UFSP1 Human

UFSP1 was first identified in a study by Kang et al. (2007), where two novel proteases, UFSP1 and UFSP2, were discovered using a tagged UFM1 recombinant and protein fractionation techniques . UFSP1 encodes a 217-amino acid protein with a molecular mass of approximately 23 kDa . The gene encoding UFSP1 is located on chromosome 7q22.1 .

UFSP1 specifically processes the C-terminus of UFM1, a necessary step before UFM1 can conjugate with its target proteins . This proteolytic cleavage exposes a C-terminal glycine on UFM1, which is essential for its conjugation to substrate proteins . UFSP1 shows higher activity compared to UFSP2, suggesting that it plays a more significant role in the maturation of UFM1 precursors in cells .

UFSP1 transcripts are detected in various tissues, with higher expression levels observed in the brain, heart, kidney, and skeletal tissues . Despite initial reports suggesting that UFSP1 might be inactive due to the lack of critical catalytic residues, recent studies have shown that UFSP1 is indeed an active protease . It is translated from a non-canonical start site, which allows it to mature UFM1 and cleave potential autoinhibitory modifications on UFC1, thereby controlling the activation of UFMylation .

The UFMylation pathway, regulated by UFSP1, is involved in several cellular processes, including protein quality control, stress responses, and the regulation of ribosomal function . Dysregulation of this pathway has been associated with various diseases, highlighting the importance of UFSP1 in maintaining cellular homeostasis .