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Interleukin-6 (IL-6) (B-cell stimulatory factor 2) (BSF-2) (CTL differentiation factor) (CDF) (Hybridoma growth factor) (Interferon beta-2) (IFN-beta-2)

 IL6_HUMAN               Reviewed;         212 AA.
P05231; Q9UCU2; Q9UCU3; Q9UCU4;
13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
13-AUG-1987, sequence version 1.
13-FEB-2019, entry version 219.
RecName: Full=Interleukin-6;
Short=IL-6;
AltName: Full=B-cell stimulatory factor 2;
Short=BSF-2;
AltName: Full=CTL differentiation factor;
Short=CDF;
AltName: Full=Hybridoma growth factor;
AltName: Full=Interferon beta-2;
Short=IFN-beta-2;
Flags: Precursor;
Name=IL6; Synonyms=IFNB2;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
PubMed=3491322; DOI=10.1038/324073a0;
Hirano T., Yasukawa K., Harada H., Taga T., Watanabe Y., Matsuda T.,
Kashiwamura S., Nakajima K., Koyama K., Iwamatsu A., Tsunasawa S.,
Sakiyama F., Matsui H., Takahara Y., Taniguchi T., Kishimoto T.;
"Complementary DNA for a novel human interleukin (BSF-2) that induces
B lymphocytes to produce immunoglobulin.";
Nature 324:73-76(1986).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=3500852;
Yasukawa K., Hirano T., Watanabe Y., Muratani K., Matsuda T.,
Nakai S., Kishimoto T.;
"Structure and expression of human B cell stimulatory factor-2 (BSF-
2/IL-6) gene.";
EMBO J. 6:2939-2945(1987).
[3]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=3538015; DOI=10.1073/pnas.83.23.8957;
May L.T., Helfgott D.C., Sehgal P.B.;
"Anti-beta-interferon antibodies inhibit the increased expression of
HLA-B7 mRNA in tumor necrosis factor-treated human fibroblasts:
structural studies of the beta 2 interferon involved.";
Proc. Natl. Acad. Sci. U.S.A. 83:8957-8961(1986).
[4]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=3023045;
Zilberstein A., Ruggieri R., Korn J.H., Revel M.;
"Structure and expression of cDNA and genes for human interferon-beta-
2, a distinct species inducible by growth-stimulatory cytokines.";
EMBO J. 5:2529-2537(1986).
[5]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=3320204;
Brakenhoff J.P.J., de Groot E.R., Evers R.F., Pannekoek H.,
Aarden L.A.;
"Molecular cloning and expression of hybridoma growth factor in
Escherichia coli.";
J. Immunol. 139:4116-4121(1987).
[6]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=2789513; DOI=10.1016/0006-291X(89)92328-0;
Tonouchi N., Miwa K., Karasuyama H., Matsui H.;
"Deletion of 3' untranslated region of human BSF-2 mRNA causes
stabilization of the mRNA and high-level expression in mouse NIH3T3
cells.";
Biochem. Biophys. Res. Commun. 163:1056-1062(1989).
[7]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
TISSUE=Fibroblast;
PubMed=3758081; DOI=10.1111/j.1432-1033.1986.tb09931.x;
Haegeman G., Content J., Volckaert G., Derynck R., Tavernier J.,
Fiers W.;
"Structural analysis of the sequence coding for an inducible 26-kDa
protein in human fibroblasts.";
Eur. J. Biochem. 159:625-632(1986).
[8]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=3266463;
Wong G., Witek-Giannotti J., Hewick R., Clark S., Ogawa M.;
"Interleukin 6: identification as a hematopoietic colony-stimulating
factor.";
Behring Inst. Mitt. 83:40-47(1988).
[9]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=1291290;
Chen Q.Y.;
"Stable and efficient expression of human interleukin-6 cDNA in
mammalian cells after gene transfer.";
Zhonghua Zhong Liu Za Zhi 14:340-344(1992).
[10]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-32 AND VAL-162.
SeattleSNPs variation discovery resource;
Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
[11]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Lung;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[12]
PROTEIN SEQUENCE OF 30-63.
PubMed=3279116;
van Damme J., van Beeumen J., Decock B., van Snick J., de Ley M.,
Billiau A.;
"Separation and comparison of two monokines with lymphocyte-activating
factor activity: IL-1 beta and hybridoma growth factor (HGF).
Identification of leukocyte-derived HGF as IL-6.";
J. Immunol. 140:1534-1541(1988).
[13]
PROTEIN SEQUENCE OF 30-50.
