GRK2
entrez
156
canonical
uniprot
P25098
canonical
ensembl
ENSG00000173020
resolver
ensp
ENSP00000312262
resolver
enst
ENST00000308595
resolver
genesymbol
ADRBK1
resolver
genesymbol
GRK2
resolver
genesymbol_syn
ADRBK1
resolver
genesymbol_syn
BARK
resolver
genesymbol_syn
BARK1
resolver
hgnc
HGNC:289
resolver
uniprot
A0A0S2Z392
resolver
uniprot
B0ZBE1
resolver
uniprot
Q13837
resolver
uniprot
Q6GTT3
resolver
uniprot_entry
A0A0S2Z392_HUMAN
resolver
uniprot_entry
GRK2_HUMAN
resolver
uniprot_sec
B0ZBE1
resolver
uniprot_sec
Q13837
resolver
uniprot_sec
Q6GTT3
resolver
activity_regulation
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:0000250|UniProtKB:P21146}.
uniprot
proteins
amino_acid_sequence
MADLEAVLADVSYLMAMEKSKATPAARASKKILLPEPSIRSVMQKYLEDRGEVTFEKIFSQKLGYLLFRDFCLNHLEEARPLVEFYEEIKKYEKLETEEERVARSREIFDSYIMKELLACSHPFSKSATEHVQGHLGKKQVPPDLFQPYIEEICQNLRGDVFQKFIESDKFTRFCQWKNVELNIHLTMNDFSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKRIKMKQGETLALNERIMLSLVSTGDCPFIVCMSYAFHTPDKLSFILDLMNGGDLHYHLSQHGVFSEADMRFYAAEIILGLEHMHNRFVVYRDLKPANILLDEHGHVRISDLGLACDFSKKKPHASVGTHGYMAPEVLQKGVAYDSSADWFSLGCMLFKLLRGHSPFRQHKTKDKHEIDRMTLTMAVELPDSFSPELRSLLEGLLQRDVNRRLGCLGRGAQEVKESPFFRSLDWQMVFLQKYPPPLIPPRGEVNAADAFDIGSFDEEDTKGIKLLDSDQELYRNFPLTISERWQQEVAETVFDTINAETDRLEARKKAKNKQLGHEEDYALGKDCIMHGYMSKMGNPFLTQWQRRYFYLFPNRLEWRGEGEAPQSLLTMEEIQSVEETQIKERKCLLLKIRGGKQFILQCDSDPELVQWKKELRDAYREAQQLVQRVPKMKNKPRSPVVELSKVPLVQRGSANGL
uniprot
proteins
ec_number
2.7.11.15
uniprot
proteins
ec_number
2.7.11.16
uniprot
proteins
function
FUNCTION: Specifically phosphorylates the activated forms of G protein-coupled receptors (PubMed:14976224, PubMed:16179383, PubMed:19306925, PubMed:19715378, PubMed:21799898, PubMed:23077507, PubMed:30284927, PubMed:33859231, PubMed:39138140, PubMed:40384633). Such receptor phosphorylation initiates beta-arrestin-mediated receptor internalization, and signaling events leading to their desensitization (PubMed:14976224, PubMed:16179383, PubMed:19306925, PubMed:19715378, PubMed:21799898, PubMed:23077507, PubMed:30284927, PubMed:33859231, PubMed:39138140, PubMed:40384633). Phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them (PubMed:19715378). Phosphorylates catecholamine-activated ADRB2 to regulate physiological cardiomyocyte contraction rate responses (By similarity). Also phosphorylates ligand-bound C3a and C5a anaphylatoxin receptors (C3AR1 and C5AR1, respectively), leading to receptor desensitization (PubMed:21799898, PubMed:23077507). Positively regulates ciliary smoothened (SMO) signaling pathway by mediating phosphorylation of SMO, facilitating SMO trafficking into the cilium and the stimulation of SMO activity (PubMed:39138140). Also positively regulates SMO signaling by mediating phosphorylation of GPR161, a key inhibitor SMO signaling, promoting ciliary export of GPR161 (PubMed:40384633). Key regulator of LPAR1 signaling (PubMed:19306925). Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor (PubMed:19306925). Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner (PubMed:19306925). Inhibits relaxation of airway smooth muscle in response to blue light (PubMed:30284927). Also able to mediate phosphorylation-independent desensitization of dopamine receptor DRD2 (By similarity). {ECO:0000250|UniProtKB:P21146, ECO:0000250|UniProtKB:P26817, ECO:0000250|UniProtKB:Q99MK8, ECO:0000269|PubMed:14976224, ECO:0000269|PubMed:16179383, ECO:0000269|PubMed:19306925, ECO:0000269|PubMed:19715378, ECO:0000269|PubMed:21799898, ECO:0000269|PubMed:23077507, ECO:0000269|PubMed:30284927, ECO:0000269|PubMed:33859231, ECO:0000269|PubMed:39138140, ECO:0000269|PubMed:40384633}.
