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    IL6 interleukin 6 [ Homo sapiens (human) ]

    Gene ID: 3569, updated on 26-Jul-2016
    Official Symbol
    IL6provided by HGNC
    Official Full Name
    interleukin 6provided by HGNC
    Primary source
    HGNC: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
    CDF; HGF; HSF; BSF2; IL-6; BSF-2; IFNB2; IFN-beta-2
    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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
    Orthologs
    Location:
    7p21
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 7 NC_000007.14 (22725889..22732002)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (22766766..22771621)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC100506178 Neighboring gene uncharacterized LOC401312 Neighboring gene uncharacterized LOC541472 Neighboring gene ribosomal protein S26 pseudogene 32 Neighboring gene translocase of outer mitochondrial membrane 7

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Associated conditions

    Description Tests
    Cerebral arteriovenous malformation
    MedGen: C0917804 OMIM: 108010 GeneReviews: Not available
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    Classic Kaposi sarcoma
    MedGen: C0036220 OMIM: 148000 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
    Compare labs

    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
    Envelope surface glycoprotein gp120 env Curcumin, a potent and safe anti-inflammatory compound, inhibits HIV-1 gp120-mediated upregulation of the proinflammatory cytokines TNF-alpha and IL-6, and the chemokines IL-8, RANTES, and IP-10 in primary human genital epithelial cells 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-induced release of IL-6 activates STAT3 in primary human monocyte-derived dendritic cells PubMed
    env HIV-1 gp120-induced release of IL-6 is regulated by p38 MAPK, IkappaBalpha, and p65 NF-kappaB activation in primary human monocyte-derived dendritic cells PubMed
    env Interaction of HIV-1 gp120 with CCR5 upregulates IL-6 expression in primary human monocyte-derived dendritic cells PubMed
    env HIV-1 gp120-induced release of IL-6 and MCP-1 is partially responsible for the impairment of barrier function in human retinal pigment epithelial cells 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 HIV-1 gp120 upregulates the expression of IL-6 and IL-8 via the p38 signaling pathway and the PI3K/Akt signaling pathway in astrocytes PubMed
    env HIV-1 gp120-induced expansion of myeloid derived suppressor cells is dependent on the upregulation of IL-6 by gp120 PubMed
    env HIV-1 gp120 recruits SOCS-3 through IL-10 activation for suppressing IL-6 and IL-6 dependent STAT3 in immature dentritic cells PubMed
    env HIV-1 gp120-induced release of IL-10 inhibits STAT3 activation, leading to suppress HIV-1 Nef-induced IL-6 secretion in immature dentritic cells PubMed
    env HIV-1 gp120 downregulates HIV-1 Nef dependent IL-6 release, which requires the interaction of gp120 with DC-SIGN PubMed
    env HIV-1 gp120 induces the release of cytokines MIP-1 alpha, MIP-1 beta, IL-6, IL-10, and TNF-alpha in immature dentritic cells PubMed
    env HIV-1 gp120 inhibits CpG-A-induced secretion of TNF-alpha, IL-6, and IP-10 proteins in plasmacytoid dendritic cells and PBMCs PubMed
