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P25098 (ARBK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 161. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·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:BARK, BARK1, GRK2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

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. Ref.9

Catalytic activity

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

Subunit structure

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. Ref.6 Ref.7 Ref.9

Tissue specificity

Expressed in peripheral blood leukocytes. Ref.7

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

Inferred from sequence or structural similarity. Source: BHF-UCL

activation of phospholipase C activity

Traceable author statement. Source: Reactome

cardiac muscle contraction

Inferred from mutant phenotype PubMed 15051637. Source: BHF-UCL

desensitization of G-protein coupled receptor protein signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

heart development

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

negative regulation of striated muscle contraction

Inferred from mutant phenotype PubMed 15051637. Source: BHF-UCL

negative regulation of the force of heart contraction by chemical signal

Inferred from mutant phenotype PubMed 15051637. Source: BHF-UCL

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

peptidyl-serine phosphorylation

Inferred from sequence or structural similarity. Source: BHF-UCL

peptidyl-threonine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of catecholamine secretion

Inferred from sequence or structural similarity. Source: BHF-UCL

receptor internalization

Inferred from direct assay PubMed 20074556. Source: UniProtKB

signal transduction

Traceable author statement. Source: Reactome

tachykinin receptor signaling pathway

Inferred from direct assay PubMed 17986524. Source: BHF-UCL

termination of G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 17986524. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

membrane

Inferred from sequence or structural similarity. Source: BHF-UCL

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

Edg-2 lysophosphatidic acid receptor binding

Inferred from direct assay Ref.9. Source: UniProtKB

G-protein coupled receptor kinase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

alpha-2A adrenergic receptor binding

Inferred from sequence or structural similarity. Source: BHF-UCL

beta-adrenergic receptor kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein kinase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 689689Beta-adrenergic receptor kinase 1
PRO_0000085627

Regions

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

Sites

Active site3171Proton acceptor By similarity
Binding site2201ATP By similarity

Amino acid modifications

Modified residue6701Phosphoserine Ref.8

Natural variations

Natural variant1841I → T. Ref.12
Corresponds to variant rs55696045 [ dbSNP | Ensembl ].
VAR_040378
Natural variant5781R → Q in a colorectal adenocarcinoma sample; somatic mutation. Ref.12
VAR_040379

Experimental info

Sequence conflict168 – 18518SDKFT…ELNIH → RISSHGFASGRMWSSTST in AAB60689. Ref.3
Sequence conflict2111A → R in CAA43470. Ref.1
Sequence conflict2111A → R in AAB60689. Ref.3
Sequence conflict4221R → H in CAA43470. Ref.1
Sequence conflict4221R → H in AAB60689. Ref.3
Sequence conflict4651K → R in CAA43470. Ref.1

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
P25098 [UniParc].

Last modified February 20, 2007. Version 2.
Checksum: 4DB68F62841AFA7D

FASTA68979,574
        10         20         30         40         50         60 
MADLEAVLAD VSYLMAMEKS KATPAARASK KILLPEPSIR SVMQKYLEDR GEVTFEKIFS 

        70         80         90        100        110        120 
QKLGYLLFRD FCLNHLEEAR PLVEFYEEIK KYEKLETEEE RVARSREIFD SYIMKELLAC 

       130        140        150        160        170        180 
SHPFSKSATE HVQGHLGKKQ 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 
KAKNKQLGHE EDYALGKDCI MHGYMSKMGN PFLTQWQRRY FYLFPNRLEW RGEGEAPQSL 

