Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0010804
UniProt IDQ99558
Primary gene name(s)MAP3K14
Synonym gene name(s)NIK
Protein nameMitogen-activated protein kinase kinase kinase 14
Protein functionLymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Promotes proteolytic processing of NFKB2/P100, which leads to activation of NF-kappa-B via the non-canonical pathway. Could act in a receptor-selective manner. {ECO:0000269|PubMed:15084608}.
Subcellular locationCytoplasm.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q99558
Gene Ontology
(Biological Process)
Complete annatation
cellular response to mechanical stimulus [GO:0071260];
I-kappaB kinase/NF-kappaB signaling [GO:0007249];
immune response [GO:0006955];
NIK/NF-kappaB signaling [GO:0038061];
positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123];
T cell costimulation [GO:0031295];
tumor necrosis factor-mediated signaling pathway [GO:0033209]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
kinase activity [GO:0016301];
MAP kinase kinase kinase activity [GO:0004709];
NF-kappaB-inducing kinase activity [GO:0004704];
protein kinase activity [GO:0004672];
protein serine/threonine kinase activity [GO:0004674];
receptor signaling protein serine/threonine kinase activity [GO:0004702]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829]
Protein-protein interaction114487
Phylogenetic treeQ99558
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: HCV
      Viral life cycle: translation
      Mechanism related to antiviral activity: unknown; possiblyNF-?B activation
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. CD31.564235522394354.97253093253436e-050.000260138792832898
AZA vs. DISU0.06478162285180920.7983365448912160.982858957668261
AZA vs. IL7-0.04103489234375610.8318698361068240.999311006273513
AZA vs. SAHA0.0843108755924650.7307196172594210.925385827990297
DISU vs. CD3-1.51250030764819.68778408171334e-050.000549876177233799
DISU vs. IL7-0.1153681598362470.6476794519528440.897947408772405
DISU vs. SAHA0.0224170837064620.9387568368866740.985406773108689
DMSO vs. AZA0.05049074595349270.7648047284886091
DMSO vs. CD3-1.527612824451373.40197204754533e-050.00017209774646162
DMSO vs. DISU-0.01676432652912340.9453561398345040.992938081932553
DMSO vs. IL7-0.08374211894910450.6432449652961240.923164304249721
DMSO vs. SAHA0.02947960449951260.900939554507760.975996264087583
HIV vs. Mock in Activation0.1773344910813940.8256989805063130.999983755607037
HIV vs. Mock in Latency0.02484708419760830.8809738270473090.999834320637052
IL7 vs. CD3-1.6000614324662.29878313990906e-050.000161762643640753
SAHA vs. CD3-1.503364569987130.0001186405757871430.000558373977861415
SAHA vs. IL70.1231530767225990.6144583963460430.805911934788154
(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 -0.269723 0.0620668
(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
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
4DN5 X-ray 2.5Å A/B=330-680.
4G3D X-ray 2.9Å A/B/D/E=308-673.
4IDT X-ray 2.4Å A/B=330-680.
4IDV X-ray 2.9Å A/B/C/D=330-680.

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

HIV Partner Interaction Type PubMed
Tat enhances 11511100
HIV-1 virus replication enhanced by expression of human gene 18976975

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)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04660 T cell receptor signaling pathway - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa04672 Intestinal immune network for IgA production - Homo sapiens (human)
hsa05120 Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)