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Information on EC 2.7.11.15 - beta-adrenergic-receptor kinase and Organism(s) Bos taurus and UniProt Accession P21146

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EC Tree
IUBMB Comments
Requires G-protein for activation and therefore belongs to the family of G-protein-dependent receptor kinases (GRKs). Acts on the agonist-occupied form of the receptor; also phosphorylates rhodopsin, but more slowly. Does not act on casein or histones. The enzyme is inhibited by Zn2+ and digitonin but is unaffected by cyclic-AMP (cf. EC 2.7.11.14, rhodopsin kinase and EC 2.7.11.16, G-protein-coupled receptor kinase).
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Bos taurus
UNIPROT: P21146
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Word Map
The taxonomic range for the selected organisms is: Bos taurus
The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria
Synonyms
g protein-coupled receptor kinase 2, beta-adrenergic receptor kinase, betaark1, betaark, g-protein-coupled receptor kinase 2, gprk2, g protein-coupled receptor kinase-2, beta-adrenergic receptor kinase 1, g protein coupled receptor kinase, beta-ark, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
beta-adrenergic receptor kinase
-
G protein-coupled receptor kinase 2
-
bARKct
-
-
beta-adrenergic receptor kinase
beta-adrenergic receptor kinase 2
-
beta-adrenergic receptor-specific kinase
-
-
-
-
beta-AR kinase
-
-
-
-
beta-ARK
-
-
-
-
beta-ARK 1
-
-
-
-
beta-ARK 2
-
-
-
-
beta-receptor kinase
-
-
-
-
betaARK1
-
-
betaARK2
-
-
carboxyl-terminus of beta-adrenergic receptor kinase
-
-
G protein-coupled receptor kinase 2
-
-
G protein-coupled receptor kinase 3
-
-
G protein-coupled receptor kinase-2
-
-
guanine nucleotide-binding protein-coupled receptor kinase
-
-
kinase (phosphorylating), beta-adrenergic-receptor
-
-
-
-
additional information
-
the enzymes belong to the family of G protein-coupled receptor kinases
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + [beta-adrenergic receptor] = ADP + phospho-[beta-adrenergic receptor]
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:[beta-adrenergic receptor] phosphotransferase
Requires G-protein for activation and therefore belongs to the family of G-protein-dependent receptor kinases (GRKs). Acts on the agonist-occupied form of the receptor; also phosphorylates rhodopsin, but more slowly. Does not act on casein or histones. The enzyme is inhibited by Zn2+ and digitonin but is unaffected by cyclic-AMP (cf. EC 2.7.11.14, rhodopsin kinase and EC 2.7.11.16, G-protein-coupled receptor kinase).
CAS REGISTRY NUMBER
COMMENTARY hide
102925-39-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
dark-adapted and light-activated rhodopsin in urea-washed rod outer segment membranes
-
-
?
ATP + [beta-adrenergic receptor]
ADP + phospho-[beta-adrenergic receptor]
show the reaction diagram
-
-
-
?
ATP + alpha2-adrenergic receptor
ADP + phospho-alpha2-adrenergic receptor
show the reaction diagram
ATP + alpha2A-adrenergic receptor
ADP + phosphorylated alpha2A-adrenergic receptor
show the reaction diagram
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
agonist-activated receptor substrate
-
-
?
ATP + dopamine D3 receptor
ADP + phosphorylated dopamine D3 receptor
show the reaction diagram
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
ATP + LEESSSSDHAERPPG
?
show the reaction diagram
-
-
-
-
?
ATP + micro-opioid receptor
ADP + phosphorylated micro-opioid receptor
show the reaction diagram
-
mutant C221V GRK2 shows slightly higher effect on morphine-induced internalization of the micro-opioid receptor compared to the wild-type GRK2, while the effects of mutants L271G, L273Y, and L336F are reduced, overview
-
-
?
ATP + muscarinic acetylcholine receptor
ADP + phospho-muscarinic acetylcholine receptor
show the reaction diagram
-
agonist-dependent phosphorylation, subtype 2
-
-
?
ATP + muscarinic cholinergic receptor
ADP + phospho-muscarinic cholinergic receptor
show the reaction diagram
ATP + peptide
ADP + phosphopeptide
show the reaction diagram
ATP + platelet-derived growth factor receptor-beta
ADP + phosphorylated platelet-derived growth factor receptor-beta
show the reaction diagram
ATP + protein
ADP + phosphoprotein
show the reaction diagram
specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G protein-coupled receptors
-
-
?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
ATP + RRRAEAAASAAA
ADP + RRRAEAAApSAAA
show the reaction diagram
-
-
-
-
?
ATP + RRRAEASAA
ADP + RRRAEApSAA
show the reaction diagram
-
poor peptide substrate
-
-
?
ATP + RRRASAAASAA
?
show the reaction diagram
-
poor peptide substrate
-
-
?
ATP + RRRASASAA
?
show the reaction diagram
-
poor peptide substrate
-
-
?
ATP + RRRASpAAASAA
ADP + RRRASpAAASpAA
show the reaction diagram
-
poor peptide substrate, higher catalytic efficiency than RRRASAAASAA
-
-
?
ATP + RRRASpASAA
?
show the reaction diagram
-
poor peptide substrate
-
-
?
ATP + RRREEEEESAAA
?
show the reaction diagram
ATP + Smoothened protein
ADP + phopshorylated Smoothened
show the reaction diagram
-
a seven-transmembrane signaling protein
-
-
?
ATP + Smoothened protein
ADP + phosphorylated Smoothened
show the reaction diagram
-
GRK2 promotes smoothened signal transduction involved in regulation of cellular proliferation and differentiation through activation of the transcription factor Gli, overview
-
-
?
ATP + tubulin
ADP + phosphorylated tubulin
show the reaction diagram
-
-
-
-
?
ATP + [beta-adrenergic receptor]
ADP + phospho-[beta-adrenergic receptor]
show the reaction diagram
-
-
-
-
?
