Family includes granulocyte colony-stimulating factor (G-CSF) and myelomonocytic growth factor (MGF). IL-6 is also known as B-cell stimulatory factor 2.
Interleukin-6 (IL6), also refered to as B-cell stimulatory factor-2 (BSF-2) and interferon beta-2, is a cytokine involved in a wide variety of biological functions [ (PUBMED:3491322) ]. It plays an essential role in the final differentiation of B-cells into IG-secreting cells, as well as inducing myeloma/plasmacytoma growth, nerve cell differentiation and, in hepatocytes, acute phase reactants [ (PUBMED:3491322) (PUBMED:2037043) ].
A number of other cytokines may be grouped with IL6 on the basis of sequence similarity [ (PUBMED:3491322) (PUBMED:2037043) (PUBMED:2472117) ]: these include granulocyte colony-stimulating factor (GCSF) and myelomonocytic growth factor (MGF). GCSF acts in hematopoiesis by affecting the production, differentiation and function of 2 related white cell groups in the blood [ (PUBMED:2472117) ]. MGF also acts in hematopoiesis, stimulating proliferation and colony formation of normal and transformed avian cells of the myeloid lineage.
1.9 A crystal structure of interleukin 6: implications for a novel mode of receptor dimerization and signaling.
EMBO J. 1997; 16: 989-97
Display abstract
Interleukin 6 (IL-6) has many biological activities in vivo, and deregulation has been implicated in many disease processes. IL-6, a 185 amino acid polypeptide was refolded, purified and crystallized. The crystals diffracted to beyond 1.9 A and the structure was solved using single isomorphous replacement. The X-ray structure of IL-6 is composed of a four helix bundle linked by loops and an additional mini-helix. 157 out of 185 residues are well defined in the final structure, with 18 N-terminal and 8 A-B loop amino acids displaying no interpretable electron density. The three-dimensional structure has been used to construct a model of IL-6 interacting with the IL-6 receptor (alpha-chain) and gp130 (beta-chain) that gives new insight into the process of molecular recognition and signaling. Based on this model, we predict a fourth binding site on IL-6, a low affinity IL-6-IL-6 interaction, which may be necessary for the sequential assembly of a functional hexameric IL-6 receptor complex.
Crystal structure of canine and bovine granulocyte-colony stimulating factor (G-CSF).
J Mol Biol. 1993; 234: 640-53
Display abstract
The crystal structures of recombinant canine and bovine granulocyte colony stimulating factor (G-CSF) have been determined by X-ray crystallography, using molecular replacement with recombinant human G-CSF as a model. G-CSF is a member of the cytokine family of glycoproteins that stimulate the differentiation and proliferation of blood cells. Human, bovine and canine G-CSF all have a molecular mass of about 19 kDa and share an amino acid sequence identity of about 80%. Two crystal forms of canine G-CSF have been solved. Form I recombinant canine G-CSF (rcG-CSFI; space group C2) contains one molecule in the asymmetric unit while form II canine G-CSF (rcG-CSFII; space group P2(1)) has two molecules in the asymmetric unit and bovine G-CSF (rbG-CSF; space group P2(1)2(1)2(1)) contains one molecule in the asymmetric unit. rcG-CSFI has been refined to an R factor of 20.7% with data to 2.3 A resolution and rcG-CSFII has been refined to an R factor of 19.3% with data to 2.2 A resolution. rbG-CSF has been refined to an R factor of 21.3% with data to 1.7 A resolution. The structure of human, canine and bovine G-CSF is an antiparallel 4-alpha-helical bundle with up-up-down-down connectivity. With the exception of one highly exposed loop (residues 66 to 74), the human, canine and bovine structures are very similar to each other. Using our series of G-CSF crystal structures we developed a function that describes the probability that a particular residue position (i) contributes to a G-CSF receptor binding site based on two principles, (1) high sequence conservation in the primary sequence of human, bovine, canine and murine G-CSF and (2) conservation of high solvent accessibility in the human, bovine and canine crystal structures. On the basis of this probability function as well as a comparison of G-CSF to the crystal structure of human growth hormone (hGH) complexed with the extracellular domain of the human growth hormone receptor (hGHbp), residues that contribute to potential G-CSF receptor binding sites are identified.
Metabolism (metabolic pathways involving proteins which contain this domain)
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with IL6 domain which could be assigned to a KEGG orthologous group, and not all proteins containing IL6 domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
