Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0013824
UniProt IDP05231
Primary gene name(s)IL6
Synonym gene name(s)IFNB2
Protein nameInterleukin-6
Protein functionCytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Involved in lymphocyte and monocyte differentiation. Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Required for the generation of T(H17 cells. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation.
Subcellular locationSecreted.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P05231
Gene Ontology
(Biological Process)
Complete annatation
acute-phase response [GO:0006953];
aging [GO:0007568];
bone remodeling [GO:0046849];
branching involved in salivary gland morphogenesis [GO:0060445];
cell growth [GO:0016049];
cell redox homeostasis [GO:0045454];
cellular response to dexamethasone stimulus [GO:0071549];
cellular response to estradiol stimulus [GO:0071392];
cellular response to hepatocyte growth factor stimulus [GO:0035729];
cellular response to hydrogen peroxide [GO:0070301];
cellular response to interleukin-1 [GO:0071347];
cellular response to lipopolysaccharide [GO:0071222];
cellular response to nutrient levels [GO:0031669];
cellular response to prolactin [GO:1990646];
cellular response to tumor necrosis factor [GO:0071356];
cytokine-mediated signaling pathway [GO:0019221];
defense response to Gram-negative bacterium [GO:0050829];
defense response to Gram-positive bacterium [GO:0050830];
defense response to protozoan [GO:0042832];
defense response to virus [GO:0051607];
endocrine pancreas development [GO:0031018];
epithelial cell proliferation involved in salivary gland morphogenesis [GO:0060664];
glucagon secretion [GO:0070091];
glucose homeostasis [GO:0042593];
hepatic immune response [GO:0002384];
humoral immune response [GO:0006959];
inflammatory response [GO:0006954];
interleukin-6-mediated signaling pathway [GO:0070102];
monocyte chemotaxis [GO:0002548];
muscle cell cellular homeostasis [GO:0046716];
negative regulation of apoptotic process [GO:0043066];
negative regulation of bone resorption [GO:0045779];
negative regulation of cell proliferation [GO:0008285];
negative regulation of chemokine biosynthetic process [GO:0045079];
negative regulation of collagen biosynthetic process [GO:0032966];
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043154];
negative regulation of cytokine secretion [GO:0050710];
negative regulation of fat cell differentiation [GO:0045599];
negative regulation of gluconeogenesis [GO:0045721];
negative regulation of hormone secretion [GO:0046888];
negative regulation of interleukin-1-mediated signaling pathway [GO:2000660];
negative regulation of lipid storage [GO:0010888];
negative regulation of membrane potential [GO:0045837];
negative regulation of muscle organ development [GO:0048635];
negative regulation of neuron death [GO:1901215];
negative regulation of protein kinase activity [GO:0006469];
neuron projection development [GO:0031175];
neutrophil apoptotic process [GO:0001781];
neutrophil mediated immunity [GO:0002446];
platelet activation [GO:0030168];
positive regulation of acute inflammatory response [GO:0002675];
positive regulation of apoptotic process [GO:0043065];
positive regulation of B cell activation [GO:0050871];
positive regulation of cell proliferation [GO:0008284];
positive regulation of cell proliferation in bone marrow [GO:0071864];
positive regulation of chemokine production [GO:0032722];
positive regulation of DNA replication [GO:0045740];
positive regulation of epithelial cell proliferation [GO:0050679];
positive regulation of ERK1 and ERK2 cascade [GO:0070374];
positive regulation of gene expression [GO:0010628];
positive regulation of immunoglobulin secretion [GO:0051024];
positive regulation of interleukin-6 production [GO:0032755];
