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Interleukin-6 (IL-6)

 IL6_RAT                 Reviewed;         211 AA.
P20607;
01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
01-FEB-1991, sequence version 1.
22-NOV-2017, entry version 140.
RecName: Full=Interleukin-6;
Short=IL-6;
Flags: Precursor;
Name=Il6; Synonyms=Il-6;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
PubMed=2789217;
Northemann W., Braciak T.A., Hattori M., Lee F., Fey G.H.;
"Structure of the rat interleukin 6 gene and its expression in
macrophage-derived cells.";
J. Biol. Chem. 264:16072-16082(1989).
[2]
SUBCELLULAR LOCATION, AND INDUCTION BY ENDOCANNABINOID ANANDAMIDE AND
IL1B.
PubMed=23955712; DOI=10.1038/nm.3265;
Jourdan T., Godlewski G., Cinar R., Bertola A., Szanda G., Liu J.,
Tam J., Han T., Mukhopadhyay B., Skarulis M.C., Ju C., Aouadi M.,
Czech M.P., Kunos G.;
"Activation of the Nlrp3 inflammasome in infiltrating macrophages by
endocannabinoids mediates beta cell loss in type 2 diabetes.";
Nat. Med. 19:1132-1140(2013).
-!- 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 (By similarity). {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:23955712}.
-!- INDUCTION: In pancreatic islets, secretion is stimulated by IL1B.
In islets from Zucker diabetic fatty (ZDF) rats, but not lean
animals, secretion is also increased by endocannabinoid
anandamide/AEA. {ECO:0000269|PubMed:23955712}.
-!- SIMILARITY: Belongs to the IL-6 superfamily. {ECO:0000305}.
-----------------------------------------------------------------------
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; M26744; AAA77659.1; -; mRNA.
EMBL; M26745; AAA41430.1; -; Genomic_DNA.
PIR; A34247; A34247.
RefSeq; NP_036721.1; NM_012589.2.
UniGene; Rn.9873; -.
ProteinModelPortal; P20607; -.
MINT; MINT-189606; -.
STRING; 10116.ENSRNOP00000013732; -.
PaxDb; P20607; -.
PRIDE; P20607; -.
Ensembl; ENSRNOT00000013732; ENSRNOP00000013732; ENSRNOG00000010278.
GeneID; 24498; -.
KEGG; rno:24498; -.
UCSC; RGD:2901; rat.
CTD; 3569; -.
RGD; 2901; Il6.
eggNOG; ENOG410IW11; Eukaryota.
eggNOG; ENOG4112BXV; LUCA.
GeneTree; ENSGT00390000000878; -.
HOGENOM; HOG000236330; -.
HOVERGEN; HBG000471; -.
InParanoid; P20607; -.
KO; K05405; -.
OMA; LQAQNQW; -.
OrthoDB; EOG091G0NW5; -.
PhylomeDB; P20607; -.
Reactome; R-RNO-110056; MAPK3 (ERK1) activation.
Reactome; R-RNO-112411; MAPK1 (ERK2) activation.
Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
Reactome; R-RNO-6783589; Interleukin-6 family signaling.
Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
PRO; PR:P20607; -.
Proteomes; UP000002494; Chromosome 4.
Bgee; ENSRNOG00000010278; -.
Genevisible; P20607; RN.
GO; GO:0005737; C:cytoplasm; IDA:RGD.
GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
GO; GO:0005615; C:extracellular space; IDA:RGD.
GO; GO:0005896; C:interleukin-6 receptor complex; ISO:RGD.
GO; GO:0005125; F:cytokine activity; IDA:RGD.
GO; GO:0008083; F:growth factor activity; ISO:RGD.
GO; GO:0005138; F:interleukin-6 receptor binding; IDA:RGD.
GO; GO:0005102; F:receptor binding; IDA:RGD.
GO; GO:0002526; P:acute inflammatory response; IEP:RGD.
GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW.
GO; GO:0007568; P:aging; IEP:RGD.
