| Literature References | 1. HIRANO, T., YASUKAWA, K., HARADA, H., TAGA, T., WATANABE, Y., MATSUDA,
T., KASHIWAMURA, S., NAKAJIMA, K., KOYAMA, K., IWAMATSU, A., TSUNASAWA, S.,
SAKIYAMA, F., MATSUI, H., TAKAHARA, Y., TANIGUCHI, T. AND KISHIMOTO, T.
Complementary DNA for a novel human interleukin (BSF-2) that induces B
lymphocytes to produce immunoglobulins.
NATURE 324 73-76 (1986).
2. LUETTICKEN, C., KRUETTGEN, A., MOELLER, C., HEINRICH, P.C. AND
ROSE-JOHN, S.
Evidence for the importance of a positive charge and an alpha-helical
structure of the C-terminus for biological activity of human IL-6.
FEBS LETT. 282 265-267 (1991).
3. CLOGSTON, C.L., BOONE, T.C., CRANDALL, B.C., MENDIAZ, E.A. AND LU, H.S.
Disulfide structures of human interleukin-6 are similar to those of human
granulocyte colony stimulating factor.
ARCH.BIOCHEM.BIOPHYS. 272 144-151 (1989).
4. WALTER, M.R., COOK, W.J., ZHAO, B.G., CAMERON, R.P., EALICK. S.E.,
WALTER, R.L., REICHERT, P., NAGABHUSHAN, T.L., TROTTA, P.P. AND BUGG, C.E.
Crystal structure of recombinant human interleukin-4.
J.BIOL.CHEM. 267 20371-20376 (1992).
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| Documentation | Interleukin-6 (IL6) is a cytokine involved in a number of biological
functions: e.g., it induces the final maturation of B-cells into immuno-
globulin-producing cells, and induces nerve cell differentiation [1]. A
number of other cytokines may be grouped with IL6 on the basis of sequence
similarity [1-3]: 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 [3]. MGF also acts in hematopoiesis, stimulating
proliferation and colony formation of normal and transformed avian cells
of the myeloid lineage.
Proteins belonging to the IL6/GCSF/MGF family have a compact, globular
fold (similar to other interleukins), stabilised by 2 disulphide bonds [3].
One half of the structure is dominated by a 4 alpha-helix bundle with a
left-handed twist [4]: the helices are anti-parallel, with 2 overhand
connections, which fall into a 2-stranded anti-parallel beta-sheet [4]. The
fourth helix is important to the biological activity of the molecule [2].
IL6GCSFMGF is a 4-element fingerprint that provides a signature for the
IL6/GCSF/MGF cytokine family. The fingerprint was derived from an initial
alignment of 8 sequences: the motifs were drawn from conserved regions
spanning virtually the full alignment length - motif 1 encodes the first
helix; motif 2 encodes part of the first strand; motif 3 spans part of the
first strand and the second helix, and corresponds to the region encoded by
PROSITE pattern INTERLEUKIN_6 (PS00254), the 2 Cys residues of which form a
disulphide bond; and motif 4 encodes the fourth helix. Two iterations on
OWL26.3 were required to reach convergence, at which point a true set
comprising 21 sequences was identified. Two partial matches (NRL_1RHGA1 and
NRL_1RHGB1) were also found, both of which are GCSF fragments lacking the
portion of sequence bearing motifs 3 and 4.
An update on SPTR37_9f identified a true set of 23 sequences.
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