GRK4
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGRK4, GPRK2L, GPRK4, GRK4a, IT11, G protein-coupled receptor kinase 4
External IDsOMIM: 137026 MGI: 95801 HomoloGene: 23158 GeneCards: GRK4
Orthologs
SpeciesHumanMouse
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 MbChr 5: 34.66 – 34.76 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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. 1 2 3 GRCh38: Ensembl release 89: ENSG00000125388 - Ensembl, May 2017
  2. 1 2 3 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


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