Reversible phosphorylation of RNA polymerase (RNAP) II's largest subunit C-terminal domain (CTD) is a key event during mRNA metabolism. The CID phosphatase, FCP1, catalyzes the dephosphorylation of RNAP II and is thought to play a major role in polymerase recycling. In this study, we isolated a novel phosphatase gene by large-scale sequencing analysis of a human fetal brain cDNA library. Its cDNA is 2215 by in length, encoding a 318-amino acid polypeptide that contains a ubiquitin-like domain and a CTD phosphatase domain. Therefore, it was termed ubiquitin-like domain containing CTD phosphatase 1 (UBLCPI). Reverse transcription PCR (RT-PCR) revealed that UBLCPI was expressed with relatively lower levels in most adult normal tissues and higher levels in fast growing or tumor tissues. Transient transfection experiment suggested that UBLCP1 was localized in the nucleus of COS-7 cells. Significantly, UBLCPI could dephosphorylate GST-CTD in vitro. Accordingly, UBLCPI may play a role in the regulation of phosphorylation state of RNA polymerase II C-terminal domain. (c) 2005 Elsevier Inc. All rights reserved.