ID   GRK4_RAT                Reviewed;         575 AA.
AC   P70507; P70508;
DT   24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1997, sequence version 1.
DT   24-JAN-2024, entry version 154.
DE   RecName: Full=G protein-coupled receptor kinase 4;
DE            EC=2.7.11.16;
DE   AltName: Full=G protein-coupled receptor kinase GRK4;
GN   Name=Grk4; Synonyms=Gprk2l;
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] (ISOFORMS GRK4A AND GRK4B), CHARACTERIZATION,
RP   AND TISSUE SPECIFICITY.
RX   PubMed=9607785; DOI=10.1210/endo.139.6.6078;
RA   Virlon B., Firsov D., Cheval L., Reiter E., Troispoux C., Guillou F.,
RA   Elalouf J.-M.;
RT   "Rat G protein-coupled receptor kinase GRK4: identification, functional
RT   expression, and differential tissue distribution of two splice variants.";
RL   Endocrinology 139:2784-2795(1998).
RN   [2]
RP   FUNCTION.
RX   PubMed=16636192; DOI=10.1161/01.hyp.0000222004.74872.17;
RA   Sanada H., Yatabe J., Midorikawa S., Katoh T., Hashimoto S., Watanabe T.,
RA   Xu J., Luo Y., Wang X., Zeng C., Armando I., Felder R.A., Jose P.A.;
RT   "Amelioration of genetic hypertension by suppression of renal G protein-
RT   coupled receptor kinase type 4 expression.";
RL   Hypertension 47:1131-1139(2006).
RN   [3]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-484, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
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).
CC   -!- FUNCTION: Specifically phosphorylates the activated forms of G protein-
CC       coupled receptors. Plays an important role in the regulation of renal
CC       sodium handling and blood pressure. {ECO:0000269|PubMed:16636192}.
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   -!- ACTIVITY REGULATION: Inhibited by heparin. {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with DRD3. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cell cortex {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=GRK4A;
CC         IsoId=P70507-1; Sequence=Displayed;
CC       Name=GRK4B;
CC         IsoId=P70507-2; Sequence=VSP_010352;
CC   -!- TISSUE SPECIFICITY: Isoform GRK4A is expressed in testis. Isoform GRK4B
CC       is heterogeneously distributed in the kidney, with 20-fold enrichment
CC       in the outer medulla. Has a widespread but low level of expression in
CC       tissues other than testis. {ECO:0000269|PubMed:9607785}.
CC   -!- PTM: Palmitoylated. {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; X97568; CAA66180.1; -; mRNA.
DR   EMBL; X97568; CAA66181.1; -; mRNA.
DR   RefSeq; NP_075217.1; NM_022928.1. [P70507-1]
DR   RefSeq; XP_006251421.1; XM_006251359.2. [P70507-2]
DR   AlphaFoldDB; P70507; -.
DR   SMR; P70507; -.
DR   STRING; 10116.ENSRNOP00000015894; -.
DR   iPTMnet; P70507; -.
DR   PhosphoSitePlus; P70507; -.
DR   PaxDb; 10116-ENSRNOP00000015894; -.
DR   Ensembl; ENSRNOT00000015894.5; ENSRNOP00000015894.2; ENSRNOG00000011847.6. [P70507-1]
DR   Ensembl; ENSRNOT00000094171.1; ENSRNOP00000088283.1; ENSRNOG00000011847.6. [P70507-2]
DR   Ensembl; ENSRNOT00055028539; ENSRNOP00055022978; ENSRNOG00055016786. [P70507-1]
DR   Ensembl; ENSRNOT00060039274; ENSRNOP00060032477; ENSRNOG00060022523. [P70507-1]
DR   Ensembl; ENSRNOT00065055144; ENSRNOP00065045337; ENSRNOG00065031984. [P70507-1]
DR   GeneID; 59077; -.
DR   KEGG; rno:59077; -.
DR   AGR; RGD:61858; -.
DR   CTD; 2868; -.
DR   RGD; 61858; Grk4.
DR   eggNOG; KOG0986; Eukaryota.
