To improve security and privacy, we are moving our web pages and services from HTTP to HTTPS.
To give users of web services time to transition to HTTPS, we will support separate HTTP and HTTPS services until the end of 2017.
From January 2018 most HTTP traffic will be automatically redirected to HTTPS. [more...]
View this page in https
PROSITE documentation PDOC00223 [for PROSITE entry PS00250]

TGF-beta family signature and profile





Description

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.

                                                     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.

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)


References

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
DOI10.1038/368639a0

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



PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to
Prosite License or see: prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)