P08505 (IL6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	211 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. 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 By similarity.
Subcellular location	Secreted.
Sequence similarities	Belongs to the IL-6 superfamily.

Ontologies

Keywords
Biological process	Acute phase
Cellular component	Secreted
Domain	Signal
Molecular function	Cytokine Growth factor
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	T cell activation Inferred from genetic interaction PubMed 18792410. Source: MGI acute-phase response Inferred from electronic annotation. Source: UniProtKB-KW aging Inferred from electronic annotation. Source: Compara bone remodeling Inferred from electronic annotation. Source: Compara branching involved in salivary gland morphogenesis Inferred from direct assay PubMed 11275690. Source: MGI cell growth Inferred from electronic annotation. Source: Compara cell redox homeostasis Inferred from electronic annotation. Source: Compara cellular response to hydrogen peroxide Inferred from electronic annotation. Source: Compara defense response to Gram-negative bacterium Inferred from electronic annotation. Source: Compara defense response to Gram-positive bacterium Inferred from electronic annotation. Source: Compara defense response to protozoan Inferred from mutant phenotype PubMed 17109471. Source: MGI defense response to virus Inferred from electronic annotation. Source: Compara 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 immune response Inferred from electronic annotation. Source: InterPro interleukin-6-mediated signaling pathway Inferred from direct assay PubMed 1312474. Source: MGI muscle cell homeostasis Inferred from genetic interaction PubMed 18056981. Source: MGI negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara 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: Compara negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of cytokine secretion Inferred from electronic annotation. Source: Compara negative regulation of gluconeogenesis Inferred from electronic annotation. Source: Compara negative regulation of hormone secretion Inferred from direct assay PubMed 7867561. Source: MGI negative regulation of muscle organ development Inferred from electronic annotation. Source: Compara negative regulation of neuron death Inferred from electronic annotation. Source: Compara negative regulation of protein kinase activity Inferred from electronic annotation. Source: Compara neuron projection development Inferred from electronic annotation. Source: Compara neutrophil apoptotic process Inferred from direct assay PubMed 12925700. Source: MGI positive regulation of B cell activation Inferred from electronic annotation. Source: Compara positive regulation of DNA replication Inferred from electronic annotation. Source: Compara positive regulation of ERK1 and ERK2 cascade Inferred from electronic annotation. Source: Compara positive regulation of T cell proliferation Inferred from electronic annotation. Source: Compara 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: Compara positive regulation of chemokine production Inferred from electronic annotation. Source: Compara positive regulation of epithelial cell proliferation Inferred from direct assay PubMed 11275690. Source: MGI positive regulation of immunoglobulin secretion Inferred from electronic annotation. Source: Compara positive regulation of interleukin-6 production Inferred from electronic annotation. Source: Compara positive regulation of neuron differentiation Inferred from electronic annotation. Source: Compara positive regulation of nitric oxide biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of protein import into nucleus, translocation Inferred from electronic annotation. Source: Compara positive regulation of protein kinase B signaling cascade Inferred from electronic annotation. Source: Compara positive regulation of sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara positive regulation of smooth muscle cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from genetic interaction PubMed 19666510. Source: MGI positive regulation of translation Inferred from electronic annotation. Source: Compara positive regulation of transmission of nerve impulse Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from electronic annotation. Source: Compara regulation of apoptotic process Inferred from mutant phenotype PubMed 11275690. Source: MGI regulation of cell shape Inferred from electronic annotation. Source: Compara regulation of circadian sleep/wake cycle, non-REM sleep Inferred from electronic annotation. Source: Compara regulation of vascular endothelial growth factor production Inferred from electronic annotation. Source: Compara response to amino acid stimulus Inferred from electronic annotation. Source: Compara response to antibiotic Inferred from electronic annotation. Source: Compara response to caffeine Inferred from electronic annotation. Source: Compara response to calcium ion Inferred from electronic annotation. Source: Compara response to cold Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to electrical stimulus Inferred from electronic annotation. Source: Compara response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to heat Inferred from electronic annotation. Source: Compara response to insulin stimulus Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to mechanical stimulus Inferred from electronic annotation. Source: Compara response to nutrient levels Inferred from electronic annotation. Source: Compara response to peptidoglycan Inferred from electronic annotation. Source: Compara response to wounding Inferred from direct assay PubMed 19404405. Source: MGI
Cellular_component	external 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 19139201. Source: MGI interleukin-6 receptor complex Inferred from electronic annotation. Source: Compara
Molecular_function	cytokine 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Ref.8 Ref.9

Chain

25 – 211

187

Interleukin-6

PRO_0000015588

Amino acid modifications

Disulfide bond

70 ↔ 76

Ref.11

Disulfide bond

99 ↔ 109

Ref.11

Secondary structure

1

.

.

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.

.

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.

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.

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.

.

.

211

Helix Strand Turn

Details...

Helix

48 – 68

21

Turn

69 – 72

4

Helix

74 – 77

4

Turn

81 – 83

3

Helix

84 – 86

3

Beta strand

101 – 103

3

Helix

114 – 129

16

Helix

133 – 160

28

Helix

170 – 176

7

Helix

186 – 209

24

Sequences

	Sequence		Length	Mass (Da)
	P08505 [UniParc]. Last modified August 1, 1988. Version 1. Checksum: BBB47DDA9E86787A	FASTA	211	24,384
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
+	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.

IPI

IPI00133702.

PIR

ICMS6. A30531.

RefSeq

NP_112445.1. NM_031168.1.

UniGene

Mm.1019.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2L3Y	NMR	-	A	27-211	[»]

ProteinModelPortal

P08505.

SMR

P08505. Positions 28-211.

ModBase

Search...

Protein-protein interaction databases

IntAct

P08505. 1 interaction.

PTM databases

PhosphoSite

P08505.

Proteomic databases

PRIDE

P08505.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000026845; ENSMUSP00000026845; ENSMUSG00000025746.

GeneID

16193.

KEGG

mmu:16193.

Organism-specific databases

CTD

3569.

MGI

MGI:96559. Il6.

Phylogenomic databases

eggNOG

NOG48083.

GeneTree

ENSGT00390000000878.

HOGENOM

HOG000236330.

HOVERGEN

HBG000471.

InParanoid

P08505.

KO

K05405.

OMA

LQFSLRA.

OrthoDB

EOG44J2KH.

Gene expression databases

ArrayExpress

P08505.

Bgee

P08505.

CleanEx

MM_IL6.

Genevestigator

P08505.

GermOnline

ENSMUSG00000025746. Mus musculus.

Family and domain databases

Gene3D

1.20.1250.10. 1 hit.

InterPro

IPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR003573. IL6_MGF_GCSF.
IPR003574. Interleukin_6.
[Graphical view]

PANTHER

PTHR11457. PTHR11457. 1 hit.

Pfam

PF00489. IL6. 1 hit.
[Graphical view]

PIRSF

PIRSF001935. IL6_MGF_GCSF. 1 hit.

PRINTS

PR00433. IL6GCSFMGF.
PR00434. INTERLEUKIN6.

SMART

SM00126. IL6. 1 hit.
[Graphical view]

SUPFAM

SSF47266. 4_helix_cytokine. 1 hit.

PROSITE

PS00254. INTERLEUKIN_6. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P08505.

NextBio

289109.

SOURCE

Search...

Entry information

Entry name

IL6_MOUSE

Accession

Primary (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 3, 2013
This is version 131 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program