HMGB1 Gene (Protein Coding)

High Mobility Group Box 1

GC13M030456
GIFtS:
45
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 ident... See more...

Aliases for HMGB1 Gene

Aliases for HMGB1 Gene

  • High Mobility Group Box 1 2 3 5
  • High-Mobility Group (Nonhistone Chromosomal) Protein 1 2 3
  • Sulfoglucuronyl Carbohydrate Binding Protein 2 3
  • High Mobility Group Protein B1 3 4
  • High Mobility Group Protein 1 2 4
  • Amphoterin 2 3
  • HMG-1 3 4
  • SBP-1 2 3
  • HMG1 3 4
  • HMG3 2 3
  • High-Mobility Group Box 1 2
  • DKFZp686A04236 2
  • HMGB1 5

External Ids for HMGB1 Gene

Previous HGNC Symbols for HMGB1 Gene

  • HMG1

Previous GeneCards Identifiers for HMGB1 Gene

  • GC13M029013
  • GC13M025012
  • GC13M029963
  • GC13M028831
  • GC13M029930
  • GC13M031032
  • GC13M011850

Summaries for HMGB1 Gene

Entrez Gene Summary for HMGB1 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]

GeneCards Summary for HMGB1 Gene

HMGB1 (High Mobility Group Box 1) is a Protein Coding gene. Diseases associated with HMGB1 include 13Q12.3 Microdeletion Syndrome and Endophthalmitis. Among its related pathways are Activated TLR4 signalling and Activation of DNA fragmentation factor. Gene Ontology (GO) annotations related to this gene include chromatin binding. An important paralog of this gene is HMGB2.

