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    PRKG1 protein kinase, cGMP-dependent, type I [ Homo sapiens ]

    Gene ID: 5592, updated on 19-May-2012
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    Summary

    Official Symbol
    PRKG1provided by HGNC
    Official Full Name
    protein kinase, cGMP-dependent, type Iprovided by HGNC
    Primary source
    HGNC:9414
    Locus tag
    RP11-346D6.1
    See related
    Ensembl:ENSG00000185532; HPRD:08910; MIM:176894; Vega:OTTHUMG00000018248
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    1; PKG; cGK; cGK1; cGKI; cGK 1; PRKG1B; PRKGR1B; cGKI-BETA; cGKI-alpha; FLJ36117; MGC71944; DKFZp686K042
    Summary
    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]
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    Genomic context

    Location :
    10q11.2
    Sequence :
    Chromosome: 10; NC_000010.10 (52750945..54055274)
    See PRKG1 in Epigenomics, MapViewer

    Chromosome 10 - NC_000010.10Genomic Context describing neighboring genes Neighboring gene coiled-coil domain containing 58 pseudogene Neighboring gene APOBEC1 complementation factor Neighboring gene Ras suppressor protein 1 pseudogene Neighboring gene microRNA 605 Neighboring gene cleavage stimulation factor, 3' pre-RNA, subunit 2, 64kDa, tau variant Neighboring gene uncharacterized LOC100506939 Neighboring gene dickkopf 1 homolog (Xenopus laevis)

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. cGMP-dependent protein kinase Iα transfection inhibits hypoxia-induced migration, phenotype modulation and annexins A1 expression in human pulmonary artery smooth muscle cells. Yi B, et al. Biochem Biophys Res Commun, 2012 Feb 24. PMID 22293199.
    2. Expression and distribution of key enzymes of the cyclic GMP signaling in the human clitoris: relation to phosphodiesterase type 5 (PDE5). Ückert S, et al. Int J Impot Res, 2011 Sep-Oct. PMID 21697861.
    3. Cyclic 3',5'-guanosine monophosphate-dependent protein kinase inhibits colon cancer cell adaptation to hypoxia. Kwon IK, et al. Cancer, 2011 Dec 1. PMID 21563174.
    4. Co-crystal structures of PKG Iβ (92-227) with cGMP and cAMP reveal the molecular details of cyclic-nucleotide binding. Kim JJ, et al. PLoS One, 2011 Apr 19. PMID 21526164.
    5. Activation of cGMP-dependent protein kinase stimulates cardiac ATP-sensitive potassium channels via a ROS/calmodulin/CaMKII signaling cascade. Chai Y, et al. PLoS One, 2011 Mar 29. PMID 21479273.

