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Protein

High mobility group protein B1

Gene

HMGB1

Organism
Homo sapiens (Human)
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 proangiogdenic activity (By similarity). May be involved in platelet activation (By similarity). Binds to phosphatidylserine and phosphatidylethanolamide (By similarity). Bound to RAGE mediates signaling for neuronal outgrowth (By similarity). May play a role in accumulation of expanded polyglutamine (polyQ) proteins such as huntingtin (HTT) or TBP (PubMed:23303669, PubMed:25549101).By similarity4 Publications2 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. Can bent DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters by enhancing transcription factor binding and/or bringing distant regulatory sequences into close proximity (PubMed:20123072). May have an enhancing role in nucleotide excision repair (NER) (By similarity). However, effects in NER using in vitro systems have been reported conflictingly (PubMed:19446504, PubMed:19360789). May be involved in mismatch repair (MMR) and base excision repair (BER) pathways (PubMed:15014079, PubMed:16143102, PubMed:17803946). May be involved in double strand break repair such as non-homologous end joining (NHEJ) (By similarity). Involved in V(D)J recombination by acting as a cofactor of the RAG complex: acts by stimulating cleavage and RAG protein binding at the 23 bp spacer of conserved recombination signal sequences (RSS) (By similarity). In vitro can displace histone H1 from highly bent DNA (By similarity). Can restructure the canonical nucleosome leading to relaxation of structural constraints for transcription factor-binding (By similarity). Enhances binding of sterol regulatory element-binding proteins (SREBPs) such as SREBF1 to their cognate DNA sequences and increases their transcriptional activities (By similarity). Facilitates binding of TP53 to DNA (PubMed:23063560). Proposed to be involved in mitochondrial quality control and autophagy in a transcription-dependent fashion implicating HSPB1; however, this function has been questioned (By similarity). Can modulate the activity of the telomerase complex and may be involved in telomere maintenance (By similarity).By similarity2 Publications5 Publications
In the cytoplasm proposed to dissociate the BECN1:BCL2 complex via competitive interaction with BECN1 leading to autophagy activation (PubMed:20819940). Involved in oxidative stress-mediated autophagy (PubMed:21395369). Can protect BECN1 and ATG5 from calpain-mediated cleavage and thus proposed to control their proautophagic and proapoptotic functions and to regulate the extent and severity of inflammation-associated cellular injury (By similarity). In myeloid cells has a protective role against endotoxemia and bacterial infection by promoting autophagy (By similarity). Involved in endosomal translocation and activation of TLR9 in response to CpG-DNA in macrophages (By similarity).By similarity2 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 (By similarity). Can bind to various types of DNA and RNA including microbial unmethylated CpG-DNA to enhance the innate immune response to nucleic acids. Proposed to act in promiscuous DNA/RNA sensing which cooperates with subsequent discriminative sensing by specific pattern recognition receptors (By similarity). Promotes extracellular DNA-induced AIM2 inflammasome activation implicating AGER/RAGE (PubMed:24971542). Disulfide HMGB1 binds to transmembrane receptors, such as AGER/RAGE, TLR2, TLR4 and probably TREM1, thus activating their signal transduction pathways. Mediates the release of cytokines/chemokines such as TNF, IL-1, IL-6, IL-8, CCL2, CCL3, CCL4 and CXCL10 (PubMed:12765338, PubMed:18354232, PubMed:19264983, PubMed:20547845, PubMed:24474694). Promotes secretion of interferon-gamma by macrophage-stimulated natural killer (NK) cells in concert with other cytokines like IL-2 or IL-12 (PubMed:15607795). TLR4 is proposed to be the primary receptor promoting macrophage activation and signaling through TLR4 seems to implicate LY96/MD-2 (PubMed:20547845). In bacterial LPS- or LTA-mediated inflammatory responses binds to the endotoxins and transfers them to CD14 for signaling to the respective TLR4:LY96 and TLR2 complexes (PubMed:18354232, PubMed:21660935, PubMed:25660311). Contributes to tumor proliferation by association with ACER/RAGE (By similarity). Can bind to IL1-beta and signals through the IL1R1:IL1RAP receptor complex (PubMed:18250463). Binding to class A CpG activates cytokine production in plasmacytoid dendritic cells implicating TLR9, MYD88 and AGER/RAGE and can activate autoreactive B cells. Via HMGB1-containing chromatin immune complexes may also promote B cell responses to endogenous TLR9 ligands through a B-cell receptor (BCR)-dependent and ACER/RAGE-independent mechanism (By similarity). Inhibits phagocytosis of apoptotic cells by macrophages; the function is dependent on poly-ADP-ribosylation and involves binding to phosphatidylserine on the cell surface of apoptotic cells (By similarity). In adaptive immunity may be involved in enhancing immunity through activation of effector T cells and suppression of regulatory T (TReg) cells (PubMed:15944249, PubMed:22473704). In contrast, without implicating effector or regulatory T-cells, required for tumor infiltration and activation of T-cells expressing the lymphotoxin LTA:LTB heterotrimer thus promoting tumor malignant progression (By similarity). Also reported to limit proliferation of T-cells (By similarity). Released HMGB1:nucleosome complexes formed during apoptosis can signal through TLR2 to induce cytokine production (PubMed:19064698). Involved in induction of immunological tolerance by apoptotic cells; its pro-inflammatory activities when released by apoptotic cells are neutralized by reactive oxygen species (ROS)-dependent oxidation specifically on Cys-106 (PubMed:18631454). During macrophage activation by activated lymphocyte-derived self apoptotic DNA (ALD-DNA) promotes recruitment of ALD-DNA to endosomes (By similarity).By similarity16 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

