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Information on EC 2.7.11.16 - G-protein-coupled receptor kinase and Organism(s) Mus musculus and UniProt Accession O70293

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IUBMB Comments
Requires G-protein for activation and therefore belongs to the family of G-protein-dependent receptor kinases (GRKs). All members of this enzyme subfamily possess a highly conserved binding site for 1-phosphatidylinositol 4,5-bisphosphate. (cf. EC 2.7.11.14, rhodopsin kinase and EC 2.7.11.15, beta-adrenergic-receptor kinase).
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Mus musculus
UNIPROT: O70293
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Word Map
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
Synonyms
g-protein-coupled receptor kinase, g protein-coupled receptor kinase 5, g protein-coupled receptor kinase 4, g protein-coupled receptor kinase 6, grk4gamma, g-protein-coupled receptor kinase 5, g-protein-coupled receptor kinase 6, g-protein coupled receptor kinase 5, grk-6, g-protein coupled receptor kinase 6, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
G protein-coupled receptor kinase 6
-
G-protein coupled receptor kinase 6
-
G protein-coupled receptor kinase
G protein-coupled receptor kinase 4
-
-
G protein-coupled receptor kinase 5
G-protein coupled receptor kinase 5
-
G-protein-coupled receptor kinase 6
-
-
GPCR kinase
-
-
GRK3
-
-
additional information
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + [G protein-coupled receptor] = ADP + [G protein-coupled receptor]phosphate
show the reaction diagram
regulation mechanism
-
SYSTEMATIC NAME
IUBMB Comments
ATP:[G-protein-coupled receptor] phosphotransferase
Requires G-protein for activation and therefore belongs to the family of G-protein-dependent receptor kinases (GRKs). All members of this enzyme subfamily possess a highly conserved binding site for 1-phosphatidylinositol 4,5-bisphosphate. (cf. EC 2.7.11.14, rhodopsin kinase and EC 2.7.11.15, beta-adrenergic-receptor kinase).
CAS REGISTRY NUMBER
COMMENTARY hide
127407-08-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + a G protein-coupled receptor
ADP + a phosphorylated G protein-coupled receptor
show the reaction diagram
ATP + alpha1-adrenergic receptor
ADP + alpha1-adrenergic receptor phosphate
show the reaction diagram
GRK5 is also active with alpha1-adrenergic receptors. GRK5 activity, but not GRK2 activity, toward alpha1-adrenergic receptors can lead to transactivation of the tyrosine kinase receptor for epidermal growth factor in myocytes, cf. EC 2.7.11.15
-
-
?
ATP + ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
desensitization of the receptor by GRK4, GRK5, and GRK6
-
-
?
ATP + BLT1 receptor
ADP + phosphorylated BLT1 receptor
show the reaction diagram
ATP + central M2 muscarinic receptor
ADP + phosphorylated central M2 muscarinic receptor
show the reaction diagram
ATP + CXCR4 receptor
ADP + phosphorylated CXCR4 receptor
show the reaction diagram
ATP + dopamine D1 receptor
ADP + phosphorylated dopamine D1 receptor
show the reaction diagram
-
GRK4
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
ATP + protein p105
ADP + phosphorylated protein p105
show the reaction diagram
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
-
light-activated rhodopsin, recombinant isoforms mGRK6-A, mGRK6-B, and mGRK-C, the latter showing highest activity
-
-
?
ATP + tau protein
ADP + phosphorylated tau protein
show the reaction diagram
-
-
-
?
ATP + [G-protein-coupled receptor]
ADP + [G-protein-coupled receptor]phosphate
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 + a G protein-coupled receptor
ADP + a phosphorylated G protein-coupled receptor
show the reaction diagram
-
the GRKs are important in the cardiovascular system, the major G protein-coupled receptor regulatory pathway involves phosphorylation of activated receptors by GRKs, followed by binding of arrestin proteins, which prevent receptors from activating downstream heterotrimeric G protein pathways while allowing activation of arrestin-dependent signaling pathways, general mechanisms of GRK-arrestin regulation, overview, physiological functions and potential pathophysiological roles of GRKs and arrestins in human disorders, overview
-
-
?
ATP + ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
-
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
show the reaction diagram
-
desensitization of the receptor by GRK4, GRK5, and GRK6
-
-
?
ATP + BLT1 receptor
ADP + phosphorylated BLT1 receptor
show the reaction diagram
-
GRK6, ablation of GRK6 leads to augmented signaling by leukotriene B4 acting through the BLT1 receptor
-
-
?
