セリン／トレオニンキナーゼ
671アミノ酸がジスルフィド結合による二量体を形成する。
Ｎ末端にcGMP結合サイトが２カ所ある。Ｃ末端側にキナーゼドメインをもつ。
Short name=cGK 1
Short name=cGK1
EC=2.7.11.12
Alternative name(s):
cGMP-dependent protein kinase I
Short name=cGKI
Gene names
Name: PRKG1
Synonyms: PRKG1B, PRKGR1A, PRKGR1B
Organism Homo sapiens (Human) [Reference proteome]
Taxonomic identifier 9606 [NCBI]
Taxonomic lineage Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Protein attributes
Sequence length 671 AA.
Sequence status Complete.
Sequence processing The displayed sequence is further processed into a mature form.
Protein existence Evidence at protein level
General annotation (Comments)
Function
PRKG1によりリン酸化されるタンパク質は、
一酸化窒素／cGMPシグナル伝達経路を介在するセリントレオニンキナーゼ。GMP結合により多くの細胞質タンパク質のセリン、トレオニンをリン酸化する活性が増加する。
細胞内カルシウム代謝に係わるタンパクを含めて多くの細胞内タンパク質がリン酸化されるが、細胞の種類により寄与は異なる。血小板の活性化と接着、平滑筋の収縮、心臓機能、遺伝子発現、NOシグナリングのフィードバック、海馬や小脳の学習、概日リズムなど。
平滑筋の弛緩は細胞内カルシウム濃度の低下によってもたらされる。
Ras類似の低分子量Ｇタンパク質（RhoA）の活性を低下させることで、さまざまなプロセスに影響する。
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 Ca2+ release from intracellular stores, phosphorylation of KCNMA1 (BKCa) channels decreases intracellular Ca2+ 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. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.21
Catalytic activity
ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation
In the absence of cGMP, PRKG1 activity is suppressed by autoinhibitory contacts.
Subunit structure
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. Ref.9 Ref.11 Ref.13 Ref.15 Ref.16 Ref.17 Ref.21 Ref.22 Ref.23
Subcellular location
Cytoplasm By similarity. Note: Colocalized with TRPC7 in the plasma membrane By similarity. Ref.15 Ref.21
Tissue specificity
Primarily expressed in lung and placenta. Ref.4
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.
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.
Post-translational modification
Autophosphorylation increases kinase activity.
65 kDa monomer is produced by proteolytic cleavage By similarity.
Sequence similarities
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cGMP subfamily.
Contains 1 AGC-kinase C-terminal domain.
Contains 2 cyclic nucleotide-binding domains.
Contains 1 protein kinase domain.
