InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PRKG1

Summary

InnateDB Protein

IDBP-74553.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PRKG1

Protein Name

protein kinase, cGMP-dependent, type I

Synonyms

1; AAT8; cGK; cGK 1; cGK1; cGKI; cGKI-alpha; cGKI-BETA; PKG; PRKG1B; PRKGR1B;

Species

Homo sapiens

Ensembl Protein

ENSP00000363092

InnateDB Gene

IDBG-74547 (PRKG1)

Protein Structure

UniProt Annotation

Function

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:0000269PubMed:10567269, ECO:0000269PubMed:11162591, ECO:0000269PubMed:11723116, ECO:0000269PubMed:12082086, ECO:0000269PubMed:14608379, ECO:0000269PubMed:15194681, ECO:0000269PubMed:16990611, ECO:0000269PubMed:8182057}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Note=Colocalized with TRPC7 in the plasma membrane. {ECO:0000250}.

Disease Associations

Aortic aneurysm, familial thoracic 8 (AAT8) [MIM:615436]: 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. {ECO:0000269PubMed:23910461}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Primarily expressed in lung and placenta. {ECO:0000269PubMed:9192852}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 29 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	29 [view]
Protein-Protein	29 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004692	cGMP-dependent protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005246	calcium channel regulator activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0030553	cGMP binding

Biological Process

GO:0001764	neuron migration
GO:0006468	protein phosphorylation
GO:0007165	signal transduction
GO:0007596	blood coagulation
GO:0016358	dendrite development
GO:0019934	cGMP-mediated signaling
GO:0030036	actin cytoskeleton organization
GO:0030900	forebrain development
GO:0043087	regulation of GTPase activity
GO:0045986	negative regulation of smooth muscle contraction
GO:0060087	relaxation of vascular smooth muscle
GO:0090331	negative regulation of platelet aggregation

Cellular Component

GO:0005737	cytoplasm
GO:0005794	Golgi apparatus
GO:0005829	cytosol
GO:0005886	plasma membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000595 Cyclic nucleotide-binding domain
IPR000719 Protein kinase domain
IPR000961 AGC-kinase, C-terminal
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR002373 cAMP/cGMP-dependent protein kinase
IPR002374 cGMP-dependent kinase
IPR011009 Protein kinase-like domain
IPR016232 cGMP-dependent protein kinase
IPR018490 Cyclic nucleotide-binding-like
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00027
PF00069
PF07714

PRINTS

PR00109
PR00103
PR00104

PIRSF

PIRSF000559

SMART

SM00100
SM00133
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References