Reviewed, UniProtKB/Swiss-Prot P25098 (ARBK1_HUMAN)

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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	689 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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.
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. Ref.6
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 diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	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 muscarinic acetylcholine receptor 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 receptor signaling pathway Inferred from direct assay. Source: UniProtKB
Cellular component	cytosol Inferred from Experiment. Source: Reactome plasma membrane Inferred from Experiment. Source: Reactome soluble fraction Ref.2 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW G-protein coupled receptor kinase activity Inferred from sequence or structural similarity. Source: UniProtKB beta-adrenergic receptor kinase activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction. Source: UniProtKB signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 689

689

Beta-adrenergic receptor kinase 1

PRO_0000085627

Regions

Domain

54 – 175

122

RGS

Domain

191 – 453

263

Protein kinase

Domain

454 – 521

68

AGC-kinase C-terminal

Domain

558 – 652

95

PH

Nucleotide binding

197 – 205

9

ATP By similarity

Region

1 – 190

190

N-terminal

Sites

Active site

317

1

Proton acceptor By similarity

Binding site

220

1

ATP By similarity

Amino acid modifications

Modified residue

670

1

Phosphoserine Ref.7

Natural variations

Natural variant

184

1

I → T

VAR_040378

Natural variant

578

1

R → Q in a colorectal adenocarcinoma sample; somatic mutation. Ref.10

VAR_040379

Experimental info

Sequence conflict

168 – 185

18

SDKFT…ELNIH → RISSHGFASGRMWSSTST in AAB60689. Ref.3

Sequence conflict

211

1

A → R in CAA43470. Ref.1

Sequence conflict

211

1

A → R in AAB60689. Ref.3

Sequence conflict

422

1

R → H in CAA43470. Ref.1

Sequence conflict

422

1

R → H in AAB60689. Ref.3

Sequence conflict

465

1

K → R in CAA43470. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

689

Helix Strand Turn

Details...

Beta strand

561 – 568

8

Beta strand

578 – 583

6

Beta strand

585 – 591

7

Beta strand

600 – 604

5

Beta strand

606 – 612

7

Beta strand

619 – 624

6

Beta strand

629 – 633

5

Helix

637 – 658

22

Sequences

	Sequence		Length	Mass (Da)
	P25098-1 [UniParc]. Last modified February 20, 2007. Version 2. Checksum: 4DB68F62841AFA7D	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

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]	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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: PNS and Testis.
[6]	"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.
[7]	"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.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"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.
[10]	"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. , 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: 17344846] [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

EMBLGenBankDDBJ

X61157 mRNA. Translation: CAA43470.1.
M80776 mRNA. Translation: AAA58391.1.
U08438 , U08435, U08436, U08437 Genomic DNA. Translation: AAB60689.1.
EU326303 Genomic DNA. Translation: ACA05909.1.
BC037963 mRNA. Translation: AAH37963.1.
BC090863 mRNA. Translation: AAH90863.1.

IPI

IPI00012497.

PIR

A53791.

RefSeq

NP_001610.2.

UniGene

Hs.83636

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BAK	NMR	-	A	556-670	[»]
3CIK	X-ray	2.75	A	1-689	[»]

SMR

P25098. Positions 29-668.

ModBase

Search...

Protein-protein interaction databases

STRING

P25098.

PTM databases

PhosphoSite

P25098.

Proteomic databases

PRIDE

P25098.

Genome annotation databases

Ensembl

ENST00000308595; ENSP00000312262; ENSG00000173020; Homo sapiens. [Genome view]
ENST00000416281; ENSP00000407159; ENSG00000173020; Homo sapiens. [Genome view]

GeneID

156.

KEGG

hsa:156.

UCSC

uc009yrn.1. human.

Organism-specific databases

CTD

156.

GeneCards

GC11P066790.

H-InvDB

HIX0026185.

HGNC

HGNC:289. ADRBK1.

MIM

109635. gene.

PharmGKB

PA40.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P25098.

HOVERGEN

P25098.

OMA

YRNFPLT.

Enzyme and pathway databases

BRENDA

2.7.11.15. 247.

Pathway_Interaction_DB

hdac_classii_pathway. Signaling events mediated by HDAC Class II.
hedgehog_2pathway. Signaling events mediated by the Hedgehog family.
txa2pathway. Thromboxane A2 receptor signaling.

Reactome

REACT_11061. Signalling by NGF.
REACT_14797. Signaling by GPCR.
REACT_15295. Opioid Signalling.

Gene expression databases

ArrayExpress

P25098.

Bgee

P25098.

CleanEx

HS_ADRBK1.

Genevestigator

P25098.

GermOnline

ENSG00000173020. Homo sapiens.

Family and domain databases

InterPro

IPR000961. AGC-kinase_C.
IPR015743. B-adrenergic_rcpt_kinase.
IPR000239. GPCR_kinase.
IPR011993. PH_type.
IPR001849. Pleckstrin_homology.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
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]

ProtoNet

Search...

Other Resources

DrugBank

DB00171. Adenosine triphosphate.

NextBio

621.

SOURCE

Search...

Entry information

Entry name

ARBK1_HUMAN

Accession

Primary (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:	November 3, 2009
This is version 114 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.