    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 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 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 surface glycoprotein gp160, precursor env HIV-1 gp160 induces interleukin-6 production in CD4+ T cells PubMed
    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
    Envelope transmembrane glycoprotein gp41 env The HIV-1 gp41 transmembrane domain inhibits TLR2-induced activation of ERK1/2, and secretion of TNF-alpha, MCP-1, and IL-6 PubMed
    env A synthetic peptide corresponding to the immunosuppressive domain (amino acids 574-592) of HIV-1 gp41 inhibits activation of PBMCs and upregulates the expression of IL-6 in peptide-treated PBMCs PubMed
    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 Mutations L576A, Q577A, A578G, A582G, V583A, and E584A in the conserved immunosuppressive domain (amino acids 576-589) of HIV-1 gp41 significantly downregulate IL-6 release from human PBMCs PubMed
    env PWM, LPS, IFN-gamma and IL-6 can increase HIV-1 gp41 binding to human B cells PubMed
    Nef nef HIV-1 Nef induces IL6 and CXCL8 (IL8) expression in a PIK3-PKC dependent, AKT independent manner PubMed
    nef HIV-1 Nef induces IL6 and IL8 expression through the NF-kappaB pathway PubMed
    nef HIV-1 Nef treatment induces IL6 and IL8 production in SVGA cells and primary human fetal astrocytes PubMed
    nef HIV-1 Tat and Nef combination treatment induces release of both IL-6 and IL-8 in human mesenchymal stem cells 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 HIV-1 gp120-induced release of IL-10 inhibits STAT3 activation, leading to suppress HIV-1 Nef-induced IL-6 secretion in immature dentritic cells PubMed
    nef HIV-1 gp120 downregulates HIV-1 Nef dependent IL-6 release, which requires the interaction of gp120 with DC-SIGN in immature dentritic cells PubMed
    nef HIV-1 Nef synergizes with IL-6 to activate the AKT pathway promoting angiogenesis and tumorigenesis in achicken chorioallantoic membrane model and nude mice PubMed
    nef HIV-1 Nef synergizes with IL-6 to upregulate expression of basic fibroblast growth factor and cyclin D1 in NIH3T3-induced tissues PubMed
    nef HIV-1 Nef synergizes with IL-6 to enhance vascular tube formation, cell proliferation, VEGF expression, and phosphorylated AKT activation in human umbilical vein endothelial cells PubMed
    nef HIV-1 Nef inhibits IFN-gamma-induced apoptosis and upregulates TNF-alpha, IL-6 and MIP-3alpha 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 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
    nef Treatment of human PBMC and PBL with soluble HIV-1 Nef upregulates IL-6 production PubMed
    Pr55(Gag) gag MVA-gag induces a significant release of cytokines such as IL-2R, IL-6, IL-8, TNF-alpha, IFN-gamma, MCP-1, MIP-1alpha, MIP-1beta, and RANTES by the infected monocyte-derived dendritic cells in comparison with uninfected cells PubMed
    gag Depletion of HIV-specific CD8(+)/IL-10(+) cells from PBMCs leads to upregulation of CD38 on CD14(+) monocytes together with increased IL-6 production in response to HIV-1 gag stimulation PubMed
    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
    Tat tat HIV-1 Tat upregulates IL6 protein expression in human monocytes and monocyte-derived dendritic cells in a TLR4-CD14-MD2 dependent manner PubMed
    tat Human microglia cells treated with HIV-1 clade C Tat show more significant upregulation of IL-6 and TNF-alpha, and higher NF-kappaB activation as compared to clade B Tat-treated cells PubMed
