IL6 interleukin 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: IL6provided by HGNC
Official Full Name: interleukin 6provided by HGNC
Primary source: HGNC:HGNC:6018
See related: Ensembl:ENSG00000136244 MIM:147620; AllianceGenome:HGNC:6018
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. Elevated levels of the encoded protein have been found in virus infections, including COVID-19 (disease caused by SARS-CoV-2). [provided by RefSeq, Aug 2020]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is relevant for COVID-19 prognosis.
Expression: Broad expression in urinary bladder (RPKM 9.7), gall bladder (RPKM 7.1) and 14 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 7p15.3

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (22727200..22731998)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (22861319..22867916)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (22766819..22771617)

Chromosome 7 - NC_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Association between IL-6 -174 G/C (rs1800795) and IL-1A -889 C/T (rs1800587) cytokine variants with polycystic ovary syndrome in Iranian women: A case-control study.
Title: Association between IL-6 -174 G/C (rs1800795) and IL-1A -889 C/T (rs1800587) cytokine variants with polycystic ovary syndrome in Iranian women: A case-control study.
Association between IL-6, miRNA-146a, MALAT1 genetic polymorphisms and risk of rheumatoid arthritis.
Title: Association between IL-6, miRNA-146a, MALAT1 genetic polymorphisms and risk of rheumatoid arthritis.
Characterisation of IGF-1 (rs7136446) and IL-6 (rs1800795) polymorphisms among breast cancer patients in western Algeria.
Title: Characterisation of IGF-1 (rs7136446) and IL-6 (rs1800795) polymorphisms among breast cancer patients in western Algeria.
Exploring the role of interleukin-1beta and interleukin-6 in the pathophysiology of obsessive-compulsive disorder.
Title: Exploring the role of interleukin-1β and interleukin-6 in the pathophysiology of obsessive-compulsive disorder.
cDC2 plasticity and acquisition of a DC3-like phenotype mediated by IL-6 and PGE2 in a patient-derived colorectal cancer organoids model.
Title: cDC2 plasticity and acquisition of a DC3-like phenotype mediated by IL-6 and PGE2 in a patient-derived colorectal cancer organoids model.
Association of IL-6 G-174C (rs1800795) variant with the susceptibility to hepatocellular carcinoma in patients with chronic hepatitis.
Title: Association of IL-6 G-174C (rs1800795) variant with the susceptibility to hepatocellular carcinoma in patients with chronic hepatitis.
Astrocytic DLL4-NOTCH1 signaling pathway promotes neuroinflammation via the IL-6-STAT3 axis.
Title: Astrocytic DLL4-NOTCH1 signaling pathway promotes neuroinflammation via the IL-6-STAT3 axis.
Impact of IL-6 and IL-1beta Gene Variants on Non-small-cell Lung Cancer Risk in Egyptian Patients.
Title: Impact of IL-6 and IL-1β Gene Variants on Non-small-cell Lung Cancer Risk in Egyptian Patients.
Interleukin 6 plasma levels are associated with progression of coronary plaques.
Title: Interleukin 6 plasma levels are associated with progression of coronary plaques.
Mesenchymal stem cells-derived IL-6 promotes invasion and metastasis of oral squamous cell carcinoma via JAK-STAT3 signalling.
Title: Mesenchymal stem cells-derived IL-6 promotes invasion and metastasis of oral squamous cell carcinoma via JAK-STAT3 signalling.