GTP + beta-adrenergic receptor
GDP + phospho-beta-adrenergic receptor
show the reaction diagram
-
agonist-occupied form of beta-AR from hamster lung, GTP can substitute ATP, 2% as effective as ATP
-
?
histamine H2 receptor + ATP
phosphorylated histamine H2 receptor + ADP
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
GRK2 performs desensitization of the ligand-activated receptor by phosphorylation
-
-
?
ATP + [beta-adrenergic receptor]
ADP + phospho-[beta-adrenergic receptor]
show the reaction diagram
-
-
-
?
ATP + alpha2A-adrenergic receptor
ADP + phosphorylated alpha2A-adrenergic receptor
show the reaction diagram
-
-
-
-
?
ATP + beta-adrenergic receptor
ADP + phospho-beta-adrenergic receptor
show the reaction diagram
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
agonist-activated receptor substrate
-
-
?
ATP + dopamine D3 receptor
ADP + phosphorylated dopamine D3 receptor
show the reaction diagram
-
the receptor is activated by GRK2 and GRK3 phosphorylation involving beta-arrestins, GRK-mediated regulation of receptor-filamin complex stability and receptor-G protein signaling potential, GRK2 reduces the dopamine D3 receptor signaling, overview
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
ATP + platelet-derived growth factor receptor-beta
ADP + phosphorylated platelet-derived growth factor receptor-beta
show the reaction diagram
-
feedback inhibition mechanism, overview
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G protein-coupled receptors
-
-
?
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
-
light-activated rhodopsin
-
-
?
ATP + Smoothened protein
ADP + phosphorylated Smoothened
show the reaction diagram
-
GRK2 promotes smoothened signal transduction involved in regulation of cellular proliferation and differentiation through activation of the transcription factor Gli, overview
-
-
?
histamine H2 receptor + ATP
phosphorylated histamine H2 receptor + ADP
show the reaction diagram
-
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
not activated by Ca2+, Co2+ or Zn2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4-(3-((2,6-bis(trifluoromethyl)benzyl)carbamoyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(3-((2,6-dichlorobenzyl)carbamoyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(3-((2,6-difluorobenzyl)carbamoyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(3-((2,6-dimethoxybenzyl)carbamoyl)-4-fluorophenyl)-N-(1Hindazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(3-((2,6-dimethylbenzyl)carbamoyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5 carboxamide
-
4-(3-((2,6-dimethylbenzyl)carbamoyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-N,6-dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(3-((2,6-dimethylphenethyl)carbamoyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(3-((3,5-bis(trifluoromethyl)benzyl)carbamoyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(3-(2-((2,6-bis(trifluoromethyl)benzyl)amino)-2-oxoethyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(3-(2-((2,6-dimethoxybenzyl)amino)-2-oxoethyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(3-(2-((2,6-dimethylbenzyl)amino)-2-oxoethyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(3-(benzylcarbamoyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(4-fluoro-3-(((3-methylpyridin-2-yl)methyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(4-fluoro-3-((2-(pyridin-2-yl)ethyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(4-fluoro-3-((2-(pyridin-4-yl)ethyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(4-fluoro-3-((2-methoxybenzyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(4-fluoro-3-((3-fluorobenzyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(4-fluoro-3-((3-methoxybenzyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(4-fluoro-3-((4-methoxybenzyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(4-fluoro-3-((isoquinolin-1-ylmethyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(4-fluoro-3-((pyridin-2-ylmethyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
4-(4-fluoro-3-(methylcarbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
5-(5-((1H-indazol-5-yl)carbamoyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidin-4-yl)-2-fluorobenzoic acid
-
CCG-224406
-
GSK180736A
-
N-(benzo[d][1,3]dioxol-5-yl)-4-(4-fluoro-3-((pyridin-2-ylmethyl)-carbamoyl)phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
-
paroxetine
-
Takeda103A
-
2,3-diphosphoglycerate
4-amino-1-tert-butyl-3-(1'-naphthyl)pyrrazolo[3,4-d]pyrimidine
-
i.e. 1-Na-PP1, inhibits mutant C221V mediated morphine-induced internalization of the micro-opioid receptor, but not wild-type GRK2 and mutant L271G activities
alpha2-adrenergic antagonist
-
co-incubation completely blocks phosphorylation of alpha2-adrenergic receptor
-
atropine
-
receptor antagonist
Chloropromazine
-
IC50: 0.043 mM
chondroitin sulfate B
-
weak
chondroitin sulfate C
-
less inhibitory than heparin
D-glucosamine 2,6-disulfate
-
inhibits in the millimolar range, weak, IC50: 7.3 mM with rhodopsin as substrate
D-sphingosine
-
IC50: 0.027 mM
Dextran sulfate
-
strong, IC50: 0.00015 mM with rhodopsin as substrate
-
Digitonin
EDTA
-
-
heparan sulfate
-
less inhibitory than heparin
heparin
Inositol hexaphosphate
-
weak, IC50: 3.6 mM with rhodopsin as substrate
Inositol hexasulfate
McN-A343
-
weak, partial antagonist
NaF
-
as efficient as Cl-, I-, NO2- or acetate, less efficient than citrate, phosphate or sulfate
NaI
-
as efficient as Cl-, F-, NO2- or acetate, less efficient than citrate, phosphate or sulfate
NaNO2
-
as efficient as Cl-, I-, F- or acetate, less efficient than citrate, phosphate or sulfate
peptide
phosphatidylinositol 4,5-bisphosphate
-
inhibits receptor phosphorylation, causes membrane association, 30% inhibition of phosphorylation of RRREEEEESAAA
Polyaspartic acid
Polyglutamic acid
polylysine
propranolol
-
