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Information on EC 2.7.11.12 - cGMP-dependent protein kinase and Organism(s) Bos taurus and UniProt Accession P00516
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2.7.11.12 cGMP-dependent protein kinaseIUBMB Comments
CGMP is required to activate this enzyme. The enzyme occurs as a dimer in higher eukaryotes. The C-terminal region of each polypeptide chain contains the catalytic domain that includes the ATP and protein substrate binding sites. This domain catalyses the phosphorylation by ATP to specific serine or threonine residues in protein substrates . The enzyme also has two allosteric cGMP-binding sites (sites A and B). Binding of cGMP causes a conformational change that is associated with activation of the kinase .
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Word Map
- 2.7.11.12
- cyclase
-
guanylyl
-
guanylate
-
camp-dependent
- phosphodiesterase
- endothelial
- artery
-
natriuretic
- pka
- cardiac
- nitroprusside
- 8-br-cgmp
-
contractile
- atrial
- phosphoprotein
-
myocytes
-
vasodilation
- 8-bromo-cgmp
-
l-name
-
no-induced
- sildenafil
-
vasorelaxation
-
l-type
-
cgmp-mediated
-
vasodilator-stimulated
-
patch-clamp
-
membrane-permeable
- snap
- vasp
-
cell-attached
- monophosphorothioate
- nonoate
-
cgmp-independent
- zaprinast
-
no-cgmp
-
iberiotoxin
-
atp-sensitive
-
1h-1,2,4oxadiazolo4,3-aquinoxalin-1-one
-
large-conductance
- s-nitroso-n-acetylpenicillamine
-
8-bromo-cyclic
-
cgmp-specific
- cak
- drug development
- 8-bromoguanosine
- rp-camps
-
cgmp-inhibited
-
nitrovasodilators
- medicine
- mypt1
- pharmacology
-
no-sensitive
-
oxide-cyclic
The taxonomic range for the selected organisms is: Bos taurus
The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria
Reaction Schemes
+
a [protein]-(L-serine/L-threonine)
=
+
a [protein]-(L-serine/L-threonine) phosphate
Synonyms
cgmp-dependent protein kinase, protein kinase g, cyclic gmp-dependent protein kinase, cgkii, pkg-i, cgmp kinase, prkg1, pkg ii, cgk ii, cgmp-dependent protein kinase i, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
cGMP-dependent protein kinase 1, alpha isozyme
-
CGK
-
-
-
-
CGK 1 alpha
-
-
-
-
CGK 1 beta
-
-
-
-
CGKI-alpha
-
-
-
-
cGKI-beta
-
-
-
-
cGKII
-
-
-
-
cGMP-dependent protein kinase
Foraging protein
-
-
-
-
protein kinase G
-
-
-
-
Type II cGMP-dependent protein kinase
-
-
-
-
cGMP-dependent protein kinase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (cGMP-dependent)
CGMP is required to activate this enzyme. The enzyme occurs as a dimer in higher eukaryotes. The C-terminal region of each polypeptide chain contains the catalytic domain that includes the ATP and protein substrate binding sites. This domain catalyses the phosphorylation by ATP to specific serine or threonine residues in protein substrates [3]. The enzyme also has two allosteric cGMP-binding sites (sites A and B). Binding of cGMP causes a conformational change that is associated with activation of the kinase [4].
CAS REGISTRY NUMBER
COMMENTARY
141588-27-4
-
141588-27-4
cGMP-dependent protein kinase
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + BKCa channel protein
ADP + BKCa channel phosphoprotein
-
phosphorylation at mutiple serine residues, recombinant expressed Mus musculus BKCa channels
-
-
?
ATP + GRTGRRNSI-amide
ADP + phosphorylated GRTGRRNSI-amide
-
assay substrate
-
-
?
ATP + Kemptide
ADP + phosphorylated Kemptide
-
i.e. LRRASLG
i.e. LRRA-phosphoserine-LG
-
?
ATP + NF-kappaB
ADP + phosphorylated NF-kappaB
-
recombinant human NF-kappaB p49 and p50 expressed in 293T cells
-
-
?
ATP + peptide W15
ADP + phosphorylated peptide W15
-
peptide substrate sequence TQAKRKKSLAMA
-
-
?
