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Aliases for GRK4 Gene

Aliases for GRK4 Gene

  • G Protein-Coupled Receptor Kinase 4 2 3 5
  • EC 2.7.11.16 4 58
  • GPRK2L 3 4
  • GPRK4 3 4
  • G Protein-Coupled Receptor Kinase 2-Like (Drosophila) 2
  • G Protein-Coupled Receptor Kinase 2-Like 3
  • G Protein-Coupled Receptor Kinase GRK4 4
  • EC 2.7.11 58
  • GRK4a 3
  • IT11 3
  • ITI1 4

External Ids for GRK4 Gene

Previous HGNC Symbols for GRK4 Gene

  • GPRK2L

Previous GeneCards Identifiers for GRK4 Gene

  • GC04P002997
  • GC04P002996
  • GC04P003002

Summaries for GRK4 Gene

Entrez Gene Summary for GRK4 Gene

  • 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]

GeneCards Summary for GRK4 Gene

GRK4 (G Protein-Coupled Receptor Kinase 4) is a Protein Coding gene. Diseases associated with GRK4 include Aortic Coarctation and Hypertension, Essential. Among its related pathways are Phototransduction and Myometrial Relaxation and Contraction Pathways. GO annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is GRK5.

UniProtKB/Swiss-Prot for GRK4 Gene

  • 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 Wiki entry for GRK4 Gene

Additional gene information for GRK4 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for GRK4 Gene

Genomics for GRK4 Gene

Regulatory Elements for GRK4 Gene

Enhancers for GRK4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH04H002961 1.4 ENCODE dbSUPER 49.7 -0.5 -475 3 HDGF PKNOX1 FOXA2 MLX ARID4B SIN3A DMAP1 ZNF2 YY1 ZNF766 GRK4 FAM193A NELFA RNF4 MFSD10 HAUS3 SH3BP2 NOP14-AS1
GH04H002857 1.5 Ensembl ENCODE dbSUPER 37.4 -103.0 -103027 5 PKNOX1 FOXA2 ARID4B FEZF1 YY1 TCF12 KLF7 RUNX3 SP5 MXD4 GRK4 NOP14-AS1 NOP14 TNIP2 HTT GC04P002843 GC04P002844 GC04P002845 PIR46708 GC04P002904
GH04H002866 1.5 Ensembl ENCODE dbSUPER 37.4 -95.8 -95801 3 ATF1 FOXA2 ARNT ARID4B YY1 TCF12 ZNF766 GATA2 ELK1 SP5 GRK4 ADD1 TNIP2 MFSD10 NOP14-AS1 NOP14 GC04P002844 GC04P002845 GC04P002843 PIR46708
GH04H002978 0.9 Ensembl ENCODE 51.7 +15.2 15163 0 CTCF NFIA TRIM22 RAD21 GATA3 SMC3 ZNF143 RUNX3 CREM THAP11 GRK4 NOP14 GC04P003003
GH04H002953 1.1 ENCODE dbSUPER 38.3 -8.7 -8736 1 HDGF TBL1XR1 RB1 BATF ZNF2 ZBTB7B YY1 ZNF143 ZNF207 ATF7 GRK4 NOP14-AS1
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around GRK4 on UCSC Golden Path with GeneCards custom track

Promoters for GRK4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000165022 -105 2401 HDGF PKNOX1 FOXA2 MLX ARID4B SIN3A DMAP1 ZNF2 YY1 ZNF766

Genomic Location for GRK4 Gene

Chromosome:
4
Start:
2,963,505 bp from pter
End:
3,040,752 bp from pter
Size:
77,248 bases
Orientation:
Plus strand

Genomic View for GRK4 Gene

Genes around GRK4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GRK4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GRK4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GRK4 Gene

Proteins for GRK4 Gene

  • Protein details for GRK4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P32298-GRK4_HUMAN
    Recommended name:
    G protein-coupled receptor kinase 4
    Protein Accession:
    P32298
    Secondary Accessions:
    • O00641
    • O00642
    • Q13293
    • Q13294
    • Q13295
    • Q14453
    • Q14725
    • Q15313
    • Q15314
    • Q15315
    • Q15316
    • Q17RH6
    • Q53EQ8

    Protein attributes for GRK4 Gene

    Size:
    578 amino acids
    Molecular mass:
    66583 Da
    Quaternary structure:
    • Interacts with DRD3.

