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Protein

High mobility group protein B1

Gene

Hmgb1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 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).By similarity4 Publications1 Publication
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).By similarity6 Publications
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).By similarity5 Publications
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:22204001, PubMed:18768881). 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).By similarity1 Publication10 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi9 – 7971HMG box 1PROSITE-ProRule annotationAdd
BLAST
DNA bindingi95 – 16369HMG box 2PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • bent DNA binding Source: MGI
  • bubble DNA binding Source: AgBase
  • calcium-dependent protein kinase regulator activity Source: MGI
  • crossed form four-way junction DNA binding Source: MGI
  • cytokine activity Source: MGI
  • DNA binding, bending Source: AgBase
  • double-stranded DNA binding Source: UniProtKB
  • double-stranded RNA binding Source: UniProtKB
  • four-way junction DNA binding Source: AgBase
  • heparin binding Source: UniProtKB-KW
  • lipopolysaccharide binding Source: Ensembl
  • lyase activity Source: Ensembl
  • open form four-way junction DNA binding Source: MGI
  • phosphatidylserine binding Source: BHF-UCL
  • poly(A) RNA binding Source: Ensembl
  • protein kinase activator activity Source: MGI
  • single-stranded RNA binding Source: UniProtKB
  • supercoiled DNA binding Source: AgBase
  • transcription factor activity, sequence-specific DNA binding Source: Ensembl

GO - Biological processi

  • activation of innate immune response Source: Ensembl
  • activation of protein kinase activity Source: GOC
  • adaptive immune response Source: UniProtKB-KW
  • apoptotic cell clearance Source: UniProtKB
  • autophagy Source: UniProtKB-KW
  • base-excision repair Source: UniProtKB
  • chromatin assembly Source: UniProtKB
  • DNA geometric change Source: AgBase
  • endothelial cell chemotaxis Source: UniProtKB
  • endothelial cell proliferation Source: UniProtKB
  • eye development Source: MGI
  • induction of positive chemotaxis Source: MGI
  • inflammatory response Source: BHF-UCL
  • inflammatory response to antigenic stimulus Source: Ensembl
  • innate immune response Source: UniProtKB-KW
  • lung development Source: MGI
  • macrophage activation involved in immune response Source: UniProtKB
  • myeloid dendritic cell activation Source: UniProtKB
  • negative regulation of apoptotic cell clearance Source: BHF-UCL
  • negative regulation of blood vessel endothelial cell migration Source: Ensembl
  • negative regulation of RNA polymerase II transcriptional preinitiation complex assembly Source: Ensembl
  • neutrophil clearance Source: UniProtKB
  • plasmacytoid dendritic cell activation Source: UniProtKB
  • positive regulation of cell migration Source: MGI
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
  • positive regulation of cytosolic calcium ion concentration Source: Ensembl
  • positive regulation of DNA binding Source: Ensembl
  • positive regulation of DNA ligation Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of glycogen catabolic process Source: MGI
  • positive regulation of innate immune response Source: UniProtKB
  • positive regulation of interferon-alpha production Source: UniProtKB
  • positive regulation of interferon-beta production Source: UniProtKB
  • positive regulation of interleukin-1 beta secretion Source: UniProtKB
  • positive regulation of interleukin-6 production Source: UniProtKB
  • positive regulation of interleukin-6 secretion Source: Ensembl
  • positive regulation of JNK cascade Source: Ensembl
  • positive regulation of mesenchymal cell proliferation Source: MGI
  • positive regulation of mismatch repair Source: Ensembl
  • positive regulation of mitotic cell cycle Source: MGI
  • positive regulation of monocyte chemotaxis Source: Ensembl
  • positive regulation of myeloid cell differentiation Source: MGI
  • positive regulation of NIK/NF-kappaB signaling Source: UniProtKB
  • positive regulation of protein phosphorylation Source: MGI
  • positive regulation of sprouting angiogenesis Source: UniProtKB
  • positive regulation of toll-like receptor 2 signaling pathway Source: UniProtKB
  • positive regulation of toll-like receptor 4 signaling pathway Source: UniProtKB
  • positive regulation of toll-like receptor 9 signaling pathway Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of tumor necrosis factor production Source: UniProtKB
  • positive regulation of wound healing Source: UniProtKB
  • regulation of autophagy Source: UniProtKB
  • regulation of nucleotide-excision repair Source: UniProtKB
  • regulation of protein kinase activity Source: GOC
  • regulation of restriction endodeoxyribonuclease activity Source: Ensembl
  • regulation of T cell mediated immune response to tumor cell Source: UniProtKB
  • regulation of tolerance induction Source: UniProtKB
  • response to glucocorticoid Source: MGI
  • tumor necrosis factor secretion Source: Ensembl
  • V(D)J recombination Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Adaptive immunity, Autophagy, Chemotaxis, DNA damage, DNA recombination, DNA repair, Immunity, Inflammatory response, Innate immunity

