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Protein

High mobility group protein B1

Gene

Hmgb1

Organism
Rattus norvegicus (Rat)
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. May be involved in platelet activation. Binds to phosphatidylserine and phosphatidylethanolamide (PubMed:11154118). Bound to RAGE mediates signaling for neuronal outgrowth (PubMed:1885601, PubMed:2461949, PubMed:7592757, PubMed:12183440). May play a role in accumulation of expanded polyglutamine (polyQ) proteins.By similarity4 Publications5 Publications
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 (PubMed:2922595, PubMed:11513603). 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:12486007). 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:10866811). 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 (PubMed:24551219). 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 (By similarity). May be involved in mitochondrial quality control and autophagy in a transcription-dependent fashion implicating HSPB1 (By similarity). Can modulate the activity of the telomerase complex and may be involved in telomere maintenance (By similarity).By similarity5 Publications
In the cytoplasm proposed to dissociate the BECN1:BCL2 complex via competitive interaction with BECN1 leading to autophagy activation (By similarity). 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).By similarity
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:22869893). 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. Promotes extracellular DNA-induced AIM2 inflammasome activation implicating AGER/RAGE (By similarity). 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:10952726, PubMed:20547845, PubMed:22869893). 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 (By similarity). 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:23508573). Contributes to tumor proliferation by association with ACER/RAGE (PubMed:10830965). 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 (By similarity). 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 (By similarity). 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 (PubMed:18277947). Released HMGB1:nucleosome complexes formed during apoptosis can signal through TLR2 to induce cytokine production. Involved in induction of immunological tolerance by apoptotic cells; its pro-inflammatory activities when released by apoptotic cells are neutralized by reactive oxygen species (ROS)-dependent oxidation specifically on Cys-106 (By similarity). During macrophage activation by activated lymphocyte-derived self apoptotic DNA (ALD-DNA) promotes recruitment of ALD-DNA to endosomes (By similarity).By similarity4 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

  • 5S rRNA binding Source: RGD
  • bent DNA binding Source: MGI
  • bubble DNA binding Source: AgBase
  • crossed form four-way junction DNA binding Source: MGI
  • cytokine activity Source: UniProtKB
  • DNA binding, bending Source: RGD
  • double-stranded DNA binding Source: RGD
  • four-way junction DNA binding Source: RGD
  • glycolipid binding Source: RGD
  • heparin binding Source: RGD
  • open form four-way junction DNA binding Source: MGI
  • peptide binding Source: RGD
  • protein dimerization activity Source: RGD
  • RAGE receptor binding Source: UniProtKB
  • single-stranded DNA binding Source: RGD
  • supercoiled DNA binding Source: AgBase
  • transcription factor binding Source: RGD

GO - Biological processi

  • actin cytoskeleton reorganization Source: RGD
  • adaptive immune response Source: UniProtKB-KW
  • apoptotic cell clearance Source: UniProtKB
  • autophagy Source: UniProtKB-KW
  • cell morphogenesis Source: RGD
  • cellular response to interleukin-1 Source: RGD
  • chemotaxis Source: RGD
  • circadian rhythm Source: RGD
  • DNA geometric change Source: MGI
  • DNA recombination Source: UniProtKB-KW
  • DNA repair Source: UniProtKB-KW
  • induction of positive chemotaxis Source: MGI
  • inflammatory response Source: UniProtKB-KW
  • male-specific defense response to bacterium Source: RGD
  • myoblast proliferation Source: RGD
  • negative regulation of DNA replication Source: RGD
  • nervous system development Source: RGD
  • neuron projection development Source: UniProtKB
  • neutrophil clearance Source: UniProtKB
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of autophagy Source: RGD
  • positive regulation of cell death Source: RGD
  • positive regulation of cell migration Source: MGI
  • positive regulation of cell proliferation Source: RGD
  • positive regulation of DNA ligation Source: UniProtKB
  • positive regulation of interleukin-1 production Source: UniProtKB
  • positive regulation of interleukin-6 production Source: UniProtKB
  • positive regulation of interleukin-8 production Source: UniProtKB
  • positive regulation of macrophage inflammatory protein 1 alpha production Source: UniProtKB
  • positive regulation of mesenchymal cell proliferation Source: MGI
  • positive regulation of mitotic cell cycle Source: MGI
  • positive regulation of myeloid cell apoptotic process Source: RGD
  • positive regulation of myoblast differentiation Source: RGD
  • positive regulation of neuron projection development Source: RGD
  • positive regulation of smooth muscle cell migration Source: RGD
  • positive regulation of toll-like receptor 9 signaling pathway Source: UniProtKB
  • positive regulation of tumor necrosis factor production Source: UniProtKB
  • regulation of inflammatory response Source: RGD
  • regulation of T cell mediated immune response to tumor cell Source: UniProtKB
  • response to drug Source: RGD
  • response to glucose Source: RGD
  • response to heat Source: RGD
  • response to insulin Source: RGD
  • response to interferon-gamma Source: RGD
  • response to lipopolysaccharide Source: RGD
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

