We previously cloned and characterized a novel RNA-binding motif (RRM)-containing coactivator named coactivator activator (CoAA) as a thyroid hormone receptor-binding protein (TRBP)-interacting protein using a Sos-Ras yeast two-hybrid screening system. A database search revealed that CoAA is identical to synovial sarcoma translocation (SYT)-interacting protein (SIP). Thus, we hypothesized that SYT could also function as a coactivator. Subsequently, we isolated a cDNA encoding a larger isoform of SYT, SYT-Long (SYT-L), from the brain and liver total RNA using RT-PCR. SYT-L possesses an additional 31 amino acids in its C-terminus, compared with SYT, suggesting that these two SYT isoforms may be expressed from two mRNAs produced by alternative splicing of a transcript from a single gene. By Northern blot analysis, we found that SYT-L mRNA is expressed in several human embryonic tissues such as the brain, liver, and kidney. However, we could not detect SYT-L in adult tissues. GST pull-down studies showed that SYT binds to the C-terminus of CoAA but not to the coactivator modulator (CoAM). Both isoforms of SYT function as transcriptional coactivators of nuclear hormone receptors in a ligand- and dose-dependent manner in CV-1, Cos-1 and JEG-3 cells. However, the pattern of transactivation was different between SYT and SYT-L among these cells. SYT synergistically activates transcription with CoAA. In addition, SYT activates transcription through AP-1, suggesting that SYT may function as a general coactivator. These results indicate that SYT activates transcription, possibly through CoAA to interact with histone acetyltransferase complex.