Information on EC 2.7.11.15 - beta-adrenergic-receptor kinase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.11.15
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RECOMMENDED NAME
GeneOntology No.
beta-adrenergic-receptor kinase
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
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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
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Manually annotated by BRENDA team
North American opossum, gene GRK2
SwissProt
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
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G protein-coupled receptor kinase 2 is a RhoA effector that serves as a RhoA-activated scaffold protein for the ERK MAP kinase cascade
physiological function
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 protein
ADP + a phosphoprotein
show the reaction diagram
ATP + Ac-DEMEFTEAESNMN-NH2
ADP + Ac-DEMEFpTEAESNMN-NH2
show the reaction diagram
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highly specific substrate with phosphorylation sites at Thr409 and Ser413
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?
ATP + Ac-DEMEFTHAESNMN-NH2
ADP + Ac-DEMEFpTHAESNMN-NH2
show the reaction diagram
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?
ATP + Ac-DEMKFTEAESNMN-NH2
ADP + Ac-DEMKFpTEAESNMN-NH2
show the reaction diagram
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-
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-
?
ATP + Ac-DEMKFTHAESNMN-NH2
ADP + Ac-DEMKFpTHAESNMN-NH2
show the reaction diagram
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?
ATP + Ac-DEMSFTEAESNMN-NH2
ADP + Ac-DEMSFpTEAESNMN-NH2
show the reaction diagram
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-
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?
ATP + Ac-DEMSFTHAEANMN-NH2
ADP + Ac-DEMSFpTHAEANMN-NH2
show the reaction diagram
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?
ATP + Ac-EEMEFSEAEANMN-NH2
ADP + Ac-EEMEFpSEAEANMN-NH2
show the reaction diagram
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-
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?
ATP + Ac-EEMEFSEEAANMN-NH2
ADP + Ac-EEMEFpSEEAANMN-NH2
show the reaction diagram
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-
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?
ATP + Ac-EEMEFTEVEANMN-NH2
ADP + Ac-EEMEFpTEVEANMN-NH2
show the reaction diagram
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-
-
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?
ATP + alpha-synuclein
ADP + phosphorylated alpha-synuclein
show the reaction diagram
ATP + alpha1 beta-adrenergic receptor
ADP + phosphorylated alpha1 beta-adrenergic receptor
show the reaction diagram
ATP + alpha1-adrenergic receptor
ADP + alpha1-adrenergic receptor phosphate
show the reaction diagram
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-
-
?
ATP + alpha1D-adrenergic receptor
ADP + alpha1D-adrenergic receptor phosphate
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 + angiotensin receptor
ADP + phosphorylated angiotensin receptor
show the reaction diagram
ATP + beta-adrenergic receptor
ADP + beta-adrenergic receptor phosphate
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
ATP + beta-casein
ADP + phosphorylated beta-casein
show the reaction diagram
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recombinant HA-tagged wild-type and mutant GRK3
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?
ATP + beta-synuclein
ADP + phosphorylated beta-synuclein
show the reaction diagram
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?
ATP + beta-tubulin
ADP + phosphorylated beta-tubulin
show the reaction diagram
ATP + beta1-adrenergic receptor
ADP + beta1-adrenergic receptor phosphate
show the reaction diagram
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-
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?
ATP + beta2-adrenergic receptor
ADP + beta2-adrenergic receptor phosphate
show the reaction diagram
ATP + beta2-adrenergic receptor
ADP + phosphorylated beta2-adrenergic receptor
show the reaction diagram
ATP + calcium-sensing receptor
ADP + calcium-sensing receptor phosphate
show the reaction diagram
ATP + corticotropin-releasing factor receptor type 1
ADP + phosphorylated corticotropin-releasing factor receptor type 1
show the reaction diagram
ATP + DEMEFTEAESNMN
ADP + Ac-EEMEFpTEVEANMN-NH2
show the reaction diagram
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best substrate
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?
ATP + dopamine D1 receptor
ADP + phosphorylated dopamine D1 receptor
show the reaction diagram
ATP + dopamine D3 receptor
ADP + phosphorylated dopamine D3 receptor
show the reaction diagram
ATP + DREAM
ADP + phosphorylated DREAM
show the reaction diagram
ATP + epidermal growth factor receptor
ADP + phosphorylated epidermal growth factor receptor
show the reaction diagram
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?
ATP + epithelial Na+ channel
ADP + phosphorylated epithelial Na+ channel
show the reaction diagram
ATP + ezrin
ADP + phosphorylated ezrin
show the reaction diagram
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
ATP + insulin receptor substrate 1
ADP + phosphorylated insulin receptor substrate 1
show the reaction diagram
ATP + insulin receptor substrate-1
ADP + phosphorylated-insulin receptor substrate-1
show the reaction diagram
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?
