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Protein

Beta-adrenergic receptor kinase 1

Gene

GRK2

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity

Catalytic activityi

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

Enzyme regulationi

In contrast to other AGC family kinases, the catalytic activity is solely regulated by the binding of substrates and ligands, not by phosphorylation of the kinase domain.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei220ATPPROSITE-ProRule annotation1
Active sitei317Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi197 – 205ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • alpha-2A adrenergic receptor binding Source: BHF-UCL
  • ATP binding Source: UniProtKB-KW
  • beta-adrenergic receptor kinase activity Source: UniProtKB-EC
  • Edg-2 lysophosphatidic acid receptor binding Source: UniProtKB
  • G-protein coupled receptor kinase activity Source: BHF-UCL
  • protein kinase activity Source: BHF-UCL

GO - Biological processi

  • cardiac muscle contraction Source: BHF-UCL
  • desensitization of G-protein coupled receptor protein signaling pathway Source: BHF-UCL
  • G-protein coupled acetylcholine receptor signaling pathway Source: BHF-UCL
  • G-protein coupled receptor internalization Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: AgBase
  • intracellular protein transport Source: BHF-UCL
  • negative regulation of striated muscle contraction Source: BHF-UCL
  • negative regulation of the force of heart contraction by chemical signal Source: BHF-UCL
  • peptidyl-serine phosphorylation Source: BHF-UCL
  • protein phosphorylation Source: BHF-UCL
  • regulation of signal transduction Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.15. 908.

Names & Taxonomyi

Protein namesi
Recommended name:
Beta-adrenergic receptor kinase 1 (EC:2.7.11.15)
Short name:
Beta-ARK-1
Alternative name(s):
G-protein-coupled receptor kinase 2By similarity
Gene namesi
Name:GRK2By similarity
Synonyms:ADRBK1
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: BHF-UCL
  • membrane Source: BHF-UCL
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000856261 – 689Beta-adrenergic receptor kinase 1Add BLAST689

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei670PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP21146.
PRIDEiP21146.

PTM databases

iPTMnetiP21146.

Expressioni

Tissue specificityi

Ubiquitous; brain, spleen > heart, lung > kidney.

Gene expression databases

BgeeiENSBTAG00000005832.

Interactioni

Subunit structurei

Interacts with GIT1. 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 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
HDAC6Q9UBN73EBI-1036401,EBI-301697From a different organism.
Hdac6Q9Z2V52EBI-1036401,EBI-1009256From a different organism.

GO - Molecular functioni

  • alpha-2A adrenergic receptor binding Source: BHF-UCL
  • Edg-2 lysophosphatidic acid receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi159836. 3 interactors.
DIPiDIP-37856N.
IntActiP21146. 4 interactors.
STRINGi9913.ENSBTAP00000050806.