Keywords - Ligandi

DNA-binding, Heparin-binding

Enzyme and pathway databases

ReactomeiR-MMU-1810476. RIP-mediated NFkB activation via ZBP1.
R-MMU-211227. Activation of DNA fragmentation factor.
R-MMU-3134963. DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
R-MMU-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-MMU-879415. Advanced glycosylation endproduct receptor signaling.
R-MMU-933542. TRAF6 mediated NF-kB activation.

Names & Taxonomyi

Protein namesi
Recommended name:
High mobility group protein B1
Alternative name(s):
High mobility group protein 1
Short name:
HMG-1
Gene namesi
Name:Hmgb1
Synonyms:Hmg-1, Hmg1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:96113. Hmgb1.

Subcellular locationi

GO - Cellular componenti

  • cell surface Source: Ensembl
  • condensed chromosome Source: Ensembl
  • cytoplasm Source: MGI
  • cytosol Source: Ensembl
  • early endosome Source: UniProtKB
  • endoplasmic reticulum-Golgi intermediate compartment Source: UniProtKB-SubCell
  • extracellular region Source: BHF-UCL
  • extracellular space Source: MGI
  • neuron projection Source: MGI
  • nucleus Source: MGI
  • plasma membrane Source: UniProtKB-SubCell
  • transcriptional repressor complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Chromosome, Cytoplasm, Endosome, Membrane, Nucleus, Secreted

Pathology & Biotechi

Disruption phenotypei

Rapid death within 24 h following birth due to hypoglycaemia.1 Publication

Chemistry

ChEMBLiCHEMBL2311237.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 215214High mobility group protein B1PRO_0000048528Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei3 – 31N6-acetyllysineBy similarity
Modified residuei7 – 71N6-acetyllysineBy similarity
Modified residuei8 – 81N6-acetyllysineBy similarity
Modified residuei12 – 121N6-acetyllysineBy similarity
Disulfide bondi23 ↔ 45In disulfide HMGB1By similarity
Modified residuei23 – 231Cysteine derivative; cysteine sulfonic acid (-SO(3)H) in sulfonyl HMGB1; alternateBy similarity
Modified residuei28 – 281N6-acetyllysineBy similarity
Modified residuei29 – 291N6-acetyllysineBy similarity
Modified residuei30 – 301N6-acetyllysineCombined sources
Modified residuei35 – 351PhosphoserineBy similarity
Modified residuei43 – 431N6-acetyllysineCombined sources
Modified residuei45 – 451Cysteine derivative; cysteine sulfonic acid (-SO(3)H) in sulfonyl HMGB1; alternateBy similarity
Modified residuei90 – 901N6-acetyllysineCombined sources
Modified residuei100 – 1001PhosphoserineBy similarity
Modified residuei106 – 1061Cysteine derivative; cysteine sulfonic acid (-SO(3)H) in sulfonyl HMGB1By similarity
Cross-linki112 – 112Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei127 – 1271N6-acetyllysineBy similarity
Modified residuei128 – 1281N6-acetyllysineBy similarity
Modified residuei141 – 1411N6-acetyllysineCombined sources
Modified residuei172 – 1721N6-acetyllysineBy similarity
Modified residuei173 – 1731N6-acetyllysineBy similarity
Modified residuei177 – 1771N6-acetyllysineBy similarity
Modified residuei180 – 1801N6-acetyllysineBy similarity
Modified residuei182 – 1821N6-acetyllysineBy similarity
Modified residuei183 – 1831N6-acetyllysineBy similarity
Modified residuei184 – 1841N6-acetyllysineBy similarity
Modified residuei185 – 1851N6-acetyllysineBy similarity

