Q9MZR1 · IL6_RABIT

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).
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).

GO annotations

AspectTerm
Cellular Componentextracellular space
Cellular Componentinterleukin-6 receptor complex
Molecular Functioncytokine activity
Molecular Functiongrowth factor activity
Molecular Functioninterleukin-6 receptor binding
Biological Processacute-phase response
Biological Processglucose homeostasis
Biological Processhepatocyte proliferation
Biological Processinterleukin-6-mediated signaling pathway
Biological Processliver regeneration
Biological Processpositive regulation of multicellular organismal process
Biological Processpositive regulation of receptor signaling pathway via JAK-STAT
Biological Processpositive regulation of receptor signaling pathway via STAT
Biological Processregulation of glucagon secretion
Biological Processregulation of insulin secretion
Biological Processresponse to activity
Biological ProcessT-helper 17 cell lineage commitment
Biological Processvascular endothelial growth factor production

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Interleukin-6
  • Short names
    IL-6

Gene names

    • Name
      IL6

Organism names

  • Taxonomic identifier
  • Strain
    • Chinese white
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Lagomorpha > Leporidae > Oryctolagus

Accessions

  • Primary accession
    Q9MZR1
  • Secondary accessions
    • Q0PW36

Proteomes

Subcellular Location

Keywords

PTM/Processing

Features

Showing features for signal, chain, disulfide bond, glycosylation.

TypeIDPosition(s)Description
Signal1-26
ChainPRO_000001559227-241Interleukin-6
Disulfide bond72↔78
Disulfide bond101↔111
Glycosylation108N-linked (GlcNAc...) asparagine

Keywords

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.

TypeIDPosition(s)Description
Compositional bias32-46Polar residues
Region32-51Disordered

Sequence similarities

Belongs to the IL-6 superfamily.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    241
  • Mass (Da)
    27,021
  • Last updated
    2000-10-01 v1
  • Checksum
    781D323692C3EE97
MNSFTSALRPGPLGCSLALLLVVATAFPTSAPVREDSNTKASPDKTLTPPGRTIESIRSILETIKELRKEMCDHDVNCMNRKEALAEVNLHLPRLIEEDGCFPPAVNNETCLLRITSGLMEFRMYLEHLQAKFRSDEENTRVSMVLKNIQHLIKTLRPKVKNLNEEATLKPAVAVSLMENLQQKNQWLKTTTIHFILRGLTNFLEFTLRAVDLMECGCPCLRNFMGSASHGQNTPSCPLDT

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias32-46Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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