positive regulation of JAK-STAT cascade [GO:0046427];
positive regulation of leukocyte chemotaxis [GO:0002690];
positive regulation of MAPK cascade [GO:0043410];
positive regulation of neuron projection development [GO:0010976];
positive regulation of nitric oxide biosynthetic process [GO:0045429];
positive regulation of osteoblast differentiation [GO:0045669];
positive regulation of peptidyl-serine phosphorylation [GO:0033138];
positive regulation of peptidyl-tyrosine phosphorylation [GO:0050731];
positive regulation of protein import into nucleus, translocation [GO:0033160];
positive regulation of protein kinase B signaling [GO:0051897];
positive regulation of sequence-specific DNA binding transcription factor activity [GO:0051091];
positive regulation of smooth muscle cell proliferation [GO:0048661];
positive regulation of STAT protein import into nucleus [GO:2000366];
positive regulation of T cell proliferation [GO:0042102];
positive regulation of T-helper 2 cell cytokine production [GO:2000553];
positive regulation of T-helper 2 cell differentiation [GO:0045630];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of translation [GO:0045727];
positive regulation of transmission of nerve impulse [GO:0051971];
positive regulation of type B pancreatic cell apoptotic process [GO:2000676];
positive regulation of tyrosine phosphorylation of Stat3 protein [GO:0042517];
regulation of angiogenesis [GO:0045765];
regulation of cell shape [GO:0008360];
regulation of circadian sleep/wake cycle, non-REM sleep [GO:0045188];
regulation of vascular endothelial growth factor production [GO:0010574];
response to amino acid [GO:0043200];
response to antibiotic [GO:0046677];
response to auditory stimulus [GO:0010996];
response to caffeine [GO:0031000];
response to calcium ion [GO:0051592];
response to cold [GO:0009409];
response to drug [GO:0042493];
response to electrical stimulus [GO:0051602];
response to glucocorticoid [GO:0051384];
response to heat [GO:0009408];
response to insulin [GO:0032868];
response to peptidoglycan [GO:0032494];
response to yeast [GO:0001878];
T-helper 17 cell lineage commitment [GO:0072540]
Gene Ontology
(Molecular Function)
Complete annatation
unknown
Gene Ontology
(Cellular Component)
Complete annatation
unknown
Protein-protein interaction109783
Phylogenetic treeP05231
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. CD3unknownunknownunknown
AZA vs. DISUunknownunknownunknown
AZA vs. IL7unknownunknownunknown
AZA vs. SAHAunknownunknownunknown
DISU vs. CD3unknownunknownunknown
DISU vs. IL7unknownunknownunknown
DISU vs. SAHAunknownunknownunknown
DMSO vs. AZAunknownunknownunknown
DMSO vs. CD3unknownunknownunknown
DMSO vs. DISUunknownunknownunknown
DMSO vs. IL7unknownunknownunknown
DMSO vs. SAHAunknownunknownunknown
HIV vs. Mock in Activationunknownunknownunknown
HIV vs. Mock in Latencyunknownunknownunknown
IL7 vs. CD3unknownunknownunknown
SAHA vs. CD3unknownunknownunknown
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 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 -1.78554 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
DB01404 Ginseng approved, nutraceutical unknown antagonist
DB05250 681323 investigational unknown unknown
DB05017 YSIL6 investigational unknown unknown
DB05066 AV411 investigational unknown unknown
DB05470 VX-702 investigational unknown unknown
DB05744 CRx-139 investigational unknown unknown
DB05767 HMPL-004 investigational unknown unknown
DB09036 Siltuximab approved yes antagonist

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1ALU X-ray 1.9Å A=28-212.
1IL6 NMR - A=28-212.
1N2Q Model - E/F=30-212.
1P9M X-ray 3.6Å B=29-212.
2IL6 NMR - A=28-212.
4CNI X-ray 2.2Å C/D=42-212.
4J4L X-ray 2.3Å C/D=47-212.
4NI7 X-ray 2.4Å A=28-212.
4NI9 X-ray 2.5Å A/C=28-212.
4O9H X-ray 2.4Å A=28-212.
