IL6_MOUSE
ID IL6_MOUSE Reviewed; 211 AA.
AC P08505; Q3UCQ0; Q8BN26;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Interleukin-6 {ECO:0000305};
DE Short=IL-6;
DE AltName: Full=B-cell hybridoma growth factor;
DE AltName: Full=Interleukin HP-1;
DE Flags: Precursor;
GN Name=Il6 {ECO:0000312|MGI:MGI:96559}; Synonyms=Il-6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2965020; DOI=10.1002/eji.1830180202;
RA van Snick J., Cayphas S., Szikora J.-P., Renauld J.-C., van Roost E.,
RA Boon T., Simpson R.J.;
RT "cDNA cloning of murine interleukin-HP1: homology with human interleukin
RT 6.";
RL Eur. J. Immunol. 18:193-197(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3263439;
RA Tanabe O., Akira S., Kamiya T., Wong G.G., Hirano T., Kishimoto T.;
RT "Genomic structure of the murine IL-6 gene. High degree conservation of
RT potential regulatory sequences between mouse and human.";
RL J. Immunol. 141:3875-3881(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3262872; DOI=10.1073/pnas.85.19.7099;
RA Chiu C.P., Moulds C., Coffman R.L., Rennick D., Lee F.;
RT "Multiple biological activities are expressed by a mouse interleukin 6 cDNA
RT clone isolated from bone marrow stromal cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:7099-7103(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=2243807; DOI=10.1093/nar/18.21.6455;
RA Grenett H.E., Fuentes N.L., Fuller G.M.;
RT "Cloning and sequence analysis of the cDNA for murine interleukin-6.";
RL Nucleic Acids Res. 18:6455-6455(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Macrophage;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-6.
RC STRAIN=BALB/cJ;
RX PubMed=2106569; DOI=10.1084/jem.171.3.965;
RA Blankenstein T., Qin Z., Li W., Diamantstein T.;
RT "DNA rearrangement and constitutive expression of the interleukin 6 gene in
RT a mouse plasmacytoma.";
RL J. Exp. Med. 171:965-970(1990).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 5-211.
RC STRAIN=C57BL/6J;
RX PubMed=2563387;
RA Mock B.A., Nordan R.P., Justice M.J., Kozak C., Jenkins N.A.,
RA Copeland N.G., Clark S.C., Wong G.G., Rudikoff S.;
RT "The murine Il-6 gene maps to the proximal region of chromosome 5.";
RL J. Immunol. 142:1372-1376(1989).
RN [8]
RP PROTEIN SEQUENCE OF 25-45.
RX PubMed=2948184; DOI=10.1073/pnas.83.24.9679;
RA van Snick J., Cayphas S., Vink A., Uyttenhove C., Coulie P.G., Rubira M.R.,
RA Simpson R.J.;
RT "Purification and NH2-terminal amino acid sequence of a T-cell-derived
RT lymphokine with growth factor activity for B-cell hybridomas.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:9679-9683(1986).
RN [9]
RP PROTEIN SEQUENCE OF 25-211.
RX PubMed=3262059; DOI=10.1111/j.1432-1033.1988.tb14267.x;
RA Simpson R.J., Moritz R.L., Rubira M.R., van Snick J.;
RT "Murine hybridoma/plasmacytoma growth factor. Complete amino-acid sequence
RT and relation to human interleukin-6.";
RL Eur. J. Biochem. 176:187-197(1988).
RN [10]
RP PROTEIN SEQUENCE OF 66-75; 78-84 AND 128-148.
RX PubMed=2302197; DOI=10.1016/0006-291x(90)91922-f;
RA Jahnen W., Ward L.D., Reid G.E., Moritz R.L., Simpson R.J.;
RT "Internal amino acid sequencing of proteins by in situ cyanogen bromide
RT cleavage in polyacrylamide gels.";
RL Biochem. Biophys. Res. Commun. 166:139-145(1990).
RN [11]
RP DISULFIDE BONDS.
