Is High Mobility Group Box 1 (HMGB1) a protein?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: February 25, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Yes, HMGB1 (High Mobility Group Box 1) is a protein, as stated in the most recent and highest quality study 1.

Definition and Function

It is a highly conserved nuclear protein that functions as a DNA chaperone inside cells, helping with DNA replication, recombination, transcription, and repair.

  • HMGB1 can also be released into the extracellular environment during cell damage or death, where it acts as a damage-associated molecular pattern (DAMP) molecule.
  • In this extracellular role, HMGB1 triggers inflammation by binding to receptors like RAGE (Receptor for Advanced Glycation End Products) and TLR4 (Toll-like Receptor 4), activating immune cells and promoting the release of pro-inflammatory cytokines.

Importance in Cellular Processes

This dual function makes HMGB1 important in both normal cellular processes and in pathological conditions such as sepsis, autoimmune diseases, and cancer.

  • The protein consists of 215 amino acids organized into two DNA-binding domains (A-box and B-box) and an acidic C-terminal tail, giving it its characteristic structure and functionality.

Clinical Relevance

As noted in other studies 1, HMGB1's role in cellular senescence, immunogenic cell death, and ferroptosis highlights its significance in various biological processes and disease states, further emphasizing its importance as a protein.

  • However, the most recent and highest quality study 1 provides the most direct and relevant evidence for HMGB1's classification as a protein.

From the Research

Definition and Characteristics of HMGB1

  • High Mobility Group Box 1 (HMGB1) is defined as a protein in various studies 2, 3, 4, 5, 6.
  • It is described as an evolutionary ancient nuclear protein 2 and a highly conserved, nuclear protein present in all cell types 3.
  • HMGB1 is characterized as a multi-facet protein exerting functions both inside and outside of cells 3 and a member of the highly conserved non-histone DNA binding protein family 4.

Functions and Roles of HMGB1

  • HMGB1 has been found to have multiple roles in the pathogenesis of inflammatory diseases and mediates immune responses 2.
  • It plays a pivotal role in human pathological and pathophysiological processes such as the inflammatory response, immune reactions, cell migration, aging, and cell death 5.
  • HMGB1 is involved in inflammasome activation and pyroptosis, as well as regulation of the autophagy/apoptosis balance 2.
  • It has cytokine, chemokine, neuroimmune and metabolic activities when actively secreted or passively released into the extracellular milieu 2.

HMGB1 as a Therapeutic Target

  • HMGB1 has been identified as a therapeutic target in inflammatory diseases 2, 3, 5.
  • Targeting HMGB1 with antioxidant compounds may be an attractive therapeutic strategy for inflammation-associated diseases 6.
  • The regulation of HMGB1 might be helpful for both basic research and drug development for the treatment of sepsis and sepsis-related organ injury 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Targeting Inflammation Driven by HMGB1.

Frontiers in immunology, 2020

Research

Oxidative stress-mediated HMGB1 biology.

Frontiers in physiology, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.