PubMed=2610854;
Ming J.E., Cernetti C., Steinman R.M., Granelli-Piperno A.;
"Interleukin 6 is the principal cytolytic T lymphocyte differentiation
factor for thymocytes in human leukocyte conditioned medium.";
J. Mol. Cell. Immunol. 4:203-211(1989).
[14]
PROTEIN SEQUENCE OF 30-40, AND GLYCOSYLATION.
PubMed=1883960; DOI=10.1016/1043-4666(91)90018-9;
May L.T., Shaw J.E., Khanna A.K., Zabriskie J.B., Sehgal P.B.;
"Marked cell-type-specific differences in glycosylation of human
interleukin-6.";
Cytokine 3:204-211(1991).
[15]
PROTEIN SEQUENCE OF 50-212.
PubMed=7851440; DOI=10.1111/j.1432-1033.1995.tb20427.x;
Breton J., la Fiura A., Bertolero F., Orsini G., Valsasina B.,
Ziliotto R., de Filippis V., Polverino de Laureto P., Fontana A.;
"Structure, stability and biological properties of a N-terminally
truncated form of recombinant human interleukin-6 containing a single
disulfide bond.";
Eur. J. Biochem. 227:573-581(1995).
[16]
DISULFIDE BONDS.
PubMed=2472117; DOI=10.1016/0003-9861(89)90205-1;
Clogston C.L., Boone T.C., Crandall B.C., Mendiaz E.A., Lu H.S.;
"Disulfide structures of human interleukin-6 are similar to those of
human granulocyte colony stimulating factor.";
Arch. Biochem. Biophys. 272:144-151(1989).
[17]
MUTAGENESIS.
PubMed=2037043; DOI=10.1016/0014-5793(91)80491-K;
Luetticken C., Kruettgen A., Moeller C., Heinrich P.C., Rose-John S.;
"Evidence for the importance of a positive charge and an alpha-helical
structure of the C-terminus for biological activity of human IL-6.";
FEBS Lett. 282:265-267(1991).
[18]
STRUCTURE BY NMR.
PubMed=8555185; DOI=10.1021/bi951949e;
Nishimura C., Watanabe A., Gouda H., Shimada I., Arata Y.;
"Folding topologies of human interleukin-6 and its mutants as studied
by NMR spectroscopy.";
Biochemistry 35:273-281(1996).
[19]
STRUCTURE BY NMR.
PubMed=9159484; DOI=10.1006/jmbi.1997.0933;
Xu G.-Y., Yu H.-A., Hong J., Stahl M., McDonagh T., Kay L.E.,
Cumming D.A.;
"Solution structure of recombinant human interleukin-6.";
J. Mol. Biol. 268:468-481(1997).
[20]
X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
PubMed=9118960; DOI=10.1093/emboj/16.5.989;
Somers W., Stahl M., Seehra J.S.;
"1.9-A crystal structure of interleukin 6: implications for a novel
mode of receptor dimerization and signaling.";
EMBO J. 16:989-997(1997).
[21]
INVOLVEMENT IN RASJ.
PubMed=9769329; DOI=10.1172/JCI2629;
Fishman D., Faulds G., Jeffery R., Mohamed-Ali V., Yudkin J.S.,
Humphries S., Woo P.;
"The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on
IL-6 transcription and plasma IL-6 levels, and an association with
systemic-onset juvenile chronic arthritis.";
J. Clin. Invest. 102:1369-1376(1998).
[22]
INVOLVEMENT IN SUSCEPTIBILITY TO KAPOSI SARCOMA.
PubMed=11001912;
Foster C.B., Lehrnbecher T., Samuels S., Stein S., Mol F.,
Metcalf J.A., Wyvill K., Steinberg S.M., Kovacs J., Blauvelt A.,
Yarchoan R., Chanock S.J.;
"An IL6 promoter polymorphism is associated with a lifetime risk of
development of Kaposi sarcoma in men infected with human
immunodeficiency virus.";
Blood 96:2562-2567(2000).
[23]
INVOLVEMENT IN BMD.
PubMed=11355017; DOI=10.1007/s100380170077;
Ota N., Nakajima T., Nakazawa I., Suzuki T., Hosoi T., Orimo H.,
Inoue S., Shirai Y., Emi M.;
"A nucleotide variant in the promoter region of the interleukin-6 gene
associated with decreased bone mineral density.";
J. Hum. Genet. 46:267-272(2001).
[24]
INVOLVEMENT IN BMD.