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

       670        680 
VPKMKNKPRS PVVELSKVPL VQRGSANGL 

« Hide

References

« Hide 'large scale' references
[1]"cDNA cloning and chromosomal localization of the human beta-adrenergic receptor kinase."
Benovic J.L., Stone W.C., Huebner K., Croce C., Caron M.G., Lefkowitz R.J.
FEBS Lett. 283:122-126(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"High expression of beta-adrenergic receptor kinase in human peripheral blood leukocytes. Isoproterenol and platelet activating factor can induce kinase translocation."
Chuang T.T., Sallese M., Ambrosini G., Parruti G., de Blasi A.
J. Biol. Chem. 267:6886-6892(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Blood.
[3]"Structure of the human gene encoding the beta-adrenergic receptor kinase."
Penn R.B., Benovic J.L.
J. Biol. Chem. 269:14924-14930(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]NHLBI resequencing and genotyping service (RS&G)
Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"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].
Tissue: PNS and Testis.
[6]"Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2."
Aragay A.M., Mellado M., Frade J.M., Martin A.M., Jimenez-Sainz M.C., Martinez-A C., Mayor F. Jr.
Proc. Natl. Acad. Sci. U.S.A. 95:2985-2990(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARRB1.
[7]"Differential effects of CC chemokines on CC chemokine receptor 5 (CCR5) phosphorylation and identification of phosphorylation sites on the CCR5 carboxyl terminus."
Oppermann M., Mack M., Proudfoot A.E., Olbrich H.
J. Biol. Chem. 274:8875-8885(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CCR5, TISSUE SPECIFICITY.
[8]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-670, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[9]"Dual regulation of lysophosphatidic acid (LPA1) receptor signalling by Ral and GRK."
Aziziyeh A.I., Li T.T., Pape C., Pampillo M., Chidiac P., Possmayer F., Babwah A.V., Bhattacharya M.
Cell. Signal. 21:1207-1217(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH LPAR1; LPAR2 AND RALA.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"The solution structure and dynamics of the pleckstrin homology domain of G protein-coupled receptor kinase 2 (beta-adrenergic receptor kinase 1). A binding partner of Gbetagamma subunits."
Fushman D., Najmabadi-Haske T., Cahill S., Zheng J., Levine H. III, Cowburn D.
J. Biol. Chem. 273:2835-2843(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 552-670.
[12]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-184 AND GLN-578.
+Additional computationally mapped references.

Web resources

Wikipedia

Beta adrenergic receptor kinase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X61157 mRNA. Translation: CAA43470.1.
M80776 mRNA. Translation: AAA58391.1.
U08438 expand/collapse EMBL AC list , U08435, U08436, U08437 Genomic DNA. Translation: AAB60689.1.
EU326303 Genomic DNA. Translation: ACA05909.1.
BC037963 mRNA. Translation: AAH37963.1.
BC090863 mRNA. Translation: AAH90863.1.
PIRA53791.
RefSeqNP_001610.2. NM_001619.3.
UniGeneHs.83636.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP25098.
SMRP25098. Positions 30-670.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106665. 160 interactions.
DIPDIP-42429N.
IntActP25098. 13 interactions.
MINTMINT-1214643.
STRING9606.ENSP00000312262.

Chemistry

BindingDBP25098.
ChEMBLCHEMBL4079.
DrugBankDB00171. Adenosine triphosphate.
GuidetoPHARMACOLOGY1466.

PTM databases

PhosphoSiteP25098.

Polymorphism databases

DMDM126302521.

Proteomic databases

PaxDbP25098.
PRIDEP25098.

Protocols and materials databases

DNASU156.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000308595; ENSP00000312262; ENSG00000173020.
GeneID156.
KEGGhsa:156.
UCSCuc009yrn.1. human.

Organism-specific databases

CTD156.
GeneCardsGC11P067033.
HGNCHGNC:289. ADRBK1.
HPACAB005021.
CAB037248.
HPA048330.
MIM109635. gene.
neXtProtNX_P25098.
PharmGKBPA40.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000006742.
HOVERGENHBG050559.
InParanoidP25098.
KOK00910.
OMADFCLKHL.
OrthoDBEOG7FV3PP.
PhylomeDBP25098.
TreeFamTF313940.

Enzyme and pathway databases

BRENDA2.7.11.15. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.
SignaLinkP25098.

Gene expression databases

ArrayExpressP25098.
BgeeP25098.
CleanExHS_ADRBK1.
GenevestigatorP25098.

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

ChiTaRSADRBK1. human.
EvolutionaryTraceP25098.
GeneWikiBeta_adrenergic_receptor_kinase.
GenomeRNAi156.
NextBio621.
PROP25098.
SOURCESearch...

Entry information

Entry nameARBK1_HUMAN
AccessionPrimary (citable) accession number: P25098
Secondary accession number(s): B0ZBE1, Q13837, Q6GTT3
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: February 20, 2007
Last modified: April 16, 2014
This is version 161 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM