Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Beta-adrenergic receptor kinase 1

Gene

GRK2

Organism
Homo sapiens (Human)
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 (PubMed:19306925, PubMed:19715378). 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).By similarity2 Publications

Catalytic activityi

ATP + [beta-adrenergic receptor] = ADP + [beta-adrenergic receptor] phosphate.1 Publication

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 phosphorylation1 Publication1
Sitei4Required for receptor phosphorylation1 Publication1
Sitei10Required for receptor phosphorylation1 Publication1
Binding sitei220ATPPROSITE-ProRule annotation1
Active sitei317Proton acceptorPROSITE-ProRule annotation1

Regions

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

GO - Molecular functioni

GO - Biological processi

  • cardiac muscle contraction Source: BHF-UCL
  • desensitization of G-protein coupled receptor protein signaling pathway Source: BHF-UCL
  • G-protein coupled acetylcholine receptor signaling pathway Source: BHF-UCL
  • G-protein coupled receptor signaling pathway Source: Reactome
  • heart development Source: Ensembl
  • negative regulation of striated muscle contraction Source: BHF-UCL
  • negative regulation of the force of heart contraction by chemical signal Source: BHF-UCL
  • peptidyl-serine phosphorylation Source: BHF-UCL
  • peptidyl-threonine phosphorylation Source: Ensembl
  • positive regulation of catecholamine secretion Source: BHF-UCL
  • receptor internalization Source: UniProtKB
  • tachykinin receptor signaling pathway Source: BHF-UCL
  • viral entry into host cell Source: CACAO
  • viral genome replication Source: CACAO

Keywordsi

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

Enzyme and pathway databases

BRENDAi2.7.11.15 2681
ReactomeiR-HSA-111933 Calmodulin induced events
R-HSA-416476 G alpha (q) signalling events
R-HSA-418555 G alpha (s) signalling events
R-HSA-5635838 Activation of SMO
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
SignaLinkiP25098
SIGNORiP25098

Names & Taxonomyi

Protein namesi
Recommended name:
Beta-adrenergic receptor kinase 1 (EC:2.7.11.151 Publication)
Short name:
Beta-ARK-1
Alternative name(s):
G-protein coupled receptor kinase 2Imported
Gene namesi
Name:GRK2Imported
Synonyms:ADRBK1, BARK, BARK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000173020.10
HGNCiHGNC:289 GRK2
MIMi109635 gene
neXtProtiNX_P25098

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi3D → A: 85% reduction in phosphorylation of G-protein coupled receptor rhodopsin. 1 Publication1
Mutagenesisi3D → 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. 1 Publication1
Mutagenesisi3D → N: 60% reduction in phosphorylation of G-protein coupled receptor rhodopsin. 1 Publication1
Mutagenesisi4L → 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. 1 Publication1
Mutagenesisi4L → K: 95% reduction in phosphorylation of G-protein coupled receptor rhodopsin. 1 Publication1
Mutagenesisi5E → A: 50% reduction in phosphorylation of G-protein coupled receptor rhodopsin. 1 Publication1
Mutagenesisi7 – 8VL → AA: 95% reduction in phosphorylation of G-protein coupled receptor rhodopsin. 1 Publication2
Mutagenesisi10D → 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. 1 Publication1

Organism-specific databases

DisGeNETi156
OpenTargetsiENSG00000173020
PharmGKBiPA40

Chemistry databases

ChEMBLiCHEMBL4079
DrugBankiDB00171 Adenosine triphosphate
GuidetoPHARMACOLOGYi1466

Polymorphism and mutation databases

BioMutaiADRBK1
DMDMi126302521

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000856271 – 689Beta-adrenergic receptor kinase 1Add BLAST689

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei670PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP25098
MaxQBiP25098
PaxDbiP25098
PeptideAtlasiP25098
PRIDEiP25098

PTM databases

iPTMnetiP25098
PhosphoSitePlusiP25098

Expressioni

Tissue specificityi

Expressed in peripheral blood leukocytes.1 Publication

Gene expression databases

BgeeiENSG00000173020
CleanExiHS_ADRBK1
ExpressionAtlasiP25098 baseline and differential
GenevisibleiP25098 HS

Organism-specific databases

HPAiCAB005021
CAB037248
HPA048330

Interactioni

Subunit structurei

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).By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106665, 55 interactors
DIPiDIP-42429N
IntActiP25098, 25 interactors
MINTiP25098
STRINGi9606.ENSP00000312262