PubMed=12768442; DOI=10.1007/s10038-003-0020-8;
Chung H.W., Seo J.-S., Hur S.E., Kim H.L., Kim J.Y., Jung J.H.,
Kim L.H., Park B.L., Shin H.D.;
"Association of interleukin-6 promoter variant with bone mineral
density in pre-menopausal women.";
J. Hum. Genet. 48:243-248(2003).
[25]
PHOSPHORYLATION AT SER-81.
PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
Pinna L.A., Pagliarini D.J., Dixon J.E.;
"A single kinase generates the majority of the secreted
phosphoproteome.";
Cell 161:1619-1632(2015).
-!- FUNCTION: Cytokine with a wide variety of biological functions. It
is a potent inducer of the acute phase response. Plays an
essential role in the final differentiation of B-cells into Ig-
secreting cells Involved in lymphocyte and monocyte
differentiation. Acts on B-cells, T-cells, hepatocytes,
hematopoietic progenitor cells and cells of the CNS. Required for
the generation of T(H)17 cells. Also acts as a myokine. It is
discharged into the bloodstream after muscle contraction and acts
to increase the breakdown of fats and to improve insulin
resistance. It induces myeloma and plasmacytoma growth and induces
nerve cells differentiation.
-!- INTERACTION:
P08887:IL6R; NbExp=6; IntAct=EBI-720533, EBI-299383;
Q05516:ZBTB16; NbExp=2; IntAct=EBI-720533, EBI-711925;
-!- SUBCELLULAR LOCATION: Secreted.
-!- PTM: N- and O-glycosylated. {ECO:0000269|PubMed:1883960}.
-!- POLYMORPHISM: Genetic variations in IL6 may be correlated with
bone mineral density (BMD). Low BMD is a risk factor for
osteoporotic fracture. Osteoporosis is characterized by reduced
bone mineral density, disruption of bone microarchitecture, and
the alteration of the amount and variety of non-collagenous
proteins in bone. Osteoporotic bones are more at risk of fracture.
{ECO:0000269|PubMed:11355017, ECO:0000269|PubMed:12768442}.
-!- DISEASE: Rheumatoid arthritis systemic juvenile (RASJ)
[MIM:604302]: An inflammatory articular disorder with systemic-
onset beginning before the age of 16. It represents a subgroup of
juvenile arthritis associated with severe extraarticular features
and occasionally fatal complications. During active phases of the
disorder, patients display a typical daily spiking fever, an
evanescent macular rash, lymphadenopathy, hepatosplenomegaly,
serositis, myalgia and arthritis. {ECO:0000269|PubMed:9769329}.
Note=Disease susceptibility is associated with variations
affecting the gene represented in this entry.
-!- DISEASE: Note=A IL6 promoter polymorphism is associated with a
lifetime risk of development of Kaposi sarcoma in HIV-infected
men. {ECO:0000269|PubMed:11001912}.
-!- SIMILARITY: Belongs to the IL-6 superfamily. {ECO:0000305}.
-!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-6 entry;
URL="https://en.wikipedia.org/wiki/Interleukin_6";
-!- WEB RESOURCE: Name=SeattleSNPs;
URL="http://pga.gs.washington.edu/data/il6/";
-!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and
polymorphism database;
URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=IL6";
-!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
and Haematology;
URL="http://atlasgeneticsoncology.org/Genes/IL6ID519ch7p15.html";
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EMBL; X04430; CAA28026.1; -; mRNA.
EMBL; M14584; AAA52728.1; -; mRNA.
EMBL; X04602; CAA28268.1; -; mRNA.
EMBL; Y00081; CAA68278.1; -; Genomic_DNA.
EMBL; M18403; AAA52729.1; -; mRNA.
EMBL; M29150; AAA59154.1; -; mRNA.
EMBL; X04402; CAA27990.1; -; Genomic_DNA.
EMBL; X04403; CAA27991.1; -; mRNA.
EMBL; M54894; AAC41704.1; -; mRNA.
EMBL; S56892; AAD13886.1; -; mRNA.
EMBL; AF372214; AAK48987.1; -; Genomic_DNA.
EMBL; BC015511; AAH15511.1; -; mRNA.
CCDS; CCDS5375.1; -.
PIR; A32648; IVHUB2.
RefSeq; NP_000591.1; NM_000600.4.
RefSeq; XP_011513692.1; XM_011515390.2.
UniGene; Hs.654458; -.
PDB; 1ALU; X-ray; 1.90 A; A=28-212.
PDB; 1IL6; NMR; -; A=28-212.
PDB; 1N2Q; Model; -; E/F=30-212.
PDB; 1P9M; X-ray; 3.65 A; B=29-212.
PDB; 2IL6; NMR; -; A=28-212.
PDB; 4CNI; X-ray; 2.20 A; C/D=42-212.
