| 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. MARQUARDT, H., LIOUBIN, M.N. AND IKEDA, T.
Complete amino acid sequence of human transforming growth factor
type beta 2.
J.BIOL.CHEM. 262 12127-12131 (1987).
4. BURT, D.W. AND PATON, I.R.
Molecular cloning and primary structure of the chicken transforming
growth factor-beta 2 gene.
DNA CELL BIOL. 10 723-734 (1991).
5. DAOPIN, S., PIEZ, K.A., OGAWA, Y. AND DAVIES, D.R.
Crystal structure of transforming growth factor-beta 2: an unusual
fold for the superfamily.
SCIENCE 257 369-373 (1992).
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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 complete amino acid sequence of human beta 2 transforming growth factor
(hTGF-beta 2) has been determined by automated Edman degradation [3]. Human
TGF-beta 2 consists of 2 identical disulphide-linked subunits that share a
high degree of similarity with the functionally related TGF-beta 1, and
reveal lower levels of similarity to porcine inhibins and activins, the
C-terminal regions of human Mullerian inhibiting substance, and the putative
decapentaplegic gene complex protein of Drosophila [3].
The three-dimensional structures of several members of the TGF-beta super-
family have been deduced. The crystal structure of the TGF-beta 2 monomer
lacks a well-defined hydrophobic core and displays an unusual elongated
non-globular fold [5]. Eight cysteine residues form 4 intra-chain disulphide
bonds, creating the characteristic knotted arrangement. The dimer is
stabilised by a ninth cysteine, which forms an inter-chain disulphide bond,
and by 2 identical hydrophobic interfaces. Other members of the TGF-beta
superfamily, including activins, inhibins and various developmental factors,
are also likely to adopt the TGF-beta fold.
TGFBETA2 is an 8-element fingerprint that provides a signature for the
transforming growth factor beta 2 precursor proteins. The fingerprint was
derived from an initial alignment of 5 sequences: the motifs were drawn from
conserved regions spanning the N-terminal half of the alignment, focusing on
those sections that characterise TGF-beta 2 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 10
sequences was identified. Two partial matches were also found, TGF3_RAT and
TGF3_MOUSE, both of which are TGF-beta 3 proteins that match motifs 1 and 3.
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