beta-adrenergic antagonist, in presence no phosphorylation
Protein kinase C inhibitor H7
-
pyridoxal 5'-phosphate
quinpirole
-
inhibits GRK2 and GRK3
rhodopsin
-
intact light-activated rhodopsin slightly inhibits phosphorylation of RRREEEEESAAA
Sangivamycin
-
IC50: 0.067 mM
Sodium acetate
-
as efficient as Cl-, I-, NO2- or F-, less efficient than citrate, phosphate or sulfate
Sodium citrate
-
20 mM, 97% inhibition, more efficient than phosphate, sulfate, Cl-, F-, I-, NO2- or acetate
Sodium phosphate
-
20 mM, 76% inhibition, less efficient than citrate, as good as sulfate, more efficient than Cl-, F-, I-, NO2- or acetate
Sodium sulfate
-
less efficient than citrate, as good as phosphate, more efficient than Cl-, F-, I-, NO2- or acetate
spermidine
-
weak, less potent than polylysine
spermine
tamoxifen
-
IC50: 0.04 mM
Trifluoperazine
-
IC50: 0.035 mM
Triton X-100
-
IC50: 0.054 mM
Tween 20
-
IC50: 0.027 mM
Yohimbine
-
alpha2-adrenergic antagonist, co-incubation completely blocks phosphorylation of alpha2-adrenergic receptor
Zn2+
-
0.1-0.2 mM ZnCl2, 94-98% inhibition
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Gbetagamma subunits
required for activity on G protein-coupled receptors, binding via enzyme C-terminal pleckstrin homology domain, binding does not induce large domain rearrangements, but small rotations of the enzyme domains, the domain interfaces remain intact upon GRK2 activation, structure analysis of GRK2 in complex with G protein beta1gamma2 subunits, overview
-
(-)-Epinephrine
-
requirement, agonist, alpha2-adrenergic receptor as substrate
AlF4-
-
enhances beta-ARK activity upon stimulation of heterotrimeric G proteins
alpha2A-adrenergic receptor
-
epinephrine-activated alpha2A-adrenergic receptor activates GRK2, interaction with GRK2 via the second and third intracellular loop of the receptor, determination of regions required for specific interaction utilizing recombinant GST-tagged wild-type and several mutant alpha2A ARs, residues R225, R226, R218, K320, R322, and K358 are important, overview
-
beta-arrestin2
-
mediates GRK activity, forms a signaling complex with filamin and dopamine D3 receptor, interactions, overview
-
beta2-adrenergic receptor
-
cAMP-dependent protein kinase
-
PKA-mediated phosphorylation favors subsequent phosphorylation of beta2-AR by beta-ARK, PKA increases the phosphorylation rate of beta-ARK
-
Carbachol
-
requirement, agonist, muscarinic cholinergic receptor as substrate
cardiolipin
-
activates, phosphorylation of beta2-AR
G protein
-
G protein betagamma-subunit
-
G protein Gbetagamma subunits
-
activate both ARK1 and ARK2 about 2.5fold
-
isoproterenol
mastoparan/guanosine 5'-(3-O-thio)triphosphate
-
enhances beta-ARK activity upon stimulation of heterotrimeric G proteins
Oxytremorine
-
requirement, agonist, muscarinic cholinergic receptor as substrate
phosphatidic acid
-
activates, phosphorylation of beta2-AR
phosphatidylglycerol
-
activates, phosphorylation of beta2-AR
phosphatidylinositol
-
activates, phosphorylation of beta2-AR, 6fold activation of phosphorylation of RRREEEEESAAA
phosphatidylserine
-
activates, phosphorylation of beta2-AR
Phospholipid
-
required for phosphorylation of beta2-AR, activation is associated with a conformational change in beta-ARK 1, acidic phospholipid specificity, not activated by phosphatidylinositol 4,5-diphosphate, direct regulation of beta-ARK 1 activity by phospholipids
platelet-derived growth factor receptor-beta
-
activates the enzyme by tyrosine phosphorylation at Y13, Y86, and Y92, required, the wild-type PDGFRbeta is 60fold more active with GRK2 than PDGFRbeta mutant Y857F, GRK2 activation also increases GRK2 degradation and downregulation, independent of Gbetagamma subunits and phosphoinositide 3-kinase
-
rhodopsin
-
interaction of enzyme with light-activated rhodopsin or truncated rhodopsin lacking its C-terminal phosphorylation sites activates peptide phosphorylation, at lower concentrations, enhances both the affinity and catalytic efficiency for peptide phosphorylation, but intact light-activated rhodopsin slightly inhibits the phosphorylation of RRREEEEESAAA
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.017 - 0.149
ATP
0.00025
beta-adrenergic receptor
-
pH 7.5, 30°C
-
0.9 - 4.8
peptide
0.0038 - 0.014
rhodopsin
5.1
RRRAEASAA
-
pH 7.4, 30°C, recombinant beta-ARK 1
3.3
RRRASAAASAA
-
pH 7.4, 30°C, recombinant beta-ARK 1
5.4
RRRASASAA
-
pH 7.4, 30°C, recombinant beta-ARK 1
4.6
RRRASpAAASAA
-
pH 7.4, 30°C, recombinant beta-ARK 1
3.4
RRRASpASAA
-
pH 7.4, 30°C, recombinant beta-ARK 1
0.72 - 1.34
RRREEEEESAAA
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0001 - 0.0041
ATP
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00015
heparin
-
-
additional information
additional information
-
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0012
4-(3-((2,6-bis(trifluoromethyl)benzyl)carbamoyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.00013
4-(3-((2,6-dichlorobenzyl)carbamoyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.00022
4-(3-((2,6-difluorobenzyl)carbamoyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.00013
4-(3-((2,6-dimethoxybenzyl)carbamoyl)-4-fluorophenyl)-N-(1Hindazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.00007
4-(3-((2,6-dimethylbenzyl)carbamoyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5 carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.0046
4-(3-((2,6-dimethylbenzyl)carbamoyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-N,6-dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.00023
4-(3-((2,6-dimethylphenethyl)carbamoyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.0027
4-(3-((3,5-bis(trifluoromethyl)benzyl)carbamoyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.1
4-(3-(2-((2,6-bis(trifluoromethyl)benzyl)amino)-2-oxoethyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.00045
