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Aliases for HMGB1 Gene

Aliases for HMGB1 Gene

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

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 Adenosquamous Gallbladder Carcinoma. Among its related pathways are Activated TLR4 signalling and Immune System. GO annotations related to this gene include poly(A) RNA binding and chromatin binding. An important paralog of this gene is HMGB2.

UniProtKB/Swiss-Prot 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. 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. 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).

Gene Wiki entry for HMGB1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HMGB1 Gene

Genomics for HMGB1 Gene

Regulatory Elements for HMGB1 Gene

Enhancers for HMGB1 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH13F030462 1.1 ENCODE 30.3 +152.8 152775 5.3 HDGF ARID4B SIN3A FEZF1 DMAP1 ZNF2 YY1 CBX5 ZNF207 FOS HMGB1 LINC01058 USPL1 KATNAL1 UBL3 GC13M030460 MFAP1P1
GH13F030790 1.6 VISTA Ensembl ENCODE 16.5 -174.7 -174671 3.0 CTCF ESRRA SAP130 SIN3A THRB ZIC2 RAD21 RARA TEAD3 E2F1 HMGB1 USPL1 MEDAG LINC00398 ALOX5AP
GH13F030393 1.6 FANTOM5 Ensembl ENCODE 10.8 +222.3 222302 3.0 PKNOX1 MLX WRNIP1 ARID4B SIN3A DMAP1 YY1 FOS ZHX2 REST USPL1 HMGB1 KATNAL1 LINC00426 LINC01058
GH13F030445 1.2 Ensembl ENCODE 14.2 +171.7 171696 1.8 TBP TBL1XR1 KLF17 BMI1 ZNF48 RAD21 GLIS2 ETV6 CREM USF2 HMGB1 GC13M030443 GC13P030460
GH13F030576 1.4 FANTOM5 Ensembl ENCODE 11.3 +40.3 40297 1.8 TBL1XR1 JUN CEBPG BMI1 EBF1 RAD21 ZNF664 CBX5 EED NFE2 USPL1 HMGB1 KATNAL1 TEX26 PTPN2P2
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around HMGB1 on UCSC Golden Path with GeneCards custom track

Promoters for HMGB1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000513763 -103 5401 CREB3L1 MLX ZFP64 YBX1 FEZF1 DMAP1 YY1 SLC30A9 ZNF143 ZNF263

Genomic Location for HMGB1 Gene

Chromosome:
13
Start:
30,456,704 bp from pter
End:
30,617,597 bp from pter
Size:
160,894 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 StructureGene Density

RefSeq DNA sequence for HMGB1 Gene

Proteins for HMGB1 Gene

  • 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 immume 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).
    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 Alzheimers disease. Its nucleosome-associated release during secondory necrosis may play a role in SLE (PubMed:19064698). During chemotherapy can mediate regrowth and metastasis of remaining cells in a AGER/RAGE-depenedent manner (PubMed:23040637). Purified HMG box 1 acts as a specific antogonist to HGMB1 pro-imflammatory activities (PubMed:14695889).

    Three dimensional structures from OCA and Proteopedia for HMGB1 Gene

neXtProt entry for HMGB1 Gene

Post-translational modifications for HMGB1 Gene

  • 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).
  • 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).
  • Phosphorylated at serine residues. Phosphorylation in both NLS regions is required for cytoplasmic translocation followed by secretion (PubMed:17114460).
  • Poly-ADP-ribosylated by PARP1 when secreted following stimulation with LPS (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).
  • Ubiquitination at Lys 43, Lys 112, and Lys 128
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for HMGB1 Gene

Domains & Families for HMGB1 Gene

Gene Families for HMGB1 Gene

Protein Domains for HMGB1 Gene

Suggested Antigen Peptide Sequences for HMGB1 Gene

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).
  • Contains 2 HMG box DNA-binding domains.
Family:
  • Belongs to the HMGB family.
genes like me logo Genes that share domains with HMGB1: view

Function for HMGB1 Gene

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. 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. 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).

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:0001530 lipopolysaccharide binding IDA 21660935
GO:0001786 phosphatidylserine binding IDA 18768881
GO:0003677 DNA binding IEA --
genes like me logo Genes that share ontologies with HMGB1: view
genes like me logo Genes that share phenotypes with HMGB1: view

Animal Model Products

miRNA for HMGB1 Gene

miRTarBase miRNAs that target HMGB1

Inhibitory RNA Products

Flow Cytometry Products

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 apoptic 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). {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: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
extracellular 5
nucleus 5
plasma membrane 4
endosome 3
cytoskeleton 2
mitochondrion 2
cytosol 2
lysosome 2
endoplasmic reticulum 1

Gene Ontology (GO) - Cellular Components for HMGB1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000793 condensed chromosome IDA 12925773
GO:0005576 extracellular region IEA,TAS --
GO:0005615 extracellular space IDA 19841752
GO:0005634 nucleus IEA,IDA 8339930
GO:0005654 nucleoplasm TAS --
genes like me logo Genes that share ontologies with HMGB1: view

