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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

Activity 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

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
ProteomicsDBi54254

PTM databases

iPTMnetiP25098
PhosphoSitePlusiP25098

Expressioni

Tissue specificityi

Expressed in peripheral blood leukocytes.1 Publication

Gene expression databases

BgeeiENSG00000173020 Expressed in 178 organ(s), highest expression level in blood
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106665, 55 interactors
DIPiDIP-42429N
IntActiP25098, 24 interactors
MINTiP25098
STRINGi9606.ENSP00000312262

Chemistry databases

BindingDBiP25098

Structurei

Secondary structure

1689
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PRV7E9PRV7_HUMAN
G protein-coupled receptor kinase
GRK2
408Annotation score:

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

Cross-referencesi

Web resourcesi

Wikipedia

Beta adrenergic receptor kinase entry

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

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[»]
6C2YX-ray2.74A1-689[»]
ProteinModelPortaliP25098
SMRiP25098
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106665, 55 interactors
DIPiDIP-42429N
IntActiP25098, 24 interactors
MINTiP25098
STRINGi9606.ENSP00000312262

Chemistry databases

BindingDBiP25098
ChEMBLiCHEMBL4079
DrugBankiDB00171 Adenosine triphosphate
GuidetoPHARMACOLOGYi1466

PTM databases

iPTMnetiP25098
PhosphoSitePlusiP25098

Polymorphism and mutation databases

BioMutaiADRBK1
DMDMi126302521

Proteomic databases

EPDiP25098
MaxQBiP25098
PaxDbiP25098
PeptideAtlasiP25098
PRIDEiP25098
ProteomicsDBi54254

Protocols and materials databases

DNASUi156
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi156
DisGeNETi156
EuPathDBiHostDB:ENSG00000173020.10
GeneCardsiGRK2
HGNCiHGNC:289 GRK2
HPAiCAB005021
CAB037248
HPA048330
MIMi109635 gene
neXtProtiNX_P25098
OpenTargetsiENSG00000173020
PharmGKBiPA40
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0986 Eukaryota
ENOG410YRQZ LUCA
GeneTreeiENSGT00860000133699
HOGENOMiHOG000006742
HOVERGENiHBG050559
InParanoidiP25098
KOiK00910
OMAiSEAEMRF
OrthoDBiEOG091G0AEI
PhylomeDBiP25098
TreeFamiTF313940

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

Miscellaneous databases

ChiTaRSiGRK2 human
EvolutionaryTraceiP25098
GeneWikiiBeta_adrenergic_receptor_kinase
GenomeRNAii156
PROiPR:P25098
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000173020 Expressed in 178 organ(s), highest expression level in blood
CleanExiHS_ADRBK1
ExpressionAtlasiP25098 baseline and differential
GenevisibleiP25098 HS

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
ProtoNetiSearch...

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: September 12, 2018
This is version 204 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

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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