SUMO4 is a member of the SUMO gene family. This family of small ubiquitin-related modifiers covalently modify target lysines in proteins and control the target proteins' subcellular localization, stability, or activity. Upon oxidative stress, SUMO4 conjugates to various anti-oxidant enzymes, chaperones, and stress defense proteins. This protein may also conjugate to NFKBIA, TFAP2A and FOS, negatively regulating their transcriptional activity, and to NR3C1, positively regulating its transcriptional activity. Covalent attachment to SUMO4 substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I. In contrast to SUMO1, SUMO2 and SUMO3, SUMO4 seems to be insensitive to sentrin-specific proteases due to the presence of Pro-90. This may impair processing to mature form and conjugation to substrates. SUMO4 is located in the cytoplasm and specifically modifies IKBA, leading to negative regulation of NF-kappa-B-dependent transcription of the IL12B gene. The M55V substitution has been associated with type I diabetes.