Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001221
UniProt IDP34947
Primary gene name(s)GRK5
Synonym gene name(s)GPRK5
Protein nameG protein-coupled receptor kinase 5
Protein functionSerine/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. {ECO:0000269|PubMed:19661922, ECO:0000269|PubMed:19801552, ECO:0000269|PubMed:20038610, ECO:0000269|PubMed:20124405, ECO:0000269|PubMed:21728385}.
Subcellular locationCytoplasm. 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.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P34947
Gene Ontology
(Biological Process)
Complete annatation
adenylate cyclase-modulating G-protein coupled receptor signaling pathway [GO:0007188];
apoptotic process [GO:0006915];
fat cell differentiation [GO:0045444];
negative regulation of apoptotic process [GO:0043066];
positive regulation of cell proliferation [GO:0008284];
protein autophosphorylation [GO:0046777];
regulation of cell cycle [GO:0051726];
regulation of G-protein coupled receptor protein signaling pathway [GO:0008277];
tachykinin receptor signaling pathway [GO:0007217];
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];
phospholipid binding [GO:0005543];
protein kinase C binding [GO:0005080];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
focal adhesion [GO:0005925];
nuclear membrane [GO:0031965];
nucleus [GO:0005634];
plasma membrane [GO:0005886]
Protein-protein interaction109127
Phylogenetic treeP34947
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. CD3-0.589284722620120.07497513421083610.138874919850771
AZA vs. DISU0.1499050754584670.5578948901926520.949322467644108
AZA vs. IL7-0.283154813488210.1457346938210650.91337174218915
AZA vs. SAHA0.2929590778533130.232750746795670.603543732153301
DISU vs. CD30.7259593592972820.05155878662616530.11077496431055
DISU vs. IL7-0.4421707078302860.08284982942039520.38112944110847
DISU vs. SAHA0.1450066777562130.6233414113825950.880777622679305
DMSO vs. AZA-0.04178845849972120.8057600302841831
DMSO vs. CD30.5330983446928580.09908428185387620.169644246435064
DMSO vs. DISU-0.1943931688494770.4305047836395880.881718877024027
DMSO vs. IL7-0.2335910480990160.1996240015821010.710921763253054
DMSO vs. SAHA0.3295097328902850.1650125066988760.491667267304149
HIV vs. Mock in Activation0.3292812075628380.6010908851848520.999983755607037
HIV vs. Mock in Latency-0.03491446471070620.8341186754422460.999834320637052
IL7 vs. CD30.3124404545142980.3358102179714760.474160882012559
SAHA vs. CD30.857621774228110.01632265227166060.0388229750211373
SAHA vs. IL70.5730894725979880.01976196235066850.0996627034038064
(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) TRUE
(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 -0.197346 0.193057
(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
4TNB X-ray 2.1Å A=1-590.
4TND X-ray 1.8Å A=1-590.

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)