Post-translational modificationi

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).By similarity
Phosphorylated at serine residues (PubMed:17114460). Phosphorylation in both NLS regions is required for cytoplasmic translocation followed by secretion (By similarity).By similarity1 Publication
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).1 Publication
Poly-ADP-ribosylated by PARP1 when secreted following stimulation with LPS (PubMed:18768881, PubMed:22204001).2 Publications
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 proinflammatory activities.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei10 – 112Cleavage; by thrombin:thrombomodulinBy similarity
Sitei67 – 682Cleavage; by CASP1By similarity

Keywords - PTMi

Acetylation, Disulfide bond, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP63158.
PaxDbiP63158.
PRIDEiP63158.

PTM databases

iPTMnetiP63158.
PhosphoSiteiP63158.

Expressioni

Tissue specificityi

Serum levels are found elevated in mice with modeled systemic lupus erythematosus (SLE) and are correlated with SLE disease activity (PubMed:26078984).1 Publication

Gene expression databases

BgeeiP63158.
CleanExiMM_HMGB1.
ExpressionAtlasiP63158. baseline and differential.
GenevisibleiP63158. MM.

Interactioni

Subunit structurei

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 (By similarity). Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2 (PubMed:9184213). 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, APEX1, FEN1, POLB, TERT (PubMed:16040616, PubMed:16267105, PubMed:17548579, PubMed:17803946, PubMed:22544226). Interacts with AGER, PTPRZ1, IL1B, MSH2, XPA, XPC, HNF1A, TP53 (By similarity). 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 (By similarity). Interacts with HAVCR2; impairs HMGB1 binding to B-DNA and likely HMGB1-mediated innate immume response (PubMed:22842346). Interacts with XPO1; mediating nuclear export (By similarity).By similarity11 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AesP630023EBI-6665811,EBI-646888
Becn1O885973EBI-6665811,EBI-643716
Havcr2Q8VIM04EBI-6665811,EBI-6665112
Mecp2Q9Z2D62EBI-6665811,EBI-1188816
POU5F1Q018603EBI-6665811,EBI-475687From a different organism.
Rb1P134052EBI-6665811,EBI-971782
RelbQ048632EBI-6665811,EBI-1209145
Tle1Q624402EBI-6665811,EBI-604471
Tp53P023402EBI-6665811,EBI-474016
Zfp36P228932EBI-6665811,EBI-647803

GO - Molecular functioni

  • cytokine activity Source: MGI

Protein-protein interaction databases

BioGridi200322. 1 interaction.
IntActiP63158. 22 interactions.
MINTiMINT-225214.
STRINGi10090.ENSMUSP00000082682.

Structurei

3D structure databases

DisProtiDP00384.
ProteinModelPortaliP63158.
SMRiP63158. Positions 5-166.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 9796Sufficient for interaction with HAVCR21 PublicationAdd
BLAST
Regioni2 – 109Heparin-bindingBy similarity
Regioni3 – 1513LPS binding (delipidated)By similarityAdd
BLAST
Regioni27 – 4317NLS 1By similarityAdd
BLAST
Regioni80 – 9617LPS binding (Lipid A)By similarityAdd
BLAST
Regioni89 – 10820Cytokine-stimulating activityBy similarityAdd
BLAST
Regioni150 – 18334Binding to AGER/RAGEBy similarityAdd
BLAST
Regioni178 – 1847NLS 2By similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi27 – 4317Nuclear localization signal (NLS) 1By similarityAdd
BLAST
Motifi178 – 1847Nuclear localization signal (NLS) 2By similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi186 – 21530Asp/Glu-rich (acidic)Add
BLAST

Domaini

HMG box 2 mediates proinflammatory cytokine-stimulating activity and binding to TLR4. However, not involved in mediating immunogenic activity in the context of apoptosis-induced immune tolerance.By similarity
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.By similarity

Sequence similaritiesi

Belongs to the HMGB family.Curated
Contains 2 HMG box DNA-binding domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0381. Eukaryota.
COG5648. LUCA.
HOGENOMiHOG000197861.
HOVERGENiHBG009000.
InParanoidiP63158.
KOiK10802.
OMAiRTKGKVD.
OrthoDBiEOG7WHHBQ.
PhylomeDBiP63158.
TreeFamiTF105371.

