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FLASH GENE
Symbol PRKG1 contributors: mct - updated : 30-01-2024
HGNC name protein kinase, cGMP-dependent, type I
HGNC id 9414
Corresponding disease
TAAD6 thoracic aortic aneurysm with aortic dissection 6
Location 10q21.1      Physical location : 52.750.944 - 54.055.274
Synonym name
  • cGMP-dependent, regulatory, type I, beta
    • Synonym symbol(s) PRKGR1, PKG1, PGK, CGKI, PRKG1B, PKG, DKFZp686K042, FLJ36117, MGC71944, cGK-I, AAT8 cGK1, cGKI-BETA, cGKI-alpha
    EC.number 2.7.1.37/ 2.7.11.12
    DNA
    TYPE functioning gene
    STRUCTURE 1307.46 kb     18 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    RNA
    TRANSCRIPTS type messenger
    text with two alternatively spliced isoforms,1 alpha,1 beta
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    19 - 3824 - 671 predominantly, in lung and placenta, and in penile erectile tissue 2011 21526164
  • isoform alpha or 1alpha
    • 18 - 3792 - 686 bladder, uterus, adrenals, fallopian tube, and in penile erectile tissue 2011 21526164
  • isoform beta or 1beta
    • 7 - 1274 - 312 - 2011 21526164
    14 - 5920 - 283 - 2011 21526164
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Hearing/Equilibriumearinner    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Hearing / Equilibriumhair cell receptor Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal leucine zipper domain mediating interactions with RGS2, and &
    • 8764;50 AAs of the kinase are required for homodimerization and association with isoform-specific PKG-anchoring proteins (GKAPs), which target the kinase to specific substrates
    mono polymer homomer , dimer
    HOMOLOGY
    interspecies ortholog to Drosophila foraging
    Homologene
    FAMILY PRK family
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • relaxing vascular smooth muscle and inhibiting platelet aggregation
  • significant role in the control of smooth muscle function in human penile erectile tissue
  • key regulator of cardiovascular physiology and pathology
  • its activity prevents pathological-level nitric oxide-induced apoptosis and promotes DNA synthesis/cell proliferation in vascular smooth muscle cells
  • key mediator of the nitric oxide/cGMP signaling pathway and plays a central role in regulating cardiovascular and neuronal functions
  • modulates glucagon release from pancreatic alpha-cells
  • serves as an integral component of second messenger signaling in a number of biological contexts including cell differentiation, memory, and vasodilation
  • is a key orchestrator of VEGFA and BMP signaling during bone regeneration
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • important behavioral and physiological functions for the GUCY2C/PRKG1 signaling pathway within the brain
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • with RGS2
  • interacting with TP53 (TP53-dependent expression of PRKG1 is required for the ability of cGMP to counteract growth cone collapse)
  • exerts dual regulation of cardiac KCNJ channels
  • PRKG1 interacts with and phosphorylates rhotekin, thereby contributing to neurite outgrowth regulation
  • DAPK2 is likely one of the targets of PRKG1 in apoptosis induction
  • PRKG1 is a novel regulator of AR-mediated transcription by enhancing AR cofactor WDR77 function, which provide a novel mechanism for the growth regulation of prostate cancer cells by the androgen signaling
  • PRKG1 is a potent negative modulator of cardiac systolic mechanosignaling that requires TRPC6 as the target effector
  • OSTN protects against diabetic cardiomyopathy (DCM) via restoring PRKG1-dependent proteasomal activity
    • cell & other
    REGULATION
    Other its expression is subjected to post-transcriptional regulation in vascular smooth muscle cells through the 3 prime UTR of its mRNA
    TP53 is a transcription factor that regulates the expression of PRKG1 during neuronal maturation and cGMP-dependent inhibition of growth cone collapse
    ASSOCIATED DISORDERS
    corresponding disease(s) TAAD6
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    in non-neuronal cells results in a complex metabolic phenotype, including liver inflammation and fasting hyperglycemia (
    constitutional germinal mutation      
    de novo PRKG1 mutation in a sporadic patient with aortic dissection
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    osteoarticularboneaquired
    pharmacological PRKG1 activation is a novel therapeutic approach to enhance fracture healing
    cardiovascular  
    maintaining PRKG1 in its reduced form may optimize its intrinsic cardioprotective properties
    ANIMAL & CELL MODELS
  • greater vulnerability to Noise-induced hearing loss (NIHL) in mice with deletion of Prkg1 as compared to mice without the deletion
  • cardiac myocytes from Prkg1R177Q/+ mice showed altered phosphorylation of sarcomeric proteins and reduced contractility in response to electrical stimulation, compared to cells from wild type mice