ATP + LEESSSSDHAERPPG
?
show the reaction diagram
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?
ATP + M1 muscarinic acetylcholine receptor
ADP + phosphorylated M1 muscarinic acetylcholine receptor
show the reaction diagram
ATP + micro-opioid receptor
ADP + phosphorylated micro-opioid receptor
show the reaction diagram
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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
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?
ATP + Mst2 protein
ADP + phosphorylated Mst2 protein
show the reaction diagram
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?
ATP + muscarinic acetylcholine receptor
ADP + phospho-muscarinic acetylcholine receptor
show the reaction diagram
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agonist-dependent phosphorylation, subtype 2
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?
ATP + muscarinic cholinergic receptor
ADP + phospho-muscarinic cholinergic receptor
show the reaction diagram
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
show the reaction diagram
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recombinant HA-tagged wild-type and mutant GRK3
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?
ATP + Nedd4
ADP + phosphorylated Nedd4
show the reaction diagram
ATP + Nedd4 protein
ADP + phosphorylated Nedd4 protein
show the reaction diagram
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?
ATP + Nedd4-2
ADP + phosphorylated Nedd4-2
show the reaction diagram
ATP + Nedd4-2 protein
ADP + phosphorylated Nedd4-2 protein
show the reaction diagram
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?
ATP + p38 MAP kinase
ADP + phosphorylated p38 MAP kinase
show the reaction diagram
ATP + p38 mitogen-activated protein kinase
ADP + phosphorylated p38 mitogen-activated protein kinase
show the reaction diagram
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?
ATP + PDEgamma
ADP + phosphorylated PDEgamma
show the reaction diagram
ATP + PDGFRbeta
ADP + phosphorylated PDGFRbeta
show the reaction diagram
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?
ATP + peptide
ADP + phosphopeptide
show the reaction diagram
ATP + phosducin
ADP + phosphorylated phosducin
show the reaction diagram
ATP + phosphodiesterase gamma
ADP + phosphorylated phosphodiesterase gamma
show the reaction diagram
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?
ATP + platelet-activating factor receptor
ADP + phospho-platelet-activating factor receptor
show the reaction diagram
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PAF receptor acts as substrate
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?
ATP + platelet-derived growth factor receptor-beta
ADP + phosphorylated platelet-derived growth factor receptor-beta
show the reaction diagram
ATP + platelet-derived growth factor receptor-beta protein
ADP + phosphorylated platelet-derived growth factor receptor
show the reaction diagram
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?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
ATP + protein
ATP + phosphoprotein
show the reaction diagram
ATP + protein M33
ADP + phosphorylated protein M33
show the reaction diagram
ATP + R-smad
ADP + phosphorylated R-smad
show the reaction diagram
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GRK2
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?
ATP + rhodopsin
ADP + phosphorhodopsin
show the reaction diagram
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
ATP + rhodopsin
ADP + rhodopsin phosphate
show the reaction diagram
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cf. EC 2.7.11.14, rhodopsin is also a substrate of GRK2
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?
ATP + ribosomal protein P2
ADP + phosphorylated ribosomal protein P2
show the reaction diagram
ATP + RRRAEAAASAAA
ADP + RRRAEAAApSAAA
show the reaction diagram
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?
ATP + RRRAEASAA
ADP + RRRAEApSAA
show the reaction diagram
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poor peptide substrate
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?
ATP + RRRASAAASAA
?
show the reaction diagram
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poor peptide substrate
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?
ATP + RRRASASAA
?
show the reaction diagram
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poor peptide substrate
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?
ATP + RRRASpAAASAA
ADP + RRRASpAAASpAA
show the reaction diagram
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poor peptide substrate, higher catalytic efficiency than RRRASAAASAA
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?
ATP + RRRASpASAA
?
show the reaction diagram
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poor peptide substrate
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?
ATP + RRREEEEESAAA
?
show the reaction diagram
ATP + RRREEEEESAAA
ADP + RRREEEEEpSAAA
show the reaction diagram
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?
ATP + Smad2 protein
ADP + phosphorylated Smad2 protein
show the reaction diagram
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?
ATP + Smo
ADP + phosphorylated Smo
show the reaction diagram
ATP + Smoothened protein
ADP + phopshorylated Smoothened
show the reaction diagram
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a seven-transmembrane signaling protein
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?
ATP + Smoothened protein
ADP + phosphorylated Smoothened
show the reaction diagram
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GRK2 promotes smoothened signal transduction involved in regulation of cellular proliferation and differentiation through activation of the transcription factor Gli, overview
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?
ATP + synuclein
ADP + phosphorylated synuclein
show the reaction diagram
ATP + tubulin
ADP + phosphorylated tubulin
show the reaction diagram
ATP + [beta-adrenergic receptor]
ADP + phospho-[beta-adrenergic receptor]
show the reaction diagram
ATP + [beta2-adrenergic receptor]
ADP + phospho-[beta2-adrenergic receptor]
show the reaction diagram
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?
