Identification of a new human Smad6 splice variant.

Smad6 and Smad7 are inhibitory Smad proteins, which are essential in the negative regulation of BMP and TGF-beta/activin-signalling. While Smad7 is ubiquitously expressed and inhibits BMP and TGF-beta signalling, Smad6 is expressed in a cell-specific fashion and preferentially inhibits BMP-signalling. Here, we identified in addition to the splice variant Smad6s, possessing a different N-terminus, a novel human Smad6 splice variant, termed Smad6B, in human prostatic and rodent testicular cell lines. Due to an alternative exon, the putative Smad6B protein exhibits a truncated C-terminus lacking the entire MH-2 domain and most parts of the linker region. While full-length Smad6 was expressed in almost all tissues and cell lines studied, expression of the splice variants Smad6s and Smad6B was more heterogenous. Species-specific sequence comparison revealed that Smad6 is found in most species, while Smad6s was found only in Homo sapiens and Pan troglodytes, and Smad6B was found only in Homo sapiens. In addition, Smad6 localisation was found in round spermatids of human testis. In conclusion, we propose that alternative splicing of Smad6s and Smad6B is restricted to higher mammals.