SENP1: Proteins and Enzymes

SUMO1/Sentrin Specific Peptidase 1 (SENP1) is a member of the SENP family of proteases. SENPs are a group of cysteine-type peptidases that catalyze two essential functions in the SUMO pathways: processing of full-length small Ubiquitin-related modifiers (SUMOs) to their mature forms and deconjugation of SUMOs from SUMOylated proteins. SENP1 is 644 amino acids (aa) in length with a predicted molecular weight of 73.5 kDa. Human SENP1 shares 89% aa sequence identity with the mouse and rat orthologs. Mammalian SENPs share a conserved C-terminal catalytic domain while the N-terminal domains have no significant similarity. SENP1 has broad specificity for the three mammalian SUMOs. It is highly expressed in testis, with lower levels being seen in thymus, pancreas, spleen, liver, ovary, and small intestine. SENP1 shuttles between the nucleus and cytoplasm, and it is thought that its localization is vital for the regulation for SUMOylation status of target proteins. SENP1 has been shown to enhance Androgen Receptor (AR)-dependent transcription via deSUMOylation of HDAC1, a negative regulator of AR. Consequently, SENP1 is thought to play a role in the development, progression, and metastasis of prostate cancer. SENP1 has also been shown to regulate Erythropoietin production during hypoxia by maintaining the stability of HIF1 alpha.