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P21146 (ARBK1_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Beta-adrenergic receptor kinase 1

Short name=Beta-ARK-1
EC=2.7.11.15
Alternative name(s):
G-protein-coupled receptor kinase 2
Gene names
Name:ADRBK1
Synonyms:GRK2
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

Protein attributes

Sequence length689 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity.

Catalytic activity

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

Subunit structure

Interacts with GIT1. 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 similarity. Ref.2

Tissue specificity

Ubiquitous; brain, spleen > heart, lung > kidney.

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 1 PH domain.

Contains 1 protein kinase domain.

Contains 1 RGS domain.

Ontologies

Keywords
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled acetylcholine receptor signaling pathway

Inferred from direct assay PubMed 8798423. Source: BHF-UCL

G-protein coupled receptor internalization

Inferred from direct assay PubMed 10521508. Source: UniProtKB

G-protein coupled receptor signaling pathway

Inferred from sequence or structural similarity. Source: AgBase

cardiac muscle contraction

Inferred from mutant phenotype PubMed 7761854. Source: BHF-UCL

desensitization of G-protein coupled receptor protein signaling pathway

Inferred from mutant phenotype PubMed 7761854. Source: BHF-UCL

heart development

Inferred from sequence or structural similarity. Source: AgBase

intracellular protein transport

Inferred from mutant phenotype PubMed 11259422. Source: BHF-UCL

negative regulation of striated muscle contraction

Inferred from mutant phenotype PubMed 7761854. Source: BHF-UCL

negative regulation of the force of heart contraction by chemical signal

Inferred from mutant phenotype PubMed 7761854. Source: BHF-UCL

peptidyl-serine phosphorylation

Inferred from direct assay PubMed 7761854. Source: BHF-UCL

peptidyl-threonine phosphorylation

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay PubMed 15653687. Source: BHF-UCL

regulation of signal transduction

Inferred from mutant phenotype PubMed 11259422. Source: BHF-UCL

regulation of the force of heart contraction

Inferred from sequence or structural similarity. Source: AgBase

tachykinin receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

termination of G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcytosol

Inferred from direct assay PubMed 11259422. Source: BHF-UCL

membrane

Inferred from direct assay PubMed 11259422. Source: BHF-UCL

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

Edg-2 lysophosphatidic acid receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

G-protein coupled receptor kinase activity

Inferred from direct assay PubMed 15653687PubMed 7761854. Source: BHF-UCL

alpha-2A adrenergic receptor binding

Inferred from physical interaction PubMed 15653687. Source: BHF-UCL

beta-adrenergic receptor kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein binding

Inferred from physical interaction PubMed 22193721. Source: IntAct

protein kinase activity

Inferred from direct assay PubMed 8798423. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

HDAC6Q9UBN73EBI-1036401,EBI-301697From a different organism.
Hdac6Q9Z2V52EBI-1036401,EBI-1009256From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 689689Beta-adrenergic receptor kinase 1
PRO_0000085626

Regions

Domain54 – 175122RGS
Domain191 – 453263Protein kinase
Domain454 – 52168AGC-kinase C-terminal
Domain558 – 65295PH
Nucleotide binding197 – 2059ATP By similarity
Region1 – 190190N-terminal
Region454 – 689236C-terminal

Sites

Active site3171Proton acceptor By similarity
Binding site2201ATP By similarity

Amino acid modifications

Modified residue6701Phosphoserine By similarity

Secondary structure

................................................................................................................ 689
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P21146 [UniParc].

