EzCatDB: M00125
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DB codeM00125
RLCP classification3.103.130000.1161 : Transfer
CATH domainDomain 11.-.-.-
Domain 21.10.167.10 : Regulator of G-protein Signalling 4; domain 2
Domain 33.30.200.20 : Phosphorylase Kinase; domain 1
Domain 41.10.510.10 : Transferase(Phosphotransferase); domain 1Catalytic domain
Domain 52.30.29.30 : PH-domain like
E.C.2.7.11.15

CATH domainRelated DB codes (homologues)
1.10.510.10 : Transferase(Phosphotransferase); domain 1M00124,M00131,T00224,M00127,M00129,M00130,M00132,M00136,M00196,M00197,M00198,M00304,M00323,M00325,M00326,M00327,M00328,M00329,M00330,M00331,M00332,M00333,M00335,M00339,M00344
2.30.29.30 : PH-domain likeM00183,M00344,M00118
3.30.200.20 : Phosphorylase Kinase; domain 1M00124,M00131,T00224,M00127,M00129,M00130,M00132,M00136,M00196,M00197,M00198,M00304,M00323,M00325,M00326,M00327,M00328,M00329,M00330,M00331,M00332,M00333,M00335,M00339,M00344,D00298

Enzyme Name
UniProtKBKEGG

P21146P25098
Protein nameBeta-adrenergic receptor kinase 1Beta-adrenergic receptor kinase 1beta-adrenergic-receptor kinase
ATP:beta-adrenergic-receptor phosphotransferase
[beta-adrenergic-receptor] kinase
beta-adrenergic receptor-specific kinase
beta-AR kinase
beta-ARK
beta-ARK 1
beta-ARK 2
beta-receptor kinase
GRK2
GRK3
beta-adrenergic-receptor kinase (phosphorylating)
beta2ARK
betaARK1
beta-adrenoceptor kinase
beta-adrenoceptor kinase 1
beta-adrenoceptor kinase 2
ADRBK1
BARK1
adrenergic receptor kinase
STK15
SynonymsBeta-ARK-1
EC 2.7.11.15
G-protein-coupled receptor kinase 2
Beta-ARK-1
EC 2.7.11.15
G-protein coupled receptor kinase 2
RefSeqNP_777135.1 (Protein)
NM_174710.2 (DNA/RNA sequence)
NP_001610.2 (Protein)
NM_001619.3 (DNA/RNA sequence)
PfamPF00169 (PH)
PF00069 (Pkinase)
PF00615 (RGS)
[Graphical view]
PF00169 (PH)
PF00069 (Pkinase)
PF00615 (RGS)
[Graphical view]


UniProtKB:Accession NumberP21146P25098
Entry nameARBK1_BOVINARBK1_HUMAN
ActivityATP + [beta-adrenergic receptor] = ADP + [beta-adrenergic receptor] phosphate.ATP + [beta-adrenergic receptor] = ADP + [beta-adrenergic receptor] phosphate.
SubunitInteracts with GIT1. Interacts with, and phosphorylates chemokine-stimulated CCR5 (By similarity).Interacts with GIT1 (By similarity). Interacts with, and phosphorylates chemokine-stimulated CCR5.
Subcellular location

Cofactor


Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00002C01141C00008C04141
CompoundMagnesiumATPbeta-Adrenergic receptorADPPhospho-beta-adrenergic receptor
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotidepeptide/proteinamine group,nucleotidepeptide/protein,phosphate group/phosphate ion
ChEBI18420
15422

16761

PubChem888
5957

6022

             
1omwA01UnboundUnboundUnboundUnboundUnbound
1omwA02UnboundUnboundUnboundUnboundUnbound
1omwA03UnboundUnboundUnboundUnboundUnbound
1omwA04UnboundUnboundUnboundUnboundUnbound
1omwA05UnboundUnboundUnboundUnboundUnbound
1bakAUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P21146 & similarity with M00129
pdbCatalytic residuesCofactor-binding residuescomment
           
1omwA01 
 
 
1omwA02 
 
 
1omwA03 
 
 
1omwA04ASP 317
ASN 322;ASP 335(Magnesium binding)
 