Structurei

Secondary structure

1689
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi39 – 48Combined sources10
Turni49 – 51Combined sources3
Helixi55 – 59Combined sources5
Helixi62 – 75Combined sources14
Turni77 – 79Combined sources3
Helixi80 – 93Combined sources14
Helixi98 – 112Combined sources15
Helixi114 – 118Combined sources5
Helixi126 – 137Combined sources12
Turni143 – 146Combined sources4
Helixi147 – 158Combined sources12
Helixi160 – 167Combined sources8
Helixi169 – 182Combined sources14
Helixi188 – 190Combined sources3
Beta strandi191 – 199Combined sources9
Beta strandi201 – 210Combined sources10
Turni211 – 213Combined sources3
Beta strandi216 – 223Combined sources8
Helixi224 – 230Combined sources7
Helixi233 – 244Combined sources12
Beta strandi247 – 249Combined sources3
Beta strandi252 – 254Combined sources3
Beta strandi257 – 262Combined sources6
Beta strandi264 – 272Combined sources9
Helixi279 – 286Combined sources8
Helixi291 – 310Combined sources20
Helixi320 – 322Combined sources3
Beta strandi323 – 325Combined sources3
Beta strandi327 – 329Combined sources3
Beta strandi331 – 333Combined sources3
Helixi336 – 338Combined sources3
Beta strandi343 – 345Combined sources3
Helixi354 – 356Combined sources3
Helixi359 – 362Combined sources4
Beta strandi363 – 365Combined sources3
Helixi371 – 386Combined sources16
Helixi393 – 395Combined sources3
Helixi399 – 406Combined sources8
Beta strandi415 – 417Combined sources3
Helixi419 – 428Combined sources10
Turni433 – 435Combined sources3
Turni437 – 439Combined sources3
Beta strandi440 – 442Combined sources3
Helixi444 – 448Combined sources5
Helixi451 – 453Combined sources3
Helixi458 – 462Combined sources5
Helixi502 – 504Combined sources3
Turni505 – 508Combined sources4
Helixi514 – 522Combined sources9
Turni523 – 525Combined sources3
Helixi526 – 546Combined sources21
Turni553 – 558Combined sources6
Beta strandi561 – 567Combined sources7
Turni571 – 573Combined sources3
Beta strandi577 – 584Combined sources8
Beta strandi587 – 591Combined sources5
Beta strandi593 – 595Combined sources3
Beta strandi599 – 602Combined sources4
Turni603 – 605Combined sources3
Beta strandi606 – 614Combined sources9
Beta strandi617 – 624Combined sources8
Turni625 – 627Combined sources3
Beta strandi629 – 633Combined sources5
Helixi637 – 660Combined sources24
Turni662 – 664Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1OMWX-ray2.50A1-689[»]
1YM7X-ray4.50A/B/C/D1-689[»]
2BCJX-ray3.06A1-689[»]
3PSCX-ray2.67A1-689[»]
3PVUX-ray2.48A1-689[»]
3PVWX-ray2.49A1-689[»]
3UZSX-ray4.52A1-681[»]
3UZTX-ray3.51A1-689[»]
5HE0X-ray2.56A30-670[»]
5HE2X-ray2.79A30-670[»]
5HE3X-ray2.74A30-670[»]
ProteinModelPortaliP21146.
SMRiP21146.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21146.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini54 – 175RGSPROSITE-ProRule annotationAdd BLAST122
Domaini191 – 453Protein kinasePROSITE-ProRule annotationAdd BLAST263
Domaini454 – 521AGC-kinase C-terminalAdd BLAST68
Domaini558 – 652PHPROSITE-ProRule annotationAdd BLAST95

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 190N-terminalAdd BLAST190
Regioni454 – 689C-terminalAdd BLAST236

Domaini

The PH domain binds anionic phospholipids and helps recruiting ADRBK1 from the cytoplasm to plasma membrane close to activated receptors. It mediates binding to G protein beta and gamma subunits, competing with G-alpha subunits and other G-betagamma effectors.1 Publication

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 RGS domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0986. Eukaryota.
ENOG410YRQZ. LUCA.
HOGENOMiHOG000006742.
HOVERGENiHBG050559.
InParanoidiP21146.
KOiK00910.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR000239. GPCR_kinase.
IPR011009. Kinase-like_dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016137. RGS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSiPR00717. GPCRKINASE.
SMARTiSM00233. PH. 1 hit.
SM00315. RGS. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF48097. SSF48097. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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]

Sequencei

Sequence statusi: Complete.

