GRK4

GRK4
Available structures PDB Ortholog search: PDBe RCSB 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) [1] Band 4p16.3 Start 2,963,571 bp [1] End 3,040,760 bp [1]
Gene location (Mouse) Chr. Chromosome 5 (mouse) [2] Band 5 B2|5 17.91 cM Start 34,660,379 bp [2] End 34,755,305 bp [2]
RNA expression pattern 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 soma 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 PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

G protein-coupled receptor kinase 4 (GRK4) is an enzyme that is encoded by the GRK4 gene in humans. ^[5]

This gene encodes a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinase family, and is most similar to GRK5 and GRK6. ^[6]

G protein-coupled receptor kinases phosphorylate activated G protein-coupled receptors, which promotes the binding of an arrestin protein to the receptor. Arrestin binding to a phosphorylated, active receptor prevents receptor stimulation of heterotrimeric G protein transducer proteins, blocking their cellular signaling and resulting in receptor desensitization. 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. ^[7]

GRK4 is most highly expressed in the testes, with lower amounts found in the brain, kidney and other tissues. It exists in four alternatively-spliced variants. ^[8]

Polymorphisms in the GRK4 gene have been linked to both genetic and acquired hypertension, partly acting through kidney dopamine receptors. ^{[9] [10]}

References

1. GRCh38: Ensembl release 89: ENSG00000125388 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000052783 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Ambrose C, James M, Barnes G, Lin C, Bates G, Altherr M, Duyao M, Groot N, Church D, Wasmuth JJ, et al. (Jun 1993). "A novel G protein-coupled receptor kinase gene cloned from 4p16.3". Hum Mol Genet. 1 (9): 697–703. doi:10.1093/hmg/1.9.697. PMID   1338872.
6. Premont RT, Inglese J, Lefkowitz RJ (1995). "Protein kinases that phosphorylate activated G protein-coupled receptors". FASEB J. 9 (2): 175–182. doi: 10.1096/fasebj.9.2.7781920 . PMID   7781920. S2CID   20428064.
7. Gurevich VV, Gurevich EV (2019). "GPCR Signaling Regulation: The Role of GRKs and Arrestins". Front Pharmacol. 10 125. doi: 10.3389/fphar.2019.00125 . PMC   6389790 . PMID   30837883.
8. Premont RT, Macrae AD, Stoffel RH, et al. (1996). "Characterization of the G protein-coupled receptor kinase GRK4. Identification of four splice variants". J. Biol. Chem. 271 (11): 6403–10. doi: 10.1074/jbc.271.11.6403 . PMID   8626439.
9. Yang J, Villar VA, Jones JE, Jose PA, Zeng C (2015). "G protein-coupled receptor kinase 4: role in hypertension". Hypertension. 65 (6): 1148–1155. doi:10.1161/HYPERTENSIONAHA.115.05189. PMC   6350509 . PMID   25870190.
10. Zhang H, Sun ZQ, Liu SS, Yang LN (2016). "Association between GRK4 and DRD1 gene polymorphisms and hypertension: a meta-analysis". Clin Interv Aging. 11: 17–27. doi: 10.2147/CIA.S94510 . PMC   4694673 . PMID   26730182.

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. Bibcode:1994BBRC..199..848S. doi:10.1006/bbrc.1994.1306. PMID   8135832.
• 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 . PMID   9092566.
• 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 . PMID   10379886.
• 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 . PMID   11517230.
• 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 . PMID   12164861.
• 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. PMC   169056 . PMID   12881416.
• 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. PMID   15097232. S2CID   40225611.
• 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. PMID   16338988. S2CID   509393.
• 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 . PMID   16461192.
• 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 . PMID   16940246.
• 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. PMID   17044852. S2CID   46694387.
• 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. PMID   17259440. S2CID   25145956.