UniProtKB/Swiss-Prot Summary for HMGB1 Gene

  • 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 (Ref.70). 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 (PubMed:27362237). 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 (PubMed:23519706, PubMed:23446148, PubMed:23994764, PubMed:25048472). Has proangiogdenic activity (By similarity). May be involved in platelet activation (By similarity). Binds to phosphatidylserine and phosphatidylethanolamide (By similarity). Bound to RAGE mediates signaling for neuronal outgrowth (By similarity). May play a role in accumulation of expanded polyglutamine (polyQ) proteins such as huntingtin (HTT) or TBP (PubMed:23303669, PubMed:25549101).
  • Nuclear functions are attributed to fully reduced HGMB1. Associates with chromatin and binds DNA with a preference to non-canonical DNA structures such as single-stranded DNA, DNA-containing cruciforms or bent structures, supercoiled DNA and ZDNA. Can bent DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters by enhancing transcription factor binding and/or bringing distant regulatory sequences into close proximity (PubMed:20123072). May have an enhancing role in nucleotide excision repair (NER) (By similarity). However, effects in NER using in vitro systems have been reported conflictingly (PubMed:19446504, PubMed:19360789). May be involved in mismatch repair (MMR) and base excision repair (BER) pathways (PubMed:15014079, PubMed:16143102, PubMed:17803946). May be involved in double strand break repair such as non-homologous end joining (NHEJ) (By similarity). Involved in V(D)J recombination by acting as a cofactor of the RAG complex: acts by stimulating cleavage and RAG protein binding at the 23 bp spacer of conserved recombination signal sequences (RSS) (By similarity). In vitro can displace histone H1 from highly bent DNA (By similarity). Can restructure the canonical nucleosome leading to relaxation of structural constraints for transcription factor-binding (By similarity). Enhances binding of sterol regulatory element-binding proteins (SREBPs) such as SREBF1 to their cognate DNA sequences and increases their transcriptional activities (By similarity). Facilitates binding of TP53 to DNA (PubMed:23063560). Proposed to be involved in mitochondrial quality control and autophagy in a transcription-dependent fashion implicating HSPB1; however, this function has been questioned (By similarity). Can modulate the activity of the telomerase complex and may be involved in telomere maintenance (By similarity).
  • In the cytoplasm proposed to dissociate the BECN1:BCL2 complex via competitive interaction with BECN1 leading to autophagy activation (PubMed:20819940). Involved in oxidative stress-mediated autophagy (PubMed:21395369). Can protect BECN1 and ATG5 from calpain-mediated cleavage and thus proposed to control their proautophagic and proapoptotic functions and to regulate the extent and severity of inflammation-associated cellular injury (By similarity). In myeloid cells has a protective role against endotoxemia and bacterial infection by promoting autophagy (By similarity). Involved in endosomal translocation and activation of TLR9 in response to CpG-DNA in macrophages (By similarity).
  • In the extracellular compartment (following either active secretion or passive release) involved in regulation of the inflammatory response. Fully reduced HGMB1 (which subsequently gets oxidized after release) in association with CXCL12 mediates the recruitment of inflammatory cells during the initial phase of tissue injury; the CXCL12:HMGB1 complex triggers CXCR4 homodimerization (PubMed:22370717). Induces the migration of monocyte-derived immature dendritic cells and seems to regulate adhesive and migratory functions of neutrophils implicating AGER/RAGE and ITGAM (By similarity). Can bind to various types of DNA and RNA including microbial unmethylated CpG-DNA to enhance the innate immune response to nucleic acids. Proposed to act in promiscuous DNA/RNA sensing which cooperates with subsequent discriminative sensing by specific pattern recognition receptors (By similarity). Promotes extracellular DNA-induced AIM2 inflammasome activation implicating AGER/RAGE (PubMed:24971542). Disulfide HMGB1 binds to transmembrane receptors, such as AGER/RAGE, TLR2, TLR4 and probably TREM1, thus activating their signal transduction pathways. Mediates the release of cytokines/chemokines such as TNF, IL-1, IL-6, IL-8, CCL2, CCL3, CCL4 and CXCL10 (PubMed:12765338, PubMed:18354232, PubMed:19264983, PubMed:20547845, PubMed:24474694). Promotes secretion of interferon-gamma by macrophage-stimulated natural killer (NK) cells in concert with other cytokines like IL-2 or IL-12 (PubMed:15607795). TLR4 is proposed to be the primary receptor promoting macrophage activation and signaling through TLR4 seems to implicate LY96/MD-2 (PubMed:20547845). In bacterial LPS- or LTA-mediated inflammatory responses binds to the endotoxins and transfers them to CD14 for signaling to the respective TLR4:LY96 and TLR2 complexes (PubMed:18354232, PubMed:21660935, PubMed:25660311). Contributes to tumor proliferation by association with ACER/RAGE (By similarity). Can bind to IL1-beta and signals through the IL1R1:IL1RAP receptor complex (PubMed:18250463). Binding to class A CpG activates cytokine production in plasmacytoid dendritic cells implicating TLR9, MYD88 and AGER/RAGE and can activate autoreactive B cells. Via HMGB1-containing chromatin immune complexes may also promote B cell responses to endogenous TLR9 ligands through a B-cell receptor (BCR)-dependent and ACER/RAGE-independent mechanism (By similarity). Inhibits phagocytosis of apoptotic cells by macrophages; the function is dependent on poly-ADP-ribosylation and involves binding to phosphatidylserine on the cell surface of apoptotic cells (By similarity). In adaptive immunity may be involved in enhancing immunity through activation of effector T cells and suppression of regulatory T (TReg) cells (PubMed:15944249, PubMed:22473704). In contrast, without implicating effector or regulatory T-cells, required for tumor infiltration and activation of T-cells expressing the lymphotoxin LTA:LTB heterotrimer thus promoting tumor malignant progression (By similarity). Also reported to limit proliferation of T-cells (By similarity). Released HMGB1:nucleosome complexes formed during apoptosis can signal through TLR2 to induce cytokine production (PubMed:19064698). Involved in induction of immunological tolerance by apoptotic cells; its pro-inflammatory activities when released by apoptotic cells are neutralized by reactive oxygen species (ROS)-dependent oxidation specifically on Cys-106 (PubMed:18631454). During macrophage activation by activated lymphocyte-derived self apoptotic DNA (ALD-DNA) promotes recruitment of ALD-DNA to endosomes (By similarity).
  • (Microbial infection) Critical for entry of human coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus NL63/HCoV-NL63. Regulates the expression of the pro-viral genes ACE2 and CTSL through chromatin modulation.

