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Aliases for GRK5 Gene

Aliases for GRK5 Gene

  • G Protein-Coupled Receptor Kinase 5 2 3
  • GPRK5 3 4 6
  • G Protein-Coupled Receptor Kinase GRK5 3 4
  • EC 2.7.11.16 4 63
  • EC 2.7.11 63
  • FP2025 3

External Ids for GRK5 Gene

Previous HGNC Symbols for GRK5 Gene

  • GPRK5

Previous GeneCards Identifiers for GRK5 Gene

  • GC10P120631
  • GC10P120957
  • GC10P114596

Summaries for GRK5 Gene

Entrez Gene Summary for GRK5 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 their deactivation. It has also been shown to play a role in regulating the motility of polymorphonuclear leukocytes (PMNs). [provided by RefSeq, Jul 2008]

GeneCards Summary for GRK5 Gene

GRK5 (G Protein-Coupled Receptor Kinase 5) is a Protein Coding gene. Among its related pathways are Signaling by GPCR and Signaling by GPCR. GO annotations related to this gene include protein serine/threonine kinase activity and protein kinase C binding. An important paralog of this gene is AKT1.

UniProtKB/Swiss-Prot for GRK5 Gene

  • Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their down-regulation. Phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, also phosphorylates various substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates internalization of the chemokine receptor. Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in vitro).

Gene Wiki entry for GRK5 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for GRK5 Gene

Genomics for GRK5 Gene

Regulatory Elements for GRK5 Gene

Genomic Location for GRK5 Gene

Start:
119,207,589 bp from pter
End:
119,459,742 bp from pter
Size:
252,154 bases
Orientation:
Plus strand

Genomic View for GRK5 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for GRK5 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GRK5 Gene

Proteins for GRK5 Gene

  • Protein details for GRK5 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P34947-GRK5_HUMAN
    Recommended name:
    G protein-coupled receptor kinase 5
    Protein Accession:
    P34947
    Secondary Accessions:
    • D3DRD0
    • Q5T059

    Protein attributes for GRK5 Gene

    Size:
    590 amino acids
    Molecular mass:
    67787 Da
    Quaternary structure:
    • Interacts with ST13 (via the C-terminus 303-319 AA). Interacts with TP53/p53. Interacts with HTR4 (via C-terminus 330-346 AA); this interaction is promoted by 5-HT (serotonin). Interacts with HDAC5 (By similarity).

neXtProt entry for GRK5 Gene

Proteomics data for GRK5 Gene at MOPED

Post-translational modifications for GRK5 Gene

  • Autophosphorylated. Autophosphorylation may play a critical role in the regulation of GRK5 kinase activity.
  • Ubiquitination at Lys194
  • Modification sites at PhosphoSitePlus

Other Protein References for GRK5 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for GRK5 Gene

Graphical View of Domain Structure for InterPro Entry

P34947

UniProtKB/Swiss-Prot:

GRK5_HUMAN :
  • P34947
Domain:
  • Contains 1 AGC-kinase C-terminal domain.
  • Contains 1 protein kinase domain.
  • Contains 1 RGS domain.
Family:
  • Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.
genes like me logo Genes that share domains with GRK5: view

Function for GRK5 Gene

Molecular function for GRK5 Gene

UniProtKB/Swiss-Prot CatalyticActivity: ATP + [G-protein-coupled receptor] = ADP + [G-protein-coupled receptor] phosphate
UniProtKB/Swiss-Prot EnzymeRegulation: Inhibited by calmodulin with an IC(50) of 50 nM. Calmodulin inhibits GRK5 association with receptor and phospholipid.
UniProtKB/Swiss-Prot Function: Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their down-regulation. Phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, also phosphorylates various substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates internalization of the chemokine receptor. Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in vitro).
UniProtKB/Swiss-Prot Induction: Overexpressed during heart failure.