ATP + RKISASEFDRPL
ADP + phosphorylated RKISASEFDRPL
-
BPDEtide, substrate in activity assay
-
-
?
ATP + septin 3
ADP + phosphorylated septin 3
-
substrate from rat nerves: recombinant His-tagged septin 3 expressed in Escherichia coli or purified from brain and prepared in synaptosomes, phosphorylation at Ser91 and Ser92, no activity with septin 3 mutants S91A and S92A
-
-
?
ATP + septin 3 peptide 86-98
ADP + phosphorylated septin 3 peptide 86-98
-
-
-
-
?
additional information
?
-
amino acid sequence at the ATP-binding site of cGMP-dependent protein kinase
-
-
?
additional information
?
-
-
guanylate cyclase and cyclic GMP-dependent protein kinase regulate agrin signaling at the postsynaptic differentiation of developing neuromuscular junctions, molecular mechanism
-
-
?
additional information
?
-
-
PKGIalpha is a major branch point in the nitric oxide and natriuretic peptide-induced cGMP-signaling pathway. PKG plays a pivotal role in several important biological processes such as the regulation of smooth muscle relaxation, and synaptic plasticity
-
-
?
additional information
?
-
-
peptide substrates with a primary amino acid sequence motif RRX(S/T)X are in general recognized by PKG
-
-
?
additional information
?
-
-
PKG phosphorylates several substrates and interacts, by engaging its N-terminal, with numerous proteins
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
amino acid sequence at the ATP-binding site of cGMP-dependent protein kinase
-
-
?
additional information
?
-
-
guanylate cyclase and cyclic GMP-dependent protein kinase regulate agrin signaling at the postsynaptic differentiation of developing neuromuscular junctions, molecular mechanism
-
-
?
additional information
?
-
-
PKGIalpha is a major branch point in the nitric oxide and natriuretic peptide-induced cGMP-signaling pathway. PKG plays a pivotal role in several important biological processes such as the regulation of smooth muscle relaxation, and synaptic plasticity
-
-
?
additional information
?
-
-
PKG phosphorylates several substrates and interacts, by engaging its N-terminal, with numerous proteins
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
regulatory subunit of photoreceptor cGMP phosphodiesterase
-
inhibits PKGIalpha, the N-terminal 61 amino acids are important containing a cationic region
-
Rp-8-Br-PET-cGMPS
-
beta-phenyl-1,N2-etheno-8-bromoguanosine-3',5'-cyclic monophosphorothioate
additional information
-
the enzyme possesses an N-terminal autoinhibitory sequence
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cGMP
large conformational changes accompany cGMP binding to the enzyme. A distinct and segregated architecture with an extended central helix separates the two cGMPbinding domains. Additionally, a helical domain (switch helix) promotes the formation of a hydrophobic interface between protomers
additional information
aminoterminal dimerization site of cGMP-dependent protein kinase and the autophosphorylation site, present in this part, control not only the activation of the enzyme but also the cooperative binding characteristics of the intact enzyme
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
thermodynamics of PKGIalpha activation by cGMP, overview
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
PKG maintains both its regulatory and catalytic elements on the same polypeptide chain.in contrast to PKA, EC 2.7.11.11
physiological function
cGMP-dependent protein kinase serves as an integral component of second messenger signaling in a number of biological contexts including cell differentiation, memory, and vasodilation
malfunction
-
acute inhibition of cGKI prevented stimulus-evoked enhancement of BKCa channel activity
metabolism
-
molecular mechanisms governing the transcriptional and posttranscriptional regulation of PKG-I expression in vascular smooth muscle cells, overview
physiological function
additional information
physiological function
-
PKG-I is a serine/threonine-specific protein kinase that is activated by the NO/sGC/cGMP system. PKG-I is involved in many cell functions, such as relaxation, platelet aggregation, remodelling, hypertrophy, apoptosis, differentiation, neuronal plasticity, and erectile dysfunction
physiological function
-
the activity of large conductance, Ca2+-activated K+ channels, i.e. BKCa channels, can be increased after modulation by type I cGMP-dependent protein kinase via nitric oxide/cGMP signaling
additional information
docking studies with enzyme fragments PKG78-326, PKG78-341, and PKG78-355, a Cys117-Cys195 disulfide bond locks A and B helices in the A-domain and is involved in the metal-induced activation of PKG Ialpha, overview
