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P08505

- IL6_MOUSE

UniProt

P08505 - IL6_MOUSE

Protein

Interleukin-6

Gene

Il6

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 144 (01 Oct 2014)
      Sequence version 1 (01 Aug 1988)
      Previous versions | rss
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    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
    3. protein 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. negative regulation of apoptotic process Source: Ensembl
    19. negative regulation of cell proliferation Source: Ensembl
    20. negative regulation of chemokine biosynthetic process Source: MGI
    21. negative regulation of collagen biosynthetic process Source: Ensembl
    22. negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
    23. negative regulation of cytokine secretion Source: Ensembl
    24. negative regulation of gluconeogenesis Source: Ensembl
    25. negative regulation of hormone secretion Source: MGI
    26. negative regulation of muscle organ development Source: Ensembl
    27. negative regulation of neuron death Source: Ensembl
    28. negative regulation of protein kinase activity Source: Ensembl
    29. neuron projection development Source: Ensembl
    30. neutrophil apoptotic process Source: MGI
    31. positive regulation of acute inflammatory response Source: Ensembl
    32. positive regulation of apoptotic process Source: Ensembl
    33. positive regulation of B cell activation Source: Ensembl
    34. positive regulation of chemokine production Source: Ensembl
    35. positive regulation of DNA replication Source: Ensembl
    36. positive regulation of epithelial cell proliferation Source: MGI
    37. positive regulation of ERK1 and ERK2 cascade Source: Ensembl
    38. positive regulation of immunoglobulin secretion Source: Ensembl
    39. positive regulation of interleukin-6 production Source: Ensembl
    40. positive regulation of neuron differentiation Source: Ensembl
    41. positive regulation of nitric oxide biosynthetic process Source: Ensembl
    42. positive regulation of peptidyl-serine phosphorylation Source: Ensembl
    43. positive regulation of protein import into nucleus, translocation Source: Ensembl
    44. positive regulation of protein kinase B signaling Source: Ensembl
    45. positive regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
    46. positive regulation of smooth muscle cell proliferation Source: Ensembl
    47. positive regulation of T cell proliferation Source: Ensembl
    48. positive regulation of T-helper 2 cell differentiation Source: MGI
    49. positive regulation of transcription, DNA-templated Source: MGI
    50. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    51. positive regulation of translation Source: Ensembl
    52. positive regulation of transmission of nerve impulse Source: Ensembl
    53. positive regulation of tyrosine phosphorylation of Stat3 protein Source: Ensembl
    54. regulation of apoptotic process Source: MGI
    55. regulation of cell proliferation Source: MGI
    56. regulation of cell shape Source: Ensembl
    57. regulation of circadian sleep/wake cycle, non-REM sleep Source: Ensembl
    58. regulation of vascular endothelial growth factor production Source: Ensembl
    59. response to amino acid Source: Ensembl
    60. response to antibiotic Source: Ensembl
    61. response to caffeine Source: Ensembl
    62. response to calcium ion Source: Ensembl
    63. response to cold Source: Ensembl
    64. response to drug Source: Ensembl
    65. response to electrical stimulus Source: Ensembl
    66. response to glucocorticoid Source: Ensembl
    67. response to heat Source: Ensembl
    68. response to insulin Source: Ensembl
    69. response to mechanical stimulus Source: Ensembl
    70. response to nutrient levels Source: Ensembl
    71. response to peptidoglycan Source: Ensembl
    72. response to wounding Source: MGI
    73. T cell activation Source: MGI
    74. T-helper 17 cell lineage commitment Source: UniProtKB

    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).

    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

    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

    ArrayExpressiP08505.
    BgeeiP08505.
    CleanExiMM_IL6.
    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 – 6821
    Turni69 – 724
    Helixi74 – 774
    Turni81 – 833
    Helixi84 – 863
    Beta strandi101 – 1033
    Helixi114 – 12916
    Helixi133 – 16028
    Helixi170 – 1767
    Helixi186 – 20924

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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

    MKFLSARDFH PVAFLGLMLV TTTAFPTSQV RRGDFTEDTT PNRPVYTTSQ    50
    VGGLITHVLW EIVEMRKELC NGNSDCMNND DALAENNLKL PEIQRNDGCY 100
    QTGYNQEICL LKISSGLLEY HSYLEYMKNN LKDNKKDKAR VLQRDTETLI 150
    HIFNQEVKDL HKIVLPTPIS NALLTDKLES QKEWLRTKTI QFILKSLEEF 200
    LKVTLRSTRQ T 211
    Length:211
    Mass (Da):24,384
    Last modified:August 1, 1988 - v1
    Checksum:iBBB47DDA9E86787A
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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:
    PDBe
    RCSB PDB
    PDBj
    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).

    Miscellaneous databases

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

    Gene expression databases

    ArrayExpressi P08505.
    Bgeei P08505.
    CleanExi MM_IL6.
    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

    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: October 1, 2014
    This is version 144 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