Desumoylating isopeptidase 1 (DESI1)

Desumoylating isopeptidase 1 (DESI1) is a cytosolic enzyme that specifically removes Small Ubiquitin-like Modifier (SUMO) proteins from lysine residues of targeted substrates, thereby reversing SUMOylation. DESI1 is structurally and mechanistically distinct from the canonical SUMO protease family SENPs, forming a homodimer with a catalytic cysteine-histidine dyad responsible for its activity[1][2][3][5]. DESI1 exhibits highly selective substrate specificity by deconjugating SUMO1, SUMO2, and SUMO3 moieties, including poly-SUMO2/3 chains, while sparing canonical SUMO targets like PML or ΔNp63, which are processed by SENPs[3][5]. This substrate selectivity positions DESI1 as a critical factor in the fine-tuning of SUMO signaling, with potential implications in cellular metabolism, protein export from the nucleus, and proteostasis. While not clinically targeted by drugs as of 2025, DESI1's role in regulating protein modifications makes it of interest for diseases where SUMOylation dynamics are disrupted, such as cancer and neurodegeneration. Its activity is detected in the cytosol, associates with protein complexes, and is predicted to participate in various regulatory pathways[1][2][3][5].

Other names

FAM152BPPPDE2DESI-1D15Wsu75eDJ347H13.4DESI2POSTPPPDE peptidase domain-containing protein 2

Null (no drugs available; mechanism would hypothetically be inhibition or enhancement of DESI1's isopeptidase activity)