Reactome | UniProt:Q99MK8 Grk2

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UniProt:Q99MK8 Grk2 Show undefined attributes

chain	chain:1-689
checksum	508F32B287DD99C6
comment	FUNCTION Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them (By similarity). Phosphorylates catecholamine-activated ADRB2 to regulate physiological cardiomyocyte contraction rate responses (PubMed:18056263). Also phosphorylates ligand-bound C3a and C5a anaphylatoxin receptors (C3AR1 and C5AR1, respectively), leading to receptor desensitization (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 (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 (By similarity). Interacts with ARRB1 (By similarity). Interacts with LPAR1 and LPAR2. 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).SUBCELLULAR LOCATION 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.
created	[InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10
crossReference	[DatabaseIdentifier:12333954] RefSeq:NP_001277747.1 [DatabaseIdentifier:12250528] PRO:Q99MK8 [DatabaseIdentifier:11930927] MGI:87940 [DatabaseIdentifier:11670934] ENSEMBL:ENSMUST00000088737 [DatabaseIdentifier:11548235] ENSEMBL:ENSMUSP00000086114 [DatabaseIdentifier:11456895] ENSEMBL:ENSMUSG00000024858
databaseName	UniProt
dbId	144182
description	recommendedName: Beta-adrenergic receptor kinase 1 shortName: Beta-ARK-1 ecNumber evidence="3"2.7.11.15 alternativeName: fullName evidence="12"G-protein-coupled receptor kinase 2
displayName	UniProt:Q99MK8 Grk2
geneName	Grk2 Adrbk1
identifier	Q99MK8
isSequenceChanged	false
keyword	ATP-binding Cell membrane Cell projection Cytoplasm Kinase Membrane Nucleotide-binding Phosphoprotein Reference proteome Serine/threonine-protein kinase Synapse Transferase
modified	[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType	Protein
name	Grk2
otherIdentifier	104270_at 10464704 109767_at 110355 1426249_at 1451992_at 17361223 4311935 4430130 4438242 4456724 4499560 4514041 4731056 4735018 4766704 4787514 4835091 4851204 4924581 4940318 4951451 5062586 5098384 5106000 5141527 5182627 5187512 5192862 5208379 5347302 5353830 5363532 5421118 5439463 5455408 5495510 5528557 5531852 5534595 5559193 5600321 A_51_P460302 A_52_P580974 A_52_P664532 A_55_P1999269 GE112236 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:0007217 GO:0007507 GO:0016020 GO:0016192 GO:0016301 GO:0016740 GO:0019079 GO:0031623 GO:0031755 GO:0032473 GO:0042995 GO:0043226 GO:0045202 GO:0045988 GO:0046718 GO:0047696 GO:0048856 GO:0060048 GO:0098793 GO:0098794 GO:0140096 GO:1901081 ILMN_3000318 Msa.28719.0_s_at
physicalEntity	[EntityWithAccessionedSequence:R-MMU-9645318] phospho-p-S29-ADRBK1 [cytosol] - Mus musculus [EntityWithAccessionedSequence:R-MMU-5632501] Adrbk1 [cilium] - Mus musculus [EntityWithAccessionedSequence:R-MMU-111969] phospho-p-S29-ADRBK1 [plasma membrane] - Mus musculus [EntityWithAccessionedSequence:R-MMU-50270] GRK2 [plasma membrane] - Mus musculus
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:12729034] UCSC:Q99MK8 Grk2 [ReferenceDNASequence:12035571] NCBI Gene:110355 Grk2 [ReferenceDNASequence:11951478] Monarch:110355 Grk2 [ReferenceDNASequence:11864420] KEGG:mmu:110355 Grk2 [ReferenceDNASequence:11321689] BioGPS Gene:110355 Grk2
referenceTranscript	[ReferenceRNASequence:12515847] RefSeq:NM_001290818.2 Grk2
schemaClass	ReferenceGeneProduct
secondaryIdentifier	ARBK1_MOUSE Q99LL8
sequenceLength	689
species	[Species:48892] Mus musculus
stId	uniprot:Q99MK8
url	http://purl.uniprot.org/uniprot/Q99MK8

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-MMU-9645318] phospho-p-S29-ADRBK1 [cytosol] [EntityWithAccessionedSequence:R-MMU-5632501] Adrbk1 [cilium] [EntityWithAccessionedSequence:R-MMU-111969] phospho-p-S29-ADRBK1 [plasma membrane] [EntityWithAccessionedSequence:R-MMU-50270] GRK2 [plasma membrane]
(referenceSequence)	[ModifiedResidue:9992411] O-phospho-L-serine at 29 (in Homo sapiens)

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