UniProtKB - P79341 (IL6_MACFA)
Interleukin-6
IL6
Functioni
Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway. The interaction with the membrane-bound IL6R and IL6ST stimulates 'classic signaling', whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells.
By similarityIL6 is a potent inducer of the acute phase response. Rapid production of IL6 contributes to host defense during infection and tissue injury, but excessive IL6 synthesis is involved in disease pathology. In the innate immune response, is synthesized by myeloid cells, such as macrophages and dendritic cells, upon recognition of pathogens through toll-like receptors (TLRs) at the site of infection or tissue injury (By similarity).
In the adaptive immune response, is required for the differentiation of B cells into immunoglobulin-secreting cells. Plays a major role in the differentiation of CD4+ T cell subsets. Essential factor for the development of T follicular helper (Tfh) cells that are required for the induction of germinal-center formation. Required to drive naive CD4+ T cells to the Th17 lineage. Also required for proliferation of myeloma cells and the survival of plasmablast cells (By similarity).
By similarityActs as an essential factor in bone homeostasis and on vessels directly or indirectly by induction of VEGF, resulting in increased angiogenesis activity and vascular permeability. Induces, through 'trans-signaling' and synergistically with IL1B and TNF, the production of VEGF. Involved in metabolic controls, is discharged into the bloodstream after muscle contraction increasing lipolysis and improving insulin resistance (By similarity).
'Trans-signaling' in central nervous system also regulates energy and glucose homeostasis. Mediates, through GLP-1, crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand (By similarity).
Also acts as a myokine (By similarity).
Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity).
Also has a pivotal role in iron metabolism by regulating HAMP/hepcidin expression upon inflammation or bacterial infection (By similarity).
Through activation of IL6ST-YAP-NOTCH pathway, induces inflammation-induced epithelial regeneration (By similarity).
By similarityGO - Molecular functioni
- cytokine activity Source: UniProtKB-KW
- growth factor activity Source: UniProtKB-KW
- interleukin-6 receptor binding Source: InterPro
GO - Biological processi
- acute-phase response Source: UniProtKB-KW
- glucose homeostasis Source: UniProtKB
- hepatocyte proliferation Source: UniProtKB
- interleukin-6-mediated signaling pathway Source: UniProtKB
- liver regeneration Source: UniProtKB
- positive regulation of receptor signaling pathway via STAT Source: UniProtKB
- regulation of glucagon secretion Source: UniProtKB
- regulation of insulin secretion Source: UniProtKB
- response to activity Source: UniProtKB
- T-helper 17 cell lineage commitment Source: UniProtKB
- vascular endothelial growth factor production Source: UniProtKB
Keywordsi
Molecular function | Cytokine, Growth factor |
Biological process | Acute phase |
Names & Taxonomyi
Protein namesi | Recommended name: Interleukin-6Short name: IL-6 |
Gene namesi | Name:IL6 |
Organismi | Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey) |
Taxonomic identifieri | 9541 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Cercopithecidae › Cercopithecinae › Macaca |
Proteomesi |
|
Organism-specific databases
VEuPathDBi | HostDB:ENSMFAG00000000229 |
Subcellular locationi
Extracellular region or secreted
- Secreted By similarity
Extracellular region or secreted
- extracellular space Source: UniProtKB-KW
Keywords - Cellular componenti
SecretedPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 27 | Sequence analysisAdd BLAST | 27 | |
ChainiPRO_0000015584 | 28 – 212 | Interleukin-6Add BLAST | 185 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 72 ↔ 78 | By similarity | ||
Glycosylationi | 73 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 81 | PhosphoserineBy similarity | 1 | |
Disulfide bondi | 101 ↔ 111 | By similarity | ||
Glycosylationi | 172 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Disulfide bond, Glycoprotein, PhosphoproteinInteractioni
Subunit structurei
Component of a hexamer of two molecules each of IL6, IL6R and IL6ST; first binds to IL6R to associate with the signaling subunit IL6ST.
Interacts with IL6R (via the N-terminal ectodomain); this interaction may be affected by IL6R-binding with SORL1, hence decreasing IL6 cis signaling.
Interacts with SORL1 (via the N-terminal ectodomain); this interaction leads to IL6 internalization and lysosomal degradation. May form a trimeric complex with the soluble SORL1 ectodomain and soluble IL6R receptor; this interaction might stabilize circulating IL6, hence promoting IL6 trans signaling.