ATP + [beta2-adrenergic receptor]
ADP + [beta2-adrenergic receptor] phosphate
show the reaction diagram
ATP + [delta opioid receptor]
ADP + phospho-[delta opioid receptor]
show the reaction diagram
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?
ATP + [neurotensin receptor]
ADP + phospho-[neurotensin receptor]
show the reaction diagram
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the enzyme phosphorylates only the C-terminal serine residues
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?
ATP + [TSH receptor]
ADP + [TSH receptor]phosphate
show the reaction diagram
ezrin + ATP
phosphorylated ezrin + ADP
show the reaction diagram
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?
GTP + beta-adrenergic receptor
GDP + phospho-beta-adrenergic receptor
show the reaction diagram
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agonist-occupied form of beta-AR from hamster lung, GTP can substitute ATP, 2% as effective as ATP
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?
histamine H2 receptor + ATP
phosphorylated histamine H2 receptor + ADP
show the reaction diagram
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?
moesin + ATP
phosphorylated moesin + ADP
show the reaction diagram
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?
radixin + ATP
phosphorylated radixin + ADP
show the reaction diagram
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?
tubulin + ATP
phosphorylated-tubulin + ADP
show the reaction diagram
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?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
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?
ATP + alpha-synuclein
ADP + phosphorylated alpha-synuclein
show the reaction diagram
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colocalization of GRK2, GRK5, alpha-synuclein, and tau in neurodegenerative disorders characterized by fibrillary tau inclusions and/or alpha-synuclein-enriched Lewy bodies, overview
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?
ATP + alpha1 beta-adrenergic receptor
ADP + phosphorylated alpha1 beta-adrenergic receptor
show the reaction diagram
P26819
substrate specificities of GRK2 and GRK3 in cardiac myocytes, overview
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?
ATP + alpha1-adrenergic receptor
ADP + alpha1-adrenergic receptor phosphate
show the reaction diagram
P26819
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?
ATP + alpha1D-adrenergic receptor
ADP + alpha1D-adrenergic receptor phosphate
show the reaction diagram
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inhibition of vascular smooth muscle G protein-coupled receptor kinase 2 enhances alpha1D-adrenergic receptor constriction and signalling, overview
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?
ATP + alpha2A-adrenergic receptor
ADP + phosphorylated alpha2A-adrenergic receptor
show the reaction diagram
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?
ATP + angiotensin receptor
ADP + phosphorylated angiotensin receptor
show the reaction diagram
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phosphorylation by GRK2 preceeds the binding of arrestins, which inhibits the seven-transmembrane receptor, but initiates internalization, overview
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?
ATP + beta-adrenergic receptor
ADP + beta-adrenergic receptor phosphate
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
ATP + beta1-adrenergic receptor
ADP + beta1-adrenergic receptor phosphate
show the reaction diagram
P26819
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?
ATP + beta2-adrenergic receptor
ADP + beta2-adrenergic receptor phosphate
show the reaction diagram
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role of GRK activity in the regulation of beta2 adrenergic signaling, feedback mechanism, overview
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?
ATP + beta2-adrenergic receptor
ADP + phosphorylated beta2-adrenergic receptor
show the reaction diagram
ATP + calcium-sensing receptor
ADP + calcium-sensing receptor phosphate
show the reaction diagram
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homologous desensitization of G protein-coupled receptors is generally mediated by GRKs through phosphorylation-dependent and independent mechanisms, GRK2 can phosphorylate calcium-sensing receptor and, along with beta-arrestins, can attenuate calcium-sensing receptor-mediated signaling, mechanism, overview
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?
ATP + corticotropin-releasing factor receptor type 1
ADP + phosphorylated corticotropin-releasing factor receptor type 1
show the reaction diagram
ATP + dopamine D1 receptor
ADP + phosphorylated dopamine D1 receptor
show the reaction diagram
O97627
phosphorylation by GRK2 has a regulatory role as part of the PI3K-PKC-GRK2 cascade
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?
ATP + dopamine D3 receptor
ADP + phosphorylated dopamine D3 receptor
show the reaction diagram
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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
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?
ATP + DREAM
ADP + phosphorylated DREAM
show the reaction diagram
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i.e. downstream regulatory element antagonist modulator protein, GRK2 mediates phosphorylation of DREAM/potassium channel interacting protein KChIP3, a multifunctional protein of the neuronal calcium sensor subfamily of Ca2+-binding proteins with specific roles in different cell compartments, regulating membrane trafficking of Kv4.2 potassium channel, phosphorylation of Ser95 affects cell surface localization, but not Kv4 channel tetramerization, overview
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?
ATP + epithelial Na+ channel
ADP + phosphorylated epithelial Na+ channel
show the reaction diagram
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channel inactivation
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?
