Homo sapiens Protein: PRKG1 | |||||||||||||||||||||||
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Summary | |||||||||||||||||||||||
InnateDB Protein | IDBP-293256.5 | ||||||||||||||||||||||
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 | ENSP00000384200 | ||||||||||||||||||||||
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.
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Gene Ontology | |||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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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 IPR018490 Cyclic nucleotide-binding-like IPR020635 Tyrosine-protein kinase, catalytic domain |
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PFAM |
PF00027
PF00069 PF07714 |
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PRINTS |
PR00109
PR00103 PR00104 |
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PIRSF | |||||||||||||||||||||||
SMART |
SM00100
SM00133 SM00220 SM00219 |
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TIGRFAMs | |||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||
Modification | |||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||
SwissProt | Q13976 | ||||||||||||||||||||||
PhosphoSite | PhosphoSite-Q13976 | ||||||||||||||||||||||
TrEMBL | |||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||
Entrez Gene | 5592 | ||||||||||||||||||||||
UniGene | Hs.641130 | ||||||||||||||||||||||
RefSeq | |||||||||||||||||||||||
HUGO | HGNC:9414 | ||||||||||||||||||||||
OMIM | 176894 | ||||||||||||||||||||||
CCDS | |||||||||||||||||||||||
HPRD | 08910 | ||||||||||||||||||||||
IMGT | |||||||||||||||||||||||
EMBL | AC009986 AC022025 AC022537 AC026228 AC027118 AL157399 AL391378 AL731537 AL928686 BC062688 BC127090 CH471083 D45864 Y07512 Z92867 Z92868 Z92869 Z92870 Z92871 Z92872 Z92873 Z92874 Z92875 Z92876 Z92877 Z92878 Z92879 Z92880 Z92881 Z92882 Z92883 Z92884 Z92885 | ||||||||||||||||||||||
GenPept | AAH62688 AAI27091 BAA08297 CAA68810 CAB07436 CAB07437 CAI17115 CAI39626 CAI40743 CAI41305 EAW54140 | ||||||||||||||||||||||