RX PubMed=3264160; DOI=10.1016/s0006-291x(88)80056-1;
RA Simpson R.J., Moritz R.L., van Roost E., van Snick J.;
RT "Characterization of a recombinant murine interleukin-6: assignment of
RT disulphide bonds.";
RL Biochem. Biophys. Res. Commun. 157:364-372(1988).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=8910279; DOI=10.1126/science.274.5291.1379;
RA Cressman D.E., Greenbaum L.E., DeAngelis R.A., Ciliberto G., Furth E.E.,
RA Poli V., Taub R.;
RT "Liver failure and defective hepatocyte regeneration in interleukin-6-
RT deficient mice.";
RL Science 274:1379-1383(1996).
RN [13]
RP FUNCTION.
RX PubMed=11113088; DOI=10.1053/gast.2000.20236;
RA Peters M., Blinn G., Jostock T., Schirmacher P.,
RA Meyer zum Bueschenfelde K.H., Galle P.R., Rose-John S.;
RT "Combined interleukin 6 and soluble interleukin 6 receptor accelerates
RT murine liver regeneration.";
RL Gastroenterology 119:1663-1671(2000).
RN [14]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11786910; DOI=10.1038/nm0102-75;
RA Wallenius V., Wallenius K., Ahren B., Rudling M., Carlsten H.,
RA Dickson S.L., Ohlsson C., Jansson J.O.;
RT "Interleukin-6-deficient mice develop mature-onset obesity.";
RL Nat. Med. 8:75-79(2002).
RN [15]
RP FUNCTION.
RX PubMed=15124018; DOI=10.1172/jci200420945;
RA Nemeth E., Rivera S., Gabayan V., Keller C., Taudorf S., Pedersen B.K.,
RA Ganz T.;
RT "IL-6 mediates hypoferremia of inflammation by inducing the synthesis of
RT the iron regulatory hormone hepcidin.";
RL J. Clin. Invest. 113:1271-1276(2004).
RN [16]
RP FUNCTION.
RX PubMed=17075861; DOI=10.1002/art.22175;
RA De Benedetti F., Rucci N., Del Fattore A., Peruzzi B., Paro R., Longo M.,
RA Vivarelli M., Muratori F., Berni S., Ballanti P., Ferrari S., Teti A.;
RT "Impaired skeletal development in interleukin-6-transgenic mice: a model
RT for the impact of chronic inflammation on the growing skeletal system.";
RL Arthritis Rheum. 54:3551-3563(2006).
RN [17]
RP FUNCTION IN TH17 DIFFERENTIATION, AND DISRUPTION PHENOTYPE.
RX PubMed=16990136; DOI=10.1016/j.cell.2006.07.035;
RA Ivanov I.I., McKenzie B.S., Zhou L., Tadokoro C.E., Lepelley A.,
RA Lafaille J.J., Cua D.J., Littman D.R.;
RT "The orphan nuclear receptor RORgammat directs the differentiation program
RT of proinflammatory IL-17+ T helper cells.";
RL Cell 126:1121-1133(2006).
RN [18]
RP FUNCTION, AND INDUCTION BY EXERCISE.
RX PubMed=22037645; DOI=10.1038/nm.2513;
RA Ellingsgaard H., Hauselmann I., Schuler B., Habib A.M., Baggio L.L.,
RA Meier D.T., Eppler E., Bouzakri K., Wueest S., Muller Y.D., Hansen A.M.,
RA Reinecke M., Konrad D., Gassmann M., Reimann F., Halban P.A., Gromada J.,
RA Drucker D.J., Gribble F.M., Ehses J.A., Donath M.Y.;
RT "Interleukin-6 enhances insulin secretion by increasing glucagon-like
RT peptide-1 secretion from L cells and alpha cells.";
RL Nat. Med. 17:1481-1489(2011).
RN [19]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND INDUCTION BY VIRAL
RP INFECTION.