Gene Wiki entry for HMGB1 Gene

Additional gene information for HMGB1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HMGB1 Gene

Genomics for HMGB1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for HMGB1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HMGB1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HMGB1

Top Transcription factor binding sites by QIAGEN in the HMGB1 gene promoter:
  • GATA-1
  • GATA-2
  • GATA-3
  • STAT3
  • TBP
  • TFIID

Genomic Locations for HMGB1 Gene

Latest Assembly
chr13:30,456,704-30,617,597
(GRCh38/hg38)
Size:
160,894 bases
Orientation:
Minus strand

Previous Assembly
chr13:31,030,841-31,191,734
(GRCh37/hg19 by Entrez Gene)
Size:
160,894 bases
Orientation:
Minus strand

chr13:31,032,884-31,191,734
(GRCh37/hg19 by Ensembl)
Size:
158,851 bases
Orientation:
Minus strand

Genomic View for HMGB1 Gene

Genes around HMGB1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HMGB1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HMGB1 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for HMGB1 Gene

Proteins for HMGB1 Gene

Products:

  1. Antibodies for research
  2. Protein products for research
  3. Assay products for research

  • Protein details for HMGB1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P09429-HMGB1_HUMAN
    Recommended name:
    High mobility group protein B1
    Protein Accession:
    P09429
    Secondary Accessions:
    • A5D8W9
    • Q14321
    • Q5T7C3
    • Q6IBE1

    Protein attributes for HMGB1 Gene

    Size:
    215 amino acids
    Molecular mass:
    24894 Da
    Quaternary structure:
    • Interacts (fully reduced HMGB1) with CXCL12; probably in a 1:2 ratio involving two molecules of CXCL12, each interacting with one HMG box of HMGB1; inhibited by glycyrrhizin (PubMed:22370717). Associates with the TLR4:LY96 receptor complex (PubMed:20547845). Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2 (By similarity). Interacts (in cytoplasm upon starvation) with BECN1; inhibits the interaction of BECN1 and BCL2 leading to promotion of autophagy (PubMed:20819940). Interacts with KPNA1; involved in nuclear import (PubMed:17114460). Interacts with SREBF1, TLR2, TLR4, TLR9, PTPRZ1, APEX1, FEN1, POLB, TERT (By similarity). Interacts with IL1B, AGER, MSH2, XPA, XPC, HNF1A, TP53 (PubMed:15014079, PubMed:18250463, PubMed:18160415, PubMed:19446504, PubMed:24474694, PubMed:23063560). Interacts with CD24; the probable CD24:SIGLEC10 complex is proposed to inhibit HGMB1-mediated tissue damage immune response (PubMed:19264983). Interacts with THBD; prevents HGMB1 interaction with ACER/RAGE and inhibits HGMB1 proinflammatory activity (PubMed:15841214). Interacts with HAVCR2; impairs HMGB1 binding to B-DNA and likely HMGB1-mediated innate immune response (By similarity). Interacts with XPO1; mediating nuclear export (By similarity). Interacts with HTT (wild-type and mutant HTT with expanded polyglutamine repeat) (PubMed:23303669).
    • (Microbial infection) Interacts with adenovirus protein pVII; this interaction immobilizes HMGB1 on chromatin, thus preventing its release from cell and subsequent inflammation activation.
    Miscellaneous:
    • Proposed to contribute to the pathogenesis of various chronic inflammatory and autoimmune diseases, and cancer. High serum levels are found in several inflammatory events including sepsis, rheumatoid arthritis, artherosclerosis chronic kidney disease, systemic lupus erythematosus (SLE). Seems to be implicated in other diseases characterized by cell death and damage, including diabetes and Alzheimer's disease. Its nucleosome-associated release during secondary necrosis may play a role in SLE (PubMed:19064698). During chemotherapy can mediate regrowth and metastasis of remaining cells in a AGER/RAGE-dependent manner (PubMed:23040637). Purified HMG box 1 acts as a specific antagonist to HGMB1 pro-inflammatory activities (PubMed:14695889).

    Three dimensional structures from OCA and Proteopedia for HMGB1 Gene

neXtProt entry for HMGB1 Gene

Protein Expression for HMGB1 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for HMGB1 Gene

  • Phosphorylated at serine residues. Phosphorylation in both NLS regions is required for cytoplasmic translocation followed by secretion (PubMed:17114460).
  • Acetylated on multiple sites upon stimulation with LPS (PubMed:22801494). 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 (PubMed:24474694). Can be proteolytically cleaved by a thrombin:thrombomodulin complex; reduces binding to heparin and proinflammatory activities (By similarity).
  • Ubiquitination at Lys43 and Lys128
  • Modification sites at PhosphoSitePlus

Other Protein References for HMGB1 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibodies for research

No data available for DME Specific Peptides for HMGB1 Gene

Domains & Families for HMGB1 Gene

Gene Families for HMGB1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for HMGB1 Gene

