ARBK1_MESAU
ID ARBK1_MESAU Reviewed; 689 AA.
AC Q64682;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Beta-adrenergic receptor kinase 1;
DE Short=Beta-ARK-1;
DE EC=2.7.11.15 {ECO:0000250|UniProtKB:P26817};
DE AltName: Full=G-protein-coupled receptor kinase 2 {ECO:0000250|UniProtKB:P25098};
GN Name=GRK2 {ECO:0000250|UniProtKB:P25098}; Synonyms=ADRBK1;
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=8619818; DOI=10.1006/bbrc.1996.0175;
RA Urasawa K., Yoshida I., Takagi C., Onozuka H., Mikami T., Kawaguchi H.,
RA Kitabatake A.;
RT "Enhanced expression of beta-adrenergic receptor kinase 1 in the hearts of
RT cardiomyopathic Syrian hamsters, BIO53.58.";
RL Biochem. Biophys. Res. Commun. 219:26-30(1996).
CC -!- FUNCTION: Specifically phosphorylates the agonist-occupied form of the
CC beta-adrenergic and closely related receptors, probably inducing a
CC desensitization of them. Key regulator of LPAR1 signaling (By
CC similarity). Competes with RALA for binding to LPAR1 thus affecting the
CC signaling properties of the receptor (By similarity). Desensitizes
CC LPAR1 and LPAR2 in a phosphorylation-independent manner (By
CC similarity). Positively regulates ciliary smoothened (SMO)-dependent
CC Hedgehog (Hh) signaling pathway by facilitating the trafficking of SMO
CC into the cilium and the stimulation of SMO activity (By similarity).
CC Inhibits relaxation of airway smooth muscle in response to blue light
CC (By similarity). {ECO:0000250|UniProtKB:P21146,
CC ECO:0000250|UniProtKB:P25098, ECO:0000250|UniProtKB:Q99MK8}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[beta-adrenergic receptor] + ATP = [beta-adrenergic receptor]-
CC phosphate + ADP + H(+); Xref=Rhea:RHEA:19429, Rhea:RHEA-COMP:11222,
CC Rhea:RHEA-COMP:11223, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43176, ChEBI:CHEBI:68546, ChEBI:CHEBI:456216;
CC EC=2.7.11.15; Evidence={ECO:0000250|UniProtKB:P26817};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19430;
CC Evidence={ECO:0000250|UniProtKB:P26817};
CC -!- ACTIVITY REGULATION: In contrast to other AGC family kinases, the
CC catalytic activity is solely regulated by the binding of substrates and
CC ligands, not by phosphorylation of the kinase domain.
CC {ECO:0000250|UniProtKB:P21146}.
CC -!- SUBUNIT: Interacts with the heterodimer formed by GNB1 and GNG2 (By
CC similarity). Interacts with GIT1 (By similarity). Interacts with, and
CC phosphorylates chemokine-stimulated CCR5 (By similarity). Interacts
CC with ARRB1 (By similarity). Interacts with LPAR1 and LPAR2 (By
CC similarity). Interacts with RALA in response to LPAR1 activation (By
CC similarity). ADRBK1 and RALA mutually inhibit each other's binding to
CC LPAR1 (By similarity). Interacts with ADRB2 (By similarity).
CC {ECO:0000250|UniProtKB:P21146, ECO:0000250|UniProtKB:P25098,
CC ECO:0000250|UniProtKB:P26817}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P26817}. Cell
CC membrane {ECO:0000250|UniProtKB:P21146}. Postsynapse
CC {ECO:0000250|UniProtKB:P26817}. Presynapse
CC {ECO:0000250|UniProtKB:P26817}.
CC -!- DOMAIN: The PH domain binds anionic phospholipids and helps recruiting
CC ADRBK1 from the cytoplasm to plasma membrane close to activated
CC receptors. It mediates binding to G protein beta and gamma subunits,
CC competing with G-alpha subunits and other G-betagamma effectors.