Names & Taxonomyi

Protein namesi
Recommended name:
High mobility group protein B1
Alternative name(s):
Amphoterin
Heparin-binding protein p30
High mobility group protein 1
Short name:
HMG-1
Gene namesi
Name:Hmgb1
Synonyms:Hmg-1, Hmg1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2802. Hmgb1.

Subcellular locationi

GO - Cellular componenti

  • chromosome Source: UniProtKB-SubCell
  • cytoplasm Source: RGD
  • endoplasmic reticulum-Golgi intermediate compartment Source: UniProtKB-SubCell
  • endosome Source: UniProtKB-SubCell
  • extracellular space Source: RGD
  • nucleus Source: RGD
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi23 – 231C → S: No effect on nuclear localization. Decreases interaction with BCN1 and impairs in autophagy induction. Abolishes cytokine-stimulating activity and no effect on chemoattractant activity; when associated with S-45. 3 Publications
Mutagenesisi28 – 303KKK → AAA: Partial cytoplasmic localization; when associated with 181-A--A-183. 1 Publication
Mutagenesisi28 – 303KKK → QQQ: Partial cytoplasmic localization (mimicks acetylation); when associated with 181-Q--Q-183. 1 Publication
Mutagenesisi38 – 381F → A: Disrupts association with chromatin; when associated A-103 and A-122. 1 Publication
Mutagenesisi45 – 451C → A: Reduces TNF-stimulating activity. 1 Publication
Mutagenesisi45 – 451C → S: No effect on nuclear localization. Decreases interaction with BCN1 and impairs autophagy induction. Abolishes cytokine-stimulating activity and no effect on chemoattractant activity; when associated with S-23. 3 Publications
Mutagenesisi103 – 1031F → A: Disrupts association with chromatin; when associated A-38 and A-122. 1 Publication
Mutagenesisi106 – 1061C → A: Disrupts interaction with TLR4:LY96 receptor complex and abolishes TNF release from macrophages. 1 Publication
Mutagenesisi106 – 1061C → S: Abolishes cytokine-stimulating activity; no effect on chemoattractant activity; impaired nuclear and enhanced cytoplasmic localization, retained activity in autophagy regulation. 3 Publications
Mutagenesisi122 – 1221I → A: Disrupts association with chromatin; when associated A-38 and A-103. 1 Publication
Mutagenesisi182 – 1843KKK → AAA: Partial cytoplasmic localization; when associated with 27-A--A-29. 1 Publication
Mutagenesisi182 – 1843KKK → QQQ: Partial cytoplasmic localization (mimicks acetylation); when associated with 27-Q--Q-29. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved1 Publication
Chaini2 – 215214High mobility group protein B1PRO_0000048530Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei3 – 31N6-acetyllysine1 Publication
Modified residuei7 – 71N6-acetyllysineBy similarity
Modified residuei8 – 81N6-acetyllysineBy similarity
Modified residuei12 – 121N6-acetyllysineBy similarity
Disulfide bondi23 ↔ 45In disulfide HMGB13 Publications
Modified residuei23 – 231Cysteine derivative; cysteine sulfonic acid (-SO(3)H) in sulfonyl HMGB1; alternate1 Publication
Modified residuei28 – 281N6-acetyllysineBy similarity
Modified residuei29 – 291N6-acetyllysineBy similarity
Modified residuei30 – 301N6-acetyllysineBy similarity
Modified residuei35 – 351PhosphoserineBy similarity
Modified residuei43 – 431N6-acetyllysineBy similarity
Modified residuei45 – 451Cysteine derivative; cysteine sulfonic acid (-SO(3)H) in sulfonyl HMGB1; alternate1 Publication
Modified residuei90 – 901N6-acetyllysineBy similarity
Modified residuei100 – 1001PhosphoserineBy similarity
Modified residuei106 – 1061Cysteine derivative; cysteine sulfonic acid (-SO(3)H) in sulfonyl HMGB11 Publication
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-acetyllysineBy similarity
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

