Reactome | UniProt:P25098 GRK2

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UniProt:P25098 GRK2 Show undefined attributes

chain	chain:1-689
checksum	4DB68F62841AFA7D
comment	FUNCTION Specifically 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). 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). 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 (By similarity). Inhibits relaxation of airway smooth muscle in response to blue light (PubMed:30284927).CATALYTIC ACTIVITY [beta-adrenergic receptor] + ATP = [beta-adrenergic receptor]-phosphate + ADP + H(+)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.SUBUNIT Interacts with the heterodimer formed by GNB1 and GNG2 (By similarity). Interacts with GIT1 (By similarity). Interacts with, and phosphorylates chemokine-stimulated CCR5 (PubMed:10085131). Interacts with ARRB1 (PubMed:9501202). Interacts with LPAR1 and LPAR2 (PubMed:19306925). Interacts with RALA in response to LPAR1 activation (PubMed:19306925). ADRBK1 and RALA mutually inhibit each other's binding to LPAR1 (PubMed:19306925). Interacts with ADRB2 (PubMed:19715378).INTERACTION Expressed in peripheral blood leukocytes.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.SIMILARITY Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.ONLINE INFORMATION Beta adrenergic receptor kinase entry
crossReference	[DatabaseIdentifier:12157632] PDB:5HE1 [DatabaseIdentifier:12815962] ZINC target:P25098 [DatabaseIdentifier:12812588] ZINC - Substances:ARBK1_HUMAN [DatabaseIdentifier:12808084] ZINC - Predictions - Purchasable:ARBK1_HUMAN [DatabaseIdentifier:12803957] ZINC - Biogenic:ARBK1_HUMAN [DatabaseIdentifier:12445369] RefSeq:NP_001610.2 [DatabaseIdentifier:12282319] Pharos - Targets:P25098 [DatabaseIdentifier:12260291] PRO:P25098 [DatabaseIdentifier:12157644] PDB:5UKK [DatabaseIdentifier:12157636] PDB:6C2Y [DatabaseIdentifier:12157629] PDB:3KRW [DatabaseIdentifier:12157634] PDB:3CIK [DatabaseIdentifier:12157628] PDB:4PNK [DatabaseIdentifier:12157639] PDB:7K7L [DatabaseIdentifier:12157633] PDB:5WG5 [DatabaseIdentifier:12157642] PDB:5WG3 [DatabaseIdentifier:12157638] PDB:6U7C [DatabaseIdentifier:12157641] PDB:5WG4 [DatabaseIdentifier:11507903] ENSEMBL:ENSG00000173020 [DatabaseIdentifier:11621925] ENSEMBL:ENSP00000312262 [DatabaseIdentifier:11744624] ENSEMBL:ENST00000308595 [DatabaseIdentifier:11778570] Guide to Pharmacology - Targets:1466 [DatabaseIdentifier:11784403] GeneCards:GRK2 [DatabaseIdentifier:11831846] HMDB Protein:HMDBP01262 [DatabaseIdentifier:11837500] HPA:ENSG00000173020-GRK2 [DatabaseIdentifier:12121995] OpenTargets:ENSG00000173020 [DatabaseIdentifier:12157646] PDB:7PWD [DatabaseIdentifier:12157631] PDB:4MK0 [DatabaseIdentifier:12157637] PDB:7K7Z [DatabaseIdentifier:12157643] PDB:5UKL [DatabaseIdentifier:12157645] PDB:5UUU [DatabaseIdentifier:12157630] PDB:3KRX [DatabaseIdentifier:12157647] PDB:3V5W [DatabaseIdentifier:12157635] PDB:1BAK [DatabaseIdentifier:12157640] PDB:5UVC
databaseName	UniProt
dbId	50271
description	recommendedName: Beta-adrenergic receptor kinase 1 shortName: Beta-ARK-1 ecNumber evidence="12"2.7.11.15 alternativeName: fullName evidence="18"G-protein coupled receptor kinase 2
displayName	UniProt:P25098 GRK2
geneName	GRK2 ADRBK1 BARK BARK1
identifier	P25098
isSequenceChanged	false
keyword	3D-structure ATP-binding Cell membrane Cell projection Cytoplasm Kinase Membrane Nucleotide-binding Phosphoprotein Proteomics identification Reference proteome Serine/threonine-protein kinase Synapse Transferase
modified	[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType	Protein
name	GRK2
otherIdentifier	11716022_at 11716023_s_at 156 16727702 201401_PM_s_at 201401_s_at 201402_PM_at 201402_at 3336802 3336803 3336808 3336809 3336815 3336816 3336817 3336818 3336820 3336821 3336822 3336823 3336824 3336825 3336826 3336827 3336828 3336829 3336830 3336831 3336832 3336833 3336834 3336835 3336836 3336837 3336838 3336839 3336840 3336841 3336842 3336843 3336844 3336845 3336846 3336847 3336848 3336849 3336850 3336851 3336852 3336853 3336854 3336855 3336856 38447_PM_at 38447_at 7941797 A_23_P202667 A_24_P326635 A_33_P3384392 GE81046 GE87490 GO:0000166 GO:0001664 GO:0002026 GO:0002029 GO:0003012 GO:0003108 GO:0003824 GO:0004672 GO:0004674 GO:0004703 GO:0005515 GO:0005524 GO:0005737 GO:0005829 GO:0005886 GO:0005929 GO:0006468 GO:0007165 GO:0007186 GO:0007213 GO:0007217 GO:0007507 GO:0016020 GO:0016192 GO:0016301 GO:0016740 GO:0019079 GO:0031623 GO:0031694 GO:0031755 GO:0032473 GO:0033605 GO:0042995 GO:0043226 GO:0045202 GO:0045988 GO:0046718 GO:0047696 GO:0048856 GO:0060048 GO:0098793 GO:0098794 GO:0140096 GO:1901081 HMNXSV003043248 ILMN_1673330 PH_hs_0004771 TC11000682.hg U08438_at g179334_3p_s_at g6138971_3p_at g6138971_3p_s_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-50270] GRK2 [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-111969] p-S29-ADRBK1 [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5632504] ADRBK1 [cilium] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9645318] p-S29-ADRBK1 [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000173020] ENSEMBL:ENSG00000173020 GRK2 [ReferenceDNASequence:12707541] UCSC:P25098 GRK2 [ReferenceDNASequence:11372983] BioGPS Gene:156 GRK2 [ReferenceDNASequence:11395404] COSMIC - genes:GRK2 GRK2 [ReferenceDNASequence:11408323] CTD Gene:156 GRK2 [ReferenceDNASequence:11431632] dbSNP Gene:156 GRK2 [ReferenceDNASequence:11816028] HGNC:289 GRK2 [ReferenceDNASequence:11910884] KEGG:hsa:156 GRK2 [ReferenceDNASequence:12002772] Monarch:156 GRK2 [ReferenceDNASequence:12086865] NCBI Gene:156 GRK2 [ReferenceDNASequence:12107648] OMIM:109635 GRK2
referenceTranscript	[ReferenceRNASequence:12626907] RefSeq:NM_001619.5 GRK2
schemaClass	ReferenceGeneProduct
secondaryIdentifier	ARBK1_HUMAN B0ZBE1 Q13837 Q6GTT3
sequenceLength	689
species	[Species:48887] Homo sapiens
stId	uniprot:P25098
url	http://purl.uniprot.org/uniprot/P25098

