Human Gene GRK4 (ENST00000398052.9) from GENCODE V44
  Description: Homo sapiens G protein-coupled receptor kinase 4 (GRK4), transcript variant 1, mRNA. (from RefSeq NM_182982)
RefSeq Summary (NM_182982): 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. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013].
Gencode Transcript: ENST00000398052.9
Gencode Gene: ENSG00000125388.20
Transcript (Including UTRs)
   Position: hg38 chr4:2,963,571-3,040,760 Size: 77,190 Total Exon Count: 16 Strand: +
Coding Region
   Position: hg38 chr4:2,964,071-3,040,625 Size: 76,555 Coding Exon Count: 16 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr4:2,963,571-3,040,760)mRNA (may differ from genome)Protein (578 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: GRK4_HUMAN
DESCRIPTION: RecName: Full=G protein-coupled receptor kinase 4; EC=2.7.11.16; AltName: Full=G protein-coupled receptor kinase GRK4; AltName: Full=ITI1;
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.
CATALYTIC ACTIVITY: ATP + [G-protein-coupled receptor] = ADP + [G- protein-coupled receptor] phosphate.
ENZYME REGULATION: Inhibited by heparine.
SUBUNIT: Interacts with DRD3.
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 co-localization with DRD3 is observed strongly at 5 and 15 minutes. DRD3 and GRK4 co-localize in lipid rafts of renal proximal tubule cells.
TISSUE SPECIFICITY: Isoform 1, isoform 2, isoform 3, and isoform 4 are expressed in testis. Isoform 4 is expressed in myometrium.
PTM: Palmitoylated.
SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.
SIMILARITY: Contains 1 AGC-kinase C-terminal domain.
SIMILARITY: Contains 1 protein kinase domain.
SIMILARITY: Contains 1 RGS domain.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: GRK4
Diseases sorted by gene-association score: aortic coarctation (9), hypertension, essential (4)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 27.06 RPKM in Testis
Total median expression: 104.52 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -277.70500-0.555 Picture PostScript Text
3' UTR -36.10135-0.267 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000961 - AGC-kinase_C
IPR000239 - GPCR_kinase
IPR011009 - Kinase-like_dom
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR000342 - Regulat_G_prot_signal
IPR016137 - Regulat_G_prot_signal_superfam
IPR002290 - Ser/Thr_dual-sp_kinase_dom
IPR008271 - Ser/Thr_kinase_AS

Pfam Domains:
PF00069 - Protein kinase domain
PF00615 - Regulator of G protein signaling domain

ModBase Predicted Comparative 3D Structure on P32298
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004703 G-protein coupled receptor kinase activity
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0050254 rhodopsin kinase activity

Biological Process:
GO:0002029 desensitization of G-protein coupled receptor protein signaling pathway
GO:0002031 G-protein coupled receptor internalization
GO:0006468 protein phosphorylation
GO:0007165 signal transduction
GO:0008277 regulation of G-protein coupled receptor protein signaling pathway
GO:0016310 phosphorylation
GO:0022400 regulation of rhodopsin mediated signaling pathway
GO:0031623 receptor internalization

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005938 cell cortex
GO:0030425 dendrite
GO:0043025 neuronal cell body
GO:0097381 photoreceptor disc membrane


-  Descriptions from all associated GenBank mRNAs
  AK292390 - Homo sapiens cDNA FLJ76938 complete cds, highly similar to Homo sapiens G protein-coupled receptor kinase 4 (GRK4), transcript variant 1, mRNA.
AK223581 - Homo sapiens mRNA for G protein-coupled receptor kinase 2-like isoform 2 variant, clone: FCC130B05.
BC027597 - Homo sapiens cDNA clone IMAGE:4830673, containing frame-shift errors.
BC117320 - Homo sapiens G protein-coupled receptor kinase 4, mRNA (cDNA clone MGC:150929 IMAGE:40125871), complete cds.
U33054 - Human G protein-coupled receptor kinase GRK4 mRNA, alpha splice variant, complete cds.
U33055 - Human G protein-coupled receptor kinase GRK4 mRNA, beta splice variant, complete cds.
U33056 - Human G protein-coupled receptor kinase GRK4 mRNA, gamma splice variant, complete cds.
X97879 - H.sapiens mRNA for G protein coupled receptor kinase, GRK4B.
X97880 - H.sapiens mRNA for G protein coupled receptor kinase, GRK4C.
X97881 - H.sapiens mRNA for G protein coupled receptor kinase, GRK4D.
X98118 - H.sapiens GRK4A gene.
HQ258463 - Synthetic construct Homo sapiens clone IMAGE:100072892 G protein-coupled receptor kinase 4 (GRK4) gene, encodes complete protein.
KJ896927 - Synthetic construct Homo sapiens clone ccsbBroadEn_06321 GRK4 gene, encodes complete protein.
BC110825 - Homo sapiens cDNA clone IMAGE:5770511.
BC039732 - Homo sapiens, clone IMAGE:5770079, mRNA.
AK293569 - Homo sapiens cDNA FLJ57709 complete cds.
X75897 - H.sapiens mRNA for G-protein coupled kinase 4.
JD272776 - Sequence 253800 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04062 - Chemokine signaling pathway
hsa04144 - Endocytosis

BioCarta from NCI Cancer Genome Anatomy Project
h_agpcrPathway - Attenuation of GPCR Signaling

Reactome (by CSHL, EBI, and GO)

Protein P32298 (Reactome details) participates in the following event(s):

R-HSA-2581474 GRK1,4,7 phosphorylate MII to p-MII
R-HSA-2514859 Inactivation, recovery and regulation of the phototransduction cascade
R-HSA-2514856 The phototransduction cascade
R-HSA-2187338 Visual phototransduction
R-HSA-418594 G alpha (i) signalling events
R-HSA-388396 GPCR downstream signalling
R-HSA-372790 Signaling by GPCR
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000398052.1, ENST00000398052.2, ENST00000398052.3, ENST00000398052.4, ENST00000398052.5, ENST00000398052.6, ENST00000398052.7, ENST00000398052.8, GPRK2L, GPRK4, GRK4_HUMAN, NM_182982, O00641, O00642, P32298, Q13293, Q13294, Q13295, Q14453, Q14725, Q15313, Q15314, Q15315, Q15316, Q17RH6, Q53EQ8, uc003ggn.1, uc003ggn.2, uc003ggn.3
UCSC ID: ENST00000398052.9
RefSeq Accession: NM_182982
Protein: P32298 (aka GRK4_HUMAN)
CCDS: CCDS33946.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.