By similarityGO - Molecular functioni
- cytokine activity Source: UniProtKB-KW
- growth factor activity Source: UniProtKB-KW
- interleukin-6 receptor binding Source: InterPro
Protein-protein interaction databases
STRINGi | 9541.XP_005550057.1 |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502S7Q4, Eukaryota |
GeneTreei | ENSGT00390000000878 |
OMAi | YDKCENS |
Family and domain databases
Gene3Di | 1.20.1250.10, 1 hit |
InterProi | View protein in InterPro IPR009079, 4_helix_cytokine-like_core IPR003574, IL-6 IPR030474, IL-6/GCSF/MGF IPR030473, IL6/GCSF/MGF_CS |
PANTHERi | PTHR10511, PTHR10511, 1 hit PTHR10511:SF3, PTHR10511:SF3, 1 hit |
Pfami | View protein in Pfam PF00489, IL6, 1 hit |
PIRSFi | PIRSF001935, IL6_MGF_GCSF, 1 hit |
PRINTSi | PR00433, IL6GCSFMGF |
SMARTi | View protein in SMART SM00126, IL6, 1 hit |
SUPFAMi | SSF47266, SSF47266, 1 hit |
PROSITEi | View protein in PROSITE PS00254, INTERLEUKIN_6, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MNSVSTSAFG PVAFSLGLLL VLPAAFPAPV LPGEDSKDVA APHSQPLTSS
60 70 80 90 100
ERIDKHIRYI LDGISALRKE TCNRSNMCES SKEALAENNL NLPKMAEKDG
110 120 130 140 150
CFQSGFNEDT CLVKIITGLL EFEVYLEYLQ NRFESSEEQA RAVQMSTKVL
160 170 180 190 200
IQFLQKKAKN LDAITTPEPT TNASLLTKLQ AQNQWLQDMT THLILRSFKE
210
FLQSSLRALR QM
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A2K5X6C0 | A0A2K5X6C0_MACFA | Interleukin-6 | 266 | Annotation score: | |||
A0A2K5X693 | A0A2K5X693_MACFA | Interleukin-6 | 210 | Annotation score: | |||
A0A805RSY6 | A0A805RSY6_MACFA | Interleukin-6 | 214 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB000554 mRNA Translation: BAA19148.1 |
RefSeqi | XP_005550059.1, XM_005550002.2 XP_005550060.1, XM_005550003.2 |
Genome annotation databases
Ensembli | ENSMFAT00000019321; ENSMFAP00000045020; ENSMFAG00000000229 |
GeneIDi | 102138971 |
KEGGi | mcf:102138971 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB000554 mRNA Translation: BAA19148.1 |
RefSeqi | XP_005550059.1, XM_005550002.2 XP_005550060.1, XM_005550003.2 |
3D structure databases
SMRi | P79341 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9541.XP_005550057.1 |
Genome annotation databases
Ensembli | ENSMFAT00000019321; ENSMFAP00000045020; ENSMFAG00000000229 |
GeneIDi | 102138971 |
KEGGi | mcf:102138971 |
Organism-specific databases
CTDi | 3569 |
VEuPathDBi | HostDB:ENSMFAG00000000229 |
Phylogenomic databases
eggNOGi | ENOG502S7Q4, Eukaryota |
GeneTreei | ENSGT00390000000878 |
OMAi | YDKCENS |
Family and domain databases
Gene3Di | 1.20.1250.10, 1 hit |
InterProi | View protein in InterPro IPR009079, 4_helix_cytokine-like_core IPR003574, IL-6 IPR030474, IL-6/GCSF/MGF IPR030473, IL6/GCSF/MGF_CS |
PANTHERi | PTHR10511, PTHR10511, 1 hit PTHR10511:SF3, PTHR10511:SF3, 1 hit |
Pfami | View protein in Pfam PF00489, IL6, 1 hit |
PIRSFi | PIRSF001935, IL6_MGF_GCSF, 1 hit |
PRINTSi | PR00433, IL6GCSFMGF |
SMARTi | View protein in SMART SM00126, IL6, 1 hit |
SUPFAMi | SSF47266, SSF47266, 1 hit |
PROSITEi | View protein in PROSITE PS00254, INTERLEUKIN_6, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | IL6_MACFA | |
Accessioni | P79341Primary (citable) accession number: P79341 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1998 |
Last sequence update: | May 1, 1997 | |
Last modified: | September 29, 2021 | |
This is version 107 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families