Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001222
UniProt IDP43250
Primary gene name(s)GRK6
Synonym gene name(s)GPRK6
Protein nameG protein-coupled receptor kinase 6
Protein functionSpecifically phosphorylates the activated forms of G protein-coupled receptors. Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their desensitization. Seems to be involved in the desensitization of D2-like dopamine receptors in striatum and chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis, By similarity. Phosphorylates rhodopsin, RHO, in vitro and a non G-protein-coupled receptor: LRP6 during Wnt signaling, in vitro. {ECO:0000250, ECO:0000269|PubMed:19801552, ECO:0000269|PubMed:20048153}.
Subcellular locationMembrane;
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P43250
Gene Ontology
(Biological Process)
Complete annatation
regulation of G-protein coupled receptor protein signaling pathway [GO:0008277];
Wnt signaling pathway [GO:0016055]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
beta-adrenergic receptor kinase activity [GO:0047696];
G-protein coupled receptor kinase activity [GO:0004703]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
membrane [GO:0016020];
plasma membrane [GO:0005886]
Protein-protein interaction109128
Phylogenetic treeP43250
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3-1.127477017437720.0006670218098367990.00254837838222059
AZA vs. DISU-0.506995718668970.04588502390646850.485039366672959
AZA vs. IL7-0.04638184814141120.8090964928610410.999311006273513
AZA vs. SAHA-0.3560663508912860.14446776641910.484042478551126
DISU vs. CD30.6073138845152460.09643145091870040.18118006869606
DISU vs. IL70.4518539724690050.07403760445548630.362024352964695
DISU vs. SAHA0.1529877276689990.59991559409570.872437121160766
DMSO vs. AZA0.09605996896484050.5658570005983961
DMSO vs. CD31.205476104388420.0001981343481773920.000824101036800777
DMSO vs. DISU0.5993568645671690.01471363840706760.254282718801043
DMSO vs. IL7-0.1341536787311660.4550242806638780.871380160180109
DMSO vs. SAHA-0.4563976206599090.05325190116531660.261923163593001
HIV vs. Mock in Activation-0.06276294835064710.9197748801785840.999983755607037
HIV vs. Mock in Latency-0.3188878307372750.05311662636932040.905746635623456
IL7 vs. CD31.088830305091980.0007978116634103080.00350084867615242
SAHA vs. CD30.7473019004038180.03543463415547090.0746957527938098
SAHA vs. IL7-0.3131194074566830.1985646625562470.430607316923252
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -0.283398 0.0337045
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2ACX X-ray 2.6Å A/B=1-576.
3NYN X-ray 2.7Å A/B=2-576.
3NYO X-ray 2.9Å A/B=2-576.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04144 Endocytosis - Homo sapiens (human)
hsa05032 Morphine addiction - Homo sapiens (human)