SUMO4

SUMO4 is a member of the SUMO family of small ubiquitin-like modifiers that regulate protein function through sumoylation. The SUMO4 gene encodes a protein related to other SUMO paralogs and is processed by SUMO-specific proteases to expose a C-terminal motif essential for covalent attachment to target lysines. In cells, SUMO4 can be conjugated to substrates via the SUMO E1 and E2 enzymes and removed by SENP proteases. SUMOylation generally modulates substrate activity, stability, localization, or interactions, influencing processes such as transcription, signaling, and stress responses.

Expression of SUMO4 has been reported in multiple human tissues, with some studies noting higher levels in immune-related cells. While the best-characterized role of SUMO proteins is to regulate transcription factors and chromatin-associated proteins, SUMO4 substrates are less well defined than those of SUMO1–3. Some data suggest SUMO4 participates in cellular stress responses and immune signaling, but the extent and context of its contribution remain active areas of research. Reports in the literature sometimes differ on the efficiency of SUMO4 conjugation in vivo.

Clinical genetics: Polymorphisms in SUMO4, including a methionine-to-valine substitution at position 55 (M55V), have been explored for associations with autoimmune diseases such as type 1 diabetes. Early studies suggested a possible link, but subsequent larger studies and meta-analyses have yielded inconsistent results, and no clear causal effect has been established. Overall, SUMO4 is acknowledged as part of the sumoylation machinery, but its precise physiological substrates and disease relevance require further investigation.