Family and domain databases

Gene3Di1.10.30.10. 2 hits.
InterProiIPR009071. HMG_box_dom.
IPR017967. HMG_boxA_CS.
IPR031076. HMGB1.
[Graphical view]
PANTHERiPTHR13711:SF157. PTHR13711:SF157. 1 hit.
PfamiPF00505. HMG_box. 1 hit.
PF09011. HMG_box_2. 1 hit.
[Graphical view]
SMARTiSM00398. HMG. 2 hits.
[Graphical view]
SUPFAMiSSF47095. SSF47095. 2 hits.
PROSITEiPS00353. HMG_BOX_1. 1 hit.
PS50118. HMG_BOX_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P63158-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKKCSERWK
60 70 80 90 100
TMSAKEKGKF EDMAKADKAR YEREMKTYIP PKGETKKKFK DPNAPKRPPS
110 120 130 140 150
AFFLFCSEYR PKIKGEHPGL SIGDVAKKLG EMWNNTAADD KQPYEKKAAK
160 170 180 190 200
LKEKYEKDIA AYRAKGKPDA AKKGVVKAEK SKKKKEEEDD EEDEEDEEEE
210
EEEEDEDEEE DDDDE
Length:215
Mass (Da):24,894
Last modified:January 23, 2007 - v2
Checksum:i8A868DE266D552B5
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti179 – 1791E → V in AAA57042 (PubMed:9047378).Curated
Sequence conflicti190 – 1901D → E in CAA56631 (PubMed:7961836).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z11997 mRNA. Translation: CAA78042.1.
X80457 Genomic DNA. Translation: CAA56631.1.
U00431 mRNA. Translation: AAA20508.1.
L38477 mRNA. Translation: AAA57042.1.
BC006586 mRNA. Translation: AAH06586.1.
BC008565 mRNA. Translation: AAH08565.1.
BC083067 mRNA. Translation: AAH83067.1.
BC085090 mRNA. Translation: AAH85090.1.
CCDSiCCDS19883.1.
PIRiI48688.
RefSeqiNP_001300823.1. NM_001313894.1.
NP_034569.1. NM_010439.4.
XP_003945388.1. XM_003945339.3.
UniGeneiMm.207047.
Mm.313345.

Genome annotation databases

EnsembliENSMUST00000085546; ENSMUSP00000082682; ENSMUSG00000066551.
ENSMUST00000093196; ENSMUSP00000106131; ENSMUSG00000066551.
ENSMUST00000110505; ENSMUSP00000106132; ENSMUSG00000066551.
GeneIDi100862258.
15289.
KEGGimmu:100862258.
mmu:15289.
UCSCiuc009apb.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z11997 mRNA. Translation: CAA78042.1.
X80457 Genomic DNA. Translation: CAA56631.1.
U00431 mRNA. Translation: AAA20508.1.
L38477 mRNA. Translation: AAA57042.1.
BC006586 mRNA. Translation: AAH06586.1.
BC008565 mRNA. Translation: AAH08565.1.
BC083067 mRNA. Translation: AAH83067.1.
BC085090 mRNA. Translation: AAH85090.1.
CCDSiCCDS19883.1.
PIRiI48688.
RefSeqiNP_001300823.1. NM_001313894.1.
NP_034569.1. NM_010439.4.
XP_003945388.1. XM_003945339.3.
UniGeneiMm.207047.
Mm.313345.

3D structure databases

DisProtiDP00384.
ProteinModelPortaliP63158.
SMRiP63158. Positions 5-166.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200322. 1 interaction.
IntActiP63158. 22 interactions.
MINTiMINT-225214.
STRINGi10090.ENSMUSP00000082682.

Chemistry

ChEMBLiCHEMBL2311237.

PTM databases

iPTMnetiP63158.
PhosphoSiteiP63158.

Proteomic databases

EPDiP63158.
PaxDbiP63158.
PRIDEiP63158.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000085546; ENSMUSP00000082682; ENSMUSG00000066551.
ENSMUST00000093196; ENSMUSP00000106131; ENSMUSG00000066551.
ENSMUST00000110505; ENSMUSP00000106132; ENSMUSG00000066551.
GeneIDi100862258.
15289.
KEGGimmu:100862258.
mmu:15289.
UCSCiuc009apb.2. mouse.

Organism-specific databases

CTDi3146.
MGIiMGI:96113. Hmgb1.