additional information
-
the PKG-Ialpha isoform is more sensitive to ubiquitination compared with the PKG-Ibeta isoform
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). KGP1_BOVIN
671
0
76419
Swiss-Prot
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40000
-
catalytic domain of PKG Ialpha, PKG-CD, His-tagged, determined by SDS-PAGE and Western blot analysis
76000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
the switch helix is a critical site of dimer communication in PKG biology, PKG Ialpha domain organization and general architecture of PKG78-355, overview. PKG maintains both its regulatory and catalytic elements on the same polypeptide chain
additional information
additional information
switch helix-mediated dimer interface and modeling of PKG78-355 protomers, overview
additional information
-
peptide fragment identification by mass spectrometry after limited proteolysis of wild-type PKG in the absence and presence of cGMP, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
additional information
-
the PKG-Ialpha isoform is more sensitive to ubiquitination compared with the PKG-Ibeta isoform
phosphoprotein
-
autophosphorylation of isozymes at a Thr in the catalytic domain is essential, phosphorylation sites, also for other kinases, overview
phosphoprotein
-
PKG-I isoforms undergo autophosphorylation, in response to sustained activation/autophosphorylation, PKG-I might becomes ubiquitinated and degraded
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
a recombinant regulatory domain construct, comprising amino acid residues 78-355, containing both cGMP binding sites of PKGIalpha, hanging drop vapor diffusion, from 2.2 M (NH4)2SO4, 100 mM Tris, pH 8.0, 0.2% MPD at a protein concentration of 25-35 mg/ml at 20°C, X-ray diffraction structure determination and analysis at 2.5 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
R77L
-
site-directed mutagenesis, the PKGIalpha mutation not only stabilizes the N-terminus but extends a stabilizing effect on the remaining domains of the enzyme as well
additional information
additional information
construction of enzyme fragments PKG78-326, PKG78-341, and PKG78-355. Mutational disruption of the Knob-Nest interface in full-length PKG Ia decreases the activation constant and suggests a tethering mechanism for the catalytic domain
additional information
-
overexpression in Xenopus laevis of either guanylate cyclase or PKG in embryos increases acetylcholine receptor aggregate area by 60170%, whereas expression of a dominant negative form of guanylate cyclase inhibits endogenous aggregation by 50%, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant N-terminally His6-tagged enzyme fragments PKG78-326, PKG78-341,and PKG78-355 by nickel affinity chromatography and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of wild-type and mutant PKG Ialpha in HEK-293 cells, expression of N-terminally His6-tagged enzyme fragments PKG78-326, PKG78-341,and PKG78-355 in Escherichia coli strain BL21
overexpression of wild-type and mutant enzymes in Spodoptera frugiperda Sf9 cells using the baculovirus infection method
-
the cDNA of bovine catalytic domain of PKG Ialpha, PKG-CD, is inserted in expression vector of pcDNA4/TO/myc-His C/CD
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
data obtained with Rp-8-Br-PET-cGMPS as cGKI inhibitor should be interpreted with caution and not be used as sole evidence to dissect the role of cGKI in signaling processes
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hashimoto, E.; Takio, K.; Krebs, E.G.
Amino acid sequence at the ATP-binding site of cGMP-dependent protein kinase
J. Biol. Chem.
257
727-733
1982
Bos taurus (P00516)
Heil, W.G.; Landgraf, W.; Hofmann, F.
A catalytically active fragment of cGMP-dependent protein kinase. Occupation of its cGMP-binding sites does not affect its phosphotransferase activity
Eur. J. Biochem.
168
117-121
1987
Bos taurus (P00516)
Takio, K.; Smith, S.B.; Walsh, K.A.; Krebs, E.G.; Titani, K.
Amino acid sequence around a "hinge" region and its "autophosphorylation" site in bovine Lung cGMP-dependent protein kinase
J. Biol. Chem.
258
5531-5536
1983
Bos taurus (P00516), Bos taurus
Takio, K.; Wade, R.D.; Smith, S.B.; Krebs, E.G.; Walsh, K.A.; Titani, K.
Guanosine cyclic 3',5'-phosphate dependent protein kinase, a chimeric protein homologous with two separate protein families
Biochemistry
23
4207-4218
1984
Bos taurus (P00516), Bos taurus
Wernet, W.; Flockerzi, V.; Hofmann, F.