  • bubble DNA binding Source: AgBase
  • calcium-dependent protein kinase regulator activity Source: Ensembl
  • chemoattractant activity Source: UniProtKB
  • C-X-C chemokine binding Source: UniProtKB
  • cytokine activity Source: UniProtKB
  • damaged DNA binding Source: UniProtKB
  • DNA binding, bending Source: UniProtKB
  • DNA polymerase binding Source: UniProtKB
  • double-stranded DNA binding Source: UniProtKB
  • double-stranded RNA binding Source: Ensembl
  • four-way junction DNA binding Source: AgBase
  • lipopolysaccharide binding Source: UniProtKB
  • lyase activity Source: UniProtKB
  • phosphatidylserine binding Source: UniProtKB
  • poly(A) RNA binding Source: UniProtKB
  • protein kinase activator activity Source: Ensembl
  • RAGE receptor binding Source: UniProtKB
  • repressing transcription factor binding Source: UniProtKB
  • single-stranded DNA binding Source: UniProtKB
  • single-stranded RNA binding Source: Ensembl
  • supercoiled DNA binding Source: AgBase
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB

GO - Biological processi

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

Enzyme and pathway databases

ReactomeiR-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-211227. Activation of DNA fragmentation factor.
R-HSA-3134963. DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
R-HSA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-HSA-879415. Advanced glycosylation endproduct receptor signaling.
R-HSA-933542. TRAF6 mediated NF-kB activation.
SIGNORiP09429.

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:HMG1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:4983. HMGB1.

