ID   F1LMA4_RAT              Unreviewed;       707 AA.
AC   F1LMA4;
DT   03-MAY-2011, integrated into UniProtKB/TrEMBL.
DT   25-MAY-2022, sequence version 3.
DT   04-NOV-2026, entry version 90.
DE   RecName: Full=G protein-coupled receptor kinase {ECO:0000256|RuleBase:RU000308};
DE            EC=2.7.11.- {ECO:0000256|RuleBase:RU000308};
GN   Name=Grk2 {ECO:0000313|Ensembl:ENSRNOP00000025847.6,
GN   ECO:0000313|RGD:2062}; Synonyms=Adrbk1 {ECO:0000313|RGD:2062};
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 {ECO:0000313|Ensembl:ENSRNOP00000025847.6, ECO:0000313|Proteomes:UP000002494};
RN   [1] {ECO:0007829|PubMed:22673903}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
RN   [2] {ECO:0000313|Ensembl:ENSRNOP00000025847.6}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000025847.6};
RA   Doris P.A., Kalbfleisch T., Li K., Howe K., Wood J.;
RT   "GRCr8: a new rat reference genome assembly contstructed from accurate long
RT   reads and long range scaffolding.";
RL   Submitted (JAN-2024) to the EMBL/GenBank/DDBJ databases.
RN   [3] {ECO:0000313|Ensembl:ENSRNOP00000025847.6}
RP   IDENTIFICATION.
RC   STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000025847.6};
RG   Ensembl;
RL   Submitted (JUL-2026) to UniProtKB.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP +
CC         H(+); Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC         Evidence={ECO:0000256|PROSITE-ProRule:PRU10027};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] +
CC         ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC         COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC         Evidence={ECO:0000256|PROSITE-ProRule:PRU10027};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=[G protein-coupled receptor] + ATP = [G protein-coupled
CC         receptor]-phosphate + ADP + H(+); Xref=Rhea:RHEA:12008, Rhea:RHEA-
CC         COMP:11260, Rhea:RHEA-COMP:11261, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:43176, ChEBI:CHEBI:68546,
CC         ChEBI:CHEBI:456216; EC=2.7.11.16;
CC         Evidence={ECO:0000256|ARBA:ARBA00095570};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12009;
CC         Evidence={ECO:0000256|ARBA:ARBA00095570};
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:0000256|ARBA:ARBA00036224};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19430;
CC         Evidence={ECO:0000256|ARBA:ARBA00036224};
CC   -!- SUBUNIT: Interacts with the heterodimer formed by GNB1 and GNG2.
CC       Interacts with GIT1. Interacts with, and phosphorylates chemokine-
CC       stimulated CCR5. Interacts with ARRB1. Interacts with LPAR1 and LPAR2.
CC       Interacts with RALA in response to LPAR1 activation. ADRBK1 and RALA
CC       mutually inhibit each other's binding to LPAR1. Interacts with ADRB2.
CC       {ECO:0000256|ARBA:ARBA00046847}.
CC   -!- SUBCELLULAR LOCATION: Cell projection, cilium membrane
CC       {ECO:0000256|ARBA:ARBA00004309}. Cytoplasm
CC       {ECO:0000256|ARBA:ARBA00004496}. Postsynapse
CC       {ECO:0000256|ARBA:ARBA00034110}. Presynapse
CC       {ECO:0000256|ARBA:ARBA00034106}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC       protein kinase family. GPRK subfamily. {ECO:0000256|ARBA:ARBA00009793,
CC       ECO:0000256|RuleBase:RU000308}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC       kinase family. {ECO:0000256|PROSITE-ProRule:PRU00159}.
CC   -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC       feature annotation. {ECO:0000256|PROSITE-ProRule:PRU00618}.
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DR   AlphaFoldDB; F1LMA4; -.
DR   jPOST; F1LMA4; -.
DR   Ensembl; ENSRNOT00000025847.9; ENSRNOP00000025847.6; ENSRNOG00000018985.9.
DR   RGD; 2062; Grk2.
DR   GeneTree; ENSGT00940000161626; -.
DR   HOGENOM; CLU_000288_63_41_1; -.
DR   OMA; AGMDWQQ; -.
DR   OrthoDB; 354826at2759; -.
DR   Proteomes; UP000002494; Chromosome 1.
DR   Bgee; ENSRNOG00000018985; Expressed in thymus and 19 other cell types or tissues.
DR   ExpressionAtlas; F1LMA4; baseline and differential.
DR   GO; GO:0032473; C:cytoplasmic side of mitochondrial outer membrane; IEA:Ensembl.
DR   GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR   GO; GO:0098804; C:non-motile cilium membrane; IEA:Ensembl.
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-UniRule.
DR   GO; GO:0047696; F:beta-adrenergic receptor kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0031755; F:Edg-2 lysophosphatidic acid receptor binding; IEA:Ensembl.
DR   GO; GO:0004703; F:G protein-coupled receptor kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0060048; P:cardiac muscle contraction; IEA:Ensembl.
DR   GO; GO:0002029; P:desensitization of G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0035721; P:intraciliary retrograde transport; IEA:Ensembl.
