Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0008475
UniProt IDP01374
Primary gene name(s)LTA
Synonym gene name(s)TNFB, TNFSF1
Protein nameLymphotoxin-alpha
Protein functionCytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1, TNFRSF1B/TNFBR and TNFRSF14/HVEM. In its heterotrimeric form with LTB binds to TNFRSF3/LTBR. Lymphotoxin is produced by lymphocytes and cytotoxic for a wide range of tumor cells in vitro and in vivo.
Subcellular locationSecreted. Membrane. Note=The homotrimer is secreted. The heterotrimer is membrane-associated.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P01374
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
cell-cell signaling [GO:0007267];
defense response to Gram-positive bacterium [GO:0050830];
humoral immune response [GO:0006959];
lymph node development [GO:0048535];
negative regulation of fibroblast proliferation [GO:0048147];
negative regulation of growth of symbiont in host [GO:0044130];
positive regulation of apoptotic process [GO:0043065];
positive regulation of chronic inflammatory response to antigenic stimulus [GO:0002876];
positive regulation of glial cell proliferation [GO:0060252];
positive regulation of humoral immune response mediated by circulating immunoglobulin [GO:0002925];
positive regulation of interferon-gamma production [GO:0032729];
response to drug [GO:0042493];
response to hypoxia [GO:0001666];
response to lipopolysaccharide [GO:0032496];
response to nutrient [GO:0007584];
signal transduction [GO:0007165];
tumor necrosis factor-mediated signaling pathway [GO:0033209]
Gene Ontology
(Molecular Function)
Complete annatation
receptor binding [GO:0005102]
Gene Ontology
(Cellular Component)
Complete annatation
extracellular space [GO:0005615];
plasma membrane [GO:0005886]
Protein-protein interaction110227
Phylogenetic treeP01374
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. CD35.874892302867500
AZA vs. DISU0.3861850012865520.2473443499168980.829470240410971
AZA vs. IL71.351839042857224.19355959335732e-060.00141919731051419
AZA vs. SAHA0.2213262509661180.3766229040165830.741712808489076
DISU vs. CD3-5.501720745780644.41868763800812e-141.95903816045101e-12
DISU vs. IL70.9578649908003990.01983701376892410.176114830722339
DISU vs. SAHA-0.163619003360980.6650031913888770.898199431342554
DMSO vs. AZA0.04057056782771770.817092865799331
DMSO vs. CD3-5.8509892471520400
DMSO vs. DISU-0.3490803250673770.2997144707746730.807887568985919
DMSO vs. IL71.319447897888261.04530443160167e-050.00200490077777424
DMSO vs. SAHA0.1746999564630030.4893391937906960.808210107630622
HIV vs. Mock in Activation-0.7398763790501550.483621091826930.999983755607037
HIV vs. Mock in Latency-0.7389795846508276.37028195171752e-050.00721997219099172
IL7 vs. CD3-4.511889733674281.37125866217502e-113.36628368321891e-10
SAHA vs. CD3-5.679121288636181.11022302462516e-166.17382324025871e-15
SAHA vs. IL7-1.134299719993280.001042270904172750.0120208045979342
(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
-0.4365 0.02816

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 1.496 1.07E-13 1.30E-10
Infected vs. Bystander 1.423 3.16E-13 1.12E-10
(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 0.78892 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
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

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00005 Etanercept approved, investigational unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1TNR X-ray 2.8Å A=62-205.
4MXV X-ray 3.2Å A/B/D=62-205.
4MXW X-ray 3.6Å A/X=62-205.

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

HIV Partner Interaction Type PubMed
Tat upregulates 1279199
2243081
7695626
7818827
8139045
1637575523364796
Envelope surface glycoprotein gp120 upregulates 16934308
Tat downregulates 9282784
16375755

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04060 Cytokine-cytokine receptor interaction - Homo sapiens (human)
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa04940 Type I diabetes mellitus - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
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