ID   F1LMA4_RAT              Unreviewed;       707 AA.
AC   F1LMA4;
DT   03-MAY-2011, integrated into UniProtKB/TrEMBL.
DT   25-MAY-2022, sequence version 3.
DT   27-MAR-2024, entry version 78.
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:0000313|Ensembl:ENSRNOP00000025847.6, ECO:0000313|Proteomes:UP000002494}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000025847.6,
RC   ECO:0000313|Proteomes:UP000002494};
RX   PubMed=15057822; DOI=10.1038/nature02426;
RG   Rat Genome Sequencing Project Consortium;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [2] {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   [3] {ECO:0000313|Ensembl:ENSRNOP00000025847.6}
RP   IDENTIFICATION.
RC   STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000025847.6};
RG   Ensembl;
RL   Submitted (NOV-2023) to UniProtKB.
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   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|ARBA:ARBA00004236}.
CC       Cytoplasm {ECO:0000256|ARBA:ARBA00004496}. Membrane
CC       {ECO:0000256|ARBA:ARBA00004370}. Postsynapse
CC       {ECO:0000256|ARBA:ARBA00034110}. Presynapse
CC       {ECO:0000256|ARBA:ARBA00034106}. Synapse
CC       {ECO:0000256|ARBA:ARBA00034103}.
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}.
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DR   AlphaFoldDB; F1LMA4; -.
DR   jPOST; F1LMA4; -.
DR   Ensembl; ENSRNOT00000025847.8; ENSRNOP00000025847.6; ENSRNOG00000018985.8.
DR   RGD; 2062; Grk2.
DR   GeneTree; ENSGT00940000161626; -.
DR   HOGENOM; CLU_000288_63_41_1; -.
DR   OMA; MYIMKEL; -.
DR   TreeFam; TF313940; -.
DR   Proteomes; UP000002494; Chromosome 1.
DR   Bgee; ENSRNOG00000018985; Expressed in thymus and 19 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
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-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:Ensembl.
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:0007507; P:heart development; 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:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0031623; P:receptor internalization; IEA:Ensembl.
DR   GO; GO:0007217; P:tachykinin receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0046718; P:viral entry into host cell; 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   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}; Coiled coil {ECO:0000256|SAM:Coils};
KW   Kinase {ECO:0000256|ARBA:ARBA00022777, ECO:0000256|RuleBase:RU000308};
KW   Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741, ECO:0000256|PROSITE-
KW   ProRule:PRU10141};
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|RuleBase:RU000308}; Synapse {ECO:0000256|ARBA:ARBA00023018};
KW   Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|RuleBase:RU000308}.
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   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
//