aortic Dissection. Among its related pathways are Sweet Taste Signaling and Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.. 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.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0003824 | catalytic activity | IEA | -- |
GO:0004672 | protein kinase activity | IEA,IMP | 25447536 |
GO:0004674 | protein serine/threonine kinase activity | IEA | -- |
GO:0004692 | cGMP-dependent protein kinase activity | IEA,IDA | 21402151 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005737 | cytoplasm | IEA,IDA | 21402151 |
GO:0005794 | Golgi apparatus | IEA | -- |
GO:0005829 | cytosol | TAS | -- |
GO:0005886 | plasma membrane | IEA,IDA | 21402151 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Sweet Taste Signaling |
Cellular Effects of Sildenafil
.46
|
Sperm Motility
.37
|
2 | Regulation of activated PAK-2p34 by proteasome mediated degradation |
.41
|
|
3 | Nitric oxide stimulates guanylate cyclase |
.01
|
|
4 | MicroRNAs in cardiomyocyte hypertrophy | ||
5 | Cytoskeletal Signaling |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001764 | neuron migration | IEA | -- |
GO:0006468 | NOT protein phosphorylation | IEA,IDA | 15905169 |
GO:0007165 | signal transduction | IEA,TAS | 2792381 |
GO:0008152 | metabolic process | IEA | -- |
GO:0016310 | phosphorylation | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
ATP | Investigational | Nutra | Agonist, Activator, Partial agonist, Antagonist, Full agonist, Gating inhibitor, Pore Blocker, Potentiation | 0 | ||
KT 5823 | Pharma | Allosteric regulator, Positive | Selective protein kinase G inhibitor | 0 | ||
Rp-8-Br-PET-cGMPS | Pharma | Protein kinase G inhibitor | 0 | |||
Rp-8-CPT-cGMPS | Pharma | Inhibitor, Inhibition | 0 | |||
cGMP Dependent Kinase Inhibitor Peptide | Pharma | Inhibitor of protein kinases G and A | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 | |||
Rp-8-pCPT-cGMPS sodium |
|
208445-07-2 |
|
|
Compound | Action | Cas Number |
---|---|---|
KT 5823 | Selective protein kinase G inhibitor | 126643-37-6 |
Rp-8-Br-PET-cGMPS | Protein kinase G inhibitor | 185246-32-6 |
Rp-8-pCPT-cGMPS sodium | PKG inhibitor | 208445-07-2 |
Compound | Action | Cas Number |
---|---|---|
cGMP Dependent Kinase Inhibitor Peptide | 82801-73-8 | |
KT 5823 | 126643-37-6 | |
Rp-8-Br-PET-cGMPS | 185246-32-6 |
This gene was present in the common ancestor of animals and fungi.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Oppossum (Monodelphis domestica) |
Mammalia | PRKG1 31 |
|
OneToOne | |
Chimpanzee (Pan troglodytes) |
Mammalia | PRKG1 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | PRKG1 30 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | PRKG1 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | PRKG1 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Prkg1 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Prkg1 30 |
|
||
Chicken (Gallus gallus) |
Aves | PRKG1 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | PRKG1 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | LOC100494278 30 |
|
||
African clawed frog (Xenopus laevis) |
Amphibia | Xl.4902 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | prkg1b 31 |
|
OneToMany | |
prkg1a 30 31 |
|
OneToMany | |||
zgc63955 30 |
|
||||
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP008863 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | for 30 31 32 |
|
OneToOne | |
Pkg21D 32 |
|
|
|||
CG4839 32 |
|
|
|||
Worm (Caenorhabditis elegans) |
Secernentea | egl-4 31 32 |
|
OneToOne | |
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | TPK2 31 |
|
ManyToMany | |
TPK1 31 |
|
ManyToMany | |||
TPK3 31 |
|
ManyToMany | |||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToMany | |
-- 31 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 10 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
157166 | Not Provided: Gestational diabetes mellitus uncontrolled | 51,447,873(+) | TTATCATCTAGCACAT | INTRON_VARIANT | |
644970 | Uncertain Significance: Aortic aneurysm, familial thoracic 8 | 51,153,292(+) | A/AAGAAGG | INFRAME_INSERTION | |
646864 | Uncertain Significance: Aortic aneurysm, familial thoracic 8 | 52,272,469(+) | T/C | MISSENSE_VARIANT | |
647122 | Uncertain Significance: Aortic aneurysm, familial thoracic 8 | 52,288,730(+) | C/A | MISSENSE_VARIANT | |
648390 | Uncertain Significance: Aortic aneurysm, familial thoracic 8 | 52,054,560(+) | C/T | MISSENSE_VARIANT |
Disorder | Aliases | PubMed IDs |
---|---|---|
aortic aneurysm, familial thoracic 8 |
|
|
familial thoracic aortic aneurysm and aortic dissection |
|
|
phosphoglycerate kinase 1 deficiency |
|
|
aortic aneurysm |
|
|
aortic dissection |
|
|