IL6 (interleukin 6)

Gene

• Entrez ID: 3569
• Gene name: Interleukin 6
• Gene symbol: IL6
• Synonyms: BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2, IFNB2, IL-6
• Chromosome: 7
• Chromosome location: 7p15.3
• 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]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005420	hsa-let-7a-5p	Luciferase reporter assay, qRT-PCR, Western blot	19878981
MIRT006061	hsa-miR-203a-3p	ELISA, qRT-PCR	21279994
MIRT006790	hsa-miR-142-3p	ELISA, Immunoblot, Microarray, qRT-PCR	21474672
MIRT007374	hsa-miR-26a-5p	Luciferase reporter assay	23389848
MIRT016949	hsa-miR-335-5p	Microarray	18185580
MIRT020073	hsa-miR-365a-3p	Reporter assay	21518763
MIRT021049	hsa-miR-155-5p	Proteomics	20584899
MIRT021049	hsa-miR-155-5p	Proteomics	18668040
MIRT022183	hsa-miR-124-3p	Microarray	18668037
MIRT023501	hsa-miR-1-3p	Microarray	18668037
MIRT027449	hsa-miR-98-5p	Microarray	19088304
MIRT027449	hsa-miR-98-5p	Luciferase reporter assay, qRT-PCR, Western blot	26367177
MIRT027449	hsa-miR-98-5p	Luciferase reporter assay, qRT-PCR, Western blot	26587789
MIRT054777	hsa-miR-107	Luciferase reporter assay, qRT-PCR, Western blot, Coimmunoprecipitation, Chromatin immunoprecipitation, Immunofluorescence microscopy	24429361
MIRT438050	hsa-let-7c-5p	Luciferase reporter assay, qRT-PCR, ELISA	23977098
MIRT438284	hsa-miR-223-3p	Luciferase reporter assay	24084739
MIRT438344	hsa-miR-149-5p	ELISA, Luciferase reporter assay, qRT-PCR, Western blot	25916550
MIRT731223	hsa-let-7f-5p	ELISA, Luciferase reporter assay	26810534
MIRT731232	hsa-miR-146b-5p	Luciferase reporter assay, qRT-PCR, Western blot	26338965
MIRT731346	hsa-miR-9-5p	Luciferase reporter assay	25809226
MIRT732454	hsa-miR-146a-5p	Microarray, Luciferase reporter assay,	25265569
MIRT733375	hsa-miR-125a-3p	Luciferase reporter assay, qRT-PCR, Western blot	26563755
MIRT734163	hsa-miR-106a-5p	qRT-PCR	25950430
MIRT734880	hsa-miR-136-5p	Immunofluorescence, Luciferase reporter assay, qRT-PCR, Western blot	26450567
MIRT735462	hsa-miR-451a	Luciferase reporter assay, qRT-PCR, Western blot	27461244

Transcription factors

Transcription factor	Regulation	Reference
AHR	Activation	20511231
AHR	Unknown	18483242;23349129
ATF4	Unknown	16931790
CEBPA	Unknown	11975924
CEBPB	Activation	10903137;8725624
CEBPB	Unknown	11120852
CREB1	Activation	8725624
DDIT3	Activation	12706815
EGR1	Repression	15517885
EGR2	Unknown	24007274
EP300	Unknown	19966855
FOXO1	Activation	21185807
GBX2	Activation	10690529
JUN	Activation	20225236
JUN	Unknown	10542237;11120852
JUND	Activation	11337499
KLF4	Activation	23846700
MYC	Unknown	19259613
NFKB1	Activation	10329846;10903137;11327783;11504280;12058956;12887736;14532843;15756023;16984731;17040605;17196927;18057724;18061164;18243142;18942706;18996370;19124729;19164127;20066113;22547075;7876168;8679226;8725624
NFKB1	Repression	15517885
NFKB1	Unknown	10823821;10963848;11120852;11975924;15158360;16112536;17490702;17532054;19469019;19707556;2405250;8752656;9516466
OTX2	Activation	21047732
PPARA	Unknown	15001458
RBPJ	Activation	10329846
RBPJ	Unknown	9516466
REL	Repression	1372388
RELA	Activation	10329846;10903137;11327783;11504280;12058956;12887736;14532843;15756023;16984731;17040605;17196927;18057724;18061164;18243142;18942706;18996370;19124729;19164127;20066113;22547075;7499267;7876168;8679226
RELA	Repression	15517885
RELA	Unknown	10542237;10823821;10963848;11120852;11975924;15158360;16112536;17490702;17532054;19469019;19707556;19966855;20457835;8752656;9516466
SP1	Activation	18502099
STAT1	Repression	18616672
STAT3	Activation	10391682;18765795;20930550;22547075;22927445
STAT3	Repression	18616672
STAT3	Unknown	22105366;22363173
TBP	Repression	9209275
VDR	Repression	11050002
XBP1	Unknown	16931790
ZFP36	Repression	21656745
ZMYND11	Activation	19379743
ZNF300	Activation	21777376

