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Overview

Uniprot IDP26817
Protein NameG protein-coupled receptor kinase 2
Gene NameGrk2
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
448 GRGAQEIKESPFFRS
545 ARKKAKNKQLGHEED

Function

Specifically phosphorylates the activated forms of G protein-coupled receptors (PubMed:1403099). Such receptor phosphorylation initiates beta-arrestin-mediated receptor internalization, and signaling events leading to their desensitization (PubMed:1403099). Phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them (PubMed:1403099). 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 (By similarity). Key regulator of LPAR1 signaling (By similarity). Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor (By similarity). Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner (By similarity). Positively regulates ciliary smoothened (SMO) signaling pathway by mediating phosphorylation of SMO, facilitating SMO trafficking into the cilium and the stimulation of SMO activity (By similarity). Also positively regulates SMO signaling by mediating phosphorylation of GPR161, a key inhibitor SMO signaling, promoting ciliary export of GPR161 (By similarity). Inhibits relaxation of airway smooth muscle in response to blue light (By similarity)

Protein Sequence

10 MADLEAVLAD 20 VSYLMAMEKS 30 KATPAARASK 40 KILLPEPSIR 50 SVMQKYLEDR 60 GEVTFEKIFS 70 QKLGYLLFRD 80 FYLNHLEEAK 90 PLVEFYEEIE 100 KYEKLETEEE 110 RVVRSREIFD 120 SYIMKELLAC 130 SHPFSKNATE 140 HVQGHLVKKQ 150 VPPDLFQPYI 160 EEICQNLRGD 170 VFHKFIESDK 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 GRGAQEIKES 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 RGEDEAPQSL 610 LTMEEIQSVE 620 ETQIKERKCL 630 LLKIRGGKQF 640 VLQCDSDPEL 650 VQWKKELRDA 660 YREAQQLVQR 670 VPKMKNKPRS 680 PVVELSKVPL IQRGSANGL

Gene Ontology

Classification GO ID Description
Cellular Component GO:0016324 apical plasma membrane
Cellular Component GO:0043679 axon terminus
Cellular Component GO:0016323 basolateral plasma membrane
Cellular Component GO:0005901 caveola
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0032473 cytoplasmic side of mitochondrial outer membrane
Cellular Component GO:0005829 cytosol
Cellular Component GO:0043198 dendritic shaft
Cellular Component GO:0043197 dendritic spine
Cellular Component GO:0098978 glutamatergic synapse
Cellular Component GO:0016020 membrane
Cellular Component GO:0043025 neuronal cell body
Cellular Component GO:0005634 nucleus
Cellular Component GO:0014069 postsynaptic density
Cellular Component GO:0098793 presynapse
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0047696 beta-adrenergic receptor kinase activity
Molecular Function GO:0031850 delta-type opioid receptor binding
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:0031851 kappa-type opioid receptor binding
Molecular Function GO:0004672 protein kinase activity
Molecular Function GO:0004674 protein serine/threonine kinase activity
Molecular Function GO:0097110 scaffold protein binding
Molecular Function GO:0031625 ubiquitin protein ligase binding
Biological Process GO:0060048 cardiac muscle contraction
Biological Process GO:0071870 cellular response to catecholamine stimulus
Biological Process GO:1990869 cellular response to chemokine
Biological Process GO:0071364 cellular response to epidermal growth factor stimulus
Biological Process GO:0071333 cellular response to glucose stimulus
Biological Process GO:1904628 cellular response to phorbol 13-acetate 12-myristate
Biological Process GO:0072752 cellular response to rapamycin
Biological Process GO:0002029 desensitization of G protein-coupled receptor signaling pathway
Biological Process GO:0042699 follicle-stimulating hormone signaling pathway
Biological Process GO:0007186 G protein-coupled receptor signaling pathway
Biological Process GO:0007507 heart development
Biological Process GO:0051457 maintenance of protein location in nucleus
Biological Process GO:0106072 negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway
Biological Process GO:0043066 negative regulation of apoptotic process
Biological Process GO:2001234 negative regulation of apoptotic signaling pathway
Biological Process GO:1900077 negative regulation of cellular response to insulin stimulus
Biological Process GO:0046325 negative regulation of D-glucose import across plasma membrane
Biological Process GO:0033137 negative regulation of peptidyl-serine phosphorylation
Biological Process GO:0010801 negative regulation of peptidyl-threonine phosphorylation
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:0048709 oligodendrocyte differentiation
Biological Process GO:0018105 peptidyl-serine phosphorylation
Biological Process GO:0018107 peptidyl-threonine phosphorylation
Biological Process GO:0033605 positive regulation of catecholamine secretion
Biological Process GO:0070374 positive regulation of ERK1 and ERK2 cascade
Biological Process GO:2000463 positive regulation of excitatory postsynaptic potential
Biological Process GO:0048146 positive regulation of fibroblast proliferation
Biological Process GO:0032755 positive regulation of interleukin-6 production
Biological Process GO:0010661 positive regulation of muscle cell apoptotic process
Biological Process GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation
Biological Process GO:0045907 positive regulation of vasoconstriction
Biological Process GO:0006468 protein phosphorylation
Biological Process GO:0031623 receptor internalization
Biological Process GO:0032960 regulation of inositol trisphosphate biosynthetic process
Biological Process GO:0002026 regulation of the force of heart contraction
Biological Process GO:0061771 response to caloric restriction
Biological Process GO:0042542 response to hydrogen peroxide
Biological Process GO:0044321 response to leptin
Biological Process GO:0014850 response to muscle activity
Biological Process GO:0006979 response to oxidative stress
Biological Process GO:0046718 symbiont entry into host cell
Biological Process GO:0007217 tachykinin receptor signaling pathway
Biological Process GO:0042311 vasodilation
Biological Process GO:0019079 viral genome replication

Reference

[1] Yao Y, Bade R, Li G, Zhang A, Zhao H et al.. Global-Scale Profiling of Differential Expressed Lysine-Lactylated Proteins in the Cerebral Endothelium of Cerebral Ischemia-Reperfusion Injury Rats.. Cell Mol Neurobiol 43(5):1989-2004. 2023 Jul. PMID: 36030297.

[2] Chen Y, Sun W, Sun Z, Zhao H, Wu T et al.. Effect of electroacupuncture on hippocampal protein lactylation in a rat model of vascular dementia.. Front Neurol 16:1629474. 2025. PMID: 40963935.