InterPro:
Blocks:
  • High mobility group proteins HMG1 and HMG2

Suggested Antigen Peptide Sequences for HMGB1 Gene

GenScript: Design optimal peptide antigens:
  • High mobility group protein 1 (HMGB1_HUMAN)
  • High mobility group protein HMG1 (Q9NYD7_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P09429

UniProtKB/Swiss-Prot:

HMGB1_HUMAN :
  • HMG box 2 mediates proinflammatory cytokine-stimulating activity and binding to TLR4 (PubMed:12765338, PubMed:20547845). However, not involved in mediating immunogenic activity in the context of apoptosis-induced immune tolerance (PubMed:24474694).
  • Belongs to the HMGB family.
Domain:
  • HMG box 2 mediates proinflammatory cytokine-stimulating activity and binding to TLR4 (PubMed:12765338, PubMed:20547845). However, not involved in mediating immunogenic activity in the context of apoptosis-induced immune tolerance (PubMed:24474694).
  • The acidic C-terminal domain forms a flexible structure which can reversibly interact intramolecularily with the HMG boxes and modulate binding to DNA and other proteins (PubMed:23063560).
Family:
  • Belongs to the HMGB family.
genes like me logo Genes that share domains with HMGB1: view

Function for HMGB1 Gene

Products:

  1. Animal Models for research
  2. CRISPR products for research
  3. miRNA products for research
  4. Inhibitory RNAs for research
  5. Clone products for research
  6. Cell Lines for research