P21146-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADLEAVLAD VSYLMAMEKS KATPAARASK KILLPEPSIR SVMQKYLEDR
60 70 80 90 100
GEVTFEKIFS QKLGYLLFRD FCLKHLEEAK PLVEFYEEIK KYEKLETEEE
110 120 130 140 150
RLVCSREIFD TYIMKELLAC SHPFSKSAIE HVQGHLVKKQ VPPDLFQPYI
160 170 180 190 200
EEICQNLRGD VFQKFIESDK FTRFCQWKNV ELNIHLTMND FSVHRIIGRG
210 220 230 240 250
GFGEVYGCRK ADTGKMYAMK CLDKKRIKMK QGETLALNER IMLSLVSTGD
260 270 280 290 300
CPFIVCMSYA FHTPDKLSFI LDLMNGGDLH YHLSQHGVFS EADMRFYAAE
310 320 330 340 350
IILGLEHMHN RFVVYRDLKP ANILLDEHGH VRISDLGLAC DFSKKKPHAS
360 370 380 390 400
VGTHGYMAPE VLQKGVAYDS SADWFSLGCM LFKLLRGHSP FRQHKTKDKH
410 420 430 440 450
EIDRMTLTMA VELPDSFSPE LRSLLEGLLQ RDVNRRLGCL GRGAQEVKES
460 470 480 490 500
PFFRSLDWQM VFLQKYPPPL IPPRGEVNAA DAFDIGSFDE EDTKGIKLLD
510 520 530 540 550
SDQELYRNFP LTISERWQQE VAETVFDTIN AETDRLEARK KTKNKQLGHE
560 570 580 590 600
EDYALGKDCI MHGYMSKMGN PFLTQWQRRY FYLFPNRLEW RGEGEAPQSL
610 620 630 640 650
LTMEEIQSVE ETQIKERKCL LLKIRGGKQF VLQCDSDPEL VQWKKELRDA
660 670 680
YREAQQLVQR VPKMKNKPRS PVVELSKVPL IQRGSANGL
Length:689
Mass (Da):79,647
Last modified:May 1, 1991 - v1
Checksum:i4AB95DB5E630B9DA
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34019 mRNA. Translation: AAA30384.1.
PIRiA40088.
RefSeqiNP_777135.1. NM_174710.2.
UniGeneiBt.4693.

Genome annotation databases

GeneIDi282682.
KEGGibta:282682.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34019 mRNA. Translation: AAA30384.1.
PIRiA40088.
RefSeqiNP_777135.1. NM_174710.2.
UniGeneiBt.4693.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1OMWX-ray2.50A1-689[»]
1YM7X-ray4.50A/B/C/D1-689[»]
2BCJX-ray3.06A1-689[»]
3PSCX-ray2.67A1-689[»]
3PVUX-ray2.48A1-689[»]
3PVWX-ray2.49A1-689[»]
3UZSX-ray4.52A1-681[»]
3UZTX-ray3.51A1-689[»]
5HE0X-ray2.56A30-670[»]
5HE2X-ray2.79A30-670[»]
5HE3X-ray2.74A30-670[»]
ProteinModelPortaliP21146.
SMRiP21146.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi159836. 3 interactors.
DIPiDIP-37856N.
IntActiP21146. 4 interactors.
STRINGi9913.ENSBTAP00000050806.

PTM databases

iPTMnetiP21146.

Proteomic databases

PaxDbiP21146.
PRIDEiP21146.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi282682.
KEGGibta:282682.

Organism-specific databases

CTDi110355.

Phylogenomic databases

eggNOGiKOG0986. Eukaryota.
ENOG410YRQZ. LUCA.
HOGENOMiHOG000006742.
HOVERGENiHBG050559.
InParanoidiP21146.
KOiK00910.

Enzyme and pathway databases

BRENDAi2.7.11.15. 908.

Miscellaneous databases

EvolutionaryTraceiP21146.

Gene expression databases

BgeeiENSBTAG00000005832.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR000239. GPCR_kinase.
IPR011009. Kinase-like_dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016137. RGS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSiPR00717. GPCRKINASE.
SMARTiSM00233. PH. 1 hit.
SM00315. RGS. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF48097. SSF48097. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiARBK1_BOVIN
AccessioniPrimary (citable) accession number: P21146
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: May 1, 1991
Last modified: November 2, 2016
This is version 158 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.