| Literature References | 1. ARCHER, S.J., BAX, A., ROBERTS, A.B., SPORN, M.B., OGAWA, Y., PIEZ, K.A.,
WEATHERBEE, J.A., TSANG, M.L., LUCAS, R. AND ZHENG, B.L.
Transforming growth factor beta 1: NMR signal assignments of the recombinant
protein expressed and isotopically enriched using Chinese hamster ovary cells.
BIOCHEMISTRY 32 1152-1163 (1993).
2. CHEIFETZ, S., WEATHERBEE, J.A., TSANG, M.L.S., ANDERSON, J.K.,
MOLE, J.E., LUCAS, R. AND MASSAGUE, J.
The transforming growth factor-beta system, a complex pattern of
cross-reactive ligands and receptors.
CELL 48 409-415 (1987).
3. SUTTON, R., WARD, W.G., RAPHAEL, K.A. AND CAM, G.R.
Growth factor expression in skin during wool follicle development.
COMP.BIOCHEM.PHYSIOL. 110B 697-705 (1995).
4. DERYNCK, R. AND RHEE, L.
Sequence of the porcine transforming growth factor-beta precursor.
NUCLEIC ACIDS RES. 15 3187-3187 (1987).
5. MASSAGUE, J. AND LIKE, B.
Cellular receptors for type beta transforming growth factor. Ligand
binding and affinity labeling in human and rodent cell lines.
J.BIOL.CHEM. 260 2636-2645 (1985).
6. HINCK, A.P., ARCHER, S.J., QIAN, S.W., ROBERTS, A.B.,
SPORN, M.B., WEATHERBEE, J.A., TSANG, M.L.-S., LUCAS, R.,
ZHENG, B.-L., WENKER, J. AND TORCHIA, D.A.
Transforming growth factor beta 1: three-dimensional structure in
solution and comparison with the X-ray structure of transforming
growth factor beta 2.
BIOCHEMISTRY 35 8517-8534 (1996).
7. MILLER, D.A., LEE, A., MATSUI, Y., CHEN, E.Y., MOSES H.L. AND DERYNCK, R.
Complementary DNA cloning of the murine transforming growth factor-beta 3
beta 1 messenger RNA in murine embryos and adult tissues.
MOL.ENDOCRINOL. 3 1926-1934 (1989).
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| Documentation | The transforming growth factors-beta (TGF-beta 1-5) constitute a family of
multi-functional cytokines that regulate cell growth and differentiation [1].
Many cells synthesise TGF-beta, and essentially all have specific receptors
for this peptide [2]. TGF-beta regulates the actions of many other peptide
growth factors and determines a positive or negative direction of their
effects. The protein functions as a disulphide-linked homodimer. Its
sequence is characterised by the presence of several C-terminal cysteine
residues, which form interlocking disulphide links arranged in a knot-like
topology. A similar "cystine-knot" arrangement has been noted in the
structures of some enzyme inhibitors and neurotoxins that bind to voltage-
gated Ca2+ channels, although the precise topology here differs.
The three-dimensional structures of several members of the TGF-beta super-
family have been deduced. The solution structure of human TGF-beta 1 has
been determined using multinuclear magnetic resonance spectroscopy with
hybrid distance geometry/simulated annealing [6]. The structure shows a high
degree of similarity to that of TGF-beta 2, but there are several notable
differences in structure and flexibility, which might relate to function [6].
TGF-beta genes are expressed differentially, suggesting that the various TGF-
beta species may have distinct physiological roles in vivo. Examination of
TGF-beta 1 mRNA levels in adult murine tissues indicates that expression is
predominant in spleen, lung and placenta [7]. TGF-beta 1 is believed to play
important roles in pathologic processes.
TGFBETA1 is a 6-element fingerprint that provides a signature for the
transforming growth factor beta 1 precursor proteins. The fingerprint was
derived from an initial alignment of 8 sequences: the motifs were drawn from
conserved regions spanning the N-terminal half of the alignment, focusing on
those sections that characterise TGF-beta 1 proteins but distinguish them
from the rest of the TGF-beta superfamily. Two iterations on SPTR39_14f were
required to reach convergence, at which point a true set comprising 11
sequences was identified. A single partial match was also found, O93449,
a transforming growth factor beta precursor from Oncorhynchus mykiss
(Rainbow trout) that only matches motifs 2, 3 and 5.
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