The USPL1 peptidase (MEROPS identifier C98.001) is an isopeptidase that releases the SUMO protein from tagged proteins []. USPL1 does not release ubiquitin from conjugates []. USPL1 colocalizes with coilin in Cajal body []. RNAi knockdown of USPL1 leads to disruption of Cajal bodies, relocalization of coilin to the nucleolus and impaired cell proliferation []. These effects do not require USPL1 to be catalytically active, and further studies have shown that USPL1 plays a role in snRNA transcription by RNA polymerase II [].Cajal bodies are spherical sub-organelles of 0.3-1.0 micrometers in diameter found in the nucleus of proliferative cells such as embryonic and tumour cells, or metabolically active cells such as neurons, involved in small nuclear ribonucleoprotein (RNP) and spliceosomal small nuclear RNP biogenesis, maintenance of telomeres and processing of histone RNA.
Peptidase C98 is a small family of SUMO - small ubiquitin-related modifier - isopeptidases found in eukaryotes. Reversible attachment of SUMO is an essential protein modification in all eukaryotic cells. SUMO-specific isopeptidase USPL1 neither binds nor cleaves ubiquitin, but is a potent SUMO isopeptidase. The invariant residues required for SUMO binding and cleavage, in are Cys-236, His-456 and Asp-472, all of which are fully conserved in the family. Member proteins are low-abundance proteins that colocalise with coilin in Cajal bodies. Peptidase C98 depletion does not affect global sumoylation, but causes striking coilin mis-localisation and impairs cell proliferation, functions that are not dependent on the catalytic activity. Thus, Peptidase C98 represents a third type of SUMO protease, with essential functions in Cajal body biology [].This entry represents the catalytic domain.
