PROSITE documentation PDOC51256
GS domain profile


Transforming growth factor β (TGF-β) is a member of a large family of secreted growth factors of central importance in eukaryotic development and homeostasis. Members of this family, which includes the activins, inhibins and bone morphogenic proteins (BMPs), bind to receptors that consist of two transmembrane serine/threonine (Ser/Thr) kinases called the type I and type II receptors (TβR-I and TβR-II, respectively). TβR-II activates TβR-I upon formation of the ligand receptor complex by multiply phosphorylating the GS domain, a short (~30 residues), highly conserved regulatory sequence just N-terminal to the kinase domain on the cytoplasmic side of the receptor. The GS domain is found only in the type I receptor family and is named for the TTSGSGSG sequence at its core. At least three, and perhaps four to five of the serines and threonines in the GS domain, must be phosphorylated to fully activate TβR-1 [1].

The GS domain forms a helix-loop-helix structure in which the sites of activating phosphorylation are situated in the loop (the GS loop) (see <PDB:1B6C>). One key role for phosphorylation is to block the adoption of an inactivating configuration by the GS domain [2].

The profile we developed covers the entire GS domain.

Last update:

October 2006 / First entry.


Technical section

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

GS, PS51256; GS domain profile  (MATRIX)


1AuthorsHuse M. Muir T.W. Xu L. Chen Y.-G. Kuriyan J. Massague J.
TitleThe TGF beta receptor activation process: an inhibitor- to substrate-binding switch.
SourceMol. Cell 8:671-682(2001).
PubMed ID11583628

2AuthorsHuse M. Chen Y.-G. Massague J. Kuriyan J.
TitleCrystal structure of the cytoplasmic domain of the type I TGF beta receptor in complex with FKBP12.
SourceCell 96:425-436(1999).
PubMed ID10025408

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