GRK5_BOVIN
ID GRK5_BOVIN Reviewed; 590 AA.
AC P43249;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=G protein-coupled receptor kinase 5;
DE EC=2.7.11.16;
DE AltName: Full=G protein-coupled receptor kinase GRK5;
GN Name=GRK5; Synonyms=GPRK5;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 479-491, TISSUE
RP SPECIFICITY, FUNCTION, AND PHOSPHORYLATION AT SER-484 AND THR-485.
RC TISSUE=Tongue epithelium;
RX PubMed=8120045; DOI=10.1016/s0021-9258(17)37451-3;
RA Premont R.T., Koch W.J., Inglese J., Lefkowitz R.J.;
RT "Identification, purification, and characterization of GRK5, a member of
RT the family of G protein-coupled receptor kinases.";
RL J. Biol. Chem. 269:6832-6841(1994).
CC -!- FUNCTION: Serine/threonine kinase that phosphorylates preferentially
CC the activated forms of a variety of G-protein-coupled receptors
CC (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated
CC receptor desensitization, internalization, and signaling events leading
CC to their down-regulation. Phosphorylates a variety of GPCRs, including
CC adrenergic receptors (Beta-2 adrenergic receptor), muscarinic
CC acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes),
CC dopamine receptors and opioid receptors. In addition to GPCRs, also
CC phosphorylates various substrates: Hsc70-interacting protein/ST13,
CC TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5
CC inhibits G-protein independent MAPK1/MAPK3 signaling downstream of
CC 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte
CC enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and
CC allowing MEF2-mediated transcription. Phosphorylation of TP53/p53, a
CC crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis.
CC Phosphorylation of ST13 regulates internalization of the chemokine
CC receptor. Phosphorylates rhodopsin (RHO) (in vitro) and a non G-
CC protein-coupled receptor, LRP6 during Wnt signaling (in vitro) (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:8120045}.
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 calmodulin with an IC(50) of 50 nM.
CC Calmodulin inhibits GRK5 association with receptor and phospholipid (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with ST13 (via the C-terminus 303-319 AA) (By
CC similarity). Interacts with TP53/p53 (By similarity). Interacts with
CC HTR4 (via C-terminus 330-346 AA); this interaction is promoted by 5-HT
CC (serotonin) (By similarity). Interacts with HDAC5 (By similarity).
CC Interacts with GIT1 (By similarity). {ECO:0000250|UniProtKB:P34947,
CC ECO:0000250|UniProtKB:Q62833, ECO:0000250|UniProtKB:Q8VEB1}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
CC Note=Predominantly localized at the plasma membrane, targeted to the
CC cell surface through the interaction with phospholipids. Nucleus
CC localization is regulated in a GPCR and Ca(2+)/calmodulin-dependent
CC fashion (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highest levels in lung, heart, retina, lingual
CC epithelium. Very little in brain, liver, kidney.
CC {ECO:0000269|PubMed:8120045}.
CC -!- PTM: Autophosphorylated. Autophosphorylation may play a critical role
CC in the regulation of GRK5 kinase activity.
CC {ECO:0000269|PubMed:8120045}.
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; U01206; AAA17561.1; -; mRNA.
DR PIR; A54372; A54372.
DR RefSeq; NP_776756.1; NM_174331.2.
DR PDB; 4WNK; X-ray; 2.42 A; A=1-590.
DR PDBsum; 4WNK; -.
DR AlphaFoldDB; P43249; -.
DR SMR; P43249; -.
DR DIP; DIP-60782N; -.
DR IntAct; P43249; 2.
DR STRING; 9913.ENSBTAP00000010492; -.
DR BindingDB; P43249; -.
DR ChEMBL; CHEMBL3879830; -.
DR iPTMnet; P43249; -.
DR PaxDb; P43249; -.
DR PRIDE; P43249; -.
DR Ensembl; ENSBTAT00000071544; ENSBTAP00000073444; ENSBTAG00000007981.
DR GeneID; 281801; -.
DR KEGG; bta:281801; -.
DR CTD; 2869; -.
DR VEuPathDB; HostDB:ENSBTAG00000007981; -.
DR VGNC; VGNC:29656; GRK5.
DR eggNOG; KOG0986; Eukaryota.
DR GeneTree; ENSGT00940000160702; -.
DR HOGENOM; CLU_000288_63_41_1; -.
DR InParanoid; P43249; -.
DR OMA; YIVNRIF; -.
DR OrthoDB; 1104340at2759; -.
DR TreeFam; TF313940; -.
DR BRENDA; 2.7.11.16; 908.
