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P08505

- IL6_MOUSE

UniProt

P08505 - IL6_MOUSE

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Protein

Interleukin-6

Gene

Il6

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  1. cytokine activity Source: MGI
  2. interleukin-6 receptor binding Source: MGI

GO - Biological processi

  1. acute-phase response Source: UniProtKB-KW
  2. aging Source: Ensembl
  3. bone remodeling Source: Ensembl
  4. branching involved in salivary gland morphogenesis Source: MGI
  5. cell growth Source: Ensembl
  6. cell redox homeostasis Source: Ensembl
  7. cellular response to hydrogen peroxide Source: Ensembl
  8. cellular response to lipopolysaccharide Source: MGI
  9. defense response to Gram-negative bacterium Source: Ensembl
  10. defense response to Gram-positive bacterium Source: Ensembl
  11. defense response to protozoan Source: MGI
  12. defense response to virus Source: Ensembl
  13. endocrine pancreas development Source: BHF-UCL
  14. epithelial cell proliferation involved in salivary gland morphogenesis Source: MGI
  15. glucagon secretion Source: BHF-UCL
  16. interleukin-6-mediated signaling pathway Source: MGI
  17. muscle cell cellular homeostasis Source: MGI
  18. myeloid cell homeostasis Source: MGI
  19. negative regulation of apoptotic process Source: Ensembl
  20. negative regulation of cell proliferation Source: Ensembl
  21. negative regulation of chemokine biosynthetic process Source: MGI
  22. negative regulation of collagen biosynthetic process Source: Ensembl
  23. negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
  24. negative regulation of cytokine secretion Source: Ensembl
  25. negative regulation of gluconeogenesis Source: Ensembl
  26. negative regulation of hormone secretion Source: MGI
  27. negative regulation of muscle organ development Source: Ensembl
  28. negative regulation of neuron death Source: Ensembl
  29. negative regulation of protein kinase activity Source: Ensembl
  30. neuron projection development Source: Ensembl
  31. neutrophil apoptotic process Source: MGI
  32. positive regulation of acute inflammatory response Source: Ensembl
  33. positive regulation of apoptotic process Source: Ensembl
  34. positive regulation of B cell activation Source: Ensembl
  35. positive regulation of chemokine production Source: Ensembl
  36. positive regulation of DNA replication Source: Ensembl
  37. positive regulation of epithelial cell proliferation Source: MGI
  38. positive regulation of ERK1 and ERK2 cascade Source: Ensembl
  39. positive regulation of immunoglobulin secretion Source: Ensembl
  40. positive regulation of interleukin-6 production Source: Ensembl
  41. positive regulation of neuron differentiation Source: Ensembl
  42. positive regulation of nitric oxide biosynthetic process Source: Ensembl
  43. positive regulation of peptidyl-serine phosphorylation Source: Ensembl
  44. positive regulation of protein import into nucleus, translocation Source: Ensembl
  45. positive regulation of protein kinase B signaling Source: Ensembl
  46. positive regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
  47. positive regulation of smooth muscle cell proliferation Source: Ensembl
  48. positive regulation of T cell proliferation Source: Ensembl
  49. positive regulation of T-helper 2 cell differentiation Source: MGI
  50. positive regulation of transcription, DNA-templated Source: MGI
  51. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  52. positive regulation of translation Source: Ensembl
  53. positive regulation of transmission of nerve impulse Source: Ensembl
  54. positive regulation of tyrosine phosphorylation of Stat3 protein Source: Ensembl
  55. regulation of apoptotic process Source: MGI
  56. regulation of cell proliferation Source: MGI
  57. regulation of cell shape Source: Ensembl
  58. regulation of circadian sleep/wake cycle, non-REM sleep Source: Ensembl
  59. regulation of vascular endothelial growth factor production Source: Ensembl
  60. response to amino acid Source: Ensembl
  61. response to antibiotic Source: Ensembl
  62. response to caffeine Source: Ensembl
  63. response to calcium ion Source: Ensembl
  64. response to cold Source: Ensembl
  65. response to drug Source: Ensembl
  66. response to electrical stimulus Source: Ensembl
  67. response to glucocorticoid Source: Ensembl
  68. response to heat Source: Ensembl
  69. response to insulin Source: Ensembl
  70. response to mechanical stimulus Source: Ensembl
  71. response to nutrient levels Source: Ensembl
  72. response to peptidoglycan Source: Ensembl
  73. response to wounding Source: MGI
  74. T cell activation Source: MGI
  75. T-helper 17 cell lineage commitment Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Keywords - Biological processi

Acute phase

Enzyme and pathway databases

ReactomeiREACT_199118. Interleukin-6 signaling.
REACT_206033. Senescence-Associated Secretory Phenotype (SASP).
REACT_247448. ERK1 activation.
REACT_263321. ERK2 activation.

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-6
Short name:
IL-6
Alternative name(s):
B-cell hybridoma growth factor
Interleukin HP-1
Gene namesi
Name:Il6
Synonyms:Il-6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 5

Organism-specific databases

MGIiMGI:96559. Il6.

Subcellular locationi

GO - Cellular componenti

  1. external side of plasma membrane Source: MGI
  2. extracellular space Source: MGI
  3. interleukin-6 receptor complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Disruption phenotypei

Animals have normal T-cell numbers in the lamina propria but the T(H)17 cells are reduced by about 10-fold.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 24242 PublicationsAdd
BLAST
Chaini25 – 211187Interleukin-6PRO_0000015588Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi70 ↔ 761 Publication
Disulfide bondi99 ↔ 1091 Publication

Keywords - PTMi

Disulfide bond

Proteomic databases

MaxQBiP08505.
PRIDEiP08505.

