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IL6 interleukin 6 [ Homo sapiens (human) ]

Gene ID: 3569, updated on 21-Apr-2014
Official Symbol
IL6provided by HGNC
Official Full Name
interleukin 6provided by HGNC
Primary source
HGNC:6018
See related
Ensembl:ENSG00000136244; HPRD:00970; MIM:147620; Vega:OTTHUMG00000023178
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HGF; HSF; BSF2; IL-6; IFNB2
Summary
This gene encodes a cytokine that functions in inflammation and the maturation of B cells. In addition, the encoded protein has been shown to be an endogenous pyrogen capable of inducing fever in people with autoimmune diseases or infections. The protein is primarily produced at sites of acute and chronic inflammation, where it is secreted into the serum and induces a transcriptional inflammatory response through interleukin 6 receptor, alpha. The functioning of this gene is implicated in a wide variety of inflammation-associated disease states, including suspectibility to diabetes mellitus and systemic juvenile rheumatoid arthritis. [provided by RefSeq, Jun 2011]
Location :
7p21
Sequence :
Chromosome: 7; NC_000007.14 (22727147..22732002)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC100506178 Neighboring gene uncharacterized LOC102724162 Neighboring gene uncharacterized LOC401312 Neighboring gene ribosomal protein S26 pseudogene 32 Neighboring gene translocase of outer mitochondrial membrane 7 homolog (yeast)

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Cerebral arteriovenous malformation
MedGen: C0917804 OMIM: 108010 GeneReviews: Not available
Compare labs
Classic Kaposi sarcoma
MedGen: C0036220 OMIM: 148000 GeneReviews: Not available
not available
Diabetes mellitus type 2
MedGen: C0011860 OMIM: 125853 GeneReviews: Not available
Compare labs
Inflammatory bowel disease 1
MedGen: C0678202 OMIM: 266600 GeneReviews: Not available
Compare labs
Rheumatoid arthritis, systemic juvenile
MedGen: C1858558 OMIM: 604302 GeneReviews: Not available
not available

NHGRI GWAS Catalog

Description
Genome-wide association scan for survival on dialysis in African-Americans with type 2 diabetes.
NHGRI GWA Catalog
Genome-wide association study for C-reactive protein levels identified pleiotropic associations in the IL6 locus.
NHGRI GWA Catalog
Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.
NHGRI GWA Catalog

