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P05231

- IL6_HUMAN

UniProt

P05231 - IL6_HUMAN

Protein

Interleukin-6

Gene

IL6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 178 (01 Oct 2014)
      Sequence version 1 (13 Aug 1987)
      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.

    GO - Molecular functioni

    1. cytokine activity Source: BHF-UCL
    2. growth factor activity Source: BHF-UCL
    3. interleukin-6 receptor binding Source: UniProtKB
    4. protein binding Source: IntAct

    GO - Biological processi

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

    Keywords - Molecular functioni

    Cytokine, Growth factor

    Keywords - Biological processi

    Acute phase

    Enzyme and pathway databases

    ReactomeiREACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_27307. Interleukin-6 signaling.
    SignaLinkiP05231.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Interleukin-6
    Short name:
    IL-6
    Alternative name(s):
    B-cell stimulatory factor 2
    Short name:
    BSF-2
    CTL differentiation factor
    Short name:
    CDF
    Hybridoma growth factor
    Interferon beta-2
    Short name:
    IFN-beta-2
    Gene namesi
    Name:IL6
    Synonyms:IFNB2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:6018. IL6.

    Subcellular locationi

    GO - Cellular componenti

    1. external side of plasma membrane Source: Ensembl
    2. extracellular region Source: Reactome
    3. extracellular space Source: BHF-UCL
    4. interleukin-6 receptor complex Source: BHF-UCL

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302]: An inflammatory articular disorder with systemic-onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis.
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    A IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in HIV-infected men.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi173 – 1731A → V: Almost no loss of activity. 1 Publication
    Mutagenesisi185 – 1851W → R: No loss of activity. 1 Publication
    Mutagenesisi204 – 2041S → P: 87% loss of activity. 1 Publication
    Mutagenesisi210 – 2101R → K, E, Q, T, A or P: Loss of activity. 1 Publication
    Mutagenesisi212 – 2121M → T, N, S or R: Loss of activity. 1 Publication

    Organism-specific databases

    MIMi148000. phenotype.
    604302. phenotype.
    Orphaneti206. Crohn disease.
    85414. Systemic-onset juvenile idiopathic arthritis.
    PharmGKBiPA198.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 29293 PublicationsAdd
    BLAST
    Chaini30 – 212183Interleukin-6PRO_0000015582Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi72 ↔ 781 Publication
    Glycosylationi73 – 731N-linked (GlcNAc...)1 Publication
    Disulfide bondi101 ↔ 1111 Publication

    Post-translational modificationi

    N- and O-glycosylated.1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiP05231.
    PRIDEiP05231.

    PTM databases

    PhosphoSiteiP05231.

    Miscellaneous databases

    PMAP-CutDBP05231.

    Expressioni

    Gene expression databases

    ArrayExpressiP05231.
    BgeeiP05231.
    CleanExiHS_IL6.
    GenevestigatoriP05231.

    Organism-specific databases

    HPAiCAB023406.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    IL6RP088875EBI-720533,EBI-299383
    ZBTB16Q055162EBI-720533,EBI-711925

    Protein-protein interaction databases

    BioGridi109783. 2 interactions.
    DIPiDIP-482N.
    IntActiP05231. 5 interactions.
    MINTiMINT-190042.
    STRINGi9606.ENSP00000258743.

    Structurei

    Secondary structure

    1
    212
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi49 – 7527
    Beta strandi76 – 794
    Turni81 – 833
    Helixi84 – 874
    Helixi97 – 993
    Beta strandi102 – 1054
    Helixi108 – 13225
    Beta strandi134 – 1363
    Helixi137 – 15721
    Beta strandi159 – 1613
    Helixi169 – 18012
    Helixi184 – 20926

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1ALUX-ray1.90A28-212[»]
    1IL6NMR-A28-212[»]
    1N2Qmodel-E/F30-212[»]
    1P9MX-ray3.65B29-212[»]
    2IL6NMR-A28-212[»]
    4CNIX-ray2.20C/D42-212[»]
    4J4LX-ray2.30C/D47-212[»]
    4NI7X-ray2.40A28-212[»]
    4NI9X-ray2.55A/C28-212[»]
    ProteinModelPortaliP05231.
    SMRiP05231. Positions 47-212.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP05231.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the IL-6 superfamily.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG48083.
    HOGENOMiHOG000236330.
    HOVERGENiHBG000471.
    InParanoidiP05231.
    KOiK05405.
    OMAiFNQETCL.
    OrthoDBiEOG7QG453.
    PhylomeDBiP05231.
    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.