1omwA05 
 
 
1bakA 
 
mutant D552G;Y553S;A554H;I555M


references
[1]
PubMed ID7673171
JournalJ Biol Chem
Year1995
Volume270
Pages21346-53
AuthorsOnorato JJ, Gillis ME, Liu Y, Benovic JL, Ruoho AE
TitleThe beta-adrenergic receptor kinase (GRK2) is regulated by phospholipids.
[2]
PubMed ID7744811
JournalJ Biol Chem
Year1995
Volume270
Pages11707-10
AuthorsPitcher JA, Touhara K, Payne ES, Lefkowitz RJ
TitlePleckstrin homology domain-mediated membrane association and activation of the beta-adrenergic receptor kinase requires coordinate interaction with G beta gamma subunits and lipid.
[3]
PubMed ID9010620
JournalDrug Des Discov
Year1996
Volume14
Pages145-55
AuthorsIino M, Shibano T
TitleSubstrate recognition mechanism of human beta-adrenergic receptor kinase 1 based on a three-dimensional model structure.
[4]
PubMed ID9477943
JournalBiochemistry
Year1998
Volume37
Pages1192-8
AuthorsNishimura K, Warabi K, Roush ED, Frederick J, Schwinn DA, Kwatra MM
TitleCharacterization of GRK2-catalyzed phosphorylation of the human substance P receptor in Sf9 membranes.
[5]
CommentsSTRUCTURE BY NMR OF 552-670
Medline ID98112832
PubMed ID9446593
JournalJ Biol Chem
Year1998
Volume273
Pages2835-43
AuthorsFushman D, Najmabadi-Haske T, Cahill S, Zheng J, LeVine H 3rd, Cowburn D
TitleThe 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.
Related PDB1bak
Related UniProtKBP25098
[6]
PubMed ID10571539
JournalCirc Res
Year1999
Volume85
Pages1077-84
AuthorsCross HR, Steenbergen C, Lefkowitz RJ, Koch WJ, Murphy E
TitleOverexpression of the cardiac beta(2)-adrenergic receptor and expression of a beta-adrenergic receptor kinase-1 (betaARK1) inhibitor both increase myocardial contractility but have differential effects on susceptibility to ischemic injury.
[7]
PubMed ID10567430
JournalJ Biol Chem
Year1999
Volume274
Pages34483-92
AuthorsCarman CV, Parent JL, Day PW, Pronin AN, Sternweis PM, Wedegaertner PB, Gilman AG, Benovic JL, Kozasa T
TitleSelective regulation of Galpha(q/11) by an RGS domain in the G protein-coupled receptor kinase, GRK2.
[8]
PubMed ID0223293
JournalProteins
Year1999
Volume35
Pages206-17
AuthorsPfeiffer S, Fushman D, Cowburn D
TitleImpact of Cl- and Na+ ions on simulated structure and dynamics of betaARK1 PH domain.
[9]
PubMed ID10542412
JournalTrends Biochem Sci
Year1999
Volume24
Pages441-5
AuthorsBlomberg N, Baraldi E, Nilges M, Saraste M
TitleThe PH superfold: a structural scaffold for multiple functions.
[10]
PubMed ID10926821
JournalBiochem J
Year2000
Volume350 Pt 1
Pages1-18
AuthorsLemmon MA, Ferguson KM
TitleSignal-dependent membrane targeting by pleckstrin homology (PH) domains.
[11]
PubMed ID10744734
JournalJ Biol Chem
Year2000
Volume275
Pages10443-52
AuthorsCarman CV, Barak LS, Chen C, Liu-Chen LY, Onorato JJ, Kennedy SP, Caron MG, Benovic JL
TitleMutational analysis of Gbetagamma and phospholipid interaction with G protein-coupled receptor kinase 2.
[12]
PubMed ID10913124
JournalJ Biol Chem
Year2000
Volume275
Pages32816-21
AuthorsKlarlund JK, Tsiaras W, Holik JJ, Chawla A, Czech MP
TitleDistinct polyphosphoinositide binding selectivities for pleckstrin homology domains of GRP1-like proteins based on diglycine versus triglycine motifs.
[13]
PubMed ID11457013
JournalJ Am Chem Soc
Year2001
Volume123
Pages3021-36
AuthorsPfeiffer S, Fushman D, Cowburn D
TitleSimulated and NMR-derived backbone dynamics of a protein with significant flexibility: a comparison of spectral densities for the betaARK1 PH domain.
[14]
PubMed ID12631274
JournalEur J Biochem
Year2003
Volume270
Pages1154-63
AuthorsYoshida N, Haga K, Haga T
TitleIdentification of sites of phosphorylation by G-protein-coupled receptor kinase 2 in beta-tubulin.
[15]
PubMed ID12764189
JournalScience
Year2003
Volume300
Pages1256-62
AuthorsLodowski DT, Pitcher JA, Capel WD, Lefkowitz RJ, Tesmer JJ
TitleKeeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and Gbetagamma.
Related PDB1omw

comments
The E.C. was transferred from 2.7.1.126 to 2.7.11.15.
This receptor enzyme is composed of N-terminal domain, catalytic domain, and C-terminal domain. The PDB structure, 1bak, corresponds to Pleckstrin Homology (PH) region in the C-terminal domain, which seems to be involved in protein-protein interaction with G-beta/gamma subunits of G-protein (see [5], [11], [15]).
Although the catalytic residues are mostly the same as that of homologous tyrosine kinases (see M00129), the arginine residue at the active site of the homologous enzyme is changed to alanine residue. Instead, Lys319 seems to occupy the position of arginine residue.

createdupdated
2003-07-222009-02-26


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Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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