The cDNA of the two isoforms of bovine cGMP-dependent protein kinase
FEBS Lett.
251
191-196
1989
Bos taurus (P00516), Bos taurus
Ruth, P.; Pfeifer, A.; Kamm, S.; Klatt, P.; Dostmann, W.R.; Hofmann, F.
Identification of the amino acid sequences responsible for high affinity activation of cGMP kinase Ialpha
J. Biol. Chem.
272
10522-10528
1997
Bos taurus (P00516)
Xue, J.; Milburn, P.J.; Hanna, B.T.; Graham, M.E.; Rostas, J.A.; Robinson, P.J.
Phosphorylation of septin 3 on Ser-91 by cGMP-dependent protein kinase-I in nerve terminals
Biochem. J.
381
753-760
2004
Bos taurus
He, B.; Weber, G.F.
Phosphorylation of NF-kappaB proteins by cyclic GMP-dependent kinase. A noncanonical pathway to NF-kappaB activation
Eur. J. Biochem.
270
2174-2185
2003
Bos taurus, Mus musculus
Baker, D.A.; Deng, W.
Cyclic GMP-dependent protein kinases in protozoa
Front. Biosci.
10
1229-1238
2005
Aplysia californica, Bos taurus, Caenorhabditis elegans, Chlamydomonas reinhardtii, Homo sapiens, Plasmodium falciparum, Plasmodium yoelii, Tetrahymena sp., Hydra oligactis (O17474), Drosophila melanogaster (P32023), Paramecium tetraurelia (Q869J9), Paramecium tetraurelia (Q869K0), Toxoplasma gondii (Q8MMP4), Eimeria maxima (Q8MMZ5), Cryptosporidium parvum (Q8MMZ6), Eimeria tenella (Q8MMZ8), Apis mellifera (Q8SSX4)
Godfrey, E.W.; Longacher, M.; Neiswender, H.; Schwarte, R.C.; Browning, D.D.
Guanylate cyclase and cyclic GMP-dependent protein kinase regulate agrin signaling at the developing neuromuscular junction
Dev. Biol.
307
195-201
2007
Bos taurus
Scholten, A.; Fuss, H.; Heck, A.J.; Dostmann, W.R.
The hinge region operates as a stability switch in cGMP-dependent protein kinase I alpha
FEBS J.
274
2274-2286
2007
Bos taurus
Guo, L.W.; Ruoho, A.E.
Inhibition of cGMP-dependent protein kinase by the regulatory subunit of photoreceptor cGMP phosphodiesterase
Neurosci. Lett.
401
252-255
2006
Bos taurus
Wang, S.; Li, Y.
Expression of constitutively active cGMP-dependent protein kinase inhibits glucose-induced vascular smooth muscle cell proliferation
Am. J. Physiol. Heart Circ. Physiol.
297
H2075-H2083
2009
Bos taurus, Homo sapiens, Mus musculus, Rattus norvegicus
Pinkse, M.W.; Rijkers, D.T.; Dostmann, W.R.; Heck, A.J.
Mode of action of cGMP-dependent protein kinase-specific inhibitors probed by photoaffinity cross-linking mass spectrometry
J. Biol. Chem.
284
16354-16368
2009
Bos taurus
Valtcheva, N.; Nestorov, P.; Beck, A.; Russwurm, M.; Hillenbrand, M.; Weinmeister, P.; Feil, R.
The commonly used cGMP-dependent protein kinase type I (cGKI) inhibitor Rp-8-Br-PET-cGMPS can activate cGKI in vitro and in intact cells
J. Biol. Chem.
284
556-562
2009
Bos taurus, Mus musculus
Sellak, H.; Choi, C.S.; Dey, N.B.; Lincoln, T.M.
Transcriptional and post-transcriptional regulation of cGMP-dependent protein kinase (PKG-I): pathophysiological significance
Cardiovasc. Res.
97
200-207
2013
Bos taurus, Oryctolagus cuniculus, Ovis aries, Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
Kyle, B.D.; Hurst, S.; Swayze, R.D.; Sheng, J.; Braun, A.P.
Specific phosphorylation sites underlie the stimulation of a large conductance, Ca2+-activated K+ channel by cGMP-dependent protein kinase
FASEB J.
27
2027-2038
2013
Bos taurus, Rattus norvegicus
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