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GRK4

From Wikipedia, the free encyclopedia
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; OMA:GRK4 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000125388Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000052783Ensembl, 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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