    tat HIV-1 Tat and Nef combination treatment induces release of both IL-6 and IL-8 in human mesenchymal stem cells 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 HIV-1 Tat-induced upregulation of IL-6 in a time-dependent manner involves NF-kappaB and AP-1 transcription factors, activation of the p38 MAPK beta and delta subunits, and PI3K/Akt pathway in astrocytes 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 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 inhibits CpG-A-induced secretion of TNF-alpha, IL-6, and IP-10 proteins in plasmacytoid dendritic cells and PBMCs PubMed
    tat LRRK2 is involved in HIV-1 Tat-induced cytokine TNF-alpha, IL-6, and MCP-1 expression in microglia cells PubMed
    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 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 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 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 vpr Treatment of human primary astrocytes with HIV-1 Vpr upregulates secretion of IL6, CXCL8 (IL-8), MCP-1, and MIF and downregulates secretion of serpin E1, a serine proteinase inhibitor (known as PAI-1) PubMed
    vpr HIV-1 Vpr induces IL6 production via activation of MAPK p38 PubMed
    vpr HIV-1 Vpr induced upregulation of IL6 involves PI3K/Akt mediated activation of NFKB1 (NF-kappaB) in astrocytes PubMed
    vpr HIV-1 Vpr upregulation of IL6 involves NFKB1 (NF-kappaB) PubMed
    vpr HIV-1 Vpr enhances the secretion of IL6 from human fetal astrocytes PubMed
    vpr HIV-1 Vpr upregulates the expression of IL6 mRNA in human fetal astrocytes PubMed
    vpr HIV-1 Vpr upregulates the expression of IL6 mRNA in SVGA in a dose-dependent manner PubMed
    vpr HIV-1 Vpr upregulates the expression of IL6 mRNA in SVGA astrocytes in a time dependent fashion PubMed
    vpr HIV-1 Vpr enhances the secretion of IL6 from SVGA astrocytes in a time dependent fashion PubMed
    vpr HIV-1 involves the JUN (AP-1) transcription factor in the induction of IL6 in astrocytes PubMed
    vpr HIV-1 Vpr involves the CEBPD (C/EBP-delta) transcription factor in the induction of IL6 in astrocytes PubMed
    vpr HIV-1 Vpr-mediated regulation of IL6 involves MAPK8 (Jnk-MAPK8) in astrocytes PubMed
    vpr Vpr-mediated upregulation of IL6 involves p38-MAPK11 (beta isoform of p38-MAPK) in astrocytes PubMed
    vpr Soluble HIV-1 Vpr induces a markedly reduced expression of IL6 in monocytoid cells PubMed
    vpr Concurrent exposure of HIV-1 Vpr with HCV core protein causes higher IL6 expression than HIV-1 Vpr-treated human fetal microglia PubMed
    vpr HIV-1 Vpr-induced IL6 production depends on the activation of NFkappaB and the involvement of C/EBP-beta, TLR4, and MyD88 PubMed
    vpr HIV-1 Vpr upregulates IL6 expression in primary macrophages and in A549 cells PubMed
    capsid gag PLA-p24-loaded human monocyte-derived dendritic cells enhance the secretion of MIP-1beta, IL-6, IL-8, and TNF-alpha in comparison with PLA-loaded cells alone PubMed
    gag Unactivated memory CD4+ T cells infected by HIV-1 in the presence of IL-2 and IL-15 alone or IL-6/IL-7/TNF-alpha combination, upregulate granzyme B and HIV-1 CA production PubMed
    matrix gag HIV-1 MA natural variant S75X upregulates the expression of two cyclins D2 and D3, and induces significant release of cytokine IL-6 in both Epstein-Barr virus (EBV)-infected primary and fully transformed B-lymphocytes PubMed
    gag HIV-1 Matrix upregulates IL-6 production in placental mononuclear cells PubMed

