HMGB1 report

I. Expression across cell types

II. Expression across tissues

III. Associated gene sets

GO_0042104Biological processpositive regulation of activated T cell proliferation
GO_0006954Biological processinflammatory response
GO_0017055Biological processnegative regulation of RNA polymerase II transcription preinitiation complex assembly
GO_0050918Biological processpositive chemotaxis
GO_0033151Biological processV(D)J recombination
GO_0001773Biological processmyeloid dendritic cell activation
GO_1905564Biological processpositive regulation of vascular endothelial cell proliferation
GO_0032732Biological processpositive regulation of interleukin-1 production
GO_0002437Biological processinflammatory response to antigenic stimulus
GO_0043537Biological processnegative regulation of blood vessel endothelial cell migration
GO_0034165Biological processpositive regulation of toll-like receptor 9 signaling pathway
GO_0006265Biological processDNA topological change
GO_0032689Biological processnegative regulation of type II interferon production
GO_0006914Biological processautophagy
GO_0070374Biological processpositive regulation of ERK1 and ERK2 cascade
GO_0006303Biological processdouble-strand break repair via nonhomologous end joining
GO_0043371Biological processnegative regulation of CD4-positive, alpha-beta T cell differentiation
GO_0045087Biological processinnate immune response
GO_0006357Biological processregulation of transcription by RNA polymerase II
GO_0031175Biological processneuron projection development
GO_0007165Biological processsignal transduction
GO_0002840Biological processregulation of T cell mediated immune response to tumor cell
GO_0032425Biological processpositive regulation of mismatch repair
GO_0031507Biological processheterochromatin formation
GO_2000343Biological processpositive regulation of chemokine (C-X-C motif) ligand 2 production
GO_0043277Biological processapoptotic cell clearance
GO_0010508Biological processpositive regulation of autophagy
GO_0032757Biological processpositive regulation of interleukin-8 production
GO_2001200Biological processpositive regulation of dendritic cell differentiation
GO_0071222Biological processcellular response to lipopolysaccharide
GO_2000426Biological processnegative regulation of apoptotic cell clearance
GO_0032760Biological processpositive regulation of tumor necrosis factor production
GO_0032755Biological processpositive regulation of interleukin-6 production
GO_0002407Biological processdendritic cell chemotaxis
GO_0045063Biological processT-helper 1 cell differentiation
GO_0043536Biological processpositive regulation of blood vessel endothelial cell migration
GO_0002643Biological processregulation of tolerance induction
GO_0032072Biological processregulation of restriction endodeoxyribonuclease activity
GO_0046598Biological processpositive regulation of viral entry into host cell
GO_0007204Biological processpositive regulation of cytosolic calcium ion concentration
GO_0043388Biological processpositive regulation of DNA binding
GO_0006310Biological processDNA recombination
GO_0043065Biological processpositive regulation of apoptotic process
GO_0045944Biological processpositive regulation of transcription by RNA polymerase II
GO_0097350Biological processneutrophil clearance
GO_0051106Biological processpositive regulation of DNA ligation
GO_0046330Biological processpositive regulation of JNK cascade
GO_0032735Biological processpositive regulation of interleukin-12 production
GO_0035711Biological processT-helper 1 cell activation
GO_0090026Biological processpositive regulation of monocyte chemotaxis
GO_0032733Biological processpositive regulation of interleukin-10 production
GO_0043410Biological processpositive regulation of MAPK cascade
GO_0000122Biological processnegative regulation of transcription by RNA polymerase II
GO_0043280Biological processpositive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO_0002218Biological processactivation of innate immune response
GO_0032392Biological processDNA geometric change
GO_0009986Cellular componentcell surface
GO_1904813Cellular componentficolin-1-rich granule lumen
GO_0005768Cellular componentendosome
GO_0000793Cellular componentcondensed chromosome
GO_0005634Cellular componentnucleus
GO_0005576Cellular componentextracellular region
GO_0005654Cellular componentnucleoplasm
GO_0017053Cellular componenttranscription repressor complex
GO_0005793Cellular componentendoplasmic reticulum-Golgi intermediate compartment
GO_0035868Cellular componentalphav-beta3 integrin-HMGB1 complex
GO_0005615Cellular componentextracellular space
GO_0034774Cellular componentsecretory granule lumen
GO_0005783Cellular componentendoplasmic reticulum
GO_0140297Molecular functionDNA-binding transcription factor binding
GO_0048018Molecular functionreceptor ligand activity
GO_0000405Molecular functionbubble DNA binding
GO_0019958Molecular functionC-X-C chemokine binding
GO_0003690Molecular functiondouble-stranded DNA binding
GO_0061629Molecular functionRNA polymerase II-specific DNA-binding transcription factor binding
GO_0042056Molecular functionchemoattractant activity
GO_0097100Molecular functionsupercoiled DNA binding
GO_0005125Molecular functioncytokine activity
GO_0070182Molecular functionDNA polymerase binding
GO_0000976Molecular functiontranscription cis-regulatory region binding
GO_0001786Molecular functionphosphatidylserine binding
GO_0003723Molecular functionRNA binding
GO_0050786Molecular functionRAGE receptor binding
GO_0001530Molecular functionlipopolysaccharide binding
GO_0005515Molecular functionprotein binding
GO_0008301Molecular functionDNA binding, bending
GO_0003697Molecular functionsingle-stranded DNA binding
GO_0003714Molecular functiontranscription corepressor activity
GO_0005178Molecular functionintegrin binding
GO_0000400Molecular functionfour-way junction DNA binding
GO_0003713Molecular functiontranscription coactivator activity
GO_0016829Molecular functionlyase activity
GO_0003684Molecular functiondamaged DNA binding