Subcellular locationi

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • condensed chromosome Source: UniProtKB
  • early endosome Source: Ensembl
  • endoplasmic reticulum-Golgi intermediate compartment Source: UniProtKB-SubCell
  • extracellular region Source: Reactome
  • extracellular space Source: UniProtKB
  • neuron projection Source: Ensembl
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • 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
Mutagenesisi35 – 351S → A: Greatly reduces phosphorylation, nuclear localization; when associated with A-39; A-42; A-46; A-53 and A-181. 1 Publication
Mutagenesisi35 – 351S → E: Cytoplasmic localization (phosphorylation mimicking); when associated with E-39; E-42; E-46; E-53 and E-181. 1 Publication
Mutagenesisi39 – 391S → A: Greatly reduces phosphorylation, nuclear localization; when associated with A-35; A-42; A-46; A-53 and A-181. 1 Publication
Mutagenesisi39 – 391S → E: Cytoplasmic localization (phosphorylation mimicking); when associated with E-35; E-42; E-46; E-53 and E-181. 1 Publication
Mutagenesisi42 – 421S → A: Greatly reduces phosphorylation, nuclear localization; when associated with A-35; A-39; A-46; A-53 and A-181. 1 Publication
Mutagenesisi42 – 421S → E: Cytoplasmic localization (phosphorylation mimicking); when associated with E-35; E-39; E-46; E-53 and E-181. 1 Publication
Mutagenesisi46 – 461S → A: Greatly reduces phosphorylation, nuclear localization; when associated with A-35; A-39; A-42; A-53 and A-181. 1 Publication
Mutagenesisi46 – 461S → E: Cytoplasmic localization (phosphorylation mimicking); when associated with E-35; E-39; E-42; E-53 and E-181. 1 Publication
Mutagenesisi53 – 531S → A: Greatly reduces phosphorylation, nuclear localization; when associated with A-35; A-39; A-42; A-46 and A-181. 1 Publication
Mutagenesisi53 – 531S → E: Cytoplasmic localization (phosphorylation mimicking); when associated with E-35; E-39; E-42; E-46 and E-181. 1 Publication
Mutagenesisi67 – 671D → A: Abolishes cleavage by CASP1 and impairs ability to antagonize apoptosis-induced immune tolerance. 1 Publication
Mutagenesisi106 – 1061C → S: Inhibits oxidation-dependent inactivation of immunostimmulatory activity in apoptotic cells. 1 Publication
Mutagenesisi181 – 1811S → A: Greatly reduces phosphorylation, nuclear localization; when associated with A-35; A-39; A-42; A-46 and A-53. 1 Publication
Mutagenesisi181 – 1811S → E: Cytoplasmic localization (phosphorylation mimicking); when associated with E-35; E-39; E-42; E-46 and E-53. 1 Publication

Organism-specific databases

PharmGKBiPA188.

Chemistry

ChEMBLiCHEMBL2311236.

Polymorphism and mutation databases

BioMutaiHMGB1.
DMDMi123369.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 215214High mobility group protein B1PRO_0000048526Add
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 – 351PhosphoserineCombined sources
Modified residuei43 – 431N6-acetyllysineBy similarity
Modified residuei45 – 451Cysteine derivative; cysteine sulfonic acid (-SO(3)H) in sulfonyl HMGB1; alternateBy similarity
Modified residuei90 – 901N6-acetyllysineBy similarity
Modified residuei100 – 1001PhosphoserineCombined sources
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)1 Publication
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 (PubMed:17114460).1 Publication
Acetylated on multiple sites upon stimulation with LPS (PubMed:22801494). Acetylation on lysine residues in the nuclear localization signals (NLS 1 and NLS 2) leads to cytoplasmic localization and subsequent secretion (By similarity). Acetylation on Lys-3 results in preferential binding to DNA ends and impairs DNA bending activity (By similarity).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 HMGB1 (HMGB1C23hC45hC106h), 2- disulfide HMGB1 (HMGB1C23-C45C106h) and 3- sulfonyl HMGB1 (HMGB1C23soC45soC106so).1 Publication3 Publications
Poly-ADP-ribosylated by PARP1 when secreted following stimulation with LPS (By similarity).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 (PubMed:24474694). Can be proteolytically cleaved by a thrombin:thrombomodulin complex; reduces binding to heparin and proinflammatory activities (By similarity).By similarity1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei10 – 112Cleavage; by thrombin:thrombomodulinBy similarity
Sitei67 – 682Cleavage; by CASP11 Publication

Keywords - PTMi

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

Proteomic databases

EPDiP09429.
MaxQBiP09429.
PaxDbiP09429.
PeptideAtlasiP09429.
PRIDEiP09429.
TopDownProteomicsiP09429.

2D gel databases

DOSAC-COBS-2DPAGEP09429.

PTM databases

iPTMnetiP09429.
PhosphoSiteiP09429.
SwissPalmiP09429.

Expressioni

Tissue specificityi

Ubiquituous. Expressed in platelets (PubMed:11154118).1 Publication

Gene expression databases

BgeeiP09429.
CleanExiHS_HMGB1.
ExpressionAtlasiP09429. baseline and differential.
GenevisibleiP09429. HS.

Organism-specific databases

HPAiCAB005873.
HPA003506.

