CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-006404
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 G protein-coupled receptor kinase 5 
Protein Synonyms/Alias
 G protein-coupled receptor kinase GRK5 
Gene Name
 GRK5 
Gene Synonyms/Alias
 GPRK5 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
14VANTVLLKAREGGGGubiquitination[1]
443EEGAAEVKRHPFFRNubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein- coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their down-regulation. Phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, also phosphorylates various substrates: Hsc70- interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and allowing MEF2- mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates internalization of the chemokine receptor. Phosphorylates rhodopsin (RHO) (in vitro) and a non G- protein-coupled receptor, LRP6 during Wnt signaling (in vitro). 
Sequence Annotation
 DOMAIN 53 171 RGS.
 DOMAIN 186 448 Protein kinase.
 DOMAIN 449 514 AGC-kinase C-terminal.
 NP_BIND 192 200 ATP (By similarity).
 REGION 1 185 N-terminal.
 REGION 20 39 Interaction with calmodulin.
 REGION 546 565 Sufficient for membrane localization.
 MOTIF 388 395 Nuclear localization signal.
 ACT_SITE 311 311 Proton acceptor (By similarity).
 BINDING 215 215 ATP (By similarity).
 MOD_RES 484 484 Phosphoserine; by autocatalysis.
 MOD_RES 485 485 Phosphothreonine; by autocatalysis.  
Keyword
 Apoptosis; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Kinase; Lipid-binding; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase; Wnt signaling pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 590 AA 
Protein Sequence
MELENIVANT VLLKAREGGG GKRKGKSKKW KEILKFPHIS QCEDLRRTID RDYCSLCDKQ 60
PIGRLLFRQF CETRPGLECY IQFLDSVAEY EVTPDEKLGE KGKEIMTKYL TPKSPVFIAQ 120
VGQDLVSQTE EKLLQKPCKE LFSACAQSVH EYLRGEPFHE YLDSMFFDRF LQWKWLERQP 180
VTKNTFRQYR VLGKGGFGEV CACQVRATGK MYACKRLEKK RIKKRKGESM ALNEKQILEK 240
VNSQFVVNLA YAYETKDALC LVLTIMNGGD LKFHIYNMGN PGFEEERALF YAAEILCGLE 300
DLHRENTVYR DLKPENILLD DYGHIRISDL GLAVKIPEGD LIRGRVGTVG YMAPEVLNNQ 360
RYGLSPDYWG LGCLIYEMIE GQSPFRGRKE KVKREEVDRR VLETEEVYSH KFSEEAKSIC 420
KMLLTKDAKQ RLGCQEEGAA EVKRHPFFRN MNFKRLEAGM LDPPFVPDPR AVYCKDVLDI 480
EQFSTVKGVN LDHTDDDFYS KFSTGSVSIP WQNEMIETEC FKELNVFGPN GTLPPDLNRN 540
HPPEPPKKGL LQRLFKRQHQ NNSKSSPSSK TSFNHHINSN HVSSNSTGSS 590 
Gene Ontology
 GO:0005737; C:cytoplasm; TAS:ProtInc.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0005886; C:plasma membrane; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004703; F:G-protein coupled receptor kinase activity; IEA:EC.
 GO:0005543; F:phospholipid binding; TAS:ProtInc.
 GO:0005080; F:protein kinase C binding; TAS:ProtInc.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0007188; P:adenylate cyclase-modulating G-protein coupled receptor signaling pathway; TAS:ProtInc.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
 GO:0008277; P:regulation of G-protein coupled receptor protein signaling pathway; TAS:ProtInc.
 GO:0007217; P:tachykinin receptor signaling pathway; IDA:BHF-UCL.
 GO:0038032; P:termination of G-protein coupled receptor signaling pathway; IEA:InterPro.
 GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW. 
Interpro
 IPR000961; AGC-kinase_C.
 IPR000239; GPCR_kinase.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR000342; Regulat_G_prot_signal.
 IPR016137; Regulat_G_prot_signal_superfam.
 IPR002290; Ser/Thr_dual-sp_kinase_dom. 
Pfam
 PF00069; Pkinase
 PF00615; RGS 
SMART
 SM00315; RGS
 SM00133; S_TK_X
 SM00220; S_TKc 
PROSITE
 PS51285; AGC_KINASE_CTER
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST
 PS50132; RGS 
PRINTS
 PR00717; GPCRKINASE.