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)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › 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, hematopoeitic 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. Source: MGI acute-phase response Inferred from electronic annotation. Source: UniProtKB-KW branching involved in salivary gland morphogenesis Inferred from direct assay. Source: MGI defense response to protozoan Inferred from mutant phenotype. Source: MGI endocrine pancreas development Inferred from mutant phenotype. Source: BHF-UCL epithelial cell proliferation involved in salivary gland morphogenesis Inferred from direct assay. Source: MGI glucagon secretion Inferred from mutant phenotype. Source: BHF-UCL interleukin-6-mediated signaling pathway Inferred from direct assay. Source: MGI muscle cell homeostasis Inferred from genetic interaction. Source: MGI negative regulation of chemokine biosynthetic process Inferred from direct assay. Source: MGI negative regulation of hormone secretion Inferred from direct assay. Source: MGI neutrophil apoptosis Inferred from direct assay. Source: MGI positive regulation of T-helper 2 cell differentiation Inferred from direct assay. Source: MGI positive regulation of epithelial cell proliferation Inferred from direct assay. Source: MGI
Cellular component	external side of plasma membrane Inferred from direct assay. Source: MGI extracellular space Inferred from direct assay. Source: MGI
Molecular function	cytokine activity Inferred from direct assay. Source: MGI growth factor activity Inferred from electronic annotation. Source: UniProtKB-KW interleukin-6 receptor binding Inferred from direct assay. 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

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: 2965020] [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: 3263439] [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: 3262872] [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: 2243807] [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: 16141072] [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: 2106569] [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: 2563387] [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: 2948184] [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: 3262059] [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: 2302197] [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: 3264160] [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.

STRING

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

HOVERGEN

HBG000471.

InParanoid

P08505.

OMA

LQFSLRA.

OrthoDB

EOG44J2KH.

PhylomeDB

P08505.

Gene expression databases

ArrayExpress

P08505.

Bgee

P08505.

CleanEx

MM_IL6.

Genevestigator

P08505.

GermOnline

ENSMUSG00000025746. Mus musculus.

Family and domain databases

InterPro

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

Gene3D

G3DSA:1.20.1250.10. 4_helix_cytokine_core. 1 hit.

KO

K05405.

PANTHER

PTHR11457. Interleukin_6. 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

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:	January 25, 2012
This is version 119 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program