PTM databases

PhosphoSiteiP08505.

Expressioni

Gene expression databases

BgeeiP08505.
CleanExiMM_IL6.
ExpressionAtlasiP08505. differential.
GenevestigatoriP08505.

Interactioni

Protein-protein interaction databases

BioGridi200641. 2 interactions.
IntActiP08505. 1 interaction.

Structurei

Secondary structure

1
211
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi48 – 6821Combined sources
Turni69 – 724Combined sources
Helixi74 – 774Combined sources
Turni81 – 833Combined sources
Helixi84 – 863Combined sources
Beta strandi101 – 1033Combined sources
Helixi114 – 12916Combined sources
Helixi133 – 16028Combined sources
Helixi170 – 1767Combined sources
Helixi186 – 20924Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2L3YNMR-A27-211[»]
ProteinModelPortaliP08505.
SMRiP08505. Positions 28-211.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08505.

Family & Domainsi

Sequence similaritiesi

Belongs to the IL-6 superfamily.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG48083.
GeneTreeiENSGT00390000000878.
HOGENOMiHOG000236330.
HOVERGENiHBG000471.
InParanoidiP08505.
KOiK05405.
OMAiFNQETCL.
OrthoDBiEOG7QG453.
PhylomeDBiP08505.
TreeFamiTF335984.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR003574. IL-6.
IPR003573. IL-6/IL-23/GCSF/MGF.
[Graphical view]
PANTHERiPTHR11457. PTHR11457. 1 hit.
PfamiPF00489. IL6. 1 hit.
[Graphical view]
PIRSFiPIRSF001935. IL6_MGF_GCSF. 1 hit.
PRINTSiPR00433. IL6GCSFMGF.
PR00434. INTERLEUKIN6.
SMARTiSM00126. IL6. 1 hit.
[Graphical view]
SUPFAMiSSF47266. SSF47266. 1 hit.
PROSITEiPS00254. INTERLEUKIN_6. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P08505-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MKFLSARDFH PVAFLGLMLV TTTAFPTSQV RRGDFTEDTT PNRPVYTTSQ
60 70 80 90 100
VGGLITHVLW EIVEMRKELC NGNSDCMNND DALAENNLKL PEIQRNDGCY
110 120 130 140 150
QTGYNQEICL LKISSGLLEY HSYLEYMKNN LKDNKKDKAR VLQRDTETLI
160 170 180 190 200
HIFNQEVKDL HKIVLPTPIS NALLTDKLES QKEWLRTKTI QFILKSLEEF
210
LKVTLRSTRQ T
Length:211
Mass (Da):24,384
Last modified:August 1, 1988 - v1
Checksum:iBBB47DDA9E86787A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS19153.1.
PIRiA30531. ICMS6.
RefSeqiNP_112445.1. NM_031168.1.
UniGeneiMm.1019.

Genome annotation databases

EnsembliENSMUST00000026845; ENSMUSP00000026845; ENSMUSG00000025746.
GeneIDi16193.
KEGGimmu:16193.
UCSCiuc008wuu.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS19153.1.
PIRi A30531. ICMS6.
RefSeqi NP_112445.1. NM_031168.1.
UniGenei Mm.1019.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2L3Y NMR - A 27-211 [» ]
ProteinModelPortali P08505.
SMRi P08505. Positions 28-211.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 200641. 2 interactions.
IntActi P08505. 1 interaction.

PTM databases

PhosphoSitei P08505.

Proteomic databases

MaxQBi P08505.
PRIDEi P08505.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000026845 ; ENSMUSP00000026845 ; ENSMUSG00000025746 .
GeneIDi 16193.
KEGGi mmu:16193.
UCSCi uc008wuu.1. mouse.

Organism-specific databases

CTDi 3569.
MGIi MGI:96559. Il6.

Phylogenomic databases

eggNOGi NOG48083.
GeneTreei ENSGT00390000000878.
HOGENOMi HOG000236330.
HOVERGENi HBG000471.
InParanoidi P08505.
KOi K05405.
OMAi FNQETCL.
OrthoDBi EOG7QG453.
PhylomeDBi P08505.
TreeFami TF335984.

Enzyme and pathway databases

Reactomei REACT_199118. Interleukin-6 signaling.
REACT_206033. Senescence-Associated Secretory Phenotype (SASP).
REACT_247448. ERK1 activation.
REACT_263321. ERK2 activation.

Miscellaneous databases

EvolutionaryTracei P08505.
NextBioi 289109.
PROi P08505.
SOURCEi Search...

Gene expression databases

Bgeei P08505.
CleanExi MM_IL6.
ExpressionAtlasi P08505. differential.
Genevestigatori P08505.

Family and domain databases

Gene3Di 1.20.1250.10. 1 hit.
InterProi IPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR003574. IL-6.
IPR003573. IL-6/IL-23/GCSF/MGF.
[Graphical view ]
PANTHERi PTHR11457. PTHR11457. 1 hit.
Pfami PF00489. IL6. 1 hit.
[Graphical view ]
PIRSFi PIRSF001935. IL6_MGF_GCSF. 1 hit.
PRINTSi PR00433. IL6GCSFMGF.
PR00434. INTERLEUKIN6.
SMARTi SM00126. IL6. 1 hit.
[Graphical view ]
SUPFAMi SSF47266. SSF47266. 1 hit.
PROSITEi PS00254. INTERLEUKIN_6. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
  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.

Entry informationi

Entry nameiIL6_MOUSE
AccessioniPrimary (citable) accession number: P08505
Secondary accession number(s): Q3UCQ0, Q8BN26
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: November 26, 2014
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3