UniProt functional annotation for P21146



	UniProt functional annotation for P21146

UniProt code: P21146.

Organism: Bos taurus (Bovine).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; Bovinae; Bos.

Function: Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them (By similarity). Key regulator of LPAR1 signaling (By similarity). Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor (By similarity). Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner (By similarity). Positively regulates ciliary smoothened (SMO)- dependent Hedgehog (Hh) signaling pathway by facilitating the trafficking of SMO into the cilium and the stimulation of SMO activity (PubMed:21659505). Inhibits relaxation of airway smooth muscle in response to blue light (By similarity). {ECO:0000250|UniProtKB:P25098, ECO:0000250|UniProtKB:Q99MK8, ECO:0000269|PubMed:21659505}.

Catalytic activity: Reaction=[beta-adrenergic receptor] + ATP = [beta-adrenergic receptor]- phosphate + ADP + H(+); Xref=Rhea:RHEA:19429, Rhea:RHEA-COMP:11222, Rhea:RHEA-COMP:11223, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43176, ChEBI:CHEBI:68546, ChEBI:CHEBI:456216; EC=2.7.11.15;

Activity regulation: In contrast to other AGC family kinases, the catalytic activity is solely regulated by the binding of substrates and ligands, not by phosphorylation of the kinase domain. {ECO:0000269|PubMed:12764189}.

Subunit: Interacts with the heterodimer formed by GNB1 and GNG2 (PubMed:12764189). Interacts with GIT1 (PubMed:9826657). Interacts with, and phosphorylates chemokine-stimulated CCR5 (By similarity). Interacts with ARRB1 (By similarity). Interacts with LPAR1 and LPAR2 (By similarity). Interacts with RALA in response to LPAR1 activation (By similarity). ADRBK1 and RALA mutually inhibit each other's binding to LPAR1 (By similarity). Interacts with ADRB2 (By similarity). {ECO:0000250|UniProtKB:P25098, ECO:0000269|PubMed:12764189, ECO:0000269|PubMed:9826657}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:12764189, ECO:0000269|PubMed:21659505}. Cell membrane {ECO:0000269|PubMed:12764189}.

Tissue specificity: Ubiquitous; brain, spleen > heart, lung > kidney. {ECO:0000269|PubMed:2552582}.

Domain: The PH domain binds anionic phospholipids and helps recruiting ADRBK1 from the cytoplasm to plasma membrane close to activated receptors. It mediates binding to G protein beta and gamma subunits, competing with G-alpha subunits and other G-betagamma effectors. {ECO:0000269|PubMed:12764189}.

Similarity: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Bos taurus (Bovine).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; Bovinae; Bos.



Function:		Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them (By similarity). Key regulator of LPAR1 signaling (By similarity). Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor (By similarity). Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner (By similarity). Positively regulates ciliary smoothened (SMO)- dependent Hedgehog (Hh) signaling pathway by facilitating the trafficking of SMO into the cilium and the stimulation of SMO activity (PubMed:21659505). Inhibits relaxation of airway smooth muscle in response to blue light (By similarity). {ECO:0000250\|UniProtKB:P25098, ECO:0000250\|UniProtKB:Q99MK8, ECO:0000269\|PubMed:21659505}.


Catalytic activity:		Reaction=[beta-adrenergic receptor] + ATP = [beta-adrenergic receptor]- phosphate + ADP + H(+); Xref=Rhea:RHEA:19429, Rhea:RHEA-COMP:11222, Rhea:RHEA-COMP:11223, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43176, ChEBI:CHEBI:68546, ChEBI:CHEBI:456216; EC=2.7.11.15;
Activity regulation:		In contrast to other AGC family kinases, the catalytic activity is solely regulated by the binding of substrates and ligands, not by phosphorylation of the kinase domain. {ECO:0000269\|PubMed:12764189}.
Subunit:		Interacts with the heterodimer formed by GNB1 and GNG2 (PubMed:12764189). Interacts with GIT1 (PubMed:9826657). Interacts with, and phosphorylates chemokine-stimulated CCR5 (By similarity). Interacts with ARRB1 (By similarity). Interacts with LPAR1 and LPAR2 (By similarity). Interacts with RALA in response to LPAR1 activation (By similarity). ADRBK1 and RALA mutually inhibit each other's binding to LPAR1 (By similarity). Interacts with ADRB2 (By similarity). {ECO:0000250\|UniProtKB:P25098, ECO:0000269\|PubMed:12764189, ECO:0000269\|PubMed:9826657}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:12764189, ECO:0000269\|PubMed:21659505}. Cell membrane {ECO:0000269\|PubMed:12764189}.
Tissue specificity:		Ubiquitous; brain, spleen > heart, lung > kidney. {ECO:0000269\|PubMed:2552582}.
Domain:		The PH domain binds anionic phospholipids and helps recruiting ADRBK1 from the cytoplasm to plasma membrane close to activated receptors. It mediates binding to G protein beta and gamma subunits, competing with G-alpha subunits and other G-betagamma effectors. {ECO:0000269\|PubMed:12764189}.
Similarity:		Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily. {ECO:0000305}.