RX PubMed=23045607; DOI=10.1084/jem.20111504;
RA Karnowski A., Chevrier S., Belz G.T., Mount A., Emslie D., D'Costa K.,
RA Tarlinton D.M., Kallies A., Corcoran L.M.;
RT "B and T cells collaborate in antiviral responses via IL-6, IL-21, and
RT transcriptional activator and coactivator, Oct2 and OBF-1.";
RL J. Exp. Med. 209:2049-2064(2012).
RN [20]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28402851; DOI=10.1016/j.celrep.2017.03.043;
RA Timper K., Denson J.L., Steculorum S.M., Heilinger C., Engstroem-Ruud L.,
RA Wunderlich C.M., Rose-John S., Wunderlich F.T., Bruening J.C.;
RT "IL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced
RT Central IL-6 trans-Signaling.";
RL Cell Rep. 19:267-280(2017).
RN [21]
RP INTERACTION WITH SORL1.
RX PubMed=28265003; DOI=10.1128/mcb.00641-16;
RA Larsen J.V., Petersen C.M.;
RT "SorLA in Interleukin-6 Signaling and Turnover.";
RL Mol. Cell. Biol. 37:0-0(2017).
RN [22]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=27893700; DOI=10.1038/ni.3632;
RA Heink S., Yogev N., Garbers C., Herwerth M., Aly L., Gasperi C.,
RA Husterer V., Croxford A.L., Moeller-Hackbarth K., Bartsch H.S., Sotlar K.,
RA Krebs S., Regen T., Blum H., Hemmer B., Misgeld T., Wunderlich T.F.,
RA Hidalgo J., Oukka M., Rose-John S., Schmidt-Supprian M., Waisman A.,
RA Korn T.;
RT "Trans-presentation of IL-6 by dendritic cells is required for the priming
RT of pathogenic TH17 cells.";
RL Nat. Immunol. 18:74-85(2017).
RN [23]
RP REVIEW ON FUNCTION.
RX PubMed=30995492; DOI=10.1016/j.immuni.2019.03.026;
RA Kang S., Tanaka T., Narazaki M., Kishimoto T.;
RT "Targeting Interleukin-6 Signaling in Clinic.";
RL Immunity 50:1007-1023(2019).
CC -!- FUNCTION: Cytokine with a wide variety of biological functions in
CC immunity, tissue regeneration, and metabolism (Probable). Binds to
CC IL6R, then the complex associates to the signaling subunit IL6ST/gp130
CC to trigger the intracellular IL6-signaling pathway (PubMed:8910279).
CC The interaction with the membrane-bound IL6R and IL6ST stimulates
CC 'classic signaling', whereas the binding of IL6 and soluble IL6R to
CC IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling'
CC occurs when membrane-bound IL6:IL6R complexes on transmitter cells
CC activate IL6ST receptors on neighboring receiver cells
CC (PubMed:27893700). {ECO:0000269|PubMed:27893700,
CC ECO:0000269|PubMed:8910279, ECO:0000305|PubMed:30995492}.
CC -!- FUNCTION: IL6 is a potent inducer of the acute phase response. Rapid
CC production of IL6 contributes to host defense during infection and
CC tissue injury, but excessive IL6 synthesis is involved in disease
CC pathology. In the innate immune response, is synthesized by myeloid
CC cells, such as macrophages and dendritic cells, upon recognition of
CC pathogens through toll-like receptors (TLRs) at the site of infection
CC or tissue injury. In the adaptive immune response, is required for the
CC differentiation of B-cells into immunoglolin-secreting cells
CC (Probable). Plays a major role in the differentiation of CD4(+) T cell
CC subsets. Essential factor for the development of T follicular helper
CC (Tfh) cells that are required for the induction of germinal-center
CC formation. Together with IL21, controls the early generation of Tfh
CC cells and are critical for an effective antibody response to acute
CC viral infection (PubMed:23045607). Required to drive naive CD4(+) T
CC cells to the Th17 lineage, through 'cluster signaling' by dendritic
CC cells (PubMed:16990136, PubMed:27893700). Also required for
CC proliferation of myeloma cells and the survival of plasmablast cells
CC (Probable). {ECO:0000269|PubMed:16990136, ECO:0000269|PubMed:23045607,
CC ECO:0000269|PubMed:27893700, ECO:0000305|PubMed:30995492}.
