GRK4_RAT
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 03-AUG-2022, entry version 146.
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; P70507; -.
DR PRIDE; P70507; -.
DR Ensembl; ENSRNOT00000015894; ENSRNOP00000015894; ENSRNOG00000011847. [P70507-1]
DR Ensembl; ENSRNOT00000094171; ENSRNOP00000088283; ENSRNOG00000011847. [P70507-2]
DR GeneID; 59077; -.
DR KEGG; rno:59077; -.
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 OMA; EVCFKSD; -.
DR OrthoDB; 1104340at2759; -.
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 tissues.
DR Genevisible; P70507; RN.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
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:0004703; F:G protein-coupled receptor kinase activity; IEA:UniProtKB-EC.
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: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:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 1.10.167.10; -; 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 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; SSF48097; SSF48097; 1.
DR SUPFAM; SSF56112; SSF56112; 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.
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
