HMGB1 Rabbit Polyclonal Antibody

Function

Like the histones, HMGB1, also known as high-mobility group protein 1 (HMG-1) 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 is secreted by immune cells through leaderless secretory pathway. Activated macrophages and monocytes secrete HMGB1 as a cytokine mediator of Inflammation. In recent research, HMGB1 has been reported as a novel biomarker for human ovarian cancer.

Background References

1. "The active gene that encodes human high mobility group 1 protein (HMG1) contains introns and maps to chromosome 13." Ferrari S., Finelli P., Rocchi M., Bianchi M.E. Genomics 35:367-371(1995)

2. "The genetic variation of the human HMGB1 gene." Kornblit B., Munthe-Fog L., Petersen S., Madsen H., Vindeloev L., Garred P. Tissue Antigens 70:151-156(2006)

3. "Novel role of PKR in inflammasome activation and HMGB1 release." Lu B., Nakamura T., Inouye K., Li J., Tang Y., Lundbaeck P., Valdes-Ferrer S.I., Olofsson P.S., Kalb T., Roth J., Zou Y., Erlandsson-Harris H., Yang H., Ting J.P., Wang H., Andersson U., Antoine D.J., Chavan S.S., Hotamisligil G.S., Tracey K.J. Nature 488:670-674(2011)

Sequence Similarity

Belongs to the HMGB family.

Tissue Specificity

Ubiquituous. Expressed in platelets.

Post-translational Modification

Phosphorylated at serine residues. Phosphorylation in both NLS regions is required for cytoplasmic translocation followed by secretion.; Acetylated on multiple sites upon stimulation with LPS. Acetylation on lysine residues in the nuclear localization signals (NLS 1 and NLS 2) leads to cytoplasmic localization and subsequent secretion (By similarity). Acetylation on Lys-3 results in preferential binding to DNA ends and impairs DNA bending activity (By similarity).; Reduction/oxidation of cysteine residues Cys-23, Cys-45 and Cys-106 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 HMGB1 (HMGB1C23hC45hC106h), 2- disulfide HMGB1 (HMGB1C23-C45C106h) and 3- sulfonyl HMGB1 (HMGB1C23soC45soC106so).; Poly-ADP-ribosylated by PARP1 when secreted following stimulation with LPS (By similarity).; In vitro cleavage by CASP1 is liberating a HMG box 1-containing peptide which may mediate immunogenic activity; the peptide antagonizes apoptosis-induced immune tolerance. Can be proteolytically cleaved by a thrombin:thrombomodulin complex; reduces binding to heparin and proinflammatory activities (By similarity).

Subcellular Location

Nucleus, Cell membrane, Cytoplasm, Secreted.

UNIPROT

SwissProt: P09429 Human

Synonyms