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P08505 (IL6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interleukin-6

Short name=IL-6
Alternative name(s):
B-cell hybridoma growth factor
Interleukin HP-1
Gene names
Name:Il6
Synonyms:Il-6
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length211 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.12

Subcellular location

Secreted.

Disruption phenotype

Animals have normal T-cell numbers in the lamina propria but the T(H)17 cells are reduced by about 10-fold. Ref.12

Sequence similarities

Belongs to the IL-6 superfamily.

Ontologies

Keywords
   Biological processAcute phase
   Cellular componentSecreted
   DomainSignal
   Molecular functionCytokine
Growth factor
   PTMDisulfide bond
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processT cell activation

Inferred from genetic interaction PubMed 18792410. Source: MGI

T-helper 17 cell lineage commitment

Inferred from mutant phenotype Ref.12. Source: UniProtKB

acute-phase response

Inferred from electronic annotation. Source: UniProtKB-KW

aging

Inferred from electronic annotation. Source: Ensembl

bone remodeling

Inferred from electronic annotation. Source: Ensembl

branching involved in salivary gland morphogenesis

Inferred from direct assay PubMed 11275690. Source: MGI

cell growth

Inferred from electronic annotation. Source: Ensembl

cell redox homeostasis

Inferred from electronic annotation. Source: Ensembl

cellular response to hydrogen peroxide

Inferred from electronic annotation. Source: Ensembl

defense response to Gram-negative bacterium

Inferred from electronic annotation. Source: Ensembl

defense response to Gram-positive bacterium

Inferred from electronic annotation. Source: Ensembl

defense response to protozoan

Inferred from mutant phenotype PubMed 17109471. Source: MGI

defense response to virus

Inferred from electronic annotation. Source: Ensembl

endocrine pancreas development

Inferred from mutant phenotype PubMed 18719127. Source: BHF-UCL

epithelial cell proliferation involved in salivary gland morphogenesis

Inferred from direct assay PubMed 11275690. Source: MGI

glucagon secretion

Inferred from mutant phenotype PubMed 18719127. Source: BHF-UCL

interleukin-6-mediated signaling pathway

Inferred from direct assay PubMed 1312474. Source: MGI

muscle cell cellular homeostasis

Inferred from genetic interaction PubMed 18056981. Source: MGI

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of chemokine biosynthetic process

Inferred from direct assay PubMed 12925700. Source: MGI

negative regulation of collagen biosynthetic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cytokine secretion

Inferred from electronic annotation. Source: Ensembl

negative regulation of gluconeogenesis

Inferred from electronic annotation. Source: Ensembl

negative regulation of hormone secretion

Inferred from direct assay PubMed 7867561. Source: MGI

negative regulation of muscle organ development

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron death

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein kinase activity

Inferred from electronic annotation. Source: Ensembl

neuron projection development

Inferred from electronic annotation. Source: Ensembl

neutrophil apoptotic process

Inferred from direct assay PubMed 12925700. Source: MGI

positive regulation of B cell activation

Inferred from electronic annotation. Source: Ensembl

positive regulation of DNA replication

Inferred from electronic annotation. Source: Ensembl

positive regulation of ERK1 and ERK2 cascade

Inferred from electronic annotation. Source: Ensembl

positive regulation of T cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of T-helper 2 cell differentiation

Inferred from direct assay PubMed 12594267. Source: MGI

positive regulation of acute inflammatory response

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of chemokine production

Inferred from electronic annotation. Source: Ensembl

positive regulation of epithelial cell proliferation

Inferred from direct assay PubMed 11275690. Source: MGI

positive regulation of immunoglobulin secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-6 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of nitric oxide biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein import into nucleus, translocation

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of smooth muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 19666510. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 1373998. Source: MGI

positive regulation of translation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transmission of nerve impulse

