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Protein

Interleukin-6

Gene

IL6

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

GO - Molecular functioni

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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Keywords - Biological processi

Acute phase

Enzyme and pathway databases

BioCyciZFISH:ENSG00000136244-MONOMER.
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).
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

HGNCiHGNC:6018. IL6.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: Ensembl
  • external side of plasma membrane Source: Ensembl
  • extracellular region Source: Reactome
  • extracellular space Source: BHF-UCL
  • interleukin-6 receptor complex Source: BHF-UCL
Complete GO annotation...

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.

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.
DrugBankiDB01404. Ginseng.
DB09036. Siltuximab.

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...)1 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

EPDiP05231.
PaxDbiP05231.
PeptideAtlasiP05231.
PRIDEiP05231.

PTM databases

iPTMnetiP05231.
PhosphoSitePlusiP05231.

Miscellaneous databases

PMAP-CutDBP05231.

Expressioni

Gene expression databases

BgeeiENSG00000136244.
CleanExiHS_IL6.
ExpressionAtlasiP05231. baseline and differential.
GenevisibleiP05231. HS.

Organism-specific databases

HPAiCAB023406.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
IL6RP088876EBI-720533,EBI-299383
ZBTB16Q055162EBI-720533,EBI-711925

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi109783. 4 interactors.
DIPiDIP-482N.
IntActiP05231. 5 interactors.
MINTiMINT-190042.
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[»]
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.
OMAiFNQETCL.
OrthoDBiEOG091G0NW5.
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.
IPR030474. IL-6/GCSF/MGF.
IPR030473. IL6/GCSF/MGF_CS.
[Graphical view]
PANTHERiPTHR11457. PTHR11457. 1 hit.
PfamiPF00489. IL6. 1 hit.
[Graphical view]
PIRSFiPIRSF001935. IL6_MGF_GCSF. 1 hit.
PRINTSiPR00433. IL6GCSFMGF.
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

        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 → S.1 PublicationCorresponds to variant rs2069830dbSNPEnsembl.1
Natural variantiVAR_029266162D → E.Corresponds to variant rs13306435dbSNPEnsembl.1
Natural variantiVAR_013076162D → V.1 PublicationCorresponds to variant rs2069860dbSNPEnsembl.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

Cross-referencesi

Web resourcesi

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:
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.

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[»]
ProteinModelPortaliP05231.
SMRiP05231.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109783. 4 interactors.
DIPiDIP-482N.
IntActiP05231. 5 interactors.
MINTiMINT-190042.
STRINGi9606.ENSP00000258743.

Chemistry databases

BindingDBiP05231.
ChEMBLiCHEMBL1795129.
DrugBankiDB01404. Ginseng.
DB09036. Siltuximab.

PTM databases

iPTMnetiP05231.
PhosphoSitePlusiP05231.

Polymorphism and mutation databases

BioMutaiIL6.
DMDMi124347.

Proteomic databases

EPDiP05231.
PaxDbiP05231.
PeptideAtlasiP05231.
PRIDEiP05231.

Protocols and materials databases

DNASUi3569.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3569.
DisGeNETi3569.
GeneCardsiIL6.
H-InvDBHIX0167872.
HGNCiHGNC:6018. IL6.
HPAiCAB023406.
MalaCardsiIL6.
MIMi147620. gene.
148000. phenotype.
604302. phenotype.
neXtProtiNX_P05231.
OpenTargetsiENSG00000136244.
Orphaneti206. Crohn disease.
85414. Systemic-onset juvenile idiopathic arthritis.
PharmGKBiPA198.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000136244-MONOMER.
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).
SignaLinkiP05231.
SIGNORiP05231.

Miscellaneous databases

ChiTaRSiIL6. human.
EvolutionaryTraceiP05231.
GeneWikiiInterleukin_6.
GenomeRNAii3569.
PMAP-CutDBP05231.
PROiP05231.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136244.
CleanExiHS_IL6.
ExpressionAtlasiP05231. baseline and differential.
GenevisibleiP05231. HS.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR003574. IL-6.
IPR030474. IL-6/GCSF/MGF.
IPR030473. IL6/GCSF/MGF_CS.
[Graphical view]
PANTHERiPTHR11457. PTHR11457. 1 hit.
PfamiPF00489. IL6. 1 hit.
[Graphical view]
PIRSFiPIRSF001935. IL6_MGF_GCSF. 1 hit.
PRINTSiPR00433. IL6GCSFMGF.
SMARTiSM00126. IL6. 1 hit.
[Graphical view]
SUPFAMiSSF47266. SSF47266. 1 hit.
PROSITEiPS00254. INTERLEUKIN_6. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 200 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.