Ubiquitin-like domain-containing C-terminal domain phosphatase 1 (UBLCP1)

Ubiquitin-like domain-containing C-terminal domain phosphatase 1 (UBLCP1) is a nuclear phosphatase and one of the few enzymes with both an FCP/SCP-like phosphatase domain and a ubiquitin-like (UBL) domain[1][3]. UBLCP1 directly interacts with the 19S regulatory particle of the nuclear 26S proteasome by binding the Rpn1 subunit through its UBL domain, but does not interact with the 20S core particle[1][3]. Its principal biological function is the dephosphorylation of specific proteasome subunits, particularly Rpt1, leading to impaired ATPase activity of Rpt1 and disruption of 26S proteasome assembly and activity[1]. UBLCP1 thereby acts as a negative regulator of nuclear proteasome activity: knockdown or depletion of UBLCP1 enhances proteasome assembly and activity, while its overexpression disrupts the association between the regulatory and core particles, resulting in stabilization of proteins normally targeted for degradation[1][3]. UBLCP1’s functions are relevant for maintaining protein homeostasis in the nucleus, and perturbation of its expression affects cellular protein degradation rates, but there are no currently known drugs that specifically target UBLCP1, nor is there strong evidence for its direct involvement in major diseases, although imbalances in proteasomal activity are broadly implicated in cancer, neurodegeneration, and other disorders[1][3].

Other names

Ubiquitin-like domain-containing CTD phosphatase 1UBLCP1MGC10067CPUB1Nuclear proteasome inhibitor UBLCP1CTD phosphatase-like with ubiquitin domain 1CTD-like phosphatase domain-containing protein

Dephosphorylation of proteasome subunit(s), negative regulation of nuclear proteasome assembly/activity, binding to 19S regulatory particle via Rpn1