HMGB1
High mobility group protein B1
Also known as: DKFZp686A04236, HMG1, HMG3, HMGB1_HUMAN, SBP-1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P09429
- Gene
- HMGB1
- Ensembl
- ENSG00000189403
- Chromosome
- 13
- Canonical length
- 215 aa
- Protein class
- Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins
- Subcellular location
- Nucleoplasm
- Secretome location
- Secreted to blood
OverviewNCBI Gene
This gene encodes a protein that belongs to the High Mobility Group-box superfamily. The encoded non-histone, nuclear DNA-binding protein regulates transcription, and is involved in organization of DNA. This protein plays a role in several cellular processes, including inflammation, cell differentiation and tumor cell migration. Multiple pseudogenes of this gene have been identified. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2015]
Canonical amino-acid sequenceUniProt
215 residues, UniProt reviewed canonical sequence.
>P09429|HMGB1
1 MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKKCSERWK TMSAKEKGKF
61 EDMAKADKAR YEREMKTYIP PKGETKKKFK DPNAPKRPPS AFFLFCSEYR PKIKGEHPGL
121 SIGDVAKKLG EMWNNTAADD KQPYEKKAAK LKEKYEKDIA AYRAKGKPDA AKKGVVKAEK
181 SKKKKEEEED EEDEEDEEEE EDEEDEDEEE DDDDELocalizationUniProt · AlphaFold · HPA
Whether an antibody against HMGB1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.48
- Highest tissue expression
- 801 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 801 nTPM
- thymus: 702 nTPM
- tonsil: 588 nTPM
- lymph node: 494 nTPM
- spinal cord: 374 nTPM
- skeletal muscle: 312 nTPM
Single-cell type
- erythrocyte progenitors: 1,881 nCPM
- platelets: 1,550 nCPM
- megakaryocyte progenitors: 1,467 nCPM
- megakaryocytes: 1,403 nCPM
- monocyte progenitors: 1,272 nCPM
- extravillous trophoblasts: 1,164 nCPM
Immune cell
- total PBMC: 759 nTPM
- basophil: 757 nTPM
- eosinophil: 660 nTPM
- T-reg: 497 nTPM
- neutrophil: 453 nTPM
- NK-cell: 447 nTPM
Brain region
- white matter: 259 nTPM
- medulla oblongata: 224 nTPM
- spinal cord: 215 nTPM
- hypothalamus: 215 nTPM
- basal ganglia: 214 nTPM
- midbrain: 202 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about HMGB1.
Disease | GeneticClinVar
6 pathogenic / likely-pathogenic of 37 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Brachyphalangy, polydactyly, and tibial aplasia/hypoplasia
- HMGB1-associated disorder
- Neurodevelopmental disorder
Disease | ImmuneIEDB
Conditions an epitope on HMGB1 was assayed in.
- rheumatoid arthritis B cell
- systemic lupus erythematosus B cell
- dermatomyositis B cell
Disease | AutoantibodyPubMed
Conditions in which antibodies against HMGB1 are reported. Each links to that disease's full target list.
ReferencesPubMed · IEDB
Publications for HMGB1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
25 publications
- High mobility group box 1 (HMGB1) and anti-HMGB1 antibodies and their relation to disease characteristics in systemic lupus erythematosus.
2011 · Arthritis Res Ther · RCR 3.7 · 129 citations - High-mobility group box 1 represents a potential marker of disease activity and novel therapeutic target in systemic lupus erythematosus.
2011 · J Intern Med · RCR 2 · 70 citations - Prevalence and characterization of novel pANCA, antibodies to the high mobility group non-histone chromosomal proteins HMG1 and HMG2, in systemic rheumatic diseases.
1998 · J Rheumatol · RCR 1.6 · 61 citations - Emergence of autoantibodies to HMGB1 is associated with survival in patients with septic shock.
2011 · Intensive Care Med · RCR 1.5 · 51 citations - Protective targeting of high mobility group box chromosomal protein 1 in a spontaneous arthritis model.
2010 · Arthritis Rheum · RCR 1.3 · 47 citations
Show 20 more
- Prevalence and characterization of perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) directed against HMG1 and HMG2 in ulcerative colitis (UC).
1998 · Clin Exp Immunol · RCR 1.3 · 47 citations - Elevated serum autoantibody against high mobility group box 1 as a potent surrogate biomarker for amyotrophic lateral sclerosis.