    P05231-1 [UniParc]FASTAAdd to Basket

    « Hide

    MNSFSTSAFG PVAFSLGLLL VLPAAFPAPV PPGEDSKDVA APHRQPLTSS    50
    ERIDKQIRYI LDGISALRKE TCNKSNMCES SKEALAENNL NLPKMAEKDG 100
    CFQSGFNEET CLVKIITGLL EFEVYLEYLQ NRFESSEEQA RAVQMSTKVL 150
    IQFLQKKAKN LDAITTPDPT TNASLLTKLQ AQNQWLQDMT THLILRSFKE 200
    FLQSSLRALR QM 212
    Length:212
    Mass (Da):23,718
    Last modified:August 13, 1987 - v1
    Checksum:i1F1ED1FE1B734079
    GO

    Polymorphismi

    Genetic variations in IL6 may be correlated with bone mineral density (BMD). Low BMD is a risk factor for osteoporotic fracture. Osteoporosis is characterized by reduced bone mineral density, disrutption of bone microarchitecture, and the alteration of the amount and variety of non-collagenous proteins in bone. Osteoporotic bones are more at risk of fracture.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti32 – 321P → S.1 Publication
    Corresponds to variant rs2069830 [ dbSNP | Ensembl ].
    VAR_013075
    Natural varianti162 – 1621D → E.
    Corresponds to variant rs13306435 [ dbSNP | Ensembl ].
    VAR_029266
    Natural varianti162 – 1621D → V.1 Publication
    Corresponds to variant rs2069860 [ dbSNP | Ensembl ].
    VAR_013076

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X04430 mRNA. Translation: CAA28026.1.
    M14584 mRNA. Translation: AAA52728.1.
    X04602 mRNA. Translation: CAA28268.1.
    Y00081 Genomic DNA. Translation: CAA68278.1.
    M18403 mRNA. Translation: AAA52729.1.
    M29150 mRNA. Translation: AAA59154.1.
    X04402 Genomic DNA. Translation: CAA27990.1.
    X04403 mRNA. Translation: CAA27991.1.
    M54894 mRNA. Translation: AAC41704.1.
    S56892 mRNA. Translation: AAD13886.1.
    AF372214 Genomic DNA. Translation: AAK48987.1.
    BC015511 mRNA. Translation: AAH15511.1.
    CCDSiCCDS5375.1.
    PIRiA32648. IVHUB2.
    RefSeqiNP_000591.1. NM_000600.3.
    UniGeneiHs.654458.

    Genome annotation databases

    EnsembliENST00000258743; ENSP00000258743; ENSG00000136244.
    ENST00000404625; ENSP00000385675; ENSG00000136244.
    GeneIDi3569.
    KEGGihsa:3569.
    UCSCiuc003svj.4. human.

    Polymorphism databases

    DMDMi124347.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    R&D Systems' cytokine mini-reviews: IL-6
    Wikipedia

    Interleukin-6 entry

    SeattleSNPs
    SHMPD

    The Singapore human mutation and polymorphism database

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X04430 mRNA. Translation: CAA28026.1 .
    M14584 mRNA. Translation: AAA52728.1 .
    X04602 mRNA. Translation: CAA28268.1 .
    Y00081 Genomic DNA. Translation: CAA68278.1 .
    M18403 mRNA. Translation: AAA52729.1 .
    M29150 mRNA. Translation: AAA59154.1 .
    X04402 Genomic DNA. Translation: CAA27990.1 .
    X04403 mRNA. Translation: CAA27991.1 .
    M54894 mRNA. Translation: AAC41704.1 .
    S56892 mRNA. Translation: AAD13886.1 .
    AF372214 Genomic DNA. Translation: AAK48987.1 .
    BC015511 mRNA. Translation: AAH15511.1 .
    CCDSi CCDS5375.1.
    PIRi A32648. IVHUB2.
    RefSeqi NP_000591.1. NM_000600.3.
    UniGenei Hs.654458.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1ALU X-ray 1.90 A 28-212 [» ]
    1IL6 NMR - A 28-212 [» ]
    1N2Q model - E/F 30-212 [» ]
    1P9M X-ray 3.65 B 29-212 [» ]
    2IL6 NMR - A 28-212 [» ]
    4CNI X-ray 2.20 C/D 42-212 [» ]
    4J4L X-ray 2.30 C/D 47-212 [» ]
    4NI7 X-ray 2.40 A 28-212 [» ]
    4NI9 X-ray 2.55 A/C 28-212 [» ]
    ProteinModelPortali P05231.
    SMRi P05231. Positions 47-212.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109783. 2 interactions.
    DIPi DIP-482N.
    IntActi P05231. 5 interactions.
    MINTi MINT-190042.
    STRINGi 9606.ENSP00000258743.

