Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002551
UniProt IDO75582
Primary gene name(s)RPS6KA5
Synonym gene name(s)MSK1
Protein nameRibosomal protein S6 kinase alpha-5
Protein functionSerine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor, EGF and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression. In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress. In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential. Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1, HMGN1/HMG14. In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10, IL10, via CREB1 and ATF1 transcription factors. Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury. {ECO:0000269|PubMed:11909979, ECO:0000269|PubMed:12569367, ECO:0000269|PubMed:12628924, ECO:0000269|PubMed:12763138, ECO:0000269|PubMed:12773393, ECO:0000269|PubMed:15010469, ECO:0000269|PubMed:18511904, ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9873047}.
Subcellular locationNucleus. Cytoplasm. Note=Predominantly nuclear. Exported into cytoplasm in response to glucocorticoid.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O75582
Gene Ontology
(Biological Process)
Complete annatation
axon guidance [GO:0007411];
epidermal growth factor receptor signaling pathway [GO:0007173];
histone H2A-S1 phosphorylation [GO:0043990];
histone H3-S10 phosphorylation [GO:0043987];
histone H3-S28 phosphorylation [GO:0043988];
histone phosphorylation [GO:0016572];
inflammatory response [GO:0006954];
interleukin-1-mediated signaling pathway [GO:0070498];
intracellular signal transduction [GO:0035556];
negative regulation of cytokine production [GO:0001818];
negative regulation of transcription, DNA-templated [GO:0045892];
positive regulation of CREB transcription factor activity [GO:0032793];
positive regulation of histone acetylation [GO:0035066];
positive regulation of histone phosphorylation [GO:0033129];
positive regulation of NF-kappaB transcription factor activity [GO:0051092];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
protein phosphorylation [GO:0006468];
regulation of transcription, DNA-templated [GO:0006355];
stimulatory C-type lectin receptor signaling pathway [GO:0002223]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
histone kinase activity, H3-S10 specific [GO:0035175];
magnesium ion binding [GO:0000287];
protein kinase activity [GO:0004672];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction114676
Phylogenetic treeO75582
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. CD3-0.9290231084173510.005537536133835010.015804155388972
AZA vs. DISU0.04297923804987370.8657206058308770.991133096247651
AZA vs. IL70.19168721254770.3195341966335790.999311006273513
AZA vs. SAHA-0.06993823591726490.7745783909614740.941023832147722
DISU vs. CD30.9602044322269940.008761650534048980.0259017690037761
DISU vs. IL70.1392869071351330.5807652663452210.867436479753712
DISU vs. SAHA-0.1113980477585180.7050811419953250.91288546904155
DMSO vs. AZA-0.1066805789330410.5250240589459661
DMSO vs. CD30.8137998039107150.0130476928535170.0312600974615512
DMSO vs. DISU-0.1506425365431350.5401502091703930.921635859189505
DMSO vs. IL70.3050893020172680.09095078199194470.55848596274076
DMSO vs. SAHA0.02980147294963760.8994330685880560.975555582924909
HIV vs. Mock in Activation0.07362282837822720.9061090576203320.999983755607037
HIV vs. Mock in Latency0.06146122694821620.7385785139411080.999834320637052
IL7 vs. CD31.127675111860110.0005728166769909390.0026366181456145
SAHA vs. CD30.8348190463798340.02177419201046550.0494853074344314
SAHA vs. IL7-0.2642106837589650.2801920420895740.527490301293648
(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 0.619426 0.000305467
(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
0.961 0.951 1.109 1.407 1.164
(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
1VZO X-ray 1.8Å A=2-348.
3KN5 X-ray 2.4Å A/B=414-738.
3KN6 X-ray 2.0Å A/B=414-738.

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

HIV Partner Interaction Type PubMed
Vpu binds 23047923
Tat inhibits 20433920

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04261 Adrenergic signaling in cardiomyocytes - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa04713 Circadian entrainment - Homo sapiens (human)
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)
hsa05219 Bladder cancer - Homo sapiens (human)