Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001421
UniProt IDP05112
Primary gene name(s)IL4
Synonym gene name(s)unknown
Protein nameInterleukin-4
Protein functionParticipates in at least several B-cell activation processes as well as of other cell types, PubMed:3016727. It is a costimulator of DNA-synthesis. It induces the expression of class II MHC molecules on resting B-cells. It enhances both secretion and cell surface expression of IgE and IgG1. It also regulates the expression of the low affinity Fc receptor for IgE, CD23 on both lymphocytes and monocytes. Positively regulates IL31RA expression in macrophages, By similarity. {ECO:0000250|UniProtKB:P07750, ECO:0000269|PubMed:3016727}.
Subcellular locationSecreted.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P05112
Gene Ontology
(Biological Process)
Complete annatation
B cell costimulation [GO:0031296];
B cell differentiation [GO:0030183];
cellular defense response [GO:0006968];
cellular response to mercury ion [GO:0071288];
chemotaxis [GO:0006935];
cholesterol metabolic process [GO:0008203];
connective tissue growth factor biosynthetic process [GO:0045189];
defense response to protozoan [GO:0042832];
dendritic cell differentiation [GO:0097028];
extrinsic apoptotic signaling pathway in absence of ligand [GO:0097192];
female pregnancy [GO:0007565];
immune response [GO:0006955];
innate immune response in mucosa [GO:0002227];
microglial cell activation [GO:0001774];
myeloid dendritic cell differentiation [GO:0043011];
negative regulation of acute inflammatory response [GO:0002674];
negative regulation of apoptotic process [GO:0043066];
negative regulation of chronic inflammatory response [GO:0002677];
negative regulation of complement-dependent cytotoxicity [GO:1903660];
negative regulation of endothelial cell apoptotic process [GO:2000352];
negative regulation of epithelial cell migration [GO:0010633];
negative regulation of extrinsic apoptotic signaling pathway [GO:2001237];
negative regulation of macrophage activation [GO:0043031];
negative regulation of nitric oxide biosynthetic process [GO:0045019];
negative regulation of osteoclast differentiation [GO:0045671];
negative regulation of T-helper 17 cell differentiation [GO:2000320];
negative regulation of transcription, DNA-templated [GO:0045892];
negative regulation of white fat cell proliferation [GO:0070351];
positive regulation of activated T cell proliferation [GO:0042104];
positive regulation of B cell proliferation [GO:0030890];
positive regulation of chemokine biosynthetic process [GO:0045080];
positive regulation of defense response to virus by host [GO:0002230];
positive regulation of eosinophil chemotaxis [GO:2000424];
positive regulation of interleukin-10 production [GO:0032733];
positive regulation of interleukin-13 production [GO:0032736];
positive regulation of isotype switching to IgE isotypes [GO:0048295];
positive regulation of isotype switching to IgG isotypes [GO:0048304];
positive regulation of mast cell degranulation [GO:0043306];
positive regulation of MHC class II biosynthetic process [GO:0045348];
positive regulation of mononuclear cell migration [GO:0071677];
positive regulation of myoblast fusion [GO:1901741];
positive regulation of reactive oxygen species biosynthetic process [GO:1903428];
positive regulation of sequence-specific DNA binding transcription factor activity [GO:0051091];
positive regulation of T cell differentiation [GO:0045582];
positive regulation of T cell proliferation [GO:0042102];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of tyrosine phosphorylation of Stat5 protein [GO:0042523];
regulation of immune response [GO:0050776];
regulation of isotype switching [GO:0045191];
regulation of phosphorylation [GO:0042325];
regulation of proton transport [GO:0010155];
response to cytokine [GO:0034097];
response to drug [GO:0042493];
response to ethanol [GO:0045471];
response to nutrient [GO:0007584];
response to organic cyclic compound [GO:0014070];