ATP + central M2 muscarinic receptor
ADP + phosphorylated central M2 muscarinic receptor
show the reaction diagram
-
desensitization of the receptor by GRK5, GRK5 regulates pulmmonary responses by activation of the airway receptor, but does not regulate the peripheral cardiac muscarinic receptors
-
-
?
ATP + CXCR4 receptor
ADP + phosphorylated CXCR4 receptor
show the reaction diagram
-
GRK6, the pathway is important in facilitating neutrophil retention in the bone marrow
-
-
?
ATP + dopamine D1 receptor
ADP + phosphorylated dopamine D1 receptor
show the reaction diagram
-
GRK4
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
ATP + protein p105
ADP + phosphorylated protein p105
show the reaction diagram
-
-
-
-
?
ATP + [G-protein-coupled receptor]
ADP + [G-protein-coupled receptor]phosphate
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
inhibits GRK5
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
actinin
-
inhibits GRK5
-
Ca2+
-
inhibits GRK5
Ca2+/calmodulin
-
inhibit GRK5 with an IC50 of 40-50 nM, inhibition mechanism via inducing inhibitory autophosphorylation and blocking of membrane association
-
Calmodulin
-
inhibits GRK5
caveolin
-
inhibits GRK5
-
GRK2ct
carboxylterminal portion of GRK2
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
arrestins
-
arrestins modulate the enzyme activity having a regulatory role, regulation of arrestins, overview
-
phosphatidylinositol 4,5-bisphosphate
-
activates the receptor phosphorylation activity of GRK5, but not its autophosphorylation or peptide phosphorylation activity
additional information
-
autophosphorylation of GRK5 is stimulated by phospholipids, such as phosphatidylinositol-4,5-bisphosphate
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00004 - 0.00005
Ca2+/calmodulin
Mus musculus
-
inhibit GRK5 with an IC50 of 40-50 nM, inhibition mechanism via inducing inhibitory autophosphorylation and blocking of membrane association
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
physiologic activity of lungs in wild-type and GRK5-deficient mice, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
peritoneal macrophages, activation of Toll-like receptors selectively decreases arrestin-2 and GRK6 protein level in primary macrophages, mechanism, overview
Manually annotated by BRENDA team
-
expression of GRK4 in the brain is limited to cerebellar Purkinje cells
Manually annotated by BRENDA team
-
GRK4, GRK5, and GRK6
Manually annotated by BRENDA team
-
airway, GRK5
Manually annotated by BRENDA team
-
GRK4, mainly
Manually annotated by BRENDA team
-
GRK5
Manually annotated by BRENDA team
additional information
-
GRK5 and GRK6 are expressed in a wide variety of tissues, expression patterns, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
GRK5 negatively regulates CXCL1/KC levels during bacterial pneumonia
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
GRK6_MOUSE
576
0
65979
Swiss-Prot
other Location (Reliability: 2)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
lipoprotein
phosphoprotein
additional information
-
mechanisms of regulation of GRK protein stability and degradation, e.g. via ubiquitination or protease cleavage, overview
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
GRK2 by gel filtration from Sf9 cells
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recombinant isozymes mGRK6-A, mGRK6-B, and mGRK-C from Sf9 insect cells by sequential gel filtration and heparin affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
co-overexpression of GRK5 with MEF2 receptor leads to increased MEF2 activity in myocytes
expression of isoforms mGRK6-A, mGRK6-B, mGRK-C, and mGRK-D in Spodoptera frugiperda Sf9 cells via baculovirus infection system, transient expression of isoforms mGRK6-A, mGRK6-B, mGRK-C, and mGRK-D in COS-7 cells, recombinant isoforms mGRK6-A, mGRK6-B, and mGRK-C are membrane-associated, recombinant isoform mGRK6-D is inactive and located in the nucleus
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
GRK2 is increased in expression and activity in lymphocytes and vascular smooth muscle in human hypertension
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Walker, J.K.; Gainetdinov, R.R.; Feldman, D.S.; McFawn, P.K.; Caron, M.G.; Lefkowitz, R.J.; Premont, R.T.; Fisher, J.T.
G protein-coupled receptor kinase 5 regulates airway responses induced by muscarinic receptor activation
Am. J. Physiol.
286
L312-319
2004
Mus musculus
Manually annotated by BRENDA team
Penela, P.; Ribas, C.; Mayor, F.