Submit: New GeneRIF Correction See all GeneRIFs (4597)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Cerebral arteriovenous malformation MedGen: C0917804 OMIM: 108010 GeneReviews: Not available	not available
Diabetes mellitus type 1 MedGen: C0011854 OMIM: 222100 GeneReviews: Not available	not available
Inflammatory bowel disease 1 MedGen: CN260071 OMIM: 266600 GeneReviews: Not available	not available
Kaposi sarcoma, susceptibility to MedGen: C3538945 OMIM: 148000 GeneReviews: Not available	not available
Systemic-onset juvenile idiopathic arthritis MedGen: C1858558 OMIM: 604302 GeneReviews: Not available	not available
Type 2 diabetes mellitus MedGen: C0011860 OMIM: 125853 GeneReviews: WFS1 Spectrum Disorder	not available

EBI GWAS Catalog

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

Variation

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See Variation Viewer (GRCh37.p13)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 infection increases basal mRNA levels of JUN, IL6, STAT1, CEBPA, RELA, and CEBPG in monocyte derived macrophages	PubMed
HIV-1 ADA infection decreases production of CXCL8 (IL8), CCL2 (MCP-1), and IL6 at a basal level or after Fc receptor, complement receptor 3, or bacterial stimulation in primary human macrophages	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 CN54, JRFL, and Ada Env (gp120) upregulates IL-6, CCL2, CCL4, CXCL8, and IL-1b through TLR4 and CCR5 induction in monocyte derived macrophages and hepatic stellate cells because treatment with an anti-TLR4 antibody mitigated the response	PubMed
	env	HIV-1 IIIB Env (gp120) upregulates production of TNF (TNF-a), IL-17A, CCL2 (MCP1), CCL5 (RANTES), IL6, IL10, CXCL8 (IL8), CXCL1 (GRO-a), and CCL1 (I309) in stimulated monocyte derived macrophages	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	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	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	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
	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
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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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-M14584 (e-PCR)
- UniSTS:73733