DR   GO; GO:1903568; P:negative regulation of protein localization to ciliary membrane; IEA:Ensembl.
DR   GO; GO:1901081; P:negative regulation of relaxation of smooth muscle; IEA:Ensembl.
DR   GO; GO:0045988; P:negative regulation of striated muscle contraction; IEA:Ensembl.
DR   GO; GO:0003108; P:negative regulation of the force of heart contraction by chemical signal; IEA:Ensembl.
DR   GO; GO:1905801; P:positive regulation of intraciliary retrograde transport; IEA:Ensembl.
DR   GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IEA:Ensembl.
DR   GO; GO:0031623; P:receptor internalization; IEA:Ensembl.
DR   GO; GO:0046718; P:symbiont entry into host cell; IEA:Ensembl.
DR   GO; GO:0007217; P:tachykinin receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0019079; P:viral genome replication; IEA:Ensembl.
DR   CDD; cd01240; PH_GRK2_subgroup; 1.
DR   CDD; cd08747; RGS_GRK2_GRK3; 1.
DR   FunFam; 1.10.510.10:FF:000118; G protein-coupled receptor kinase; 1.
DR   FunFam; 2.30.29.30:FF:000084; G protein-coupled receptor kinase; 1.
DR   FunFam; 3.30.200.20:FF:000068; G protein-coupled receptor kinase; 1.
DR   Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR   Gene3D; 1.10.167.10; Regulator of G-protein Signalling 4, domain 2; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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   PANTHER; PTHR24355:SF22; BETA-ADRENERGIC RECEPTOR KINASE 1; 1.
DR   PANTHER; PTHR24355; G PROTEIN-COUPLED RECEPTOR KINASE/RIBOSOMAL PROTEIN S6 KINASE; 1.
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; SSF50729; PH domain-like; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   SUPFAM; SSF48097; Regulator of G-protein signaling, RGS; 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 {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PROSITE-
KW   ProRule:PRU10141}; Cell membrane {ECO:0000256|ARBA:ARBA00022475};
KW   Cell projection {ECO:0000256|ARBA:ARBA00023273};
KW   Coiled coil {ECO:0000256|SAM:Coils};
KW   Cytoplasm {ECO:0000256|ARBA:ARBA00022490};
KW   Kinase {ECO:0000256|ARBA:ARBA00022777, ECO:0000256|PROSITE-
KW   ProRule:PRU00159}; Membrane {ECO:0000256|ARBA:ARBA00023136};
KW   Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741, ECO:0000256|PROSITE-
KW   ProRule:PRU10141}; Phosphoprotein {ECO:0000256|ARBA:ARBA00022553};
KW   Proteomics identification {ECO:0007829|PeptideAtlas:F1LMA4};
KW   Reference proteome {ECO:0000313|Proteomes:UP000002494};
KW   Serine/threonine-protein kinase {ECO:0000256|ARBA:ARBA00022527,
KW   ECO:0000256|PROSITE-ProRule:PRU00159};
KW   Synapse {ECO:0000256|ARBA:ARBA00023018};
KW   Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PROSITE-
KW   ProRule:PRU00159}.
FT   DOMAIN          54..175
FT                   /note="RGS"
FT                   /evidence="ECO:0000259|PROSITE:PS50132"
FT   DOMAIN          191..471
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000259|PROSITE:PS50011"
FT   DOMAIN          472..539
FT                   /note="AGC-kinase C-terminal"
FT                   /evidence="ECO:0000259|PROSITE:PS51285"
FT   DOMAIN          576..670
FT                   /note="PH"
FT                   /evidence="ECO:0000259|PROSITE:PS50003"
FT   COILED          658..685
FT                   /evidence="ECO:0000256|SAM:Coils"
FT   ACT_SITE        317
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR600239-51,
FT                   ECO:0000256|PROSITE-ProRule:PRU10027"
FT   BINDING         220
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000256|PROSITE-ProRule:PRU10141"
SQ   SEQUENCE   707 AA;  81593 MW;  509C3CA87E627EFB CRC64;
     MADLEAVLAD VSYLMAMEKS KATPAARASK KILLPEPSIR SVMQKYLEDR GEVTFEKIFS
     QKLGYLLFRD FCLNHLEEAK PLVEFYEEIK 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 LFKLLRGLPY LLPASSIILP HFSHSCFLTL HKTKDKHEID
     RMTLTMVSVR LPDSFSPELR SLLEGLLQRD VNRRLGCLGR GAQEVKESPF FRSLDWQMVF
     LQKYPPPLIP PRGEVNAADA FDIGSFDEED TKGIKLLDSD QELYRNFPLT ISERWQQEVA
     ETVFDTINAE TDRLEARKKA KNKQLGHEED YALGKDCIMH GYMSKMGNPF LTQWQRRYFY
     LFPNRLEWRG EGEAPQSLLT MEEIQSVEET QIKERKCLLL KIRGGKQFVL QCDSDPELVQ
     WKKELRDAYR EAQQLVQRVP KMKNKPRSPV VELSKVPLIQ RGSANGL
//