Enzyme Numbers (IUBMB) for GRK5 Gene

Gene Ontology (GO) - Molecular Function for GRK5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity --
GO:0004674 protein serine/threonine kinase activity IDA 20124405
GO:0004703 G-protein coupled receptor kinase activity IEA --
GO:0004713 protein tyrosine kinase activity --
GO:0005080 protein kinase C binding TAS 9813065
genes like me logo Genes that share ontologies with GRK5: view
genes like me logo Genes that share phenotypes with GRK5: view

Animal Models for GRK5 Gene

MGI Knock Outs for GRK5:

miRNA for GRK5 Gene

miRTarBase miRNAs that target GRK5

No data available for Transcription Factor Targeting and HOMER Transcription for GRK5 Gene

Localization for GRK5 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GRK5 Gene

Cytoplasm. Nucleus. Cell membrane; Peripheral membrane protein. Note=Predominantly localized at the plasma membrane; targeted to the cell surface through the interaction with phospholipids. Nucleus localization is regulated in a GPCR and Ca(2+)/calmodulin-dependent fashion.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for GRK5 Gene COMPARTMENTS Subcellular localization image for GRK5 gene
Compartment Confidence
nucleus 5
plasma membrane 5
cytosol 3
cytoskeleton 1
endosome 1

Gene Ontology (GO) - Cellular Components for GRK5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA --
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IDA --
GO:0005886 plasma membrane IDA --
GO:0005925 focal adhesion IDA --
genes like me logo Genes that share ontologies with GRK5: view

Pathways for GRK5 Gene

genes like me logo Genes that share pathways with GRK5: view

Gene Ontology (GO) - Biological Process for GRK5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation --
GO:0006915 apoptotic process IEA --
GO:0007188 adenylate cyclase-modulating G-protein coupled receptor signaling pathway TAS 8626574
GO:0007217 tachykinin receptor signaling pathway IDA 17986524
GO:0008277 regulation of G-protein coupled receptor protein signaling pathway TAS 8288567
genes like me logo Genes that share ontologies with GRK5: view

Compounds for GRK5 Gene

(15) Novoseek inferred chemical compound relationships for GRK5 Gene

Compound -log(P) Hits PubMed IDs
pip2 48.6 5
threonine 46.5 1
serine 37.6 1
dextran sulfate 31.4 2
isoproterenol 28.5 1

(3) PharmGKB related drug/compound annotations for GRK5 Gene

Drug/compound Annotation
Beta Blocking Agents CA
citalopram CA
escitalopram CA
genes like me logo Genes that share compounds with GRK5: view

Transcripts for GRK5 Gene

Unigene Clusters for GRK5 Gene

G protein-coupled receptor kinase 5:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for GRK5 Gene

No ASD Table

Relevant External Links for GRK5 Gene

GeneLoc Exon Structure for
GRK5
ECgene alternative splicing isoforms for
GRK5

Expression for GRK5 Gene

mRNA expression in normal human tissues for GRK5 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for GRK5 Gene

SOURCE GeneReport for Unigene cluster for GRK5 Gene Hs.524625

mRNA Expression by UniProt/SwissProt for GRK5 Gene

P34947-GRK5_HUMAN
Tissue specificity: Highest levels in heart, placenta, lung > skeletal muscle > brain, liver, pancreas > kidney.
genes like me logo Genes that share expressions with GRK5: view

No data available for mRNA differential expression in normal tissues for GRK5 Gene

Orthologs for GRK5 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for GRK5 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GRK5 35
  • 97.08 (n)
  • 96.91 (a)
GRK5 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia GRK5 35
  • 92.43 (n)
  • 97.12 (a)
GRK5 36
  • 97 (a)
OneToOne
dog
(Canis familiaris)
Mammalia GRK5 35
  • 92.49 (n)
  • 96.78 (a)
GRK5 36
  • 97 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Grk5 35
  • 88.31 (n)
  • 95.25 (a)
Grk5 16
Grk5 36
  • 95 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia GRK5 36
  • 92 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia GRK5 36
  • 86 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Grk5 35
  • 88.76 (n)
  • 95.08 (a)
chicken
(Gallus gallus)
Aves GRK5 35
  • 80.45 (n)
  • 91.02 (a)
GRK5 36
  • 90 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia GRK5 36
  • 91 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100497344 35
  • 77.85 (n)
  • 85.76 (a)
zebrafish
(Danio rerio)
Actinopterygii grk5l 36
  • 73 (a)
ManyToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP004117 35
  • 64.3 (n)
  • 67.85 (a)
fruit fly
(Drosophila melanogaster)
Insecta Gprk2 35
  • 63.9 (n)
  • 65.05 (a)
Gprk2 36
  • 52 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea grk-1 35
  • 57.49 (n)
  • 59.6 (a)
grk-1 36
  • 51 (a)
OneToMany
rice
(Oryza sativa)
Liliopsida Os.47505 35
sea squirt
(Ciona savignyi)
Ascidiacea CSA.9515 36
  • 65 (a)
OneToMany
Species with no ortholog for GRK5:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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 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 GRK5 Gene

