Overview
| Uniprot ID | P25098 |
|---|
| Protein Name | G protein-coupled receptor kinase 2 |
|---|
| Gene Name | GRK2 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 677 |
SPVVELSKVPLVQRG |
Function
Specifically phosphorylates the activated forms of G protein-coupled receptors (PubMed:14976224, PubMed:16179383, PubMed:19306925, PubMed:19715378, PubMed:21799898, PubMed:23077507, PubMed:30284927, PubMed:39138140, PubMed:40384633). Such receptor phosphorylation initiates beta-arrestin-mediated receptor internalization, and signaling events leading to their desensitization (PubMed:14976224, PubMed:16179383, PubMed:19306925, PubMed:19715378, PubMed:21799898, PubMed:23077507, PubMed:30284927, PubMed:39138140, PubMed:40384633). Phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them (PubMed:19715378). Phosphorylates catecholamine-activated ADRB2 to regulate physiological cardiomyocyte contraction rate responses (By similarity). Also phosphorylates ligand-bound C3a and C5a anaphylatoxin receptors (C3AR1 and C5AR1, respectively), leading to receptor desensitization (PubMed:21799898, PubMed:23077507). Positively regulates ciliary smoothened (SMO) signaling pathway by mediating phosphorylation of SMO, facilitating SMO trafficking into the cilium and the stimulation of SMO activity (PubMed:39138140). Also positively regulates SMO signaling by mediating phosphorylation of GPR161, a key inhibitor SMO signaling, promoting ciliary export of GPR161 (PubMed:40384633). Key regulator of LPAR1 signaling (PubMed:19306925). Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor (PubMed:19306925). Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner (PubMed:19306925). Inhibits relaxation of airway smooth muscle in response to blue light (PubMed:30284927)
Protein Sequence
10
MADLEAVLAD
20
VSYLMAMEKS
30
KATPAARASK
40
KILLPEPSIR
50
SVMQKYLEDR
60
GEVTFEKIFS
70
QKLGYLLFRD
80
FCLNHLEEAR
90
PLVEFYEEIK
100
KYEKLETEEE
110
RVARSREIFD
120
SYIMKELLAC
130
SHPFSKSATE
140
HVQGHLGKKQ
150
VPPDLFQPYI
160
EEICQNLRGD
170
VFQKFIESDK
180
FTRFCQWKNV
190
ELNIHLTMND
200
FSVHRIIGRG
210
GFGEVYGCRK
220
ADTGKMYAMK
230
CLDKKRIKMK
240
QGETLALNER
250
IMLSLVSTGD
260
CPFIVCMSYA
270
FHTPDKLSFI
280
LDLMNGGDLH
290
YHLSQHGVFS
300
EADMRFYAAE
310
IILGLEHMHN
320
RFVVYRDLKP
330
ANILLDEHGH
340
VRISDLGLAC
350
DFSKKKPHAS
360
VGTHGYMAPE
370
VLQKGVAYDS
380
SADWFSLGCM
390
LFKLLRGHSP
400
FRQHKTKDKH
410
EIDRMTLTMA
420
VELPDSFSPE
430
LRSLLEGLLQ
440
RDVNRRLGCL
450
GRGAQEVKES
460
PFFRSLDWQM
470
VFLQKYPPPL
480
IPPRGEVNAA
490
DAFDIGSFDE
500
EDTKGIKLLD
510
SDQELYRNFP
520
LTISERWQQE
530
VAETVFDTIN
540
AETDRLEARK
550
KAKNKQLGHE
560
EDYALGKDCI
570
MHGYMSKMGN
580
PFLTQWQRRY
590
FYLFPNRLEW
600
RGEGEAPQSL
610
LTMEEIQSVE
620
ETQIKERKCL
630
LLKIRGGKQF
640
ILQCDSDPEL
650
VQWKKELRDA
660
YREAQQLVQR
670
VPKMKNKPRS
680
PVVELSKVPL
VQRGSANGL
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005929 |
cilium |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0032473 |
cytoplasmic side of mitochondrial outer membrane |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0016020 |
membrane |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Cellular Component |
GO:0098794 |
postsynapse |
| Cellular Component |
GO:0098793 |
presynapse |
| Molecular Function |
GO:0031694 |
alpha-2A adrenergic receptor binding |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0047696 |
beta-adrenergic receptor kinase activity |
| Molecular Function |
GO:0031755 |
Edg-2 lysophosphatidic acid receptor binding |
| Molecular Function |
GO:0001664 |
G protein-coupled receptor binding |
| Molecular Function |
GO:0004703 |
G protein-coupled receptor kinase activity |
| Molecular Function |
GO:0004672 |
protein kinase activity |
| Biological Process |
GO:0060048 |
cardiac muscle contraction |
| Biological Process |
GO:0002029 |
desensitization of G protein-coupled receptor signaling pathway |
| Biological Process |
GO:0007213 |
G protein-coupled acetylcholine receptor signaling pathway |
| Biological Process |
GO:0007186 |
G protein-coupled receptor signaling pathway |
| Biological Process |
GO:1901081 |
negative regulation of relaxation of smooth muscle |
| Biological Process |
GO:0045988 |
negative regulation of striated muscle contraction |
| Biological Process |
GO:0003108 |
negative regulation of the force of heart contraction by chemical signal |
| Biological Process |
GO:0033605 |
positive regulation of catecholamine secretion |
| Biological Process |
GO:0031623 |
receptor internalization |
| Biological Process |
GO:0002026 |
regulation of the force of heart contraction |
| Biological Process |
GO:0046718 |
symbiont entry into host cell |
| Biological Process |
GO:0007217 |
tachykinin receptor signaling pathway |
| Biological Process |
GO:0019079 |
viral genome replication |
Reference
PMID: N/A