HUEST-M14584 (e-PCR)
- UniSTS:73733

IL6 (e-PCR), detects polymorphism
- UniSTS:73733

D7S2743 (e-PCR)
- UniSTS:20883

IL6 (e-PCR), detects polymorphism
- UniSTS:55457

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytokine activity	IBA Inferred from Biological aspect of Ancestor more info
enables cytokine activity	IDA Inferred from Direct Assay more info	PubMed
enables cytokine activity	ISS Inferred from Sequence or Structural Similarity more info
enables cytokine activity	NAS Non-traceable Author Statement more info	PubMed
enables cytokine activity	TAS Traceable Author Statement more info	PubMed
enables growth factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables growth factor activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to interleukin-6 receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables interleukin-6 receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables interleukin-6 receptor binding	NAS Non-traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in T follicular helper cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in T-helper 17 cell lineage commitment	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in acute-phase response	TAS Traceable Author Statement more info	PubMed
involved_in cell surface receptor signaling pathway via JAK-STAT	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell surface receptor signaling pathway via STAT	IDA Inferred from Direct Assay more info	PubMed
involved_in cell surface receptor signaling pathway via STAT	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to hydrogen peroxide	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within cellular response to lipopolysaccharide	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to virus	ISS Inferred from Sequence or Structural Similarity more info
involved_in cytokine-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in defense response to Gram-negative bacterium	TAS Traceable Author Statement more info	PubMed
involved_in defense response to Gram-positive bacterium	TAS Traceable Author Statement more info	PubMed
involved_in defense response to virus	IDA Inferred from Direct Assay more info	PubMed
involved_in endocrine pancreas development	ISS Inferred from Sequence or Structural Similarity more info
involved_in germinal center B cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in glucagon secretion	ISS Inferred from Sequence or Structural Similarity more info
involved_in glucose homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in hepatic immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in hepatic immune response	TAS Traceable Author Statement more info	PubMed
involved_in hepatocyte proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in humoral immune response	IC Inferred by Curator more info	PubMed
involved_in inflammatory response	IDA Inferred from Direct Assay more info	PubMed
involved_in inflammatory response	TAS Traceable Author Statement more info	PubMed
involved_in inflammatory response to wounding	IDA Inferred from Direct Assay more info	PubMed
involved_in interleukin-6-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in interleukin-6-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in interleukin-6-mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in liver regeneration	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within maintenance of blood-brain barrier	TAS Traceable Author Statement more info	PubMed
involved_in monocyte chemotaxis	IC Inferred by Curator more info	PubMed
involved_in negative regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of bone resorption	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cell population proliferation	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of chemokine production	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of collagen biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of fat cell differentiation	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of interleukin-1-mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of lipid storage	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of neurogenesis	TAS Traceable Author Statement more info	PubMed
acts_upstream_of negative regulation of primary miRNA processing	IGI Inferred from Genetic Interaction more info	PubMed
involved_in neuron cellular homeostasis	TAS Traceable Author Statement more info	PubMed
involved_in neuron projection development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neutrophil apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in neutrophil mediated immunity	TAS Traceable Author Statement more info	PubMed
involved_in platelet activation	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of B cell activation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of T cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of T-helper 2 cell cytokine production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of acute inflammatory response	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of apoptotic DNA fragmentation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell population proliferation	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell population proliferation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of chemokine production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of chemokine production	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of cytokine production involved in inflammatory response	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of epithelial to mesenchymal transition	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of extracellular matrix disassembly	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of gene expression	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of glial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of immunoglobulin production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of immunoglobulin production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-1 beta production	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of interleukin-10 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-17 production	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of interleukin-21 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-6 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-8 production	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of leukocyte adhesion to vascular endothelial cell	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of leukocyte chemotaxis	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of miRNA transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of neuroinflammatory response	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of osteoblast differentiation	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within positive regulation of peptidyl-serine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of positive regulation of platelet aggregation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of receptor signaling pathway via JAK-STAT	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of receptor signaling pathway via JAK-STAT	IC Inferred by Curator more info	PubMed
involved_in positive regulation of receptor signaling pathway via JAK-STAT	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of positive regulation of receptor signaling pathway via STAT	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of smooth muscle cell proliferation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of translation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of tumor necrosis factor production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of type B pancreatic cell apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of vascular endothelial growth factor production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of angiogenesis	IC Inferred by Curator more info	PubMed
involved_in regulation of astrocyte activation	TAS Traceable Author Statement more info	PubMed
involved_in regulation of glucagon secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of insulin secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of microglial cell activation	TAS Traceable Author Statement more info	PubMed
involved_in regulation of neuroinflammatory response	TAS Traceable Author Statement more info	PubMed
involved_in regulation of vascular endothelial growth factor production	IDA Inferred from Direct Assay more info	PubMed
involved_in response to activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to glucocorticoid	IDA Inferred from Direct Assay more info	PubMed
involved_in response to peptidoglycan	NAS Non-traceable Author Statement more info	PubMed
involved_in vascular endothelial growth factor production	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
is_active_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
part_of interleukin-6 receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of interleukin-6 receptor complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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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

NCBI Reference Sequences (RefSeq)

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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

NG_011640.1 RefSeqGene

Range

5054..9852

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000600.5 → NP_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

Consensus CDS

CCDS5375.1

UniProtKB/Swiss-Prot

P05231, Q9UCU2, Q9UCU3, Q9UCU4

UniProtKB/TrEMBL

H9C875, Q75MH2

Related

ENSP00000258743.5, ENST00000258743.10

Conserved Domains (1) summary

pfam00489
Location:33 → 211

IL6; Interleukin-6/G-CSF/MGF family
NM_001318095.2 → NP_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

Consensus CDS

CCDS83166.1

UniProtKB/TrEMBL

B5MC21

Related

ENSP00000385043.1, ENST00000407492.5

Conserved Domains (1) summary

cl02473
Location:1 → 135

IL6; Interleukin-6/G-CSF/MGF family
NM_001371096.1 → NP_001358025.1 interleukin-6 isoform 3

Status: REVIEWED

Source sequence(s)

AC073072

Consensus CDS

CCDS94066.1

UniProtKB/TrEMBL

B5MCZ3, H9C875

Related

ENSP00000384928.3, ENST00000401630.7