Phosphorylated at serine residues. Phosphorylation in both NLS regions is required for cytoplasmic translocation followed by secretion.By similarity
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 (PubMed:14532127). Acetylation on Lys-3 results in preferential binding to DNA ends and impairs DNA bending activity (PubMed:17269659).By similarity2 Publications
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).Curated4 Publications
Poly-ADP-ribosylated by PARP1 when secreted following stimulation with LPS.By similarity
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. Can be proteolytically cleaved by a thrombin:thrombomodulin complex; reduces binding to heparin and proinflammatory activities (By similarity).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

PaxDbiP63159.
PRIDEiP63159.

PTM databases

PhosphoSiteiP63159.

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:22869893). Associates with the TLR4:LY96 receptor complex (PubMed:20547845). Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2 (By similarity). 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 (By similarity). Interacts with AGER (PubMed:12183440). Interacts with PTPRZ1 isoform 3/phosphacan (PubMed:9507007). Interacts with SREBF1, TLR2, TLR4, TLR9, APEX1, FEN1, POLB, TERT, 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. Interacts with THBD; prevents HGMB1 interaction with ACER/RAGE and inhibits HGMB1 proinflammatory activity. Interacts with HAVCR2; impairs HMGB1 binding to B-DNA and likely HMGB1-mediated innate immume response (By similarity). Interacts with XPO1; mediating nuclear export (PubMed:14532127).By similarity5 Publications

GO - Molecular functioni

  • cytokine activity Source: UniProtKB
  • protein dimerization activity Source: RGD
  • RAGE receptor binding Source: UniProtKB
  • transcription factor binding Source: RGD

Protein-protein interaction databases

BioGridi247493. 7 interactions.
IntActiP63159. 2 interactions.
STRINGi10116.ENSRNOP00000040874.

Structurei

Secondary structure

1
215
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi15 – 3016Combined sources
Turni32 – 343Combined sources
Helixi38 – 5114Combined sources
Helixi54 – 7623Combined sources
Helixi86 – 883Combined sources
Helixi103 – 11614Combined sources
Helixi122 – 13514Combined sources
Helixi138 – 1403Combined sources
Helixi142 – 15918Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AABNMR-A2-84[»]
1CKTX-ray2.50A8-78[»]
1HMENMR-A89-165[»]
1HMFNMR-A89-165[»]
2GZKNMR-A82-165[»]
4QR9X-ray2.00A/B8-81[»]
ProteinModelPortaliP63159.
SMRiP63159. Positions 5-166.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP63159.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 9796Sufficient for interaction with HAVCR2By similarityAdd
BLAST
Regioni2 – 109Heparin-bindingBy similarity
Regioni3 – 1513LPS binding (delipidated)By similarityAdd
BLAST
Regioni80 – 9617LPS binding (Lipid A)By similarityAdd
BLAST
Regioni89 – 10820Cytokine-stimulating activityBy similarityAdd
BLAST
Regioni150 – 18334Binding to AGER/RAGE1 PublicationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi27 – 4317Nuclear localization signal (NLS) 11 PublicationAdd
BLAST
Motifi178 – 1847Nuclear localization signal (NLS) 21 Publication

Compositional bias

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

Domaini

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.2 Publications

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.
InParanoidiP63159.
KOiK10802.
PhylomeDBiP63159.

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.

P63159-1 [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

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64986 mRNA. Translation: AAA40729.1.
Y00463 mRNA. Translation: CAA68526.1.
AF275734 mRNA. Translation: AAF82799.1.
BC061779 mRNA. Translation: AAH61779.1.
BC081839 mRNA. Translation: AAH81839.1.
BC088402 mRNA. Translation: AAH88402.1.
PIRiA41175. NSRTH1.
RefSeqiNP_037095.1. NM_012963.2.
UniGeneiRn.144565.
Rn.15185.
Rn.4121.