    See all (108) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. cGMP-dependent protein kinase (PKG) Ialpha transfection significantly attenuated the hypoxia-induced down-regulation of the expressions of SM-alpha-actin, MHC and calponin.
      Title: cGMP-dependent protein kinase Iα transfection inhibits hypoxia-induced migration, phenotype modulation and annexins A1 expression in human pulmonary artery smooth muscle cells.
    2. found in smooth muscle wall of blood vessels transversing the clitoral supepithelial and stromal space
      Title: Expression and distribution of key enzymes of the cyclic GMP signaling in the human clitoris: relation to phosphodiesterase type 5 (PDE5).
    3. Cyclic 3',5'-guanosine monophosphate-dependent protein kinase inhibits colon cancer cell adaptation to hypoxia.
      Title: Cyclic 3',5'-guanosine monophosphate-dependent protein kinase inhibits colon cancer cell adaptation to hypoxia.
    4. cGMP dependent kinase 1 alpha interacts with and phosphorylates transient receptor potential cation channel subfamily C member 7
      Title: Functional regulation of transient receptor potential canonical 7 by cGMP-dependent protein kinase Iα.
    5. data suggest that activation of PKG signaling in pericytes inhibits focal adhesion formation by inhibiting Rac1
      Title: Protein kinase G signaling disrupts Rac1-dependent focal adhesion assembly in liver specific pericytes.
    6. NO, depending on its concentration, may act in human PBMCs as a stimulator of IL-6 expression and modulator of NF-KB involving the sGC/cGMP/PKG pathway
      Title: Nitric oxide affects IL-6 expression in human peripheral blood mononuclear cells involving cGMP-dependent modulation of NF-κB activity.
    7. The mechanism of cyclic nucleotide binding to PKG was investigated by determining crystal structures of the amino-terminal cyclic nucleotide-binding domain (CNBD-A) of human PKG I bound to either cGMP or cAMP.
      Title: Co-crystal structures of PKG Iβ (92-227) with cGMP and cAMP reveal the molecular details of cyclic-nucleotide binding.
    8. The novel cGMP/PKG/ROS/calmodulin/CaMKII signaling pathway may regulate cardiomyocyte excitability by opening K(ATP) channels and contribute to cardiac protection against ischemia-reperfusion injury.
      Title: Activation of cGMP-dependent protein kinase stimulates cardiac ATP-sensitive potassium channels via a ROS/calmodulin/CaMKII signaling cascade.
    9. These findings provide evidence of a physical and compartmentalized association between SERT and PKGIalpha that supports.
      Title: cGMP-dependent protein kinase Ialpha associates with the antidepressant-sensitive serotonin transporter and dictates rapid modulation of serotonin uptake.
    10. A novel mechanism has been elucidated that is able to increase PKG-I protein content in contractile cells, with hypotensive consequences in rat thoracic aorta.
      Title: Fibronectin upregulates cGMP-dependent protein kinase type Iβ through C/EBP transcription factor activation in contractile cells.
    Submit: New GeneRIF Correction See all (55)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    P14619 P13569 CFTR    HPRD  PubMed  
    P14619 P16220 CREB1    HPRD  PubMed  
    P14619 P52943 CRIP2    HPRD  PubMed  
    P14619 Q9Y613 FHOD1    HPRD  PubMed  
    P14619 P24046 GABRR1    HPRD  PubMed  
    P14619 G kinase anchoring protein 1 GKAP1    HPRD  PubMed  
    P14619 P78347 GTF2I    HPRD  PubMed  
    P14619 Q14643 ITPR1    HPRD  PubMed  
    P14619 Q14847 LASP1    HPRD  PubMed  
    P14619 MRVI1 MRVI1    HPRD  PubMed  
    P14619 P16066 NPR1    HPRD  PubMed  
    P14619 O76074 PDE5A    HPRD  PubMed  
    P14619 Q01970 PLCB3    HPRD  PubMed  
    P14619 O14974 PPP1R12A    HPRD  PubMed  
    P14619 O96001 PPP1R17    HPRD  PubMed  
    P14619 P17252 PRKCA    HPRD  PubMed  
    P14619 P04049 RAF1    HPRD  PubMed  
    P14619 P41220 RGS2    HPRD  PubMed  
    P14619 P21817 RYR1    HPRD  PubMed  
    P14619 Q9UH03 SEPT3    HPRD  PubMed  
    P14619 Q15637 SF1    HPRD  PubMed  
    P14619 P10451 SPP1    HPRD  PubMed  
    P14619 P13805 TNNT1    HPRD  PubMed  
    P14619 Q13507 TRPC3    HPRD  PubMed  
    P14619 P50552 VASP    HPRD  PubMed  
    BioGRID:111578 BioGRID:108868 GAPDH    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:111578 BioGRID:109224 GTF2I    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:111578 BioGRID:109315 HDAC1    BioGRID  PubMed Biochemical Activity 
    BioGRID:111578 BioGRID:109913 ITPR1    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity 
    BioGRID:111578 BioGRID:115617 MRVI1    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity; Two-hybrid 
    BioGRID:111578 BioGRID:110941 NPR1    BioGRID  PubMed Two-hybrid 
    BioGRID:111578 BioGRID:110742 PPP1R12A    BioGRID  PubMed Reconstituted Complex 
    BioGRID:111578 BioGRID:110743 PPP1R12B    BioGRID  PubMed Two-hybrid 
    BioGRID:111578 BioGRID:111831 RAF1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:111578 BioGRID:111929 RGS2    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:111578 BioGRID:112992 TNNT1    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity; Reconstituted Complex; Two-hybrid 
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    General gene information

    Markers

    Genotypes

    Homology

    • Homologs of the PRKG1 gene: The PRKG1 gene is conserved in chimpanzee, , dog, cow, mouse, rat, chicken, zebrafish, fruit fly, C.elegans, and P.falciparum.
    • Map Viewer (Mouse, Rat)

