Hmgb1
entrez
15289
canonical
uniprot
P63158
canonical
ensembl
ENSMUSG00000066551
resolver
ensp
ENSMUSP00000082682
resolver
ensp
ENSMUSP00000106131
resolver
ensp
ENSMUSP00000106132
resolver
enst
ENSMUST00000085546
resolver
enst
ENSMUST00000093196
resolver
enst
ENSMUST00000110505
resolver
genesymbol
Hmgb1
resolver
genesymbol_syn
Hmg-1
resolver
genesymbol_syn
Hmg1
resolver
uniprot
P07155
resolver
uniprot
P27109
resolver
uniprot
P27428
resolver
uniprot
Q58EV5
resolver
uniprot_entry
HMGB1_MOUSE
resolver
uniprot_entry
Q58EV5_MOUSE
resolver
uniprot_sec
P07155
resolver
uniprot_sec
P27109
resolver
uniprot_sec
P27428
resolver
amino_acid_sequence
MGKGDPKKPRGKMSSYAFFVQTCREEHKKKHPDASVNFSEFSKKCSERWKTMSAKEKGKFEDMAKADKARYEREMKTYIPPKGETKKKFKDPNAPKRPPSAFFLFCSEYRPKIKGEHPGLSIGDVAKKLGEMWNNTAADDKQPYEKKAAKLKEKYEKDIAAYRAKGKPDAAKKGVVKAEKSKKKKEEEDDEEDEEDEEEEEEEEDEDEEEDDDDE
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. 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 (PubMed:23446148, PubMed:23519706, PubMed:23994764, PubMed:25048472). Has proangiogenic activity (PubMed:16365390). May be involved in platelet activation. Binds to phosphatidylserine and phosphatidylethanolamide. Bound to RAGE mediates signaling for neuronal outgrowth. May play a role in accumulation of expanded polyglutamine (polyQ) proteins (By similarity). {ECO:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P12682, ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:16365390, 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. May be involved in nucleotide excision repair (NER), mismatch repair (MMR) and base excision repair (BER) pathways, and double strand break repair such as non-homologous end joining (NHEJ) (PubMed:17803946, PubMed:18650382). 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). In vitro can displace histone H1 from highly bent DNA. 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 (PubMed:16040616). Facilitates binding of TP53 to DNA (By similarity). Proposed to be involved in mitochondrial quality control and autophagy in a transcription-dependent fashion implicating HSPB1; however, this function has been questioned (PubMed:21641551, PubMed:24606906). Can modulate the activity of the telomerase complex and may be involved in telomere maintenance (PubMed:22544226). {ECO:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:16040616, ECO:0000269|PubMed:17803946, ECO:0000269|PubMed:18650382, ECO:0000269|PubMed:21641551, ECO:0000269|PubMed:22544226, ECO:0000269|PubMed:24606906}.; FUNCTION: In the cytoplasm proposed to dissociate the BECN1:BCL2 complex via competitive interaction with BECN1 leading to autophagy activation (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 (PubMed:25642769). In myeloid cells has a protective role against endotoxemia and bacterial infection by promoting autophagy (PubMed:24302768). Involved in endosomal translocation and activation of TLR9 in response to CpG-DNA in macrophages (PubMed:17548579). {ECO:0000250|UniProtKB:P09429, ECO:0000269|PubMed:17548579, ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:21395369, ECO:0000269|PubMed:24302768, ECO:0000269|PubMed:25642769}.; 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 (PubMed:17268551). 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 (PubMed:19890330). 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 (PubMed:17568691, PubMed:19264983, PubMed:21419643). Mediates the release of cytokines/chemokines such as TNF, IL-1, IL-6, IL-8, CCL2, CCL3, CCL4 and CXCL10 (PubMed:12110890, PubMed:17548579). 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 (By similarity). Contributes to tumor proliferation by association with ACER/RAGE (By similarity). Can bind to IL1-beta and signals through the IL1R1:IL1RAP receptor complex (By similarity). 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 (PubMed:18768881, PubMed:22204001). In adaptive immunity may be involved in enhancing immunity through activation of effector T-cells and suppression of regulatory T (TReg) cells (PubMed:21419643). 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 (PubMed:23108142). 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 (By similarity). 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 (By similarity). During macrophage activation by activated lymphocyte-derived self apoptotic DNA (ALD-DNA) promotes recruitment of ALD-DNA to endosomes (PubMed:25660970). {ECO:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:12110890, ECO:0000269|PubMed:17268551, ECO:0000269|PubMed:17568691, ECO:0000269|PubMed:18768881, ECO:0000269|PubMed:19264983, ECO:0000269|PubMed:21419643, ECO:0000269|PubMed:22204001, ECO:0000269|PubMed:22370717, ECO:0000269|PubMed:23108142, ECO:0000269|PubMed:25660970, ECO:0000305|PubMed:19890330}.
