Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0003599
UniProt IDP25098
Primary gene name(s)GRK2
Synonym gene name(s)ADRBK1, BARK, BARK1
Protein nameBeta-adrenergic receptor kinase 1
Protein functionSpecifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them. Key regulator of LPAR1 signaling. Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner. {ECO:0000269|PubMed:19306925}.
Subcellular locationCytoplasm {ECO:0000250|UniProtKB:P21146}. Cell membrane {ECO:0000250|UniProtKB:P21146}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P25098
Gene Ontology
(Biological Process)
Complete annatation
cardiac muscle contraction [GO:0060048];
desensitization of G-protein coupled receptor protein signaling pathway [GO:0002029];
G-protein coupled acetylcholine receptor signaling pathway [GO:0007213];
heart development [GO:0007507];
negative regulation of striated muscle contraction [GO:0045988];
negative regulation of the force of heart contraction by chemical signal [GO:0003108];
peptidyl-serine phosphorylation [GO:0018105];
peptidyl-threonine phosphorylation [GO:0018107];
positive regulation of catecholamine secretion [GO:0033605];
receptor internalization [GO:0031623];
tachykinin receptor signaling pathway [GO:0007217];
viral entry into host cell [GO:0046718];
viral genome replication [GO:0019079]
Gene Ontology
(Molecular Function)
Complete annatation
alpha-2A adrenergic receptor binding [GO:0031694];
ATP binding [GO:0005524];
beta-adrenergic receptor kinase activity [GO:0047696];
Edg-2 lysophosphatidic acid receptor binding [GO:0031755];
G-protein coupled receptor kinase activity [GO:0004703];
protein kinase activity [GO:0004672]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
membrane [GO:0016020];
plasma membrane [GO:0005886];
primary cilium [GO:0072372]
Protein-protein interaction106665
Phylogenetic treeP25098
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      Yes - Two siRNA pools inhibit HIV replication and inhibition of Tat-mediated transactivation of the HIV LTR is not observed
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. CD3-1.28198251486970.0001423601063742510.000659467586879657
AZA vs. DISU-0.07107705720649930.7784247538775380.976444104025318
AZA vs. IL7-0.1370221458767420.4744025674532560.999311006273513
AZA vs. SAHA-0.3826370384336550.1170026973629910.43556537439224
DISU vs. CD31.198895554088470.001175065583699510.00476795117326686
DISU vs. IL7-0.07548657405213080.7640077378858860.944592524286864
DISU vs. SAHA-0.309061166386130.2881900251425030.671074418295975
DMSO vs. AZA0.03530498021426370.8322582424945171
DMSO vs. CD31.304192826384717.31332806297447e-050.00034088888387596
DMSO vs. DISU0.1041396490993070.6690021270753390.954184134825904
DMSO vs. IL7-0.1647084145028620.3578223351906650.821745082570931
DMSO vs. SAHA-0.4225507926455950.07321974335492550.31612097084335
HIV vs. Mock in Activation0.2277822063466320.7353304311526020.999983755607037
HIV vs. Mock in Latency0.04085515835861530.8036178221958720.999834320637052
IL7 vs. CD31.15056659770310.0004649117463687570.002202959683438
SAHA vs. CD30.876700083801880.01420887019854260.0344922155109595
SAHA vs. IL7-0.2481137610144570.3077168862120840.556727987914221
(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) unknown
(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 0.059846 0.740542
(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
0.958 0.987 0.963 0.939 1.049
(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

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00171 Adenosine triphosphate approved, nutraceutical unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1BAK NMR - A=556-670.
3CIK X-ray 2.7Å A=1-689.
3KRW X-ray 2.9Å A=2-689.
3KRX X-ray 3.1Å A=2-689.
3V5W X-ray 2.0Å A=1-689.
4MK0 X-ray 2.4Å A=30-668.
4PNK X-ray 2.5Å A=1-689.
5HE1 X-ray 3.1Å A=29-670.

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

HIV Partner Interaction Type PubMed
HIV-1 virus replication enhanced by expression of human gene 18854154

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04144 Endocytosis - Homo sapiens (human)
hsa04340 Hedgehog signaling pathway - Homo sapiens (human)
hsa04724 Glutamatergic synapse - Homo sapiens (human)
hsa04740 Olfactory transduction - Homo sapiens (human)
hsa05032 Morphine addiction - Homo sapiens (human)