DR   GeneTree; ENSGT00940000160151; -.
DR   HOGENOM; CLU_000288_63_41_1; -.
DR   InParanoid; P70507; -.
DR   OrthoDB; 2906348at2759; -.
DR   PhylomeDB; P70507; -.
DR   TreeFam; TF313940; -.
DR   Reactome; R-RNO-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR   PRO; PR:P70507; -.
DR   Proteomes; UP000002494; Chromosome 14.
DR   Bgee; ENSRNOG00000011847; Expressed in testis and 19 other cell types or tissues.
DR   GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0030425; C:dendrite; IDA:RGD.
DR   GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR   GO; GO:0050254; F:rhodopsin kinase activity; IDA:RGD.
DR   GO; GO:0002029; P:desensitization of G protein-coupled receptor signaling pathway; IMP:RGD.
DR   GO; GO:0002031; P:G protein-coupled receptor internalization; IMP:RGD.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0031623; P:receptor internalization; ISO:RGD.
DR   GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central.
DR   GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR   CDD; cd05605; STKc_GRK4_like; 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; 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:SF14; G PROTEIN-COUPLED RECEPTOR KINASE 4; 1.
DR   PANTHER; PTHR24355; G PROTEIN-COUPLED RECEPTOR KINASE/RIBOSOMAL PROTEIN S6 KINASE; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   Pfam; PF00615; RGS; 1.
DR   PRINTS; PR00717; GPCRKINASE.
DR   SMART; SM00315; RGS; 1.
DR   SMART; SM00220; S_TKc; 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; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   PROSITE; PS50132; RGS; 1.
DR   Genevisible; P70507; RN.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; ATP-binding; Cytoplasm; Kinase;
KW   Lipoprotein; Nucleotide-binding; Palmitate; Phosphoprotein;
KW   Reference proteome; Serine/threonine-protein kinase; Transferase.
FT   CHAIN           1..575
FT                   /note="G protein-coupled receptor kinase 4"
FT                   /id="PRO_0000085969"
FT   DOMAIN          51..171
FT                   /note="RGS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT   DOMAIN          186..448
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   DOMAIN          449..514
FT                   /note="AGC-kinase C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT   REGION          1..153
FT                   /note="N-terminal"
FT   ACT_SITE        311
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         192..200
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         215
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000250|UniProtKB:P32298"
FT   MOD_RES         484
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   VAR_SEQ         148..178
FT                   /note="Missing (in isoform GRK4B)"
FT                   /evidence="ECO:0000303|PubMed:9607785"
FT                   /id="VSP_010352"
SQ   SEQUENCE   575 AA;  66788 MW;  4328ACD85D718560 CRC64;
     MELENFMANT LLLKARQGFT KKTGRSKKWR ELLKLPPVSM CSDLRHSIEK DFSSLCDQQP
     IGRLLFRQFC NTKPDLKRCI EFLDAAAEYE VTIEEEQREF GLSIYSRFFK ENSEVSLPQI
     PPDLVKECKC NLKQSSPSQN VFQDCAGVIY KYLSEKPFEE YQESTYYNRF LQWKWLERRP
     VTKNTFRQYR VLGKGGFGEV CACQVRATGK MYACKKLEKK RIKKRKGEAM ALNEKRILEK
     LHSRFVVSLA YTYETKDALC LVLTIMNGGD LKYHIYNLGN PGFEEQRAVF YAAELCCGLE
     DLQRERIVYR DLKPENILLD DHGHIRISDL GLALEIPEGE MVRGRVGTVG YMAPEIISHE
     KYTFSPDWWG LGCLIYEMIA GHSPFRKYKE KVNREEMERR VKTETEEYSE RFSENAKSIC
     SMLLTKDPSK RLGCQSDGAS AVKQHPIFKD INFSRLEANM LDPPFCPDPE AIYCKDILDI
     GQFSVVKGVN LDTNDEIFYT QFATGCVTIP WQNEMIESGC FKDLNEYEDK GLSPLEKHKI
     CSCILRPKRN FFHRLFRRAA CLNIAHSEER EPTEH
//