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Information about Cgmp Dependent Protein Kinase

protein kinase, cGMP-dependent, type I
Identifiers
SymbolPRKG1
Alt. SymbolsPRKGR1B, PRKG1B
Entrez5592
HUGO9414
OMIM176894
RefSeqNM_006258
UniProtP14619
Other data
LocusChr. 10 q11.2
protein kinase, cGMP-dependent, type II
Identifiers
SymbolPRKG2
Entrez5593
HUGO9416
OMIM601591
RefSeqNM_006259
UniProtQ13237
Other data
LocusChr. 4 q13.1-21.1


cGMP-dependent protein kinase or Protein Kinase G (PKG) is a serine/threonine-specific protein kinase that is activated by cGMP. It phosphorylates a number of biologically important targets and is implicated in the regulation of smooth muscle relaxation, platelet function, sperm metabolism, cell division ,and nucleic acid synthesis.

Genes and proteins

PKG are serine/threonine kinases that are present in a variety of eukaryotes ranging from the unicellular organism Paramecium to humans. Two PKG genes, coding for PKG type I (PKG-I) and type II (PKG-II), have been identified in mammals. The N-terminus of PKG-I is encoded by two alternatively spliced exons that specify for the PKG-Iα and PKG-Iβ isoforms. PKG-Iβ is activated at ~10-fold higher cGMP concentrations than PKG-Iα. The PKG-I and PKG-II are homodimers of two identical subunits (~75 kDa and ~85 kDa, respectively) and share common structural features.

Each subunit is composed of three functional domains:
  • (1) an N-terminal domain that mediates homodimerization, suppression of the kinase activity in the absence of cGMP, and interactions with other proteins including protein substrates
  • (2) a regulatory domain that contains two non-identical cGMP-binding sites
  • (3) a kinase domain that catalyzes the phosphate transfer from ATP to the hydroxyl group of a serine/threonine side chain of the target protein
Binding of cGMP to the regulatory domain induces a conformational change that releases the inhibition of the catalytic core by the N-terminus and allows the phosphorylation of substrate proteins. Whereas PKG-I is predominantly localized in the cytoplasm, PKG-II is anchored to the plasma membrane by N-terminal myristoylation.

Tissue distribution

In general, PKG-I and PKG-II are expressed in different cell types. Specifically, in smooth muscle tissue, PKG phosphorylates the Myosin light chain phosphatase which dephosphorylates the myosin light chains initiating smooth muscle relaxation.

Role in Cancer

On 18 July 2007 it was discovered that cancerous colon cells stop producing PKG, which apparently limits beta-catenin thus allowing the VEGF enzyme to solicit angiogenesis.[1]

See also

References

External links

 •  • [ e]
Kinases: Serine/threonine-specific protein kinases (primarily EC 2.7.11)
2.7.11Pyruvate dehydrogenase kinase - Protein kinase A - Protein kinase G - Protein kinase C (Protein kinase Mζ) - Rhodopsin - Beta adrenergic receptor - G-protein coupled receptor kinases - Ca2+/calmodulin-dependent - Myosin light-chain) - Phosphorylase - Cyclin-dependent - Mitogen-activated (Extracellular signal-regulated, C-Jun N-terminal, P38 mitogen-activated protein) - MAP3K - GSK-3 - AMP-activated
2.7.12MAP2K
2.7.1.37, or unknownAnti-Mullerian hormone receptor - Ataxia telangiectasia mutated - Aurora (A, B) - Mammalian target of rapamycin - Bone morphogenetic protein receptors (1, 2) - CDKL5 - c-Raf - EIF-2 - Ribosomal s6 - Protein kinase B - PDK1
The Entrez Global Query Cross-Database Search System is a powerful federated search engine, or web portal that allows users to search many discrete health sciences databases at the National Center for Biotechnology Information (NCBI) website.
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Hugo is a male given name, a latinized form of the name Hugh, a German/Teutonic name meaning "Bright in Mind and Spirit".

