Transforming growth factor β 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-β contains a conserved domain, the TGF-β 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 β-strands and two α-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-β signaling.
• Vertebrate latent TGF-β binding proteins (LTBPs) 1, 2, 3 and 4. LTBPs regulate TGF-β signaling by forming a latent complex with the cleaved TGF-β proproteins.
• Vertebrate follistatin. It is an extracellular antagonist of various TGF- β proteins. The TB domain of follistatin mimic a type I receptor of TGF- β and binds TGF-β which leads to the formation of a receptor-ligand- antagonist complex [4].

The profile we developed covers the whole TB domain.