HMGB1

Description

The HMGB1 (high mobility group box 1) is a protein-coding gene located on chromosome 13.

High mobility group box 1 protein, also known as high-mobility group protein 1 (HMG-1) and amphoterin, is a protein that in humans is encoded by the HMGB1 gene. HMG-1 belongs to the high mobility group and contains a HMG-box domain.

== Function == Like the histones, HMGB1 is among the most important chromatin proteins. In the nucleus HMGB1 interacts with nucleosomes, transcription factors, and histones. This nuclear protein organizes the DNA and regulates transcription. After binding, HMGB1 bends DNA, which facilitates the binding of other proteins. HMGB1 supports transcription of many genes in interactions with many transcription factors. It also interacts with nucleosomes to loosen packed DNA and remodel the chromatin. Contact with core histones changes the structure of nucleosomes. The presence of HMGB1 in the nucleus depends on posttranslational modifications.

HMGB1 is a multifunctional redox-sensitive protein with roles in different cellular compartments. In the nucleus, it's a key chromatin-associated non-histone protein, acting as a DNA chaperone involved in replication, transcription, chromatin remodeling, V(D)J recombination, DNA repair, and genome stability. It's proposed to be a universal biosensor for nucleic acids. HMGB1 promotes host inflammatory responses to sterile and infectious signals and plays a role in coordinating innate and adaptive immune responses. In the cytoplasm, it acts as a sensor or chaperone for immunogenic nucleic acids, activating TLR9-mediated immune responses and mediating autophagy. HMGB1 is a danger-associated molecular pattern (DAMP) molecule that amplifies immune responses during tissue injury. When released into the extracellular environment, it binds to DNA, nucleosomes, IL-1 beta, CXCL12, AGER isoform 2/sRAGE, lipopolysaccharide (LPS), and lipoteichoic acid (LTA), activating cells through multiple surface receptors. In the extracellular compartment, fully reduced HMGB1 (released by necrosis) acts as a chemokine, disulfide HMGB1 (actively secreted) acts as a cytokine, and sulfonyl HMGB1 (released from apoptotic cells) promotes immunological tolerance. HMGB1 has proangiogenic activity and may be involved in platelet activation. It binds to phosphatidylserine and phosphatidylethanolamide and, when bound to RAGE, mediates signaling for neuronal outgrowth. HMGB1 may play a role in the accumulation of expanded polyglutamine (polyQ) proteins such as huntingtin (HTT) or TBP.

HMGB1 is also known as HMG-1, HMG1, HMG3, SBP-1.

Associated Diseases

WES Whole Exome Sequencing