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Protein

Interleukin-6

Gene

IL6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.

GO - Molecular functioni

  • cytokine activity Source: BHF-UCL
  • growth factor activity Source: BHF-UCL
  • interleukin-6 receptor binding Source: BHF-UCL

GO - Biological processi

  • acute-phase response Source: BHF-UCL
  • cellular protein metabolic process Source: Reactome
  • cellular response to hydrogen peroxide Source: BHF-UCL
  • cellular response to lipopolysaccharide Source: MGI
  • cytokine-mediated signaling pathway Source: BHF-UCL
  • defense response to Gram-negative bacterium Source: BHF-UCL
  • defense response to Gram-positive bacterium Source: BHF-UCL
  • defense response to virus Source: BHF-UCL
  • endocrine pancreas development Source: BHF-UCL
  • glucagon secretion Source: BHF-UCL
  • hepatic immune response Source: BHF-UCL
  • humoral immune response Source: BHF-UCL
  • inflammatory response Source: BHF-UCL
  • interleukin-6-mediated signaling pathway Source: BHF-UCL
  • monocyte chemotaxis Source: BHF-UCL
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of bone resorption Source: BHF-UCL
  • negative regulation of cell proliferation Source: ProtInc
  • negative regulation of chemokine biosynthetic process Source: UniProtKB
  • negative regulation of collagen biosynthetic process Source: BHF-UCL
  • negative regulation of fat cell differentiation Source: BHF-UCL
  • negative regulation of interleukin-1-mediated signaling pathway Source: BHF-UCL
  • negative regulation of lipid storage Source: BHF-UCL
  • neuron projection development Source: BHF-UCL
  • neutrophil apoptotic process Source: UniProtKB
  • neutrophil mediated immunity Source: BHF-UCL
  • platelet activation Source: BHF-UCL
  • positive regulation of acute inflammatory response Source: BHF-UCL
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of B cell activation Source: BHF-UCL
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of chemokine production Source: BHF-UCL
  • positive regulation of DNA binding transcription factor activity Source: BHF-UCL
  • positive regulation of gene expression Source: BHF-UCL
  • positive regulation of immunoglobulin secretion Source: BHF-UCL
  • positive regulation of interleukin-6 production Source: BHF-UCL
  • positive regulation of JAK-STAT cascade Source: BHF-UCL
  • positive regulation of leukocyte chemotaxis Source: BHF-UCL
  • positive regulation of MAPK cascade Source: BHF-UCL
  • positive regulation of osteoblast differentiation Source: BHF-UCL
  • positive regulation of peptidyl-serine phosphorylation Source: MGI
  • positive regulation of peptidyl-tyrosine phosphorylation Source: MGI
  • positive regulation of smooth muscle cell proliferation Source: BHF-UCL
  • positive regulation of T cell proliferation Source: BHF-UCL
  • positive regulation of T-helper 2 cell cytokine production Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: BHF-UCL
  • positive regulation of translation Source: UniProtKB
  • positive regulation of type B pancreatic cell apoptotic process Source: BHF-UCL
  • positive regulation of tyrosine phosphorylation of STAT protein Source: BHF-UCL
  • post-translational protein modification Source: Reactome
  • regulation of angiogenesis Source: BHF-UCL
  • regulation of vascular endothelial growth factor production Source: BHF-UCL
  • response to glucocorticoid Source: BHF-UCL
  • response to peptidoglycan Source: BHF-UCL
  • T-helper 17 cell lineage commitment Source: UniProtKB

Keywordsi

Molecular functionCytokine, Growth factor
Biological processAcute phase

Enzyme and pathway databases

ReactomeiR-HSA-1059683 Interleukin-6 signaling
R-HSA-110056 MAPK3 (ERK1) activation
R-HSA-112411 MAPK1 (ERK2) activation
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP)
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-6783783 Interleukin-10 signaling
R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-8957275 Post-translational protein phosphorylation
SignaLinkiP05231
SIGNORiP05231

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
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000136244.11
HGNCiHGNC:6018 IL6
MIMi147620 gene
neXtProtiNX_P05231

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Rheumatoid arthritis systemic juvenile (RASJ)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:604302
A IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in HIV-infected men.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi173A → V: Almost no loss of activity. 1 Publication1
Mutagenesisi185W → R: No loss of activity. 1 Publication1
Mutagenesisi204S → P: 87% loss of activity. 1 Publication1
Mutagenesisi210R → K, E, Q, T, A or P: Loss of activity. 1 Publication1
Mutagenesisi212M → T, N, S or R: Loss of activity. 1 Publication1

Organism-specific databases

DisGeNETi3569
MalaCardsiIL6
MIMi148000 phenotype
604302 phenotype
OpenTargetsiENSG00000136244
Orphaneti206 Crohn disease
85414 Systemic-onset juvenile idiopathic arthritis
PharmGKBiPA198

