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Protein

Beta-adrenergic receptor kinase 1

Gene

GRK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.1 Publication

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
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
  • 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
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS10607-MONOMER.
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:2.7.11.15)
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

HGNCiHGNC:289. GRK2.

Subcellular locationi

  • Cytoplasm By similarity
  • Cell membrane By similarity

GO - Cellular componenti

  • cytoplasm Source: BHF-UCL
  • cytosol Source: Reactome
  • membrane Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

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. 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.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
FPR1P214623EBI-3904795,EBI-2869495
GIT1Q9Y2X75EBI-3904795,EBI-466061
MDM2Q009874EBI-3904795,EBI-389668
UBCP0CG483EBI-3904795,EBI-3390054

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106665. 55 interactors.
DIPiDIP-42429N.
IntActiP25098. 22 interactors.
MINTiMINT-1214643.
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 strandi331 – 333Combined sources3
Helixi336 – 338Combined sources3
Beta strandi343 – 345Combined sources3
Helixi354 – 356Combined sources3
Helixi359 – 362Combined sources4
Helixi371 – 386Combined sources16
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
Helixi500 – 503Combined sources4
Turni504 – 508Combined sources5
Helixi514 – 522Combined sources9
Turni523 – 525Combined sources3
Helixi526 – 546Combined sources21
Beta strandi555 – 557Combined sources3
Beta strandi561 – 568Combined sources8
Helixi571 – 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[»]
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

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 RGS domain.PROSITE-ProRule annotation

Phylogenomic databases

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

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR000239. GPCR_kinase.
IPR011009. Kinase-like_dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016137. RGS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSiPR00717. GPCRKINASE.
SMARTiSM00233. PH. 1 hit.
SM00315. RGS. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF48097. SSF48097. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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.
[Graphical view]

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 → T.1 PublicationCorresponds to variant rs55696045dbSNPEnsembl.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

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[»]
ProteinModelPortaliP25098.
SMRiP25098.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106665. 55 interactors.
DIPiDIP-42429N.
IntActiP25098. 22 interactors.
MINTiMINT-1214643.
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.

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.
GeneCardsiADRBK1.
HGNCiHGNC:289. GRK2.
HPAiCAB005021.
CAB037248.
HPA048330.
MIMi109635. gene.
neXtProtiNX_P25098.
OpenTargetsiENSG00000173020.
PharmGKBiPA40.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS10607-MONOMER.
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

ChiTaRSiADRBK1. human.
EvolutionaryTraceiP25098.
GeneWikiiBeta_adrenergic_receptor_kinase.
GenomeRNAii156.
PROiP25098.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000173020.
CleanExiHS_ADRBK1.
ExpressionAtlasiP25098. baseline and differential.
GenevisibleiP25098. HS.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR000239. GPCR_kinase.
IPR011009. Kinase-like_dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016137. RGS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSiPR00717. GPCRKINASE.
SMARTiSM00233. PH. 1 hit.
SM00315. RGS. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF48097. SSF48097. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiARBK1_HUMAN
AccessioniPrimary (citable) accession number: P25098
Secondary accession number(s): B0ZBE1, Q13837, Q6GTT3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: February 20, 2007
Last modified: November 30, 2016
This is version 189 of the entry and version 2 of the sequence. [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 chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.