    Chemistry

    ChEMBLi CHEMBL1795129.
    DrugBanki DB01169. Arsenic trioxide.
    DB01128. Bicalutamide.
    DB01404. Ginseng.
    DB00641. Simvastatin.

    PTM databases

    PhosphoSitei P05231.

    Polymorphism databases

    DMDMi 124347.

    Proteomic databases

    PaxDbi P05231.
    PRIDEi P05231.

    Protocols and materials databases

    DNASUi 3569.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000258743 ; ENSP00000258743 ; ENSG00000136244 .
    ENST00000404625 ; ENSP00000385675 ; ENSG00000136244 .
    GeneIDi 3569.
    KEGGi hsa:3569.
    UCSCi uc003svj.4. human.

    Organism-specific databases

    CTDi 3569.
    GeneCardsi GC07P022732.
    H-InvDB HIX0167872.
    HGNCi HGNC:6018. IL6.
    HPAi CAB023406.
    MIMi 147620. gene.
    148000. phenotype.
    604302. phenotype.
    neXtProti NX_P05231.
    Orphaneti 206. Crohn disease.
    85414. Systemic-onset juvenile idiopathic arthritis.
    PharmGKBi PA198.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG48083.
    HOGENOMi HOG000236330.
    HOVERGENi HBG000471.
    InParanoidi P05231.
    KOi K05405.
    OMAi FNQETCL.
    OrthoDBi EOG7QG453.
    PhylomeDBi P05231.
    TreeFami TF335984.

    Enzyme and pathway databases

    Reactomei REACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_27307. Interleukin-6 signaling.
    SignaLinki P05231.

    Miscellaneous databases

    ChiTaRSi IL6. human.
    EvolutionaryTracei P05231.
    GeneWikii Interleukin_6.
    GenomeRNAii 3569.
    NextBioi 13950.
    PMAP-CutDB P05231.
    PROi P05231.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P05231.
    Bgeei P05231.
    CleanExi HS_IL6.
    Genevestigatori P05231.