Phylogenomic databases

eggNOGiKOG0381. Eukaryota.
COG5648. LUCA.
HOGENOMiHOG000197861.
HOVERGENiHBG009000.
InParanoidiP63158.
KOiK10802.
OMAiRTKGKVD.
OrthoDBiEOG7WHHBQ.
PhylomeDBiP63158.
TreeFamiTF105371.

Enzyme and pathway databases

ReactomeiR-MMU-1810476. RIP-mediated NFkB activation via ZBP1.
R-MMU-211227. Activation of DNA fragmentation factor.
R-MMU-3134963. DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
R-MMU-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-MMU-879415. Advanced glycosylation endproduct receptor signaling.
R-MMU-933542. TRAF6 mediated NF-kB activation.

Miscellaneous databases

NextBioi287931.
PROiP63158.
SOURCEiSearch...

Gene expression databases

BgeeiP63158.
CleanExiMM_HMGB1.
ExpressionAtlasiP63158. baseline and differential.
GenevisibleiP63158. MM.

Family and domain databases

Gene3Di1.10.30.10. 2 hits.
InterProiIPR009071. HMG_box_dom.
IPR017967. HMG_boxA_CS.
IPR031076. HMGB1.
[Graphical view]
PANTHERiPTHR13711:SF157. PTHR13711:SF157. 1 hit.
PfamiPF00505. HMG_box. 1 hit.
PF09011. HMG_box_2. 1 hit.
[Graphical view]
SMARTiSM00398. HMG. 2 hits.
[Graphical view]
SUPFAMiSSF47095. SSF47095. 2 hits.
PROSITEiPS00353. HMG_BOX_1. 1 hit.
PS50118. HMG_BOX_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