Genome annotation databases

GeneIDi25459.
KEGGirno:25459.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64986 mRNA. Translation: AAA40729.1.
Y00463 mRNA. Translation: CAA68526.1.
AF275734 mRNA. Translation: AAF82799.1.
BC061779 mRNA. Translation: AAH61779.1.
BC081839 mRNA. Translation: AAH81839.1.
BC088402 mRNA. Translation: AAH88402.1.
PIRiA41175. NSRTH1.
RefSeqiNP_037095.1. NM_012963.2.
UniGeneiRn.144565.
Rn.15185.
Rn.4121.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AABNMR-A2-84[»]
1CKTX-ray2.50A8-78[»]
1HMENMR-A89-165[»]
1HMFNMR-A89-165[»]
2GZKNMR-A82-165[»]
4QR9X-ray2.00A/B8-81[»]
ProteinModelPortaliP63159.
SMRiP63159. Positions 5-166.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247493. 7 interactions.
IntActiP63159. 2 interactions.
STRINGi10116.ENSRNOP00000040874.

PTM databases

PhosphoSiteiP63159.

Proteomic databases

PaxDbiP63159.
PRIDEiP63159.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25459.
KEGGirno:25459.

Organism-specific databases

CTDi3146.
RGDi2802. Hmgb1.

Phylogenomic databases

eggNOGiKOG0381. Eukaryota.
COG5648. LUCA.
HOGENOMiHOG000197861.
HOVERGENiHBG009000.
InParanoidiP63159.
KOiK10802.
PhylomeDBiP63159.

Miscellaneous databases

EvolutionaryTraceiP63159.
NextBioi606729.
PROiP63159.