uniprot
proteins
mass_dalton
79574
uniprot
proteins
mutagenesis
MUTAGEN 3; /note="D->A: 85% reduction in phosphorylation of G protein coupled receptor rhodopsin."; /evidence="ECO:0000269|PubMed:19715378"; MUTAGEN 3; /note="D->K: 95% reduction in phosphorylation of G protein coupled receptor rhodopsin. 60% reduction in phosphorylation of beta-2 adrenergic receptor ADRB2. Does not affect binding to ADRB2. Not activated by receptor binding. No effect on phosphorylation of the non-receptor substrate tubulin."; /evidence="ECO:0000269|PubMed:19715378"; MUTAGEN 3; /note="D->N: 60% reduction in phosphorylation of G protein coupled receptor rhodopsin."; /evidence="ECO:0000269|PubMed:19715378"; MUTAGEN 4; /note="L->A: 95% reduction in phosphorylation of G protein coupled receptor rhodopsin. 90% reduction in phosphorylation of beta-2 adrenergic receptor ADRB2. Does not affect binding to ADRB2. Not activated by receptor binding. No effect on phosphorylation of the non-receptor substrate tubulin."; /evidence="ECO:0000269|PubMed:19715378"; MUTAGEN 4; /note="L->K: 95% reduction in phosphorylation of G protein coupled receptor rhodopsin."; /evidence="ECO:0000269|PubMed:19715378"; MUTAGEN 5; /note="E->A: 50% reduction in phosphorylation of G protein coupled receptor rhodopsin."; /evidence="ECO:0000269|PubMed:19715378"; MUTAGEN 7..8; /note="VL->AA: 95% reduction in phosphorylation of G protein-coupled receptor rhodopsin."; /evidence="ECO:0000269|PubMed:19715378"; MUTAGEN 10; /note="D->A: 95% reduction in phosphorylation of G protein coupled receptor rhodopsin and beta-2 adrenergic receptor ADRB2. Does not affect binding to ADRB2. Not activated by receptor binding. No effect on phosphorylation of the non-receptor substrate tubulin."; /evidence="ECO:0000269|PubMed:19715378"; MUTAGEN 220; /note="K->M: Abolished G protein-coupled receptor kinase activity."; /evidence="ECO:0000269|PubMed:14976224, ECO:0000269|PubMed:16179383
uniprot
proteins
protein_family
AGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
GPRK subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10085131
uniprot
proteins
pubmed
1339451
uniprot
proteins
pubmed
14976224
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16179383
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
18088087
uniprot
proteins
pubmed
19306925
uniprot
proteins
pubmed
19715378
uniprot
proteins
pubmed
2037065
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21799898
uniprot
proteins
pubmed
23077507
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
30284927
uniprot
proteins
pubmed
33859231
uniprot
proteins
pubmed
39138140
uniprot
proteins
pubmed
40384633
uniprot
proteins
pubmed
8195124
uniprot
proteins
pubmed
9446593
uniprot
proteins
pubmed
9501202
uniprot
proteins
sequence_length
689
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P26817}. Cell membrane {ECO:0000250|UniProtKB:P21146}. Cell projection, cilium membrane {ECO:0000269|PubMed:39138140}. Postsynapse {ECO:0000250|UniProtKB:P26817}. Presynapse {ECO:0000250|UniProtKB:P26817}.
uniprot
proteins