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  1. "Nucleotide sequence of a mouse cDNA encoding the nonhistone chromosomal high mobility group protein-1 (HMG1)."
    Yotov W.V., St Arnaud R.
    Nucleic Acids Res. 20:3516-3516(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C3H/He.
  2. "The mouse gene coding for high mobility group 1 protein (HMG1)."
    Ferrari S., Ronfani L., Calogero S., Bianchi M.
    J. Biol. Chem. 269:28803-28808(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 129/Sv.
    Tissue: Liver.
  3. "Molecular cloning, expression analysis, and chromosomal localization of mouse Hmg1-containing sequences."
    Pauken C.M., Nagle D.L., Bucan M., Lo C.W.
    Mamm. Genome 5:91-99(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "The conserved lymphokine element-0 in the IL5 promoter binds to a high mobility group-1 protein."
    Marrugo J., Marsh D.G., Ghosh B.
    Mol. Immunol. 33:1119-1125(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: AKR/J.
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  6. Lubec G., Kang S.U.
    Submitted (APR-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 31-43 AND 113-127, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: C57BL/6J.
    Tissue: Brain.
  7. "The adhesive and neurite-promoting molecule p30: analysis of the amino-terminal sequence and production of antipeptide antibodies that detect p30 at the surface of neuroblastoma cells and of brain neurons."
    Rauvala H., Merenmies J., Pihlaskari R., Korkolainen M., Huhtala M.L., Panula P.
    J. Cell Biol. 107:2293-2305(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  8. "Stimulation of V(D)J cleavage by high mobility group proteins."
    van Gent D.C., Hiom K., Paull T.T., Gellert M.
    EMBO J. 16:2665-2670(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, IDENTIFICATION IN THE RAG COMPLEX.
  9. "The lack of chromosomal protein Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice."
    Calogero S., Grassi F., Aguzzi A., Voigtlaender T., Ferrier P., Ferrari S., Bianchi M.E.
    Nat. Genet. 22:276-280(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  10. Cited for: INVOLVEMENT IN SEPSIS.
  11. "Release of chromatin protein HMGB1 by necrotic cells triggers inflammation."
    Scaffidi P., Misteli T., Bianchi M.E.
    Nature 418:191-195(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  12. Cited for: FUNCTION, INTERACTION WITH SREBF1.
  13. Cited for: INTERACTION WITH TLR2 AND TLR4.
  14. "Extracellular high mobility group box-1 protein is a proangiogenic cytokine."
    Mitola S., Belleri M., Urbinati C., Coltrini D., Sparatore B., Pedrazzi M., Melloni E., Presta M.
    J. Immunol. 176:12-15(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  15. "Nucleocytoplasmic shuttling of HMGB1 is regulated by phosphorylation that redirects it toward secretion."
    Youn J.H., Shin J.S.
    J. Immunol. 177:7889-7897(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION, SUBCELLULAR LOCATION, INTERACTION WITH KPNA1.
  16. Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TLR9.
  17. "A novel pathway of HMGB1-mediated inflammatory cell recruitment that requires Mac-1-integrin."
    Orlova V.V., Choi E.Y., Xie C., Chavakis E., Bierhaus A., Ihanus E., Ballantyne C.M., Gahmberg C.G., Bianchi M.E., Nawroth P.P., Chavakis T.
    EMBO J. 26:1129-1139(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  18. "Endogenous signals released from necrotic cells augment inflammatory responses to bacterial endotoxin."
    El Mezayen R., El Gazzar M., Seeds M.C., McCall C.E., Dreskin S.C., Nicolls M.R.
    Immunol. Lett. 111:36-44(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  19. Cited for: FUNCTION, INTERACTION WITH APEX1; FEN1 AND POLB.
  20. "High mobility group protein-1 inhibits phagocytosis of apoptotic neutrophils through binding to phosphatidylserine."
    Liu G., Wang J., Park Y.J., Tsuruta Y., Lorne E.F., Zhao X., Abraham E.
    J. Immunol. 181:4240-4246(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, POLY-ADP-RIBOSYLATION, PHOSPHATIDYLSERINE-BINDING.
  21. "High mobility group protein B1 enhances DNA repair and chromatin modification after DNA damage."
    Lange S.S., Mitchell D.L., Vasquez K.M.
    Proc. Natl. Acad. Sci. U.S.A. 105:10320-10325(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  22. Cited for: FUNCTION, SUBCELLULAR LOCATION.
  23. "CD24 and Siglec-10 selectively repress tissue damage-induced immune responses."
    Chen G.Y., Tang J., Zheng P., Liu Y.
    Science 323:1722-1725(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CD24.
  24. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen and Testis.
  25. Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH BECN1.
  26. Cited for: ROLE OF NRLC4 AND NLRP3 INFLAMMASOMES IN HMGB1 RELEASE, SUBCELLULAR LOCATION.
  27. "High mobility group box 1 (HMGB1) activates an autophagic response to oxidative stress."
    Tang D., Kang R., Livesey K.M., Zeh H.J., Lotze M.T.
    Antioxid. Redox Signal. 15:2185-2195(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  28. "High-mobility group box 1 is essential for mitochondrial quality control."
    Tang D., Kang R., Livesey K.M., Kroemer G., Billiar T.R., Van Houten B., Zeh H.J., Lotze M.T.
    Cell Metab. 13:701-711(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  29. "High mobility group box-1 protein regulate immunosuppression of regulatory T cells through toll-like receptor 4."
    Zhu X.M., Yao Y.M., Liang H.P., Xu C.T., Dong N., Yu Y., Sheng Z.Y.