PDB; 4J4L; X-ray; 2.30 A; C/D=47-212.
PDB; 4NI7; X-ray; 2.40 A; A=28-212.
PDB; 4NI9; X-ray; 2.55 A; A/C=28-212.
PDB; 4O9H; X-ray; 2.42 A; A=28-212.
PDB; 4ZS7; X-ray; 2.93 A; A=42-212.
PDB; 5FUC; X-ray; 2.70 A; A/B=49-212.
PDBsum; 1ALU; -.
PDBsum; 1IL6; -.
PDBsum; 1N2Q; -.
PDBsum; 1P9M; -.
PDBsum; 2IL6; -.
PDBsum; 4CNI; -.
PDBsum; 4J4L; -.
PDBsum; 4NI7; -.
PDBsum; 4NI9; -.
PDBsum; 4O9H; -.
PDBsum; 4ZS7; -.
PDBsum; 5FUC; -.
ProteinModelPortal; P05231; -.
SMR; P05231; -.
BioGrid; 109783; 4.
DIP; DIP-482N; -.
IntAct; P05231; 6.
STRING; 9606.ENSP00000258743; -.
BindingDB; P05231; -.
ChEMBL; CHEMBL1795129; -.
DrugBank; DB05250; 681323.
DrugBank; DB05066; AV411.
DrugBank; DB05744; CRx-139.
DrugBank; DB01404; Ginseng.
DrugBank; DB05767; HMPL-004.
DrugBank; DB09036; Siltuximab.
DrugBank; DB05470; VX-702.
DrugBank; DB05017; YSIL6.
iPTMnet; P05231; -.
PhosphoSitePlus; P05231; -.
BioMuta; IL6; -.
DMDM; 124347; -.
PaxDb; P05231; -.
PeptideAtlas; P05231; -.
PRIDE; P05231; -.
ProteomicsDB; 51828; -.
DNASU; 3569; -.
Ensembl; ENST00000258743; ENSP00000258743; ENSG00000136244.
Ensembl; ENST00000404625; ENSP00000385675; ENSG00000136244.
GeneID; 3569; -.
KEGG; hsa:3569; -.
CTD; 3569; -.
DisGeNET; 3569; -.
EuPathDB; HostDB:ENSG00000136244.11; -.
GeneCards; IL6; -.
H-InvDB; HIX0167872; -.
HGNC; HGNC:6018; IL6.
HPA; CAB023406; -.
HPA; CAB072821; -.
MalaCards; IL6; -.
MIM; 147620; gene.
MIM; 148000; phenotype.
MIM; 604302; phenotype.
neXtProt; NX_P05231; -.
OpenTargets; ENSG00000136244; -.
Orphanet; 206; NON RARE IN EUROPE: Crohn disease.
Orphanet; 85414; Systemic-onset juvenile idiopathic arthritis.
PharmGKB; PA198; -.
eggNOG; ENOG410IW11; Eukaryota.
eggNOG; ENOG4112BXV; LUCA.
GeneTree; ENSGT00390000000878; -.
HOGENOM; HOG000236330; -.
HOVERGEN; HBG000471; -.
InParanoid; P05231; -.
KO; K05405; -.
OMA; GFNKETC; -.
OrthoDB; 1186029at2759; -.
PhylomeDB; P05231; -.
TreeFam; TF335984; -.
Reactome; R-HSA-1059683; Interleukin-6 signaling.
Reactome; R-HSA-110056; MAPK3 (ERK1) activation.
Reactome; R-HSA-112411; MAPK1 (ERK2) activation.
Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP).
Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
Reactome; R-HSA-6783783; Interleukin-10 signaling.
Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
SignaLink; P05231; -.
SIGNOR; P05231; -.
ChiTaRS; IL6; human.
EvolutionaryTrace; P05231; -.
GeneWiki; Interleukin_6; -.
GenomeRNAi; 3569; -.
PMAP-CutDB; P05231; -.
PRO; PR:P05231; -.
Proteomes; UP000005640; Chromosome 7.
Bgee; ENSG00000136244; Expressed in 143 organ(s), highest expression level in left coronary artery.
ExpressionAtlas; P05231; baseline and differential.
Genevisible; P05231; HS.
GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
GO; GO:0005896; C:interleukin-6 receptor complex; IDA:BHF-UCL.
GO; GO:0005125; F:cytokine activity; IDA:BHF-UCL.
GO; GO:0008083; F:growth factor activity; IDA:BHF-UCL.
GO; GO:0005138; F:interleukin-6 receptor binding; IPI:BHF-UCL.