Protein interactions

Protein Gene Interaction Pubs
Env, gp160, envelope glycoprotein env HIV-1 gp140 monomer and trimer induce a time-dependent IL-6 upregulation in human astrocyte cells PubMed
env Chimeric HIV-1 gp140 - CD40L trimers can target and activate dendritic cells to release IL-6, IL-10 and IL-12 PubMed
env HIV-1 gp160 induces interleukin-6 production in CD4+ T cells PubMed
Envelope surface glycoprotein gp120 env HIV-1 gp120 induces a time-dependent IL-6 upregulation by translocating NF-kappaB1 from cytoplasm to nucleus in human astrocyte cells PubMed
env HIV-1 gp120 inhibits CpG-A-induced secretion of TNF-a, IL-6, and IP-10 proteins in plasmacytoid dendritic cells and PBMCs PubMed
env HIV-1 gp120 inhibits TLR9-mediated upregulation of CD83 and the secretion of inflammatory cytokines TNF-alpha and IL-6, and chemokine IP10 in plasmacytoid dendritic cells (pDC) PubMed
env Cytokines induced in vitro by HIV-1 gp120 in normal peripheral blood mononuclear cells (PBMC) include interferon-alpha (IFN-alpha) and IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-10, IL-1 alpha and IL-1 beta PubMed
env HIV-1 gp120 stimulates monocytes to release TNF-alpha, IL-1 beta, IL-6, and granulocyte-macrophage-CSF, and this effect can be blocked with soluble CD4 PubMed
env Treatment of human hepatic stellate cells with gp120 significantly increases secretion and gene expression of CCL2, metalloprotease-1 and interleukin-6. Gp120 also induces activation of Akt, NF-kappaB, and p38(MAPK) PubMed
env HIV-1 gp120 activates human brain micro vascular endothelial cells (HBMEC) via CD4 in upregulating ICAM-1 and VCAM-1 expression, IL-6 secretion and increased monocyte transmigration across monolayers PubMed
Envelope transmembrane glycoprotein gp41 env HIV-1 gp41 induces significant IL-6 production by human monocytic cells; IL-10 inhibits gp41-induced IL-6 production and reduces the expression of IL-6 mRNA PubMed
env PWM, LPS, IFN-gamma and IL-6 can increase HIV-1 gp41 binding to human B cells PubMed
Gag, Pr55 gag HIV-1 Gag virus-like particles expressed by recombinant baculoviruses activate human PBMC to release IL-6 in a dose and time dependent manner PubMed
gag The Matrix protein of HIV-1 Gag increases IL-6 production in placental mononuclear cells PubMed
Nef, p27 nef HIV-1 Nef inhibits IFN-gamma-induced apoptosis and upregulates TNF-alpha, IL-6 and MIP-3a production by Caco-2 cells while downregulates IL-10 production PubMed
nef Both the myristoylation site and the acidic cluster in HIV-1 Nef are required for the activation of NF-kappaB, which induces upregulation of TNFalpha and IL6 expression PubMed
nef Treatment of human PBMC and PBL with soluble HIV-1 Nef upregulates IL-6 production PubMed
nef The expression of HIV-1 Nef in primary human monocyte-derived macrophages (MDM) induces a significant increase in the concentration of IL-6 PubMed
nef Intracisternal HIV-1 Nef injection upregulates levels of IL-6, TNF-alpha, and IFN-gamma in rat cerebrospinal fluid PubMed
nef HIV-1 Nef expression by immature human and macaque dendritic cells (DCs) upregulates IL-6, IL-12, TNF-alpha, CXCL8, CCL3, and CCL4 release, but without upregulating co-stimulatory and other molecules characteristic of mature DCs PubMed
Tat, p14 tat HIV-1 Tat significantly decreases TNF-alpha and IL-6 secretion but increases IL-4 levels in human hepatocellular carcinoma cells PubMed
tat HIV-1 Tat inhibits CpG-A-induced secretion of TNF-a, IL-6, and IP-10 proteins in plasmacytoid dendritic cells and PBMCs PubMed
tat HIV-1 Tat downregulates the expression of adiponectin protein and upregulates the expression of IL-6, IL-8, and MCP-1 proteins in human SGBS preadipocytes PubMed
tat Monocytes treated with HIV-1 clade B Tat show significant upregulation of proinflammatory cytokines, IL-6 and TNF-alpha, as compared to clade C Tat-treated cultures PubMed
tat Sulfated polymannuroguluronate (SPMG) significantly reverses HIV-1 Tat-induced release of pro-inflammatory cytokines such as TNF-alpha, IL-1beta, and IL-6 in THP-1 cells PubMed
tat Ectopic expression of HIV-1 Tat induces the production of human IL-6 (huIL-6) and its receptor (huIL-6Ra) and activates STAT3 signaling; these effects are involved in Tat-mediated activation of Kaposi's sarcoma-associated herpes virus (KSHV) replication PubMed
tat Upregulation of IL-6 by HIV-1 Tat in human brain endothelial cells is mediated through activation of protein kinase C (PK-C) and cAMP-dependent protein kinase (PK-A) PubMed
tat HIV-1 Tat upregulates IL-6 expression in monocytes, astrocytes, microglial cells, human brain endothelial cells, THP-1 and Jurkat T-cells, MC3 B-cells, HeLa, and cells from Kaposi's sarcoma lesions PubMed
tat Treatment of T lymphocytes with IL-2, IL-6 and TNFalpha increases CDK9 and cyclin T1 protein levels, suggesting a mechanism for activation of HIV-1 Tat function and reactivation of HIV-1 in CD4+ T lymphocytes harboring a latent provirus PubMed
tat Hydroxyurea and IL-6 synergistically enhance HIV-1 Tat activation of HIV-1 LTR-driven transcription via the Sp1 binding site PubMed
tat HIV-1 Tat protein upregulates expression of IL-6 and IL-8 in human breast cancer cells by an NF-kappaB-dependent pathway PubMed
tat Astrocyte cultures treated with morphine and HIV-1 Tat show exaggerated increases in chemokine release, including monocyte chemoattractant protein-1 (MCP-1), RANTES, and IL-6 PubMed
tat IL-6 and IL-6 receptor are upregulated in human epithelial cells by HIV-1 Tat treatment PubMed
tat HIV-1 Tat upregulates IL-6 expression by transactivating the IL-6 promoter, an effect mediated through enhancement of CAAT enhancer-binding protein (C/EBP; nuclear factor-IL-6) DNA binding activity PubMed
Vpr, p15 vpr Concurrent exposure of HIV-1 Vpr with HCV core protein causes higher IL-6 expression than HIV-1 Vpr-treated human fetal microglia PubMed
vpr HIV-1 Vpr-induced IL-6 production depends on the activation of NFkappaB and the involvement of C/EBP-beta, TLR4, and MyD88 PubMed
vpr Soluble HIV-1 Vpr induces a markedly reduced expression of IL-6 in monocytoid cells PubMed
vpr HIV-1 Vpr upregulates IL-6 expression in primary macrophages and in A549 cells PubMed
matrix gag HIV-1 Matrix upregulates IL-6 production in placental mononuclear cells PubMed

