Multifunctional protein with various roles in different cellular compartments. May act in a redox sensitive manner. Associates with chromatin and binds DNA with a preference to non-canonical DNA structures such as single-stranded DNA. Can bent DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters (By similarity). Proposed to be involved in the innate immune response to nucleic acids by acting as a cytoplasmic promiscuous immunogenic DNA/RNA sensor (By similarity). Negatively regulates B-cell and myeloid cell differentiation. In hematopoietic stem cells may regulate the balance between self-renewal and differentiation. Involved in negative regulation of canonical Wnt signaling (By similarity). Expressed predominantly in placenta. Reduction/oxidation of cysteine residues Cys-23, Cys-45 and Cys-104 and a possible intramolecular disulfide bond involving Cys-23 and Cys-45 give rise to different redox forms with specific functional activities in various cellular compartments: 1- fully reduced HMGB3 (HMGB3C23hC45hC104h), 2- disulfide HMGB3 (HMGB3C23-C45C104h) and 3- sulfonyl HMGB3 (HMGB3C23soC45soC104so). The disease is caused by variants affecting the gene represented in this entry. Belongs to the HMGB family.