Mechanisms of regulation of the expression and function of G protein-coupled receptor kinases
Cell. Signal.
15
973-981
2003
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Vatter, P.; Stoesser, C.; Samel, I.; Gierschik, P.; Moepps, B.
The variable C-terminal extension of G-protein-coupled receptor kinase 6 constitutes an accessorial autoregulatory domain
FEBS J.
272
6039-6051
2005
Mus musculus
Manually annotated by BRENDA team
Kohout, T.A.; Lefkowitz, R.J.
Regulation of G protein-coupled receptor kinases and arrestins during receptor desensitization
Mol. Pharmacol.
63
9-18
2003
Mus musculus
Manually annotated by BRENDA team
Premont, R.T.; Gainetdinov, R.R.
Physiological roles of G protein-coupled receptor kinases and arrestins
Annu. Rev. Physiol.
69
511-534
2007
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Parameswaran, N.; Pao, C.S.; Leonhard, K.S.; Kang, D.S.; Kratz, M.; Ley, S.C.; Benovic, J.L.
Arrestin-2 and G protein-coupled receptor kinase 5 interact with NFkappaB1 p105 and negatively regulate lipopolysaccharide-stimulated ERK1/2 activation in macrophages
J. Biol. Chem.
281
34159-34170
2006
Mus musculus
Manually annotated by BRENDA team
Cohn, H.I.; Harris, D.M.; Pesant, S.; Pfeiffer, M.; Zhou, R.H.; Koch, W.J.; Dorn, G.W.; Eckhart, A.D.
Inhibition of vascular smooth muscle G protein-coupled receptor kinase 2 enhances alpha1D-adrenergic receptor constriction
Am. J. Physiol. Heart Circ. Physiol.
295
H1695-H1704
2008
Mus musculus, Mus musculus (Q99MK8)
Manually annotated by BRENDA team
Eijkelkamp, N.; Heijnen, C.J.; Elsenbruch, S.; Holtmann, G.; Schedlowski, M.; Kavelaars, A.
G protein-coupled receptor kinase 6 controls post-inflammatory visceral hyperalgesia
Brain Behav. Immun.
23
18-26
2008
Mus musculus (O70293)
Manually annotated by BRENDA team
Eijkelkamp, N.; Heijnen, C.J.; Lucas, A.; Premont, R.T.; Elsenbruch, S.; Schedlowski, M.; Kavelaars, A.
G protein-coupled receptor kinase 6 controls chronicity and severity of dextran sodium sulphate-induced colitis in mice
Gut
56
847-854
2007
Mus musculus
Manually annotated by BRENDA team
Loniewski, K.; Shi, Y.; Pestka, J.; Parameswaran, N.
Toll-like receptors differentially regulate GPCR kinases and arrestins in primary macrophages
Mol. Immunol.
45
2312-2322
2008
Mus musculus (O70293), Mus musculus (Q8VEB1), Mus musculus C57BL/6 (O70293), Mus musculus C57BL/6 (Q8VEB1)
Manually annotated by BRENDA team
Martini, J.S.; Raake, P.; Vinge, L.E.; DeGeorge, B.; Chuprun, J.K.; Harris, D.M.; Gao, E.; Eckhart, A.D.; Pitcher, J.A.; Koch, W.J.
Uncovering G protein-coupled receptor kinase-5 as a histone deacetylase kinase in the nucleus of cardiomyocytes
Proc. Natl. Acad. Sci. USA
105
12457-12462
2008
Mus musculus (Q8VEB1)
Manually annotated by BRENDA team
Packiriswamy, N.; Steury, M.; McCabe, I.C.; Fitzgerald, S.D.; Parameswaran, N.
Bacterial dose-dependent role of G protein-coupled receptor kinase 5 in Escherichia coli-induced pneumonia
Infect. Immun.
84
1633-1641
2016
Mus musculus (Q8VEB1)
Manually annotated by BRENDA team
Zhao, J.; Li, X.; Chen, X.; Cai, Y.; Wang, Y.; Sun, W.; Mai, H.; Yang, J.; Fan, W.; Tang, P.; Ou, M.; Zhang, Y.; Huang, X.; Zhao, B.; Cui, L.
GRK5 influences the phosphorylation of tau via GSK3beta and contributes to Alzheimer's disease
J. Cell. Physiol.
234
10411-10420
2019
Mus musculus (Q8VEB1), Mus musculus
Manually annotated by BRENDA team