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

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Liver.
  2. Bianchi M.
    Submitted (DEC-1988) to the EMBL/GenBank/DDBJ databases
    Cited for: SEQUENCE REVISION.
  3. "30-kDa heparin-binding protein of brain (amphoterin) involved in neurite outgrowth. Amino acid sequence and localization in the filopodia of the advancing plasma membrane."
    Merenmies J., Pihlaskari R., Laitinen J., Wartiovaara J., Rauvala H.
    J. Biol. Chem. 266:16722-16729(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION, FUNCTION.
  4. "Amphoterin is associated with the development of the kidney."
    Ito T., Suzuki A., Horimoto N., Imai E., Hori M.
    Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Kidney.
  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].
    Tissue: Kidney, Prostate and Testis.
  6. "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: PROTEIN SEQUENCE OF 2-21, SUBCELLULAR LOCATION, FUNCTION.
  7. "Specific recognition of cruciform DNA by nuclear protein HMG1."
    Bianchi M.E., Beltrame M., Paonessa G.
    Science 243:1056-1059(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: DNA-BINDING.
  8. "The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system."
    Hori O., Brett J., Slattery T., Cao R., Zhang J., Chen J.X., Nagashima M., Lundh E.R., Vijay S., Nitecki D.
    J. Biol. Chem. 270:25752-25761(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "High affinity binding and overlapping localization of neurocan and phosphacan/protein-tyrosine phosphatase-zeta/beta with tenascin-R, amphoterin, and the heparin-binding growth-associated molecule."
    Milev P., Chiba A., Haring M., Rauvala H., Schachner M., Ranscht B., Margolis R.K., Margolis R.U.
    J. Biol. Chem. 273:6998-7005(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PTPRZ1.
  10. "HMG1 protein stimulates DNA end joining by promoting association of DNA molecules via their ends."
    Stros M., Cherny D., Jovin T.M.
    Eur. J. Biochem. 267:4088-4097(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. "High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes."
    Andersson U., Wang H., Palmblad K., Aveberger A.C., Bloom O., Erlandsson-Harris H., Janson A., Kokkola R., Zhang M., Yang H., Tracey K.J.
    J. Exp. Med. 192:565-570(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  12. Cited for: FUNCTION.
  13. "Occurrence of amphoterin (HMG1) as an endogenous protein of human platelets that is exported to the cell surface upon platelet activation."
    Rouhiainen A., Imai S., Rauvala H., Parkkinen J.
    Thromb. Haemost. 84:1087-1094(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHOLIPID-BINDING.
  14. "Thermodynamics of HMGB1 interaction with duplex DNA."
    Mueller S., Bianchi M.E., Knapp S.
    Biochemistry 40:10254-10261(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: DNA-BINDING, DOMAIN.
  15. "Receptor for advanced glycation end products-binding COOH-terminal motif of amphoterin inhibits invasive migration and metastasis."
    Huttunen H.J., Fages C., Kuja-Panula J., Ridley A.J., Rauvala H.
    Cancer Res. 62:4805-4811(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, LIGAND FOR AGER RECEPTOR.
  16. "The DNA chaperone HMGB1 facilitates ACF/CHRAC-dependent nucleosome sliding."
    Bonaldi T., Langst G., Strohner R., Becker P.B., Bianchi M.E.
    EMBO J. 21:6865-6873(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  17. "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: SUBCELLULAR LOCATION.
  18. "Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion."
    Bonaldi T., Talamo F., Scaffidi P., Ferrera D., Porto A., Bachi A., Rubartelli A., Agresti A., Bianchi M.E.
    EMBO J. 22:5551-5560(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF 28-LYS--LYS-30 AND 182-LYS--LYS-184, INTERACTION WITH XPO1.
  19. "The long acidic tail of high mobility group box 1 (HMGB1) protein forms an extended and flexible structure that interacts with specific residues within and between the HMG boxes."
    Knapp S., Mueller S., Digilio G., Bonaldi T., Bianchi M.E., Musco G.
    Biochemistry 43:11992-11997(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN.
  20. "GR and HMGB1 interact only within chromatin and influence each other's residence time."
    Agresti A., Scaffidi P., Riva A., Caiolfa V.R., Bianchi M.E.
    Mol. Cell 18:109-121(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, CHROMATIN-BINDING, MUTAGENESIS OF PHE-38; PHE-103 AND ILE-122.
  21. "Molecular basis for the redox control of nuclear transport of the structural chromatin protein Hmgb1."
    Hoppe G., Talcott K.E., Bhattacharya S.K., Crabb J.W., Sears J.E.
    Exp. Cell Res. 312:3526-3538(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BRIDGE, REDOX FORMS, MUTAGENESIS OF CYS-23; CYS-45 AND CYS-106.
  22. "DNA bending versus DNA end joining activity of HMGB1 protein is modulated in vitro by acetylation."
    Ugrinova I., Mitkova E., Moskalenko C., Pashev I., Pasheva E.
    Biochemistry 46:2111-2117(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION AT LYS-3.
  23. "Relationship between high-mobility group box 1 protein release and T-cell suppression in rats after thermal injury."
    Zhang L.T., Yao Y.M., Dong Y.Q., Dong N., Yu Y., Sheng Z.Y.
    Shock 30:449-455(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  24. Cited for: INTERACTION WITH BECN1, MUTAGENESIS OF CYS-23; CYS-45 AND CYS-106.
  25. "A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release."
    Yang H., Hreggvidsdottir H.S., Palmblad K., Wang H., Ochani M., Li J., Lu B., Chavan S., Rosas-Ballina M., Al-Abed Y., Akira S., Bierhaus A., Erlandsson-Harris H., Andersson U., Tracey K.J.
    Proc. Natl. Acad. Sci. U.S.A. 107:11942-11947(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, LIGAND FOR TLR4:LY96 RECEPTOR COMPLEX, MUTAGENESIS OF CYS-106.
  26. Cited for: REDOX FORMS, FUNCTION, INTERACTION WITH CXCL12, SUBCELLULAR LOCATION.
  27. "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: REDOX FORMS, MUTAGENESIS OF CYS-45.
  28. "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.
  29. "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.
  30. "Signaling of high mobility group box 1 (HMGB1) through toll-like receptor 4 in macrophages requires CD14."
    Kim S., Kim S.Y., Pribis J.P., Lotze M., Mollen K.P., Shapiro R., Loughran P., Scott M.J., Billiar T.R.
    Mol. Med. 19:88-98(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  31. "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.
  32. "Binding of histone H1 to DNA is differentially modulated by redox state of HMGB1."
    Polanska E., Pospisilova S., Stros M.
    PLoS ONE 9:E89070-E89070(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, REDOX FORMS.
  33. "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.
  34. "Structure of the HMG box motif in the B-domain of HMG1."
    Weir H.M., Kraulis P.J., Hill C.S., Raine A.R.C., Laue E.D., Thomas J.O.
    EMBO J. 12:1311-1319(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 88-165.
  35. "Structure of the A-domain of HMG1 and its interaction with DNA as studied by heteronuclear three- and four-dimensional NMR spectroscopy."
    Hardman C.H., Broadhurst R.W., Raine A.R.C., Grasser K.D., Thomas J.O., Laue E.D.
    Biochemistry 34:16596-16607(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 1-84.
    Strain: Sprague-Dawley.

Entry informationi

Entry nameiHMGB1_RAT
AccessioniPrimary (citable) accession number: P63159
Secondary accession number(s): P07155
, P27109, P27428, Q548R9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: January 23, 2007
Last modified: May 11, 2016
This is version 120 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  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.