GRK4

GRK4
Available structures PDB Ortholog search:PDBeRCSB List of PDB id codes 4YHJ
Identifiers
Aliases	GRK4,GPRK2L, GPRK4, GRK4a, IT11, G protein-coupled receptor kinase 4
External IDs	OMIM:137026;MGI:95801;HomoloGene:23158;GeneCards:GRK4;OMA:GRK4 - orthologs
Gene location (Human) Chr. Chromosome 4 (human) Band 4p16.3 Start 2,963,571bp End 3,040,760bp
Gene location (Mouse) Chr. Chromosome 5 (mouse) Band 5 B2|5 17.91 cM Start 34,660,379bp End 34,755,305bp
RNA expressionpattern Bgee Human Mouse(ortholog) Top expressed in left testis sperm right testis cerebellar hemisphere right hemisphere of cerebellum apex of heart C1 segment anterior pituitary right frontal lobe cingulate gyrus Top expressed in spermatid spermatocyte seminiferous tubule granulocyte neural layer of retina retinal pigment epithelium zygote morula epithelium of lens right kidney More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding protein kinase activity G protein-coupled receptor kinase activity kinase activity protein serine/threonine kinase activity ATP binding rhodopsin kinase activity Cellular component cytoplasm cytosol neuronal cell body dendrite cell cortex photoreceptor disc membrane Biological process G protein-coupled receptor internalization regulation of G protein-coupled receptor signaling pathway phosphorylation regulation of rhodopsin mediated signaling pathway receptor internalization protein phosphorylation desensitization of G protein-coupled receptor signaling pathway signal transduction Sources:Amigo/QuickGO
Orthologs Species Human Mouse Entrez 2868 14772 Ensembl ENSG00000125388 ENSMUSG00000052783 UniProt P32298 O70291 RefSeq (mRNA) NM_001004056 NM_001004057 NM_005307 NM_182982 NM_001350173 NM_001080743 NM_019497 RefSeq (protein) NP_001004056 NP_001004057 NP_005298 NP_892027 NP_001337102 NP_001074212 NP_062370 Location (UCSC) Chr 4: 2.96 – 3.04 Mb Chr 5: 34.66 – 34.76 Mb PubMedsearch
Wikidata
View/Edit Human View/Edit Mouse

G protein-coupled receptor kinase 4(GRK4) is anenzymethat is encoded by theGRK4genein humans.

This gene encodes a member of theG protein-coupled receptor kinasesubfamily of the Ser/Thrprotein kinasefamily, and is most similar toGRK5andGRK6.

G protein-coupled receptor kinasesphosphorylateactivatedG protein-coupled receptors,which promotes the binding of anarrestinprotein to the receptor. Arrestin binding to a phosphorylated, active receptor prevents receptor stimulation ofheterotrimeric G proteintransducer proteins, blocking their cellular signaling and resulting in receptordesensitization.Moreover Arrestin binding to a phosphorylated, active receptor also enables receptor signaling through arrestin partner proteins. Consequently the GRK/arrestin system serves as a signaling switch for G protein-coupled receptors.

GRK4 is most highly expressed in thetestes,with lower amounts found in thebrain,kidneyand other tissues. It exists in fouralternatively-splicedvariants.

Polymorphismsin the GRK4 gene have been linked to both genetic and acquiredhypertension,partly acting through kidneydopaminereceptors.

Further reading

• Sallese M, Lombardi MS, De Blasi A (1994). "Two isoforms of G protein-coupled receptor kinase 4 identified by molecular cloning".Biochem. Biophys. Res. Commun.199(2): 848–54.doi:10.1006/bbrc.1994.1306.PMID8135832.
• Sallese M, Mariggiò S, Collodel G, et al. (1997)."G protein-coupled receptor kinase GRK4. Molecular analysis of the four isoforms and ultrastructural localization in spermatozoa and germinal cells".J. Biol. Chem.272(15): 10188–95.doi:10.1074/jbc.272.15.10188.PMID9092566.
• Lazari MF, Liu X, Nakamura K, et al. (1999)."Role of G protein-coupled receptor kinases on the agonist-induced phosphorylation and internalization of the follitropin receptor".Mol. Endocrinol.13(6): 866–78.doi:10.1210/mend.13.6.0289.PMID10379886.
• Blaukat A, Pizard A, Breit A, et al. (2001)."Determination of bradykinin B2 receptor in vivo phosphorylation sites and their role in receptor function".J. Biol. Chem.276(44): 40431–40.doi:10.1074/jbc.M107024200.PMID11517230.
• Watanabe H, Xu J, Bengra C, et al. (2003)."Desensitization of human renal D1 dopamine receptors by G protein-coupled receptor kinase 4".Kidney Int.62(3): 790–8.doi:10.1046/j.1523-1755.2002.00525.x.PMID12164861.
• Perroy J, Adam L, Qanbar R, et al. (2003)."Phosphorylation-independent desensitization of GABAB receptor by GRK4".EMBO J.22(15): 3816–24.doi:10.1093/emboj/cdg383.PMC169056.PMID12881416.
• Speirs HJ, Katyk K, Kumar NN, et al. (2004). "Association of G-protein-coupled receptor kinase 4 haplotypes, but not HSD3B1 or PTP1B polymorphisms, with essential hypertension".J. Hypertens.22(5): 931–6.doi:10.1097/00004872-200405000-00014.PMID15097232.S2CID40225611.
• Rankin ML, Marinec PS, Cabrera DM, et al. (2006). "The D1 dopamine receptor is constitutively phosphorylated by G protein-coupled receptor kinase 4".Mol. Pharmacol.69(3): 759–69.doi:10.1124/mol.105.019901.PMID16338988.S2CID509393.
• Zhu H, Lu Y, Wang X, et al. (2006)."The G protein-coupled receptor kinase 4 gene affects blood pressure in young normotensive twins".Am. J. Hypertens.19(1): 61–6.doi:10.1016/j.amjhyper.2005.07.007.PMID16461192.
• Zhu H, Lu Y, Wang X, et al. (2006)."The G protein-coupled receptor kinase 4 gene modulates stress-induced sodium excretion in black normotensive adolescents".Pediatr. Res.60(4): 440–2.doi:10.1203/01.pdr.0000238250.64591.44.PMID16940246.
• Wang Y, Li B, Zhao W, et al. (2006). "Association study of G protein-coupled receptor kinase 4 gene variants with essential hypertension in northern Han Chinese".Ann. Hum. Genet.70(Pt 6): 778–83.doi:10.1111/j.1469-1809.2006.00278.x.PMID17044852.S2CID46694387.
• Wang Z, Armando I, Asico LD, et al. (2007). "The elevated blood pressure of human GRK4gamma A142V transgenic mice is not associated with increased ROS production".Am. J. Physiol. Heart Circ. Physiol.292(5): H2083–92.doi:10.1152/ajpheart.00944.2006.PMID17259440.S2CID25145956.