    Pathways from BioSystems

    • Adaptive Immune System, organism-specific biosystem (from REACTOME)
      Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
    • Gap junction, organism-specific biosystem (from KEGG)
      Gap junction, organism-specific biosystemGap junctions contain intercellular channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is formed by docking of two 'hemichannels'...
    • Gap junction, conserved biosystem (from KEGG)
      Gap junction, conserved biosystemGap junctions contain intercellular channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is formed by docking of two 'hemichannels'...
    • Hemostasis, organism-specific biosystem (from REACTOME)
      Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Long-term depression, organism-specific biosystem (from KEGG)
      Long-term depression, organism-specific biosystemCerebellar long-term depression (LTD), thought to be a molecular and cellular basis for cerebellar learning, is a process involving a decrease in the synaptic strength between parallel fiber (PF) and...
    • Long-term depression, conserved biosystem (from KEGG)
      Long-term depression, conserved biosystemCerebellar long-term depression (LTD), thought to be a molecular and cellular basis for cerebellar learning, is a process involving a decrease in the synaptic strength between parallel fiber (PF) and...
    • MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystem (from WikiPathways)
      MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystemThis pathway shows the role of microRNAs in the process of cardiac hypertrophy. MicroRNA targets were predicted by the TargetScan algorithm, and the predicted interactions are shown in red dashed lin...
    • Nitric oxide stimulates guanylate cyclase, organism-specific biosystem (from REACTOME)
      Nitric oxide stimulates guanylate cyclase, organism-specific biosystemNitric Oxide (NO) inhibits smooth muscle cell proliferation and migration, oxidation of low-density lipoproteins, and platelet aggregation and adhesion. It can stimulate vasodilatation of the endothe...
    • Olfactory transduction, organism-specific biosystem (from KEGG)
      Olfactory transduction, organism-specific biosystemWithin the compact cilia of the olfactory receptor neurons (ORNs) a cascade of enzymatic activity transduces the binding of an odorant molecule to a receptor into an electrical signal that can be tra...
    • Olfactory transduction, conserved biosystem (from KEGG)
      Olfactory transduction, conserved biosystemWithin the compact cilia of the olfactory receptor neurons (ORNs) a cascade of enzymatic activity transduces the binding of an odorant molecule to a receptor into an electrical signal that can be tra...
    • Platelet homeostasis, organism-specific biosystem (from REACTOME)
      Platelet homeostasis, organism-specific biosystemUnder normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhesion and activation, suppresses coagulation, enhances fibrin cleavage and is anti-inflammatory in charact...
    • Rap1 signalling, organism-specific biosystem (from REACTOME)
      Rap1 signalling, organism-specific biosystemRap1 (Ras-proximate-1) is a small G protein in the Ras superfamily. Like all G proteins, Rap1 is activated when bound GDP is exchanged for GTP. Rap1 is targeted to lipid membranes by the covalent att...
    • Salivary secretion, organism-specific biosystem (from KEGG)
      Salivary secretion, organism-specific biosystemSaliva has manifold functions in maintaining the integrity of the oral tissues, in protecting teeth from caries, in the tasting and ingestion of food, in speech and in the tolerance of tenures, for e...
    • Salivary secretion, conserved biosystem (from KEGG)
      Salivary secretion, conserved biosystemSaliva has manifold functions in maintaining the integrity of the oral tissues, in protecting teeth from caries, in the tasting and ingestion of food, in speech and in the tolerance of tenures, for e...
    • Vascular smooth muscle contraction, organism-specific biosystem (from KEGG)
      Vascular smooth muscle contraction, organism-specific biosystemThe vascular smooth muscle cell (VSMC) is a highly specialized cell whose principal function is contraction. On contraction, VSMCs shorten, thereby decreasing the diameter of a blood vessel to regula...
    • Vascular smooth muscle contraction, conserved biosystem (from KEGG)
      Vascular smooth muscle contraction, conserved biosystemThe vascular smooth muscle cell (VSMC) is a highly specialized cell whose principal function is contraction. On contraction, VSMCs shorten, thereby decreasing the diameter of a blood vessel to regula...
    • cGMP effects, organism-specific biosystem (from REACTOME)
      cGMP effects, organism-specific biosystemCyclic guanosine monophosphate (cGMP) is an important secondary messenger synthesized by guanylate cyclases. cGMP has effects on phosphodiesterases (PDE), ion-gated channels, and the cGMP-dependent p...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    cGMP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    cGMP-dependent protein kinase activity IDA
    Inferred from Direct Assay
    more info
    		  
    calcium channel regulator activity IDA
    Inferred from Direct Assay
    more info
    		  
    nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		  
    protein serine/threonine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    actin cytoskeleton organization TAS
    Traceable Author Statement
    more info
    		 PubMed 
    blood coagulation TAS
    Traceable Author Statement
    more info
    		  
    negative regulation of platelet aggregation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    protein phosphorylation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    regulation of GTPase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    plasma membrane IDA
    Inferred from Direct Assay
    more info
    		  
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    General protein information