    Three dimensional structures from OCA and Proteopedia for GRK4 Gene

    Alternative splice isoforms for GRK4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GRK4 Gene

Selected DME Specific Peptides for GRK4 Gene

P32298:
  • SLCDKQP
  • GRVGTVGYMAPE
  • MNGGDLK
  • GHIRISDLGL
  • IPWQNEM
  • FLQWKWLERQPVTKNTFR
  • YRVLGKGGFGEVCACQVRA
  • TIMNGGD
  • RDLKPEN
  • LQWKWLE
  • YETKDALCLVLT
  • KKRIKKRKGE
  • RISDLGLA
  • KPENILLD

Post-translational modifications for GRK4 Gene

Antibody Products

  • Abcam antibodies for GRK4

Domains & Families for GRK4 Gene

Gene Families for GRK4 Gene

Suggested Antigen Peptide Sequences for GRK4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P32298

UniProtKB/Swiss-Prot:

GRK4_HUMAN :
  • Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.
Family:
  • Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.
genes like me logo Genes that share domains with GRK4: view

Function for GRK4 Gene

Molecular function for GRK4 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
ATP + [G-protein-coupled receptor] = ADP + [G-protein-coupled receptor] phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by heparin.
UniProtKB/Swiss-Prot 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.

Enzyme Numbers (IUBMB) for GRK4 Gene

Phenotypes From GWAS Catalog for GRK4 Gene

Gene Ontology (GO) - Molecular Function for GRK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity IEA --
GO:0004674 protein serine/threonine kinase activity IEA --
GO:0004703 G-protein coupled receptor kinase activity IEA --
GO:0005524 ATP binding IEA --
GO:0016301 kinase activity IEA --
genes like me logo Genes that share ontologies with GRK4: view
genes like me logo Genes that share phenotypes with GRK4: view

Animal Models for GRK4 Gene

MGI Knock Outs for GRK4:

Animal Model Products

  • Taconic Biosciences Mouse Models for GRK4

CRISPR Products

Inhibitory RNA Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for GRK4 Gene

Localization for GRK4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GRK4 Gene

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.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GRK4 gene
Compartment Confidence
plasma membrane 5
cytosol 4
nucleus 2
cytoskeleton 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for GRK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol IEA --
GO:0005938 cell cortex IEA --
GO:0030425 dendrite IEA --
GO:0043025 neuronal cell body IEA --
genes like me logo Genes that share ontologies with GRK4: view

Pathways & Interactions for GRK4 Gene

genes like me logo Genes that share pathways with GRK4: view

Interacting Proteins for GRK4 Gene

Gene Ontology (GO) - Biological Process for GRK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002029 desensitization of G-protein coupled receptor protein signaling pathway IEA --
GO:0002031 G-protein coupled receptor internalization IEA --
GO:0006468 protein phosphorylation IEA --
GO:0007165 signal transduction IEA --
GO:0008277 regulation of G-protein coupled receptor protein signaling pathway TAS 1338872
genes like me logo Genes that share ontologies with GRK4: view

No data available for SIGNOR curated interactions for GRK4 Gene

Drugs & Compounds for GRK4 Gene

(7) Drugs for GRK4 Gene - From: PharmGKB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Atenolol Approved Pharma Antagonist 107
Metoprolol Approved, Investigational Pharma Antagonist 214
Verapamil Approved Pharma Channel blocker 130

(2) Additional Compounds for GRK4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with GRK4: view

Transcripts for GRK4 Gene

Unigene Clusters for GRK4 Gene

G protein-coupled receptor kinase 4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Alternative Splicing Database (ASD) splice patterns (SP) for GRK4 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18a · 18b
SP1: - - -
SP2: - - - - -
SP3: - - - -
SP4: - - - - - -
SP5: - - - - -
SP6: -
SP7:
SP8:

Relevant External Links for GRK4 Gene

GeneLoc Exon Structure for
GRK4
ECgene alternative splicing isoforms for
GRK4

Expression for GRK4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for GRK4 Gene

mRNA differential expression in normal tissues according to GTEx for GRK4 Gene

This gene is overexpressed in Testis (x9.0).

Protein differential expression in normal tissues from HIPED for GRK4 Gene

This gene is overexpressed in CD8 Tcells (40.5) and NK cells (22.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for GRK4 Gene



Protein tissue co-expression partners for GRK4 Gene

NURSA nuclear receptor signaling pathways regulating expression of GRK4 Gene:

GRK4

SOURCE GeneReport for Unigene cluster for GRK4 Gene:

Hs.32959

mRNA Expression by UniProt/SwissProt for GRK4 Gene:

P32298-GRK4_HUMAN
Tissue specificity: Isoform 1, isoform 2, isoform 3, and isoform 4 are expressed in testis. Isoform 4 is expressed in myometrium.

Evidence on tissue expression from TISSUES for GRK4 Gene

  • Kidney(4.3)
  • Nervous system(4.3)
genes like me logo Genes that share expression patterns with GRK4: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for GRK4 Gene

Orthologs for GRK4 Gene

This gene was present in the common ancestor of animals.