Inferred from electronic annotation. Source: Ensembl

positive regulation of tyrosine phosphorylation of Stat3 protein

Inferred from electronic annotation. Source: Ensembl

regulation of apoptotic process

Inferred from mutant phenotype PubMed 11275690. Source: MGI

regulation of cell proliferation

Inferred from genetic interaction PubMed 18056981. Source: MGI

regulation of cell shape

Inferred from electronic annotation. Source: Ensembl

regulation of circadian sleep/wake cycle, non-REM sleep

Inferred from electronic annotation. Source: Ensembl

regulation of vascular endothelial growth factor production

Inferred from electronic annotation. Source: Ensembl

response to amino acid

Inferred from electronic annotation. Source: Ensembl

response to antibiotic

Inferred from electronic annotation. Source: Ensembl

response to caffeine

Inferred from electronic annotation. Source: Ensembl

response to calcium ion

Inferred from electronic annotation. Source: Ensembl

response to cold

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to electrical stimulus

Inferred from electronic annotation. Source: Ensembl

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

response to heat

Inferred from electronic annotation. Source: Ensembl

response to insulin

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

response to nutrient levels

Inferred from electronic annotation. Source: Ensembl

response to peptidoglycan

Inferred from electronic annotation. Source: Ensembl

response to wounding

Inferred from direct assay PubMed 19404405. Source: MGI

   Cellular_componentexternal side of plasma membrane

Inferred from direct assay PubMed 11275690. Source: MGI

extracellular space

Inferred from direct assay PubMed 10549626PubMed 11016935PubMed 11894098PubMed 12855817PubMed 14764707PubMed 15240714PubMed 15292196PubMed 15692051PubMed 1577194PubMed 16236719PubMed 16275384PubMed 17277142PubMed 17693256PubMed 18261938PubMed 18559975PubMed 19139201PubMed 23460747. Source: MGI

interleukin-6 receptor complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functioncytokine activity

Inferred from direct assay PubMed 12925700PubMed 1373998. Source: MGI

interleukin-6 receptor binding

Inferred from direct assay PubMed 1312474. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Ref.8 Ref.9
Chain25 – 211187Interleukin-6
PRO_0000015588

Amino acid modifications

Disulfide bond70 ↔ 76 Ref.11
Disulfide bond99 ↔ 109 Ref.11

Secondary structure

................... 211
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P08505 [UniParc].

Last modified August 1, 1988. Version 1.
Checksum: BBB47DDA9E86787A

FASTA21124,384
        10         20         30         40         50         60 
MKFLSARDFH PVAFLGLMLV TTTAFPTSQV RRGDFTEDTT PNRPVYTTSQ VGGLITHVLW 

        70         80         90        100        110        120 
EIVEMRKELC NGNSDCMNND DALAENNLKL PEIQRNDGCY QTGYNQEICL LKISSGLLEY 

       130        140        150        160        170        180 
HSYLEYMKNN LKDNKKDKAR VLQRDTETLI HIFNQEVKDL HKIVLPTPIS NALLTDKLES 