Molecular function for HMGB1 Gene

UniProtKB/Swiss-Prot Function:
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 (Ref.70). 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 (PubMed:27362237). 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 (PubMed:23519706, PubMed:23446148, PubMed:23994764, PubMed:25048472). Has proangiogdenic activity (By similarity). May be involved in platelet activation (By similarity). Binds to phosphatidylserine and phosphatidylethanolamide (By similarity). Bound to RAGE mediates signaling for neuronal outgrowth (By similarity). May play a role in accumulation of expanded polyglutamine (polyQ) proteins such as huntingtin (HTT) or TBP (PubMed:23303669, PubMed:25549101).
UniProtKB/Swiss-Prot Function:
Nuclear functions are attributed to fully reduced HGMB1. Associates with chromatin and binds DNA with a preference to non-canonical DNA structures such as single-stranded DNA, DNA-containing cruciforms or bent structures, supercoiled DNA and ZDNA. Can bent DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters by enhancing transcription factor binding and/or bringing distant regulatory sequences into close proximity (PubMed:20123072). May have an enhancing role in nucleotide excision repair (NER) (By similarity). However, effects in NER using in vitro systems have been reported conflictingly (PubMed:19446504, PubMed:19360789). May be involved in mismatch repair (MMR) and base excision repair (BER) pathways (PubMed:15014079, PubMed:16143102, PubMed:17803946). May be involved in double strand break repair such as non-homologous end joining (NHEJ) (By similarity). Involved in V(D)J recombination by acting as a cofactor of the RAG complex: acts by stimulating cleavage and RAG protein binding at the 23 bp spacer of conserved recombination signal sequences (RSS) (By similarity). In vitro can displace histone H1 from highly bent DNA (By similarity). Can restructure the canonical nucleosome leading to relaxation of structural constraints for transcription factor-binding (By similarity). Enhances binding of sterol regulatory element-binding proteins (SREBPs) such as SREBF1 to their cognate DNA sequences and increases their transcriptional activities (By similarity). Facilitates binding of TP53 to DNA (PubMed:23063560). Proposed to be involved in mitochondrial quality control and autophagy in a transcription-dependent fashion implicating HSPB1; however, this function has been questioned (By similarity). Can modulate the activity of the telomerase complex and may be involved in telomere maintenance (By similarity).
UniProtKB/Swiss-Prot Function:
In the cytoplasm proposed to dissociate the BECN1:BCL2 complex via competitive interaction with BECN1 leading to autophagy activation (PubMed:20819940). Involved in oxidative stress-mediated autophagy (PubMed:21395369). Can protect BECN1 and ATG5 from calpain-mediated cleavage and thus proposed to control their proautophagic and proapoptotic functions and to regulate the extent and severity of inflammation-associated cellular injury (By similarity). In myeloid cells has a protective role against endotoxemia and bacterial infection by promoting autophagy (By similarity). Involved in endosomal translocation and activation of TLR9 in response to CpG-DNA in macrophages (By similarity).
UniProtKB/Swiss-Prot Function:
In the extracellular compartment (following either active secretion or passive release) involved in regulation of the inflammatory response. Fully reduced HGMB1 (which subsequently gets oxidized after release) in association with CXCL12 mediates the recruitment of inflammatory cells during the initial phase of tissue injury; the CXCL12:HMGB1 complex triggers CXCR4 homodimerization (PubMed:22370717). Induces the migration of monocyte-derived immature dendritic cells and seems to regulate adhesive and migratory functions of neutrophils implicating AGER/RAGE and ITGAM (By similarity). Can bind to various types of DNA and RNA including microbial unmethylated CpG-DNA to enhance the innate immune response to nucleic acids. Proposed to act in promiscuous DNA/RNA sensing which cooperates with subsequent discriminative sensing by specific pattern recognition receptors (By similarity). Promotes extracellular DNA-induced AIM2 inflammasome activation implicating AGER/RAGE (PubMed:24971542). Disulfide HMGB1 binds to transmembrane receptors, such as AGER/RAGE, TLR2, TLR4 and probably TREM1, thus activating their signal transduction pathways. Mediates the release of cytokines/chemokines such as TNF, IL-1, IL-6, IL-8, CCL2, CCL3, CCL4 and CXCL10 (PubMed:12765338, PubMed:18354232, PubMed:19264983, PubMed:20547845, PubMed:24474694). Promotes secretion of interferon-gamma by macrophage-stimulated natural killer (NK) cells in concert with other cytokines like IL-2 or IL-12 (PubMed:15607795). TLR4 is proposed to be the primary receptor promoting macrophage activation and signaling through TLR4 seems to implicate LY96/MD-2 (PubMed:20547845). In bacterial LPS- or LTA-mediated inflammatory responses binds to the endotoxins and transfers them to CD14 for signaling to the respective TLR4:LY96 and TLR2 complexes (PubMed:18354232, PubMed:21660935, PubMed:25660311). Contributes to tumor proliferation by association with ACER/RAGE (By similarity). Can bind to IL1-beta and signals through the IL1R1:IL1RAP receptor complex (PubMed:18250463). Binding to class A CpG activates cytokine production in plasmacytoid dendritic cells implicating TLR9, MYD88 and AGER/RAGE and can activate autoreactive B cells. Via HMGB1-containing chromatin immune complexes may also promote B cell responses to endogenous TLR9 ligands through a B-cell receptor (BCR)-dependent and ACER/RAGE-independent mechanism (By similarity). Inhibits phagocytosis of apoptotic cells by macrophages; the function is dependent on poly-ADP-ribosylation and involves binding to phosphatidylserine on the cell surface of apoptotic cells (By similarity). In adaptive immunity may be involved in enhancing immunity through activation of effector T cells and suppression of regulatory T (TReg) cells (PubMed:15944249, PubMed:22473704). In contrast, without implicating effector or regulatory T-cells, required for tumor infiltration and activation of T-cells expressing the lymphotoxin LTA:LTB heterotrimer thus promoting tumor malignant progression (By similarity). Also reported to limit proliferation of T-cells (By similarity). Released HMGB1:nucleosome complexes formed during apoptosis can signal through TLR2 to induce cytokine production (PubMed:19064698). Involved in induction of immunological tolerance by apoptotic cells; its pro-inflammatory activities when released by apoptotic cells are neutralized by reactive oxygen species (ROS)-dependent oxidation specifically on Cys-106 (PubMed:18631454). During macrophage activation by activated lymphocyte-derived self apoptotic DNA (ALD-DNA) promotes recruitment of ALD-DNA to endosomes (By similarity).
UniProtKB/Swiss-Prot Function:
(Microbial infection) Critical for entry of human coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus NL63/HCoV-NL63. Regulates the expression of the pro-viral genes ACE2 and CTSL through chromatin modulation.
UniProtKB/Swiss-Prot Induction:
(Microbial infection) Protein levels increase upon infection by human coronavirus SARS-CoV-2.