ATP + ezrin
ADP + phosphorylated ezrin
show the reaction diagram
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phosphorylation of ezrin affects the 7TM receptor mediated cytoskeletal reorganization
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?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
show the reaction diagram
ATP + insulin receptor substrate 1
ADP + phosphorylated insulin receptor substrate 1
show the reaction diagram
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role of GRK2 in insulin receptor IR signaling
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?
ATP + insulin receptor substrate-1
ADP + phosphorylated-insulin receptor substrate-1
show the reaction diagram
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-
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?
ATP + M1 muscarinic acetylcholine receptor
ADP + phosphorylated M1 muscarinic acetylcholine receptor
show the reaction diagram
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phosphorylation-dependent and -independent mechanisms in the regulation of M1 muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 in hippocampal neurons, GRK2 can inhibit the receptor-dependent signaling via phospholipase C, overview
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?
ATP + Nedd4
ADP + phosphorylated Nedd4
show the reaction diagram
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GRK2 interacts with and phosphorylates the ubiquitin protein ligase Nedd4 preventing the binding to proline-rich motifs present in the C-termini of epithelial Na+ channel subunits and inhibition of the channels, overview
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?
ATP + Nedd4-2
ADP + phosphorylated Nedd4-2
show the reaction diagram
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GRK2 interacts with and phosphorylates the ubiquitin protein ligase Nedd4-2 preventing the binding to proline-rich motifs present in the C-termini of epithelial Na+ channel subunits and inhibition of the channels, overview
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?
ATP + p38 MAP kinase
ADP + phosphorylated p38 MAP kinase
show the reaction diagram
ATP + PDEgamma
ADP + phosphorylated PDEgamma
show the reaction diagram
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phosphorylation of PDEgamma possibly stimulates EGFR-mediated ERK activation
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?
ATP + PDGFRbeta
ADP + phosphorylated PDGFRbeta
show the reaction diagram
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-
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?
ATP + phosducin
ADP + phosphorylated phosducin
show the reaction diagram
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phosducin is activated to inhibit Gbetagamma protein
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?
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
ATP + phosphoprotein
show the reaction diagram
ATP + protein M33
ADP + phosphorylated protein M33
show the reaction diagram
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GRK2 is a potent regulator of the mouse cytomegalovirus GPCR protein M33-induced Gq/11 signaling through its ability to phosphorylate M33 and sequester Galphaq/11 proteins dependent on an intact RH domain, the protein M33 is able to induce inositol phosphate accumulation, activate NF-kappaB, and promote smooth muscle cell migration, viral GPCRs like M33 play a role in viral dissemination in vivo, M33 is required for efficient murine cytomegalovirus replication in the mouse, and induces several signlaing pathways, overview
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?
ATP + rhodopsin
ADP + phosphorylated rhodopsin
show the reaction diagram
ATP + ribosomal protein P2
ADP + phosphorylated ribosomal protein P2
show the reaction diagram
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activation of P2
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?
ATP + Smo
ADP + phosphorylated Smo
show the reaction diagram
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GPRK2 participates in Hedgehog signaling in Drosophila melanogaster, and plays a key role in the Smo signal transduction pathway, when Gprk2 levels are lowered, Smo still accumulates at the cell membrane, but its activation is reduced, overview
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?
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 + synuclein
ADP + phosphorylated synuclein
show the reaction diagram
-
-
-
-
?
ATP + [beta-adrenergic receptor]
ADP + phospho-[beta-adrenergic receptor]
show the reaction diagram
ATP + [beta2-adrenergic receptor]
ADP + phospho-[beta2-adrenergic receptor]
show the reaction diagram
-
-
-
-
?
ATP + [beta2-adrenergic receptor]
ADP + [beta2-adrenergic receptor] phosphate
show the reaction diagram
-
-
-
-
?
ATP + [delta opioid receptor]
ADP + phospho-[delta opioid receptor]
show the reaction diagram
-
-
-
-
?
ATP + [neurotensin receptor]
ADP + phospho-[neurotensin receptor]
show the reaction diagram
-
the enzyme phosphorylates only the C-terminal serine residues
-
-
?
ATP + [TSH receptor]
ADP + [TSH receptor]phosphate
show the reaction diagram
-
GRK2 and GRK3, receptor activation
-
-
?
ezrin + ATP
phosphorylated ezrin + ADP
show the reaction diagram
-
-
-
-
?
histamine H2 receptor + ATP
phosphorylated histamine H2 receptor + ADP
show the reaction diagram
-
-
-
-
?
moesin + ATP
phosphorylated moesin + ADP
show the reaction diagram
-
-
-
-
?
radixin + ATP
phosphorylated radixin + ADP
show the reaction diagram
-
-
-
-
?
additional information
?
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