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Protein

Beta-adrenergic receptor kinase 1

Gene

Adrbk1

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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei220 – 2201ATPPROSITE-ProRule annotation
Active sitei317 – 3171Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi197 – 2059ATPPROSITE-ProRule annotation

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
  • termination of G-protein coupled receptor signaling pathway Source: InterPro
  • 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.
ReactomeiREACT_329133. Activation of SMO.
REACT_332567. Calmodulin induced events.
REACT_347934. G alpha (q) signalling events.

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 2
Gene namesi
Name:Adrbk1
Synonyms:Grk2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:87940. Adrbk1.

Subcellular locationi

  • Cytoplasm By similarity
  • Cell membrane By similarity

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 689689Beta-adrenergic receptor kinase 1PRO_0000085629Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei670 – 6701PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ99MK8.
PaxDbiQ99MK8.
PRIDEiQ99MK8.

PTM databases

PhosphoSiteiQ99MK8.

Expressioni

Gene expression databases

BgeeiQ99MK8.
CleanExiMM_ADRBK1.
ExpressionAtlasiQ99MK8. baseline and differential.

Interactioni

Subunit structurei

Interacts with GIT1. Interacts with, and phosphorylates chemokine-stimulated CCR5. Interacts with ARRB1 (By similarity).By similarity

Protein-protein interaction databases

BioGridi225525. 8 interactions.
DIPiDIP-32413N.
IntActiQ99MK8. 4 interactions.
MINTiMINT-4088166.
STRINGi10090.ENSMUSP00000025791.

Structurei

3D structure databases

ProteinModelPortaliQ99MK8.
SMRiQ99MK8. Positions 30-668.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini54 – 175122RGSPROSITE-ProRule annotationAdd
BLAST
Domaini191 – 453263Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini454 – 52168AGC-kinase C-terminalAdd
BLAST
Domaini558 – 65295PHPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 190190N-terminalAdd
BLAST

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-apha 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

eggNOGiCOG0515.
GeneTreeiENSGT00770000120493.
HOGENOMiHOG000006742.
HOVERGENiHBG050559.
InParanoidiQ99MK8.
KOiK00910.
OMAiDFCLKHL.
PhylomeDBiQ99MK8.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR000239. GPCR_kinase.
IPR011009. Kinase-like_dom.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016137. RGS.
IPR002290. Ser/Thr_dual-sp_kinase.
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.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti160 – 1601D → N in AAK21896 (PubMed:8638670).Curated
Sequence conflicti374 – 3741W → C in AAK21896 (PubMed:8638670).Curated
Sequence conflicti520 – 5201E → V in AAK21896 (PubMed:8638670).Curated
Sequence conflicti600 – 6001L → F in AAK21896 (PubMed:8638670).Curated
Sequence conflicti679 – 6791P → R in AAK21896 (PubMed:8638670).Curated

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.1. 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. Positions 30-668.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi225525. 8 interactions.
DIPiDIP-32413N.
IntActiQ99MK8. 4 interactions.
MINTiMINT-4088166.
STRINGi10090.ENSMUSP00000025791.

PTM databases

PhosphoSiteiQ99MK8.

Proteomic databases

MaxQBiQ99MK8.
PaxDbiQ99MK8.
PRIDEiQ99MK8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000088737; ENSMUSP00000086114; ENSMUSG00000024858.
GeneIDi110355.
KEGGimmu:110355.
UCSCiuc008fzu.1. mouse.

Organism-specific databases

CTDi156.
MGIiMGI:87940. Adrbk1.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00770000120493.
HOGENOMiHOG000006742.
HOVERGENiHBG050559.
InParanoidiQ99MK8.
KOiK00910.
OMAiDFCLKHL.
PhylomeDBiQ99MK8.

Enzyme and pathway databases

BRENDAi2.7.11.16. 3474.
ReactomeiREACT_329133. Activation of SMO.
REACT_332567. Calmodulin induced events.
REACT_347934. G alpha (q) signalling events.

Miscellaneous databases

PROiQ99MK8.
SOURCEiSearch...

Gene expression databases

BgeeiQ99MK8.
CleanExiMM_ADRBK1.
ExpressionAtlasiQ99MK8. baseline and differential.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR000239. GPCR_kinase.
IPR011009. Kinase-like_dom.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016137. RGS.
IPR002290. Ser/Thr_dual-sp_kinase.
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.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning of GRK2 cDNA from S49 murine lymphoma cells."
    Hughes R.J., Anderson K.L., Kiel D., Insel P.A.
    Am. J. Physiol. 270:C885-C891(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Lymphoma.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-689.
  3. "Comprehensive identification of phosphorylation sites in postsynaptic density preparations."
    Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.
    Mol. Cell. Proteomics 5:914-922(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain.

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: June 24, 2015
This is version 126 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

External Data

Dasty 3

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 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.