GO; GO:0006953; P:acute-phase response; TAS:BHF-UCL.
GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome.
GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:BHF-UCL.
GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:MGI.
GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:BHF-UCL.
GO; GO:0050829; P:defense response to Gram-negative bacterium; TAS:BHF-UCL.
GO; GO:0050830; P:defense response to Gram-positive bacterium; TAS:BHF-UCL.
GO; GO:0051607; P:defense response to virus; IDA:BHF-UCL.
GO; GO:0031018; P:endocrine pancreas development; ISS:BHF-UCL.
GO; GO:0070091; P:glucagon secretion; ISS:BHF-UCL.
GO; GO:0002384; P:hepatic immune response; IDA:BHF-UCL.
GO; GO:0006959; P:humoral immune response; IC:BHF-UCL.
GO; GO:0006954; P:inflammatory response; IDA:BHF-UCL.
GO; GO:0070102; P:interleukin-6-mediated signaling pathway; IDA:BHF-UCL.
GO; GO:0002548; P:monocyte chemotaxis; IC:BHF-UCL.
GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
GO; GO:0045779; P:negative regulation of bone resorption; ISS:BHF-UCL.
GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc.
GO; GO:0045079; P:negative regulation of chemokine biosynthetic process; ISS:UniProtKB.
GO; GO:0032966; P:negative regulation of collagen biosynthetic process; IDA:BHF-UCL.
GO; GO:0045599; P:negative regulation of fat cell differentiation; NAS:BHF-UCL.
GO; GO:2000660; P:negative regulation of interleukin-1-mediated signaling pathway; ISS:BHF-UCL.
GO; GO:0010888; P:negative regulation of lipid storage; NAS:BHF-UCL.
GO; GO:0050768; P:negative regulation of neurogenesis; TAS:ARUK-UCL.
GO; GO:0070050; P:neuron cellular homeostasis; TAS:ARUK-UCL.
GO; GO:0031175; P:neuron projection development; IMP:BHF-UCL.
GO; GO:0001781; P:neutrophil apoptotic process; IDA:UniProtKB.
GO; GO:0002446; P:neutrophil mediated immunity; TAS:BHF-UCL.
GO; GO:0030168; P:platelet activation; TAS:BHF-UCL.
GO; GO:0002675; P:positive regulation of acute inflammatory response; IDA:BHF-UCL.
GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
GO; GO:0050871; P:positive regulation of B cell activation; IDA:BHF-UCL.
GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
GO; GO:0032722; P:positive regulation of chemokine production; IDA:BHF-UCL.
GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IDA:ARUK-UCL.
GO; GO:0090091; P:positive regulation of extracellular matrix disassembly; IMP:ARUK-UCL.
GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL.
GO; GO:0060252; P:positive regulation of glial cell proliferation; IDA:ARUK-UCL.
GO; GO:0051024; P:positive regulation of immunoglobulin secretion; IDA:BHF-UCL.
GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:BHF-UCL.
GO; GO:0002690; P:positive regulation of leukocyte chemotaxis; TAS:BHF-UCL.
GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:BHF-UCL.
GO; GO:0150078; P:positive regulation of neuroinflammatory response; TAS:ARUK-UCL.
GO; GO:0045669; P:positive regulation of osteoblast differentiation; TAS:BHF-UCL.
GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:MGI.
GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:MGI.
GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IDA:BHF-UCL.
GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:BHF-UCL.
GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:BHF-UCL.
GO; GO:2000553; P:positive regulation of T-helper 2 cell cytokine production; ISS:BHF-UCL.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0045727; P:positive regulation of translation; IDA:UniProtKB.
GO; GO:2000676; P:positive regulation of type B pancreatic cell apoptotic process; TAS:BHF-UCL.
GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:BHF-UCL.
GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
GO; GO:0045765; P:regulation of angiogenesis; IC:BHF-UCL.
GO; GO:0061888; P:regulation of astrocyte activation; TAS:ARUK-UCL.
GO; GO:1905603; P:regulation of maintenance of permeability of blood-brain barrier; TAS:ARUK-UCL.
GO; GO:1903978; P:regulation of microglial cell activation; TAS:ARUK-UCL.
GO; GO:0150077; P:regulation of neuroinflammatory response; TAS:ARUK-UCL.
GO; GO:0010574; P:regulation of vascular endothelial growth factor production; IDA:BHF-UCL.
GO; GO:0051384; P:response to glucocorticoid; IDA:BHF-UCL.
GO; GO:0032494; P:response to peptidoglycan; NAS:BHF-UCL.
GO; GO:0072540; P:T-helper 17 cell lineage commitment; ISS:UniProtKB.