Chemistry databases

BindingDBiP25098

Structurei

Secondary structure

1689
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi39 – 49Combined sources11
Helixi55 – 59Combined sources5
Helixi62 – 75Combined sources14
Helixi77 – 79Combined sources3
Helixi80 – 93Combined sources14
Helixi98 – 109Combined sources12
Helixi112 – 118Combined sources7
Beta strandi119 – 122Combined sources4
Helixi126 – 137Combined sources12
Turni143 – 146Combined sources4
Helixi147 – 157Combined sources11
Helixi160 – 167Combined sources8
Helixi169 – 181Combined sources13
Helixi188 – 190Combined sources3
Beta strandi191 – 199Combined sources9
Beta strandi201 – 210Combined sources10
Turni211 – 213Combined sources3
Beta strandi216 – 223Combined sources8
Helixi224 – 229Combined sources6
Helixi233 – 246Combined sources14
Beta strandi247 – 249Combined sources3
Beta strandi252 – 254Combined sources3
Beta strandi257 – 262Combined sources6
Beta strandi264 – 271Combined sources8
Beta strandi276 – 278Combined sources3
Helixi279 – 286Combined sources8
Helixi291 – 309Combined sources19
Turni310 – 312Combined sources3
Helixi320 – 322Combined sources3
Beta strandi323 – 325Combined sources3
Beta strandi327 – 329Combined sources3
Beta strandi331 – 333Combined sources3
Helixi336 – 338Combined sources3
Beta strandi343 – 345Combined sources3
Helixi354 – 356Combined sources3
Helixi359 – 362Combined sources4
Beta strandi363 – 365Combined sources3
Helixi371 – 386Combined sources16
Beta strandi390 – 392Combined sources3
Helixi393 – 395Combined sources3
Helixi399 – 408Combined sources10
Beta strandi415 – 417Combined sources3
Helixi419 – 428Combined sources10
Helixi433 – 435Combined sources3
Beta strandi440 – 442Combined sources3
Helixi444 – 447Combined sources4
Helixi451 – 453Combined sources3
Helixi458 – 462Combined sources5
Turni477 – 480Combined sources4
Turni492 – 495Combined sources4
Helixi500 – 503Combined sources4
Turni504 – 508Combined sources5
Helixi514 – 522Combined sources9
Turni523 – 525Combined sources3
Helixi526 – 546Combined sources21
Beta strandi555 – 557Combined sources3
Beta strandi561 – 568Combined sources8
Turni571 – 573Combined sources3
Beta strandi577 – 584Combined sources8
Beta strandi587 – 591Combined sources5
Beta strandi593 – 595Combined sources3
Beta strandi599 – 602Combined sources4
Helixi603 – 605Combined sources3
Beta strandi606 – 616Combined sources11
Beta strandi618 – 624Combined sources7
Turni625 – 627Combined sources3
Beta strandi628 – 633Combined sources6
Helixi637 – 658Combined sources22
Turni662 – 664Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BAKNMR-A556-670[»]
3CIKX-ray2.75A1-689[»]
3KRWX-ray2.90A2-689[»]
3KRXX-ray3.10A2-689[»]
3V5WX-ray2.07A1-689[»]
4MK0X-ray2.40A30-668[»]
4PNKX-ray2.56A1-689[»]
5HE1X-ray3.15A29-670[»]
5UKKX-ray2.60A30-671[»]
5UKLX-ray2.15A30-671[»]
5UUUX-ray2.70A23-538[»]
5UVCX-ray2.65A23-538[»]
5WG3X-ray2.90A1-689[»]
5WG4X-ray2.31A1-689[»]
5WG5X-ray3.10A1-689[»]
ProteinModelPortaliP25098
SMRiP25098
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP25098

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
InParanoidiP25098
KOiK00910
OMAiSEAEMRF
OrthoDBiEOG091G0AEI
PhylomeDBiP25098
TreeFamiTF313940

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.

P25098-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADLEAVLAD VSYLMAMEKS KATPAARASK KILLPEPSIR SVMQKYLEDR
60 70 80 90 100
GEVTFEKIFS QKLGYLLFRD FCLNHLEEAR PLVEFYEEIK KYEKLETEEE
110 120 130 140 150
RVARSREIFD SYIMKELLAC SHPFSKSATE HVQGHLGKKQ 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 DFSKKKPHAS
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 MHGYMSKMGN PFLTQWQRRY FYLFPNRLEW RGEGEAPQSL
610 620 630 640 650
LTMEEIQSVE ETQIKERKCL LLKIRGGKQF ILQCDSDPEL VQWKKELRDA
660 670 680
YREAQQLVQR VPKMKNKPRS PVVELSKVPL VQRGSANGL
Length:689
Mass (Da):79,574
Last modified:February 20, 2007 - v2
Checksum:i4DB68F62841AFA7D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti168 – 185SDKFT…ELNIH → RISSHGFASGRMWSSTST in AAB60689 (PubMed:8195124).CuratedAdd BLAST18
Sequence conflicti211A → R in CAA43470 (PubMed:2037065).Curated1
Sequence conflicti211A → R in AAB60689 (PubMed:8195124).Curated1
Sequence conflicti422R → H in CAA43470 (PubMed:2037065).Curated1
Sequence conflicti422R → H in AAB60689 (PubMed:8195124).Curated1
Sequence conflicti465K → R in CAA43470 (PubMed:2037065).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040378184I → T1 PublicationCorresponds to variant dbSNP:rs55696045Ensembl.1
Natural variantiVAR_040379578R → Q in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X61157 mRNA Translation: CAA43470.1
M80776 mRNA Translation: AAA58391.1
U08438
, U08435, U08436, U08437 Genomic DNA Translation: AAB60689.1
EU326303 Genomic DNA Translation: ACA05909.1
BC037963 mRNA Translation: AAH37963.1
BC090863 mRNA Translation: AAH90863.1
CCDSiCCDS8156.1
PIRiA53791
RefSeqiNP_001610.2, NM_001619.3
UniGeneiHs.83636

Genome annotation databases

EnsembliENST00000308595; ENSP00000312262; ENSG00000173020
GeneIDi156
KEGGihsa:156
UCSCiuc009yrn.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiARBK1_HUMAN
AccessioniPrimary (citable) accession number: P25098
Secondary accession number(s): B0ZBE1, Q13837, Q6GTT3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: February 20, 2007
Last modified: April 25, 2018
This is version 200 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health