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Protein

Beta-adrenergic receptor kinase 1

Gene

Grk2

Organism
Mus musculus (Mouse)
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: UniProtKB-EC
  • Edg-2 lysophosphatidic acid receptor binding Source: MGI
  • G-protein coupled receptor kinase activity Source: MGI
  • protein kinase activity Source: MGI
  • protein serine/threonine kinase activity Source: MGI

GO - Biological processi

  • cardiac muscle contraction Source: MGI
  • desensitization of G-protein coupled receptor protein signaling pathway Source: MGI
  • G-protein coupled receptor signaling pathway Source: MGI
  • heart development Source: MGI
  • negative regulation of striated muscle contraction Source: MGI
  • negative regulation of the force of heart contraction by chemical signal Source: MGI
  • peptidyl-serine phosphorylation Source: MGI
  • peptidyl-threonine phosphorylation Source: MGI
  • protein phosphorylation Source: MGI
  • receptor internalization Source: MGI
  • regulation of the force of heart contraction Source: MGI
  • tachykinin receptor signaling pathway Source: MGI
  • viral entry into host cell Source: MGI
  • viral genome replication Source: MGI

Keywordsi

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

Enzyme and pathway databases

BRENDAi2.7.11.16 3474
ReactomeiR-MMU-111933 Calmodulin induced events
R-MMU-416476 G alpha (q) signalling events
R-MMU-418555 G alpha (s) signalling events
R-MMU-5635838 Activation of SMO

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:87940 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

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3711486

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000856291 – 689Beta-adrenergic receptor kinase 1Add BLAST689

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei670PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ99MK8
MaxQBiQ99MK8
PaxDbiQ99MK8
PRIDEiQ99MK8

PTM databases

iPTMnetiQ99MK8
PhosphoSitePlusiQ99MK8

Expressioni

Gene expression databases

BgeeiENSMUSG00000024858
CleanExiMM_ADRBK1
ExpressionAtlasiQ99MK8 baseline and differential
GenevisibleiQ99MK8 MM

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi225525, 7 interactors
DIPiDIP-32413N
ELMiQ99MK8
IntActiQ99MK8, 5 interactors
MINTiQ99MK8
STRINGi10090.ENSMUSP00000025791

Structurei

3D structure databases

ProteinModelPortaliQ99MK8
SMRiQ99MK8
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
GeneTreeiENSGT00860000133699
HOGENOMiHOG000006742
HOVERGENiHBG050559
InParanoidiQ99MK8
KOiK00910
OMAiSEAEMRF
OrthoDBiEOG091G0AEI
PhylomeDBiQ99MK8

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.

Q99MK8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADLEAVLAD VSYLMAMEKS KATPAARASK KILLPEPSIR SVMQKYLEDR
60 70 80 90 100
GEVTFEKIFS QKLGYLLFRD FCLNHLEEAK PLVEFYEEIK KYEKLETEEE
110 120 130 140 150
RVVRSREIFD SYIMKELLAC SHPFSKNATE HVQGHLVKKQ VPPDLFQPYI
160 170 180 190 200
EEICQNLRGD VFQKFIESDK 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 DFSKKRPHAS
360 370 380 390 400
VGTHGYMAPE VLQKGVAYDS SADWFSLGCM LFKLLRGHSP FRQHKTKDKH
410 420 430 440 450
EIDRMTLTMA VELPDSFSPE LRSLLEGLLQ RDVNRRLGCL GRGAQEVKES
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 VHGYMSKMGN PFLTQWQRRY FYLFPNRLEW RGEGEAPQSL
610 620 630 640 650
LTMEEIQSVE ETQIKERKCL LLKIRGGKQF VLQCDSDPEL VQWKKELRDA
660 670 680
YREAQQLVQR VPKMKNKPRS PVVELSKVPL IQRGSANGL
Length:689
Mass (Da):79,639
Last modified:May 24, 2004 - v2
Checksum:i508F32B287DD99C6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti160D → N in AAK21896 (PubMed:8638670).Curated1
Sequence conflicti374W → C in AAK21896 (PubMed:8638670).Curated1
Sequence conflicti520E → V in AAK21896 (PubMed:8638670).Curated1
Sequence conflicti600L → F in AAK21896 (PubMed:8638670).Curated1
Sequence conflicti679P → R in AAK21896 (PubMed:8638670).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF333028 mRNA Translation: AAK21896.1
BC003196 mRNA Translation: AAH03196.1
CCDSiCCDS70915.1
RefSeqiNP_001277747.1, NM_001290818.1
UniGeneiMm.254144

Genome annotation databases

EnsembliENSMUST00000088737; ENSMUSP00000086114; ENSMUSG00000024858
GeneIDi110355
KEGGimmu:110355
UCSCiuc008fzu.2 mouse

Similar proteinsi

Entry informationi

Entry nameiARBK1_MOUSE
AccessioniPrimary (citable) accession number: Q99MK8
Secondary accession number(s): Q99LL8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: May 24, 2004
Last modified: May 23, 2018
This is version 154 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

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