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      MAPK family signaling cascades, organism-specific biosystemThe mitogen activated protein kinases (MAPKs) are a family of conserved protein serine threonine kinases that respond to varied extracellular stimuli to activate intracellular processes including gen...
    • MAPK1 (ERK2) activation, organism-specific biosystem (from REACTOME)
      MAPK1 (ERK2) activation, organism-specific biosystemMitogen-activated protein kinase kinase MAP2K2 (also known as MEK2) is a dual threonine and tyrosine recognition kinase that phosphorylates and activates MAPK1 (ERK2) (Ohren et al. 2004; Roskoski 201...
    • MAPK1/MAPK3 signaling, organism-specific biosystem (from REACTOME)
      MAPK1/MAPK3 signaling, organism-specific biosystemThe extracellular signal regulated kinases (ERKs) 1 and 2, also known as MAPK3 and MAPK1, are phosphorylated by the MAP2Ks 1 and 2 in response to a wide range of extracellular stimuli to promote diff...
    • MAPK3 (ERK1) activation, organism-specific biosystem (from REACTOME)
      MAPK3 (ERK1) activation, organism-specific biosystemMitogen-activated protein kinase kinase MAP2K1 (also known as MEK1) is a dual threonine and tyrosine recognition kinase that phosphorylates and activates MAPK3 (ERK1) (Ohren et al. 2004; Roskoski 201...
    • Malaria, organism-specific biosystem (from KEGG)
      Malaria, organism-specific biosystemPlasmodium protozoa are parasites that account for malaria infection. Sporozoite forms of the parasite are injected by mosquito bites under the skin and are carried to the liver where they develop in...
    • Malaria, conserved biosystem (from KEGG)
      Malaria, conserved biosystemPlasmodium protozoa are parasites that account for malaria infection. Sporozoite forms of the parasite are injected by mosquito bites under the skin and are carried to the liver where they develop in...
    • Measles, organism-specific biosystem (from KEGG)
      Measles, organism-specific biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
    • Measles, conserved biosystem (from KEGG)
      Measles, conserved biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
    • Myometrial Relaxation and Contraction Pathways, organism-specific biosystem (from WikiPathways)
      Myometrial Relaxation and Contraction Pathways, organism-specific biosystemThis pathway illustrates signaling networks implicated in uterine muscle contraction at labor and quiescence throughout gestation (pregnancy). The muscle of the uterus, responsible for contractile ac...
    • NOD-like receptor signaling pathway, organism-specific biosystem (from KEGG)
      NOD-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains mo...
    • NOD-like receptor signaling pathway, conserved biosystem (from KEGG)
      NOD-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains mo...
    • Non-alcoholic fatty liver disease (NAFLD), organism-specific biosystem (from KEGG)
      Non-alcoholic fatty liver disease (NAFLD), organism-specific biosystemNon-alcoholic fatty liver disease (NAFLD) represents a spectrum ranging from simple steatosis to more severe steatohepatitis with hepatic inflammation and fibrosis, known as nonalcoholic steatohepati...
    • Non-alcoholic fatty liver disease (NAFLD), conserved biosystem (from KEGG)
      Non-alcoholic fatty liver disease (NAFLD), conserved biosystemNon-alcoholic fatty liver disease (NAFLD) represents a spectrum ranging from simple steatosis to more severe steatohepatitis with hepatic inflammation and fibrosis, known as nonalcoholic steatohepati...
    • PI3K-Akt signaling pathway, organism-specific biosystem (from KEGG)
      PI3K-Akt signaling pathway, organism-specific biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
    • PI3K-Akt signaling pathway, conserved biosystem (from KEGG)
      PI3K-Akt signaling pathway, conserved biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
    • Pathways in cancer, organism-specific biosystem (from KEGG)
      Pathways in cancer, organism-specific biosystem
      Pathways in cancer
    • Pertussis, organism-specific biosystem (from KEGG)
      Pertussis, organism-specific biosystemPertussis, also known as whooping cough, is an acute respiratory infectious disease caused by a bacteria called Bordetella Pertussis. The characteristic symptoms are paroxysmal cough, inspiratory whe...
    • Pertussis, conserved biosystem (from KEGG)
      Pertussis, conserved biosystemPertussis, also known as whooping cough, is an acute respiratory infectious disease caused by a bacteria called Bordetella Pertussis. The characteristic symptoms are paroxysmal cough, inspiratory whe...
    • Prion diseases, organism-specific biosystem (from KEGG)
      Prion diseases, organism-specific biosystemPrion diseases, also termed transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative diseases that affect humans and a number of other animal species. The etiology of ...
    • Prion diseases, conserved biosystem (from KEGG)
      Prion diseases, conserved biosystemPrion diseases, also termed transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative diseases that affect humans and a number of other animal species. The etiology of ...
    • RAF-independent MAPK1/3 activation, organism-specific biosystem (from REACTOME)