2013 · Neurobiol Dis · RCR 1.2 · 36 citations - Lupus antibodies to the HMGB1 chromosomal protein: epitope mapping and association with disease activity.
2009 · Mod Rheumatol · RCR 1 · 37 citations - Is serum HMGB1 a biomarker in ANCA-associated vasculitis?
2013 · Arthritis Res Ther · RCR 1 · 29 citations - Quantification of Serum High Mobility Group Box 1 by Liquid Chromatography/High-Resolution Mass Spectrometry: Implications for Its Role in Immunity, Inflammation, and Cancer.
2018 · Anal Chem · RCR 0.9 · 22 citations - Antibodies against High Mobility Group Box protein-1 (HMGB1) versus other anti-nuclear antibody fine-specificities and disease activity in systemic lupus erythematosus.
2015 · Arthritis Res Ther · RCR 0.9 · 27 citations - HMGB1/anti-HMGB1 antibodies define a molecular signature of early stages of HIV-Associated Neurocognitive Isorders (HAND).
2017 · Heliyon · RCR 0.8 · 19 citations - Relationship between sex and antibodies to high mobility group proteins 1 and 2 in juvenile idiopathic arthritis.
2000 · J Rheumatol · RCR 0.8 · 31 citations - Primary pulmonary hypertension: immunogenetic response to high-mobility group (HMG) proteins and histone.
1996 · Clin Exp Immunol · RCR 0.6 · 26 citations - Lack of IL-17 Receptor A signaling aggravates lymphoproliferation in C57BL/6 lpr mice.
2019 · Sci Rep · RCR 0.6 · 13 citations - HMGB1-Neutralizing IgM Antibody Is a Normal Component of Blood Plasma.
2020 · J Immunol · RCR 0.6 · 10 citations - Anti-HMGB1 antibody is a potential characteristic autoantibody for Sjögren's syndrome.
2022 · Sci Rep · RCR 0.6 · 6 citations - Endogenous HMGB1 is required in endotoxin tolerance.
2013 · J Surg Res · RCR 0.5 · 13 citations - Autoantibodies to the transcriptional factor SOX13 in primary biliary cirrhosis compared with other diseases.
2002 · J Autoimmun · RCR 0.4 · 19 citations - Emergence of antibodies endowed with proteolytic activity against High-mobility group box 1 protein (HMGB1) in patients surviving septic shock.
2020 · Cell Immunol · RCR 0.3 · 6 citations - Association of anti-CLIC2 and anti-HMGB1 autoantibodies with higher disease activity in systemic lupus erythematosus patients.
2017 · J Postgrad Med · RCR 0.3 · 6 citations - The role of anti-HMGB1 antibody and anti-moesin antibody in ANCA-associated vasculitis.
2023 · Med Clin (Barc) · RCR 0.2 · 2 citations - Role of antinuclear antibodies in experimental and clinical liver transplantation.
2006 · Transplant Proc · RCR 0.2 · 9 citations - Apoptotic cells, autoantibodies, and the role of HMGB1 in the subcellular localization of an autoantigen.
2005 · J Autoimmun · RCR 0.2 · 8 citations - Age-related decline in HMGB1-neutralizing IgM autoantibody response impairs resistance to high-fat diet in mice.
2025 · J Immunol
Reference: B cellIEDB
2 publications
- Disordered Antigens and Epitope Overlap Between Anti-Citrullinated Protein Antibodies and Rheumatoid Factor in Rheumatoid Arthritis.
2020 · Arthritis Rheumatol · RCR 1.7 · 30 citations - Lupus antibodies to the HMGB1 chromosomal protein: epitope mapping and association with disease activity.