       190        200        210 
QKEWLRTKTI QFILKSLEEF LKVTLRSTRQ T 

« Hide

References

« Hide 'large scale' references
[1]"cDNA cloning of murine interleukin-HP1: homology with human interleukin 6."
van Snick J., Cayphas S., Szikora J.-P., Renauld J.-C., van Roost E., Boon T., Simpson R.J.
Eur. J. Immunol. 18:193-197(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]"Genomic structure of the murine IL-6 gene. High degree conservation of potential regulatory sequences between mouse and human."
Tanabe O., Akira S., Kamiya T., Wong G.G., Hirano T., Kishimoto T.
J. Immunol. 141:3875-3881(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Multiple biological activities are expressed by a mouse interleukin 6 cDNA clone isolated from bone marrow stromal cells."
Chiu C.P., Moulds C., Coffman R.L., Rennick D., Lee F.
Proc. Natl. Acad. Sci. U.S.A. 85:7099-7103(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Cloning and sequence analysis of the cDNA for murine interleukin-6."
Grenett H.E., Fuentes N.L., Fuller G.M.
Nucleic Acids Res. 18:6455-6455(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: BALB/c.
[5]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Macrophage.
[6]"DNA rearrangement and constitutive expression of the interleukin 6 gene in a mouse plasmacytoma."
Blankenstein T., Qin Z., Li W., Diamantstein T.
J. Exp. Med. 171:965-970(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-6.
Strain: BALB/c.
[7]"The murine Il-6 gene maps to the proximal region of chromosome 5."
Mock B.A., Nordan R.P., Justice M.J., Kozak C., Jenkins N.A., Copeland N.G., Clark S.C., Wong G.G., Rudikoff S.
J. Immunol. 142:1372-1376(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 5-211.
Strain: C57BL/6J.
[8]"Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas."
van Snick J., Cayphas S., Vink A., Uyttenhove C., Coulie P.G., Rubira M.R., Simpson R.J.
Proc. Natl. Acad. Sci. U.S.A. 83:9679-9683(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 25-45.
[9]"Murine hybridoma/plasmacytoma growth factor. Complete amino-acid sequence and relation to human interleukin-6."
Simpson R.J., Moritz R.L., Rubira M.R., van Snick J.
Eur. J. Biochem. 176:187-197(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 25-211.
[10]"Internal amino acid sequencing of proteins by in situ cyanogen bromide cleavage in polyacrylamide gels."
Jahnen W., Ward L.D., Reid G.E., Moritz R.L., Simpson R.J.
Biochem. Biophys. Res. Commun. 166:139-145(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 66-75; 78-84 AND 128-148.
[11]"Characterization of a recombinant murine interleukin-6: assignment of disulphide bonds."
Simpson R.J., Moritz R.L., van Roost E., van Snick J.
Biochem. Biophys. Res. Commun. 157:364-372(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS.
[12]"The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells."
Ivanov I.I., McKenzie B.S., Zhou L., Tadokoro C.E., Lepelley A., Lafaille J.J., Cua D.J., Littman D.R.
Cell 126:1121-1133(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN TH17 DIFFERENTIATION, DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X06203 mRNA. Translation: CAA29560.1.
M20572 Genomic DNA. Translation: AAA39302.1.
J03783 mRNA. Translation: AAA39301.1.
X54542 mRNA. Translation: CAA38411.1.
AK150440 mRNA. Translation: BAE29562.1.
X51457 Genomic DNA. Translation: CAA35824.1.
M24221 Genomic DNA. Translation: AAA68814.1.
PIRICMS6. A30531.
RefSeqNP_112445.1. NM_031168.1.
UniGeneMm.1019.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2L3YNMR-A27-211[»]
ProteinModelPortalP08505.
SMRP08505. Positions 28-211.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid200641. 2 interactions.
IntActP08505. 1 interaction.

PTM databases

PhosphoSiteP08505.

Proteomic databases

PRIDEP08505.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000026845; ENSMUSP00000026845; ENSMUSG00000025746.
GeneID16193.
KEGGmmu:16193.
UCSCuc008wuu.1. mouse.

Organism-specific databases

CTD3569.
MGIMGI:96559. Il6.

Phylogenomic databases

eggNOGNOG48083.
GeneTreeENSGT00390000000878.
HOGENOMHOG000236330.
HOVERGENHBG000471.
InParanoidP08505.
KOK05405.
OMALQFSLRA.
OrthoDBEOG7QG453.
PhylomeDBP08505.
TreeFamTF335984.

Gene expression databases

ArrayExpressP08505.
BgeeP08505.
CleanExMM_IL6.
GenevestigatorP08505.

Family and domain databases

Gene3D1.20.1250.10. 1 hit.
InterProIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR003574. IL-6.
IPR003573. IL-6/IL-23/GCSF/MGF.
[Graphical view]
PANTHERPTHR11457. PTHR11457. 1 hit.
PfamPF00489. IL6. 1 hit.
[Graphical view]
PIRSFPIRSF001935. IL6_MGF_GCSF. 1 hit.
PRINTSPR00433. IL6GCSFMGF.
PR00434. INTERLEUKIN6.
SMARTSM00126. IL6. 1 hit.
[Graphical view]
SUPFAMSSF47266. SSF47266. 1 hit.
PROSITEPS00254. INTERLEUKIN_6. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP08505.
NextBio289109.
PROP08505.
SOURCESearch...

Entry information

Entry nameIL6_MOUSE
AccessionPrimary (citable) accession number: P08505
Secondary accession number(s): Q3UCQ0, Q8BN26
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: April 16, 2014
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot