Myostatin is a new member of the transforming growth factor-beta (TGFbeta) superfamily and functions as a negative regulator of skeletal muscle growth. Herein, we report the identification of a myostatin-associated protein hSGT (human small glutamine-rich tetratricopeptide repeat-containing protein) by using a yeast two-hybrid system. The physical interaction between hSGT and myostatin was further confirmed by pull-down and co-immunoprecipitation experiments. To identify regions involved in the interaction between hSGT and myostatin, we constructed various deletion mutants of hSGT and myostatin, respectively, and examined their interactions in yeast cells. Our results showed that the N-terminal signal peptide of myostatin is essential for its association with hSGT and the C-terminal region of hSGT containing the third TPR motif was indispensable for its interaction with myostatin. Recent studies indicate that hSGT probably functions as a molecular chaperone involved in protein folding and processing. These findings suggest that hSGT may play a role in the regulation of myostatin secretion and activation. (C) 2003 Elsevier Inc. All rights reserved.