CC -!- FUNCTION: Acts as an essential factor in bone homeostasis and on
CC vessels directly or indirectly by induction of VEGF, resulting in
CC increased angiogenesis activity and vascular permeability. Induces,
CC through 'trans-signaling' and synergistically with IL1B and TNF, the
CC production of VEGF (PubMed:17075861). Involved in metabolic controls,
CC is discharged into the bloodstream after muscle contraction increasing
CC lipolysis and improving insulin resistance (PubMed:11786910). 'Trans-
CC signaling' in central nervous system regulates energy and glucose
CC homeostasis (PubMed:28402851). Mediates, through GLP-1, crosstalk
CC between insulin-sensitive tissues, intestinal L cells and pancreatic
CC islets to adapt to changes in insulin demand (PubMed:11113088). Also
CC acts as a myokine (By similarity). Plays a protective role during liver
CC injury, being required for maintenance of tissue regeneration
CC (PubMed:11113088, PubMed:8910279). Also has a pivotal role in iron
CC metabolism by regulating HAMP/hepcidin expression upon inflammation or
CC bacterial infection (PubMed:15124018). Through activation of IL6ST-YAP-
CC NOTCH pathway, induces inflammation-induced epithelial regeneration (By
CC similarity). {ECO:0000250|UniProtKB:P05231,
CC ECO:0000269|PubMed:11113088, ECO:0000269|PubMed:11786910,
CC ECO:0000269|PubMed:15124018, ECO:0000269|PubMed:17075861,
CC ECO:0000269|PubMed:28402851, ECO:0000269|PubMed:8910279}.
CC -!- SUBUNIT: Component of a hexamer of two molecules each of IL6, IL6R and
CC IL6ST; first binds to IL6R to associate with the signaling subunit
CC IL6ST (PubMed:28265003). Interacts with IL6R (via the N-terminal
CC ectodomain); this interaction may be affected by IL6R-binding with
CC SORL1, hence decreasing IL6 cis signaling. Interacts with SORL1 (via
CC the N-terminal ectodomain); this interaction leads to IL6
CC internalization and lysosomal degradation. May form a trimeric complex
CC with the soluble SORL1 ectodomain and soluble IL6R receptor; this
CC interaction might stabilize circulating IL6, hence promoting IL6 trans
CC signaling (PubMed:28265003). {ECO:0000269|PubMed:28265003}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:27893700}.
CC -!- TISSUE SPECIFICITY: Expressed by dendritic cells and macrophages
CC (PubMed:27893700, PubMed:23045607). Expressed by activated follicular B
CC cells (PubMed:23045607). Abundantly expressed in the central nervous
CC system (CNS), particularly the hypothalamic region (PubMed:28402851).
CC {ECO:0000269|PubMed:23045607, ECO:0000269|PubMed:27893700,
CC ECO:0000269|PubMed:28402851}.
CC -!- INDUCTION: In activated follicular B cells, expression is induced early
CC after influenza virus infection (PubMed:23045607). Plasma levels are
CC highly increased upon exercise, due to enhanced production by
CC contracting skeletal muscles (PubMed:22037645).
CC {ECO:0000269|PubMed:22037645, ECO:0000269|PubMed:23045607}.
CC -!- PTM: N- and O-glycosylated. {ECO:0000250|UniProtKB:P05231}.