Orthologs for GRK4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GRK4 33 34
  • 99.37 (n)
dog
(Canis familiaris)
Mammalia GRK4 33 34
  • 83.65 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia GRK4 34
  • 82 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Grk4 33
  • 81.07 (n)
mouse
(Mus musculus)
Mammalia Grk4 33 16 34
  • 80.94 (n)
cow
(Bos Taurus)
Mammalia GRK4 33 34
  • 77.72 (n)
oppossum
(Monodelphis domestica)
Mammalia GRK4 34
  • 77 (a)
OneToOne
chicken
(Gallus gallus)
Aves GRK4 33 34
  • 75.28 (n)
lizard
(Anolis carolinensis)
Reptilia -- 34
  • 56 (a)
ManyToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia grk4 33
  • 71.8 (n)
zebrafish
(Danio rerio)
Actinopterygii grk4 33 34 34
  • 68.73 (n)
fruit fly
(Drosophila melanogaster)
Insecta Gprk2 34
  • 47 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea grk-1 34
  • 49 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.9515 34
  • 58 (a)
OneToMany
Species where no ortholog for GRK4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for GRK4 Gene

ENSEMBL:
Gene Tree for GRK4 (if available)
TreeFam:
Gene Tree for GRK4 (if available)

Paralogs for GRK4 Gene

Paralogs for GRK4 Gene

genes like me logo Genes that share paralogs with GRK4: view

Variants for GRK4 Gene

Sequence variations from dbSNP and Humsavar for GRK4 Gene

SNP ID Clin Chr 04 pos Sequence Context AA Info Type
rs1000044579 -- 3,000,553(+) TCTTT(G/T)CTTTT intron-variant
rs1000081126 -- 3,004,433(+) TAGAG(C/T)GTAGT intron-variant
rs1000115863 -- 2,962,812(+) GCAGA(A/G)CTCAA intron-variant, upstream-variant-2KB
rs10001308 -- 2,999,307(+) aatgc(C/T)gcaac intron-variant
rs1000150787 -- 2,966,942(+) CCCCA(A/G)AATTC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for GRK4 Gene

Variant ID Type Subtype PubMed ID
dgv5082n100 CNV gain 25217958
esv2661728 CNV deletion 23128226
esv2662217 CNV deletion 23128226
esv2726868 CNV deletion 23290073
esv3387765 CNV duplication 20981092
esv3563265 CNV deletion 23714750
esv3575673 CNV gain 25503493
esv3599412 CNV gain 21293372
esv3599415 CNV gain 21293372
esv3599416 CNV gain 21293372
esv3599417 CNV loss 21293372
esv3599418 CNV loss 21293372
nsv461163 CNV gain 19166990
nsv593437 CNV gain 21841781
nsv593438 CNV gain 21841781
nsv998311 CNV loss 25217958

Variation tolerance for GRK4 Gene

Residual Variation Intolerance Score: 91% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 15.91; 97.44% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for GRK4 Gene

Human Gene Mutation Database (HGMD)
GRK4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GRK4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GRK4 Gene

Disorders for GRK4 Gene

MalaCards: The human disease database

(2) MalaCards diseases for GRK4 Gene - From: HGMD, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
aortic coarctation
  • coarctation of the aorta
hypertension, essential
  • hypertension, essential 3
- elite association - COSMIC cancer census association via MalaCards
Search GRK4 in MalaCards View complete list of genes associated with diseases

Relevant External Links for GRK4

Genetic Association Database (GAD)
GRK4
Human Genome Epidemiology (HuGE) Navigator
GRK4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
GRK4
genes like me logo Genes that share disorders with GRK4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GRK4 Gene

Publications for GRK4 Gene

  1. G protein-coupled receptor kinase 4 (GRK4) regulates the phosphorylation and function of the dopamine D3 receptor. (PMID: 19520868) Villar VA … Jose PA (The Journal of biological chemistry 2009) 3 4 22 60
  2. Blood pressure and renal sodium handling in relation to genetic variation in the DRD1 promoter and GRK4. (PMID: 18413491) Staessen JA … Brand E (Hypertension (Dallas, Tex. : 1979) 2008) 3 22 45 60
  3. The G protein-coupled receptor kinase 4 gene affects blood pressure in young normotensive twins. (PMID: 16461192) Zhu H … Dong Y (American journal of hypertension 2006) 3 22 45 60
  4. Association study of G protein-coupled receptor kinase 4 gene variants with essential hypertension in northern Han Chinese. (PMID: 17044852) Wang Y … Gu D (Annals of human genetics 2006) 3 22 45 60
  5. Association of G-protein-coupled receptor kinase 4 haplotypes, but not HSD3B1 or PTP1B polymorphisms, with essential hypertension. (PMID: 15097232) Speirs HJ … Morris BJ (Journal of hypertension 2004) 3 22 45 60

Products for GRK4 Gene

  • Addgene plasmids for GRK4

Sources for GRK4 Gene

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