Ubiquitin-Like Domain Containing CTD Phosphatase 1 (UBLCP1) is a protein encoded by the UBLCP1 gene in humans. This protein is part of the FCP/SCP phosphatase family and plays a crucial role in cellular processes, particularly in the regulation of proteasome activity and RNA polymerase II function.
The UBLCP1 gene is located on chromosome 5q33.3 and spans over 22.7 kb, containing 11 exons . The protein encoded by this gene consists of 318 amino acids with a predicted molecular mass of 36.8 kDa . UBLCP1 has a C-terminal domain (CTD) phosphatase catalytic domain, which is essential for its enzymatic activity. Additionally, it contains an N-terminal ubiquitin-like domain that harbors a proteasome-interacting motif .
UBLCP1 is expressed in various tissues, with relatively high expression in the placenta, lung, testis, and ovary. It is also expressed, albeit at lower levels, in the heart, liver, kidney, spleen, thymus, colon, and peripheral blood leukocytes . Notably, UBLCP1 expression is particularly high in breast, lung, colon, prostate, ovarian, and pancreas tumor tissues . Immunofluorescence analysis has shown that UBLCP1 is localized to the nucleus .
UBLCP1 is involved in protein dephosphorylation, specifically targeting the C-terminal domain of RNA polymerase II . This dephosphorylation activity is magnesium-dependent and optimal at pH 5 . UBLCP1 dephosphorylates the 26S nuclear proteasomes, thereby decreasing their proteolytic activity . It is recruited to the 19S regulatory particle of the 26S proteasome through its interaction with the 19S component PSMD2/RPN1 . Once recruited, UBLCP1 dephosphorylates the 19S component PSMC2/RPT1, impairing PSMC2 ATPase activity and disrupting 26S proteasome assembly . Interestingly, UBLCP1 has also been reported to stimulate the proteolytic activity of the 26S proteasome .
The discovery and characterization of UBLCP1 have significant implications for understanding cellular processes and disease mechanisms. Given its role in dephosphorylating RNA polymerase II and proteasomes, UBLCP1 is a critical regulator of transcription and protein degradation. Its high expression in various tumor tissues suggests a potential role in cancer biology, making it a target for further research and potential therapeutic interventions.