Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001698
UniProt IDQ12851
Primary gene name(s)MAP4K2
Synonym gene name(s)GCK, RAB8IP
Protein nameMitogen-activated protein kinase kinase kinase kinase 2
Protein functionSerine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase, MAP4K and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase, SAP/JNK signaling pathway and to a lesser extent of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns, PAMPs such as polyinosine-polycytidine, poly(IC, lipopolysaccharides, LPS, lipid A, peptidoglycan, PGN, or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Mediates also the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion. {ECO:0000269|PubMed:11784851, ECO:0000269|PubMed:15456887, ECO:0000269|PubMed:17584736, ECO:0000269|PubMed:7477268, ECO:0000269|PubMed:7515885, ECO:0000269|PubMed:9712898}.
Subcellular locationCytoplasm {ECO:0000250}. Basolateral cell membrane {ECO:0000250};
Peripheral membrane protein {ECO:0000250}. Golgi apparatus membrane {ECO:0000250};
Peripheral membrane protein {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q12851
Gene Ontology
(Biological Process)
Complete annatation
activation of JUN kinase activity [GO:0007257];
immune response [GO:0006955];
innate immune response [GO:0045087];
intracellular signal transduction [GO:0035556];
JNK cascade [GO:0007254];
positive regulation of JNK cascade [GO:0046330];
protein phosphorylation [GO:0006468];
vesicle targeting [GO:0006903]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
MAP kinase kinase kinase kinase activity [GO:0008349];
mitogen-activated protein kinase kinase kinase binding [GO:0031435];
protein serine/threonine kinase activity [GO:0004674];
receptor signaling protein serine/threonine kinase activity [GO:0004702]
Gene Ontology
(Cellular Component)
Complete annatation
basolateral plasma membrane [GO:0016323];
Golgi membrane [GO:0000139]
Protein-protein interaction111809
Phylogenetic treeQ12851
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. CD3-1.36771477872190.001999281184253520.00661685683115263
AZA vs. DISU0.08078086074676920.7496186396130530.976021571236163
AZA vs. IL7-0.2314949473148640.229792141934150.989589389892523
AZA vs. SAHA0.3698155917818760.1312331131702870.461551084444448
DISU vs. CD31.435686697924730.001053196428843490.00434004455122658
DISU vs. IL7-0.3219060747254550.2018160513117510.578419203147394
DISU vs. SAHA0.2919604861320440.319571770714780.701908660937137
DMSO vs. AZA0.06472476308131160.6998371766331251
DMSO vs. CD31.418675361069470.0008882224707794650.00308390678089252
DMSO vs. DISU-0.01840167378835770.9399027646929080.992373876590717
DMSO vs. IL7-0.2885355341642230.1095559972621690.594771976229253
DMSO vs. SAHA0.3009063285798690.203691829685110.54420130565224
HIV vs. Mock in Activation0.3127065618170840.7410933914520110.999983755607037
HIV vs. Mock in Latency0.1039113381710940.529651251802370.999834320637052
IL7 vs. CD31.14121123792120.01009236659871330.0300755717165688
SAHA vs. CD31.714370327972590.0002649899456358410.00112776009057671
SAHA vs. IL70.5989630848325820.01483562140086110.0823994683111941
(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 -0.0440315 0.83563
(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
1.046 0.915 0.937 1.461 1.003
(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

not found

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

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04010 MAPK signaling pathway - Homo sapiens (human)