      RAF-independent MAPK1/3 activation, organism-specific biosystemDepending upon the stimulus and cell type mitogen-activated protein kinases (MAPK) signaling pathway can transmit signals to regulate many different biological processes by virtue of their ability to...
    • Regulation of toll-like receptor signaling pathway, organism-specific biosystem (from WikiPathways)
      Regulation of toll-like receptor signaling pathway, organism-specific biosystem
      Regulation of toll-like receptor signaling pathway
    • Rheumatoid arthritis, organism-specific biosystem (from KEGG)
      Rheumatoid arthritis, organism-specific biosystemRheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune...
    • Rheumatoid arthritis, conserved biosystem (from KEGG)
      Rheumatoid arthritis, conserved biosystemRheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune...
    • SIDS Susceptibility Pathways, organism-specific biosystem (from WikiPathways)
      SIDS Susceptibility Pathways, organism-specific biosystemIn this model, we provide an integrated view of Sudden Infant Death Syndrome (SIDS) at the level of implicated tissues, signaling networks and genetics. The purpose of this model is to serve as an ov...
    • Salmonella infection, organism-specific biosystem (from KEGG)
      Salmonella infection, organism-specific biosystemSalmonella infection usually presents as a self-limiting gastroenteritis or the more severe typhoid fever and bacteremia. The common disease-causing Salmonella species in human is a single species, S...
    • Salmonella infection, conserved biosystem (from KEGG)
      Salmonella infection, conserved biosystemSalmonella infection usually presents as a self-limiting gastroenteritis or the more severe typhoid fever and bacteremia. The common disease-causing Salmonella species in human is a single species, S...
    • Selenium Pathway, organism-specific biosystem (from WikiPathways)
      Selenium Pathway, organism-specific biosystem
      Selenium Pathway
    • Senescence and Autophagy, organism-specific biosystem (from WikiPathways)
      Senescence and Autophagy, organism-specific biosystemSenescense and Autophagy Pathways in Cancer
    • Senescence-Associated Secretory Phenotype (SASP), organism-specific biosystem (from REACTOME)
      Senescence-Associated Secretory Phenotype (SASP), organism-specific biosystemThe culture medium of senescent cells in enriched in secreted proteins when compared with the culture medium of quiescent i.e. presenescent cells and these secreted proteins constitute the so-called ...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by Interleukins, organism-specific biosystem (from REACTOME)
      Signaling by Interleukins, organism-specific biosystemInterleukins are low molecular weight proteins that bind to cell surface receptors and act in an autocrine and/or paracrine fashion. They were first identified as factors produced by leukocytes but a...
    • Spinal Cord Injury, organism-specific biosystem (from WikiPathways)
      Spinal Cord Injury, organism-specific biosystemThis pathway provides an overview of cell types, therapeutic targets, drugs, new proposed targets and pathways implicated in spinal cord injury. Spinal cord injury is a complex multistep process that...
    • TCR Signaling Pathway, organism-specific biosystem (from WikiPathways)
      TCR Signaling Pathway, organism-specific biosystemThe T-cell antigen receptor (TCR) complex is composed of a ligand-binding subunit, the ? and ? chains, and a signaling subunit, namely the CD3?, ? and ? chains and the TCR? chain. This complex partic...
    • TNF signaling pathway, organism-specific biosystem (from KEGG)
      TNF signaling pathway, organism-specific biosystemTumor necrosis factor (TNF), as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. Activated TNF...
    • TNF signaling pathway, conserved biosystem (from KEGG)
      TNF signaling pathway, conserved biosystemTumor necrosis factor (TNF), as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. Activated TNF...
    • TSLP Signaling Pathway, organism-specific biosystem (from WikiPathways)
      TSLP Signaling Pathway, organism-specific biosystemThymic stromal lymphopoietin (TSLP) is a type I cytokine member of interleukin-2 cytokine family. TSLP signals through interleukin-7 receptor a chain (IL-7Ra) and the TSLP receptor subunit (TSLPR), h...
    • TWEAK Signaling Pathway, organism-specific biosystem (from WikiPathways)
      TWEAK Signaling Pathway, organism-specific biosystemTNF related weak inducer of apoptosis (TWEAK) is a small pleiotropic cytokine of the TNF super family and its gene is located at chromosome 17p13.1. TWEAK has been reported to be expressed in tissues...
    • Toll-like receptor signaling pathway, organism-specific biosystem (from KEGG)
      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 ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    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 dexamethasone stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to hepatocyte growth factor stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to hydrogen peroxide IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cellular response to interleukin-1 IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to lipopolysaccharide IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    cellular response to tumor necrosis factor IEA
    Inferred from Electronic Annotation
    more info
     
