Version 5.4
Homo sapiens Gene: IL6
Summary
InnateDB Gene IDBG-9462.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol IL6
Gene Name interleukin 6 (interferon, beta 2)
Synonyms BSF2; HGF; HSF; IFNB2; IL-6
Species Homo sapiens
Ensembl Gene ENSG00000136244
Encoded Proteins
IDBP-9464
interleukin 6 (interferon, beta 2)
IDBP-294916
interleukin 6 (interferon, beta 2)
IDBP-294917
interleukin 6 (interferon, beta 2)
IDBP-294915
interleukin 6 (interferon, beta 2)
IDBP-294919
interleukin 6 (interferon, beta 2)
IDBP-294918
interleukin 6 (interferon, beta 2)
IDBP-367686
interleukin 6 (interferon, beta 2)
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
PMID 21148800
IL6 trans-signalling via STAT3 is a critical modulator of LPS-driven pro-inflammatory responses through cross-talk regulation of the TLR4/Mal signalling pathway broader mechanism that regulates the severity of the host inflammatory response.
PMID 22096605
IL6 synthesis is regulated by the opposing effects of prostaglandin (PG)E(2) and PGD(2) in human chondrocytes. IL6 synthesis is increased by PGE2 and decreased by PGD2 through the modulation of TLR4 synthesis.
PMID 22030478
Activation of either TLR4 or TLR2/6 significantly increased IL6 expression by U937 mononuclear cells. Co-activation of TLR4 and TLR2/6, led to a further augmentation on IL-6 expression.
PMID 22426116
IL6 is strategically upregulated by virulent Mycobacterium tuberculosis to inhibit the induction of innate immunity.
PMID 23735697
Hyperglycemia abrogates the ability of IL6 to induce neutrophil extracellular traps.
PMID 24012417
IFN gamma creates a primed chromatin environment in macrophages to augment TLR-induced IL6 transcription
PMID 26287468
TET2 selectively mediates active repression of IL6 transcription via NFKBIZ and HDAC2 during inflammation resolution in innate myeloid cells, including dendritic cells and macrophages.
Entrez Gene
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]
Gene Information
Type Protein coding
Genomic Location Chromosome 7:22725884-22732002
Strand Forward strand
Band p15.3
Transcripts
ENST00000258743 ENSP00000258743
ENST00000404625 ENSP00000385675
ENST00000401630 ENSP00000384928
ENST00000406575 ENSP00000385227
ENST00000407492 ENSP00000385043
ENST00000401651 ENSP00000385718
ENST00000426291 ENSP00000405150
ENST00000485300
ENST00000464710
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 31 experimentally validated interaction(s) in this database.
Experimentally validated
Total 31 [view]
Protein-Protein 12 [view]
Protein-DNA 18 [view]
Protein-RNA 0
DNA-DNA 0
RNA-RNA 1 [view]
DNA-RNA 0
Gene Ontology

Molecular Function
Accession GO Term
GO:0005102 receptor binding
GO:0005125 cytokine activity
GO:0005138 interleukin-6 receptor binding
GO:0005515 protein binding
GO:0008083 growth factor activity
Biological Process
GO:0001781 neutrophil apoptotic process
GO:0002384 hepatic immune response
GO:0002446 neutrophil mediated immunity
GO:0002548 monocyte chemotaxis
GO:0002675 positive regulation of acute inflammatory response
GO:0002690 positive regulation of leukocyte chemotaxis
GO:0006469 negative regulation of protein kinase activity
GO:0006953 acute-phase response
GO:0006954 inflammatory response
GO:0006955 immune response
GO:0006959 humoral immune response
GO:0007568 aging
GO:0008284 positive regulation of cell proliferation
GO:0008285 negative regulation of cell proliferation
GO:0008360 regulation of cell shape
GO:0009408 response to heat
GO:0009409 response to cold
GO:0009611 response to wounding
GO:0009612 response to mechanical stimulus
GO:0009617 response to bacterium
GO:0010574 regulation of vascular endothelial growth factor production
GO:0010628 positive regulation of gene expression
GO:0010888 negative regulation of lipid storage
GO:0010996 response to auditory stimulus
GO:0014070 response to organic cyclic compound
GO:0016049 cell growth
GO:0019221 cytokine-mediated signaling pathway
GO:0030168 platelet activation
GO:0031000 response to caffeine
GO:0031018 endocrine pancreas development
GO:0031175 neuron projection development
GO:0031667 response to nutrient levels
GO:0032494 response to peptidoglycan
GO:0032496 response to lipopolysaccharide
GO:0032722 positive regulation of chemokine production
GO:0032755 positive regulation of interleukin-6 production
GO:0032868 response to insulin
GO:0032966 negative regulation of collagen biosynthetic process
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0033160 positive regulation of protein import into nucleus, translocation
GO:0034097 response to cytokine
GO:0042060 wound healing