Pathways & Interactions for HMGB1 Gene

SuperPathways for HMGB1 Gene

SuperPathway Contained pathways
1 Activated TLR4 signalling
2 Cytosolic sensors of pathogen-associated DNA
3 Apoptosis induced DNA fragmentation
4 Regulation of activated PAK-2p34 by proteasome mediated degradation
.32
5 Immune System
genes like me logo Genes that share pathways with HMGB1: view

Pathways by source for HMGB1 Gene

Gene Ontology (GO) - Biological Process for HMGB1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription from RNA polymerase II promoter 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

No data available for SIGNOR curated interactions for HMGB1 Gene

Drugs & Compounds for HMGB1 Gene

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
CTI-01 Investigational Pharma Target 0

(25) 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

Unigene Clusters for HMGB1 Gene

High mobility group box 1:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

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

No ASD Table

Relevant External Links for HMGB1 Gene

GeneLoc Exon Structure for
HMGB1
ECgene alternative splicing isoforms for
HMGB1

Expression for HMGB1 Gene

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

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



Protein tissue co-expression partners for HMGB1 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of HMGB1 Gene:

HMGB1

SOURCE GeneReport for Unigene cluster for HMGB1 Gene:

Hs.434102

mRNA Expression by UniProt/SwissProt for HMGB1 Gene:

P09429-HMGB1_HUMAN
Tissue specificity: Ubiquituous. Expressed in platelets (PubMed:11154118).
genes like me logo Genes that share expression patterns with HMGB1: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Protein differential expression in normal tissues 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 34 35
  • 99.69 (n)
mouse
(Mus musculus)
Mammalia Hmgb1 35
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia -- 35
  • 98 (a)
OneToMany
HMGB1 35 34
  • 94.26 (n)
OneToMany
oppossum
(Monodelphis domestica)
Mammalia -- 35
  • 98 (a)
OneToMany
-- 35
  • 85 (a)
OneToMany
-- 35
  • 83 (a)
OneToMany
-- 35
  • 80 (a)
OneToMany
dog
(Canis familiaris)
Mammalia HMGB1 34 35
  • 95.19 (n)
rat
(Rattus norvegicus)
Mammalia LOC685520 34
  • 90.34 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia HMGB1 35
  • 62 (a)
OneToOne
chicken
(Gallus gallus)
Aves HMGB1 34 35
  • 85.8 (n)
lizard
(Anolis carolinensis)
Reptilia HMGB1 35
  • 87 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii hmgb1b 35
  • 82 (a)
OneToMany
hmgb1a 34 35
  • 77.51 (n)
wufb23c02 34
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8407 34
Species where no ortholog for HMGB1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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 squirt (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)

Paralogs for HMGB1 Gene

Paralogs for HMGB1 Gene

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

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

Variants for HMGB1 Gene

Sequence variations from dbSNP and Humsavar for HMGB1 Gene

SNP ID Clin Chr 13 pos Sequence Context AA Info Type
VAR_046451 Gastric-carcinoma cell line
VAR_046452 Gastric-carcinoma cell line
VAR_046454 Gastric-carcinoma cell line
rs1028729 -- 30,588,219(-) GTGTT(A/G)CTATG intron-variant
rs10444627 -- 30,461,053(+) AACTA(C/T)CATCC utr-variant-3-prime

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)

Relevant External Links for HMGB1 Gene

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

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

Disorders for HMGB1 Gene

MalaCards: The human disease database

(18) MalaCards diseases for HMGB1 Gene - From: DISEASES, Novoseek, and GeneCards

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

Relevant External Links for HMGB1

Genetic Association Database (GAD)
HMGB1
Human Genome Epidemiology (HuGE) Navigator
HMGB1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
HMGB1
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. Oxidation of the alarmin high-mobility group box 1 protein (HMGB1) during apoptosis. (PMID: 19811284) Urbonaviciute V. … Voll R.E. (Autoimmunity 2009) 3 4 22 64
  2. Proteomic screen defines the hepatocyte nuclear factor 1alpha-binding partners and identifies HMGB1 as a new cofactor of HNF1alpha. (PMID: 18160415) Yu M. … Yang X.M. (Nucleic Acids Res. 2008) 3 4 22 64
  3. The genetic variation of the human HMGB1 gene. (PMID: 17610420) Kornblit B. … Garred P. (Tissue Antigens 2007) 3 4 46 64
  4. The extracellular release of HMGB1 during apoptotic cell death. (PMID: 16855214) Bell C.W. … Pisetsky D.S. (Am. J. Physiol., Cell Physiol. 2006) 3 4 22 64
  5. The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway. (PMID: 12231511) Gardella S. … Rubartelli A. (EMBO Rep. 2002) 3 4 22 64

Products for HMGB1 Gene

Sources for HMGB1 Gene

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