Phenotypes From GWAS Catalog for HMGB1 Gene

Gene Ontology (GO) - Molecular Function for HMGB1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000400 four-way junction DNA binding ISS --
GO:0000405 bubble DNA binding ISS --
GO:0000976 transcription regulatory region sequence-specific DNA binding IDA 19158276
GO:0001530 lipopolysaccharide binding IDA 21660935
GO:0001786 phosphatidylserine binding IDA 18768881
genes like me logo Genes that share ontologies with HMGB1: view
genes like me logo Genes that share phenotypes with HMGB1: view

Animal Models for research

miRNA for HMGB1 Gene

miRTarBase miRNAs that target HMGB1

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HMGB1

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for HMGB1 Gene

Localization for HMGB1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HMGB1 Gene

Nucleus. Chromosome. Cytoplasm. Secreted. Cell membrane. Peripheral membrane protein. Extracellular side. Endosome. Endoplasmic reticulum-Golgi intermediate compartment. Note=In basal state predominantly nuclear. Shuttles between the cytoplasm and the nucleus (PubMed:12231511, PubMed:17114460). Translocates from the nucleus to the cytoplasm upon autophagy stimulation (PubMed:20819940). Release from macrophages in the extracellular milieu requires the activation of NLRC4 or NLRP3 inflammasomes (By similarity). Passively released to the extracellular milieu from necrotic cells by diffusion, involving the fully reduced HGMB1 which subsequently gets oxidized (PubMed:19811284). Also released from apoptotic cells (PubMed:16855214, PubMed:18631454). Active secretion from a variety of immune and non-immune cells such as macrophages, monocytes, neutrophils, dendritic cells and natural killer cells in response to various stimuli such as LPS and cytokines involves a nonconventional secretory process via secretory lysosomes (PubMed:12231511, PubMed:14532127, PubMed:15944249). Secreted by plasma cells in response to LPS (By similarity). Found on the surface of activated platelets (PubMed:11154118). An increased chromatin association is observed when associated with the adenovirus protein pVII (PubMed:27362237). {ECO:0000250 UniProtKB:P63158, ECO:0000269 PubMed:11154118, ECO:0000269 PubMed:12231511, ECO:0000269 PubMed:14532127, ECO:0000269 PubMed:15944249, ECO:0000269 PubMed:16855214, ECO:0000269 PubMed:17114460, ECO:0000269 PubMed:18631454, ECO:0000269 PubMed:19811284, ECO:0000269 PubMed:20819940, ECO:0000269 PubMed:27362237, ECO:0000305 PubMed:20123072}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HMGB1 gene
Compartment Confidence
plasma membrane 5
extracellular 5
nucleus 5
mitochondrion 3
endosome 3
cytosol 3
cytoskeleton 2
endoplasmic reticulum 2
lysosome 2
peroxisome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for HMGB1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin IBA --
GO:0000793 condensed chromosome IDA 12925773
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space ISS --
GO:0005634 nucleus IEA,ISS --
genes like me logo Genes that share ontologies with HMGB1: view

Pathways & Interactions for HMGB1 Gene

PathCards logo

SuperPathways for HMGB1 Gene

SuperPathway Contained pathways
1 Activated TLR4 signalling
Toll Like Receptor 9 (TLR9) Cascade
.94
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
.94
Activated TLR4 signalling
.91
Toll Like Receptor 4 (TLR4) Cascade
.91
MyD88 cascade initiated on plasma membrane
.88
Toll Like Receptor 10 (TLR10) Cascade
.88
Toll Like Receptor 5 (TLR5) Cascade
.88
MyD88 dependent cascade initiated on endosome
.86
Toll Like Receptor 7/8 (TLR7/8) Cascade
.86
MyD88-independent TLR3/TLR4 cascade
.86
Toll Like Receptor 3 (TLR3) Cascade
.86
TRIF-mediated TLR3/TLR4 signaling
.86
MyD88-Mal cascade initiated on plasma membrane
.85
Toll Like Receptor 2 (TLR2) Cascade
.85
Toll Like Receptor TLR1-TLR2 Cascade
.85
Toll Like Receptor TLR6-TLR2 Cascade
.85
Toll-Like Receptors Cascades
.82
Regulation of TLR by endogenous ligand
.01
2 Cytosolic sensors of pathogen-associated DNA
RIP-mediated NFkB activation via ZBP1
.84
ZBP1(DAI) mediated induction of type I IFNs
.84
TRAF6 mediated NF-kB activation
.53
TAK1 activates NFkB by phosphorylation and activation of IKKs complex
.47
Cytosolic sensors of pathogen-associated DNA
.37
DEx/H-box helicases activate type I IFN and inflammatory cytokines production
.01
3 Innate Immune System
Immune System
.61
Innate Immune System
.61
Neutrophil degranulation
.38
4 Activation of DNA fragmentation factor
Apoptosis induced DNA fragmentation
.01
Activation of DNA fragmentation factor
-
5 CDK-mediated phosphorylation and removal of Cdc6
Apoptosis
.31
Programmed Cell Death
.31
genes like me logo Genes that share pathways with HMGB1: view