    Cytokine 54:296-304(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  30. "Proteome profiling suggests a pro-inflammatory role for plasma cells through release of high-mobility group box 1 protein."
    Vettermann C., Castor D., Mekker A., Gerrits B., Karas M., Jack H.M.
    Proteomics 11:1228-1237(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  31. "HMGB1 gene knockout in mouse embryonic fibroblasts results in reduced telomerase activity and telomere dysfunction."
    Polanska E., Dobsakova Z., Dvorackova M., Fajkus J., Stros M.
    Chromosoma 121:419-431(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TERT.
  32. "HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4."
    Schiraldi M., Raucci A., Munoz L.M., Livoti E., Celona B., Venereau E., Apuzzo T., De Marchis F., Pedotti M., Bachi A., Thelen M., Varani L., Mellado M., Proudfoot A., Bianchi M.E., Uguccioni M.
    J. Exp. Med. 209:551-563(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CXCL12.
  33. "Redox modification of cysteine residues regulates the cytokine activity of high mobility group box-1 (HMGB1)."
    Yang H., Lundback P., Ottosson L., Erlandsson-Harris H., Venereau E., Bianchi M.E., Al-Abed Y., Andersson U., Tracey K.J., Antoine D.J.
    Mol. Med. 18:250-259(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: CYSTEINE REDOX STATES, SUBCELLULAR LOCATION.
  34. "Poly(ADP-ribosyl)ation of high mobility group box 1 (HMGB1) protein enhances inhibition of efferocytosis."
    Davis K., Banerjee S., Friggeri A., Bell C., Abraham E., Zerfaoui M.
    Mol. Med. 18:359-369(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, POLY-ADP-RIBOSYLATION.
  35. "Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1."
    Chiba S., Baghdadi M., Akiba H., Yoshiyama H., Kinoshita I., Dosaka-Akita H., Fujioka Y., Ohba Y., Gorman J.V., Colgan J.D., Hirashima M., Uede T., Takaoka A., Yagita H., Jinushi M.
    Nat. Immunol. 13:832-842(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HAVCR2.
  36. "Tissue damage-associated 'danger signals' influence T-cell responses that promote the progression of preneoplasia to cancer."
    He Y., Zha J., Wang Y., Liu W., Yang X., Yu P.
    Cancer Res. 73:629-639(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  37. "HMGB1: The central cytokine for all lymphoid cells."
    Li G., Liang X., Lotze M.T.
    Front. Immunol. 4:68-68(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION RELATED TO ADAPTIVE IMUNNITY.
  38. "The many faces of HMGB1: molecular structure-functional activity in inflammation, apoptosis, and chemotaxis."
    Yang H., Antoine D.J., Andersson U., Tracey K.J.
    J. Leukoc. Biol. 93:865-873(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION RELATED TO INFLAMMATION.
  39. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
    Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
    Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-30; LYS-43; LYS-90 AND LYS-141, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic fibroblast.
  40. "Conditional ablation of HMGB1 in mice reveals its protective function against endotoxemia and bacterial infection."
    Yanai H., Matsuda A., An J., Koshiba R., Nishio J., Negishi H., Ikushima H., Onoe T., Ohdan H., Yoshida N., Taniguchi T.
    Proc. Natl. Acad. Sci. U.S.A. 110:20699-20704(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  41. "Menage a Trois in stress: DAMPs, redox and autophagy."
    Li G., Tang D., Lotze M.T.
    Semin. Cancer Biol. 23:380-390(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  42. "High-mobility group box 1 is dispensable for autophagy, mitochondrial quality control, and organ function in vivo."
    Huebener P., Gwak G.Y., Pradere J.P., Quinzii C.M., Friedman R., Lin C.S., Trent C.M., Mederacke I., Zhao E., Dapito D.H., Lin Y., Goldberg I.J., Czaja M.J., Schwabe R.F.
    Cell Metab. 19:539-547(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  43. "The role of high mobility group box 1 in innate immunity."
    Lee S.A., Kwak M.S., Kim S., Shin J.S.
    Yonsei Med. J. 55:1165-1176(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION RELATED TO INNATE IMMUNITY.
  44. "Cytosolic HMGB1 controls the cellular autophagy/apoptosis checkpoint during inflammation."
    Zhu X., Messer J.S., Wang Y., Lin F., Cham C.M., Chang J., Billiar T.R., Lotze M.T., Boone D.L., Chang E.B.
    J. Clin. Invest. 125:1098-1110(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  45. "HMGB1 promotes systemic lupus erythematosus by enhancing macrophage inflammatory response."
    Lu M., Yu S., Xu W., Gao B., Xiong S.
    J. Immunol. Res. 2015:946748-946748(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, INVOLVEMENT IN AUTOIMMUNE DISEASE.
  46. "Extracellular, but not intracellular HMGB1, facilitates self-DNA induced macrophage activation via promoting DNA accumulation in endosomes and contributes to the pathogenesis of lupus nephritis."
    Li X., Yue Y., Zhu Y., Xiong S.
    Mol. Immunol. 65:177-188(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiHMGB1_MOUSE
AccessioniPrimary (citable) accession number: P63158
Secondary accession number(s): P07155, P27109, P27428
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: January 23, 2007
Last modified: April 13, 2016
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Plays a role in acute sepsis; administration of antibodies to HMGB1 attenuates endotoxin lethality; administration of HMGB1 itself is lethal (PubMed:10398600). Overexpression in ALD-DNA-immunized mice significantly enhances the severity of modeled SLE (PubMed:26078984).2 Publications

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.