4-(3-(2-((2,6-dimethoxybenzyl)amino)-2-oxoethyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.025
4-(3-(2-((2,6-dimethylbenzyl)amino)-2-oxoethyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.00069
4-(3-(benzylcarbamoyl)-4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.0019
4-(4-fluoro-3-(((3-methylpyridin-2-yl)methyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.00028
4-(4-fluoro-3-((2-(pyridin-2-yl)ethyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.0048
4-(4-fluoro-3-((2-(pyridin-4-yl)ethyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.00006
4-(4-fluoro-3-((2-methoxybenzyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.0002
4-(4-fluoro-3-((3-fluorobenzyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.00042
4-(4-fluoro-3-((3-methoxybenzyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.00046
4-(4-fluoro-3-((4-methoxybenzyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.00028
4-(4-fluoro-3-((isoquinolin-1-ylmethyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.00015
4-(4-fluoro-3-((pyridin-2-ylmethyl)carbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.0043
4-(4-fluoro-3-(methylcarbamoyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.02
5-(5-((1H-indazol-5-yl)carbamoyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidin-4-yl)-2-fluorobenzoic acid
Bos taurus
at pH 7.0, temperature not specified in the publication
0.00013
CCG-224406
Bos taurus
at pH 7.0, temperature not specified in the publication
0.00077
GSK180736A
Bos taurus
at pH 7.0, temperature not specified in the publication
0.1
N-(benzo[d][1,3]dioxol-5-yl)-4-(4-fluoro-3-((pyridin-2-ylmethyl)-carbamoyl)phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
Bos taurus
at pH 7.0, temperature not specified in the publication
0.00138
paroxetine
Bos taurus
at pH 7.0, temperature not specified in the publication
0.00002
Takeda103A
Bos taurus
at pH 7.0, temperature not specified in the publication
1.1
2,3-diphosphoglycerate
Bos taurus
-
inhibits in the millimolar range, IC50: 1.1 mM with rhodopsin as substrate
0.043
Chloropromazine
Bos taurus
-
IC50: 0.043 mM
7.3
D-glucosamine 2,6-disulfate
Bos taurus
-
inhibits in the millimolar range, weak, IC50: 7.3 mM with rhodopsin as substrate
0.027
D-sphingosine
Bos taurus
-
IC50: 0.027 mM
0.00015
Dextran sulfate
Bos taurus
-
strong, IC50: 0.00015 mM with rhodopsin as substrate
-
0.05
Digitonin
Bos taurus
-
IC50: 0.05 mM
0.00003 - 0.0014
heparin
3.6
Inositol hexaphosphate
Bos taurus
-
weak, IC50: 3.6 mM with rhodopsin as substrate
0.0135
Inositol hexasulfate
Bos taurus
-
IC50: 0.0135 mM with rhodopsin as substrate
0.0013
Polyaspartic acid
Bos taurus
-
IC50: 0.0013 mM with rhodopsin as substrate
0.002
Polyglutamic acid
Bos taurus
-
IC50: 0.002 mM with rhodopsin as substrate
0.069
polylysine
Bos taurus
-
IC50: 0.069 mM with rhodopsin as substrate
0.25
Protein kinase C inhibitor H7
Bos taurus
-
IC50: 0.25 mM
-
0.9
pyridoxal 5'-phosphate
Bos taurus
-
weak, IC50: 0.9 mM with rhodopsin as substrate
0.067
Sangivamycin
Bos taurus
-
IC50: 0.067 mM
1.6
spermine
Bos taurus
-
IC50: 1.6 mM
0.04
tamoxifen
Bos taurus
-
IC50: 0.04 mM
0.035
Trifluoperazine
Bos taurus
-
IC50: 0.035 mM
0.054
Triton X-100
Bos taurus
-
IC50: 0.054 mM
0.027
Tween 20
Bos taurus
-
IC50: 0.027 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00873
-
pH 7.5, 30°C
0.05 - 0.08
-
pH 7.5, 30°C
1
-
about, recombinant beta-ARK 1, expressed in SF9 cells
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
assay at
6 - 7.5
-
-
7.8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
assay at
23
-
assay at
37
-
assay at, intact cell phosphorylation of muscarinic receptor subtype 2 and alpha2-adrenergic receptor by recombinant mutant beta-ARK
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
beta-ARK 2 has a higher isoelectric point than beta-ARK 1
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
about 40% of beta-ARK mRNA concentration in brain
Manually annotated by BRENDA team
about 20% of beta-ARK mRNA concentration in brain
Manually annotated by BRENDA team
about 40% of beta-ARK mRNA concentration in brain
Manually annotated by BRENDA team
about 20% of beta-ARK mRNA concentration in brain
Manually annotated by BRENDA team
highest beta-ARK mRNA concentrations in brain and spleen
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
associated, GRK2 in complex with G protein beta1gamma2 subunits
Manually annotated by BRENDA team
-
predominantly cytoplasmic, enzyme activity depends upon its translocation from the cytoplasm to the membrane, the betagamma subunits of G proteins bind to enzyme and recruit it to the membrane, beta-ARK 1 binds to Gbeta2
Manually annotated by BRENDA team
-
after myocardial ischemic and oxidative stress there is increased mitochondrial GRK2 translocation
Manually annotated by BRENDA team
-
soluble enzyme, that transiently translocates to the plasma membrane
-
Manually annotated by BRENDA team
additional information
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
GRK2 kinase activity and, therefore, histamine H2 receptor phosphorylation, is required to achieve H2R internalization but not receptor desensitization
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
ARBK1_BOVIN
689
0
79647
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
79700
x * 79700, calculated from the amino acid sequence
80000
additional information
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
-
1 * 80000, SDS-PAGE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
GRK2 is phosphorylated by MAP kinase at S670
phosphoprotein
additional information
-
no autophosphorylation of beta-ARK 1
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in complex with inhibitors, hanging drop vapor diffusion method, using 50 mM MES pH 6.0, 0.8-1.2 M NaCl, and 8-16% (w/v) PEG 3350