GO; GO:0046849; P:bone remodeling; IEP:RGD.
GO; GO:0060445; P:branching involved in salivary gland morphogenesis; ISO:RGD.
GO; GO:0016049; P:cell growth; IDA:RGD.
GO; GO:0045454; P:cell redox homeostasis; IMP:RGD.
GO; GO:0071345; P:cellular response to cytokine stimulus; IEP:RGD.
GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
GO; GO:0071392; P:cellular response to estradiol stimulus; IEP:RGD.
GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; ISO:RGD.
GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD.
GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
GO; GO:0031669; P:cellular response to nutrient levels; IEP:RGD.
GO; GO:1990646; P:cellular response to prolactin; IEP:RGD.
GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:RGD.
GO; GO:0042832; P:defense response to protozoan; ISO:RGD.
GO; GO:0051607; P:defense response to virus; ISO:RGD.
GO; GO:0031018; P:endocrine pancreas development; ISO:RGD.
GO; GO:0060664; P:epithelial cell proliferation involved in salivary gland morphogenesis; ISO:RGD.
GO; GO:0070091; P:glucagon secretion; ISO:RGD.
GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
GO; GO:0002384; P:hepatic immune response; ISO:RGD.
GO; GO:0006954; P:inflammatory response; ISO:RGD.
GO; GO:0070102; P:interleukin-6-mediated signaling pathway; ISO:RGD.
GO; GO:0031294; P:lymphocyte costimulation; IEP:RGD.
GO; GO:0046716; P:muscle cell cellular homeostasis; ISO:RGD.
GO; GO:0002262; P:myeloid cell homeostasis; ISO:RGD.
GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
GO; GO:0045779; P:negative regulation of bone resorption; ISO:RGD.
GO; GO:0008285; P:negative regulation of cell proliferation; IMP:RGD.
GO; GO:0045079; P:negative regulation of chemokine biosynthetic process; ISO:RGD.
GO; GO:0032966; P:negative regulation of collagen biosynthetic process; ISO:RGD.
GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:RGD.
GO; GO:0050710; P:negative regulation of cytokine secretion; IDA:RGD.
GO; GO:0045721; P:negative regulation of gluconeogenesis; IDA:RGD.
GO; GO:0046888; P:negative regulation of hormone secretion; ISO:RGD.
GO; GO:2000660; P:negative regulation of interleukin-1-mediated signaling pathway; ISO:RGD.
GO; GO:0045837; P:negative regulation of membrane potential; IMP:RGD.
GO; GO:0048635; P:negative regulation of muscle organ development; IDA:RGD.
GO; GO:1901215; P:negative regulation of neuron death; IDA:RGD.
GO; GO:0006469; P:negative regulation of protein kinase activity; IDA:RGD.
GO; GO:0031175; P:neuron projection development; ISO:RGD.
GO; GO:0001781; P:neutrophil apoptotic process; ISO:RGD.
GO; GO:0002675; P:positive regulation of acute inflammatory response; ISO:RGD.
GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
GO; GO:0050871; P:positive regulation of B cell activation; ISO:RGD.
GO; GO:0008284; P:positive regulation of cell proliferation; ISO:RGD.
GO; GO:0071864; P:positive regulation of cell proliferation in bone marrow; ISO:RGD.
GO; GO:0032722; P:positive regulation of chemokine production; ISO:RGD.
GO; GO:0045740; P:positive regulation of DNA replication; IMP:RGD.
GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:RGD.
GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:RGD.
GO; GO:0010628; P:positive regulation of gene expression; IDA:RGD.
GO; GO:0051024; P:positive regulation of immunoglobulin secretion; ISO:RGD.
GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:RGD.
GO; GO:0046427; P:positive regulation of JAK-STAT cascade; IDA:RGD.
GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
GO; GO:0045666; P:positive regulation of neuron differentiation; IMP:RGD.
GO; GO:0010976; P:positive regulation of neuron projection development; IMP:RGD.
GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:RGD.
GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:RGD.
GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
GO; GO:0033160; P:positive regulation of protein import into nucleus, translocation; IDA:RGD.
GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:RGD.
GO; GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; ISO:RGD.
GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:RGD.
GO; GO:0042102; P:positive regulation of T cell proliferation; ISO:RGD.
GO; GO:2000553; P:positive regulation of T-helper 2 cell cytokine production; ISO:RGD.
GO; GO:0045630; P:positive regulation of T-helper 2 cell differentiation; ISO:RGD.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISO:RGD.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
GO; GO:0045727; P:positive regulation of translation; ISO:RGD.
GO; GO:0051971; P:positive regulation of transmission of nerve impulse; IDA:RGD.
GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:RGD.
GO; GO:0042981; P:regulation of apoptotic process; ISO:RGD.
GO; GO:0042127; P:regulation of cell proliferation; ISO:RGD.
GO; GO:0008360; P:regulation of cell shape; IDA:RGD.
GO; GO:0045188; P:regulation of circadian sleep/wake cycle, non-REM sleep; IMP:RGD.
GO; GO:0010574; P:regulation of vascular endothelial growth factor production; ISO:RGD.
GO; GO:0043200; P:response to amino acid; IEP:RGD.
GO; GO:0046677; P:response to antibiotic; IEP:RGD.
GO; GO:0010996; P:response to auditory stimulus; IEP:RGD.
GO; GO:0009617; P:response to bacterium; IEP:RGD.
GO; GO:0031000; P:response to caffeine; IEP:RGD.
GO; GO:0051592; P:response to calcium ion; IEP:RGD.
GO; GO:0009409; P:response to cold; IEP:RGD.
GO; GO:0034097; P:response to cytokine; IEP:RGD.
GO; GO:0042493; P:response to drug; IEP:RGD.
GO; GO:0051602; P:response to electrical stimulus; IEP:RGD.
GO; GO:0051384; P:response to glucocorticoid; ISO:RGD.
GO; GO:0009408; P:response to heat; IEP:RGD.
GO; GO:0032868; P:response to insulin; IEP:RGD.
GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
GO; GO:0009611; P:response to wounding; IEP:RGD.
GO; GO:0001878; P:response to yeast; IEP:RGD.
GO; GO:0042110; P:T cell activation; ISO:RGD.
GO; GO:0072540; P:T-helper 17 cell lineage commitment; ISS:UniProtKB.
GO; GO:0042060; P:wound healing; IEP:RGD.
InterPro; IPR009079; 4_helix_cytokine-like_core.
InterPro; IPR003574; IL-6.
InterPro; IPR030474; IL-6/GCSF/MGF.
InterPro; IPR030473; IL6/GCSF/MGF_CS.
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.
2: Evidence at transcript level;
Acute phase; Complete proteome; Cytokine; Disulfide bond;
Growth factor; Phosphoprotein; Reference proteome; Secreted; Signal.
SIGNAL 1 24 {ECO:0000255}.
CHAIN 25 211 Interleukin-6.
/FTId=PRO_0000015593.
MOD_RES 79 79 Phosphoserine.
{ECO:0000250|UniProtKB:P05231}.
DISULFID 70 76 {ECO:0000250}.
DISULFID 99 109 {ECO:0000250}.
SEQUENCE 211 AA; 24357 MW; 17D248A14F96B5C1 CRC64;
MKFLSARDFQ PVAFLGLMLL TATAFPTSQV RRGDFTEDTT HNRPVYTTSQ VGGLITYVLR
EILEMRKELC NGNSDCMNSD DALSENNLKL PEIQRNDGCF QTGYNQEICL LKICSGLLEF
RFYLEFVKNN LQDNKKDKAR VIQSNTETLV HIFKQEIKDS YKIVLPTPTS NALLMEKLES
QKEWLRTKTI QLILKALEEF LKVTMRSTRQ T


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