Pathways by source for HMGB1 Gene

1 Sino Biological pathway for HMGB1 Gene
1 PharmGKB pathway for HMGB1 Gene
1 Qiagen pathway for HMGB1 Gene
  • HMGB1 Pathway
1 Cell Signaling Technology pathway for HMGB1 Gene

SIGNOR curated interactions for HMGB1 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for HMGB1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IMP 19158276
GO:0001654 eye development IEA --
GO:0001773 myeloid dendritic cell activation ISS --
GO:0001934 positive regulation of protein phosphorylation IEA --
GO:0001935 endothelial cell proliferation IEA --
genes like me logo Genes that share ontologies with HMGB1: view

Drugs & Compounds for HMGB1 Gene

Products:

  1. Drug products for research

(29) Drugs for HMGB1 Gene - From: DrugBank and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
chloroquine Approved, Investigational, Vet_approved Pharma Target, inhibitor 224
Ethyl pyruvate Investigational Pharma Target 0

(26) Additional Compounds for HMGB1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with HMGB1: view

Transcripts for HMGB1 Gene

Products:

  1. CRISPR products for research
  2. miRNA products for research
  3. Inhibitory RNAs for research
  4. Clone products for research

mRNA/cDNA for HMGB1 Gene

7 REFSEQ mRNAs :
29 NCBI additional mRNA sequence :
8 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HMGB1

Alternative Splicing Database (ASD) splice patterns (SP) for HMGB1 Gene

No ASD Table

Relevant External Links for HMGB1 Gene

GeneLoc Exon Structure for
HMGB1

Expression for HMGB1 Gene

Products:

  1. Primer products for research
  2. Gene Expression Assays for research

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HMGB1 Gene

mRNA expression in normal human tissues for HMGB1 Gene
mRNA expression by GTEx for HMGB1 GenemRNA expression by BioGPS for HMGB1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

  • Tonsil (Hematopoietic System)

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for HMGB1 Gene



Protein tissue co-expression partners for HMGB1 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HMGB1

SOURCE GeneReport for Unigene cluster for HMGB1 Gene:

Hs.434102

mRNA Expression by UniProt/SwissProt for HMGB1 Gene:

P09429-HMGB1_HUMAN
Tissue specificity: Ubiquitous. Expressed in platelets (PubMed:11154118).

Evidence on tissue expression from TISSUES for HMGB1 Gene

  • Nervous system(5)
  • Liver(5)
  • Intestine(4.9)
  • Lung(4.8)
  • Blood(4.7)
  • Skin(4.6)
  • Kidney(4.5)
  • Pancreas(4.4)
  • Eye(4.3)
  • Muscle(4.3)
  • Heart(4.2)
  • Spleen(3.9)
  • Stomach(3.8)
  • Lymph node(3.7)
  • Bone(3.6)
  • Bone marrow(3.5)
  • Thyroid gland(3.1)
  • Adrenal gland(2.8)
  • Gall bladder(2.7)
genes like me logo Genes that share expression patterns with HMGB1: view

Primer products for research

No data available for mRNA differential expression in normal tissues , Protein differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for HMGB1 Gene

Orthologs for HMGB1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for HMGB1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia HMGB1 29 30
  • 99.69 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Hmgb1 30
  • 99 (a)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia -- 30
  • 98 (a)
 OneToMany
-- 30
  • 85 (a)
 OneToMany
-- 30
  • 83 (a)
 OneToMany
-- 30
  • 80 (a)
 OneToMany
Cow
(Bos Taurus)
 Mammalia -- 30
  • 98 (a)
 OneToMany
HMGB1 29 30
  • 94.26 (n)
 OneToMany
Dog
(Canis familiaris)
 Mammalia HMGB1 29 30
  • 95.19 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia LOC685520 29
  • 90.34 (n)
Platypus
(Ornithorhynchus anatinus)
 Mammalia HMGB1 30
  • 62 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves HMGB1 29 30
  • 85.8 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia HMGB1 30
  • 87 (a)
 OneToOne
Zebrafish
(Danio rerio)
 Actinopterygii hmgb1b 30
  • 82 (a)
 OneToMany
hmgb1a 29 30
  • 77.51 (n)
 OneToMany
wufb23c02 29
Rainbow Trout
(Oncorhynchus mykiss)
 Actinopterygii Omy.8407 29
Species where no ortholog for HMGB1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for HMGB1 Gene

