Recombinant Human G protein-coupled receptor kinase 4 (GRK4)

Code CSB-YP009925HU
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Source Yeast
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Code CSB-EP009925HU
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Source E.coli
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Code CSB-EP009925HU-B
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Source E.coli
Conjugate Avi-tag Biotinylated
E. coli biotin ligase (BirA) is highly specific in covalently attaching biotin to the 15 amino acid AviTag peptide. This recombinant protein was biotinylated in vivo by AviTag-BirA technology, which method is BriA catalyzes amide linkage between the biotin and the specific lysine of the AviTag.
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Code CSB-BP009925HU
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Source Baculovirus
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Code CSB-MP009925HU
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Source Mammalian cell
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Product Details

Purity
>85% (SDS-PAGE)
Target Names
GRK4
Uniprot No.
Alternative Names
G protein coupled receptor kinase 4; G protein-coupled receptor kinase 2 (Drosophila)-like; G protein-coupled receptor kinase 4; G protein-coupled receptor kinase GRK4; G proteinm coupled receptor kinase GRK4; GPRK2L; GPRK4; GRK4; GRK4_HUMAN; GRK4a; ITI1
Species
Homo sapiens (Human)
Expression Region
1-578
Target Protein Sequence
MELENIVANS LLLKARQGGY GKKSGRSKKW KEILTLPPVS QCSELRHSIE KDYSSLCDKQ PIGRRLFRQF CDTKPTLKRH IEFLDAVAEY EVADDEDRSD CGLSILDRFF NDKLAAPLPE IPPDVVTECR LGLKEENPSK KAFEECTRVA HNYLRGEPFE EYQESSYFSQ FLQWKWLERQ PVTKNTFRHY RVLGKGGFGE VCACQVRATG KMYACKKLQK KRIKKRKGEA MALNEKRILE KVQSRFVVSL AYAYETKDAL CLVLTIMNGG DLKFHIYNLG NPGFDEQRAV FYAAELCCGL EDLQRERIVY RDLKPENILL DDRGHIRISD LGLATEIPEG QRVRGRVGTV GYMAPEVVNN EKYTFSPDWW GLGCLIYEMI QGHSPFKKYK EKVKWEEVDQ RIKNDTEEYS EKFSEDAKSI CRMLLTKNPS KRLGCRGEGA AGVKQHPVFK DINFRRLEAN MLEPPFCPDP HAVYCKDVLD IEQFSVVKGI YLDTADEDFY ARFATGCVSI PWQNEMIESG CFKDINKSES EEALPLDLDK NIHTPVSRPN RGFFYRLFRR GGCLTMVPSE KEVEPKQC
Protein Length
Full length protein
Tag Info
The following tags are available.
N-terminal His-tagged
Tag-Free
The tag type will be determined during production process. If you have specified tag type, please tell us and we will develop the specified tag preferentially.
Form
Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer before Lyophilization
Tris/PBS-based buffer, 6% Trehalose, pH 8.0
Reconstitution
We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20℃/-80℃. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting and FAQs
Storage Condition
Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life
The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time
Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet
Please contact us to get it.