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-50270] GRK2 [plasma membrane] [EntityWithAccessionedSequence:R-HSA-111969] p-S29-ADRBK1 [plasma membrane] [EntityWithAccessionedSequence:R-HSA-5632504] ADRBK1 [cilium] [EntityWithAccessionedSequence:R-HSA-9645318] p-S29-ADRBK1 [cytosol]
(referenceSequence)	[ModifiedResidue:111968] O-phospho-L-serine at 29
(interactor)	[UndirectedInteraction:11158675] UniProt:P0CG48 <-> UniProt:P25098 (IntAct) [UndirectedInteraction:11173233] UniProt:P13591 <-> UniProt:P25098 (IntAct) [UndirectedInteraction:11175049] UniProt:P21462 <-> UniProt:P25098 (IntAct) [UndirectedInteraction:11205063] UniProt:P25098 <-> UniProt:P35626 (IntAct) [UndirectedInteraction:11205065] UniProt:P25098 <-> UniProt:P25963 (IntAct) [UndirectedInteraction:11205067] UniProt:P25098 <-> UniProt:P48730-2 (IntAct) [UndirectedInteraction:11205069] UniProt:P25098 <-> UniProt:P21860 (IntAct) [UndirectedInteraction:11205071] UniProt:P25098 <-> UniProt:P05067 (IntAct) [UndirectedInteraction:11205073] UniProt:P25098 <-> UniProt:Q9P2M4 (IntAct) [UndirectedInteraction:11205075] UniProt:P25098 <-> UniProt:Q13085 (IntAct) [UndirectedInteraction:11205077] UniProt:P25098 <-> UniProt:Q96T49 (IntAct) [UndirectedInteraction:11205079] UniProt:P25098 <-> UniProt:Q13635 (IntAct) [UndirectedInteraction:11205081] UniProt:P25098 <-> UniProt:Q9Y2X7 (IntAct) [UndirectedInteraction:11205083] UniProt:P25098 <-> UniProt:P00533 (IntAct) [UndirectedInteraction:11205085] UniProt:P25098 <-> UniProt:Q9UBN7 (IntAct)