Last modified May 1, 1991. Version 1.
Checksum: 4AB95DB5E630B9DA

FASTA68979,647
        10         20         30         40         50         60 
MADLEAVLAD VSYLMAMEKS KATPAARASK KILLPEPSIR SVMQKYLEDR GEVTFEKIFS 

        70         80         90        100        110        120 
QKLGYLLFRD FCLKHLEEAK PLVEFYEEIK KYEKLETEEE RLVCSREIFD TYIMKELLAC 

       130        140        150        160        170        180 
SHPFSKSAIE HVQGHLVKKQ VPPDLFQPYI EEICQNLRGD VFQKFIESDK FTRFCQWKNV 

       190        200        210        220        230        240 
ELNIHLTMND FSVHRIIGRG GFGEVYGCRK ADTGKMYAMK CLDKKRIKMK QGETLALNER 

       250        260        270        280        290        300 
IMLSLVSTGD CPFIVCMSYA FHTPDKLSFI LDLMNGGDLH YHLSQHGVFS EADMRFYAAE 

       310        320        330        340        350        360 
IILGLEHMHN RFVVYRDLKP ANILLDEHGH VRISDLGLAC DFSKKKPHAS VGTHGYMAPE 

       370        380        390        400        410        420 
VLQKGVAYDS SADWFSLGCM LFKLLRGHSP FRQHKTKDKH EIDRMTLTMA VELPDSFSPE 

       430        440        450        460        470        480 
LRSLLEGLLQ RDVNRRLGCL GRGAQEVKES PFFRSLDWQM VFLQKYPPPL IPPRGEVNAA 

       490        500        510        520        530        540 
DAFDIGSFDE EDTKGIKLLD SDQELYRNFP LTISERWQQE VAETVFDTIN AETDRLEARK 

       550        560        570        580        590        600 
KTKNKQLGHE EDYALGKDCI MHGYMSKMGN PFLTQWQRRY FYLFPNRLEW RGEGEAPQSL 

       610        620        630        640        650        660 
LTMEEIQSVE ETQIKERKCL LLKIRGGKQF VLQCDSDPEL VQWKKELRDA YREAQQLVQR 

       670        680 
VPKMKNKPRS PVVELSKVPL IQRGSANGL 

« Hide

References

[1]"Beta-adrenergic receptor kinase: primary structure delineates a multigene family."
Benovic J.L., Deblasi A., Stone W.C., Caron M.G., Lefkowitz R.J.
Science 246:235-240(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]"Beta2-adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein."
Premont R.T., Claing A., Vitale N., Freeman J.L.R., Pitcher J.A., Patton W.A., Moss J., Vaughan M., Lefkowitz R.J.
Proc. Natl. Acad. Sci. U.S.A. 95:14082-14087(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GIT1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M34019 mRNA. Translation: AAA30384.1.
PIRA40088.
RefSeqNP_777135.1. NM_174710.2.
UniGeneBt.4693.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1OMWX-ray2.50A1-689[»]
1YM7X-ray4.50A/B/C/D1-689[»]
2BCJX-ray3.06A1-689[»]
3PSCX-ray2.67A1-689[»]
3PVUX-ray2.48A1-689[»]
3PVWX-ray2.49A1-689[»]
3UZSX-ray4.52A1-681[»]
3UZTX-ray3.51A1-689[»]
ProteinModelPortalP21146.
SMRP21146. Positions 28-667.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid159836. 3 interactions.
DIPDIP-37856N.
IntActP21146. 4 interactions.
STRING9913.ENSBTAP00000050806.

Proteomic databases

PRIDEP21146.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID282682.
KEGGbta:282682.

Organism-specific databases

CTD156.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000006742.
HOVERGENHBG050559.
InParanoidP21146.
KOK00910.

Enzyme and pathway databases

BRENDA2.7.11.15. 908.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
InterProIPR000961. AGC-kinase_C.
IPR000239. GPCR_kinase.
IPR011009. Kinase-like_dom.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016137. Regulat_G_prot_signal_superfam.
IPR000342. RGS_dom.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSPR00717. GPCRKINASE.
SMARTSM00233. PH. 1 hit.
SM00315. RGS. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF48097. SSF48097. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS51285. 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]
ProtoNetSearch...

Other

EvolutionaryTraceP21146.
NextBio20806352.

Entry information

Entry nameARBK1_BOVIN
AccessionPrimary (citable) accession number: P21146
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: May 1, 1991
Last modified: July 9, 2014
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references