{PDOC51364}
{PS51364; TB}
{BEGIN}
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* TGF-beta binding (TB) domain profile *
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Transforming   growth   factor  beta  family  of  cytokines,  are  potent  and
multifunctional   signaling  molecules  (see  <PDOC00223>).  Prior  to  ligand
receptor  binding  there  exist  extracellular  regulators  that  target these
cytokines  and  facilitate  the  formation of morphogen gradiants that control
developmental  processes.  Some  of these proteins that are known to sequester
latent TGF-beta contains a conserved domain, the TGF-beta binding (TB) domain.
It is characterised by 8 conserved cysteine residues, which include an unusual
cysteine triplet [1,2].

The  TB  fold  is  globular  with  six beta-strands and two alpha-helices (see
<PDB:1APJ>)  [1,2,3]. The pairing of the eight cysteines is 1-3, 2-6, 4-7, and
5-8, creating a fairly rigid structure. In follistatin and in the first repeat
of fibrillin and LTBPs the last disulfide bridge is absent.

The proteins that contain a TB domain are listed below:

 - Vertebrate  fibrillin-1,  2  and  3.  Fibrillins  form  tissue-specific and
   temporally  regulated  microfibril  networks.  They  are  implicated in the
   regulation of TGF-beta signaling.
 - Vertebrate  latent  TGF-beta  binding proteins (LTBPs) 1, 2, 3 and 4. LTBPs
   regulate  TGF-beta  signaling  by forming a latent complex with the cleaved
   TGF-beta proproteins.
 - Vertebrate  follistatin. It is an extracellular antagonist of various  TGF-
   beta proteins. The TB domain of follistatin mimic a type I receptor of TGF-
   beta and binds TGF-beta  which leads to the formation of a receptor-ligand-
   antagonist complex [4].

The profile we developed covers the whole TB domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: January 2008 / First entry.

[ 1] Yuan X., Downing A.K., Knott V., Handford P.A.
     "Solution structure of the transforming growth factor beta-binding
     protein-like module, a domain associated with matrix fibrils."
     EMBO J. 16:6659-6666(1997).
     PubMed=9362480; DOI=10.1093/emboj/16.22.6659
[ 2] Lack J., O'Leary J.M., Knott V., Yuan X., Rifkin D.B., Handford P.A.,
     Downing A.K.
     "Solution structure of the third TB domain from LTBP1 provides insight
     into assembly of the large latent complex that sequesters latent
     TGF-beta."
     J. Mol. Biol. 334:281-291(2003).
     PubMed=14607119
[ 3] Lee S.S., Knott V., Jovanovic J., Harlos K., Grimes J.M., Choulier L.,
     Mardon H.J., Stuart D.I., Handford P.A.
     "Structure of the integrin binding fragment from fibrillin-1 gives new
     insights into microfibril organization."
     Structure 12:717-729(2004).
     PubMed=15062093; DOI=10.1016/j.str.2004.02.023
[ 4] Thompson T.B., Lerch T.F., Cook R.W., Woodruff T.K., Jardetzky T.S.
     "The structure of the follistatin:activin complex reveals antagonism
     of both type I and type II receptor binding."
     Dev. Cell 9:535-543(2005).
     PubMed=16198295; DOI=10.1016/j.devcel.2005.09.008

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