Go to the HIV-1, Human Protein Interaction Database

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    Toll-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
  • Toll-like receptor signaling pathway, organism-specific biosystem (from WikiPathways)
    Toll-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
  • Toll-like receptor signaling pathway, conserved biosystem (from KEGG)
    Toll-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
  • Transcriptional misregulation in cancer, organism-specific biosystem (from KEGG)
    Transcriptional misregulation in cancer, organism-specific biosystem
    Transcriptional misregulation in cancer
  • Transcriptional misregulation in cancer, conserved biosystem (from KEGG)
    Transcriptional misregulation in cancer, conserved biosystem
    Transcriptional misregulation in cancer
  • Tuberculosis, organism-specific biosystem (from KEGG)
    Tuberculosis, organism-specific biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
  • Tuberculosis, conserved biosystem (from KEGG)
    Tuberculosis, conserved biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
  • Validated transcriptional targets of AP1 family members Fra1 and Fra2, organism-specific biosystem (from Pathway Interaction Database)
    Validated transcriptional targets of AP1 family members Fra1 and Fra2, organism-specific biosystem
    Validated transcriptional targets of AP1 family members Fra1 and Fra2
  • amb2 Integrin signaling, organism-specific biosystem (from Pathway Interaction Database)
    amb2 Integrin signaling, organism-specific biosystem
    amb2 Integrin signaling
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
cytokine activity IDA
Inferred from Direct Assay
more info
PubMed 
cytokine activity NAS
Non-traceable Author Statement
more info
PubMed 
growth factor activity IDA
Inferred from Direct Assay
more info
PubMed 
interleukin-6 receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
contributes_to interleukin-6 receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
interleukin-6 receptor binding NAS
Non-traceable Author Statement
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
T-helper 17 cell lineage commitment ISS
Inferred from Sequence or Structural Similarity
more info
 
acute-phase response TAS
Traceable Author Statement
more info
PubMed 
aging IEA
Inferred from Electronic Annotation
more info
 
bone remodeling IEA
Inferred from Electronic Annotation
more info
 
branching involved in salivary gland morphogenesis IEA
Inferred from Electronic Annotation
more info
 
cell growth IEA
Inferred from Electronic Annotation
more info
 
cell redox homeostasis IEA
Inferred from Electronic Annotation
more info
 
cellular response to hydrogen peroxide IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to lipopolysaccharide IMP
Inferred from Mutant Phenotype
more info
 
cytokine-mediated signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
defense response to Gram-negative bacterium IEP
Inferred from Expression Pattern
more info
PubMed 
defense response to Gram-positive bacterium IEP
Inferred from Expression Pattern
more info
PubMed 
defense response to protozoan IEA
Inferred from Electronic Annotation
more info
 
defense response to virus IDA
Inferred from Direct Assay
more info
PubMed 
endocrine pancreas development ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
epithelial cell proliferation involved in salivary gland morphogenesis IEA
Inferred from Electronic Annotation
more info
 
glucagon secretion ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
hepatic immune response IDA
Inferred from Direct Assay
more info
PubMed 
hepatic immune response TAS
Traceable Author Statement
more info
PubMed 
humoral immune response IC
Inferred by Curator
more info
PubMed 
inflammatory response IDA
Inferred from Direct Assay
more info
PubMed 
interleukin-6-mediated signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
monocyte chemotaxis IC
Inferred by Curator
more info
PubMed 
muscle cell cellular homeostasis IEA
Inferred from Electronic Annotation
more info
 
negative regulation of apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cell proliferation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of chemokine biosynthetic process ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of collagen biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process IEA
Inferred from Electronic Annotation
more info
 
negative regulation of cytokine secretion IEA
Inferred from Electronic Annotation
more info
 
negative regulation of fat cell differentiation NAS
Non-traceable Author Statement
more info
PubMed 
negative regulation of gluconeogenesis IEA
Inferred from Electronic Annotation
more info
 
negative regulation of hormone secretion IEA
Inferred from Electronic Annotation
more info
 
negative regulation of lipid storage NAS
Non-traceable Author Statement
more info
PubMed 
negative regulation of muscle organ development IEA
Inferred from Electronic Annotation
more info
 
negative regulation of neuron death IEA
Inferred from Electronic Annotation
more info
 
negative regulation of protein kinase activity IEA
Inferred from Electronic Annotation
more info
 
neuron projection development IMP
Inferred from Mutant Phenotype
more info
PubMed 
neutrophil apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
neutrophil mediated immunity IC
Inferred by Curator
more info
PubMed 
platelet activation TAS
Traceable Author Statement
more info
PubMed 
positive regulation of B cell activation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of DNA replication IEA
Inferred from Electronic Annotation
more info
 
