Beta-adrenergic receptor kinase 1 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P25098 (ARBK1_HUMAN)

Last modified July 22, 2008. Version 99. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	689 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them.
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.
Tissue specificity	Expressed in peripheral blood leukocytes.
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.

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Ontologies

Keywords
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	acetylcholine receptor signaling, muscarinic pathway Inferred from sequence or structural similarity. Source: UniProtKB cardiac muscle contraction Inferred from mutant phenotype. Source: UniProtKB desensitization of G-protein coupled receptor protein signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of striated muscle contraction Inferred from mutant phenotype. Source: UniProtKB negative regulation of the force of heart contraction by chemical signal Inferred from mutant phenotype. Source: UniProtKB peptidyl-serine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of catecholamine secretion Inferred from sequence or structural similarity. Source: UniProtKB tachykinin signaling pathway Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: UniProtKB membrane Inferred from sequence or structural similarity. Source: UniProtKB soluble fraction Ref.2 Traceable author statement. Source: ProtInc
Molecular function	G-protein coupled receptor kinase activity Inferred from sequence or structural similarity. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 689

689

Beta-adrenergic receptor kinase 1

Regions

Domain

54 – 175

122

RGS

Domain

191 – 453

263

Protein kinase

Domain

454 – 521

AGC-kinase C-terminal

Domain

558 – 652

Nucleotide binding

197 – 205

ATP By similarity

Region

1 – 190

190

N-terminal

Sites

Active site

317

Proton acceptor By similarity

Binding site

220

ATP By similarity

Amino acid modifications

Modified residue

670

Phosphoserine

Natural variations

Natural variant

184

I → T

Natural variant

578

R → Q in a colorectal adenocarcinoma sample; somatic mutation.

Experimental info

Sequence conflict

168 – 185

SDKFT…ELNIH → RISSHGFASGRMWSSTST in AAB60689. Ref.3

Sequence conflict

211

A → R in CAA43470. Ref.1

Sequence conflict

211

A → R in AAB60689. Ref.3

Sequence conflict

422

R → H in CAA43470. Ref.1

Sequence conflict

422

R → H in AAB60689. Ref.3

Sequence conflict

465

K → R in CAA43470. Ref.1

Secondary structure

689

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P25098-1 [UniParc].

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

689

79,574

        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

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References

	« Hide 'large scale' referencesShow '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: 2037065] [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: 1339451] [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: 8195124] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: PNS and Testis.
[5]	"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: 10085131] [Abstract] Cited for: INTERACTION WITH CCR5, TISSUE SPECIFICITY.
[6]	"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: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-670, MASS SPECTROMETRY. Tissue: Platelet.
[7]	"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: 9446593] [Abstract] Cited for: STRUCTURE BY NMR OF 552-670.
[8]	"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. Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-184 AND GLN-578.
+	Additional computationally mapped references.

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Web resources

Wikipedia

Beta adrenergic receptor kinase entry

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Cross-references

Sequence databases

X61157 mRNA. Translation: CAA43470.1.
M80776 mRNA. Translation: AAA58391.1.
U08438

U08437 Genomic DNA. Translation: AAB60689.1.
BC037963 mRNA. Translation: AAH37963.1.
BC090863 mRNA. Translation: AAH90863.1.

PIR

A53791.

RefSeq

NP_001610.2.

UniGene

Hs.83636

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BAK	NMR	-	A	556-670	[»]

SMR

P25098. Positions 29-668.

ModBase

Search...

PTM databases

PhosphoSite

P25098.

Genome annotation databases

Ensembl

ENSG00000173020. Homo sapiens. [Contig view]

GeneID

156.

KEGG

hsa:156.

Organism-specific databases

H-InvDB

HIX0026185.

HGNC

HGNC:289. ADRBK1.

MIM

109635. gene.

PharmGKB

PA40.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P25098.

HOVERGEN

P25098.

Gene expression databases

ArrayExpress

P25098.

CleanEx

HS_ADRBK1.

GermOnline

ENSG00000173020. Homo sapiens.

Family and domain databases

InterPro

IPR015743. BARK.
IPR000239. GPCR_kinase.
IPR001849. PH.
IPR011993. PH_type.
IPR000961. Pkinase_C.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_bd_CS.
IPR000342. Regulat_G_prot_signal.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 1 hit.

PANTHER

PTHR22985:SF5. BARK. 1 hit.

Pfam

PF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view]

PRINTS

PR00717. GPCRKINASE.

ProDom

PD000001. Prot_kinase. 1 hit.
PD001580. Regl_Gprotein. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00233. PH. 1 hit.
SM00315. RGS. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

PROSITE

PS51285. 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]

BLOCKS

Search...

Other Resources

DrugBank

DB00171. Adenosine triphosphate.

LinkHub

P25098.

SOURCE

Search...

ProtoNet

Search...

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Entry information

Entry name

ARBK1_HUMAN

Accession

Primary (citable) accession number: P25098
Secondary accession number(s): Q13837, Q6GTT3

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	February 20, 2007
Last modified:	July 22, 2008
This is version 99 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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