GO:0042102 positive regulation of T cell proliferation
GO:0042110 T cell activation
GO:0042127 regulation of cell proliferation
GO:0042493 response to drug
GO:0042517 positive regulation of tyrosine phosphorylation of Stat3 protein
GO:0042832 defense response to protozoan
GO:0042981 regulation of apoptotic process
GO:0043065 positive regulation of apoptotic process
GO:0043066 negative regulation of apoptotic process
GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043200 response to amino acid
GO:0043410 positive regulation of MAPK cascade
GO:0045079 negative regulation of chemokine biosynthetic process
GO:0045087 innate immune response (InnateDB)
GO:0045188 regulation of circadian sleep/wake cycle, non-REM sleep
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045454 cell redox homeostasis
GO:0045599 negative regulation of fat cell differentiation
GO:0045630 positive regulation of T-helper 2 cell differentiation
GO:0045666 positive regulation of neuron differentiation
GO:0045669 positive regulation of osteoblast differentiation
GO:0045721 negative regulation of gluconeogenesis
GO:0045727 positive regulation of translation
GO:0045740 positive regulation of DNA replication
GO:0045765 regulation of angiogenesis
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046427 positive regulation of JAK-STAT cascade
GO:0046677 response to antibiotic
GO:0046716 muscle cell cellular homeostasis
GO:0046849 bone remodeling
GO:0046888 negative regulation of hormone secretion
GO:0048635 negative regulation of muscle organ development
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0050679 positive regulation of epithelial cell proliferation
GO:0050710 negative regulation of cytokine secretion
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050829 defense response to Gram-negative bacterium
GO:0050830 defense response to Gram-positive bacterium
GO:0050871 positive regulation of B cell activation
GO:0051024 positive regulation of immunoglobulin secretion
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051384 response to glucocorticoid
GO:0051592 response to calcium ion
GO:0051602 response to electrical stimulus
GO:0051607 defense response to virus
GO:0051897 positive regulation of protein kinase B signaling
GO:0051971 positive regulation of transmission of nerve impulse
GO:0060445 branching involved in salivary gland morphogenesis
GO:0060664 epithelial cell proliferation involved in salivary gland morphogenesis
GO:0070091 glucagon secretion
GO:0070102 interleukin-6-mediated signaling pathway
GO:0070301 cellular response to hydrogen peroxide
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0071222 cellular response to lipopolysaccharide
GO:0071347 cellular response to interleukin-1
GO:0071356 cellular response to tumor necrosis factor
GO:0071549 cellular response to dexamethasone stimulus
GO:0072540 T-helper 17 cell lineage commitment
GO:1901215 negative regulation of neuron death
GO:2000366 positive regulation of STAT protein import into nucleus
GO:2000676 positive regulation of type B pancreatic cell apoptotic process
Cellular Component
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005737 cytoplasm
GO:0005896 interleukin-6 receptor complex
GO:0009897 external side of plasma membrane
Orthologs
No orthologs found for this gene
Pathways
NETPATH
NetPath_18
IL6 pathway
REACTOME
REACT_1391
ERK1 activation pathway
REACT_1183
ERK2 activation pathway
REACT_1482
ERK activation pathway
REACT_147814
DAP12 signaling pathway
REACT_147694
DAP12 interactions pathway
REACT_6809
MyD88-independent cascade pathway
REACT_6783
Toll Like Receptor 3 (TLR3) Cascade pathway
REACT_6788
MyD88:Mal cascade initiated on plasma membrane pathway
REACT_8005
Toll Like Receptor TLR1:TLR2 Cascade pathway
REACT_8006
Toll Like Receptor TLR6:TLR2 Cascade pathway
REACT_25024
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
REACT_25222
MyD88 dependent cascade initiated on endosome pathway
REACT_9047
Toll Like Receptor 9 (TLR9) Cascade pathway
REACT_27215
MyD88 cascade initiated on plasma membrane pathway
REACT_9027
Toll Like Receptor 10 (TLR10) Cascade pathway
REACT_6894
Toll Like Receptor 4 (TLR4) Cascade pathway
REACT_9061
Toll Like Receptor 5 (TLR5) Cascade pathway
REACT_27307
Interleukin-6 signaling pathway
REACT_27283
Interleukin-2 signaling pathway
REACT_12076
Frs2-mediated activation pathway
REACT_12002
ARMS-mediated activation pathway
REACT_12077
Signalling to p38 via RIT and RIN pathway
REACT_12033
Signalling to RAS pathway
REACT_524
SOS-mediated signalling pathway
REACT_12579
