Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0005638
UniProt IDO43318
Primary gene name(s)MAP3K7
Synonym gene name(s)TAK1
Protein nameMitogen-activated protein kinase kinase kinase 7
Protein functionSerine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1, IL-1, transforming growth factor-beta, TGFB, TGFB-related factors like BMP2 and BMP4, toll-like receptors, TLR, tumor necrosis factor receptor CD40 and B-cell receptor, BCR. Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases, JNKs and I-kappa-B kinase complex, IKK. Both p38 MAPK and JNK pathways control the transcription factors activator protein-1, AP-1, while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity. {ECO:0000269|PubMed:10094049, ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:12589052, ECO:0000269|PubMed:16845370, ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:21512573, ECO:0000269|PubMed:8663074, ECO:0000269|PubMed:9079627}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:12242293}. Cell membrane {ECO:0000269|PubMed:12242293};
Peripheral membrane protein {ECO:0000269|PubMed:12242293};
Cytoplasmic side {ECO:0000269|PubMed:12242293}. Note=Although the majority of MAP3K7/TAK1 is found in the cytosol, when complexed with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2, it is also localized at the cell membrane.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O43318
Gene Ontology
(Biological Process)
Complete annatation
activation of MAPK activity [GO:0000187];
activation of MAPKK activity [GO:0000186];
activation of NF-kappaB-inducing kinase activity [GO:0007250];
apoptotic process [GO:0006915];
Fc-epsilon receptor signaling pathway [GO:0038095];
histone H3 acetylation [GO:0043966];
I-kappaB kinase/NF-kappaB signaling [GO:0007249];
I-kappaB phosphorylation [GO:0007252];
JNK cascade [GO:0007254];
MyD88-dependent toll-like receptor signaling pathway [GO:0002755];
nucleotide-binding oligomerization domain containing signaling pathway [GO:0070423];
positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123];
positive regulation of interleukin-2 production [GO:0032743];
positive regulation of JUN kinase activity [GO:0043507];
positive regulation of NF-kappaB transcription factor activity [GO:0051092];
positive regulation of T cell activation [GO:0050870];
positive regulation of T cell cytokine production [GO:0002726];
stimulatory C-type lectin receptor signaling pathway [GO:0002223];
stress-activated MAPK cascade [GO:0051403];
T cell receptor signaling pathway [GO:0050852];
transcription, DNA-templated [GO:0006351];
transforming growth factor beta receptor signaling pathway [GO:0007179];
Wnt signaling pathway, calcium modulating pathway [GO:0007223]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
magnesium ion binding [GO:0000287];
MAP kinase kinase kinase activity [GO:0004709];
protein kinase activity [GO:0004672];
protein serine/threonine kinase activity [GO:0004674];
scaffold protein binding [GO:0097110]
Gene Ontology
(Cellular Component)
Complete annatation
Ada2/Gcn5/Ada3 transcription activator complex [GO:0005671];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endosome membrane [GO:0010008];
nucleus [GO:0005634];
plasma membrane [GO:0005886]
Protein-protein interaction112748
Phylogenetic treeO43318
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 also 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. CD30.4332355780391620.1867917814776020.289225984223384
AZA vs. DISU0.0559740815382630.8252902342117350.985177903861482
AZA vs. IL7-0.004645994140930240.9807561145277450.999311006273513
AZA vs. SAHA0.2294216936640370.348962318738640.719925486621394
DISU vs. CD3-0.390025431382420.2853620256722440.415402027225107
DISU vs. IL7-0.06940191804323890.7833638869179490.950465331549835
DISU vs. SAHA0.174099297759390.5543420473238680.853369662432892
DMSO vs. AZA-0.1281940191710360.4456919607387911
DMSO vs. CD3-0.5722000668568850.0745402567956150.134324039309323
DMSO vs. DISU-0.1858851720261960.4475865083094710.887750550174221
DMSO vs. IL70.1307132498753050.4683380189375320.877499426457811
DMSO vs. SAHA0.3499374250692130.1395078956281290.447535865264268
HIV vs. Mock in Activation-0.1668021919164690.7887550123882980.999983755607037
HIV vs. Mock in Latency-0.01088691207473630.9474833449163030.999834320637052
IL7 vs. CD3-0.4293119338752410.182599167667990.301128802435407
SAHA vs. CD3-0.2295084569367780.5158925654662060.623606397816292
SAHA vs. IL70.2299672094000830.3472516423328560.596520940914584
(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 -0.317618 0.115594
(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
0.951 0.995 1.085 1.146 1.048
(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
2EVA X-ray 2.0Å A=31-412.
2YIY X-ray 2.4Å A=31-303.
4GS6 X-ray 2.2Å A=31-303.
4L3P X-ray 2.6Å A=31-303.
4L52 X-ray 2.5Å A=31-303.
4L53 X-ray 2.5Å A=31-303.
4O91 X-ray 2.3Å A=31-303.
5E7R X-ray 2.1Å A=31-303.
5JGA X-ray 2.0Å A=31-303.
5JGB X-ray 2.8Å A=31-303.
5JGD X-ray 3.1Å A=31-303.

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

HIV Partner Interaction Type PubMed
Nef induces phosphorylation of 24874739
Envelope surface glycoprotein gp160; precursor co-localizes with 22341466
capsid requires 26468522
Nef interacts with 24874739
Envelope transmembrane glycoprotein gp41 interacts with 22341466
HIV-1 virus replication enhanced by expression of human gene 18976975
Vpr interacts with 24912525
Vpr induces phosphorylation of 24912525
capsid inhibited by 21512569
Nef activates 24874739
Vpr enhances 26401039
Envelope transmembrane glycoprotein gp41 cooperates with 22341466
Vpr activates 24912525

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04152 AMPK signaling pathway - Homo sapiens (human)
hsa04310 Wnt signaling pathway - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04520 Adherens 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)
hsa04660 T cell receptor signaling pathway - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa05140 Leishmaniasis - Homo sapiens (human)
hsa05145 Toxoplasmosis - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)