    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. "Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin."
      Hirano T., Yasukawa K., Harada H., Taga T., Watanabe Y., Matsuda T., Kashiwamura S., Nakajima K., Koyama K., Iwamatsu A., Tsunasawa S., Sakiyama F., Matsui H., Takahara Y., Taniguchi T., Kishimoto T.
      Nature 324:73-76(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
    2. "Structure and expression of human B cell stimulatory factor-2 (BSF-2/IL-6) gene."
      Yasukawa K., Hirano T., Watanabe Y., Muratani K., Matsuda T., Nakai S., Kishimoto T.
      EMBO J. 6:2939-2945(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "Anti-beta-interferon antibodies inhibit the increased expression of HLA-B7 mRNA in tumor necrosis factor-treated human fibroblasts: structural studies of the beta 2 interferon involved."
      May L.T., Helfgott D.C., Sehgal P.B.
      Proc. Natl. Acad. Sci. U.S.A. 83:8957-8961(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "Structure and expression of cDNA and genes for human interferon-beta-2, a distinct species inducible by growth-stimulatory cytokines."
      Zilberstein A., Ruggieri R., Korn J.H., Revel M.
      EMBO J. 5:2529-2537(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    5. "Molecular cloning and expression of hybridoma growth factor in Escherichia coli."
      Brakenhoff J.P.J., de Groot E.R., Evers R.F., Pannekoek H., Aarden L.A.
      J. Immunol. 139:4116-4121(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    6. "Deletion of 3' untranslated region of human BSF-2 mRNA causes stabilization of the mRNA and high-level expression in mouse NIH3T3 cells."
      Tonouchi N., Miwa K., Karasuyama H., Matsui H.
      Biochem. Biophys. Res. Commun. 163:1056-1062(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    7. "Structural analysis of the sequence coding for an inducible 26-kDa protein in human fibroblasts."
      Haegeman G., Content J., Volckaert G., Derynck R., Tavernier J., Fiers W.
      Eur. J. Biochem. 159:625-632(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
      Tissue: Fibroblast.
    8. "Interleukin 6: identification as a hematopoietic colony-stimulating factor."
      Wong G., Witek-Giannotti J., Hewick R., Clark S., Ogawa M.
      Behring Inst. Mitt. 83:40-47(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    9. "Stable and efficient expression of human interleukin-6 cDNA in mammalian cells after gene transfer."
      Chen Q.Y.
      Zhonghua Zhong Liu Za Zhi 14:340-344(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    10. SeattleSNPs variation discovery resource
      Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-32 AND VAL-162.
    11. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Lung.
    12. "Separation and comparison of two monokines with lymphocyte-activating factor activity: IL-1 beta and hybridoma growth factor (HGF). Identification of leukocyte-derived HGF as IL-6."
      van Damme J., van Beeumen J., Decock B., van Snick J., de Ley M., Billiau A.
      J. Immunol. 140:1534-1541(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 30-63.
    13. "Interleukin 6 is the principal cytolytic T lymphocyte differentiation factor for thymocytes in human leukocyte conditioned medium."
      Ming J.E., Cernetti C., Steinman R.M., Granelli-Piperno A.
      J. Mol. Cell. Immunol. 4:203-211(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 30-50.
    14. "Marked cell-type-specific differences in glycosylation of human interleukin-6."
      May L.T., Shaw J.E., Khanna A.K., Zabriskie J.B., Sehgal P.B.
      Cytokine 3:204-211(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 30-40, GLYCOSYLATION.
    15. "Structure, stability and biological properties of a N-terminally truncated form of recombinant human interleukin-6 containing a single disulfide bond."
      Breton J., la Fiura A., Bertolero F., Orsini G., Valsasina B., Ziliotto R., de Filippis V., Polverino de Laureto P., Fontana A.
      Eur. J. Biochem. 227:573-581(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 50-212 OF RECOMBINANT FORM LACKING FIRST DISULFIDE BOND.
    16. "Disulfide structures of human interleukin-6 are similar to those of human granulocyte colony stimulating factor."
      Clogston C.L., Boone T.C., Crandall B.C., Mendiaz E.A., Lu H.S.
      Arch. Biochem. Biophys. 272:144-151(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISULFIDE BONDS.
    17. "Evidence for the importance of a positive charge and an alpha-helical structure of the C-terminus for biological activity of human IL-6."
      Luetticken C., Kruettgen A., Moeller C., Heinrich P.C., Rose-John S.
      FEBS Lett. 282:265-267(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS.
    18. "Folding topologies of human interleukin-6 and its mutants as studied by NMR spectroscopy."
      Nishimura C., Watanabe A., Gouda H., Shimada I., Arata Y.
      Biochemistry 35:273-281(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR.
    19. Cited for: STRUCTURE BY NMR.
    20. "1.9-A crystal structure of interleukin 6: implications for a novel mode of receptor dimerization and signaling."
      Somers W., Stahl M., Seehra J.S.
      EMBO J. 16:989-997(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
    21. "The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis."
      Fishman D., Faulds G., Jeffery R., Mohamed-Ali V., Yudkin J.S., Humphries S., Woo P.
      J. Clin. Invest. 102:1369-1376(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO SYSTEMIC JUVENILE RHEUMATOID ARTHRITIS.
    22. "An IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in men infected with human immunodeficiency virus."
      Foster C.B., Lehrnbecher T., Samuels S., Stein S., Mol F., Metcalf J.A., Wyvill K., Steinberg S.M., Kovacs J., Blauvelt A., Yarchoan R., Chanock S.J.
      Blood 96:2562-2567(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO KAPOSI SARCOMA.
    23. "A nucleotide variant in the promoter region of the interleukin-6 gene associated with decreased bone mineral density."
      Ota N., Nakajima T., Nakazawa I., Suzuki T., Hosoi T., Orimo H., Inoue S., Shirai Y., Emi M.
      J. Hum. Genet. 46:267-272(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN BMD.
    24. "Association of interleukin-6 promoter variant with bone mineral density in pre-menopausal women."
      Chung H.W., Seo J.-S., Hur S.E., Kim H.L., Kim J.Y., Jung J.H., Kim L.H., Park B.L., Shin H.D.
      J. Hum. Genet. 48:243-248(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN BMD.

    Entry informationi

    Entry nameiIL6_HUMAN
    AccessioniPrimary (citable) accession number: P05231
    Secondary accession number(s): Q9UCU2, Q9UCU3, Q9UCU4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 13, 1987
    Last sequence update: August 13, 1987
    Last modified: October 1, 2014
    This is version 178 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

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

    Documents

    1. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3