Multifunctional redox sensitive protein with various roles indifferent cellular compartments. In the nucleus is one of the majorchromatin-associated non-histone proteins and acts as a DNA chaperoneinvolved in replication, transcription, chromatin remodeling, V (D) Jrecombination, DNA repair and genome stability. Proposed to bean universal biosensor for nucleic acids. Promotes host inflammatoryresponse to sterile and infectious signals and is involved in thecoordination and integration of innate and adaptive immune responses. In the cytoplasm functions as sensor and/or chaperone for immunogenicnucleic acids implicating the activation of TLR9-mediated immuneresponses, and mediates autophagy. Acts as danger associated molecularpattern (DAMP) molecule that amplifies immune responses during tissueinjury. Released to the extracellular environment canbind DNA, nucleosomes, IL-1 beta, CXCL12, AGER isoform 2/sRAGE, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and activatescells through engagement of multiple surface receptors. In theextracellular compartment fully reduced HMGB1 (released by necrosis) acts as a chemokine, disulfide HMGB1 (actively secreted) as a cytokine, and sulfonyl HMGB1 (released from apoptotic cells) promotesimmunological tolerance. Has proangiogdenic activity. May be involved in platelet activation. Binds to phosphatidylserine and phosphatidylethanolamide. Bound to RAGE mediates signaling for neuronal outgrowth. May play a role in accumulation of expandedpolyglutamine (polyQ) proteins such as huntingtin (HTT) or TBP. [1-7]

MGKGDPKKPRGKMSSYAFFVQTCREEHKKKHPDASVNFSEFSKKCSERWKTMSAKEKGKFEDMAKADKARYEREMKTYIPPKGETKKKFKDPNAPKRPPSAFFLFCSEYRPKIKGEHPGLSIGDVAKKLGEMWNNTAADDKQPYEKKAAKLKEKYEKDIAAYRAKGKPDAAKKGVVKAEKSKKKKEEEEDEEDEEDEEEEEDEEDEDEEEDDDDE