Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0011695
UniProt IDQ15759
Primary gene name(s)MAPK11
Synonym gene name(s)PRKM11, SAPK2, SAPK2B
Protein nameMitogen-activated protein kinase 11
Protein functionSerine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK11 functions are mostly redundant with those of MAPK14. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36, tristetraprolin and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Additional examples of p38 MAPK substrates are the FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10', H3S10ph in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:15356147, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510}.
Subcellular locationCytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q15759
Gene Ontology
(Biological Process)
Complete annatation
activation of MAPK activity [GO:0000187];
cellular response to virus [GO:0098586];
intracellular signal transduction [GO:0035556];
negative regulation of cardiac muscle cell proliferation [GO:0060044];
positive regulation of gene expression [GO:0010628];
positive regulation of interleukin-12 secretion [GO:2001184];
positive regulation of muscle cell differentiation [GO:0051149];
Ras protein signal transduction [GO:0007265];
regulation of sequence-specific DNA binding transcription factor activity [GO:0051090];
regulation of signal transduction by p53 class mediator [GO:1901796];
response to stress [GO:0006950];
signal transduction [GO:0007165];
transcription, DNA-templated [GO:0006351];
vascular endothelial growth factor receptor signaling pathway [GO:0048010]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
MAP kinase activity [GO:0004707];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
nucleoplasm [GO:0005654]
Protein-protein interaction111586
Phylogenetic treeQ15759
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
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. CD31.474607165197551.3305884334236e-057.98989197950615e-05
AZA vs. DISU-0.287971644756860.3954566439477950.902586488791209
AZA vs. IL70.2573629460781130.3323359732592680.999311006273513
AZA vs. SAHA-0.4027609041453070.1316512098795950.462697677249946
DISU vs. CD3-1.774407243903351.08133058818183e-057.97845192670234e-05
DISU vs. IL70.5342990556735070.1342813703520480.478950468966487
DISU vs. SAHA-0.111710589153240.7495499659654670.928764494218228
DMSO vs. AZA0.01006453885759640.9615095783110681
DMSO vs. CD3-1.473908621071528.21444074250444e-064.81519648972099e-05
DMSO vs. DISU0.2961190736401820.3368273633520470.836517528957705
DMSO vs. IL70.2544413977238270.2672387626992190.767539423873874
DMSO vs. SAHA-0.4173576095226130.08662069205982880.343913614178161
HIV vs. Mock in Activation0.1337462621243180.8302802896448720.999983755607037
HIV vs. Mock in Latency0.2521382586213480.1509444351045840.999834320637052
IL7 vs. CD3-1.212590711063750.0002154876725797280.00113915916373628
SAHA vs. CD3-1.899278060659072.80308364963844e-072.60274002464888e-06
SAHA vs. IL7-0.660822657611760.02085074676027170.103393619810645
(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 -0.0877842 0.654306
(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

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB05157 KC706 investigational unknown unknown
DB08896 Regorafenib approved yes inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
3GC8 X-ray 2.4Å A/B=1-364.
3GC9 X-ray 2.0Å A/B=1-364.
3GP0 X-ray 1.9Å A=5-350.

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

HIV Partner Interaction Type PubMed
Vpr involves 26270987
26270987
Tat activates 20378550
Nef involves 26075907
Envelope surface glycoprotein gp120 activates 12239168

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01522 Endocrine resistance - Homo sapiens (human)
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04015 Rap1 signaling pathway - Homo sapiens (human)
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04071 Sphingolipid signaling pathway - Homo sapiens (human)
hsa04261 Adrenergic signaling in cardiomyocytes - Homo sapiens (human)
hsa04370 VEGF signaling pathway - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04550 Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
hsa04611 Platelet activation - Homo sapiens (human)
hsa04620 Toll-like receptor signaling pathway - Homo sapiens (human)
hsa04621 NOD-like receptor signaling pathway - Homo sapiens (human)
hsa04622 RIG-I-like receptor signaling pathway - Homo sapiens (human)
hsa04657 IL-17 signaling pathway - Homo sapiens (human)
hsa04658 Th1 and Th2 cell differentiation - Homo sapiens (human)
hsa04659 Th17 cell differentiation - Homo sapiens (human)
hsa04660 T cell receptor signaling pathway - Homo sapiens (human)
hsa04664 Fc epsilon RI signaling pathway - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa04670 Leukocyte transendothelial migration - Homo sapiens (human)
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)
hsa04723 Retrograde endocannabinoid signaling - Homo sapiens (human)
hsa04728 Dopaminergic synapse - Homo sapiens (human)
hsa04750 Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
hsa04912 GnRH signaling pathway - Homo sapiens (human)
hsa04914 Progesterone-mediated oocyte maturation - Homo sapiens (human)
hsa04917 Prolactin signaling pathway - Homo sapiens (human)
hsa04933 AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
hsa05014 Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human)
hsa05120 Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
hsa05131 Shigellosis - Homo sapiens (human)
hsa05132 Salmonella infection - Homo sapiens (human)
hsa05133 Pertussis - Homo sapiens (human)
hsa05140 Leishmaniasis - Homo sapiens (human)
hsa05142 Chagas disease (American trypanosomiasis) - Homo sapiens (human)
hsa05145 Toxoplasmosis - Homo sapiens (human)
hsa05152 Tuberculosis - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05205 Proteoglycans in cancer - Homo sapiens (human)
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