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Swiss-Prot is a manually curated biological database of protein sequences. Swiss-Prot was created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute.
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locus (plural loci) is a fixed position on a chromosome, such as the position of a gene or a biomarker (genetic marker). A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map.
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The Entrez Global Query Cross-Database Search System is a powerful federated search engine, or web portal that allows users to search many discrete health sciences databases at the National Center for Biotechnology Information (NCBI) website.
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Hugo is a male given name, a latinized form of the name Hugh, a German/Teutonic name meaning "Bright in Mind and Spirit".

Hugo is one of the most popular names in Europe ranking as high as #2 in France, #6 in Spain, and #7 in Belgium in 2006.
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The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988.
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Swiss-Prot is a manually curated biological database of protein sequences. Swiss-Prot was created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute.
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locus (plural loci) is a fixed position on a chromosome, such as the position of a gene or a biomarker (genetic marker). A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map.
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Serine/threonine protein kinases (EC 2.7.11.1 ) phosphorylate the OH group of serine or threonine (which have similar sidechains).

Regulation

Activity of these protein kinases can be regulated by specific events (e.g.
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Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP, most notably by activating intracellular protein kinases in response to the binding of membrane-impermeable peptide
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Smooth muscle is a type of non-striated muscle, found within the "walls" of hollow organs and elsewhere like the bladder and abdominal cavity, the uterus, male and female reproductive tracts, the gastrointestinal tract, the respiratory tract, the vasculature, the skin and the
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Platelets, or thrombocytes, are the cell fragments circulating in the blood that are involved in the cellular mechanisms of primary hemostasis leading to the formation of blood clots.
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A spermatozoon or spermatozoan (pl. spermatozoa), from the ancient Greek σπέρμα (seed) and ζῷον (living being) and more commonly known as a sperm cell
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Cell division is a process by which a cell, called the parent cell, divides into two cells, called daughter cells. Cell division is usually a small segment of a larger cell cycle. In meiosis however, a cell is permanently transformed and cannot divide again.
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A nucleic acid is a macromolecule composed of nucleotide chains. In biochemistry these molecules carry genetic information or form structures within cells. The most common nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).
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Paramecium
Müller, 1773

Species
Paramecium tetraurelia
Paramecium aurelia
Paramecium caudatum
Paramecium is a group of unicellular ciliate protozoa formerly known as slipper animalcules from their slipper shape.
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For a non-technical introduction to the topic, see .
A gene is a locatable region of genomic sequence, corresponding to a unit of inheritance, which is associated with regulatory regions, transcribed regions and/or other functional sequence regions.
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Mammalia
Linnaeus, 1758

Subclasses & Infraclasses
  • Subclass †Allotheria*
  • Subclass Prototheria
  • Subclass Theria

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The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) refers to the end of a protein or polypeptide terminated by an amino acid with a free amine group (-NH2).
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An exon is any region of DNA within a gene that is transcribed to the final messenger RNA (mRNA) molecule, rather than being spliced out from the transcribed RNA molecule. Exons of many eukaryotic genes interleave with segments of non-coding DNA (introns).
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A protein isoform is a version of a protein with only small differences to another isoform of the same protein. Different forms of a protein may be produced from different but related genes, or may arise from the same gene by alternative splicing.
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dimer refers to a molecule composed of two identical subunits or monomers linked together.

Chemistry

The molecules in a dimer are connected by covalent bonds or weaker interactions such as hydrogen bonds.
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In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles (or "coassembles") with other protein molecules to form a multimeric or oligomeric protein.
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citation, footnoting or external linking.


A structural domain is an element of overall structure within a protein that is self-stabilizing and often folds independently of the rest of the protein chain.
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A phosphate, in inorganic chemistry, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Phosphates are important in biochemistry and biogeochemistry.
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Adenosine 5'-triphosphate (ATP) is a multifunctional nucleotide that is most important as a "molecular currency" of intracellular energy transfer. In this role, ATP transports chemical energy within cells for metabolism.
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Hydroxyl in chemistry stands for a molecule consisting of an oxygen atom and a hydrogen atom connected by a covalent bond. The neutral form is a hydroxyl radical and the hydroxyl anion is called a hydroxide.
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