Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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 STAT protein import into nucleus 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.

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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4O9HX-ray2.42A28-212[»]
4ZS7X-ray2.93A42-212[»]
5FUCX-ray2.70A/B49-212[»]
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: March 28, 2018
This is version 212 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