Chemistry databases

ChEMBLiCHEMBL1795129
DrugBankiDB05250 681323
DB05066 AV411
DB05744 CRx-139
DB01404 Ginseng
DB05767 HMPL-004
DB09036 Siltuximab
DB05470 VX-702
DB05017 YSIL6

Polymorphism and mutation databases

BioMutaiIL6
DMDMi124347

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 293 PublicationsAdd BLAST29
ChainiPRO_000001558230 – 212Interleukin-6Add BLAST183

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi72 ↔ 781 Publication
Glycosylationi73N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei81Phosphoserine; by FAM20C1 Publication1
Disulfide bondi101 ↔ 1111 Publication

Post-translational modificationi

N- and O-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP05231
PeptideAtlasiP05231
PRIDEiP05231
ProteomicsDBi51828

PTM databases

iPTMnetiP05231
PhosphoSitePlusiP05231

Miscellaneous databases

PMAP-CutDBiP05231

Expressioni

Gene expression databases

BgeeiENSG00000136244
CleanExiHS_IL6
ExpressionAtlasiP05231 baseline and differential
GenevisibleiP05231 HS

Organism-specific databases

HPAiCAB023406
CAB072821

Interactioni

Binary interactionsi

Show more details

GO - Molecular functioni

  • cytokine activity Source: BHF-UCL
  • growth factor activity Source: BHF-UCL
  • interleukin-6 receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi109783, 4 interactors
DIPiDIP-482N
IntActiP05231, 6 interactors
STRINGi9606.ENSP00000258743

Chemistry databases

BindingDBiP05231

Structurei

Secondary structure

1212
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi49 – 75Combined sources27
Beta strandi76 – 79Combined sources4
Turni81 – 83Combined sources3
Helixi84 – 87Combined sources4
Helixi97 – 99Combined sources3
Beta strandi102 – 105Combined sources4
Helixi108 – 132Combined sources25
Beta strandi134 – 136Combined sources3
Helixi137 – 157Combined sources21
Beta strandi159 – 161Combined sources3
Helixi169 – 180Combined sources12
Helixi184 – 209Combined sources26

3D structure databases

ProteinModelPortaliP05231
SMRiP05231
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05231

Family & Domainsi

Sequence similaritiesi

Belongs to the IL-6 superfamily.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IW11 Eukaryota
ENOG4112BXV LUCA
GeneTreeiENSGT00390000000878
HOGENOMiHOG000236330
HOVERGENiHBG000471
InParanoidiP05231
KOiK05405
OMAiLQAQNQW
OrthoDBiEOG091G0NW5
PhylomeDBiP05231
TreeFamiTF335984

Family and domain databases

InterProiView protein in InterPro
IPR009079 4_helix_cytokine-like_core
IPR003574 IL-6
IPR030474 IL-6/GCSF/MGF
IPR030473 IL6/GCSF/MGF_CS
PANTHERiPTHR45110 PTHR45110, 1 hit
PfamiView protein in Pfam
PF00489 IL6, 1 hit
PIRSFiPIRSF001935 IL6_MGF_GCSF, 1 hit
PRINTSiPR00433 IL6GCSFMGF
SMARTiView protein in SMART
SM00126 IL6, 1 hit
SUPFAMiSSF47266 SSF47266, 1 hit
PROSITEiView protein in PROSITE
PS00254 INTERLEUKIN_6, 1 hit

Sequencei

Sequence statusi: Complete.

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

P05231-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNSFSTSAFG PVAFSLGLLL VLPAAFPAPV PPGEDSKDVA APHRQPLTSS
60 70 80 90 100
ERIDKQIRYI LDGISALRKE TCNKSNMCES SKEALAENNL NLPKMAEKDG
110 120 130 140 150
CFQSGFNEET CLVKIITGLL EFEVYLEYLQ NRFESSEEQA RAVQMSTKVL
160 170 180 190 200
IQFLQKKAKN LDAITTPDPT TNASLLTKLQ AQNQWLQDMT THLILRSFKE
210
FLQSSLRALR QM
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, disruption 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.2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01307532P → S1 PublicationCorresponds to variant dbSNP:rs2069830Ensembl.1
Natural variantiVAR_029266162D → E. Corresponds to variant dbSNP:rs13306435Ensembl.1
Natural variantiVAR_013076162D → V1 PublicationCorresponds to variant dbSNP:rs2069860Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_000600.4
XP_011513692.1, XM_011515390.2
UniGeneiHs.654458

Genome annotation databases

EnsembliENST00000258743; ENSP00000258743; ENSG00000136244
ENST00000404625; ENSP00000385675; ENSG00000136244
GeneIDi3569
KEGGihsa:3569

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiIL6_HUMAN
AccessioniPrimary (citable) accession number: P05231
Secondary accession number(s): Q9UCU2, Q9UCU3, Q9UCU4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: June 20, 2018
This is version 214 of the entry and version 1 of the sequence. See 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

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