IV. Literature review

[source]
Gene nameHMGB1
Protein nameHigh mobility group protein B1 (High mobility group protein 1) (HMG-1)
High mobility group protein B1 (High mobility group protein 1)
SynonymsHMG1
DescriptionFUNCTION: 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 a sensor and/or chaperone for immunogenic nucleic acids implicating the activation of TLR9-mediated immune responses, and mediates autophagy. Acts as a 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 . 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 . .; 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 . May have an enhancing role in nucleotide excision repair (NER) (By similarity). However, effects in NER using in vitro systems have been reported conflictingly . May be involved in mismatch repair (MMR) and base excision repair (BER) pathways . 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 . 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). .; FUNCTION: In the cytoplasm proposed to dissociate the BECN1:BCL2 complex via competitive interaction with BECN1 leading to autophagy activation . Involved in oxidative stress-mediated autophagy . 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). .; 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 . 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 . 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 . Promotes secretion of interferon-gamma by macrophage-stimulated natural killer (NK) cells in concert with other cytokines like IL-2 or IL-12 . TLR4 is proposed to be the primary receptor promoting macrophage activation and signaling through TLR4 seems to implicate LY96/MD-2 . 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 . Contributes to tumor proliferation by association with ACER/RAGE (By similarity). Can bind to IL1-beta and signals through the IL1R1:IL1RAP receptor complex . 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 . 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 . 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 . During macrophage activation by activated lymphocyte-derived self apoptotic DNA (ALD-DNA) promotes recruitment of ALD-DNA to endosomes (By similarity). .; 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 . Required for SARS-CoV-2 ORF3A-induced reticulophagy which induces endoplasmic reticulum stress and inflammatory responses and facilitates viral infection . .; FUNCTION: (Microbial infection) Associates with the influenza A viral protein NP in the nucleus of infected cells, promoting viral growth and enhancing the activity of the viral polymerase. .; FUNCTION: (Microbial infection) Promotes Epstein-Barr virus (EBV) latent-to-lytic switch by sustaining the expression of the viral transcription factor BZLF1 that acts as a molecular switch to induce the transition from the latent to the lytic or productive phase of the virus cycle. Mechanistically, participates in EBV reactivation through the NLRP3 inflammasome. .; FUNCTION: (Microbial infection) Facilitates dengue virus propagation via interaction with the untranslated regions of viral genome. In turn, this interaction with viral RNA may regulate secondary structure of dengue RNA thus facilitating its recognition by the replication complex. .

AccessionsENST00000405805.5
ENST00000339872.8
P09429
A0A286R9F1
Q5T7C4
ENST00000399494.5
ENST00000341423.10
A0A286R9D9
ENST00000399489.5
ENST00000326004.4