Q9MZR1 · IL6_RABIT
- ProteinInterleukin-6
- GeneIL6
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids241 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score4/5
Function
function
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.
IL6 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).
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).
Acts 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).
'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).
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | extracellular space | |
Cellular Component | interleukin-6 receptor complex | |
Molecular Function | cytokine activity | |
Molecular Function | growth factor activity | |
Molecular Function | interleukin-6 receptor binding | |
Biological Process | acute-phase response | |
Biological Process | glucose homeostasis | |
Biological Process | hepatocyte proliferation | |
Biological Process | interleukin-6-mediated signaling pathway | |
Biological Process | liver regeneration | |
Biological Process | positive regulation of multicellular organismal process | |
Biological Process | positive regulation of receptor signaling pathway via JAK-STAT | |
Biological Process | positive regulation of receptor signaling pathway via STAT | |
Biological Process | regulation of glucagon secretion | |
Biological Process | regulation of insulin secretion | |
Biological Process | response to activity | |
Biological Process | T-helper 17 cell lineage commitment | |
Biological Process | vascular endothelial growth factor production |
Keywords
- Molecular function
- Biological process
Names & Taxonomy
Protein names
- Recommended nameInterleukin-6
- Short namesIL-6
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Lagomorpha > Leporidae > Oryctolagus
Accessions
- Primary accessionQ9MZR1
- Secondary accessions
Proteomes
Subcellular Location
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-26 | |||||
Sequence: MNSFTSALRPGPLGCSLALLLVVATA | ||||||
Chain | PRO_0000015592 | 27-241 | Interleukin-6 | |||
Sequence: FPTSAPVREDSNTKASPDKTLTPPGRTIESIRSILETIKELRKEMCDHDVNCMNRKEALAEVNLHLPRLIEEDGCFPPAVNNETCLLRITSGLMEFRMYLEHLQAKFRSDEENTRVSMVLKNIQHLIKTLRPKVKNLNEEATLKPAVAVSLMENLQQKNQWLKTTTIHFILRGLTNFLEFTLRAVDLMECGCPCLRNFMGSASHGQNTPSCPLDT | ||||||
Disulfide bond | 72↔78 | |||||
Sequence: CDHDVNC | ||||||
Disulfide bond | 101↔111 | |||||
Sequence: CFPPAVNNETC | ||||||
Glycosylation | 108 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
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.
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 32-46 | Polar residues | ||||
Sequence: PVREDSNTKASPDKT | ||||||
Region | 32-51 | Disordered | ||||
Sequence: PVREDSNTKASPDKTLTPPG |
Sequence similarities
Belongs to the IL-6 superfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length241
- Mass (Da)27,021
- Last updated2000-10-01 v1
- Checksum781D323692C3EE97
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 32-46 | Polar residues | ||||
Sequence: PVREDSNTKASPDKT |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF169176 EMBL· GenBank· DDBJ | AAF86660.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ680161 EMBL· GenBank· DDBJ | ABG73600.1 EMBL· GenBank· DDBJ | mRNA | ||
EF126499 EMBL· GenBank· DDBJ | ABL76067.1 EMBL· GenBank· DDBJ | mRNA |