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Protein

Beta-adrenergic receptor kinase 1

Gene

Grk2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them. Key regulator of LPAR1 signaling. Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner. Positively regulates ciliary smoothened (SMO)-dependent Hedgehog (Hh) signaling pathway by faciltating the trafficking of SMO into the cilium and the stimulation of SMO activity.By similarity

Catalytic activityi

ATP + [beta-adrenergic receptor] = ADP + [beta-adrenergic receptor] phosphate.

Enzyme regulationi

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.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei3Required for receptor phosphorylationBy similarity1
Sitei4Required for receptor phosphorylationBy similarity1
Sitei10Required for receptor phosphorylationBy similarity1
Binding sitei220ATPPROSITE-ProRule annotation1
Active sitei317Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi197 – 205ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • beta-adrenergic receptor kinase activity Source: RGD
  • G-protein coupled receptor kinase activity Source: RGD

GO - Biological processi

  • aging Source: RGD
  • desensitization of G-protein coupled receptor protein signaling pathway Source: BHF-UCL
  • follicle-stimulating hormone signaling pathway Source: RGD
  • G-protein coupled receptor signaling pathway Source: RGD
  • negative regulation of G-protein coupled receptor protein signaling pathway Source: RGD
  • positive regulation of catecholamine secretion Source: BHF-UCL
  • positive regulation of excitatory postsynaptic potential Source: RGD
  • positive regulation of sensory perception of pain Source: RGD
  • positive regulation of vasoconstriction Source: RGD
  • protein phosphorylation Source: RGD
  • response to hydrogen peroxide Source: RGD
  • response to morphine Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to oxidative stress Source: RGD

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.15 5301

Names & Taxonomyi

Protein namesi
Recommended name:
Beta-adrenergic receptor kinase 1 (EC:2.7.11.15)
Short name:
Beta-ARK-1
Alternative name(s):
G-protein-coupled receptor kinase 2Imported
Gene namesi
Name:Grk2Imported
Synonyms:Adrbk1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2062 Grk2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000856301 – 689Beta-adrenergic receptor kinase 1Add BLAST689

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei670PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP26817
PRIDEiP26817

PTM databases

iPTMnetiP26817
PhosphoSitePlusiP26817

Interactioni

Subunit structurei

Interacts with GIT1. Interacts with, and phosphorylates chemokine-stimulated CCR5. Interacts with ARRB1. Interacts with LPAR1 and LPAR2. Interacts with RALA in response to LPAR1 activation. ADRBK1 and RALA mutually inhibit each other's binding to LPAR1. Interacts with ADRB2.By similarity

Protein-protein interaction databases

BioGridi247278, 3 interactors
STRINGi10116.ENSRNOP00000025847

Structurei

3D structure databases

ProteinModelPortaliP26817
SMRiP26817
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini54 – 175RGSPROSITE-ProRule annotationAdd BLAST122
Domaini191 – 453Protein kinasePROSITE-ProRule annotationAdd BLAST263
Domaini454 – 521AGC-kinase C-terminalAdd BLAST68
Domaini558 – 652PHPROSITE-ProRule annotationAdd BLAST95

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 190N-terminalAdd BLAST190

Domaini

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.By similarity

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0986 Eukaryota
ENOG410YRQZ LUCA
HOGENOMiHOG000006742
HOVERGENiHBG050559
InParanoidiP26817
KOiK00910
PhylomeDBiP26817

Family and domain databases

Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR000239 GPCR_kinase
IPR011009 Kinase-like_dom_sf
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR016137 RGS
IPR036305 RGS_sf
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00169 PH, 1 hit
PF00069 Pkinase, 1 hit
PF00615 RGS, 1 hit
PRINTSiPR00717 GPCRKINASE
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00315 RGS, 1 hit
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF48097 SSF48097, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS50003 PH_DOMAIN, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
PS50132 RGS, 1 hit

Sequencei

Sequence statusi: Complete.

P26817-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADLEAVLAD VSYLMAMEKS KATPAARASK KILLPEPSIR SVMQKYLEDR
60 70 80 90 100
GEVTFEKIFS QKLGYLLFRD FYLNHLEEAK PLVEFYEEIE KYEKLETEEE
110 120 130 140 150
RVVRSREIFD SYIMKELLAC SHPFSKNATE HVQGHLVKKQ VPPDLFQPYI
160 170 180 190 200
EEICQNLRGD VFHKFIESDK FTRFCQWKNV ELNIHLTMND FSVHRIIGRG
210 220 230 240 250
GFGEVYGCRK ADTGKMYAMK CLDKKRIKMK QGETLALNER IMLSLVSTGD
260 270 280 290 300
CPFIVCMSYA FHTPDKLSFI LDLMNGGDLH YHLSQHGVFS EADMRFYAAE
310 320 330 340 350
IILGLEHMHN RFVVYRDLKP ANILLDEHGH VRISDLGLAC DFSKKKPHAS
360 370 380 390 400
VGTHGYMAPE VLQKGVAYDS SADWFSLGCM LFKLLRGHSP FRQHKTKDKH
410 420 430 440 450
EIDRMTLTMA VELPDSFSPE LRSLLEGLLQ RDVNRRLGCL GRGAQEIKES
460 470 480 490 500
PFFRSLDWQM VFLQKYPPPL IPPRGEVNAA DAFDIGSFDE EDTKGIKLLD
510 520 530 540 550
SDQELYRNFP LTISERWQQE VAETVFDTIN AETDRLEARK KAKNKQLGHE
560 570 580 590 600
EDYALGKDCI MHGYMSKMGN PFLTQWQRRY FYLFPNRLEW RGEDEAPQSL
610 620 630 640 650
LTMEEIQSVE ETQIKERKCL LLKIRGGKQF VLQCDSDPEL VQWKKELRDA
660 670 680
YREAQQLVQR VPKMKNKPRS PVVELSKVPL IQRGSANGL
Length:689
Mass (Da):79,785
Last modified:August 1, 1992 - v1
Checksum:i426A3335ACEB5A34
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti24 – 25PA → RR in AAB24228 (PubMed:1436718).Curated2
Sequence conflicti46Y → N in AAB24228 (PubMed:1436718).Curated1
Sequence conflicti72Y → C in AAB24228 (PubMed:1436718).Curated1
Sequence conflicti90E → K in AAB24228 (PubMed:1436718).Curated1
Sequence conflicti249G → V in AAB24228 (PubMed:1436718).Curated1
Sequence conflicti270I → S in AAB24228 (PubMed:1436718).Curated1
Sequence conflicti296F → Y in AAB24228 (PubMed:1436718).Curated1
Sequence conflicti447I → V in AAB24228 (PubMed:1436718).Curated1
Sequence conflicti594D → G in AAB24228 (PubMed:1436718).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M87854 mRNA Translation: AAA40802.1
S48813 mRNA Translation: AAB24228.1
PIRiI56531
RefSeqiNP_036908.1, NM_012776.1
UniGeneiRn.13010

Genome annotation databases

GeneIDi25238
KEGGirno:25238
UCSCiRGD:2062 rat

Similar proteinsi

Entry informationi

Entry nameiARBK1_RAT
AccessioniPrimary (citable) accession number: P26817
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: May 23, 2018
This is version 153 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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