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 (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 (PubMed:17114460). Interacts with SREBF1, TLR2, TLR4, TLR9, PTPRZ1, APEX1, FEN1, POLB, TERT (By similarity). Interacts with IL1B, AGER, MSH2, XPA, XPC, HNF1A, TP53 (PubMed:15014079, PubMed:18250463, PubMed:18160415, PubMed:19446504, PubMed:24474694, PubMed:23063560). 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 (PubMed:15841214). Interacts with HAVCR2; impairs HMGB1 binding to B-DNA and likely HMGB1-mediated innate immume response (By similarity). Interacts with XPO1; mediating nuclear export (By similarity). Interacts with HTT (wild-type and mutant HTT with expanded polyglutamine repeat) (PubMed:23303669).By similarity14 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AGERQ151093EBI-389432,EBI-1646426
AGTRAPQ6RW133EBI-389432,EBI-741181
BECN1Q144572EBI-389432,EBI-949378
HTTP4285813EBI-389432,EBI-466029
MSH2P432462EBI-389432,EBI-355888

GO - Molecular functioni

  • C-X-C chemokine binding Source: UniProtKB
  • cytokine activity Source: UniProtKB
  • DNA polymerase binding Source: UniProtKB
  • RAGE receptor binding Source: UniProtKB
  • repressing transcription factor binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109389. 80 interactions.
DIPiDIP-24195N.
IntActiP09429. 35 interactions.
MINTiMINT-153055.
STRINGi9606.ENSP00000343040.

Chemistry

BindingDBiP09429.

Structurei

Secondary structure

1
215
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi6 – 83Combined sources
Helixi15 – 3016Combined sources
Helixi38 – 5013Combined sources
Helixi54 – 7623Combined sources
Beta strandi92 – 943Combined sources
Helixi101 – 11616Combined sources
Beta strandi118 – 1203Combined sources
Helixi122 – 13514Combined sources
Helixi138 – 1403Combined sources
Helixi141 – 16323Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LY4NMR-A2-84[»]
2RTUNMR-A1-84[»]
2YRQNMR-A1-166[»]
ProteinModelPortaliP09429.
SMRiP09429. Positions 5-166.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP09429.

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)1 PublicationAdd
BLAST
Regioni80 – 9617LPS binding (Lipid A)1 PublicationAdd
BLAST
Regioni89 – 10820Cytokine-stimulating activity1 PublicationAdd
BLAST
Regioni150 – 18334Binding to AGER/RAGEBy similarityAdd
BLAST

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 (PubMed:12765338, PubMed:20547845). However, not involved in mediating immunogenic activity in the context of apoptosis-induced immune tolerance (PubMed:24474694).3 Publications
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 (PubMed:23063560).By similarity1 Publication

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.
GeneTreeiENSGT00760000119164.
HOGENOMiHOG000197861.
HOVERGENiHBG009000.
InParanoidiP09429.
KOiK10802.
OMAiRTKGKVD.
OrthoDBiEOG7WHHBQ.
PhylomeDBiP09429.
TreeFamiTF105371.

Family and domain databases

Gene3Di1.10.30.10. 2 hits.
InterProiIPR009071. HMG_box_dom.
IPR017967. HMG_boxA_CS.
[Graphical view]
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.

P09429-1 [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 SKKKKEEEED EEDEEDEEEE
210
EDEEDEDEEE DDDDE
Length:215
Mass (Da):24,894
Last modified:January 23, 2007 - v3
Checksum:i8A868CF277D417B5
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti143 – 1431P → H in AAI41845 (PubMed:15489334).Curated
Sequence conflicti215 – 2151E → D in CAG33144 (Ref. 8) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti11 – 111G → R in gastric-carcinoma cell line. 1 Publication
VAR_046451
Natural varianti149 – 1491A → E in gastric-carcinoma cell line. 1 Publication
VAR_046452
Natural varianti156 – 1561E → Q.1 Publication
VAR_046453
Natural varianti190 – 1901D → G in gastric-carcinoma cell line. 1 Publication
VAR_046454