    cytokine-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    defense response to Gram-negative bacterium TAS
    Traceable Author Statement
    more info
    PubMed 
    defense response to Gram-positive bacterium TAS
    Traceable Author Statement
    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
     
    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
     
    glucose homeostasis IEA
    Inferred from Electronic Annotation
    more info
     
    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 TAS
    Traceable Author Statement
    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 cell proliferation in bone marrow IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of chemokine production IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of chemokine production NAS
    Non-traceable Author Statement
    more info
    PubMed 
    positive regulation of epithelial cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of gene expression IDA
    Inferred from Direct Assay
    more info
    PubMed 
    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 TAS
    Traceable Author Statement
    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 from RNA polymerase II promoter ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    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 auditory stimulus 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 nutrient levels IEA
    Inferred from Electronic Annotation
    more info
     
    response to peptidoglycan NAS
    Non-traceable Author Statement
    more info
    PubMed 
    response to yeast IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    cytoplasm IEA
    Inferred from Electronic Annotation
    more info
     
    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
    B-cell differentiation factor
    B-cell stimulatory factor 2
    CTL differentiation factor
    hybridoma growth factor
    interferon beta-2
    interleukin BSF-2

    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
      4996..9856
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000600.4NP_000591.1  interleukin-6 isoform 1 precursor

      See identical proteins and their annotated locations for NP_000591.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AK301141, BC015511, CD013918, HY076725
      Consensus CDS
      CCDS5375.1
      UniProtKB/Swiss-Prot
      P05231
      UniProtKB/TrEMBL
      B4DVM1, Q75MH2
      Related
      ENSP00000258743, ENST00000258743
      Conserved Domains (1) summary
      pfam00489
      Location:57210
      IL6; Interleukin-6/G-CSF/MGF family
    2. NM_001318095.1NP_001305024.1  interleukin-6 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an exon in its 5' UTR and uses a downstream in-frame start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus than isoform 1.
      Source sequence(s)
      CD013918, HY076725
      UniProtKB/TrEMBL
      B5MC21
      Related
      ENSP00000385043, OTTHUMP00000198488, ENST00000407492, OTTHUMT00000320075
      Conserved Domains (1) summary
      pfam00489
      Location:1134
      IL6; Interleukin-6/G-CSF/MGF family

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000007.14 Reference GRCh38.p7 Primary Assembly

      Range
      22725889..22732002
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011515390.2XP_011513692.1  

      See identical proteins and their annotated locations for XP_011513692.1

      UniProtKB/Swiss-Prot
      P05231
      UniProtKB/TrEMBL
      Q75MH2
      Related
      ENSP00000385675, OTTHUMP00000158544, ENST00000404625, OTTHUMT00000250225
      Conserved Domains (1) summary
      pfam00489
      Location:57210
      IL6; Interleukin-6/G-CSF/MGF family
    2. XM_005249745.4XP_005249802.1  

      See identical proteins and their annotated locations for XP_005249802.1

      UniProtKB/TrEMBL
      B4DNQ5
      Conserved Domains (1) summary
      cl02473
      Location:87212
      IL6; Interleukin-6/G-CSF/MGF family

    Alternate CHM1_1.1

    Genomic

    1. NC_018918.2 Alternate CHM1_1.1

      Range
      22767664..22772524
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)