purified recombinant GRK2 S670A mutant, hanging drop vapour diffusion method, 4°C, 0.002 ml protein solution containing 15 mg/ml GRK2, 20 mM HEPES, pH 8.0, 0.2 M NaCl, and 2 mM DTT, mixed with 0.002 ml well solution containing 0.1 M HEPES, pH 7.5-8.0, 1 M NaCl, 1 M urea, 10-40 mM phosphoserine, pH 7.0, 5% v/v glycerol, and 9.5-11.5% PEG 8000, 2-3 weeks, X-ray diffraction structure determination and analysis at 4.5 A resolution
purified recombinant GRK2 in complex with purified recombinant bovine G protein beta1gamma2 subunits, two-dimensional hanging drop vapor diffusion method screen, 0.001 ml protein solution containing 5-20% PEG3350 versus pH 5.0-7.5, 1 M NaCl, 12 mg/ml protein, mixed with 0.001 ml of well solution containing 0.1 M MES, pH 5.25, 0.2 M NaCl, 1 mM inositol-3,4,5-trisphosphate, 5 mM MgCl2, and 6.9-7.8% PEG3350, versus 1 ml of well solution, inositol-3,4,5-trisphosphate can be substituted by EDTA and phosphatidylserine, both crystal types diffract differently but show identical unit-cell parameters, X-ray diffraction structure determination and analysis at 3.2 A resolution, Cu Kalpha radiation
-
purified recombinant GRK2 in complex with purified recombinant G protein beta1gamma2 subunits, X-ray diffraction structure determination and analysis at 2.5 A resolution, modeling
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E520A
site-directed mutagenesis, very low recombinant expression level, mutant GRK2 shows a dramatic loss of activity with rhodopsin as substrate
E96A
site-directed mutagenesis, slightly increased recombinant expression level compared to the wild-type GRK2, mutant GRK2 shows activity with rhodopsin as substrate similar to the wild-type enzyme
P638D
site-directed mutagenesis, RH-PH domain interface residue mutant, 40% reduced recombinant expression level compared to the wild-type GRK2, mutant GRK2 shows 15% of wild-type activity with rhodopsin as substrate
R516A
site-directed mutagenesis, 60% reduced recombinant expression level compared to the wild-type GRK2, mutant GRK2 shows slightly reduced activity with rhodopsin as substrate
S670A
site-directed mutagenesis, the MAP kinase phosphorylation site S670 is eliminated in the GRK2 mutant enzyme
V42E
site-directed mutagenesis, RH-PH domain interface residue mutant, 60% reduced recombinant expression level compared to the wild-type GRK2, mutant GRK2 shows 25% of wild-type activity with rhodopsin as substrate
Y46A
site-directed mutagenesis, RH-PH domain interface residue mutant, 80% reduced recombinant expression level compared to the wild-type GRK2, mutant GRK2 shows 50% of wild-type activity with rhodopsin as substrate
C221V
-
site-directed mutagenesis, mutant GRK2 activity is slightly increased compared to the wild-type enzyme, the requirement for initial ligand-induced internalization of a G protein-coupled receptor with subsequent rounds of internalization is different for the mutant GRK2 compared to the wild-type enzyme
D110A
D110A/K220R
-
double mutant has a disrupted RGS (regulator of G protein signalling) function. Although double mutant coimmunoprecipitates with the histamine H2 receptor, it reverses GRK2K220R-mediated histamine H2 receptor desensitization
D635K/S636K/D637K
-
triple mutant D635K/S636K/D637K, mutation in the Gbetagamma-binding region of the PH domain
D637K
-
triple mutant D635K/S636K/D637K, mutation in the Gbetagamma-binding region of the PH domain
DELTA495-689
-
carboxyl-terminus is expressed as a Flag-tagged betaARKct (GRK2 amino acids 495-689) in HeLa and HEK293 cells
E646K
-
mutation in the Gbetagamma-binding region of the PH domain
K220R
K567E
-
mutation in the PIP2-binding region of the PH domain
K645E
-
mutation in the Gbetagamma-binding region of the PH domain
L271G
-
site-directed mutagenesis, mutant GRK2 shows highly reduced activity compared to the wild-type enzyme
L273Y
-
site-directed mutagenesis, mutant GRK2 shows highly reduced activity compared to the wild-type enzyme
L336F
-
site-directed mutagenesis, mutant GRK2 shows highly reduced activity compared to the wild-type enzyme
L647G
-
residue of the PH domain, mutation completely abolishes beta-ARK activity and activation by the G protein betagamma-subunit
Q642G
-
mutation in the Gbetagamma-binding region of the PH domain
R578N
-
double mutant R578N/R579N, mutation in the PIP2-binding region of the PH domain
R579N
-
double mutant R578N/R579N, mutation in the PIP2-binding region of the PH domain
S636K
-
triple mutant D635K/S636K/D637K, mutation in the Gbetagamma-binding region of the PH domain
S670A
-
cells overexpressing the S670A-GRK2 mutant have less H2O2-induced death as determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. In cells expressing mutant GRK2, the amount of cell death is significantly reduced by 36.4%. Mutant displays significantly less Hsp90 binding in myocytes after oxidative stress compared with wild-type GRK2. Nonphosphorylated mutant S670A is not localized to mitochondria after oxidative stress
S670D
-
mutant shows the highest level of interaction with Hsp90 compared to wild-type and mutant S670A
W576A
-
mutation in the PIP2-binding region of the PH domain
W643A
-
residue of the PH domain, mutation completely abolishes beta-ARK activity and activation by the G protein betagamma-subunit
Y13F
-
site-directed mutagenesis, required activating tyrosine phosphorylation by platelet-derived growth factor receptor-beta kinase activity is reduced with the mutant GRK2, reduced activity compared to the wild-type
Y13F/Y86F/Y92F
-
site-directed mutagenesis, required activating tyrosine phosphorylation by platelet-derived growth factor receptor-beta kinase activity is eliminated with the mutant GRK2, reduced activity compared to the wild-type
Y86F
-
site-directed mutagenesis, required activating tyrosine phosphorylation by platelet-derived growth factor receptor-beta kinase activity is reduced with the mutant GRK2, reduced activity compared to the wild-type
Y86F/Y92F
-
