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P21146

- ARBK1_BOVIN

UniProt

P21146 - ARBK1_BOVIN

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Protein

Beta-adrenergic receptor kinase 1

Gene

ADRBK1

Organism
Bos taurus (Bovine)
Status
Reviewed - 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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei220 – 2201ATPPROSITE-ProRule annotation
Active sitei317 – 3171Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi197 – 2059ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. alpha-2A adrenergic receptor binding Source: BHF-UCL
  2. ATP binding Source: UniProtKB-KW
  3. beta-adrenergic receptor kinase activity Source: UniProtKB-EC
  4. Edg-2 lysophosphatidic acid receptor binding Source: UniProtKB
  5. G-protein coupled receptor kinase activity Source: BHF-UCL
  6. protein kinase activity Source: BHF-UCL

GO - Biological processi

  1. cardiac muscle contraction Source: BHF-UCL
  2. desensitization of G-protein coupled receptor protein signaling pathway Source: BHF-UCL
  3. G-protein coupled acetylcholine receptor signaling pathway Source: BHF-UCL
  4. G-protein coupled receptor internalization Source: UniProtKB
  5. G-protein coupled receptor signaling pathway Source: AgBase
  6. heart development Source: AgBase
  7. intracellular protein transport Source: BHF-UCL
  8. negative regulation of striated muscle contraction Source: BHF-UCL
  9. negative regulation of the force of heart contraction by chemical signal Source: BHF-UCL
  10. peptidyl-serine phosphorylation Source: BHF-UCL
  11. peptidyl-threonine phosphorylation Source: Ensembl
  12. protein phosphorylation Source: BHF-UCL
  13. regulation of signal transduction Source: BHF-UCL
  14. regulation of the force of heart contraction Source: AgBase
  15. tachykinin receptor signaling pathway Source: Ensembl
  16. termination of G-protein coupled receptor signaling pathway Source: InterPro
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.
ReactomeiREACT_202422. Calmodulin induced events.
REACT_209521. G alpha (q) signalling events.

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 2
Gene namesi
Name:ADRBK1
Synonyms:GRK2
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
ProteomesiUP000009136: Unplaced

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: BHF-UCL
  2. membrane Source: BHF-UCL
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 689689Beta-adrenergic receptor kinase 1PRO_0000085626Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei670 – 6701PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PRIDEiP21146.

Expressioni

Tissue specificityi

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

Gene expression databases

ExpressionAtlasiP21146. baseline.

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.

Protein-protein interaction databases

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

Structurei

Secondary structure

1
689
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi39 – 4810
Turni49 – 513
Helixi55 – 595
Helixi62 – 7514
Turni77 – 793
Helixi80 – 9314
Helixi98 – 11215
Helixi114 – 1185
Helixi126 – 13712
Turni143 – 1464
Helixi147 – 15812
Helixi160 – 1678
Helixi169 – 18214
Beta strandi191 – 1999
Beta strandi201 – 21010
Turni211 – 2133
Beta strandi216 – 2238
Helixi224 – 2307
Helixi233 – 24412
Beta strandi247 – 2493
Beta strandi252 – 2543
Beta strandi257 – 2626
Beta strandi264 – 2729
Helixi279 – 2868
Helixi291 – 31020
Helixi320 – 3223
Beta strandi323 – 3253
Beta strandi327 – 3293
Beta strandi331 – 3333
Helixi336 – 3383
Beta strandi343 – 3453
Helixi354 – 3563
Helixi359 – 3624
Helixi371 – 38616
Beta strandi393 – 3953
Helixi399 – 4068
Beta strandi415 – 4173
Helixi419 – 42810
Turni433 – 4353
Turni437 – 4393
Beta strandi440 – 4423
Helixi444 – 4485
Helixi451 – 4533
Helixi458 – 4625
Helixi502 – 5043
Turni505 – 5084
Helixi514 – 5229
Turni523 – 5253
Helixi526 – 54621
Turni553 – 5586
Beta strandi561 – 5677
Beta strandi577 – 5848
Beta strandi587 – 5915
Beta strandi593 – 5953
Beta strandi599 – 6024
Turni603 – 6053
Beta strandi606 – 6149
Beta strandi617 – 6248
Turni625 – 6273
Beta strandi629 – 6335
Helixi637 – 66024
Turni662 – 6643

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliP21146.
SMRiP21146. Positions 28-667.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21146.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini54 – 175122RGSPROSITE-ProRule annotationAdd
BLAST
Domaini191 – 453263Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini454 – 52168AGC-kinase C-terminalAdd
BLAST
Domaini558 – 65295PHPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 190190N-terminalAdd
BLAST
Regioni454 – 689236C-terminalAdd
BLAST

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

eggNOGiCOG0515.
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.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016137. Regulat_G_prot_signal_superfam.
IPR000342. RGS_dom.
IPR002290. Ser/Thr_dual-sp_kinase.
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.
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:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
M34019 mRNA. Translation: AAA30384.1 .
PIRi A40088.
RefSeqi NP_777135.1. NM_174710.2.
UniGenei Bt.4693.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1OMW X-ray 2.50 A 1-689 [» ]
1YM7 X-ray 4.50 A/B/C/D 1-689 [» ]
2BCJ X-ray 3.06 A 1-689 [» ]
3PSC X-ray 2.67 A 1-689 [» ]
3PVU X-ray 2.48 A 1-689 [» ]
3PVW X-ray 2.49 A 1-689 [» ]
3UZS X-ray 4.52 A 1-681 [» ]
3UZT X-ray 3.51 A 1-689 [» ]
ProteinModelPortali P21146.
SMRi P21146. Positions 28-667.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 159836. 3 interactions.
DIPi DIP-37856N.
IntActi P21146. 4 interactions.
STRINGi 9913.ENSBTAP00000050806.

Proteomic databases

PRIDEi P21146.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 282682.
KEGGi bta:282682.

Organism-specific databases

CTDi 156.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000006742.
HOVERGENi HBG050559.
InParanoidi P21146.
KOi K00910.

Enzyme and pathway databases

BRENDAi 2.7.11.15. 908.
Reactomei REACT_202422. Calmodulin induced events.
REACT_209521. G alpha (q) signalling events.

Miscellaneous databases

EvolutionaryTracei P21146.
NextBioi 20806352.

Gene expression databases

ExpressionAtlasi P21146. baseline.

Family and domain databases

Gene3Di 2.30.29.30. 1 hit.
InterProi IPR000961. AGC-kinase_C.
IPR000239. GPCR_kinase.
IPR011009. Kinase-like_dom.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016137. Regulat_G_prot_signal_superfam.
IPR000342. RGS_dom.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view ]
PRINTSi PR00717. GPCRKINASE.
SMARTi SM00233. PH. 1 hit.
SM00315. RGS. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF48097. SSF48097. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi 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 ]
ProtoNeti Search...

Publicationsi

  1. "Beta-adrenergic receptor kinase: primary structure delineates a multigene family."
    Benovic J.L., Deblasi A., Stone W.C., Caron M.G., Lefkowitz R.J.
    Science 246:235-240(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
  2. "Beta2-adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein."
    Premont R.T., Claing A., Vitale N., Freeman J.L.R., Pitcher J.A., Patton W.A., Moss J., Vaughan M., Lefkowitz R.J.
    Proc. Natl. Acad. Sci. U.S.A. 95:14082-14087(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GIT1.

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: October 29, 2014
This is version 139 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

External Data

Dasty 3