    Preferred Names
    cGMP-dependent protein kinase 1
    Names
    cGMP-dependent protein kinase 1
    protein kinase, cGMP-dependent, regulatory, type I, beta
    NP_001091982.1
    NP_006249.1
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029982.1 RefSeqGene

      Range
      5001..1312200
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001098512.2 → NP_001091982.1  cGMP-dependent protein kinase 1 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the shorter isoform (1; also known as alpha or 1alpha).
      Source sequence(s)
      AL599933, BC127090, BQ445850, BX097700, BX952280, CD723759, D45864, DA646702, DA915933, DB138350, DC381245
      Consensus CDS
      CCDS44399.1
      UniProtKB/Swiss-Prot
      Q13976
      Related
      ENSP00000384200, ENST00000401604
      Conserved Domains (4) summary
      cd00038
      Location:222 – 326
      Blast Score: 250
      CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...
      cd05572
      Location:366 – 626
      Blast Score: 1168
      STKc_cGK_PKG; Catalytic domain of the Protein Serine/Threonine Kinase, cGMP-dependent protein kinase
      smart00220
      Location:360 – 619
      Blast Score: 652
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl11395
      Location:621 – 648
      Blast Score: 107
      Pkinase_C; Protein kinase C terminal domain

    2. NM_006258.3 → NP_006249.1  cGMP-dependent protein kinase 1 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate exon at its 5' end which result in the use of a distinct translation initiation site, compared to variant 1. This difference results in an isoform (2; also known as beta or 1beta) with a longer and distinct N-terminus, compared to isoform 1.
      Source sequence(s)
      AL599933, BC127090, BQ445850, BX097700, BX952280, CD723759, DA150150, DA646702, DA915933, DB138350
      Consensus CDS
      CCDS7244.1
      UniProtKB/Swiss-Prot
      Q13976
      Related
      ENSP00000363092, OTTHUMP00000019619, ENST00000373980, OTTHUMT00000048103
      Conserved Domains (4) summary
      cd00038
      Location:237 – 341
      Blast Score: 250
      CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...
      cd05572
      Location:381 – 641
      Blast Score: 1164
      STKc_cGK_PKG; Catalytic domain of the Protein Serine/Threonine Kinase, cGMP-dependent protein kinase
      smart00220
      Location:375 – 634
      Blast Score: 651
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl11395
      Location:636 – 663
      Blast Score: 107
      Pkinase_C; Protein kinase C terminal domain

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000010.10 Reference GRCh37.p5 Primary Assembly

      Range
      52750945..54055274
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000142.1 Alternate HuRef

      Range
      46729561..48033476
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC009986.10 (167333..167418) None
    genomic AC022025.8 (46330..189761) None
    genomic AC022537.8 None
    genomic AC026228.6 (48451..177966) None
    genomic AC027118.9 None
    genomic AC068062.7 None
    genomic AC069079.11 None
    genomic AC073584.6 None
    genomic AL157399.14 CAI41304.1
      CAI41305.1
      CAI41306.1
    genomic AL391378.10 CAI39625.1
      CAI39626.1
      CAI39627.1
    genomic AL596105.5 (2000..26516) None
    genomic AL607031.5 (2000..6281) None
    genomic AL731537.8 CAI17114.1
      CAI17115.1
    genomic AL928686.2 CAI40742.1
      CAI40743.1
      CAI40744.1
    genomic CH471083.1 EAW54140.1
      EAW54141.1
    genomic Z92867.1 CAB07436.1
    genomic Z92868.1 CAB07437.1
    mRNA AK093436.1 BAG52715.1
    mRNA AK300110.1 BAG61905.1
    mRNA AK313416.1 None
    mRNA AL599933.1 None
    mRNA BC062688.1 AAH62688.1
    mRNA BC127090.1 AAI27091.1
    mRNA BQ445850.1 None
    mRNA BX097700.1 None
    mRNA BX952280.1 None
    mRNA CD723759.1 None
    mRNA D45864.1 BAA08297.1
    mRNA DA150150.1 None
    mRNA DA646702.1 None
    mRNA DA915933.1 None
    mRNA DB138350.1 None
    mRNA DC310312.1 None
    mRNA DC379897.1 None
    mRNA DC381245.1 None
    mRNA EF560730.1 ABQ59040.1
    mRNA Y07512.1 CAA68810.1
    other-genetic GQ129235.1 ACT64369.1
    other-genetic GQ129236.1 ACT64370.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q13976.3 GenPept UniProtKB/Swiss-Prot:Q13976
    Q5JP05 GenPept UniProtKB/TrEMBL:Q5JP05
    Q5SQU3 GenPept UniProtKB/TrEMBL:Q5SQU3
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    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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