site-directed mutagenesis, required activating tyrosine phosphorylation by platelet-derived growth factor receptor-beta kinase activity is highly reduced with the mutant GRK2, reduced activity compared to the wild-type
Y92F
-
site-directed mutagenesis, required activating tyrosine phosphorylation by platelet-derived growth factor receptor-beta kinase activity is reduced with the mutant GRK2, reduced activity compared to the wild-type
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
Triton X-100 stabilizes
-
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Triton X-100
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, purified recombinant His-tagged wild-type and mutant GRK2s, 50 mM NaH2PO4, pH 8.0, 300 mM NaCl, 250 mM imidazole, 30% glycerol, stable for 2 months
-
4°C, crude enzyme: several months, stable, purified enzyme: t1/2 of 5-10 days
-
4°C, in presence of Triton X-100, 1 year, stable
-
4°C, several months, stable
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-NTA column chromatography
20300fold, to near homogeneity
-
about 20000fold, from brain
expression in COS 7 cells
partial
-
recombinant ARK1 and ARK2 from Sf9 insect cells by sequential chromatography, including heparin affinity chromatography
-
recombinant beta-ARK 1 and 2 overexpressed in Sf9 cells
-
recombinant beta-ARK 1 expressed in Sf9 cells
-
recombinant beta-ARK expressed in Sf9 cells
-
recombinant GRK2 from Spodoptera frugiperda Sf9 cells to near homogeneity by ultracentrifugation, 3 steps of cation exchange chromatography, heparin affinity chromatography, another ion exchange chromatography step, and gel filtration, the recombinant His6-tagged G protein beta1gamma2 subunits by solubilization from membranes, Ni2+ affinity and ion exchange chromatography, and gel filtration
-
recombinant His-tagged wild-type and mutant GRK2s from Spodoptera frugiperda Sf9 cells by nickel affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
co-overexpression of GRK2 mutants and G protein beta1gamma2 subunits in Spodoptera frugiperda Sf9 cells using the baculovirus infection system, and in COS-1 cells
expressed in High Five cells
expression in COS-7 cells
adenovirus-mediated expression of beta-adrenergic receptor kinase C-terminus in pigs in endothelial cells and smooth muscle cells, overview
-
beta-ARK 1 and 2 are cloned and expressed in SF9 cells using the baculovirus expression system
-
beta-ARK 1 is cloned and expressed in SF9 cells using the baculovirus expression system
-
beta-ARK 1 is cloned and expressed in yeast strain L40
-
beta-ARK 1 is stably overexpressed in HEK-293 cells
-
beta-ARK expression in SF9 cells
-
carboxyl-terminus is expressed as a Flag-tagged betaARKct (GRK2 amino acids 495-689) in HeLa and HEK293 cells
-
cDNA encoding beta-ARK is cloned from brain, sequenced and expressed in COS-7 cells, cDNA encodes a 689 amino acids protein
cloning of GST-beta-ARK fusion proteins and expression in Escherichia coli AG1
-
co-overexpression of GRK2 and G protein beta1gamma2 subunits in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
-
co-overexpression of GRK2 and His6-tagged G protein beta1gamma2 subunits in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
-
expresed in HEK293T cells and COS7 cells
-
expression of GRK2 in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
-
expression of HA-tagged GRK2 wild-type and mutants and of FLAG-tagged platelet-derived growth factor receptor-beta wild-type and mutants in HEK-293 cells
-
expression of wild-type and mutant GRK2 in C3H10T1/2 cells, transient expression in HEK-293 cells, expression of GRK2, but not catalytically inactive GRK2, synergizes with active Smoothened to mediate Gli-dependent transcription
-
expression of wild-type GRK2 and mutants in HEK-293 cells, co-expression of GRK2 and CCR2B produces a 65-70% reduction for the wild-type GRK2 and 52% for the mutant GRK2 K220R in ERK phosphorylation by inhibition of CCL2
-
functional GRK2 overexpression in transgenic mice, tissue-specific transgenic mRNA expression analysis, tissue-specific overexpression of GRK2 in mouse osteoblasts by usage of the osteocalcin gene-2 promoter
-
overexpression of ARK1 and ARK2 in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
-
overexpression of GRK2 in HEK-293 cells and in COS-7 cells, co-expression with FLAG-tagged dopamine D3 receptor, and filamin A and/or beta-arrestin, recombinant beta-arrestin is accumulated in the plasma membrane in presence of GRK2 and absence of agonist
-
stable co-expression of C-terminally HA-tagged wild-type GRK2 and murine micro-opioid receptor in HEK-293 cells, transient expression of C-terminally HA-tagged wild-type and mutant GRK2s in HEK-293 cells, expression of His-tagged wild-type and mutant GRK2s in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
-
transient overexpression of wild-type GRK2 in NG108-15 mouse neuroblastoma x rat glioma hybrid cells
-
very similar cDNA sequences of bovine and human kinases
-
wild-type beta-ARK 1 is expressed in SF9 and COS-7 cells, mutant beta-ARK 1 is cloned and expressed in COS-7 cells
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
reconstitution of the GRK2-G protein beta1gamma2 subunits complex by mixing in a 2:3 ratio
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
biotechnology
-
engineering of a GRK2 mutant sensitive to a specific inhibitor
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Benovic, J.L.
Purification and characterization of beta-adrenergic receptor kinase
Methods Enzymol.
200
351-362
1991
Bos taurus
Manually annotated by BRENDA team
Benovic, J.L.; DeBlasi, A.; Stone, W.C.; Caron, M.G.; Lefkowitz, R.J.
Beta-adrenergic receptor kinase: primary structure delineates a multigene family
Science
246
235-240
1989
Bos taurus, Bos taurus (P21146)
Manually annotated by BRENDA team
Chuang, T.T.; Sallese, M.; Ambrosini, G.; Parruti, G.; De Blasi, A.
