||Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone involved in replication, transcription, chromatin remodeling, V(D)J recombination, DNA repair and genome stability. Proposed to be an universal biosensor for nucleic acids. Promotes host inflammatory response to sterile and infectious signals and is involved in the coordination and integration of innate and adaptive immune responses. In the cytoplasm functions as sensor and/or chaperone for immunogenic nucleic acids implicating the activation of TLR9-mediated immune responses, and mediates autophagy. Acts as danger associated molecular pattern (DAMP) molecule that amplifies immune responses during tissue injury. Released to the extracellular environment can bind DNA, nucleosomes, IL-1 beta, CXCL12, AGER isoform 2/sRAGE, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and activates cells through engagement of multiple surface receptors. In the extracellular 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) promotes immunological tolerance. Has proangiogenic 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 expanded polyglutamine (polyQ) proteins (By similarity).
|Gene References into Functions
- Systemic HMGB-1 levels were significantly elevated in both trauma groups when compared to the sham group. Haemorrhagic shock severity and duration were positively correlated with HMGB-1 levels and compared to baseline values, concentrations remained significantly increased in severe hemorrhage when compared to moderate hemorrhage. PMID: 26038024
- high levels of HMGB1 in the small intestine and its relation to high levels of HMGB1 in plasma of piglets infected with E. coli O55 that suffered from infection correlated with high levels of inflammatory cytokines and bacterial translocation; levels were higher than HMGB1 levels in piglets with mild clinical symptoms PMID: 22902066
- HMGB-1 may participate in the inflammatory response and liver injury in the late stage of acute liver failure PMID: 18278457
||Nucleus, Chromosome, Cytoplasm, Secreted, Cell membrane, Peripheral membrane protein, Extracellular side, Endosome, Endoplasmic reticulum-Golgi intermediate compartment