InterPro; IPR009079; 4_helix_cytokine-like_core.
InterPro; IPR003574; IL-6.
InterPro; IPR030474; IL-6/GCSF/MGF.
InterPro; IPR030473; IL6/GCSF/MGF_CS.
PANTHER; PTHR45110; PTHR45110; 1.
Pfam; PF00489; IL6; 1.
PIRSF; PIRSF001935; IL6_MGF_GCSF; 1.
PRINTS; PR00433; IL6GCSFMGF.
SMART; SM00126; IL6; 1.
SUPFAM; SSF47266; SSF47266; 1.
PROSITE; PS00254; INTERLEUKIN_6; 1.
1: Evidence at protein level;
3D-structure; Acute phase; Complete proteome; Cytokine;
Direct protein sequencing; Disulfide bond; Glycoprotein;
Growth factor; Phosphoprotein; Polymorphism; Reference proteome;
Secreted; Signal.
SIGNAL 1 29 {ECO:0000269|PubMed:1883960,
ECO:0000269|PubMed:2610854,
ECO:0000269|PubMed:3279116}.
CHAIN 30 212 Interleukin-6.
/FTId=PRO_0000015582.
MOD_RES 81 81 Phosphoserine; by FAM20C.
{ECO:0000269|PubMed:26091039}.
CARBOHYD 73 73 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:1883960}.
DISULFID 72 78 {ECO:0000269|PubMed:2472117}.
DISULFID 101 111 {ECO:0000269|PubMed:2472117}.
VARIANT 32 32 P -> S (in dbSNP:rs2069830).
{ECO:0000269|Ref.10}.
/FTId=VAR_013075.
VARIANT 162 162 D -> E (in dbSNP:rs13306435).
/FTId=VAR_029266.
VARIANT 162 162 D -> V (in dbSNP:rs2069860).
{ECO:0000269|Ref.10}.
/FTId=VAR_013076.
MUTAGEN 173 173 A->V: Almost no loss of activity.
{ECO:0000269|PubMed:2037043}.
MUTAGEN 185 185 W->R: No loss of activity.
{ECO:0000269|PubMed:2037043}.
MUTAGEN 204 204 S->P: 87% loss of activity.
{ECO:0000269|PubMed:2037043}.
MUTAGEN 210 210 R->K,E,Q,T,A,P: Loss of activity.
{ECO:0000269|PubMed:2037043}.
MUTAGEN 212 212 M->T,N,S,R: Loss of activity.
{ECO:0000269|PubMed:2037043}.
HELIX 49 75 {ECO:0000244|PDB:1ALU}.
STRAND 76 79 {ECO:0000244|PDB:2IL6}.
TURN 81 83 {ECO:0000244|PDB:4CNI}.
HELIX 84 87 {ECO:0000244|PDB:4CNI}.
HELIX 97 99 {ECO:0000244|PDB:1ALU}.
STRAND 102 105 {ECO:0000244|PDB:4J4L}.
HELIX 108 132 {ECO:0000244|PDB:1ALU}.
STRAND 134 136 {ECO:0000244|PDB:4J4L}.
HELIX 137 157 {ECO:0000244|PDB:1ALU}.
STRAND 159 161 {ECO:0000244|PDB:1ALU}.
HELIX 169 180 {ECO:0000244|PDB:1ALU}.
HELIX 184 209 {ECO:0000244|PDB:1ALU}.
