Browse GRK5

Summary
SymbolGRK5
NameG protein-coupled receptor kinase 5
Aliases GPRK5; FP2025; g protein-coupled receptor kinase GRK5
Chromosomal Location10q26.11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location 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.
Domain PF00069 Protein kinase domain
PF00615 Regulator of G protein signaling domain
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).

> Gene Ontology
 
Biological Process GO:0007187 G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
GO:0007188 adenylate cyclase-modulating G-protein coupled receptor signaling pathway
GO:0007217 tachykinin receptor signaling pathway
GO:0008277 regulation of G-protein coupled receptor protein signaling pathway
GO:0016055 Wnt signaling pathway
GO:0045444 fat cell differentiation
GO:0046777 protein autophosphorylation
GO:0198738 cell-cell signaling by wnt
Molecular Function GO:0004674 protein serine/threonine kinase activity
GO:0004703 G-protein coupled receptor kinase activity
GO:0005080 protein kinase C binding
GO:0005543 phospholipid binding
GO:0047696 beta-adrenergic receptor kinase activity
Cellular Component GO:0005635 nuclear envelope
GO:0005924 cell-substrate adherens junction
GO:0005925 focal adhesion
GO:0030055 cell-substrate junction
GO:0031965 nuclear membrane
> KEGG and Reactome Pathway
 
KEGG hsa04062 Chemokine signaling pathway
hsa04144 Endocytosis
Reactome R-HSA-416476: G alpha (q) signalling events
R-HSA-418555: G alpha (s) signalling events
R-HSA-388396: GPCR downstream signaling
R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR
Summary
SymbolGRK5
NameG protein-coupled receptor kinase 5
Aliases GPRK5; FP2025; g protein-coupled receptor kinase GRK5
Chromosomal Location10q26.11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between GRK5 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 

There is no record.

Summary
SymbolGRK5
NameG protein-coupled receptor kinase 5
Aliases GPRK5; FP2025; g protein-coupled receptor kinase GRK5
Chromosomal Location10q26.11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of GRK5 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA Sensitive to T cell-mediated killing
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolGRK5
NameG protein-coupled receptor kinase 5
Aliases GPRK5; FP2025; g protein-coupled receptor kinase GRK5
Chromosomal Location10q26.11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of GRK5 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.4430.146
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.3330.825
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.5230.637
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.1470.646
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.360.857
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.1190.961
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.3730.247
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.4430.718
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.2440.865
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.9230.472
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.6250.38
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.2210.0457
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of GRK5 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.74.1-0.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.75.1-1.41
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91622.26.2160.53
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59400400.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47014.3-14.31
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolGRK5
NameG protein-coupled receptor kinase 5
Aliases GPRK5; FP2025; g protein-coupled receptor kinase GRK5
Chromosomal Location10q26.11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of GRK5. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolGRK5
NameG protein-coupled receptor kinase 5
Aliases GPRK5; FP2025; g protein-coupled receptor kinase GRK5
Chromosomal Location10q26.11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of GRK5. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by GRK5.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolGRK5
NameG protein-coupled receptor kinase 5
Aliases GPRK5; FP2025; g protein-coupled receptor kinase GRK5
Chromosomal Location10q26.11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of GRK5. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolGRK5
NameG protein-coupled receptor kinase 5
Aliases GPRK5; FP2025; g protein-coupled receptor kinase GRK5
Chromosomal Location10q26.11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of GRK5 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolGRK5
NameG protein-coupled receptor kinase 5
Aliases GPRK5; FP2025; g protein-coupled receptor kinase GRK5
Chromosomal Location10q26.11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between GRK5 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolGRK5
NameG protein-coupled receptor kinase 5
Aliases GPRK5; FP2025; g protein-coupled receptor kinase GRK5
Chromosomal Location10q26.11
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting GRK5 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.