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Target Background

Function
Specifically phosphorylates the activated forms of G protein-coupled receptors. GRK4-alpha can phosphorylate rhodopsin and its activity is inhibited by calmodulin; the other three isoforms do not phosphorylate rhodopsin and do not interact with calmodulin. GRK4-alpha and GRK4-gamma phosphorylate DRD3. Phosphorylates ADRB2.
Gene References into Functions
  1. GRK4 gene variants in humans (GRK4 A>65L, A>142V, and A>486V) are associated with Hypertension in several but not all ethnic groups. GRK4 gene variants impair the function of D1R and D3R and abet the function of AT1R. These lead to enhancement of renal sodium reabsorption and impaired ability to excrete a sodium load that eventually leads to hypertension. Acknowledgments PMID: 27045027
  2. On normal salt diet, renal CuZnSOD and ECSOD proteins were similar but renal MnSOD was lower in hGRK4g486V than Non-T mice and remained low on high salt diet. hGRK4gammawild-type mice were normotensive and hGRK4g142V mice were hypertensive but both were salt-resistant and in normal redox balance. Chronic tempol treatment partially prevented the salt-sensitivity of hGRK4g486V mice. PMID: 28189851
  3. A novel function of GRK4 on triggering a p53-independent cellular senescence, which involves an intricate signaling network. PMID: 28912086
  4. the association between GRK4(142V) and a larger decrease in blood pressure with angiotensin receptor blockers in hypertensive patients. PMID: 25732908
  5. Subgroup analysis for ethnicity showed that rs1024323 locus of GRK4 gene was associated with hypertension in Caucasians (OR =1.826, 95% CI =1.215-2.745, P=0.004) but not in East Asians and Africans. [meta-analysis] PMID: 26730182
  6. Thus, we provided new insight into the function of GRKs in agonist-unstimulated GPCR trafficking using a recombinant AM1 receptor and further determined the region of the CLR C-tail responsible for this GRK function. PMID: 26820533
  7. hGRK4gamma(142V) phosphorylates histone deacetylase type 1 and promotes its nuclear export to the cytoplasm, resulting in increased AT1R expression and greater pressor response to angiotensin II. PMID: 26667412
  8. A high sodium intake markedly increased the obesity risk in variants of GRK4 A486V regardless of sex amongst Korean children. PMID: 25768006
  9. The C-terminal region of FMRP interacts with a domain of GRK4 mRNA that is folded in four stem loops. PMID: 26250109
  10. GRK4alpha is more similar to GRK2 than GRK6. A fully ordered kinase C-tail reveals interactions linking the C-tail with important determinants of kinase activity, including the alphaB helix, alphaD helix, and the P-loop PMID: 26134571
  11. GRK4 genetic polymorphism plays an important role in the regulation of hypertension. PMID: 25870190
  12. Mutations in GRK4 gene is associated with stress fracture. PMID: 25023003
  13. Buffalo colostrum beta-lactoglobulin inhibits VEGF-induced angiogenesis by interacting with G protein-coupled receptor kinase PMID: 23839509
  14. This study provides a mechanism by which GRK4, via regulation of arterial AT(1)R expression and function, participates in the pathogenesis of conduit vessel abnormalities in hypertension. PMID: 24218433
  15. internalization of agonist-activated D1R is regulated by both SNX5 and GRK4, and that SNX5 is critical to the recycling of the receptor to the plasma membrane PMID: 23195037
  16. The significant association was also found for rs2960306 polymorphism in the GRK4 gene among Europeans. PMID: 22639547
  17. GRK-4 polymorphisms predict blood pressure response to dietary modification in Black subjects with mild-to-moderate hypertension. PMID: 21544086
  18. Dopamine and G protein-coupled receptor kinase 4 in the kidney: role in blood pressure regulation. PMID: 20153824
  19. The G-protein-coupled receptor kinase 4 (T-rs1024323-C and T-rs1801058-C) polymorphisms were not associated with a risk of preeclampsia in Northern Han Chinese. PMID: 20448640
  20. critical role of GRK4, relative to GRK2, in the homologous desensitization of D1 receptors in renal proximal tubule cells. PMID: 12164861
  21. role in phosphorylation-independent desensitization of GABA(B) receptor PMID: 12881416
  22. Genetic variation in GRK4gamma was associated with hypertension PMID: 15097232
  23. GRK4 constitutively phosphorylates the D1 receptor in the absence of agonist activation. PMID: 16338988
  24. data indicate that the R65L polymorphism of the GRK4 gene plays a role in blood pressure regulation in adolescents and young adults. PMID: 16461192
  25. The 65L allele of GRK4 gene is associated with stress-induced urinary sodium excretion. PMID: 16940246
  26. Genetic variation in Gprotein-coupled receptor kinase 4 was associated with hypertension in northern Han Chinese. PMID: 17044852
  27. We conclude that the elevated blood pressure of hGRK4gamma A142V transgenic mice is due mainly to the effect of hGRK4gamma A142V transgene acting via D(1)R and increased ROS production is not a contributor. PMID: 17259440
  28. This evidence suggests the kinase domain of GRK4gamma is responsible for GPCR regulation and GRK4 binding to inactive Galpha(s) and Gbeta may explain the constitutive activity of GRK4gamma towards Galpha(s)-coupled receptors. PMID: 18190783
  29. The GRK4 Ala142Val polymorphism did not contribute to the phenotypes in renal handling of sodium PMID: 18413491
  30. The potential implication of GRK4 promoter variation in blood pressure control in humans is unmistakable. PMID: 18711006
  31. The 4 identified genetic variants within this region exert allele-specific impact on both cell type- and stimulation-dependent transcription and may affect the expression balance of renal G protein-coupled receptor kinase 4. PMID: 18711008
  32. hypertensive African American men with a GRK4 A142 variant were less responsive to metoprolol if they had a GRK4 L65 variant PMID: 19119263
  33. GRK4, specifically the GRK4-gamma and GRK4-alpha isoforms, phosphorylates the D(3) receptor and is crucial for its signaling in human proximal tubule cells PMID: 19520868

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Subcellular Location
Cytoplasm. Cytoplasm, cell cortex. Note=Both at the cell surface and dispersed in the cytoplasm under basal conditions. Receptor stimulation results in the internalization of GRK4 to the perinuclear area, where colocalization with DRD3 is observed strongly at 5 and 15 minutes. DRD3 and GRK4 colocalize in lipid rafts of renal proximal tubule cells.
Protein Families
Protein kinase superfamily, AGC Ser/Thr protein kinase family, GPRK subfamily
Tissue Specificity
Isoform 1, isoform 2, isoform 3, and isoform 4 are expressed in testis. Isoform 4 is expressed in myometrium.
Database Links

HGNC: 4543

OMIM: 137026

KEGG: hsa:2868

STRING: 9606.ENSP00000381129

UniGene: Hs.32959

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