SEQUENCE 212 AA; 23718 MW; 1F1ED1FE1B734079 CRC64;
MNSFSTSAFG PVAFSLGLLL VLPAAFPAPV PPGEDSKDVA APHRQPLTSS ERIDKQIRYI
LDGISALRKE TCNKSNMCES SKEALAENNL NLPKMAEKDG CFQSGFNEET CLVKIITGLL
EFEVYLEYLQ NRFESSEEQA RAVQMSTKVL IQFLQKKAKN LDAITTPDPT TNASLLTKLQ
AQNQWLQDMT THLILRSFKE FLQSSLRALR QM


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Kits Elisa; taq POLYMERASE

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Pathways :
WP1046: Signaling of Hepatocyte Growth Factor Receptor
WP1162: Signaling of Hepatocyte Growth Factor Receptor
WP1206: Signaling of Hepatocyte Growth Factor Receptor
WP1235: Signaling of Hepatocyte Growth Factor Receptor
WP1789: Binding of RNA by Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs)
WP1899: Regulation of Insulin-like Growth Factor (IGF) Activity by Insulin-like Growth Factor Binding Proteins (IGFBPs)
WP193: Signaling of Hepatocyte Growth Factor Receptor
WP313: Signaling of Hepatocyte Growth Factor Receptor
WP444: Signaling of Hepatocyte Growth Factor Receptor
WP810: Signaling of Hepatocyte Growth Factor Receptor
WP927: Signaling of Hepatocyte Growth Factor Receptor
WP94: Signaling of Hepatocyte Growth Factor Receptor
WP1835: Interferon alpha/beta signaling
WP1897: Regulation of beta-cell development
WP1983: Splicing factor NOVA regulated synpatic proteins
WP2148: Brain derived neurotrophic factor
WP272: Blood Clotting Cascade
WP1045: TGF-beta Receptor Signaling Pathway
WP1048: TGF Beta Signaling Pathway
WP105: Fatty Acid Beta Oxidation 2
WP1058: Senescence and Autophagy
WP1061: Fatty Acid Beta Oxidation
WP1106: Keap1-Nrf2
WP1107: Mitochondrial LC-Fatty Acid Beta-Oxidation
WP113: TGF Beta Signaling Pathway

Related Genes :
[Il2 Il-2] Interleukin-2 (IL-2) (T-cell growth factor) (TCGF)
[IL4] Interleukin-4 (IL-4) (B-cell stimulatory factor 1) (BSF-1) (Binetrakin) (Lymphocyte stimulatory factor 1) (Pitrakinra)
[IL18 IGIF IL1F4] Interleukin-18 (IL-18) (Iboctadekin) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[Il6st] Interleukin-6 receptor subunit beta (IL-6 receptor subunit beta) (IL-6R subunit beta) (IL-6R-beta) (IL-6RB) (Interleukin-6 signal transducer) (Membrane glycoprotein 130) (gp130) (Oncostatin-M receptor subunit alpha) (CD antigen CD130)
[Cebpb Crp2 Nf-il6 Sfb] CCAAT/enhancer-binding protein beta (C/EBP beta) (C/EBP-related protein 2) (Interleukin-6-dependent-binding protein) (IL-6DBP) (Liver-enriched inhibitory protein) (LIP) (Liver-enriched transcriptional activator) (LAP) (Silencer factor B) (SF-B)
[Il18 Igif] Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[IL2] Interleukin-2 (IL-2) (T-cell growth factor) (TCGF) (Aldesleukin)
[PDGFRB PDGFR PDGFR1] Platelet-derived growth factor receptor beta (PDGF-R-beta) (PDGFR-beta) (EC 2.7.10.1) (Beta platelet-derived growth factor receptor) (Beta-type platelet-derived growth factor receptor) (CD140 antigen-like family member B) (Platelet-derived growth factor receptor 1) (PDGFR-1) (CD antigen CD140b)
[Tnf Tnfa Tnfsf2] Tumor necrosis factor (Cachectin) (TNF-alpha) (Tumor necrosis factor ligand superfamily member 2) (TNF-a) [Cleaved into: Tumor necrosis factor, membrane form (N-terminal fragment) (NTF); Intracellular domain 1 (ICD1); Intracellular domain 2 (ICD2); C-domain 1; C-domain 2; Tumor necrosis factor, soluble form]
[TRAF6 RNF85] TNF receptor-associated factor 6 (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRAF6) (Interleukin-1 signal transducer) (RING finger protein 85) (RING-type E3 ubiquitin transferase TRAF6)
[Il18 Igif] Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[IFNLR1 IL28RA LICR2] Interferon lambda receptor 1 (IFN-lambda receptor 1) (IFN-lambda-R1) (Cytokine receptor class-II member 12) (Cytokine receptor family 2 member 12) (CRF2-12) (Interleukin-28 receptor subunit alpha) (IL-28 receptor subunit alpha) (IL-28R-alpha) (IL-28RA) (Likely interleukin or cytokine receptor 2) (LICR2)
[IL18 IGIF] Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[Il12rb2] Interleukin-12 receptor subunit beta-2 (IL-12 receptor subunit beta-2) (IL-12R subunit beta-2) (IL-12R-beta-2) (IL-12RB2)
