Legends: 1, ACT_SITE Proton acceptor. {ECO:0000255|PROSITE- ProRule:PRU00159, ECO:0000255|PROSITE- ProRule:PRU10027}; 2, BINDING ATP. {ECO:0000255|PROSITE- ProRule:PRU00159}; 3, Phosphoserine. {ECO:0000244|PubMed:22673903}; 4, CONFLICT Y -> N (in Ref. 2; AAB24228). {ECO:0000305}; 5, CONFLICT Y -> C (in Ref. 2; AAB24228). {ECO:0000305}; 6, CONFLICT E -> K (in Ref. 2; AAB24228). {ECO:0000305}; 7, CONFLICT G -> V (in Ref. 2; AAB24228). {ECO:0000305}; 8, CONFLICT I -> S (in Ref. 2; AAB24228). {ECO:0000305}; 9, CONFLICT F -> Y (in Ref. 2; AAB24228). {ECO:0000305}; 10, CONFLICT I -> V (in Ref. 2; AAB24228). {ECO:0000305}; 11, CONFLICT D -> G (in Ref. 2; AAB24228). {ECO:0000305}; 12, RGS. {ECO:0000255|PROSITE- ProRule:PRU00171}; 13, Protein kinase. {ECO:0000255|PROSITE- ProRule:PRU00159}; 14, AGC-kinase C-terminal; 15, PH. {ECO:0000255|PROSITE- ProRule:PRU00145}; 16, NP_BIND ATP. {ECO:0000255|PROSITE- ProRule:PRU00159}; 17, CONFLICT PA -> RR (in Ref. 2; AAB24228). {ECO:0000305}; 18, iprf:PH_DOMAIN [T]; 19, ismart:S_TK_X [T]; 20, ipat:PROTEIN_KINASE_ATP [T]; 21, iprf:AGC_KINASE_CTER [T]; 22, ipat:PROTEIN_KINASE_ST [T].
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ID ARBK1_RAT Reviewed; 689 AA.
AC P26817;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 10-MAY-2017, entry version 147.
DE RecName: Full=Beta-adrenergic receptor kinase 1;
DE Short=Beta-ARK-1;
DE EC=2.7.11.15;
DE AltName: Full=G-protein-coupled receptor kinase 2 {ECO:0000312|RGD:2062};
GN Name=Grk2 {ECO:0000312|RGD:2062}; Synonyms=Adrbk1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC Muroidea; Muridae; Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=1403099;
RA Arriza J.L., Dawson T.M., Simerly R.B., Martin L.J., Caron M.G.,
RA Snyder S.H., Lefkowitz R.J.;
RT "The G-protein-coupled receptor kinases beta ARK1 and beta ARK2 are
RT widely distributed at synapses in rat brain.";
RL J. Neurosci. 12:4045-4055(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=1436718; DOI=10.1016/0304-3940(92)90704-B;
RA Owada Y., Watanabe M., Kondo H.;
RT "Localization of mRNA for beta-adrenergic receptor kinase in the brain
RT of adult rats.";
RL Neurosci. Lett. 144:9-13(1992).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-670, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A.,
RA Lundby C., Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14
RT different rat organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Specifically phosphorylates the agonist-occupied form of
CC the beta-adrenergic and closely related receptors, probably
CC inducing a desensitization of them.
CC -!- CATALYTIC ACTIVITY: ATP + [beta-adrenergic receptor] = ADP +
CC [beta-adrenergic receptor] phosphate.
CC -!- ENZYME REGULATION: In contrast to other AGC family kinases, the
CC catalytic activity is solely regulated by the binding of
CC substrates and ligands, not by phosphorylation of the kinase
CC domain. {ECO:0000250|UniProtKB:P21146}.
CC -!- SUBUNIT: Interacts with GIT1. Interacts with, and phosphorylates
CC chemokine-stimulated CCR5. Interacts with ARRB1 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P21146}.
CC Cell membrane {ECO:0000250|UniProtKB:P21146}.
CC -!- DOMAIN: The PH domain binds anionic phospholipids and helps
CC recruiting ADRBK1 from the cytoplasm to plasma membrane close to
CC activated receptors. It mediates binding to G protein beta and
CC gamma subunits, competing with G-alpha subunits and other G-
CC betagamma effectors. {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; M87854; AAA40802.1; -; mRNA.
DR EMBL; S48813; AAB24228.1; -; mRNA.
DR PIR; I56531; I56531.
DR RefSeq; NP_036908.1; NM_012776.1.
DR UniGene; Rn.13010; -.
DR ProteinModelPortal; P26817; -.
DR SMR; P26817; -.
DR BioGrid; 247278; 3.
DR STRING; 10116.ENSRNOP00000025847; -.
DR iPTMnet; P26817; -.
DR PhosphoSitePlus; P26817; -.
DR PaxDb; P26817; -.
DR PRIDE; P26817; -.
DR GeneID; 25238; -.
DR KEGG; rno:25238; -.
DR UCSC; RGD:2062; rat.
DR CTD; 156; -.
DR RGD; 2062; Grk2.
DR eggNOG; KOG0986; Eukaryota.
DR eggNOG; ENOG410YRQZ; LUCA.
DR HOGENOM; HOG000006742; -.
DR HOVERGEN; HBG050559; -.
DR InParanoid; P26817; -.
DR KO; K00910; -.
DR PhylomeDB; P26817; -.
DR BRENDA; 2.7.11.15; 5301.
DR PRO; PR:P26817; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
DR GO; GO:0005901; C:caveola; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0043198; C:dendritic shaft; IDA:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0047696; F:beta-adrenergic receptor kinase activity; IDA:RGD.