CC -!- DISRUPTION PHENOTYPE: Animals have normal T-cell numbers in the lamina
CC propria but the T(H)17 cells are reduced by about 10-fold
CC (PubMed:16990136). They develop mature-onset obesity and have disturbed
CC carbohydrate and lipid metabolism, increased leptin levels and
CC decreased responsiveness to leptin treatment (PubMed:11786910). Animals
CC have impaired liver regeneration characterized by liver necrosis and
CC failure (PubMed:8910279). Mutants infected with influenza virus do not
CC show a significant difference on germinal center B cells compared to
CC wild-types (PubMed:23045607). Double knockouts for IL21 and IL6
CC infected with influenza virus show a significant reduction in germinal
CC centers in both the draining lymphatic nodes and the spleens to wild-
CC types. Animals show a significant reduction in virus-specific IgM and
CC IgG (PubMed:23045607). {ECO:0000269|PubMed:11786910,
CC ECO:0000269|PubMed:16990136, ECO:0000269|PubMed:23045607,
CC ECO:0000269|PubMed:8910279}.
CC -!- SIMILARITY: Belongs to the IL-6 superfamily. {ECO:0000305}.
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DR EMBL; X06203; CAA29560.1; -; mRNA.
DR EMBL; M20572; AAA39302.1; -; Genomic_DNA.
DR EMBL; J03783; AAA39301.1; -; mRNA.
DR EMBL; X54542; CAA38411.1; -; mRNA.
DR EMBL; AK150440; BAE29562.1; -; mRNA.
DR EMBL; X51457; CAA35824.1; -; Genomic_DNA.
DR EMBL; M24221; AAA68814.1; -; Genomic_DNA.
DR CCDS; CCDS19153.1; -.
DR PIR; A30531; ICMS6.
DR RefSeq; NP_001300983.1; NM_001314054.1.
DR RefSeq; NP_112445.1; NM_031168.2.
DR PDB; 2L3Y; NMR; -; A=27-211.
DR PDBsum; 2L3Y; -.
DR AlphaFoldDB; P08505; -.
DR SMR; P08505; -.
DR BioGRID; 200641; 2.
DR IntAct; P08505; 1.
DR STRING; 10090.ENSMUSP00000026845; -.
DR PhosphoSitePlus; P08505; -.
DR MaxQB; P08505; -.
DR PaxDb; P08505; -.
DR PRIDE; P08505; -.
DR ProteomicsDB; 267327; -.
DR Antibodypedia; 12025; 2864 antibodies from 50 providers.
DR DNASU; 16193; -.
DR Ensembl; ENSMUST00000026845; ENSMUSP00000026845; ENSMUSG00000025746.
DR GeneID; 16193; -.
DR KEGG; mmu:16193; -.
DR UCSC; uc008wuu.1; mouse.
DR CTD; 3569; -.
DR MGI; MGI:96559; Il6.
DR VEuPathDB; HostDB:ENSMUSG00000025746; -.
DR eggNOG; ENOG502S7Q4; Eukaryota.
DR GeneTree; ENSGT00390000000878; -.
DR HOGENOM; CLU_096521_0_0_1; -.
DR InParanoid; P08505; -.
DR OMA; ENAKAMQ; -.
DR OrthoDB; 1144279at2759; -.
DR PhylomeDB; P08505; -.
DR TreeFam; TF335984; -.
DR Reactome; R-MMU-1059683; Interleukin-6 signaling.
DR Reactome; R-MMU-110056; MAPK3 (ERK1) activation.
DR Reactome; R-MMU-112411; MAPK1 (ERK2) activation.
DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR BioGRID-ORCS; 16193; 3 hits in 73 CRISPR screens.
DR EvolutionaryTrace; P08505; -.
DR PRO; PR:P08505; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P08505; protein.
DR Bgee; ENSMUSG00000025746; Expressed in stroma of bone marrow and 24 other tissues.
DR ExpressionAtlas; P08505; baseline and differential.
DR Genevisible; P08505; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005896; C:interleukin-6 receptor complex; IDA:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; IDA:BHF-UCL.
DR GO; GO:0008083; F:growth factor activity; ISO:MGI.
DR GO; GO:0005138; F:interleukin-6 receptor binding; IDA:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW.
DR GO; GO:0060445; P:branching involved in salivary gland morphogenesis; IDA:MGI.