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001781	Process	Neutrophil apoptotic process	IDA	7595060
GO:0002314	Process	Germinal center B cell differentiation	ISS
GO:0002377	Process	Immunoglobulin production	ISS
GO:0002384	Process	Hepatic immune response	IDA	2444978
GO:0002384	Process	Hepatic immune response	TAS	12832423
GO:0002446	Process	Neutrophil mediated immunity	TAS	16034137
GO:0002548	Process	Monocyte chemotaxis	IC	10510402
GO:0002639	Process	Positive regulation of immunoglobulin production	IDA	3491322
GO:0002675	Process	Positive regulation of acute inflammatory response	IDA	2444978
GO:0002690	Process	Positive regulation of leukocyte chemotaxis	TAS	16034137
GO:0005125	Function	Cytokine activity	IDA	3023045, 3491322
GO:0005125	Function	Cytokine activity	ISS
GO:0005125	Function	Cytokine activity	NAS	10443688
GO:0005125	Function	Cytokine activity	TAS	28720735
GO:0005138	Function	Interleukin-6 receptor binding	IPI	12829785
GO:0005138	Function	Interleukin-6 receptor binding	IPI	12829785
GO:0005138	Function	Interleukin-6 receptor binding	NAS	1883960
GO:0005515	Function	Protein binding	IPI	11238858, 12829785, 16169070, 18775332, 25241761, 25401472, 28265003
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IDA	3023045, 10443688, 16034137
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0005896	Component	Interleukin-6 receptor complex	IDA	2261637, 12829785
GO:0006953	Process	Acute-phase response	TAS	12832423
GO:0006954	Process	Inflammatory response	IDA	10443688
GO:0006954	Process	Inflammatory response	TAS	28720735
GO:0006959	Process	Humoral immune response	IC	3491322
GO:0008083	Function	Growth factor activity	IDA	2261637, 12643274
GO:0008284	Process	Positive regulation of cell population proliferation	IDA	2261637, 31886314
GO:0008284	Process	Positive regulation of cell population proliferation	IGI	25809226
GO:0008284	Process	Positive regulation of cell population proliferation	IMP	18719127
GO:0008285	Process	Negative regulation of cell population proliferation	TAS	3023045
GO:0010573	Process	Vascular endothelial growth factor production	IDA	12794819
GO:0010574	Process	Regulation of vascular endothelial growth factor production	IDA	8557680
GO:0010575	Process	Positive regulation of vascular endothelial growth factor production	IMP	28433754
GO:0010628	Process	Positive regulation of gene expression	IDA	19390056
GO:0010628	Process	Positive regulation of gene expression	IGI	31886314
GO:0010628	Process	Positive regulation of gene expression	ISS
GO:0010718	Process	Positive regulation of epithelial to mesenchymal transition	IDA	25916550
GO:0010888	Process	Negative regulation of lipid storage	NAS	16464856
GO:0014823	Process	Response to activity	ISS
GO:0019221	Process	Cytokine-mediated signaling pathway	IDA	2261637, 12643274
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0030168	Process	Platelet activation	TAS	7831669
GO:0031018	Process	Endocrine pancreas development	ISS
GO:0031175	Process	Neuron projection development	IMP	3264880
GO:0032494	Process	Response to peptidoglycan	NAS	16034137
GO:0032625	Process	Interleukin-21 production	ISS
GO:0032682	Process	Negative regulation of chemokine production	ISS
GO:0032722	Process	Positive regulation of chemokine production	IDA	10510402
GO:0032722	Process	Positive regulation of chemokine production	NAS	16034137
GO:0032731	Process	Positive regulation of interleukin-1 beta production	IDA	31886314
GO:0032731	Process	Positive regulation of interleukin-1 beta production	IGI	31886314
GO:0032733	Process	Positive regulation of interleukin-10 production	IDA	31886314
GO:0032733	Process	Positive regulation of interleukin-10 production	IGI	31886314
GO:0032740	Process	Positive regulation of interleukin-17 production	ISS	25362566
GO:0032755	Process	Positive regulation of interleukin-6 production	IDA	10510402
GO:0032757	Process	Positive regulation of interleukin-8 production	IDA	31886314
GO:0032757	Process	Positive regulation of interleukin-8 production	IGI	31886314
GO:0032760	Process	Positive regulation of tumor necrosis factor production	IDA	31886314
GO:0032760	Process	Positive regulation of tumor necrosis factor production	IGI	31886314
GO:0032966	Process	Negative regulation of collagen biosynthetic process	IDA	12419823
GO:0033138	Process	Positive regulation of peptidyl-serine phosphorylation	IDA	7508917
GO:0035633	Process	Maintenance of blood-brain barrier	TAS	29702085