2009 · Mod Rheumatol · RCR 1 · 37 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.47
- gnomAD pLI
- 0.82
- gnomAD missense Z
- 2.69
- DepMap mean gene effect
- -0.5
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- activation of innate immune response
- apoptotic cell clearance
- autophagy
- base-excision repair
- cellular response to interleukin-7
- cellular response to lipopolysaccharide
- chromatin remodeling
- dendritic cell chemotaxis
- DNA geometric change
- DNA recombination
- DNA topological change
- double-strand break repair
- double-strand break repair via nonhomologous end joining
- endothelial cell chemotaxis
- endothelial cell proliferation
- eye development
- glycogen catabolic process
- heterochromatin formation
- inflammatory response
- inflammatory response to antigenic stimulus
- innate immune response
- lung development
- macrophage activation involved in immune response
- myeloid cell differentiation
- myeloid dendritic cell activation
- myeloid progenitor cell differentiation
- negative regulation of apoptotic cell clearance
- negative regulation of blood vessel endothelial cell migration
- negative regulation of CD4-positive, alpha-beta T cell differentiation
- negative regulation of RNA polymerase II transcription preinitiation complex assembly
- negative regulation of transcription by RNA polymerase II
- negative regulation of type II interferon production
- neuron projection development
- neutrophil clearance
- plasmacytoid dendritic cell activation
- positive regulation of activated T cell proliferation
- positive regulation of apoptotic process
- positive regulation of autophagy
- positive regulation of blood vessel endothelial cell migration
- positive regulation of chemokine (C-X-C motif) ligand 2 production
- positive regulation of cytosolic calcium ion concentration
- positive regulation of dendritic cell differentiation
- positive regulation of DNA binding
- positive regulation of ERK1 and ERK2 cascade
- positive regulation of glycogen catabolic process
- positive regulation of interferon-alpha production
- positive regulation of interferon-beta production
- positive regulation of interleukin-1 beta production
- positive regulation of interleukin-1 production
- positive regulation of interleukin-10 production
- positive regulation of interleukin-12 production
- positive regulation of interleukin-6 production
- positive regulation of interleukin-8 production
- positive regulation of JNK cascade
- positive regulation of MAPK cascade
- positive regulation of mismatch repair
- positive regulation of monocyte chemotactic protein-1 production
- positive regulation of monocyte chemotaxis
- positive regulation of myeloid cell differentiation
- positive regulation of non-canonical NF-kappaB signal transduction
- positive regulation of sprouting angiogenesis
- positive regulation of toll-like receptor 2 signaling pathway
- positive regulation of toll-like receptor 4 signaling pathway
- positive regulation of toll-like receptor 9 signaling pathway
- positive regulation of transcription by RNA polymerase II
- positive regulation of tumor necrosis factor production
- positive regulation of vascular endothelial cell proliferation
- positive regulation of viral entry into host cell
- positive regulation of wound healing
- regulation of nucleotide-excision repair
- regulation of tolerance induction
- response to glucocorticoid
- T-helper 1 cell activation
- T-helper 1 cell differentiation
- transcription by RNA polymerase II
- V(D)J recombination
- positive regulation of myeloid progenitor cell differentiation
- regulation of restriction endodeoxyribonuclease activity
- regulation of T cell mediated immune response to tumor cell
Molecular functions
- bubble DNA binding
- C-X-C chemokine binding
- chemoattractant activity
- cytokine activity
- damaged DNA binding
- DNA binding, bending
- DNA polymerase binding
- DNA-binding transcription factor binding
- double-stranded DNA binding
- double-stranded RNA binding
- four-way junction DNA binding
- integrin binding
- lipopolysaccharide binding
- lyase activity
- phosphatidylserine binding
- protein kinase activator activity
- RAGE receptor binding
- receptor ligand activity
- RNA binding
- RNA polymerase II-specific DNA-binding transcription factor binding
- single-stranded DNA binding
- single-stranded RNA binding
- supercoiled DNA binding
- transcription cis-regulatory region binding
- transcription coactivator activity
- transcription corepressor activity
- calcium-dependent protein kinase regulator activity
Cellular components
- alphav-beta3 integrin-HMGB1 complex
- cell surface
- condensed chromosome
- early endosome
- endoplasmic reticulum
- endoplasmic reticulum-Golgi intermediate compartment
- extracellular region
- extracellular space
- ficolin-1-rich granule lumen
- neuron projection
- nucleoplasm
- nucleus
- secretory granule lumen
- transcription repressor complex
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
- Acetylation
- Adaptive immunity
- ADP-ribosylation
- Autophagy
- Cell membrane
- Chemotaxis
- Chromosome
- Cytoplasm
- Disulfide bond
- DNA damage
- DNA recombination
- DNA repair
- DNA-binding
- Endoplasmic reticulum
- Endosome
- Host-virus interaction
- Immunity
- Inflammatory response
- Innate immunity
- Isopeptide bond
- Membrane
- Nucleus
- Oxidation
- Phosphoprotein
- Repeat
- Secreted
InteractionsUniProt · HPA
Protein binding partners of HMGB1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads HMGB1 as an antibody target. Whether an autoantibody or antibody against HMGB1 could matter depends on whether native HMGB1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
HMGB1 is annotated at the cell surface, where native HMGB1 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label HMGB1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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