DR GO; GO:0045454; P:cell redox homeostasis; ISO:MGI.
DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; IDA:MGI.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:MGI.
DR GO; GO:0071347; P:cellular response to interleukin-1; IDA:MGI.
DR GO; GO:0097398; P:cellular response to interleukin-17; IDA:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:MGI.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:MGI.
DR GO; GO:0098586; P:cellular response to virus; IMP:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:MGI.
DR GO; GO:0042832; P:defense response to protozoan; IMP:MGI.
DR GO; GO:0051607; P:defense response to virus; ISO:MGI.
DR GO; GO:0031018; P:endocrine pancreas development; IMP:BHF-UCL.
DR GO; GO:0060664; P:epithelial cell proliferation involved in salivary gland morphogenesis; IDA:MGI.
DR GO; GO:0010467; P:gene expression; IDA:MGI.
DR GO; GO:0002314; P:germinal center B cell differentiation; IMP:UniProtKB.
DR GO; GO:0070091; P:glucagon secretion; IMP:BHF-UCL.
DR GO; GO:0042593; P:glucose homeostasis; IDA:UniProtKB.
DR GO; GO:0002384; P:hepatic immune response; ISO:MGI.
DR GO; GO:0072574; P:hepatocyte proliferation; IMP:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; ISO:MGI.
DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0097421; P:liver regeneration; IMP:UniProtKB.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IGI:MGI.
DR GO; GO:0002262; P:myeloid cell homeostasis; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0045779; P:negative regulation of bone resorption; IMP:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0032682; P:negative regulation of chemokine production; IDA:MGI.
DR GO; GO:0032966; P:negative regulation of collagen biosynthetic process; ISO:MGI.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0045721; P:negative regulation of gluconeogenesis; ISO:MGI.
DR GO; GO:0046888; P:negative regulation of hormone secretion; IDA:MGI.
DR GO; GO:2000660; P:negative regulation of interleukin-1-mediated signaling pathway; IMP:BHF-UCL.
DR GO; GO:0045837; P:negative regulation of membrane potential; ISO:MGI.
DR GO; GO:0048635; P:negative regulation of muscle organ development; ISO:MGI.
DR GO; GO:1901215; P:negative regulation of neuron death; ISO:MGI.
DR GO; GO:2000635; P:negative regulation of primary miRNA processing; ISO:MGI.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISO:MGI.
DR GO; GO:0031175; P:neuron projection development; ISO:MGI.
DR GO; GO:0001781; P:neutrophil apoptotic process; IDA:MGI.
DR GO; GO:0002675; P:positive regulation of acute inflammatory response; ISO:MGI.
DR GO; GO:1902512; P:positive regulation of apoptotic DNA fragmentation; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0050871; P:positive regulation of B cell activation; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0071864; P:positive regulation of cell proliferation in bone marrow; IGI:MGI.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:MGI.
DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; ISO:MGI.
DR GO; GO:0045740; P:positive regulation of DNA replication; ISO:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IDA:MGI.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0090091; P:positive regulation of extracellular matrix disassembly; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IGI:MGI.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; ISO:MGI.
DR GO; GO:0014015; P:positive regulation of gliogenesis; IMP:ARUK-UCL.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; IMP:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:MGI.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISO:MGI.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; IDA:ARUK-UCL.
DR GO; GO:0032745; P:positive regulation of interleukin-21 production; IDA:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:MGI.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:MGI.
DR GO; GO:1904996; P:positive regulation of leukocyte adhesion to vascular endothelial cell; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR GO; GO:1903800; P:positive regulation of miRNA maturation; ISO:MGI.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:MGI.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:1901731; P:positive regulation of platelet aggregation; ISO:MGI.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISO:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; ISO:MGI.
DR GO; GO:1904894; P:positive regulation of receptor signaling pathway via STAT; IMP:UniProtKB.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; ISO:MGI.
DR GO; GO:2000553; P:positive regulation of T-helper 2 cell cytokine production; IMP:BHF-UCL.