DR Proteomes; UP000009136; Chromosome 26.
DR Bgee; ENSBTAG00000007981; Expressed in esophagus and 103 other tissues.
DR ExpressionAtlas; P43249; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0031965; C:nuclear membrane; IEA:Ensembl.
DR GO; GO:0016607; C:nuclear speck; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0047696; F:beta-adrenergic receptor kinase activity; IEA:Ensembl.
DR GO; GO:0004703; F:G protein-coupled receptor kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl.
DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central.
DR GO; GO:0007217; P:tachykinin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
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; 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; 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 3D-structure; Apoptosis; ATP-binding; Cell membrane; Cytoplasm;
KW Direct protein sequencing; Kinase; Lipid-binding; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Wnt signaling pathway.
FT CHAIN 1..590
FT /note="G protein-coupled receptor kinase 5"
FT /id="PRO_0000085970"
FT DOMAIN 53..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..185
FT /note="N-terminal"
FT REGION 20..39
FT /note="Interaction with calmodulin"
FT /evidence="ECO:0000250"
FT REGION 532..590
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 546..565
FT /note="Sufficient for membrane localization"
FT /evidence="ECO:0000250"
FT MOTIF 388..395
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 555..590
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 484
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8120045"
FT MOD_RES 485
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8120045"
FT MOD_RES 579
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VEB1"
FT HELIX 30..33
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 39..42
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 43..47
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 53..57
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 61..72
FT /evidence="ECO:0007829|PDB:4WNK"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 78..91
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 98..109
FT /evidence="ECO:0007829|PDB:4WNK"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 123..135
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 143..153
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 156..163
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 165..177
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:4WNK"
FT STRAND 186..194
FT /evidence="ECO:0007829|PDB:4WNK"
FT STRAND 196..205
FT /evidence="ECO:0007829|PDB:4WNK"
FT TURN 206..208
FT /evidence="ECO:0007829|PDB:4WNK"
FT STRAND 211..218
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 219..224
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 228..240
FT /evidence="ECO:0007829|PDB:4WNK"
FT STRAND 249..254
FT /evidence="ECO:0007829|PDB:4WNK"
FT STRAND 256..263
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 271..275
FT /evidence="ECO:0007829|PDB:4WNK"
FT STRAND 277..280
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 285..304
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 314..316
FT /evidence="ECO:0007829|PDB:4WNK"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:4WNK"
FT STRAND 325..327
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 354..357
FT /evidence="ECO:0007829|PDB:4WNK"
FT STRAND 362..364
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 365..380
FT /evidence="ECO:0007829|PDB:4WNK"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 394..403
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 414..423
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 428..430
FT /evidence="ECO:0007829|PDB:4WNK"
FT TURN 436..438
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 439..443
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 446..448
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 453..457
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 494..502
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 508..517
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 520..524
FT /evidence="ECO:0007829|PDB:4WNK"
FT STRAND 529..531
FT /evidence="ECO:0007829|PDB:4WNK"
FT HELIX 535..537
FT /evidence="ECO:0007829|PDB:4WNK"
SQ SEQUENCE 590 AA; 67889 MW; E8F353697D8BA6E2 CRC64;
MELENIVANT VLLKAREGGG GKRKGKSKKW KEILKFPHIN QCEDLRRTID RDYCSLCDKQ
PVGRLLFRQF CETRPGLESY IQFLDSVAEY EVTPDEKLGE KGKEIMTKYL TPKSPVFITQ
VGRDLVSQTE EKLLQKPCKE LFSACVQSVH DYLRGEPFHE YLDSMYFDRF LQWKWLERQP
VTKNTFRQYR VLGKGGFGEV CACQVRATGK MYACKRLEKK RIKKRKGESM ALNEKQILEK
VNSRFVVNLA YAYETKDALC LVLTIMNGGD LKFHIYNMGN PGFEEERALF YAAEILCGLE
DLHHENIVYR DLKPENILLD DYGHIRISDL GLAVKIPEGD LIRGRVGTVG YMAPEVLNNQ
RYGLSPDYWG LGCLIYEMIE GQSPFRGRKE KVKREEVDRR VLETEEVYSH KFSEEAKSIC
KMLLTKDAKQ RLGCQEEGAA EVKRHPFFRN MNFKRLEAGM LDPPFVPDPR AVYCKDVLDI
EQFSTVKGVN LDHTDDDFYS KFSTGSVPIP WQSEMIETEC FKELNVFGPH GTLSPDLNRS
HPPEPPKKGL LQRLFKRQHQ NNSKSSPNSK TSFNHHINSN HVSSNSTGSS
