SENP1
Description
The SENP1 (SUMO specific peptidase 1) is a protein-coding gene located on chromosome 12.
Sentrin-specific protease 1 is an enzyme that in humans is encoded by the SENP1 gene. There are six SUMO proteases in humans, designated SENP1-3 and SENP5-7. These proteases share a conserved C-terminal domain with catalytic activity, but have distinct N-terminal domains that regulate their cellular localization and substrate specificity. SENP1 is a 643 amino acid protease with a weight of 73 kDa. It is a member of the superfamily of cysteine proteases and contains a catalytic triad with a cysteine at position 603, a histidine at position 533, and an aspartic acid at position 550. SENP1 is located in both the nucleus and cytosol depending on cell type, but can be exported from the nucleus to the cytosol through a nuclear export sequence (NES) located at its C-terminus. SENP1 catalyzes the maturation of SUMO proteins (small ubiquitin-related modifier) by hydrolyzing a peptide bond in a conserved sequence (Gly-Gly-|-Ala-Thr-Tyr) at the C-terminus of SUMO. This allows SUMO to be added to other proteins (sumoylation). There are three members of the SUMO family in vertebrates: SUMO-1, SUMO-2, and SUMO-3. SENP1 can catalyze the maturation of all three of these SUMO proteins.
SENP1 is a protease that plays a key role in the SUMO pathway by catalyzing two essential functions: 1) hydrolyzing the C-terminal end of SUMO propeptides (SUMO1, SUMO2, and SUMO3), generating mature forms of these proteins, and 2) deconjugating SUMO1, SUMO2, and SUMO3 from target proteins, removing them from their targets. It has been shown to specifically remove SUMO1 from HIPK2, HDAC1, BHLHE40/DEC1, CLOCK, METTL3, and GPS2, and SUMO2 from MTA1. Removal of SUMO1 from HDAC1 and BHLHE40/DEC1 reduces their transcriptional repression activity, while removal of SUMO1 from CLOCK decreases its transcriptional activation activity. SENP1's deconjugation of SUMO1 from METTL3 inhibits m6A RNA methylation. It also desumoylates CCAR2, decreasing its interaction with SIRT1.
SENP1 is also known as SuPr-2.