positive regulation of ERK1 and ERK2 cascade IEA
Inferred from Electronic Annotation
more info
 
positive regulation of JAK-STAT cascade IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of MAPK cascade IDA
Inferred from Direct Assay
more info
PubMed 
NOT positive regulation of NF-kappaB transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of STAT protein import into nucleus IC
Inferred by Curator
more info
PubMed 
positive regulation of T cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of T-helper 2 cell differentiation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of acute inflammatory response IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of chemokine production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of chemokine production IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of epithelial cell proliferation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of immunoglobulin secretion IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interleukin-6 production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of leukocyte chemotaxis IC
Inferred by Curator
more info
PubMed 
positive regulation of neuron differentiation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of nitric oxide biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of osteoblast differentiation TAS
Traceable Author Statement
more info
PubMed 
positive regulation of peptidyl-serine phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of peptidyl-tyrosine phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of protein import into nucleus, translocation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of protein kinase B signaling IEA
Inferred from Electronic Annotation
more info
 
positive regulation of sequence-specific DNA binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of smooth muscle cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription from RNA polymerase II promoter IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of translation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transmission of nerve impulse IEA
Inferred from Electronic Annotation
more info
 
positive regulation of type B pancreatic cell apoptotic process TAS
Traceable Author Statement
more info
PubMed 
positive regulation of tyrosine phosphorylation of Stat3 protein IDA
Inferred from Direct Assay
more info
PubMed 
regulation of angiogenesis IC
Inferred by Curator
more info
PubMed 
regulation of cell shape IEA
Inferred from Electronic Annotation
more info
 
regulation of circadian sleep/wake cycle, non-REM sleep IEA
Inferred from Electronic Annotation
more info
 
regulation of vascular endothelial growth factor production IDA
Inferred from Direct Assay
more info
PubMed 
response to amino acid IEA
Inferred from Electronic Annotation
more info
 
response to antibiotic IEA
Inferred from Electronic Annotation
more info
 
response to caffeine IEA
Inferred from Electronic Annotation
more info
 
response to calcium ion IEA
Inferred from Electronic Annotation
more info
 
response to cold IEA
Inferred from Electronic Annotation
more info
 
response to drug IEA
Inferred from Electronic Annotation
more info
 
response to electrical stimulus IEA
Inferred from Electronic Annotation
more info
 
response to glucocorticoid IDA
Inferred from Direct Assay
more info
PubMed 
response to heat IEA
Inferred from Electronic Annotation
more info
 
response to insulin IEA
Inferred from Electronic Annotation
more info
 
response to mechanical stimulus IEA
Inferred from Electronic Annotation
more info
 
response to nutrient levels IEA
Inferred from Electronic Annotation
more info
 
response to peptidoglycan IEP
Inferred from Expression Pattern
more info
PubMed 
Component Evidence Code Pubs
external side of plasma membrane IEA
Inferred from Electronic Annotation
more info
 
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space IDA
Inferred from Direct Assay
more info
PubMed 
interleukin-6 receptor complex IDA
Inferred from Direct Assay
more info
PubMed 
Preferred Names
interleukin-6
Names
interleukin-6
CDF
BSF-2
IFN-beta-2
interferon beta-2
interleukin BSF-2
interferon, beta 2
hybridoma growth factor
CTL differentiation factor
B-cell stimulatory factor 2
B-cell differentiation factor

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011640.1 RefSeqGene

    Range
    5001..9856
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000600.3NP_000591.1  interleukin-6 precursor

    See proteins identical to NP_000591.1

    Status: REVIEWED

    Source sequence(s)
    AA721478, AK301141, BC015511
    Consensus CDS
    CCDS5375.1
    UniProtKB/TrEMBL
    B4DVM1
    UniProtKB/Swiss-Prot
    P05231
    UniProtKB/TrEMBL
    Q75MH2
    Related
    ENSP00000258743, ENST00000258743
    Conserved Domains (1) summary
    pfam00489
    Location:57210
    Blast Score: 621
    IL6; Interleukin-6/G-CSF/MGF family

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000007.14

    Range
    22727147..22732002
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005249745.2XP_005249802.1  

    See proteins identical to XP_005249802.1

    UniProtKB/TrEMBL
    B4DNQ5
    Related
    ENSP00000405994
    Conserved Domains (1) summary
    cl02473
    Location:111212
    Blast Score: 442
    IL6; Interleukin-6/G-CSF/MGF family

Alternate HuRef

Genomic

  1. AC_000139.1 Alternate HuRef

    Range
    22649846..22654701
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018918.2 Alternate CHM1_1.1

    Range
    22767669..22772524
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

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