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Protein

Beta-adrenergic receptor kinase 1

Gene

Grk2

Organism
Mus musculus (Mouse)
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.

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

  • 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
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-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.
R-MMU-8856825. Cargo recognition for clathrin-mediated endocytosis.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:87940. Grk2.

Subcellular locationi

  • Cytoplasm By similarity
  • Cell membrane By similarity

GO - Cellular componenti

  • cytoplasm Source: MGI
  • membrane Source: MGI
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

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 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi225525. 7 interactors.
DIPiDIP-32413N.
IntActiQ99MK8. 4 interactors.
MINTiMINT-4088166.
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

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.
InParanoidiQ99MK8.
KOiK00910.
OMAiLMEFYEE.
OrthoDBiEOG091G0AEI.
PhylomeDBiQ99MK8.

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.

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ99MK8.
SMRiQ99MK8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi225525. 7 interactors.
DIPiDIP-32413N.
IntActiQ99MK8. 4 interactors.
MINTiMINT-4088166.
STRINGi10090.ENSMUSP00000025791.

PTM databases

iPTMnetiQ99MK8.
PhosphoSitePlusiQ99MK8.

Proteomic databases

EPDiQ99MK8.
MaxQBiQ99MK8.
PaxDbiQ99MK8.
PRIDEiQ99MK8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi110355.
MGIiMGI:87940. Grk2.

Phylogenomic databases

eggNOGiKOG0986. Eukaryota.
ENOG410YRQZ. LUCA.
GeneTreeiENSGT00860000133699.
HOGENOMiHOG000006742.
HOVERGENiHBG050559.
InParanoidiQ99MK8.
KOiK00910.
OMAiLMEFYEE.
OrthoDBiEOG091G0AEI.
PhylomeDBiQ99MK8.

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.
R-MMU-8856825. Cargo recognition for clathrin-mediated endocytosis.

Miscellaneous databases

PROiQ99MK8.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024858.
CleanExiMM_ADRBK1.
ExpressionAtlasiQ99MK8. baseline and differential.
GenevisibleiQ99MK8. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: Q99MK8
Secondary accession number(s): Q99LL8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: May 24, 2004
Last modified: November 30, 2016
This is version 141 of the entry and version 2 of the sequence. [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

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.