4ZS7 X-ray 2.9Å A=42-212.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp160; precursor upregulates 1656094
8018916
8938574
2500891721712995
matrix upregulates 8938574
capsid upregulated by 24999042
capsid enhances 25240755
Envelope transmembrane glycoprotein gp41 inhibits 25121610
Tat upregulates 15630704
16206161
2553989815857508
16273337
1719738517151125
19621989
22301094
23190742
25539898
25879536
26048716
7494249
7523444
7526541
7693046
7803268
7986583
8113688
8179923
8510564
9169458
9378998
9671211
9792375
10358063
10964543
16375755
16539678
17197385
17376903
17716703
18003888
18276775
19526283
19621989
19622906
20121167
20138641
20588103
23190742
23898208
24044867
24073214
24418364
25539898
25847297
258795368113688
91694589671211
19526283
24359561
Nef induces 26075907
26075907
26075907
Envelope transmembrane glycoprotein gp41 downregulates 22889273
Tat activated by 11689614
2058810317150965
Envelope surface glycoprotein gp120 inhibits 22814248
23554973
23554973
Vpr involves 26270987
26270987
26270987
26270987
26270987
26270987
Envelope surface glycoprotein gp160; precursor induces release of 21689404
Envelope surface glycoprotein gp120 upregulates 11517385
1749830921712995
23251686
23999600
25008924
25856395
7511078
7815507
8764000
9108403
9225992
9658081
12089333
15481145
16160188
25036364
Tat downregulates 21900165
Nef synergizes with 23604117
23604117
23604117
Envelope surface glycoprotein gp120 downregulates 17360657
23554973
Envelope transmembrane glycoprotein gp41 interacts with 8247028
Tat induces release of 16539678
25847297
Pr55(Gag) induces release of 18945465
23897063
25240755
Pr55(Gag) upregulates 8938574
matrix induces release of 25704763
Nef induces release of 23554973
23554973
25847297
Tat inhibits 22814248
Vpr downregulates 17409234
19275586
Vpr upregulates 10775602
19275586
19275588
2014519820145198
20145198
20877724
23728617
26270987
26270987
26270987
Envelope surface glycoprotein gp120 induces release of 1346976
1656094
1918997
7511078
7536422
7704970
8806809
12089333
15288392
15481145
18003888
20121167
20817073
24043886
2492081819736361
23554973
24840331
25008924
25008924
Vpr enhances 26270987
26270987
Nef upregulates 10415019
12370346
12396456
2355497312574335
12960275
18003888
19013323
20012528
20380698
22407921
23215766
2552928321858117
21886773
232157668086129
10388525
20012528
21668366
Envelope transmembrane glycoprotein gp41 upregulates 23383108
244453667553888
10964543
24445366

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01521 EGFR tyrosine kinase inhibitor resistance - Homo sapiens (human)
hsa01523 Antifolate resistance - Homo sapiens (human)
hsa04060 Cytokine-cytokine receptor interaction - Homo sapiens (human)
hsa04066 HIF-1 signaling pathway - Homo sapiens (human)
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04620 Toll-like receptor signaling pathway - Homo sapiens (human)
hsa04621 NOD-like receptor signaling pathway - Homo sapiens (human)
hsa04623 Cytosolic DNA-sensing 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)
hsa04659 Th17 cell differentiation - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa04672 Intestinal immune network for IgA production - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa04933 AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
hsa05020 Prion diseases - Homo sapiens (human)
hsa05132 Salmonella infection - Homo sapiens (human)
hsa05133 Pertussis - Homo sapiens (human)
hsa05134 Legionellosis - Homo sapiens (human)
hsa05142 Chagas disease (American trypanosomiasis) - Homo sapiens (human)
hsa05143 African trypanosomiasis - Homo sapiens (human)
hsa05144 Malaria - Homo sapiens (human)
hsa05146 Amoebiasis - Homo sapiens (human)
hsa05152 Tuberculosis - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05202 Transcriptional misregulation in cancer - Homo sapiens (human)
hsa05321 Inflammatory bowel disease (IBD) - Homo sapiens (human)
hsa05323 Rheumatoid arthritis - Homo sapiens (human)
hsa05332 Graft-versus-host disease - Homo sapiens (human)
hsa05410 Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human)
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