[IL6ST] Interleukin-6 receptor subunit beta (IL-6 receptor subunit beta) (IL-6R subunit beta) (IL-6R-beta) (IL-6RB) (CDw130) (Interleukin-6 signal transducer) (Membrane glycoprotein 130) (gp130) (Oncostatin-M receptor subunit alpha) (CD antigen CD130)
[IL1B IL1F2] Interleukin-1 beta (IL-1 beta) (Catabolin)
[Pdgfrb Pdgfr Pdgfr1] Platelet-derived growth factor receptor beta (PDGF-R-beta) (PDGFR-beta) (EC 2.7.10.1) (Beta platelet-derived growth factor receptor) (Beta-type platelet-derived growth factor receptor) (CD140 antigen-like family member B) (Platelet-derived growth factor receptor 1) (PDGFR-1) (CD antigen CD140b)
[Eif2ak2 Pkr Prkr Tik] Interferon-induced, double-stranded RNA-activated protein kinase (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 2) (eIF-2A protein kinase 2) (Interferon-inducible RNA-dependent protein kinase) (P1/eIF-2A protein kinase) (Protein kinase RNA-activated) (PKR) (Protein kinase R) (Serine/threonine-protein kinase TIK) (Tyrosine-protein kinase EIF2AK2) (EC 2.7.10.2) (p68 kinase)
[Traf6] TNF receptor-associated factor 6 (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRAF6) (RING-type E3 ubiquitin transferase TRAF6)
[IL18 IGIF] Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[Tgfb1] Transforming growth factor beta-1 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]
[Cbfb Pebp2b Pebpb2] Core-binding factor subunit beta (CBF-beta) (Polyomavirus enhancer-binding protein 2 beta subunit) (PEA2-beta) (PEBP2-beta) (SL3-3 enhancer factor 1 subunit beta) (SL3/AKV core-binding factor beta subunit)
[PPBP CTAP3 CXCL7 SCYB7 TGB1 THBGB1] Platelet basic protein (PBP) (C-X-C motif chemokine 7) (Leukocyte-derived growth factor) (LDGF) (Macrophage-derived growth factor) (MDGF) (Small-inducible cytokine B7) [Cleaved into: Connective tissue-activating peptide III (CTAP-III) (LA-PF4) (Low-affinity platelet factor IV); TC-2; Connective tissue-activating peptide III(1-81) (CTAP-III(1-81)); Beta-thromboglobulin (Beta-TG); Neutrophil-activating peptide 2(74) (NAP-2(74)); Neutrophil-activating peptide 2(73) (NAP-2(73)); Neutrophil-activating peptide 2 (NAP-2); TC-1; Neutrophil-activating peptide 2(1-66) (NAP-2(1-66)); Neutrophil-activating peptide 2(1-63) (NAP-2(1-63))]
[Ifnar2] Interferon alpha/beta receptor 2 (IFN-R-2) (IFN-alpha/beta receptor 2) (Type I interferon receptor 2)
[Il1b] Interleukin-1 beta (IL-1 beta)
[IKBKB IKKB] Inhibitor of nuclear factor kappa-B kinase subunit beta (I-kappa-B-kinase beta) (IKK-B) (IKK-beta) (IkBKB) (EC 2.7.11.10) (I-kappa-B kinase 2) (IKK2) (Nuclear factor NF-kappa-B inhibitor kinase beta) (NFKBIKB)
[Runx1 Aml1 Cbfa2 Pebp2ab] Runt-related transcription factor 1 (Acute myeloid leukemia 1 protein) (Core-binding factor subunit alpha-2) (CBF-alpha-2) (Oncogene AML-1) (Polyomavirus enhancer-binding protein 2 alpha B subunit) (PEA2-alpha B) (PEBP2-alpha B) (SL3-3 enhancer factor 1 alpha B subunit) (SL3/AKV core-binding factor alpha B subunit)
[TGFB2] Transforming growth factor beta-2 proprotein (Cetermin) (Glioblastoma-derived T-cell suppressor factor) (G-TSF) [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-2 (TGF-beta-2)]
[TICAM1 PRVTIRB TRIF] TIR domain-containing adapter molecule 1 (TICAM-1) (Proline-rich, vinculin and TIR domain-containing protein B) (Putative NF-kappa-B-activating protein 502H) (Toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta) (MyD88-3) (TIR domain-containing adapter protein inducing IFN-beta)
[Ikbkb Ikkb] Inhibitor of nuclear factor kappa-B kinase subunit beta (I-kappa-B-kinase beta) (IKK-B) (IKK-beta) (IkBKB) (EC 2.7.11.10) (I-kappa-B kinase 2) (IKK2) (Nuclear factor NF-kappa-B inhibitor kinase beta) (NFKBIKB)

Bibliography :
[1913833] Interleukin-6 is constitutively produced by human CTL clones and is required to maintain their cytolytic function.
[2610854] Interleukin 6 is the principal cytolytic T lymphocyte differentiation factor for thymocytes in human leukocyte conditioned medium.
[3257241] B cell stimulatory factor-2 is involved in the differentiation of cytotoxic T lymphocytes.