Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0005648
UniProt IDP45983
Primary gene name(s)MAPK8
Synonym gene name(s)JNK1, PRKM8, SAPK1, SAPK1C
Protein nameMitogen-activated protein kinase 8
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 MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4, HSF4, the deacetylase SIRT1, ELK1, or the E3 ligase ITCH. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock, PubMed:22441692. {ECO:0000269|PubMed:22441692}.; FUNCTION: JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.
Subcellular locationCytoplasm {ECO:0000269|PubMed:21148294}. Nucleus {ECO:0000269|PubMed:21148294}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P45983
Gene Ontology
(Biological Process)
Complete annatation
cellular response to lipopolysaccharide [GO:0071222];
cellular response to mechanical stimulus [GO:0071260];
Fc-epsilon receptor signaling pathway [GO:0038095];
JNK cascade [GO:0007254];
JUN phosphorylation [GO:0007258];
negative regulation of apoptotic process [GO:0043066];
negative regulation of protein binding [GO:0032091];
peptidyl-serine phosphorylation [GO:0018105];
peptidyl-threonine phosphorylation [GO:0018107];
positive regulation of apoptotic process [GO:0043065];
positive regulation of cyclase activity [GO:0031281];
positive regulation of deacetylase activity [GO:0090045];
positive regulation of gene expression [GO:0010628];
positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway [GO:1900740];
positive regulation of protein metabolic process [GO:0051247];
protein phosphorylation [GO:0006468];
regulation of circadian rhythm [GO:0042752];
regulation of macroautophagy [GO:0016241];
regulation of protein localization [GO:0032880];
regulation of sequence-specific DNA binding transcription factor activity [GO:0051090];
response to stress [GO:0006950];
response to UV [GO:0009411];
rhythmic process [GO:0048511]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
enzyme binding [GO:0019899];
histone deacetylase binding [GO:0042826];
histone deacetylase regulator activity [GO:0035033];
JUN kinase activity [GO:0004705];
kinase activity [GO:0016301];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
mitochondrion [GO:0005739];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction111585
Phylogenetic treeP45983
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. CD31.350810583552385.27737323486877e-050.000273994383038037
AZA vs. DISU0.458126974971930.07159804669725090.580564258157267
AZA vs. IL70.04571580163740760.8132277290820230.999311006273513
AZA vs. SAHA0.2587580679082520.2917059882194960.664025380009163
DISU vs. CD3-0.9060167963784670.01309012122437360.0363121986264644
DISU vs. IL7-0.4211930749182990.09586927302003330.410615314183934
DISU vs. SAHA-0.1983373942877670.499478945481260.824570493207985
DMSO vs. AZA-0.04165118094670630.8054672322986571
DMSO vs. CD3-1.402847342191161.79633119308242e-059.73793789988726e-05
DMSO vs. DISU-0.5012941370583340.04124155218924630.405420868553126
DMSO vs. IL70.09434255888353080.6024445771833340.912604767320708
DMSO vs. SAHA0.2928830600478810.216434693335880.560079553712712
HIV vs. Mock in Activation0.2546133948051860.6837392602815220.999983755607037
HIV vs. Mock in Latency0.1478739067100990.3739056885317810.999834320637052
IL7 vs. CD3-1.296946877959987.27422648053588e-050.00044211457960128
SAHA vs. CD3-1.117095308686240.001980838015446350.00641961911672613
SAHA vs. IL70.2087433118939990.3944650139996450.642152189149903
(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
1.7 0.009079066 1.7 0.004171562 1.6 0.011313918
(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 0.631737 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
0.969 1.152 1.091 1.164 1.185
(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
DB01782 2,6-Dihydroanthra/1,9-Cd/Pyrazol-6-One experimental unknown unknown
DB07218 6-CHLORO-9-HYDROXY-1,3-DIMETHYL-1,9-DIHYDRO-4H-PYRAZOLO[3,4-B]QUINOLIN-4-ONE experimental unknown unknown
DB07268 2-({2-[(3-HYDROXYPHENYL)AMINO]PYRIMIDIN-4-YL}AMINO)BENZAMIDE experimental unknown unknown
DB07272 N-(4-AMINO-5-CYANO-6-ETHOXYPYRIDIN-2-YL)-2-(4-BROMO-2,5-DIMETHOXYPHENYL)ACETAMIDE experimental unknown unknown
DB07276 5-CYANO-N-(2,5-DIMETHOXYBENZYL)-6-ETHOXYPYRIDINE-2-CARBOXAMIDE experimental unknown unknown
DB07845 2-fluoro-6-{[2-({2-methoxy-4-[(methylsulfonyl)methyl]phenyl}amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}benzamide experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1UKH X-ray 2.3Å A=1-363.
1UKI X-ray 2.7Å A=1-363.
2G01 X-ray 3.5Å A/B=1-364.
2GMX X-ray 3.5Å A/B=1-364.
2H96 X-ray 3.0Å A/B=1-364.
2NO3 X-ray 3.2Å A/B=1-364.
2XRW X-ray 1.3Å A=2-364.
2XS0 X-ray 2.6Å A=1-379.
3ELJ X-ray 1.8Å A=1-364.
3O17 X-ray 3.0Å A/B=1-364.
3O2M X-ray 2.7Å A/B=1-364.
3PZE X-ray 2.0Å A=7-364.
3V3V X-ray 2.7Å A=1-366.
3VUD X-ray 3.5Å A=1-364.
3VUG X-ray 3.2Å A=1-364.
3VUH X-ray 2.7Å A=1-364.
3VUI X-ray 2.8Å A=1-364.
3VUK X-ray 2.9Å A=1-364.
3VUL X-ray 2.8Å A=1-364.
3VUM X-ray 2.6Å A=1-364.
4AWI X-ray 1.9Å A=1-364.
4E73 X-ray 2.2Å A=1-363.
4G1W X-ray 2.4Å A=1-363.
4HYS X-ray 2.4Å A=1-363.
4HYU X-ray 2.1Å A=1-363.
4IZY X-ray 2.3Å A=1-363.
4L7F X-ray 1.9Å A=7-362.
4QTD X-ray 1.5Å A=1-363.
4UX9 X-ray 2.3Å A/B/C/D=1-364.
4YR8 X-ray 2.4Å A/C/E/F=1-363.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 cooperates with 20051532
25143627
Envelope surface glycoprotein gp120 decreases phosphorylation of 12714584
Nef inhibits 23799149
Tat activates 12023963
16539678
18160848
19287189
2506415919479051
21172429
21483469
22450687
9129988
9223324
9621077
9670954
10509564
10799874
11260070
11448159
23762317
Envelope surface glycoprotein gp160; precursor inhibits 9045910
Envelope surface glycoprotein gp160; precursor activates 15603708
Tat activated by 21368226
Envelope surface glycoprotein gp120 induces phosphorylation of 16481105
20960177
2194811221483669
Tat inhibits 24862326
Vpr involves 26270987
26270987
26270987
Tat induces phosphorylation of 16395283
24044867
2506415920336759
20457808
2355591424418364
25164676
2594389426031809
Envelope surface glycoprotein gp120 upregulates 12089333
12775419
Envelope surface glycoprotein gp120 activates 11468147
11698270
12239168
12857973
1296023119319745
9403476
11504923
12089333
12775419
15246824
21948112
Nef activates 10394361
11153078
20380698
2284434510394361
1459767215827086
24874739
Vpr activates 16243842
19275580
integrase phosphorylated by 20173753
21651489
23863879

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)
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)
hsa05166 HTLV-I infection - 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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