HMGB1
entrez
3146
canonical
uniprot
P09429
canonical
ensembl
ENSG00000189403
resolver
ensp
ENSP00000343040
resolver
ensp
ENSP00000345347
resolver
ensp
ENSP00000369904
resolver
ensp
ENSP00000382412
resolver
ensp
ENSP00000382417
resolver
ensp
ENSP00000384678
resolver
ensp
ENSP00000567899
resolver
ensp
ENSP00000567900
resolver
ensp
ENSP00000567901
resolver
ensp
ENSP00000567902
resolver
ensp
ENSP00000567903
resolver
ensp
ENSP00000567904
resolver
ensp
ENSP00000567905
resolver
ensp
ENSP00000567906
resolver
ensp
ENSP00000567907
resolver
ensp
ENSP00000567908
resolver
ensp
ENSP00000567909
resolver
ensp
ENSP00000567910
resolver
ensp
ENSP00000567911
resolver
ensp
ENSP00000567912
resolver
ensp
ENSP00000567913
resolver
ensp
ENSP00000567914
resolver
ensp
ENSP00000567915
resolver
ensp
ENSP00000597840
resolver
ensp
ENSP00000597841
resolver
ensp
ENSP00000597844
resolver
ensp
ENSP00000640376
resolver
ensp
ENSP00000640377
resolver
ensp
ENSP00000668746
resolver
ensp
ENSP00000773705
resolver
enst
ENST00000326004
resolver
enst
ENST00000339872
resolver
enst
ENST00000341423
resolver
enst
ENST00000399489
resolver
enst
ENST00000399494
resolver
enst
ENST00000405805
resolver
enst
ENST00000897840
resolver
enst
ENST00000897841
resolver
enst
ENST00000897842
resolver
enst
ENST00000897843
resolver
enst
ENST00000897844
resolver
enst
ENST00000897845
resolver
enst
ENST00000897846
resolver
enst
ENST00000897847
resolver
enst
ENST00000897848
resolver
enst
ENST00000897849
resolver
enst
ENST00000897850
resolver
enst
ENST00000897851
resolver
enst
ENST00000897852
resolver
enst
ENST00000897853
resolver
enst
ENST00000897854
resolver
enst
ENST00000897855
resolver
enst
ENST00000897856
resolver
enst
ENST00000927781
resolver
enst
ENST00000927782
resolver
enst
ENST00000927785
resolver
enst
ENST00000970317
resolver
enst
ENST00000970318
resolver
genesymbol
HMGB1
resolver
genesymbol_syn
HMG1
resolver
hgnc
HGNC:4983
resolver
uniprot
A5D8W9
resolver
uniprot
B7Z965
resolver
uniprot
Q14321
resolver
uniprot
Q5T7C3
resolver
uniprot
Q5T7C4
resolver
uniprot
Q6IBE1
resolver
uniprot_entry
B7Z965_HUMAN
resolver
uniprot_entry
HMGB1_HUMAN
resolver
uniprot_entry
Q5T7C4_HUMAN
resolver
uniprot_sec
A5D8W9
resolver
uniprot_sec
Q14321
resolver
uniprot_sec
Q5T7C3
resolver
uniprot_sec
Q6IBE1
resolver
amino_acid_sequence
MGKGDPKKPRGKMSSYAFFVQTCREEHKKKHPDASVNFSEFSKKCSERWKTMSAKEKGKFEDMAKADKARYEREMKTYIPPKGETKKKFKDPNAPKRPPSAFFLFCSEYRPKIKGEHPGLSIGDVAKKLGEMWNNTAADDKQPYEKKAAKLKEKYEKDIAAYRAKGKPDAAKKGVVKAEKSKKKKEEEEDEEDEEDEEEEEDEEDEDEEEDDDDE
uniprot
proteins
function
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 (PubMed:33147444). 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 (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 (PubMed:34743181). 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:23446148, PubMed:23519706, 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:0000269|PubMed:27362237, ECO:0000269|PubMed:33147444, ECO:0000269|PubMed:34743181, 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:19360789, PubMed:19446504). 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). {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}.; FUNCTION: (Microbial infection) Critical for entry of human coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus NL63/HCoV-NL63 (PubMed:33147444). Regulates the expression of the pro-viral genes ACE2 and CTSL through chromatin modulation (PubMed:33147444). Required for SARS-CoV-2 ORF3A-induced reticulophagy which induces endoplasmic reticulum stress and inflammatory responses and facilitates viral infection (PubMed:35239449). {ECO:0000269|PubMed:33147444, ECO:0000269|PubMed:35239449}.; 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. {ECO:0000269|PubMed:22696656}.; 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. {ECO:0000269|PubMed:34922257}.; 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. {ECO:0000269|PubMed:34971702}.