GO:0042102	Process	Positive regulation of T cell proliferation	IDA	3130269
GO:0042531	Process	Positive regulation of tyrosine phosphorylation of STAT protein	IDA	12643274, 19390056, 31886314
GO:0042531	Process	Positive regulation of tyrosine phosphorylation of STAT protein	IMP	28433754
GO:0042593	Process	Glucose homeostasis	IDA	22037645
GO:0043065	Process	Positive regulation of apoptotic process	IDA	9949178
GO:0043066	Process	Negative regulation of apoptotic process	IDA	7595060
GO:0043410	Process	Positive regulation of MAPK cascade	IDA	7508917, 12419823
GO:0043687	Process	Post-translational protein modification	TAS
GO:0044267	Process	Cellular protein metabolic process	TAS
GO:0045599	Process	Negative regulation of fat cell differentiation	NAS	16464856
GO:0045669	Process	Positive regulation of osteoblast differentiation	IDA	30545407
GO:0045669	Process	Positive regulation of osteoblast differentiation	TAS	12372336
GO:0045727	Process	Positive regulation of translation	IDA	16732314
GO:0045765	Process	Regulation of angiogenesis	IC	8557680
GO:0045779	Process	Negative regulation of bone resorption	ISS
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	7749983, 16606666
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IMP	17875732
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	7508917, 16946298, 17324931
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	ISS
GO:0046427	Process	Positive regulation of receptor signaling pathway via JAK-STAT	IC	17324931
GO:0046427	Process	Positive regulation of receptor signaling pathway via JAK-STAT	IDA	12419823, 12552091, 17324931
GO:0048661	Process	Positive regulation of smooth muscle cell proliferation	IDA	10510402
GO:0050731	Process	Positive regulation of peptidyl-tyrosine phosphorylation	IDA	7508917
GO:0050768	Process	Negative regulation of neurogenesis	TAS	20018408
GO:0050796	Process	Regulation of insulin secretion	IDA	22037645
GO:0050829	Process	Defense response to Gram-negative bacterium	TAS	16034137
GO:0050830	Process	Defense response to Gram-positive bacterium	TAS	16034137
GO:0050871	Process	Positive regulation of B cell activation	IDA	3491322
GO:0051091	Process	Positive regulation of DNA-binding transcription factor activity	IDA	7749983, 30670152
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IDA	12419823
GO:0051384	Process	Response to glucocorticoid	IDA	10443688
GO:0051607	Process	Defense response to virus	IDA	3023045
GO:0060252	Process	Positive regulation of glial cell proliferation	IDA	2104886
GO:0061470	Process	T follicular helper cell differentiation	ISS
GO:0061888	Process	Regulation of astrocyte activation	TAS	29702085
GO:0070050	Process	Neuron cellular homeostasis	TAS	29702085
GO:0070091	Process	Glucagon secretion	ISS
GO:0070092	Process	Regulation of glucagon secretion	IDA	22037645
GO:0070102	Process	Interleukin-6-mediated signaling pathway	IDA	12552091, 16946298, 30670152
GO:0070102	Process	Interleukin-6-mediated signaling pathway	TAS
GO:0070301	Process	Cellular response to hydrogen peroxide	IDA	19168699
GO:0071222	Process	Cellular response to lipopolysaccharide	IMP	23776175
GO:0072540	Process	T-helper 17 cell lineage commitment	ISS
GO:0072574	Process	Hepatocyte proliferation	ISS
GO:0090091	Process	Positive regulation of extracellular matrix disassembly	IMP	26587789
GO:0097421	Process	Liver regeneration	ISS
GO:0098586	Process	Cellular response to virus	ISS
GO:0150077	Process	Regulation of neuroinflammatory response	TAS	29702085
GO:0150078	Process	Positive regulation of neuroinflammatory response	TAS	26753638
GO:1900017	Process	Positive regulation of cytokine production involved in inflammatory response	IGI	31886314
GO:1902512	Process	Positive regulation of apoptotic DNA fragmentation	IMP	28433754
GO:1903800	Process	Positive regulation of production of miRNAs involved in gene silencing by miRNA	IDA	27252421
GO:1903978	Process	Regulation of microglial cell activation	TAS	29702085
GO:1904894	Process	Positive regulation of receptor signaling pathway via STAT	IGI	30670152
GO:1904996	Process	Positive regulation of leukocyte adhesion to vascular endothelial cell	IDA	30670152
GO:2000553	Process	Positive regulation of T-helper 2 cell cytokine production	ISS
GO:2000635	Process	Negative regulation of primary miRNA processing	IGI	31507089
GO:2000660	Process	Negative regulation of interleukin-1-mediated signaling pathway	ISS
GO:2000676	Process	Positive regulation of type B pancreatic cell apoptotic process	TAS	18719127