ENSEMBL:
Gene Tree for HMGB1 (if available)
TreeFam:
Gene Tree for HMGB1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HMGB1: view image
Alliance of Genome Resources:
Additional Orthologs for HMGB1

Paralogs for HMGB1 Gene

Paralogs for HMGB1 Gene

(12) SIMAP similar genes for HMGB1 Gene using alignment to 4 proteins:

  • HMGB1_HUMAN
  • Q5T7C0_HUMAN
  • Q5T7C4_HUMAN
  • Q5T7C6_HUMAN

Pseudogenes.org Pseudogenes for HMGB1 Gene

genes like me logo Genes that share paralogs with HMGB1: view

Variants for HMGB1 Gene

Products:

  1. SNP Genotyping and Copy Number Assays for research

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HMGB1 Gene

SNP ID Clinical significance and condition Chr 13 pos Variation AA Info Type
776790 Benign: not provided 30,462,544(-) A/.
NM_002128.7(HMGB1):c.465= (p.Tyr155=) 		SYNONYMOUS_VARIANT,NO_SEQUENCE_ALTERATION
rs1171559344 Likely Benign: not provided 30,463,266(-) G/A
NM_002128.7(HMGB1):c.237C>T (p.Ile79=) 		SYNONYMOUS
rs201813276 Likely Benign: not provided 30,461,464(-) T/C
NM_002128.7(HMGB1):c.541A>G (p.Ser181Gly) 		MISSENSE_VARIANT,THREE_PRIME_UTR
VAR_046451 Gastric-carcinoma cell line p.Gly11Arg
VAR_046452 Gastric-carcinoma cell line p.Ala149Glu

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for HMGB1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for HMGB1 Gene

Variant ID Type Subtype PubMed ID
nsv1112631 CNV deletion 24896259
nsv473694 CNV novel sequence insertion 20440878
nsv561395 CNV loss 21841781
nsv952534 CNV deletion 24416366
nsv976101 CNV duplication 23825009

Variation tolerance for HMGB1 Gene

Residual Variation Intolerance Score: 50.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.01; 20.74% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HMGB1 Gene

Human Gene Mutation Database (HGMD)
HMGB1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HMGB1
Leiden Open Variation Database (LOVD)
HMGB1

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HMGB1 Gene

Disorders for HMGB1 Gene

MalaCards: The human disease database

(50) MalaCards diseases for HMGB1 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
13q12.3 microdeletion syndrome
  • del(13)(q12.3)
endophthalmitis
paraquat poisoning
toxic shock syndrome
  • toxic shock
staphylococcal toxic shock syndrome
  • bacterial toxic-shock syndrome
- elite association - COSMIC cancer census association via MalaCards
Search HMGB1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for HMGB1

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with HMGB1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HMGB1 Gene

Publications for HMGB1 Gene

  1. The genetic variation of the human HMGB1 gene. (PMID: 17610420) Kornblit B … Garred P (Tissue antigens 2007) 3 4 22 40
  2. Oxidation of the alarmin high-mobility group box 1 protein (HMGB1) during apoptosis. (PMID: 19811284) Urbonaviciute V … Voll RE (Autoimmunity 2009) 3 4 22
  3. Human HMGB1 directly facilitates interactions between nucleotide excision repair proteins on triplex-directed psoralen interstrand crosslinks. (PMID: 19446504) Lange SS … Vasquez KM (DNA repair 2009) 3 4 22
  4. Proteomic screen defines the hepatocyte nuclear factor 1alpha-binding partners and identifies HMGB1 as a new cofactor of HNF1alpha. (PMID: 18160415) Yu M … Yang XM (Nucleic acids research 2008) 3 4 22
  5. High mobility group box 1 protein binding to lipopolysaccharide facilitates transfer of lipopolysaccharide to CD14 and enhances lipopolysaccharide-mediated TNF-alpha production in human monocytes. (PMID: 18354232) Youn JH … Shin JS (Journal of immunology (Baltimore, Md. : 1950) 2008) 3 4 22

ExternalLinks

View latest publications for HMGB1 gene in Mastermind

Products for HMGB1 Gene

  • Addgene plasmids for HMGB1