DR GO; GO:0045630; P:positive regulation of T-helper 2 cell differentiation; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0045727; P:positive regulation of translation; ISO:MGI.
DR GO; GO:0051971; P:positive regulation of transmission of nerve impulse; ISO:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:MGI.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISO:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; IMP:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0008360; P:regulation of cell shape; ISO:MGI.
DR GO; GO:0045188; P:regulation of circadian sleep/wake cycle, non-REM sleep; ISO:MGI.
DR GO; GO:0070092; P:regulation of glucagon secretion; IDA:UniProtKB.
DR GO; GO:0050796; P:regulation of insulin secretion; IDA:UniProtKB.
DR GO; GO:0010574; P:regulation of vascular endothelial growth factor production; ISO:MGI.
DR GO; GO:0014823; P:response to activity; IDA:UniProtKB.
DR GO; GO:0051384; P:response to glucocorticoid; ISO:MGI.
DR GO; GO:0009611; P:response to wounding; IDA:MGI.
DR GO; GO:0042110; P:T cell activation; IGI:MGI.
DR GO; GO:0061470; P:T follicular helper cell differentiation; IMP:UniProtKB.
DR GO; GO:0072540; P:T-helper 17 cell lineage commitment; IDA:UniProtKB.
DR GO; GO:0045064; P:T-helper 2 cell differentiation; IDA:MGI.
DR GO; GO:0010573; P:vascular endothelial growth factor production; ISS:UniProtKB.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR003574; IL-6.
DR InterPro; IPR030474; IL-6/GCSF/MGF.
DR InterPro; IPR030473; IL6/GCSF/MGF_CS.
DR PANTHER; PTHR10511; PTHR10511; 1.
DR PANTHER; PTHR10511:SF3; PTHR10511:SF3; 1.
DR Pfam; PF00489; IL6; 1.
DR PIRSF; PIRSF001935; IL6_MGF_GCSF; 1.
DR PRINTS; PR00433; IL6GCSFMGF.
DR SMART; SM00126; IL6; 1.
DR SUPFAM; SSF47266; SSF47266; 1.
DR PROSITE; PS00254; INTERLEUKIN_6; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acute phase; Cytokine; Direct protein sequencing;
KW Disulfide bond; Growth factor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:2948184,
FT ECO:0000269|PubMed:3262059"
FT CHAIN 25..211
FT /note="Interleukin-6"
FT /id="PRO_0000015588"
FT DISULFID 70..76
FT /evidence="ECO:0000269|PubMed:3264160"
FT DISULFID 99..109
FT /evidence="ECO:0000269|PubMed:3264160"
FT HELIX 48..68
FT /evidence="ECO:0007829|PDB:2L3Y"
FT TURN 69..72
FT /evidence="ECO:0007829|PDB:2L3Y"
FT HELIX 74..77
FT /evidence="ECO:0007829|PDB:2L3Y"
FT TURN 81..83
FT /evidence="ECO:0007829|PDB:2L3Y"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:2L3Y"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:2L3Y"
FT HELIX 114..129
FT /evidence="ECO:0007829|PDB:2L3Y"
FT HELIX 133..160
FT /evidence="ECO:0007829|PDB:2L3Y"
FT HELIX 170..176
FT /evidence="ECO:0007829|PDB:2L3Y"
FT HELIX 186..209
FT /evidence="ECO:0007829|PDB:2L3Y"
SQ SEQUENCE 211 AA; 24384 MW; BBB47DDA9E86787A CRC64;
MKFLSARDFH PVAFLGLMLV TTTAFPTSQV RRGDFTEDTT PNRPVYTTSQ VGGLITHVLW
EIVEMRKELC NGNSDCMNND DALAENNLKL PEIQRNDGCY QTGYNQEICL LKISSGLLEY
HSYLEYMKNN LKDNKKDKAR VLQRDTETLI HIFNQEVKDL HKIVLPTPIS NALLTDKLES
QKEWLRTKTI QFILKSLEEF LKVTLRSTRQ T
