GRK5
entrez
2869
canonical
uniprot
P34947
canonical
ensembl
ENSG00000198873
resolver
ensp
ENSP00000376609
resolver
enst
ENST00000392870
resolver
genesymbol
GRK5
resolver
genesymbol_syn
GPRK5
resolver
hgnc
HGNC:4544
resolver
uniprot
D3DRD0
resolver
uniprot
Q5T059
resolver
uniprot_entry
GRK5_HUMAN
resolver
uniprot_sec
D3DRD0
resolver
uniprot_sec
Q5T059
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by calmodulin with an IC(50) of 50 nM. Calmodulin inhibits GRK5 association with receptor and phospholipid. {ECO:0000269|PubMed:9218466}.
uniprot
proteins
amino_acid_sequence
MELENIVANTVLLKAREGGGGKRKGKSKKWKEILKFPHISQCEDLRRTIDRDYCSLCDKQPIGRLLFRQFCETRPGLECYIQFLDSVAEYEVTPDEKLGEKGKEIMTKYLTPKSPVFIAQVGQDLVSQTEEKLLQKPCKELFSACAQSVHEYLRGEPFHEYLDSMFFDRFLQWKWLERQPVTKNTFRQYRVLGKGGFGEVCACQVRATGKMYACKRLEKKRIKKRKGESMALNEKQILEKVNSQFVVNLAYAYETKDALCLVLTIMNGGDLKFHIYNMGNPGFEEERALFYAAEILCGLEDLHRENTVYRDLKPENILLDDYGHIRISDLGLAVKIPEGDLIRGRVGTVGYMAPEVLNNQRYGLSPDYWGLGCLIYEMIEGQSPFRGRKEKVKREEVDRRVLETEEVYSHKFSEEAKSICKMLLTKDAKQRLGCQEEGAAEVKRHPFFRNMNFKRLEAGMLDPPFVPDPRAVYCKDVLDIEQFSTVKGVNLDHTDDDFYSKFSTGSVSIPWQNEMIETECFKELNVFGPNGTLPPDLNRNHPPEPPKKGLLQRLFKRQHQNNSKSSPSSKTSFNHHINSNHVSSNSTGSS
uniprot
proteins
ec_number
2.7.11.16
uniprot
proteins
function
FUNCTION: 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). {ECO:0000269|PubMed:19661922, ECO:0000269|PubMed:19801552, ECO:0000269|PubMed:20038610, ECO:0000269|PubMed:20124405, ECO:0000269|PubMed:21728385}.
uniprot
proteins
mass_dalton
67787
uniprot
proteins
mutagenesis
MUTAGEN 215; /note="K->R: Failed to phosphorylate p53/TP53."; /evidence="ECO:0000269|PubMed:20124405"; MUTAGEN 388; /note="R->A: Nuclear exclusion; when associated with A-389; A-391; A-393 and A-394."; /evidence="ECO:0000269|PubMed:15542828"; MUTAGEN 389; /note="K->A: Nuclear exclusion; when associated with A-388; A-391; A-393 and A-394."; /evidence="ECO:0000269|PubMed:15542828"; MUTAGEN 391; /note="K->A: Nuclear exclusion; when associated with A-388; A-389; A-393 and A-394."; /evidence="ECO:0000269|PubMed:15542828"; MUTAGEN 393; /note="K->A: Nuclear exclusion; when associated with A-388; A-389; A-391 and A-394."; /evidence="ECO:0000269|PubMed:15542828"; MUTAGEN 394; /note="R->A: Nuclear exclusion; when associated with A-388; A-389; A-391 and A-393."; /evidence="ECO:0000269|PubMed:15542828"; MUTAGEN 484; /note="S->A: 15-20 fold defects in kinase activity; when associated with A-485."; /evidence="ECO:0000269|PubMed:8144599"; MUTAGEN 485; /note="T->A: 15-20 fold defects in kinase activity; when associated with A-484."; /evidence="ECO:0000269|PubMed:8144599"; MUTAGEN 550; /note="L->A: No detectable plasma membrane localization; when associated with A-551; A-554; and A-555."; /evidence="ECO:0000269|PubMed:14976207"; MUTAGEN 551; /note="L->A: No detectable plasma membrane localization; when associated with A-550; A-554; and A-555."; /evidence="ECO:0000269|PubMed:14976207"; MUTAGEN 554; /note="L->A: No detectable plasma membrane localization; when associated with A-550; A-551; and A-555."; /evidence="ECO:0000269|PubMed:14976207"; MUTAGEN 555; /note="F->A: No detectable plasma membrane localization; when associated with A-550; A-551; and A-554."; /evidence="ECO:0000269|PubMed:14976207
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated. Autophosphorylation may play a critical role in the regulation of GRK5 kinase activity. {ECO:0000269|PubMed:8144599}.
uniprot
proteins
protein_family
AGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
GPRK subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
14976207
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15542828
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
18425130
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19661922
uniprot
proteins
pubmed
19801552
uniprot
proteins
pubmed
20038610
uniprot
proteins
pubmed
20124405
uniprot
proteins
pubmed
21728385
uniprot
proteins
pubmed
7685906
uniprot
proteins
pubmed
8144599
uniprot
proteins
pubmed
8381058
uniprot
proteins
pubmed
9218466
uniprot
proteins
sequence_length
590
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell membrane; Peripheral membrane protein. Note=Predominantly localized at the plasma membrane; targeted to the cell surface through the interaction with phospholipids. Nucleus localization is regulated in a GPCR and Ca(2+)/calmodulin-dependent fashion.
uniprot
proteins