retina development in camera-type eye [GO:0060041];
T-helper 1 cell lineage commitment [GO:0002296];
T-helper 2 cell cytokine production [GO:0035745];
T-helper 2 cell differentiation [GO:0045064];
type 2 immune response [GO:0042092]
Gene Ontology
(Molecular Function)
Complete annatation
cytokine activity [GO:0005125];
growth factor activity [GO:0008083];
interleukin-4 receptor binding [GO:0005136]
Gene Ontology
(Cellular Component)
Complete annatation
external side of plasma membrane [GO:0009897];
extracellular space [GO:0005615]
Protein-protein interaction109779
Phylogenetic treeP05112
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. CD34.511562554405241.10381277451665e-081.28866507649226e-07
AZA vs. DISUunknownunknownunknown
AZA vs. IL7unknownunknownunknown
AZA vs. SAHAunknownunknownunknown
DISU vs. CD3-4.793695535005862.64050670217841e-106.05829498152776e-09
DISU vs. IL7unknownunknownunknown
DISU vs. SAHAunknownunknownunknown
DMSO vs. AZAunknownunknownunknown
DMSO vs. CD3-4.858917290665443.56208462726215e-094.15668512081366e-08
DMSO vs. DISUunknownunknownunknown
DMSO vs. IL7unknownunknownunknown
DMSO vs. SAHAunknownunknownunknown
HIV vs. Mock in Activation-0.546761245642230.6313689081335240.999983755607037
HIV vs. Mock in Latencyunknownunknownunknown
IL7 vs. CD3-6.093167742041532.75690581474919e-127.43378199386664e-11
SAHA vs. CD3-4.371354062606862.88455936914289e-094.35138235164999e-08
SAHA vs. IL7unknownunknownunknown
(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 0.769 4.52E-06 9.36E-05
Infected vs. Bystander 0.913 3.19E-07 6.78E-06
(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) FALSE
(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 2.61968 0.412089
(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
1BBN NMR - A=25-153.
1BCN NMR - A=25-153.
1CYL NMR - A=25-153.
1HIJ X-ray 3.0Å A=25-153.
1HIK X-ray 2.6Å A=25-153.
1HZI X-ray 2.0Å A=25-153.
1IAR X-ray 2.3Å A=25-153.
1ILL Model - 4=25-153.
1ITE Model - A=25-153.
1ITI NMR - A=25-153.
1ITL NMR - A=25-153.
1ITM NMR - A=25-153.
1RCB X-ray 2.2Å A=25-153.
2B8U X-ray 1.8Å A=25-153.
2B8X X-ray 1.7Å A=25-153.
2B8Y X-ray 1.8Å A=25-153.
2B8Z X-ray 2.5Å A=25-153.
2B90 X-ray 2.1Å A=25-153.
2B91 X-ray 2.0Å A=25-153.
2CYK NMR - A=25-153.
2D48 X-ray 1.6Å A=25-153.
2INT X-ray 2.3Å A=25-153.
3BPL X-ray 2.9Å A=25-153.
3BPN X-ray 3.0Å A=25-153.
3QB7 X-ray 3.2Å A/B=25-153.
4YDY X-ray 2.0Å I/J=25-153.
5FHX X-ray 2.5Å A=30-153.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 cooperates with 16547227
Envelope surface glycoprotein gp120 downregulates 1346976
matrix inhibits 12105273
Envelope surface glycoprotein gp120 interacts with 10623799
Envelope surface glycoprotein gp160; precursor upregulates 7523014
Nef inhibits 16429138
Tat upregulates 19621989
Tat induces release of 11149986
integrase enhanced by 24049167
Tat interacts with 17151125
Vpr downregulates 9334723
Vif upregulates 23333304
Envelope surface glycoprotein gp120 upregulates 7589092
Envelope surface glycoprotein gp120 induces release of 24920818

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04060 Cytokine-cytokine receptor interaction - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04630 Jak-STAT signaling pathway - Homo sapiens (human)
hsa04640 Hematopoietic cell lineage - Homo sapiens (human)
hsa04657 IL-17 signaling pathway - Homo sapiens (human)
hsa04658 Th1 and Th2 cell differentiation - Homo sapiens (human)
hsa04659 Th17 cell differentiation - Homo sapiens (human)
hsa04660 T cell receptor signaling pathway - Homo sapiens (human)
hsa04664 Fc epsilon RI signaling pathway - Homo sapiens (human)
hsa04672 Intestinal immune network for IgA production - Homo sapiens (human)
hsa05140 Leishmaniasis - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05310 Asthma - Homo sapiens (human)
hsa05320 Autoimmune thyroid disease - Homo sapiens (human)
hsa05321 Inflammatory bowel disease (IBD) - Homo sapiens (human)
hsa05330 Allograft rejection - Homo sapiens (human)