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Aliases for GRK5 Gene

Aliases for GRK5 Gene

  • G Protein-Coupled Receptor Kinase 5 2 3 5
  • G Protein-Coupled Receptor Kinase GRK5 3 4
  • EC 2.7.11.16 4 61
  • GPRK5 3 4
  • EC 2.7.11 61
  • 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 Alpha-synuclein signaling. 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 GRK6.

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

Enhancers for GRK5 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
GH10F119403 1.5 FANTOM5 Ensembl ENCODE 16.4 +202.5 202503 13.0 PKNOX1 MLX ARID4B GLI4 DMAP1 FOS SP5 REST PPARG KAT8 GRK5 GRK5-IT1 RGS10 GC10P119418 MIR4681
GH10F119367 1.3 FANTOM5 Ensembl ENCODE 12 +164.6 164586 8.7 CTCF KLF1 KLF17 ZIC2 RAD21 ZKSCAN1 ZFHX2 POLR2A SCRT2 EED GRK5 RGS10 PRDX3 MIR4681 LOC105378511
GH10F119299 1.7 FANTOM5 Ensembl ENCODE 8.5 +97.6 97612 12.0 HDGF WRNIP1 ARID4B SIN3A DMAP1 FEZF1 YY1 ZNF143 FOS ZNF263 GRK5 LOC105378511 GC10P119246
GH10F119232 1.1 Ensembl ENCODE 12.2 +28.7 28650 6.8 PKNOX1 CBX3 KLF17 SIN3A RAD21 RARA ZNF121 ZNF366 CBX5 EGR2 GRK5 GRK5-IT1 LOC105378511 SFXN4 GC10P119246 RN7SL749P
GH10F119360 1.1 Ensembl ENCODE 10.8 +155.8 155838 6.5 HDGF ELF3 PKNOX1 RAD21 RARA YY1 MIXL1 EGR2 ZNF263 SP3 GRK5 MIR4681 LOC105378511
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around GRK5 on UCSC Golden Path with GeneCards custom track

Promoters for GRK5 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000362724 611 3601 PKNOX1 WRNIP1 ARID4B SIN3A DMAP1 ZNF2 GLIS2 ZNF143 ZNF263 SP5

Genomic Location for GRK5 Gene

Chromosome:
10
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

Genes around GRK5 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GRK5 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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).

    Three dimensional structures from OCA and Proteopedia for GRK5 Gene

neXtProt entry for GRK5 Gene

Selected DME Specific Peptides for GRK5 Gene

P34947:
  • SLCDKQP
  • RKEKVKREEV
  • ENIVANTV
  • KGKSKKW
  • QPIGRLLFR
  • GRVGTVGYMAPE
  • MNGGDLK
  • GHIRISDLGL
  • IPWQNEM
  • KDVLDIEQFSTVKGV
  • GRLLFRQFCETRPGLE
  • FLQWKWLERQPVTKNTFR
  • YRVLGKGGFGEVCACQVRA
  • TIMNGGD
  • GNPGFEE
  • RDLKPEN
  • LNEKQIL
  • LQWKWLE
  • PPFVPDP
  • YMAPEVL
  • LKAREGG
  • YETKDALCLVLT
  • KKRIKKRKGE
  • PPKKGLLQRLF
  • RISDLGLA
  • KPENILLD

Post-translational modifications for GRK5 Gene

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

Other Protein References for GRK5 Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for GRK5 Gene

Graphical View of Domain Structure for InterPro Entry

P34947

UniProtKB/Swiss-Prot:

GRK5_HUMAN :
  • Contains 1 AGC-kinase C-terminal domain.
  • Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.
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 IEA --
GO:0004674 protein serine/threonine kinase activity IDA 20124405
GO:0004703 G-protein coupled receptor kinase activity IEA --
GO:0005080 protein kinase C binding TAS 9813065
GO:0005515 protein binding IPI 17986524
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:

Animal Model Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for GRK5

Flow Cytometry Products

No data available for Human Phenotype Ontology , Transcription Factor Targets 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
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 GRK5 gene
Compartment Confidence
plasma membrane 5
nucleus 5
cytosol 5
cytoskeleton 1

Gene Ontology (GO) - Cellular Components for GRK5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA --
GO:0005737 cytoplasm IDA,TAS --
GO:0005886 plasma membrane TAS --
GO:0005925 focal adhesion IDA --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with GRK5: view

Pathways & Interactions for GRK5 Gene

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

SIGNOR curated interactions for GRK5 Gene

Activates:
Inactivates:

Gene Ontology (GO) - Biological Process for GRK5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation IEA --
GO:0006915 apoptotic process IEA --
GO:0007165 signal transduction IEA --
GO:0007188 adenylate cyclase-modulating G-protein coupled receptor signaling pathway TAS 8626574
GO:0007217 tachykinin receptor signaling pathway IDA 17986524
genes like me logo Genes that share ontologies with GRK5: view

Drugs & Compounds for GRK5 Gene

(14) Drugs for GRK5 Gene - From: PharmGKB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Citalopram Approved Pharma 503
Escitalopram Approved, Investigational Pharma 0
Antihypertensives Pharma 0
Beta Blocking Agents Pharma 0

(5) Additional Compounds for GRK5 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with GRK5: view

Transcripts for GRK5 Gene

mRNA/cDNA for GRK5 Gene

Unigene Clusters for GRK5 Gene

G protein-coupled receptor kinase 5:
Representative Sequences:

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for GRK5

Flow Cytometry Products

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 from GTEx, Illumina, BioGPS, and SAGE for GRK5 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for GRK5 Gene

This gene is overexpressed in Bone marrow mesenchymal stem cell (56.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for GRK5 Gene



NURSA nuclear receptor signaling pathways regulating expression of GRK5 Gene:

GRK5

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 expression patterns with GRK5: view

Primer Products

No data available for mRNA differential expression in normal tissues and Protein tissue co-expression partners 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 34 35
  • 97.08 (n)
dog
(Canis familiaris)
Mammalia GRK5 34 35
  • 92.49 (n)
cow
(Bos Taurus)
Mammalia GRK5 34 35
  • 92.43 (n)
oppossum
(Monodelphis domestica)
Mammalia GRK5 35
  • 92 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Grk5 34
  • 88.76 (n)
mouse
(Mus musculus)
Mammalia Grk5 34 16 35
  • 88.31 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia GRK5 35
  • 86 (a)
OneToOne
chicken
(Gallus gallus)
Aves GRK5 34 35
  • 80.45 (n)
lizard
(Anolis carolinensis)
Reptilia GRK5 35
  • 91 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100497344 34
  • 77.85 (n)
zebrafish
(Danio rerio)
Actinopterygii grk5l 35
  • 73 (a)
ManyToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP004117 34
  • 64.3 (n)
fruit fly
(Drosophila melanogaster)
Insecta Gprk2 34 35
  • 63.9 (n)
worm
(Caenorhabditis elegans)
Secernentea grk-1 34 35
  • 57.49 (n)
rice
(Oryza sativa)
Liliopsida Os.47505 34
sea squirt
(Ciona savignyi)
Ascidiacea CSA.9515 35
  • 65 (a)
OneToMany
Species where no ortholog for GRK5 was found in the sources mined by GeneCards:
  • 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

Variants for GRK5 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for GRK5 Gene

GRK5_HUMAN-P34947
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
VAR_040522 A lung neuroendocrine carcinoma sample
rs10082517 -- 119,346,569(+) AGTGC(C/T)GGCTG intron-variant
rs10128498 -- 119,293,396(+) GGATA(A/G)TTGTA intron-variant
rs1020672 -- 119,325,222(+) CCCTC(C/T)TTTCA intron-variant
rs1041703 -- 119,281,238(-) TGAAG(A/G)GGTGT intron-variant

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

Variant ID Type Subtype PubMed ID
nsv951863 CNV deletion 24416366
nsv832007 CNV gain 17160897
nsv825584 CNV gain 20364138
nsv552214 CNV loss 21841781
nsv522432 CNV loss 19592680
nsv481023 CNV novel sequence insertion 20440878
nsv1149379 CNV duplication 26484159
nsv1144519 CNV deletion 24896259
nsv1143523 CNV deletion 24896259
nsv1130649 CNV deletion 24896259
nsv1125179 CNV insertion 24896259
nsv1115225 CNV deletion 24896259
nsv1111464 CNV deletion 24896259
nsv1070895 CNV deletion 25765185
nsv1069967 CNV deletion 25765185
nsv1038739 CNV gain 25217958
esv9149 CNV loss 19470904
esv4668 CNV loss 18987735
esv3624704 CNV loss 21293372
esv3624702 CNV loss 21293372
esv2741851 CNV deletion 23290073
esv2741840 CNV deletion 23290073
esv2741807 CNV deletion 23290073
esv2741751 CNV deletion 23290073
esv2741740 CNV deletion 23290073
esv2741729 CNV deletion 23290073
esv2741718 CNV deletion 23290073
esv2741683 CNV deletion 23290073
esv2741672 CNV deletion 23290073
esv2741661 CNV deletion 23290073
esv2741650 CNV deletion 23290073
esv2671031 CNV deletion 23128226
esv2670333 CNV deletion 23128226
esv2668115 CNV deletion 23128226
esv2658883 CNV deletion 23128226
esv2639258 CNV deletion 19546169
esv1752195 CNV insertion 17803354
esv1002455 CNV deletion 20482838
dgv525n106 CNV duplication 24896259
dgv524n106 CNV deletion 24896259
dgv510e59 CNV duplication 20981092
dgv111e201 CNV deletion 23290073
dgv110e201 CNV deletion 23290073
dgv109e201 CNV deletion 23290073
dgv108e201 CNV deletion 23290073

Variation tolerance for GRK5 Gene

Residual Variation Intolerance Score: 33.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.67; 89.20% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for GRK5 Gene

Human Gene Mutation Database (HGMD)
GRK5
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GRK5

Disorders for GRK5 Gene

Relevant External Links for GRK5

Genetic Association Database (GAD)
GRK5
Human Genome Epidemiology (HuGE) Navigator
GRK5
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
GRK5

No disorders were found for GRK5 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for GRK5 Gene

Publications for GRK5 Gene

  1. 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 22 46 64
  2. 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 22 64
  3. Role for the regulator of G-protein signaling homology domain of G protein-coupled receptor kinases 5 and 6 in beta 2-adrenergic receptor and rhodopsin phosphorylation. (PMID: 20038610) Baameur F. … Clark R.B. (Mol. Pharmacol. 2010) 3 4 22 64
  4. 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 22 46 64
  5. Clinical and genetic modifiers of long-term survival in heart failure. (PMID: 19628119) Cresci S. … Dorn G.W. (J. Am. Coll. Cardiol. 2009) 3 22 46 64

Products for GRK5 Gene

Sources for GRK5 Gene

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