ENSEMBL:
Gene Tree for GRK5 (if available)
TreeFam:
Gene Tree for GRK5 (if available)

Paralogs for GRK5 Gene

genes like me logo Genes that share paralogs with GRK5: view

Variants for GRK5 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for GRK5 Gene

P34947-GRK5_HUMAN
Variant Leu-41 variant is rare in European-Americans individuals but common in African-Americans individuals (40% of the African-American individuals studied carry at least one allele). Variant leu-41 is associated with decreased mortality in African-Americans with heart failure or cardiac ischemia

Sequence variations from dbSNP and Humsavar for GRK5 Gene

SNP ID Clin Chr 10 pos Sequence Context AA Info Type MAF
rs17449 -- 119,229,658(-) GTTGA(C/T)CATGT intron-variant
rs17450 -- 119,229,606(-) AAGAG(A/C)AGAAT intron-variant
rs184116 -- 119,349,183(-) ACCAC(A/G)GCACC intron-variant
rs184117 -- 119,346,637(-) TGGCA(A/G)AAGGC intron-variant
rs291966 -- 119,347,828(-) GGAAG(A/G)CTCAG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for GRK5 Gene

Variant ID Type Subtype PubMed ID
nsv825584 CNV Gain 20364138
esv2741650 CNV Deletion 23290073
esv2741661 CNV Deletion 23290073
esv2741672 CNV Deletion 23290073
esv2741683 CNV Deletion 23290073
dgv120e201 CNV Deletion 23290073
esv2670333 CNV Deletion 23128226
esv1002455 CNV Deletion 20482838
dgv827n71 CNV Loss 21882294
esv2658883 CNV Deletion 23128226
esv2741718 CNV Deletion 23290073
nsv832007 CNV Gain 17160897
nsv896042 CNV Loss 21882294
nsv522432 CNV Loss 19592680
esv2741729 CNV Deletion 23290073
esv2639258 CNV Deletion 19546169
esv2741740 CNV Deletion 23290073
esv2741751 CNV Deletion 23290073
esv4668 CNV Deletion 18987735
dgv121e201 CNV Deletion 23290073
dgv122e201 CNV Deletion 23290073
esv2668115 CNV Deletion 23128226
esv2741807 CNV Deletion 23290073
nsv896043 CNV Loss 21882294
dgv123e201 CNV Deletion 23290073
esv9149 CNV Loss 19470904
esv1752195 CNV Insertion 17803354
esv2741840 CNV Deletion 23290073
esv2741851 CNV Deletion 23290073
esv2671031 CNV Deletion 23128226

Relevant External Links for GRK5 Gene

HapMap Linkage Disequilibrium report
GRK5
Human Gene Mutation Database (HGMD)
GRK5

Disorders for GRK5 Gene

(4) Novoseek inferred disease relationships for GRK5 Gene

Disease -log(P) Hits PubMed IDs
heart failure 33.8 2
heart failure congestive 12.1 1
huntington disease 9.95 1
neurodegenerative diseases 0 1

Relevant External Links for GRK5

Genetic Association Database (GAD)
GRK5
Human Genome Epidemiology (HuGE) Navigator
GRK5
genes like me logo Genes that share disorders with GRK5: view

No data available for UniProtKB/Swiss-Prot for GRK5 Gene

Publications for GRK5 Gene

  1. Cloning and expression of GRK5: a member of the G protein-coupled receptor kinase family. (PMID: 7685906) Kunapuli P. … Benovic J.L. (Proc. Natl. Acad. Sci. U.S.A. 1993) 2 3 4 23
  2. A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure. (PMID: 18425130) Liggett S.B. … Dorn G.W. II (Nat. Med. 2008) 3 4 23 48
  3. Clinical and genetic modifiers of long-term survival in heart failure. (PMID: 19628119) Cresci S. … Dorn G.W. (J. Am. Coll. Cardiol. 2009) 3 23 48
  4. Beta-arrestin1 phosphorylation by GRK5 regulates G protein- independent 5-HT4 receptor signalling. (PMID: 19661922) Barthet G. … Dumuis A. (EMBO J. 2009) 3 4 23
  5. L41Q polymorphism of the G protein coupled receptor kinase 5 is associated with left ventricular apical ballooning syndrome. (PMID: 20023040) Spinelli L. … Trimarco B. (Eur. J. Heart Fail. 2010) 3 23 48

Products for GRK5 Gene

  • Addgene plasmids for GRK5

Sources for GRK5 Gene

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