SHC1 events in EGFR signaling pathway
REACT_12606
GRB2 events in EGFR signaling pathway
REACT_9417
Signaling by EGFR pathway
REACT_120966
Gastrin-CREB signalling pathway via PKC and MAPK pathway
REACT_116005
SHC1 events in ERBB4 signaling pathway
REACT_115596
Signaling by ERBB4 pathway
REACT_661
SHC-mediated signalling pathway
REACT_498
Signaling by Insulin receptor pathway
REACT_150203
IRS-related events triggered by IGF1R pathway
REACT_150139
SHC-related events triggered by IGF1R pathway
REACT_150359
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) pathway
REACT_115854
GRB2 events in ERBB2 signaling pathway
REACT_115993
SHC1 events in ERBB2 signaling pathway
REACT_115755
Signaling by ERBB2 pathway
REACT_21247
FRS2-mediated cascade pathway
REACT_9470
Signaling by FGFR pathway
REACT_111040
Signaling by SCF-KIT pathway
REACT_17025
Downstream signal transduction pathway
REACT_16888
Signaling by PDGF pathway
REACT_18334
NCAM signaling for neurite out-growth pathway
REACT_120736
Signaling by FGFR in disease pathway
REACT_999
SHC-related events pathway
REACT_120956
Cellular responses to stress pathway
REACT_111045
Developmental Biology pathway
REACT_11061
Signalling by NGF pathway
REACT_9020
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
REACT_115871
Signaling by EGFR in Cancer pathway
REACT_21272
Downstream signaling of activated FGFR pathway
REACT_12529
Signaling by VEGF pathway
REACT_75790
Cytokine Signaling in Immune system pathway
REACT_14797
Signaling by GPCR pathway
REACT_6802
Innate Immune System pathway
REACT_7980
Toll Like Receptor 2 (TLR2) Cascade pathway
REACT_6966
Toll-Like Receptors Cascades pathway
REACT_18266
Axon guidance pathway
REACT_634
RAF/MAP kinase cascade pathway
REACT_163936
Fc epsilon receptor (FCERI) signaling pathway
REACT_111102
Signal Transduction pathway
REACT_21308
MAP kinase activation in TLR cascade pathway
REACT_332
IRS-mediated signalling pathway
REACT_6900
Immune System pathway
REACT_228024
VEGFR2 mediated cell proliferation pathway
REACT_1195
Insulin receptor signalling cascade pathway
REACT_169274
Cellular Senescence pathway
REACT_22232
Signaling by Interleukins pathway
REACT_228166
VEGFA-VEGFR2 Pathway pathway
REACT_12058
Signalling to ERKs pathway
REACT_12056
NGF signalling via TRKA from the plasma membrane pathway
REACT_762
IRS-related events pathway
REACT_150210
IGF1R signaling cascade pathway
REACT_12005
Prolonged ERK activation events pathway
REACT_6890
Activated TLR4 signalling pathway
REACT_169168
Senescence-Associated Secretory Phenotype (SASP) pathway
REACT_25281
TRIF-mediated TLR3/TLR4 signaling pathway
REACT_116125
Disease pathway
REACT_169118
Signaling by Leptin pathway
REACT_163701
FCERI mediated MAPK activation pathway
KEGG
hsa04640
Hematopoietic cell lineage pathway
hsa04060
Cytokine-cytokine receptor interaction pathway
hsa04620
Toll-like receptor signaling pathway pathway
hsa04630
Jak-STAT signaling pathway pathway
hsa05332
Graft-versus-host disease pathway
hsa05410
Hypertrophic cardiomyopathy (HCM) pathway
hsa05020
Prion diseases pathway
hsa05200
Pathways in cancer pathway
hsa04621
NOD-like receptor signaling pathway pathway
hsa04623
Cytosolic DNA-sensing pathway pathway
hsa04672
Intestinal immune network for IgA production pathway
hsa05146
Amoebiasis pathway
hsa05144
Malaria pathway
hsa05142
Chagas disease (American trypanosomiasis) pathway
hsa05143
African trypanosomiasis pathway
INOH
INOH website
JAK STAT pathway and regulation pathway
INOH website
IL-6 signaling pathway
INOH website
GPCR signaling pathway
PID NCI
fra_pathway
Validated transcriptional targets of AP1 family members Fra1 and Fra2
il27pathway
IL27-mediated signaling events
atf2_pathway
ATF-2 transcription factor network
ap1_pathway
AP-1 transcription factor network
reg_gr_pathway
Glucocorticoid receptor regulatory network
il23pathway
IL23-mediated signaling events
shp2_pathway
SHP2 signaling
il6_7pathway
IL6-mediated signaling events
amb2_neutrophils_pathway
amb2 Integrin signaling
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene
RefSeq NM_000600 XM_005249745
HUGO
OMIM
CCDS CCDS5375
HPRD 00970
IMGT
EMBL
GenPept
RNA Seq Atlas

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

InnateDB is being developed jointly by the Brinkman Laboratory (Simon Fraser University, British Columbia, Canada), the Hancock Laboratory (University of British Columbia, Vancouver, British Columbia) and the Lynn EMBL Australia Group (South Australian Health & Medical Research Institute and Flinders University, Adelaide, Australia).

Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca