{PDOC00223}
{PS00250; TGF_BETA_1}
{PS51362; TGF_BETA_2}
{BEGIN}
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* TGF-beta family signature and profile *
*****************************************

Transforming growth  factor-beta (TGF-beta) [1] is  a  multifunctional peptide
that controls proliferation,  differentiation and other functions in many cell
types.  TGF-beta-1 is  a  peptide  of  112  amino  acid  residues  derived  by
proteolytic cleavage from the C-terminal of a precursor protein.   A number of
proteins are known to be related to TGF-beta-1 [1,2,3]. They are listed below.

 - Two other forms of TGF-beta have been found, they are  known as  TGF-beta-2
   and TGF-beta-3.
 - Mullerian inhibitory  substance  (MIS), produced  by  the  testis, which is
   responsible for the regression of the Mullerian ducts in the male embryo.
 - Inhibins, which inhibit the  secretion  of  follitropin  by  the  pituitary
   gland, and activins which have the reverse action. Inhibins are heterodimer
   of an  alpha  chain    and  a beta-A or a beta-B chain; activins are either
   homodimers of beta-A chains or heterodimers of a beta-A and a beta-B chain.
   All three chains are related to TGF-beta.
 - Bone morphogenetic proteins [4] BMP-2, BMP-3 (osteogenin), BMP-3B (GDF-10),
   BMP-4 (BMP-2B),  BMP-5, BMP-6  (VGR-1), BMP-7 (OP-1) and BMP-8 (OP-2) which
   induce cartilage  and bone formation and which are probably involved in the
   control of the production of skeletal structures during development.
 - Embryonic  growth  factor  GDF-1,  which  may  mediate cell differentiation
   events during embryonic development.
 - Growth/development  factor GDF-5 [5], a protein whose gene, when mutated in
   mice, is  the  cause of brachypodism, a defects which alters the length and
   numbers of bones in the limbs.
 - Growth/development factor GDF-3, GDF-6, GDF-7, GDF-8 (myostatin) and GDF-9.
 - Mouse protein nodal, which seems essential for mesoderm formation.
 - Chicken  dorsalin-1  (dsl-1) which may regulate cell differentiation within
   the neural tube.
 - Xenopus vegetal hemisphere protein Vg1, which seems to induce the overlying
   animal pole cells to form mesodermal tissue.
 - Drosophila  decapentaplegic  protein (DPP-C),  which  participates  in  the
   establishment of dorsal-ventral specification.
 - Drosophila protein screw (scw) which also participates in the establishment
   of dorsal-ventral specification.
 - Drosophila protein 60A.
 - Caenorhabditis elegans larval development regulatory growth factor daf-7.
 - Mammalian endometrial bleeding-associated factor (EBAF) (Lefty).
 - Mammalian  glial  cell line-derived neurotrophic factor (GDNF), a distantly
   related member  of  this  family  which  acts  as  neurotrophic  factor for
   dopaminergic neurons of the substantia nigra.

Proteins from  the TGF-beta  family  are  only active as homo- or heterodimer;
the two chains being linked by a single disulfide bond. From X-ray studies  of
TGF-beta-2 [6],  it  is  known that all the other cysteines  are  involved  in
intrachain  disulfide bonds.      As   shown   in   the   following  schematic
representation, there are four disulfide bonds in the TGF-betas and in inhibin
beta chains, while the other members of this family lack the first bond.

                                                     interchain
                                                     |
          +------------------------------------------|+
          |                *******                   ||
 xxxcxxxxxCcxxxxxxxxxxxxxxxxxxCxxCxxxxxxxxxxxxxxxxxxxCCxxxxxxxxxxxxxxxxxxxCxCx
    |      |                  |  |                                        | |
    +------+                  +--|----------------------------------------+ |
                                 +------------------------------------------+

'C': conserved cysteine involved in a disulfide bond.
'*': position of the pattern.

As  a  pattern to detect these proteins, we use a region which includes two of
the  conserved  cysteines.  We  also  developed  a profile that covers all the
conserved cysteines.

-Consensus pattern: [LIVM]-x(2)-P-x(2)-[FY]-x(4)-C-x-G-x-C
                    [The 2 C's are involved in disulfide bonds]
-Sequences known to belong to this class detected by the profile: ALL.
 for GDNF and neurturin.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: January 2008 / Text revised; profile added.

[ 1] Roberts A.B., Sporn M.B.
     (In) Peptide growth factors and their receptors, Handbook of Experimental
     Pharmacology, Vol. 95, pp419-475, Springer Verlag, Heidelberg, (1990).
[ 2] Burt D.W.
     Biochem. Biophys. Res. Commun. 184:590-595(1992).
[ 3] Burt D.W., Law A.S.
     "Evolution of the transforming growth factor-beta superfamily."
     Prog. Growth Factor Res. 5:99-118(1994).
     PubMed=8199356
[ 4] Kingsley D.M.
     "What do BMPs do in mammals? Clues from the mouse short-ear
     mutation."
     Trends Genet. 10:16-21(1994).
     PubMed=8146910
[ 5] Storm E.E., Huynh T.V., Copeland N.G., Jenkins N.A., Kingsley D.M.,
     Lee S.-J.
     "Limb alterations in brachypodism mice due to mutations in a new
     member of the TGF beta-superfamily."
     Nature 368:639-643(1994).
     PubMed=8145850; DOI=10.1038/368639a0
[ 6] Daopin S., Piez K.A., Ogawa Y., Davies D.R.
     "Crystal structure of transforming growth factor-beta 2: an unusual
     fold for the superfamily."
     Science 257:369-373(1992).
     PubMed=1631557

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