twsg 1

Twisted Gastrulation Protein Homolog 1 (TWSG1) is a 22 kDa secreted protein that belongs to the twisted gastrulation protein family. Human TWSG1 is synthesized as a 223 aa precursor that contains a 25 aa signal peptide and a 198 aa mature chain. TWSG1 may be involved in dorsoventral axis formation. TWSG1 seems to antagonize BMP signaling by forming ternary complexes with CHRD and BMPs, thereby preventing BMPs from binding to their receptors.TWSG1 can inhibit BMP activity by binding directly to BMP proteins, and can act the anti-BMP function, partly mediated by cleavage and degradation of CHRD, which releases BMPs from ternary complexes. TWSG1 may be an important modulator of BMP-regulated cartilage development, chondrocyte differentiation and thymocyte development.

TWSG1 belongs to the twisted gastrulation protein family. TWSG1 from different species are functionally equivalent. In contrast to Drosophila where TWSG1 expression is limited to early embryos, expression of TWSG1 is found throughout mouse and human development. Mutations in the TWSG1 gene cause at least some of the cells on the dorsal half of the embryo to adopt more ventral cell fates. This is thought to involve gradients of the signaling molecule decapentaplegic. TWSG1 may function as a bone morphogenetic protein signalling agonist or antagonize these activities. It can dislodge latent bone morphogenetic proteins and thus provides a permissive signal that allows high BMP signaling in the embryo. TWSG1 is a cofactor in the antagonism of chordin to BMP signaling. It also binds both the vertebrate Decapentaplegic ortholog BMP4 and chordin and forms ternary complexes. Meanwhile, TWSG1 increases binding of chordin to BMP4, potentiates the ability of chordin to induce secondary axes in Xenopus embryos, and enhances chordin cleavage by vertebrate proteases related to tolloid at a site poorly used in the absence of TWSG1. The presence of TWSG1 enhances the secondary axis-inducing activity of 2 products of chordin cleavage.