DR GO; GO:0004703; F:G-protein coupled receptor kinase activity; IDA:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0002029; P:desensitization of G-protein coupled receptor protein signaling pathway; IDA:BHF-UCL.
DR GO; GO:0042699; P:follicle-stimulating hormone signaling pathway; IDA:RGD.
DR GO; GO:0007186; P:G-protein coupled receptor signaling pathway; IDA:RGD.
DR GO; GO:0045744; P:negative regulation of G-protein coupled receptor protein signaling pathway; IDA:RGD.
DR GO; GO:0033605; P:positive regulation of catecholamine secretion; IDA:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0042542; P:response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IDA:RGD.
DR GO; GO:0006979; P:response to oxidative stress; IDA:RGD.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR000239; GPCR_kinase.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR011993; PH_dom-like.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR016137; RGS.
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; SSF50729; SSF50729; 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 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Kinase;
KW Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1 689 Beta-adrenergic receptor kinase 1.
FT /FTId=PRO_0000085630.
FT DOMAIN 54 175 RGS. {ECO:0000255|PROSITE-
FT ProRule:PRU00171}.
FT DOMAIN 191 453 Protein kinase. {ECO:0000255|PROSITE-
FT ProRule:PRU00159}.
FT DOMAIN 454 521 AGC-kinase C-terminal.
FT DOMAIN 558 652 PH. {ECO:0000255|PROSITE-
FT ProRule:PRU00145}.
FT NP_BIND 197 205 ATP. {ECO:0000255|PROSITE-
FT ProRule:PRU00159}.
FT REGION 1 190 N-terminal.
FT ACT_SITE 317 317 Proton acceptor. {ECO:0000255|PROSITE-
FT ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027}.
FT BINDING 220 220 ATP. {ECO:0000255|PROSITE-
FT ProRule:PRU00159}.
FT MOD_RES 670 670 Phosphoserine.
FT {ECO:0000244|PubMed:22673903}.
FT CONFLICT 24 25 PA -> RR (in Ref. 2; AAB24228).
FT {ECO:0000305}.
FT CONFLICT 46 46 Y -> N (in Ref. 2; AAB24228).
FT {ECO:0000305}.
FT CONFLICT 72 72 Y -> C (in Ref. 2; AAB24228).
FT {ECO:0000305}.
FT CONFLICT 90 90 E -> K (in Ref. 2; AAB24228).
FT {ECO:0000305}.
FT CONFLICT 249 249 G -> V (in Ref. 2; AAB24228).
FT {ECO:0000305}.
FT CONFLICT 270 270 I -> S (in Ref. 2; AAB24228).
FT {ECO:0000305}.
FT CONFLICT 296 296 F -> Y (in Ref. 2; AAB24228).
FT {ECO:0000305}.
FT CONFLICT 447 447 I -> V (in Ref. 2; AAB24228).
FT {ECO:0000305}.
FT CONFLICT 594 594 D -> G (in Ref. 2; AAB24228).
FT {ECO:0000305}.
CC --------------------------------------------------------------------------
CC The following FT lines are automated annotations from the MyHits database.
CC --------------------------------------------------------------------------
FT MYHIT 560 650 ipfam:PH [T]
FT MYHIT 191 453 ismart:S_TKc [T]
FT MYHIT 558 652 iprf:PH_DOMAIN [T]
FT MYHIT 559 654 ismart:PH [T]
FT MYHIT 192 453 ipfam:Pkinase [T]
FT MYHIT 454 533 ismart:S_TK_X [T]
FT MYHIT 197 220 ipat:PROTEIN_KINASE_ATP [T]
FT MYHIT 54 175 ismart:RGS [T]
FT MYHIT 55 174 ipfam:RGS [T]
FT MYHIT 454 521 iprf:AGC_KINASE_CTER [T]
FT MYHIT 54 175 iprf:RGS [T]
FT MYHIT 313 325 ipat:PROTEIN_KINASE_ST [T]
FT MYHIT 191 453 iprf:PROTEIN_KINASE_DOM [T]
SQ SEQUENCE 689 AA; 79785 MW; 426A3335ACEB5A34 CRC64;
MADLEAVLAD VSYLMAMEKS KATPAARASK KILLPEPSIR SVMQKYLEDR GEVTFEKIFS
QKLGYLLFRD FYLNHLEEAK PLVEFYEEIE KYEKLETEEE RVVRSREIFD SYIMKELLAC
SHPFSKNATE HVQGHLVKKQ VPPDLFQPYI EEICQNLRGD VFHKFIESDK FTRFCQWKNV
ELNIHLTMND FSVHRIIGRG GFGEVYGCRK ADTGKMYAMK CLDKKRIKMK QGETLALNER
IMLSLVSTGD CPFIVCMSYA FHTPDKLSFI LDLMNGGDLH YHLSQHGVFS EADMRFYAAE
IILGLEHMHN RFVVYRDLKP ANILLDEHGH VRISDLGLAC DFSKKKPHAS VGTHGYMAPE
VLQKGVAYDS SADWFSLGCM LFKLLRGHSP FRQHKTKDKH EIDRMTLTMA VELPDSFSPE
LRSLLEGLLQ RDVNRRLGCL GRGAQEIKES PFFRSLDWQM VFLQKYPPPL IPPRGEVNAA
DAFDIGSFDE EDTKGIKLLD SDQELYRNFP LTISERWQQE VAETVFDTIN AETDRLEARK
KAKNKQLGHE EDYALGKDCI MHGYMSKMGN PFLTQWQRRY FYLFPNRLEW RGEDEAPQSL
LTMEEIQSVE ETQIKERKCL LLKIRGGKQF VLQCDSDPEL VQWKKELRDA YREAQQLVQR
VPKMKNKPRS PVVELSKVPL IQRGSANGL
//
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