Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001695
UniProt IDQ99683
Primary gene name(s)MAP3K5
Synonym gene name(s)ASK1, MAPKKK5, MEKK5
Protein nameMitogen-activated protein kinase kinase kinase 5
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 signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor, TNF or lipopolysaccharide, LPS. 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 MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases, JNKs. Both p38 MAPK and JNKs control the transcription factors activator protein-1, AP-1. {ECO:0000269|PubMed:10411906, ECO:0000269|PubMed:10688666, ECO:0000269|PubMed:10849426, ECO:0000269|PubMed:11029458, ECO:0000269|PubMed:11154276, ECO:0000269|PubMed:11689443, ECO:0000269|PubMed:11920685, ECO:0000269|PubMed:12697749, ECO:0000269|PubMed:14688258, ECO:0000269|PubMed:14749717, ECO:0000269|PubMed:15023544, ECO:0000269|PubMed:16129676, ECO:0000269|PubMed:17220297, ECO:0000269|PubMed:23102700, ECO:0000269|PubMed:8940179, ECO:0000269|PubMed:8974401, ECO:0000269|PubMed:9564042, ECO:0000269|PubMed:9774977}.
Subcellular locationCytoplasm. Endoplasmic reticulum. Note=Interaction with 14-3-3 proteins alters the distribution of MAP3K5/ASK1 and restricts it to the perinuclear endoplasmic reticulum region.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q99683
Gene Ontology
(Biological Process)
Complete annatation
activation of JUN kinase activity [GO:0007257];
activation of MAPKK activity [GO:0000186];
apoptotic signaling pathway [GO:0097190];
cellular response to hydrogen peroxide [GO:0070301];
cellular response to reactive nitrogen species [GO:1902170];
cellular response to tumor necrosis factor [GO:0071356];
endothelial cell apoptotic process [GO:0072577];
innate immune response [GO:0045087];
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress [GO:0070059];
intrinsic apoptotic signaling pathway in response to oxidative stress [GO:0008631];
JNK cascade [GO:0007254];
MAPK cascade [GO:0000165];
p38MAPK cascade [GO:0038066];
positive regulation of apoptotic process [GO:0043065];
positive regulation of cardiac muscle cell apoptotic process [GO:0010666];
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043280];
positive regulation of JNK cascade [GO:0046330];
positive regulation of JUN kinase activity [GO:0043507];
positive regulation of myoblast differentiation [GO:0045663];
positive regulation of neuron death [GO:1901216];
positive regulation of p38MAPK cascade [GO:1900745];
positive regulation of vascular smooth muscle cell proliferation [GO:1904707];
programmed necrotic cell death [GO:0097300];
protein phosphorylation [GO:0006468];
response to endoplasmic reticulum stress [GO:0034976];
response to ischemia [GO:0002931];
viral process [GO:0016032];
wound healing [GO:0042060]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
magnesium ion binding [GO:0000287];
MAP kinase kinase kinase activity [GO:0004709];
protein homodimerization activity [GO:0042803];
protein kinase activity [GO:0004672];
protein phosphatase binding [GO:0019903];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
IRE1-TRAF2-ASK1 complex [GO:1990604];
protein kinase complex [GO:1902911]
Protein-protein interaction110381
Phylogenetic treeQ99683
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. CD3-0.2322350385090530.4794674394851060.598173433318394
AZA vs. DISU-0.06711272865440620.791776154721530.981068294890813
AZA vs. IL70.2536242093069990.1916084625320360.954510558301023
AZA vs. SAHA-0.2433170010894610.3221149463833330.692933626406784
DISU vs. CD30.1533947836565650.6725890701141070.768483865906166
DISU vs. IL70.3110767914211590.2198823736975890.601911527781215
DISU vs. SAHA-0.1747821456458660.5504239987150460.851343935540555
DMSO vs. AZA-0.06650699075255480.6955434317938411
DMSO vs. CD30.1581133172427520.6218420474419320.715227549603963
DMSO vs. DISU-0.0001987453671251760.9993532143734780.999828688118659
DMSO vs. IL70.3265178869888620.07287815858225030.51287390858856
DMSO vs. SAHA-0.1843263451064570.4377763424102880.771178501939832
HIV vs. Mock in Activation0.4475477088678550.4739273295866630.999983755607037
HIV vs. Mock in Latency0.2122335335128030.2047694859993170.999834320637052
IL7 vs. CD30.4925604757193390.127561160977030.2285698263679
SAHA vs. CD3-0.03546946966779540.9202315036645830.944807791267561
SAHA vs. IL7-0.4995208951916530.04187290130429610.162469012679784
(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 -0.177733 0.266053
(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
203836_s_at 1.41 No upregulated in CD8+ cells

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
2CLQ X-ray 2.3Å A/B=659-951.
3VW6 X-ray 2.4Å A/B=671-939.
4BF2 X-ray 2.1Å A/B=660-977.
4BHN X-ray 2.3Å A/B=660-977.
4BIB X-ray 2.4Å A/B=660-977.
4BIC X-ray 2.6Å A/B=660-977.
4BID X-ray 2.8Å A/B=660-977.
4BIE X-ray 2.3Å A/B=660-977.

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

HIV Partner Interaction Type PubMed
Vif binds 25901786
Nef interacts with 23799149
Nef binds 11298454
Nef inhibits 11298454
Vif inhibited by 25901786
Envelope surface glycoprotein gp120 activates 23382671

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01524 Platinum drug resistance - Homo sapiens (human)
hsa04010 MAPK 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)
hsa04530 Tight junction - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa05014 Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human)