ID:KGP1_HUMAN DESCRIPTION: RecName: Full=cGMP-dependent protein kinase 1; Short=cGK 1; Short=cGK1; EC=2.7.11.12; AltName: Full=cGMP-dependent protein kinase I; Short=cGKI; FUNCTION: Serine/threonine protein kinasethat 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. Smoth 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. ENZYME REGULATION: In the absence of cGMP, PRKG1 activity is suppressed by autoinhibitory contacts. SUBUNIT: Isoform alpha: parallel homodimer or heterodimer and also heterotetramer. Interacts directly with PPP1R12A. Non-covalent dimer of dimer of PRKG1-PRKG1 and PPP1R12A-PPP1R12A. This interaction targets PRKG1 to stress fibers to mediate smooth muscle cell relaxation and vasodilation in responses to rises in cGMP. Isoform beta: antiparallel homodimer. Part of cGMP kinase signaling complex at least composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1 (By similarity). Interacts with MRVI1. Forms a stable complex with ITPR1, MRVI1, and isoform beta of PRKG1. Interacts with TRPC7 (via ankyrin repeat domain). Isoform alpha interacts with RGS2. Interacts with GTF2I. SUBCELLULAR LOCATION: Cytoplasm (By similarity). Note=Colocalized with TRPC7 in the plasma membrane (By similarity). TISSUE SPECIFICITY: Primarily expressed in lung and placenta. DOMAIN: Composed of an N-terminal leucine-zipper domain followed by an autoinhibitory domain, which mediate homodimer formation and inhibit kinase activity, respectively. Next, two cGMP-binding domains are followed by the catalytic domain at the C-terminus. Binding of cGMP to cGMP-binding domains results in a conformational change that activates kinase activity by removing the autoinhibitory domain from the catalytic cleft leaving the catalytic domain free to phosphorylate downstream substrates. Isoforms alpha and beta have identical cGMP-binding and catalytic domains but differ in their leucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity. DOMAIN: Heterotetramerization is mediated by the interaction between a coiled-coil of PRKG1 and the leucine/isoleucine zipper of PPP1R12A/MBS, the myosin-binding subunit of the myosin phosphatase. PTM: Autophosphorylation increases kinase activity. PTM: 65 kDa monomer is produced by proteolytic cleavage (By similarity). SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cGMP subfamily. SIMILARITY: Contains 1 AGC-kinase C-terminal domain. SIMILARITY: Contains 2 cyclic nucleotide-binding domains. SIMILARITY: Contains 1 protein kinase domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13976
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
D45864 - Homo sapiens mRNA for cGMP-dependent protein kinase type I alpha, complete cds. AK313416 - Homo sapiens cDNA, FLJ93954. EF560730 - Homo sapiens clone DKFZp686K042 PRKG1 protein (PRKG1) mRNA, complete cds. BC127090 - Homo sapiens protein kinase, cGMP-dependent, type I, mRNA (cDNA clone MGC:150609 IMAGE:40123332), complete cds. Y07512 - Human mRNA for type I beta cGMP-dependent protein kinase (EC 2.7.1.37). BC062688 - Homo sapiens protein kinase, cGMP-dependent, type I, mRNA (cDNA clone IMAGE:30350012), complete cds. AB590766 - Synthetic construct DNA, clone: pFN21AB6261, Homo sapiens PRKG1 gene for protein kinase, cGMP-dependent, type I, without stop codon, in Flexi system. GQ129235 - Synthetic construct Homo sapiens clone HAIB:100068643; DKFZo004A0436 protein kinase, cGMP-dependent, type I protein (PRKG1) gene, partial cds. GQ129236 - Synthetic construct Homo sapiens clone HAIB:100068547; DKFZo008A0435 protein kinase, cGMP-dependent, type I protein (PRKG1) gene, complete cds. KJ891891 - Synthetic construct Homo sapiens clone ccsbBroadEn_01285 PRKG1 gene, encodes complete protein. AK300110 - Homo sapiens cDNA FLJ58408 complete cds, highly similar to cGMP-dependent protein kinase 1, alphaisozyme (EC 2.7.11.12). AK093436 - Homo sapiens cDNA FLJ36117 fis, clone TESTI2022400, highly similar to cGMP-dependent protein kinase 1, beta isozyme (EC 2.7.11.12). JD491946 - Sequence 472970 from Patent EP1572962. JD139457 - Sequence 120481 from Patent EP1572962. JD557178 - Sequence 538202 from Patent EP1572962. JD298497 - Sequence 279521 from Patent EP1572962. JD260152 - Sequence 241176 from Patent EP1572962. JD267261 - Sequence 248285 from Patent EP1572962. JD428898 - Sequence 409922 from Patent EP1572962. JD354877 - Sequence 335901 from Patent EP1572962. JD297260 - Sequence 278284 from Patent EP1572962. JD249306 - Sequence 230330 from Patent EP1572962. JD434520 - Sequence 415544 from Patent EP1572962. JD101139 - Sequence 82163 from Patent EP1572962. JD312618 - Sequence 293642 from Patent EP1572962. JD558111 - Sequence 539135 from Patent EP1572962. JD360727 - Sequence 341751 from Patent EP1572962. JD284957 - Sequence 265981 from Patent EP1572962. JD053094 - Sequence 34118 from Patent EP1572962. JD095899 - Sequence 76923 from Patent EP1572962. JD422157 - Sequence 403181 from Patent EP1572962. JD453752 - Sequence 434776 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q13976 (Reactome details) participates in the following event(s):
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
