ARBK2_RAT
ID ARBK2_RAT Reviewed; 688 AA.
AC P26819;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Beta-adrenergic receptor kinase 2;
DE Short=Beta-ARK-2;
DE EC=2.7.11.15 {ECO:0000269|PubMed:1403099};
DE AltName: Full=G-protein-coupled receptor kinase 3 {ECO:0000312|RGD:2063};
GN Name=Grk3 {ECO:0000312|RGD:2063}; Synonyms=Adrbk2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP CATALYTIC ACTIVITY.
RC TISSUE=Brain;
RX PubMed=1403099; DOI=10.1523/jneurosci.12-10-04045.1992;
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 widely
RT distributed at synapses in rat brain.";
RL J. Neurosci. 12:4045-4055(1992).
RN [2]
RP INTERACTION WITH GIT1.
RX PubMed=9826657; DOI=10.1073/pnas.95.24.14082;
RA Premont R.T., Claing A., Vitale N., Freeman J.L.R., Pitcher J.A.,
RA Patton W.A., Moss J., Vaughan M., Lefkowitz R.J.;
RT "Beta2-adrenergic receptor regulation by GIT1, a G protein-coupled receptor
RT kinase-associated ADP ribosylation factor GTPase-activating protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:14082-14087(1998).
CC -!- FUNCTION: Specifically phosphorylates the agonist-occupied form of the
CC beta-adrenergic and closely related receptors.
CC {ECO:0000269|PubMed:1403099}.
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:0000269|PubMed:1403099};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19430;
CC Evidence={ECO:0000269|PubMed:1403099};
CC -!- SUBUNIT: Interacts with GIT1. {ECO:0000269|PubMed:9826657}.
CC -!- SUBCELLULAR LOCATION: Postsynapse {ECO:0000269|PubMed:1403099}.
CC Presynapse {ECO:0000269|PubMed:1403099}.
CC -!- TISSUE SPECIFICITY: Expressed in brain cortex, hippocampus, striatum,
CC hypothalamus, cerebellum and brainstem (at protein level).
CC {ECO:0000269|PubMed:1403099}.
CC -!- PTM: Ubiquitinated. {ECO:0000250}.
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; M87855; AAA40803.1; -; mRNA.
DR PIR; I73628; I73628.
DR RefSeq; NP_037029.1; NM_012897.2.
DR AlphaFoldDB; P26819; -.
DR SMR; P26819; -.
DR PhosphoSitePlus; P26819; -.
DR jPOST; P26819; -.
DR PRIDE; P26819; -.
DR DNASU; 25372; -.
DR GeneID; 25372; -.
DR KEGG; rno:25372; -.
DR CTD; 157; -.
DR RGD; 2063; Grk3.
DR InParanoid; P26819; -.
DR OrthoDB; 1104340at2759; -.
DR PhylomeDB; P26819; -.
DR BRENDA; 2.7.11.15; 5301.
DR Reactome; R-RNO-418555; G alpha (s) signalling events.
DR Reactome; R-RNO-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR PRO; PR:P26819; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0005929; C:cilium; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0044292; C:dendrite terminus; IDA:RGD.
DR GO; GO:0043198; C:dendritic shaft; IDA:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0098793; C:presynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0097225; C:sperm midpiece; IDA:RGD.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0030018; C:Z disc; 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:0031748; F:D1 dopamine receptor binding; IPI:RGD.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central.
DR GO; GO:0004703; F:G protein-coupled receptor kinase activity; IDA:RGD.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:RGD.
DR GO; GO:0002029; P:desensitization of G protein-coupled receptor signaling pathway; IDA:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IEP:RGD.
DR GO; GO:0043647; P:inositol phosphate metabolic process; IMP:RGD.
DR GO; GO:0006886; P:intracellular protein transport; IMP:RGD.
DR GO; GO:0010259; P:multicellular organism aging; IEP:RGD.
DR GO; GO:0045744; P:negative regulation of G protein-coupled receptor signaling pathway; IC:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0031623; P:receptor internalization; ISO:RGD.
DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central.
DR GO; GO:0043278; P:response to morphine; IEP:RGD.
DR GO; GO:0046154; P:rhodopsin metabolic process; IMP: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_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; 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 1: Evidence at protein level;
KW ATP-binding; Cell projection; Kinase; Nucleotide-binding;
KW Reference proteome; Serine/threonine-protein kinase; Synapse; Transferase;
KW Ubl conjugation.
FT CHAIN 1..688
FT /note="Beta-adrenergic receptor kinase 2"
FT /id="PRO_0000085633"
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"
SQ SEQUENCE 688 AA; 79887 MW; B4A077F4B48DDD3A CRC64;
MADLEAVLAD VSYLMAMEKS KATPAARASK KVVLPEPSIR SVMQRYLAER NEITFDKIFN
QKIGFLLFKD FCLNEIGEAV PQVKFYEEIK EYEKLDNEED RLHRSRQMYD AYIMRELLSS
THQFSKQAVE HVQSHLSKKQ VTPTLFQPYI EEICESLRGD IFQKFMESEK FTRFCQWKNV
ELNIHLSMND FSVHRIIGRG GFGEVYGCRK ADTGKMYAMK CLDKKRVKMK QGETLALNER
IMLSLVSTGD CPFIVCMTYA FHTPDKLCFI LDLMNGGDMH YHLSQHGVFS EKEMRFYASE
IILGLEHMHT CFVVYRDLKP ANILLDEYGH VRISDLGLAC DFSKKKPHAS VGTHGYMAPE
VLQKGTCYDS SADWFSLGCM LFKLLRGHSP FRQHKTKDKH EIDRMTLTVN VQLPDAFSPE
LRSLLEGLLQ RDVSQRLGCY GGGARELKEH IFFKGIDWQY VYLRKYPPPL IPPRGEVNAA
DAFDIGSFDE EDTKGIKLLD CDQDLYKNFP LMISERWQQE VVETIYDAVN AETDKIEARK
KAKNKQLCQE EDYAMGKDCI MHGYMLKLGN PFLTQWQRRY FYLFPNRLEW RGEGESRQNL
LTMEQIMSVE ETQIKDRKCI LLRVKGGKQF VLQCESDPEF AQWLKELTCT FNEAQRLLRR
APKFLNKPRA AILEFSKPPL CHRNSSGL