uniprot
proteins
mass_dalton
24894
uniprot
proteins
mutagenesis
MUTAGEN 35; /note="S->A: Greatly reduces phosphorylation, nuclear localization; when associated with A-39; A-42; A-46; A-53 and A-181."; /evidence="ECO:0000269|PubMed:17114460"; MUTAGEN 35; /note="S->E: Cytoplasmic localization (phosphorylation mimicking); when associated with E-39; E-42; E-46; E-53 and E-181."; /evidence="ECO:0000269|PubMed:17114460"; MUTAGEN 39; /note="S->A: Greatly reduces phosphorylation, nuclear localization; when associated with A-35; A-42; A-46; A-53 and A-181."; /evidence="ECO:0000269|PubMed:17114460"; MUTAGEN 39; /note="S->E: Cytoplasmic localization (phosphorylation mimicking); when associated with E-35; E-42; E-46; E-53 and E-181."; /evidence="ECO:0000269|PubMed:17114460"; MUTAGEN 42; /note="S->A: Greatly reduces phosphorylation, nuclear localization; when associated with A-35; A-39; A-46; A-53 and A-181."; /evidence="ECO:0000269|PubMed:17114460"; MUTAGEN 42; /note="S->E: Cytoplasmic localization (phosphorylation mimicking); when associated with E-35; E-39; E-46; E-53 and E-181."; /evidence="ECO:0000269|PubMed:17114460"; MUTAGEN 46; /note="S->A: Greatly reduces phosphorylation, nuclear localization; when associated with A-35; A-39; A-42; A-53 and A-181."; /evidence="ECO:0000269|PubMed:17114460"; MUTAGEN 46; /note="S->E: Cytoplasmic localization (phosphorylation mimicking); when associated with E-35; E-39; E-42; E-53 and E-181."; /evidence="ECO:0000269|PubMed:17114460"; MUTAGEN 53; /note="S->A: Greatly reduces phosphorylation, nuclear localization; when associated with A-35; A-39; A-42; A-46 and A-181."; /evidence="ECO:0000269|PubMed:17114460"; MUTAGEN 53; /note="S->E: Cytoplasmic localization (phosphorylation mimicking); when associated with E-35; E-39; E-42; E-46 and E-181."; /evidence="ECO:0000269|PubMed:17114460"; MUTAGEN 67; /note="D->A: Abolishes cleavage by CASP1 and impairs ability to antagonize apoptosis-induced immune tolerance."; /evidence="ECO:0000269|PubMed:24474694"; MUTAGEN 106; /note="C->S: Inhibits oxidation-dependent inactivation of immunostimmulatory activity in apoptotic cells."; /evidence="ECO:0000269|PubMed:18631454"; MUTAGEN 181; /note="S->A: Greatly reduces phosphorylation, nuclear localization; when associated with A-35; A-39; A-42; A-46 and A-53."; /evidence="ECO:0000269|PubMed:17114460"; MUTAGEN 181; /note="S->E: Cytoplasmic localization (phosphorylation mimicking); when associated with E-35; E-39; E-42; E-46 and E-53."; /evidence="ECO:0000269|PubMed:17114460
uniprot
proteins
post_translational_modification
PTM: Phosphorylated at serine residues. Phosphorylation in both NLS regions is required for cytoplasmic translocation followed by secretion (PubMed:17114460). {ECO:0000269|PubMed:17114460}.; PTM: 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). {ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:22801494}.; PTM: 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). {ECO:0000269|PubMed:16962095, ECO:0000269|PubMed:19811284, ECO:0000269|PubMed:22869893, ECO:0000305|PubMed:24531895}.; PTM: Poly-ADP-ribosylated by PARP1 when secreted following stimulation with LPS (By similarity). {ECO:0000250|UniProtKB:P63158}.; PTM: 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 pro-inflammatory activities (By similarity). {ECO:0000250|UniProtKB:P10103, ECO:0000269|PubMed:24474694}.; PTM: Forms covalent cross-links mediated by transglutaminase TGM2, between a glutamine and the epsilon-amino group of a lysine residue, forming homopolymers and heteropolymers. {ECO:0000269|PubMed:29618516}.