High expression of beta-adrenergic receptor kinase in human peripheral blood leukocytes. Isoproterenol and platelet activating factor can induce kinase translocation
J. Biol. Chem.
267
6886-6892
1992
Bos taurus, Homo sapiens, Homo sapiens (P25098)
Manually annotated by BRENDA team
Benovic, J.L.; Onorato, J.J.; Arriza, J.L.; Stone, W.C.; Lohse, M.; Jenkins, N.A.; Gilbert, D.J.; Copeland, N.G.; Caron, M.G.; Lefkowitz, R.J.
Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family
J. Biol. Chem.
266
14939-14946
1991
Bos taurus (P26818), Bos taurus
Manually annotated by BRENDA team
Parruti, G.; Ambrosini, G.; Sallese, M.; De Blasi, A.
Molecular cloning, functional expression and mRNA analysis of human beta-adrenergic receptor kinase 2
Biochem. Biophys. Res. Commun.
190
475-481
1993
Bos taurus, Homo sapiens (P35626), Homo sapiens
Manually annotated by BRENDA team
Benovic, J.L.; Mayor, F.; Somers, R.L.; Caron, M.G.; Lefkowitz, R.J.
Light-dependent phosphorylation of rhodopsin by beta-adrenergic receptor kinase
Nature
321
869-872
1986
Bos taurus
Manually annotated by BRENDA team
Onorato, J.J.; Palczewski, K.; Regan, J.W.; Caron, M.G.; Lefkowitz, R.J.; Benovic, J.L.
Role of acidic amino acids in peptide substrates of the beta-adrenergic receptor kinase and rhodopsin kinase
Biochemistry
30
5118-5125
1991
Bos taurus
Manually annotated by BRENDA team
Benovic, J.L.; Regan, J.W.; Matsui, H.; Mayor, F.; Cotecchia, S.; Leeb-Lundberg, L.M.F.; Caron, M.G.; Lefkowitz, R.J.
Agonist-dependent phosphorylation of the alpha 2-adrenergic receptor by the beta-adrenergic receptor kinase
J. Biol. Chem.
262
17251-17253
1987
Bos taurus
Manually annotated by BRENDA team
Benovic, J.L.; Mayor, F.; Staniczewski, C.; Lefkowitz, R.J.; Caron, M.G.
Purification and characterization of the beta-adrenergic receptor kinase
J. Biol. Chem.
262
9026-9032
1987
Bos taurus
Manually annotated by BRENDA team
Benovic, J.L.; Stone, W.C.; Caron, M.G.; Lefkowitz, R.J.
Inhibition of the beta-adrenergic receptor kinase by polyanions
J. Biol. Chem.
264
6707-6710
1989
Bos taurus
Manually annotated by BRENDA team
Kwatra, M.M.; Benovic, J.L.; Caron, M.G.; Lefkowitz, R.J.; Hosey, M.M.
Phosphorylation of chick heart muscarinic cholinergic receptors by the beta-adrenergic receptor kinase
Biochemistry
28
4543-4547
1989
Bos taurus
Manually annotated by BRENDA team
Shlemann, P.; Hekman, M.; Buchen, C.; Elce, J.S.; Lohse, M.J.
Purification and functional characterization of beta-adrenergic receptor kinase expressed in insect cells
FEBS Lett.
324
59-62
1993
Bos taurus, Homo sapiens
Manually annotated by BRENDA team
Kim, C.M.; Dion, S.B.; Onorato, J.J.; Benovic, J.L.
Expression and characterization of two beta-adrenergic receptor kinase isoforms using the baculovirus expression system
Receptor
3
39-55
1993
Bos taurus
Manually annotated by BRENDA team
Chen, C.Y.; Dion, S.B.; Kim, C.M.; Benovic, J.L.
Beta-adrenergic receptor kinase. Agonist-dependent receptor binding promotes kinase activation
J. Biol. Chem.
268
7825-7831
1993
Bos taurus
Manually annotated by BRENDA team
Goldman, P.S.; DeMaggio, A.J.; Hoekstra, M.F.; Goodman, R.H.
The beta-adrenergic receptor kinase interacts with the amino terminus of the G protein beta subunit
Biochem. Biophys. Res. Commun.
240
425-429
1997
Bos taurus
Manually annotated by BRENDA team
Touhara, K.
Effects of mutations in pleckstrin homology domain on beta-adrenergic receptor kinase activity in intact cells
Biochem. Biophys. Res. Commun.
252
669-674
1998
Bos taurus
Manually annotated by BRENDA team
Moffett, S.; Rousseau, G.; Lagace, M.; Bouvier, M.
The palmitoylation state of the beta2-adrenergic receptor regulates the synergistic action of cyclic AMP-dependent protein kinase and beta-adrenergic receptor kinase involved in its phosphorylation and desensitization
J. Neurochem.
76
269-279
2001
Bos taurus
Manually annotated by BRENDA team
Murga, C.; Esteban, N.; Ruiz-Gomez, A.; Mayor, F.Jr.
The basal subcellular distribution of beta-adrenergic receptor kinase is independent of G-protein betagamma subunits
FEBS Lett.
409
24-28
1997
Bos taurus
Manually annotated by BRENDA team
Mller, S.; Straub, A.; Lohse, M.J.
Selectivity of beta-adrenergic receptor kinase 2 for G protein betagamma subunits
FEBS Lett.
401
25-29
1997
Bos taurus
Manually annotated by BRENDA team
Touhara, K.
Binding of multiple ligands to pleckstrin homology domain regulates membrane translocation and enzyme activity of beta-adrenergic receptor kinase
FEBS Lett.
417
243-248
1997
Bos taurus
Manually annotated by BRENDA team
Murga, C.; Ruiz-Gomez, A.; Garcia-Higuera, I.; Kim, C.M.; Benovic, J.L.; Mayor, F.Jr.
High affinity binding of beta-adrenergic receptor kinase to microsomal membranes. Modulation of the activity of bound kinase by heterotrimeric G protein activation
J. Biol. Chem.
271
985-994
1996
Bos taurus
Manually annotated by BRENDA team
Onorato, J.J.; Gillis, M.E.; Liu, Y.; Benovic, J.L.; Ruoho, A.E.
