Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001340
UniProt IDP09429
Primary gene name(s)HMGB1
Synonym gene name(s)HMG1
Protein nameHigh mobility group protein B1
Protein functionMultifunctional 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(DJ 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. {ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P12682, ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:23303669, ECO:0000269|PubMed:25549101, ECO:0000305|PubMed:23446148, ECO:0000305|PubMed:23519706, ECO:0000305|PubMed:23994764, ECO:0000305|PubMed:25048472}.; 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(DJ 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. {ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:15014079, ECO:0000269|PubMed:16143102, ECO:0000269|PubMed:17803946, ECO:0000269|PubMed:19446504, ECO:0000269|PubMed:23063560, ECO:0000305|PubMed:19360789, ECO:0000305|PubMed:20123072}.; 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. {ECO:0000250|UniProtKB:P63158, ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:21395369}.; 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. {ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:12765338, ECO:0000269|PubMed:15607795, ECO:0000269|PubMed:15944249, ECO:0000269|PubMed:18250463, ECO:0000269|PubMed:18354232, ECO:0000269|PubMed:18631454, ECO:0000269|PubMed:19064698, ECO:0000269|PubMed:19264983, ECO:0000269|PubMed:20547845, ECO:0000269|PubMed:21660935, ECO:0000269|PubMed:22370717, ECO:0000269|PubMed:22473704, ECO:0000269|PubMed:24474694, ECO:0000269|PubMed:24971542, ECO:0000269|PubMed:25660311, ECO:0000269|Ref.8}.
Subcellular locationNucleus {ECO:0000269|PubMed:12231511, ECO:0000269|PubMed:17114460, ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:22869893}. Chromosome {ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P63159, ECO:0000305}. Cytoplasm {ECO:0000269|PubMed:11154118, ECO:0000269|PubMed:12231511, ECO:0000269|PubMed:17114460, ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:22869893}. Secreted {ECO:0000250|UniProtKB:P63158, ECO:0000269|PubMed:12231511, ECO:0000269|PubMed:14532127, ECO:0000269|PubMed:15944249, ECO:0000269|PubMed:19811284, ECO:0000269|PubMed:22869893}. Cell membrane {ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:11154118};
Peripheral membrane protein {ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:11154118};
Extracellular side {ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:11154118}. Endosome {ECO:0000250|UniProtKB:P63158}. Endoplasmic reticulum-Golgi intermediate compartment {ECO:0000250|UniProtKB:P63158}. 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}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P09429
Gene Ontology
(Biological Process)
Complete annatation
activation of innate immune response [GO:0002218];
apoptotic cell clearance [GO:0043277];
apoptotic DNA fragmentation [GO:0006309];
autophagy [GO:0006914];
base-excision repair [GO:0006284];
chromatin assembly [GO:0031497];
dendritic cell chemotaxis [GO:0002407];
DNA geometric change [GO:0032392];
DNA ligation involved in DNA repair [GO:0051103];
DNA recombination [GO:0006310];
DNA topological change [GO:0006265];
endothelial cell chemotaxis [GO:0035767];
endothelial cell proliferation [GO:0001935];
eye development [GO:0001654];
inflammatory response [GO:0006954];
inflammatory response to antigenic stimulus [GO:0002437];
innate immune response [GO:0045087];
lung development [GO:0030324];
macrophage activation involved in immune response [GO:0002281];
myeloid dendritic cell activation [GO:0001773];
negative regulation of apoptotic cell clearance [GO:2000426];
negative regulation of blood vessel endothelial cell migration [GO:0043537];
negative regulation of CD4-positive, alpha-beta T cell differentiation [GO:0043371];
negative regulation of interferon-gamma production [GO:0032689];
negative regulation of RNA polymerase II transcriptional preinitiation complex assembly [GO:0017055];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
neuron projection development [GO:0031175];
neutrophil clearance [GO:0097350];
plasmacytoid dendritic cell activation [GO:0002270];
positive regulation of activated T cell proliferation [GO:0042104];
positive regulation of apoptotic process [GO:0043065];
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043280];
positive regulation of cytosolic calcium ion concentration [GO:0007204];
positive regulation of dendritic cell differentiation [GO:2001200];
positive regulation of DNA binding [GO:0043388];
positive regulation of DNA ligation [GO:0051106];
positive regulation of ERK1 and ERK2 cascade [GO:0070374];
positive regulation of glycogen catabolic process [GO:0045819];
positive regulation of interferon-alpha production [GO:0032727];
positive regulation of interferon-beta production [GO:0032728];
positive regulation of interleukin-10 production [GO:0032733];