uniprot
proteins
protein_family
HMGB family
uniprot
proteins
pubmed
11154118
uniprot
proteins
pubmed
12231511
uniprot
proteins
pubmed
12765338
uniprot
proteins
pubmed
14532127
uniprot
proteins
pubmed
14695889
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15014079
uniprot
proteins
pubmed
15057823
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15607795
uniprot
proteins
pubmed
15841214
uniprot
proteins
pubmed
15944249
uniprot
proteins
pubmed
16143102
uniprot
proteins
pubmed
16855214
uniprot
proteins
pubmed
16962095
uniprot
proteins
pubmed
17114460
uniprot
proteins
pubmed
17610420
uniprot
proteins
pubmed
17803946
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18160415
uniprot
proteins
pubmed
18250463
uniprot
proteins
pubmed
18354232
uniprot
proteins
pubmed
18631454
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19064698
uniprot
proteins
pubmed
19264983
uniprot
proteins
pubmed
19360789
uniprot
proteins
pubmed
19446504
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19811284
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20123072
uniprot
proteins
pubmed
20547845
uniprot
proteins
pubmed
20819940
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21395369
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21660935
uniprot
proteins
pubmed
22370717
uniprot
proteins
pubmed
22473704
uniprot
proteins
pubmed
22696656
uniprot
proteins
pubmed
22801494
uniprot
proteins
pubmed
22869893
uniprot
proteins
pubmed
23040637
uniprot
proteins
pubmed
23063560
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23303669
uniprot
proteins
pubmed
23446148
uniprot
proteins
pubmed
23519706
uniprot
proteins
pubmed
23994764
uniprot
proteins
pubmed
24220159
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24427810
uniprot
proteins
pubmed
24474694
uniprot
proteins
pubmed
24531895
uniprot
proteins
pubmed
24971542
uniprot
proteins
pubmed
25048472
uniprot
proteins
pubmed
25549101
uniprot
proteins
pubmed
25660311
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26078984
uniprot
proteins
pubmed
27362237
uniprot
proteins
pubmed
28190768
uniprot
proteins
pubmed
2922262
uniprot
proteins
pubmed
29618516
uniprot
proteins
pubmed
33147444
uniprot
proteins
pubmed
34743181
uniprot
proteins
pubmed
34922257
uniprot
proteins
pubmed
34971702
uniprot
proteins
pubmed
35239449
uniprot
proteins
pubmed
36585612
uniprot
proteins
pubmed
8661151
uniprot
proteins
pubmed
9036861
uniprot
proteins
pubmed
9150946
uniprot
proteins
sequence_length
215
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12231511, ECO:0000269|PubMed:17114460, ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:22696656, ECO:0000269|PubMed:22869893, ECO:0000269|PubMed:27362237, ECO:0000269|PubMed:29618516, ECO:0000269|PubMed:33147444}. 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, ECO:0000269|PubMed:29618516, ECO:0000269|PubMed:33147444, ECO:0000269|PubMed:34971702}. 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, ECO:0000269|PubMed:33147444}. 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 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 LOCATION: Endoplasmic reticulum {ECO:0000269|PubMed:35239449}. Note=(Microbial infection) SARS-COV-2 ORF3A promotes HMGB1 translocation from the nucleus to the cytoplasm where it is recruited by and colocalizes with ORF3A at the endoplasmic reticulum. {ECO:0000269|PubMed:35239449}.
uniprot
proteins