DB code: M00125

RLCP classification 3.103.130000.1161 : Transfer
CATH domain 1.-.-.- :
1.10.167.10 : Regulator of G-protein Signalling 4; domain 2
3.30.200.20 : Phosphorylase Kinase; domain 1
1.10.510.10 : Transferase(Phosphotransferase); domain 1 Catalytic domain
2.30.29.30 : PH-domain like
E.C. 2.7.11.15
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
1.10.510.10 : Transferase(Phosphotransferase); domain 1 M00124 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 like M00183 M00344 M00118
3.30.200.20 : Phosphorylase Kinase; domain 1 M00124 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P21146 Beta-adrenergic receptor kinase 1
Beta-ARK-1
EC 2.7.11.15
G-protein-coupled receptor kinase 2
NP_777135.1 (Protein)
NM_174710.2 (DNA/RNA sequence)
PF00169 (PH)
PF00069 (Pkinase)
PF00615 (RGS)
[Graphical View]
P25098 Beta-adrenergic receptor kinase 1
Beta-ARK-1
EC 2.7.11.15
G-protein coupled receptor kinase 2
NP_001610.2 (Protein)
NM_001619.3 (DNA/RNA sequence)
PF00169 (PH)
PF00069 (Pkinase)
PF00615 (RGS)
[Graphical View]

KEGG enzyme name
beta-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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P21146 ARBK1_BOVIN ATP + [beta-adrenergic receptor] = ADP + [beta-adrenergic receptor] phosphate. Interacts with GIT1. Interacts with, and phosphorylates chemokine-stimulated CCR5 (By similarity).
P25098 ARBK1_HUMAN ATP + [beta-adrenergic receptor] = ADP + [beta-adrenergic receptor] phosphate. Interacts with GIT1 (By similarity). Interacts with, and phosphorylates chemokine-stimulated CCR5.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C01141 C00008 C04141
E.C.
Compound Magnesium ATP beta-Adrenergic receptor ADP Phospho-beta-adrenergic receptor
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide peptide/protein amine group,nucleotide peptide/protein,phosphate group/phosphate ion
ChEBI 18420
15422
16761
PubChem 888
5957
6022
1omwA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1omwA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1omwA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1omwA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1omwA05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1bakA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P21146 & similarity with M00129

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1omwA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1omwA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1omwA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1omwA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 317 ASN 322;ASP 335(Magnesium binding)
1omwA05 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1bakA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant D552G;Y553S;A554H;I555M

References for Catalytic Mechanism
References Sections No. of steps in catalysis

References
[1]
Resource
Comments
Medline ID
PubMed ID 7673171
Journal J Biol Chem
Year 1995
Volume 270
Pages 21346-53
Authors Onorato JJ, Gillis ME, Liu Y, Benovic JL, Ruoho AE
Title The beta-adrenergic receptor kinase (GRK2) is regulated by phospholipids.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 7744811
Journal J Biol Chem
Year 1995
Volume 270
Pages 11707-10
Authors Pitcher JA, Touhara K, Payne ES, Lefkowitz RJ
Title Pleckstrin homology domain-mediated membrane association and activation of the beta-adrenergic receptor kinase requires coordinate interaction with G beta gamma subunits and lipid.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9010620
Journal Drug Des Discov
Year 1996
Volume 14
Pages 145-55
Authors Iino M, Shibano T
Title Substrate recognition mechanism of human beta-adrenergic receptor kinase 1 based on a three-dimensional model structure.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9477943
Journal Biochemistry
Year 1998
Volume 37
Pages 1192-8
Authors Nishimura K, Warabi K, Roush ED, Frederick J, Schwinn DA, Kwatra MM
Title Characterization of GRK2-catalyzed phosphorylation of the human substance P receptor in Sf9 membranes.
Related PDB
Related UniProtKB
[5]
Resource
Comments STRUCTURE BY NMR OF 552-670
Medline ID 98112832
PubMed ID 9446593
Journal J Biol Chem
Year 1998
Volume 273
Pages 2835-43
Authors Fushman D, Najmabadi-Haske T, Cahill S, Zheng J, LeVine H 3rd, Cowburn D
Title 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.
Related PDB 1bak
Related UniProtKB P25098
[6]
Resource
Comments
Medline ID
PubMed ID 10571539
Journal Circ Res
Year 1999
Volume 85
Pages 1077-84
Authors Cross HR, Steenbergen C, Lefkowitz RJ, Koch WJ, Murphy E
Title Overexpression 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.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10567430
Journal J Biol Chem
Year 1999
Volume 274
Pages 34483-92
Authors Carman CV, Parent JL, Day PW, Pronin AN, Sternweis PM, Wedegaertner PB, Gilman AG, Benovic JL, Kozasa T
Title Selective regulation of Galpha(q/11) by an RGS domain in the G protein-coupled receptor kinase, GRK2.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 0223293
Journal Proteins
Year 1999
Volume 35
Pages 206-17
Authors Pfeiffer S, Fushman D, Cowburn D
Title Impact of Cl- and Na+ ions on simulated structure and dynamics of betaARK1 PH domain.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 10542412
Journal Trends Biochem Sci
Year 1999
Volume 24
Pages 441-5
Authors Blomberg N, Baraldi E, Nilges M, Saraste M
Title The PH superfold: a structural scaffold for multiple functions.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 10926821
Journal Biochem J
Year 2000
Volume 350 Pt 1
Pages 1-18
Authors Lemmon MA, Ferguson KM
Title Signal-dependent membrane targeting by pleckstrin homology (PH) domains.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 10744734
Journal J Biol Chem
Year 2000
Volume 275
Pages 10443-52
Authors Carman CV, Barak LS, Chen C, Liu-Chen LY, Onorato JJ, Kennedy SP, Caron MG, Benovic JL
Title Mutational analysis of Gbetagamma and phospholipid interaction with G protein-coupled receptor kinase 2.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 10913124
Journal J Biol Chem
Year 2000
Volume 275
Pages 32816-21
Authors Klarlund JK, Tsiaras W, Holik JJ, Chawla A, Czech MP
Title Distinct polyphosphoinositide binding selectivities for pleckstrin homology domains of GRP1-like proteins based on diglycine versus triglycine motifs.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 11457013
Journal J Am Chem Soc
Year 2001
Volume 123
Pages 3021-36
Authors Pfeiffer S, Fushman D, Cowburn D
Title Simulated and NMR-derived backbone dynamics of a protein with significant flexibility: a comparison of spectral densities for the betaARK1 PH domain.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 12631274
Journal Eur J Biochem
Year 2003
Volume 270
Pages 1154-63
Authors Yoshida N, Haga K, Haga T
Title Identification of sites of phosphorylation by G-protein-coupled receptor kinase 2 in beta-tubulin.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 12764189
Journal Science
Year 2003
Volume 300
Pages 1256-62
Authors Lodowski DT, Pitcher JA, Capel WD, Lefkowitz RJ, Tesmer JJ
Title Keeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and Gbetagamma.
Related PDB 1omw
Related UniProtKB

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.

Created Updated
2003-07-22 2009-02-26