GRK4

Available structures

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

MGI: 95801 HomoloGene: 23158 GeneCards: GRK4

Targeted by Drug

balanol^[1]

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 protein signaling pathway • phosphorylation • regulation of rhodopsin mediated signaling pathway • receptor internalization • protein phosphorylation • desensitization of G-protein coupled receptor protein signaling pathway • signal transduction
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

Entrez


2868


14772

Ensembl


ENSG00000125388


ENSMUSG00000052783

UniProt


P32298


O70291

RefSeq (mRNA)


NM_001004056 NM_001004057 NM_005307 NM_182982


NM_001080743 NM_019497

RefSeq (protein)


NP_001004056.1 NP_001004057.1 NP_005298.2 NP_892027.2


NP_001074212.1 NP_062370.2

Location (UCSC)

Chr 4: 2.96 – 3.04 Mb

Chr 5: 34.66 – 34.76 Mb

PubMed search

^[2]

^[3]

Wikidata

View/Edit Human

View/Edit Mouse

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

This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating its deactivation. This gene has been linked to both genetic and acquired hypertension.^[5]

References

↑ "Drugs that physically interact with G protein-coupled receptor kinase 4 view/edit references on wikidata".
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ 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.
1 2 "Entrez Gene: GRK4 G protein-coupled receptor kinase 4".

Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
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. PMID 8135832.
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.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
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.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
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/me.13.6.866. 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.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
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.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Hillier LW, Graves TA, Fulton RS, et al. (2005). "Generation and annotation of the DNA sequences of human chromosomes 2 and 4". Nature. 434 (7034): 724–31. doi:10.1038/nature03466. PMID 15815621.
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.
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.
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.

Kinases: Serine/threonine-specific protein kinases (EC 2.7.11-12)

Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20)

Non-specific serine/threonine protein kinases (EC 2.7.11.1)	LATS1 LATS2 MAST1 MAST2 STK38 STK38L CIT ROCK1 SGK SGK2 SGK3 Protein kinase B AKT1 AKT2 AKT3 Ataxia telangiectasia mutated Mammalian target of rapamycin EIF-2 kinases PKR HRI EIF2AK3 EIF2AK4 Wee1 WEE1

Pyruvate dehydrogenase kinase (EC 2.7.11.2)	PDK1 PDK2 PDK3

Dephospho-(reductase kinase) kinase (EC 2.7.11.3)	AMP-activated protein kinase α PRKAA1 PRKAA2 β PRKAB1 PRKAB2 γ PRKAG1 PRKAG2 PRKAG3

3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase (EC 2.7.11.4)	BCKDK BCKDHA BCKDHB

(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)	IDH2 IDH3A IDH3B IDH3G

(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)	STK4

Myosin-heavy-chain kinase (EC 2.7.11.7)	Aurora kinase Aurora A kinase Aurora B kinase

Fas-activated serine/threonine kinase (EC 2.7.11.8)	FASTK STK10

Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)	-

IκB kinase (EC 2.7.11.10)	CHUK IKK2 TBK1 IKBKE IKBKG IKBKAP

cAMP-dependent protein kinase (EC 2.7.11.11)	Protein kinase A PRKACG PRKACB PRKACA PRKY

cGMP-dependent protein kinase (EC 2.7.11.12)	Protein kinase G PRKG1

Protein kinase C (EC 2.7.11.13)	Protein kinase C Protein kinase Cζ PKC alpha PRKCB1 PRKCD PRKCE PRKCH PRKCG PRKCI PRKCQ Protein kinase N1 PKN2 PKN3

Rhodopsin kinase (EC 2.7.11.14)	Rhodopsin kinase

Beta adrenergic receptor kinase (EC 2.7.11.15)	Beta adrenergic receptor kinase Beta adrenergic receptor kinase-2

G-protein coupled receptor kinases (EC 2.7.11.16)	GRK4 GRK5 GRK6

Ca2+/calmodulin-dependent (EC 2.7.11.17)	BRSK2 CAMK1 CAMK2A CAMK2B CAMK2D CAMK2G CAMK4 MLCK CASK CHEK1 CHEK2 DAPK1 DAPK2 DAPK3 STK11 MAPKAPK2 MAPKAPK3 MAPKAPK5 MARK1 MARK2 MARK3 MARK4 MELK MKNK1 MKNK2 NUAK1 NUAK2 OBSCN PASK PHKG1 PHKG2 PIM1 PIM2 PKD1 PRKD2 PRKD3 PSKH1 SNF1LK2 KIAA0999 STK40 SNF1LK SNRK SPEG TSSK2 Kalirin TRIB1 TRIB2 TRIB3 TRIO Titin DCLK1

Myosin light-chain kinase (EC 2.7.11.18)	MYLK MYLK2 MYLK3 MYLK4

Phosphorylase kinase (EC 2.7.11.19)	PHKA1 PHKA2 PHKB PHKG1 PHKG2

Elongation factor 2 kinase (EC 2.7.11.20)	EEF2K STK19

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Cyclin-dependent kinase (EC 2.7.11.22)	CDK1 CDK2 CDKL2 CDK3 CDK4 CDK5 CDKL5 CDK6 CDK7 CDK8 CDK9 CDK10 CDK12 CDC2L5 PCTK1 PCTK2 PCTK3 PFTK1 CDC2L1

(RNA-polymerase)-subunit kinase (EC 2.7.11.23)	RPS6KA5 RPS6KA4 P70S6 kinase P70-S6 Kinase 1 RPS6KB2 RPS6KA2 RPS6KA3 RPS6KA1 RPS6KC1

Mitogen-activated protein kinase (EC 2.7.11.24)	Extracellular signal-regulated MAPK1 MAPK3 MAPK4 MAPK6 MAPK7 MAPK12 MAPK15 C-Jun N-terminal MAPK8 MAPK9 MAPK10 P38 mitogen-activated protein MAPK11 MAPK13 MAPK14

MAP3K (EC 2.7.11.25)	MAP kinase kinase kinases MAP3K1 MAP3K2 MAP3K3 MAP3K4 MAP3K5 MAP3K6 MAP3K7 MAP3K8 RAFs ARAF BRAF KSR1 KSR2 MLKs MAP3K12 MAP3K13 MAP3K9 MAP3K10 MAP3K11 MAP3K7 ZAK CDC7 MAP3K14

Tau-protein kinase (EC 2.7.11.26)	TPK1 TTK GSK-3

(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)	-

Tropomyosin kinase (EC 2.7.11.28)	-

Low-density-lipoprotein receptor kinase (EC 2.7.11.29)	-

Receptor protein serine/threonine kinase (EC 2.7.11.30)	Bone morphogenetic protein receptors BMPR1 BMPR1A BMPR1B BMPR2 ACVR1 ACVR1B ACVR1C ACVR2A ACVR2B ACVRL1 Anti-Müllerian hormone receptor

Dual-specificity kinases (EC 2.7.12)

MAP2K	MAP2K1 MAP2K2 MAP2K3 MAP2K4 MAP2K5 MAP2K6 MAP2K7

Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

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GRK4

References

Further reading