CC {ECO:0000250|UniProtKB:P21146}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. GPRK subfamily. {ECO:0000305}.
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DR EMBL; S81843; AAD14377.1; -; mRNA.
DR RefSeq; NP_001268501.1; NM_001281572.1.
DR AlphaFoldDB; Q64682; -.
DR SMR; Q64682; -.
DR STRING; 10036.XP_005064120.1; -.
DR GeneID; 101825875; -.
DR CTD; 156; -.
DR eggNOG; KOG0986; Eukaryota.
DR OrthoDB; 1104340at2759; -.
DR BRENDA; 2.7.11.15; 3239.
DR Proteomes; UP000189706; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098794; C:postsynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0098793; C:presynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0047696; F:beta-adrenergic receptor kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004703; F:G protein-coupled receptor kinase activity; IEA:InterPro.
DR GO; GO:1901081; P:negative regulation of relaxation of smooth muscle; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 1.10.167.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR000239; GPCR_kinase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR016137; RGS.
DR InterPro; IPR036305; RGS_sf.
DR InterPro; IPR044926; RGS_subdomain_2.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00615; RGS; 1.
DR PRINTS; PR00717; GPCRKINASE.
DR SMART; SM00233; PH; 1.
DR SMART; SM00315; RGS; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF48097; SSF48097; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50132; RGS; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell membrane; Cell projection; Cytoplasm; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Synapse; Transferase.
FT CHAIN 1..689
FT /note="Beta-adrenergic receptor kinase 1"
FT /id="PRO_0000085628"
FT DOMAIN 54..175
FT /note="RGS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT DOMAIN 191..453
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 454..521
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 558..652
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 1..190
FT /note="N-terminal"
FT ACT_SITE 317
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 197..205
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 220
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 3
FT /note="Required for receptor phosphorylation"
FT /evidence="ECO:0000250|UniProtKB:P25098"
FT SITE 4
FT /note="Required for receptor phosphorylation"
FT /evidence="ECO:0000250|UniProtKB:P25098"
FT SITE 10
FT /note="Required for receptor phosphorylation"
FT /evidence="ECO:0000250|UniProtKB:P25098"
FT MOD_RES 670
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P25098"
SQ SEQUENCE 689 AA; 79598 MW; 4E3F8DF50EEDE33F CRC64;
MADLEAVLAD VSYLMAMEKS KATPAARASK KILLPEPSIR SVMQKYLEDR GEVTFEKIFS
QKLGYLLFRD FCLNYLEEAK PLVEFYEEIK KYEKLETEEE RVVRSREIFD SYIMKELLAC
SHPFSKNATE HVQGHLVKKQ VPPDLFQPYI EEICQNLRGD VFQKFIESDK FTRFCQWKNV
ELNIHLTMND FSVHRIIGRG GFGEVYGCRK ADTGKMYAMK CLDKKRIKMK QGETLALNER
IMLSLVSTGD CPFIVCMSYA FRTPDNLSFI LDLMNGGDLH YHLSQHGVFS EADMRSYAAE
IILGLEHMHN RFVVYRDLKP ANILLDEHGH VRISDLGLAC DFSKKKPHAS VGTHGYMAPE
VLQKGVAYDS SADWFSLGCM LFKLLRGHSP FRQHKTKDKH EIDRMTLTMA VELPDSFSPE
LRSLLEGLLQ RDVNRRLGCL GRGAQEVKES PFFRSLDWQM VFLQKYPPPL IPPRGEVNAA
DAFDIGSFDE EDTKGIKLPD SDQELYRNFP LTISERWQQE VAETVFDTIN AETDRLEARK
KAKNKQLGHE EDYALGKDCI MHGYMSKMGN PFLTQWQRRY FYLFPNRLEW RGEGEAPQSL
LTMEEIQSVE ETQIKERKCL LLKIRGGKQF VLQCDSDPEL VQWKKELRDA YREAQQLVQR
VPKMKNKPRS PVVELSKVPL IQRGSANGL