uniprot
proteins
mass_dalton
24894
uniprot
proteins
post_translational_modification
PTM: Acetylated on multiple sites upon stimulation with LPS (By similarity). Acetylation on lysine residues in the nuclear localization signals (NLS 1 and NLS 2) leads to cytoplasmic localization and subsequent secretion. 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}.; PTM: Phosphorylated at serine residues (PubMed:17114460). Phosphorylation in both NLS regions is required for cytoplasmic translocation followed by secretion (By similarity). {ECO:0000250|UniProtKB:P09429, ECO:0000269|PubMed:17114460}.; 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 HGMB1 (HMGB1C23hC45hC106h), 2- Disulfide HMGB1 (HMGB1C23-C45C106h) and 3- Sulfonyl HMGB1 (HMGB1C23soC45soC106so). {ECO:0000250|UniProtKB:P63159}.; PTM: Poly-ADP-ribosylated by PARP1 when secreted following stimulation with LPS (PubMed:18768881, PubMed:22204001). {ECO:0000269|PubMed:18768881, ECO:0000269|PubMed:22204001}.; 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 (By similarity). Can be proteolytically cleaved by a thrombin:thrombomodulin complex; reduces binding to heparin and pro-inflammatory activities. {ECO:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P10103}.; 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:0000250|UniProtKB:P09429}.
uniprot
proteins
protein_family
HMGB family
uniprot
proteins
pubmed
10391216
uniprot
proteins
pubmed
10398600
uniprot
proteins
pubmed
12110890
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16040616
uniprot
proteins
pubmed
16267105
uniprot
proteins
pubmed
1630928
uniprot
proteins
pubmed
16365390
uniprot
proteins
pubmed
17114460
uniprot
proteins
pubmed
17268551
uniprot
proteins
pubmed
17548579
uniprot
proteins
pubmed
17568691
uniprot
proteins
pubmed
17803946
uniprot
proteins
pubmed
18650382
uniprot
proteins
pubmed
18768881
uniprot
proteins
pubmed
19264983
uniprot
proteins
pubmed
19890330
uniprot
proteins
pubmed
20802146
uniprot
proteins
pubmed
20819940
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21319304
uniprot
proteins
pubmed
21395369
uniprot
proteins
pubmed
21419643
uniprot
proteins
pubmed
21641551
uniprot
proteins
pubmed
22105604
uniprot
proteins
pubmed
22204001
uniprot
proteins
pubmed
22370717
uniprot
proteins
pubmed
22544226
uniprot
proteins
pubmed
22842346
uniprot
proteins
pubmed
23108142
uniprot
proteins
pubmed
23446148
uniprot
proteins
pubmed
23519706
uniprot
proteins
pubmed
23806337
uniprot
proteins
pubmed
23994764
uniprot
proteins
pubmed
24302768
uniprot
proteins
pubmed
24606906
uniprot
proteins
pubmed
2461949
uniprot
proteins
pubmed
25048472
uniprot
proteins
pubmed
25642769
uniprot
proteins
pubmed
25660970
uniprot
proteins
pubmed
26078984
uniprot
proteins
pubmed
33380312
uniprot
proteins
pubmed
7961836
uniprot
proteins
pubmed
8180479
uniprot
proteins
pubmed
9047378
uniprot
proteins
pubmed
9184213
uniprot
proteins
sequence_length
215
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17114460, ECO:0000269|PubMed:20819940}. Cytoplasm {ECO:0000269|PubMed:17114460, ECO:0000269|PubMed:20819940}. Chromosome {ECO:0000269|PubMed:12110890}. Cell membrane {ECO:0000269|PubMed:2461949}; Peripheral membrane protein {ECO:0000269|PubMed:2461949}; Extracellular side {ECO:0000269|PubMed:2461949}. Endosome {ECO:0000269|PubMed:19890330}. Endoplasmic reticulum-Golgi intermediate compartment {ECO:0000305|PubMed:17548579}. Secreted {ECO:0000269|PubMed:21319304}. Note=In basal state predominantly nuclear. Shuttles between the cytoplasm and the nucleus (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 (PubMed:20802146). Passively released to the extracellular milieu from necrotic cells by diffusion, involving the fully reduced form which subsequently gets oxidized (PubMed:12110890). Also released from apoptotic cells (PubMed:25660970). Actively secreted 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, involving a nonconventional secretory process via secretory lysosomes (PubMed:17548579). Secreted by plasma cells in response to LPS (PubMed:21319304). Associated with the plasma membrane of filipodia in process-growing cells, and also deposited into the substrate-attached material (By similarity). Colocalizes with RIGI on endosomal membranes (PubMed:19890330). {ECO:0000250|UniProtKB:P09429, ECO:0000269|PubMed:12110890, ECO:0000269|PubMed:17114460, ECO:0000269|PubMed:17548579, ECO:0000269|PubMed:19890330, ECO:0000269|PubMed:20802146, ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:21319304, ECO:0000269|PubMed:22105604, ECO:0000269|PubMed:2461949, ECO:0000269|PubMed:25660970}.
uniprot
proteins