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PROSITE documentation PDOC00223 [for PROSITE entry PS00250]

TGF-beta family signature and profile


Transforming growth factor-β (TGF-β) [1] is a multifunctional peptide that controls proliferation, differentiation and other functions in many cell types. TGF-β-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-β-1 [1,2,3]. They are listed below.

  • Two other forms of TGF-β have been found, they are known as TGF-β-2 and TGF-β-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 α chain and a β-A or a β-B chain; activins are either homodimers of β-A chains or heterodimers of a β-A and a β-B chain. All three chains are related to TGF-β.
  • 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-β family are only active as homo- or heterodimer; the two chains being linked by a single disulfide bond. From X-ray studies of TGF-β-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-βs and in inhibin β chains, while the other members of this family lack the first bond.

          |                *******                   ||
    |      |                  |  |                                        | |
    +------+                  +--|----------------------------------------+ |
'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.

Last update:

January 2008 / Text revised; profile added.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

TGF_BETA_1, PS00250; TGF-beta family signature  (PATTERN)

TGF_BETA_2, PS51362; TGF-beta family profile  (MATRIX)


1AuthorsRoberts A.B., Sporn M.B.
Source(In) Peptide growth factors and their receptors, Handbook of Experimental Pharmacology, Vol. 95, pp419-475, Springer Verlag, Heidelberg, (1990).

2AuthorsBurt D.W.
SourceBiochem. Biophys. Res. Commun. 184:590-595(1992).

3AuthorsBurt D.W., Law A.S.
TitleEvolution of the transforming growth factor-beta superfamily.
SourceProg. Growth Factor Res. 5:99-118(1994).
PubMed ID8199356

4AuthorsKingsley D.M.
TitleWhat do BMPs do in mammals? Clues from the mouse short-ear mutation.
SourceTrends Genet. 10:16-21(1994).
PubMed ID8146910

5AuthorsStorm E.E., Huynh T.V., Copeland N.G., Jenkins N.A., Kingsley D.M., Lee S.-J.
TitleLimb alterations in brachypodism mice due to mutations in a new member of the TGF beta-superfamily.
SourceNature 368:639-643(1994).
PubMed ID8145850

6AuthorsDaopin S., Piez K.A., Ogawa Y., Davies D.R.
TitleCrystal structure of transforming growth factor-beta 2: an unusual fold for the superfamily.
SourceScience 257:369-373(1992).
PubMed ID1631557

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