Other IDs

• MIM: 147620
• HGNC: 6018
• e!Ensembl: ENSG00000136244

Protein

• UniProt ID: P05231
• Protein name: Interleukin-6 (IL-6) (B-cell stimulatory factor 2) (BSF-2) (CTL differentiation factor) (CDF) (Hybridoma growth factor) (Interferon beta-2) (IFN-beta-2)
• Protein function: Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway (Probable). The interaction with the membrane-bound IL6R and IL6ST stimulates 'classic signaling', whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable). ; IL6 is a potent inducer of the acute phase response. Rapid production of IL6 contributes to host defense during infection and tissue injury, but excessive IL6 synthesis is involved in disease pathology. In the innate immune response, is synthesized by myeloid cells, such as macrophages and dendritic cells, upon recognition of pathogens through toll-like receptors (TLRs) at the site of infection or tissue injury (Probable). In the adaptive immune response, is required for the differentiation of B cells into immunoglobulin-secreting cells. Plays a major role in the differentiation of CD4(+) T cell subsets. Essential factor for the development of T follicular helper (Tfh) cells that are required for the induction of germinal-center formation. Required to drive naive CD4(+) T cells to the Th17 lineage. Also required for proliferation of myeloma cells and the survival of plasmablast cells (By similarity). ; Acts as an essential factor in bone homeostasis and on vessels directly or indirectly by induction of VEGF, resulting in increased angiogenesis activity and vascular permeability (PubMed:17075861, PubMed:12794819). Induces, through 'trans-signaling' and synergistically with IL1B and TNF, the production of VEGF (PubMed:12794819). Involved in metabolic controls, is discharged into the bloodstream after muscle contraction increasing lipolysis and improving insulin resistance (PubMed:20823453). 'Trans-signaling' in central nervous system also regulates energy and glucose homeostasis (By similarity). Mediates, through GLP-1, crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand (By similarity). Also acts as a myokine (Probable). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity). Also has a pivotal role in iron metabolism by regulating HAMP/hepcidin expression upon inflammation or bacterial infection (PubMed:15124018). Through activation of IL6ST-YAP-NOTCH pathway, induces inflammation-induced epithelial regeneration (By similarity).
• PDB: 1ALU, 1IL6, 1N2Q, 1P9M, 2IL6, 4CNI, 4J4L, 4NI7, 4NI9, 4O9H, 4ZS7, 5FUC
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00489	IL6	27 → 212	Interleukin-6/G-CSF/MGF family	Domain

• Sequence:

  MNSFSTSAFGPVAFSLGLLLVLPAAFPAPVPPGEDSKDVAAPHRQPLTSSERIDKQIRYI
  LDGISALRKETCNKSNMCESSKEALAENNLNLPKMAEKDGCFQSGFNEETCLVKIITGLL
  EFEVYLEYLQNRFESSEEQARAVQMSTKVLIQFLQKKAKNLDAITTPDPTTNASLLTKLQ
  AQNQWLQDMTTHLILRSFKEFLQSSLRALRQM

• Sequence length: 212