positive regulation of interleukin-12 production [GO:0032735];
positive regulation of interleukin-1 beta secretion [GO:0050718];
positive regulation of interleukin-1 secretion [GO:0050716];
positive regulation of interleukin-6 secretion [GO:2000778];
positive regulation of JNK cascade [GO:0046330];
positive regulation of MAPK cascade [GO:0043410];
positive regulation of mismatch repair [GO:0032425];
positive regulation of monocyte chemotaxis [GO:0090026];
positive regulation of myeloid cell differentiation [GO:0045639];
positive regulation of NIK/NF-kappaB signaling [GO:1901224];
positive regulation of sprouting angiogenesis [GO:1903672];
positive regulation of toll-like receptor 2 signaling pathway [GO:0034137];
positive regulation of toll-like receptor 4 signaling pathway [GO:0034145];
positive regulation of toll-like receptor 9 signaling pathway [GO:0034165];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of tumor necrosis factor production [GO:0032760];
positive regulation of wound healing [GO:0090303];
regulation of autophagy [GO:0010506];
regulation of nucleotide-excision repair [GO:2000819];
regulation of restriction endodeoxyribonuclease activity [GO:0032072];
regulation of T cell mediated immune response to tumor cell [GO:0002840];
regulation of tolerance induction [GO:0002643];
regulation of transcription from RNA polymerase II promoter [GO:0006357];
response to glucocorticoid [GO:0051384];
T-helper 1 cell activation [GO:0035711];
T-helper 1 cell differentiation [GO:0045063];
tumor necrosis factor secretion [GO:1990774];
V(DJ recombination [GO:0033151]
Gene Ontology
(Molecular Function)
Complete annatation
bubble DNA binding [GO:0000405];
calcium-dependent protein kinase regulator activity [GO:0010858];
chemoattractant activity [GO:0042056];
C-X-C chemokine binding [GO:0019958];
cytokine activity [GO:0005125];
damaged DNA binding [GO:0003684];
DNA binding, bending [GO:0008301];
DNA polymerase binding [GO:0070182];
double-stranded DNA binding [GO:0003690];
double-stranded RNA binding [GO:0003725];
four-way junction DNA binding [GO:0000400];
lipopolysaccharide binding [GO:0001530];
lyase activity [GO:0016829];
phosphatidylserine binding [GO:0001786];
poly(A RNA binding [GO:0044822];
protein kinase activator activity [GO:0030295];
RAGE receptor binding [GO:0050786];
repressing transcription factor binding [GO:0070491];
single-stranded DNA binding [GO:0003697];
single-stranded RNA binding [GO:0003727];
supercoiled DNA binding [GO:0097100];
transcription factor activity, sequence-specific DNA binding [GO:0003700];
transcription factor binding [GO:0008134]
Gene Ontology
(Cellular Component)
Complete annatation
cell surface [GO:0009986];
condensed chromosome [GO:0000793];
early endosome [GO:0005769];
endoplasmic reticulum-Golgi intermediate compartment [GO:0005793];
extracellular region [GO:0005576];
extracellular space [GO:0005615];
neuron projection [GO:0043005];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
plasma membrane [GO:0005886]
Protein-protein interaction109389
Phylogenetic treeP09429
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD30.2732019346793490.4092564787602520.531116161713169
AZA vs. DISU-0.3030575592999260.2305819128004050.817833353777248
AZA vs. IL7-0.02165834262951440.9099548362540440.999311006273513
AZA vs. SAHA-0.7278126088101330.002989129251565140.044087218164051
DISU vs. CD3-0.5887111031030560.10672651565220.196194572797716
DISU vs. IL70.272383137232910.2789960799325460.665828718441819
DISU vs. SAHA-0.4241913045551310.1453690473364140.49001496587052
DMSO vs. AZA-0.05303243894351740.7503928177223861
DMSO vs. CD3-0.3374545958611050.29788662105350.408266188698233
DMSO vs. DISU0.2482470075731690.3089084545354140.813570501546434
DMSO vs. IL70.03848560209100590.8298930817353980.963051812112721
DMSO vs. SAHA-0.6820046469682610.00401110743204580.0475995276443797
HIV vs. Mock in Activation-0.1913928173647480.770660901960250.999983755607037
HIV vs. Mock in Latency0.1750150576555430.2870664636042930.999834320637052
IL7 vs. CD3-0.2861963462053750.3771282226360720.513965072314061
SAHA vs. CD3-1.025774205972690.004108007494577630.0120583702655405
SAHA vs. IL7-0.7099139287446930.003683196988521490.0309134250584482
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.137902 0.388796
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.04 0.988 0.952 0.895 0.992
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
1.03 0.0223 -0.03 0.6432 -0.1 0.4617 T-cell activation at 20 hpi
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB05869 CTI-01 investigational unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2LY4 NMR - A=2-84.
2RTU NMR - A=1-84.
2YRQ NMR - A=1-166.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
HIV-1 virus replication enhanced by expression of human gene 18854154

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa03410 Base excision repair - Homo sapiens (human)