Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001701
UniProt IDP45984
Primary gene name(s)MAPK9
Synonym gene name(s)JNK2, PRKM9, SAPK1A
Protein nameMitogen-activated protein kinase 9
Protein functionSerine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase, SAP/JNK signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor, TCR stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock, PubMed:22441692. {ECO:0000269|PubMed:22441692}.; FUNCTION: MAPK9 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it.
Subcellular locationCytoplasm {ECO:0000269|PubMed:19675674}. Nucleus {ECO:0000269|PubMed:19675674}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P45984
Gene Ontology
(Biological Process)
Complete annatation
Fc-epsilon receptor signaling pathway [GO:0038095];
JNK cascade [GO:0007254];
positive regulation of apoptotic signaling pathway [GO:2001235];
positive regulation of gene expression [GO:0010628];
positive regulation of macrophage derived foam cell differentiation [GO:0010744];
positive regulation of podosome assembly [GO:0071803];
protein phosphorylation [GO:0006468];
regulation of circadian rhythm [GO:0042752];
regulation of sequence-specific DNA binding transcription factor activity [GO:0051090];
response to cadmium ion [GO:0046686];
response to stress [GO:0006950];
rhythmic process [GO:0048511]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
cysteine-type endopeptidase activator activity involved in apoptotic process [GO:0008656];
JUN kinase activity [GO:0004705];
transcription factor binding [GO:0008134]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
mitochondrion [GO:0005739];
nucleoplasm [GO:0005654]
Protein-protein interaction111587
Phylogenetic treeP45984
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. CD30.04935007568616110.8810510911806950.922342816352359
AZA vs. DISU0.07727474625816670.7609470858270840.976021571236163
AZA vs. IL70.05978413468925720.7566542428497330.999311006273513
AZA vs. SAHA0.3169080426355420.1975040293608730.565250757278488
DISU vs. CD30.01557311590915140.9657378192058860.978590399896604
DISU vs. IL7-0.02632496850307510.9170664574757880.984177363812193
DISU vs. SAHA0.2407684991587470.4167567395380990.771430478236783
DMSO vs. AZA-0.05368827162734690.749948327769831
DMSO vs. CD3-0.1146558033353490.7217691543898410.797290827898735
DMSO vs. DISU-0.1328177883479170.5877301073112850.934701463289767
DMSO vs. IL70.1207958391359550.5033718606903140.886542486696914
DMSO vs. SAHA0.3639165970759110.1258984426556390.423704000443315
HIV vs. Mock in Activation-0.08346767204629740.8934024061460790.999983755607037
HIV vs. Mock in Latency-0.01485251939600360.9286276728722950.999834320637052
IL7 vs. CD30.01844154225966090.9545033397443460.972438583302908
SAHA vs. CD30.2425622305127730.5035693678350230.612295495665144
SAHA vs. IL70.2534435506368850.3019513855111260.550707478512365
(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 -0.0269674 0.897785
(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
0.86 0.734 0.901 0.975 0.768
(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
DB07020 N-{3-[5-(1H-1,2,4-triazol-3-yl)-1H-indazol-3-yl]phenyl}furan-2-carboxamide experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
3E7O X-ray 2.1Å A/B=7-362.
3NPC X-ray 2.3Å A/B=1-364.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 decreases phosphorylation of 12714584
Tat induces phosphorylation of 24418364
25943894
Envelope surface glycoprotein gp160; precursor inhibits 9045910
Envelope surface glycoprotein gp160; precursor activates 15603708
Envelope surface glycoprotein gp120 activates 11468147
11698270
12239168
12857973
129602319403476
11504923
12089333
12775419
15246824
HIV-1 virus replication enhanced by expression of human gene 20174665
Pr55(Gag) interacts with 24447338
Envelope surface glycoprotein gp120 induces phosphorylation of 16481105

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)
hsa04012 ErbB signaling pathway - Homo sapiens (human)
hsa04014 Ras signaling pathway - Homo sapiens (human)
hsa04024 cAMP signaling pathway - Homo sapiens (human)
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04071 Sphingolipid signaling pathway - Homo sapiens (human)
hsa04141 Protein processing in endoplasmic reticulum - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04215 Apoptosis - multiple species - Homo sapiens (human)
hsa04310 Wnt signaling pathway - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04510 Focal adhesion - Homo sapiens (human)
hsa04530 Tight junction - 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)
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)
hsa04910 Insulin signaling pathway - 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)
hsa04920 Adipocytokine signaling pathway - Homo sapiens (human)
hsa04930 Type II diabetes mellitus - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa04933 AGE-RAGE signaling pathway in diabetic complications - 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)
hsa05142 Chagas disease (American trypanosomiasis) - Homo sapiens (human)
hsa05145 Toxoplasmosis - Homo sapiens (human)
hsa05152 Tuberculosis - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05210 Colorectal cancer - Homo sapiens (human)
hsa05212 Pancreatic cancer - Homo sapiens (human)
hsa05231 Choline metabolism in cancer - Homo sapiens (human)
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