The beta-adrenergic receptor kinase (GRK2) is regulated by phospholipids
J. Biol. Chem.
270
21346-21353
1995
Bos taurus
Manually annotated by BRENDA team
Lodowski, D.T.; Barnhill, J.F.; Pitcher, J.A.; Capel, W.D.; Lefkowitz, R.J.; Tesmer, J.J.
Purification, crystallization and preliminary X-ray diffraction studies of a complex between G protein-coupled receptor kinase 2 and Gbeta1gamma2
Acta Crystallogr. Sect. D
59
936-939
2003
Bos taurus
Manually annotated by BRENDA team
Wang, L.; Liu, S.; Quarles, L.D.; Spurney, R.F.
Targeted overexpression of G protein-coupled receptor kinase-2 in osteoblasts promotes bone loss
Am. J. Physiol.
288
E826-834
2005
Bos taurus
Manually annotated by BRENDA team
Lodowski, D.T.; Barnhill, J.F.; Pyskadlo, R.M.; Ghirlando, R.; Sterne-Marr, R.; Tesmer, J.J.
The role of Gbetagamma and domain interfaces in the activation of G protein-coupled receptor kinase 2
Biochemistry
44
6958-6970
2005
Bos taurus (P21146)
Manually annotated by BRENDA team
Ghadessy, R.S.; Willets, J.M.; Kelly, E.
G protein-coupled receptor kinase 6 (GRK6) selectively regulates endogenous secretin receptor responsiveness in NG108-15 cells
Br. J. Pharmacol.
138
660-670
2003
Bos taurus
Manually annotated by BRENDA team
Luo, Z.; Akita, G.Y.; Date, T.; Treleaven, C.; Vincent, K.A.; Woodcock, D.; Cheng, S.H.; Gregory, R.J.; Jiang, C.
Adenovirus-mediated expression of beta-adrenergic receptor kinase C-terminus reduces intimal hyperplasia and luminal stenosis of arteriovenous polytetrafluoroethylene grafts in pigs
Circulation
111
1679-1684
2005
Bos taurus
Manually annotated by BRENDA team
Pao, C.S.; Benovic, J.L.
Structure/function analysis of alpha2A-adrenergic receptor interaction with G protein-coupled receptor kinase 2
J. Biol. Chem.
280
11052-11058
2005
Bos taurus
Manually annotated by BRENDA team
Kim, K.M.; Gainetdinov, R.R.; Laporte, S.A.; Caron, M.G.; Barak, L.S.
G protein-coupled receptor kinase regulates dopamine D3 receptor signaling by modulating the stability of a receptor-filamin-beta-arrestin complex. A case of autoreceptor regulation
J. Biol. Chem.
280
12774-12780
2005
Bos taurus
Manually annotated by BRENDA team
Wu, J.H.; Goswami, R.; Kim, L.K.; Miller, W.E.; Peppel, K.; Freedman, N.J.
The platelet-derived growth factor receptor-beta phosphorylates and activates G protein-coupled receptor kinase-2. A mechanism for feedback inhibition
J. Biol. Chem.
280
31027-31035
2005
Bos taurus
Manually annotated by BRENDA team
Kenski, D.M.; Zhang, C.; von Zastrow, M.; Shokat, K.M.
Chemical genetic engineering of G protein-coupled receptor kinase 2
J. Biol. Chem.
280
35051-35061
2005
Bos taurus
Manually annotated by BRENDA team
Jimenez-Sainz, M.C.; Murga, C.; Kavelaars, A.; Jurado-Pueyo, M.; Krakstad, B.F.; Heijnen, C.J.; Mayor, F.Jr.; Aragay, A.M.
G protein-coupled receptor kinase 2 negatively regulates chemokine signaling at a level downstream from G protein subunits
Mol. Biol. Cell
17
25-31
2006
Bos taurus, Mus musculus
Manually annotated by BRENDA team
Lodowski, D.T.; Pitcher, J.A.; Capel, W.D.; Lefkowitz, R.J.; Tesmer, J.J.
Keeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and Gbetagamma
Science
300
1256-1262
2003
Bos taurus
Manually annotated by BRENDA team
Meloni, A.R.; Fralish, G.B.; Kelly, P.; Salahpour, A.; Chen, J.K.; Wechsler-Reya, R.J.; Lefkowitz, R.J.; Caron, M.G.
Smoothened signal transduction is promoted by G protein-coupled receptor kinase 2
Mol. Cell. Biol.
26
7550-7560
2006
Bos taurus
Manually annotated by BRENDA team
Chen, M.; Sato, P.Y.; Chuprun, J.K.; Peroutka, R.J.; Otis, N.J.; Ibetti, J.; Pan, S.; Sheu, S.S.; Gao, E.; Koch, W.J.
Prodeath signaling of g protein-coupled receptor kinase 2 in cardiac myocytes after ischemic stress occurs via extracellular signal-regulated kinase-dependent heat shock protein 90-mediated mitochondrial targeting
Circ. Res.
112
1121-1134
2013
Bos taurus, Rattus norvegicus
Manually annotated by BRENDA team
Fernandez, N.; Gottardo, F.L.; Alonso, M.N.; Monczor, F.; Shayo, C.; Davio, C.
Roles of phosphorylation-dependent and -independent mechanisms in the regulation of histamine H2 receptor by G protein-coupled receptor kinase 2
J. Biol. Chem.
286
28697-28706
2011
Bos taurus
Manually annotated by BRENDA team
Waldschmidt, H.V.; Homan, K.T.; Cruz-Rodriguez, O.; Cato, M.C.; Waninger-Saroni, J.; Larimore, K.M.; Cannavo, A.; Song, J.; Cheung, J.Y.; Kirchhoff, P.D.; Koch, W.J.; Tesmer, J.J.; Larsen, S.D.
Structure-based design, synthesis, and biological evaluation of highly selective and potent G protein-coupled receptor kinase 2 inhibitors
J. Med. Chem.
59
3793-3807
2016
Bos taurus (P21146)
Manually annotated by BRENDA team