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X12597 mRNA. Translation: CAA31110.1.
U51677 Genomic DNA. Translation: AAB08987.1.
D63874 mRNA. Translation: BAA09924.1.
EF157968 Genomic DNA. Translation: ABM47301.1.
AY377859 mRNA. Translation: AAQ91389.1.
AK291494 mRNA. Translation: BAF84183.1.
AK122825 mRNA. Translation: BAG53745.1.
CR749614 mRNA. Translation: CAH18408.1.
CR456863 mRNA. Translation: CAG33144.1.
BT006940 mRNA. Translation: AAP35586.1.
BT020159 mRNA. Translation: AAV38961.1.
EU012027 Genomic DNA. Translation: ABS29271.1.
AL353648 Genomic DNA. Translation: CAI15600.1.
CH471075 Genomic DNA. Translation: EAX08457.1.
BC003378 mRNA. Translation: AAH03378.1.
BC030981 mRNA. Translation: AAH30981.1.
BC066889 mRNA. Translation: AAH66889.1.
BC067732 mRNA. Translation: AAH67732.1.
BC141844 mRNA. Translation: AAI41845.1.
CCDSiCCDS9335.1.
PIRiS02826.
RefSeqiNP_001300821.1. NM_001313892.1.
NP_001300822.1. NM_001313893.1.
NP_002119.1. NM_002128.5.
XP_005266422.1. XM_005266365.1.
XP_011533357.1. XM_011535055.1.
UniGeneiHs.434102.
Hs.593339.
Hs.596078.

Genome annotation databases

EnsembliENST00000339872; ENSP00000343040; ENSG00000189403.
ENST00000341423; ENSP00000345347; ENSG00000189403.
ENST00000399494; ENSP00000382417; ENSG00000189403.
ENST00000405805; ENSP00000384678; ENSG00000189403.
GeneIDi3146.
KEGGihsa:3146.
UCSCiuc001usx.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X12597 mRNA. Translation: CAA31110.1.
U51677 Genomic DNA. Translation: AAB08987.1.
D63874 mRNA. Translation: BAA09924.1.
EF157968 Genomic DNA. Translation: ABM47301.1.
AY377859 mRNA. Translation: AAQ91389.1.
AK291494 mRNA. Translation: BAF84183.1.
AK122825 mRNA. Translation: BAG53745.1.
CR749614 mRNA. Translation: CAH18408.1.
CR456863 mRNA. Translation: CAG33144.1.
BT006940 mRNA. Translation: AAP35586.1.
BT020159 mRNA. Translation: AAV38961.1.
EU012027 Genomic DNA. Translation: ABS29271.1.
AL353648 Genomic DNA. Translation: CAI15600.1.
CH471075 Genomic DNA. Translation: EAX08457.1.
BC003378 mRNA. Translation: AAH03378.1.
BC030981 mRNA. Translation: AAH30981.1.
BC066889 mRNA. Translation: AAH66889.1.
BC067732 mRNA. Translation: AAH67732.1.
BC141844 mRNA. Translation: AAI41845.1.
CCDSiCCDS9335.1.
PIRiS02826.
RefSeqiNP_001300821.1. NM_001313892.1.
NP_001300822.1. NM_001313893.1.
NP_002119.1. NM_002128.5.
XP_005266422.1. XM_005266365.1.
XP_011533357.1. XM_011535055.1.
UniGeneiHs.434102.
Hs.593339.
Hs.596078.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LY4NMR-A2-84[»]
2RTUNMR-A1-84[»]
2YRQNMR-A1-166[»]
ProteinModelPortaliP09429.
SMRiP09429. Positions 5-166.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109389. 80 interactions.
DIPiDIP-24195N.
IntActiP09429. 35 interactions.
MINTiMINT-153055.
STRINGi9606.ENSP00000343040.

Chemistry

BindingDBiP09429.
ChEMBLiCHEMBL2311236.

PTM databases

iPTMnetiP09429.
PhosphoSiteiP09429.
SwissPalmiP09429.

Polymorphism and mutation databases

BioMutaiHMGB1.
DMDMi123369.

2D gel databases

DOSAC-COBS-2DPAGEP09429.

Proteomic databases

EPDiP09429.
MaxQBiP09429.
PaxDbiP09429.
PeptideAtlasiP09429.
PRIDEiP09429.
TopDownProteomicsiP09429.

Protocols and materials databases

DNASUi3146.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000339872; ENSP00000343040; ENSG00000189403.
ENST00000341423; ENSP00000345347; ENSG00000189403.
ENST00000399494; ENSP00000382417; ENSG00000189403.
ENST00000405805; ENSP00000384678; ENSG00000189403.
GeneIDi3146.
KEGGihsa:3146.
UCSCiuc001usx.5. human.

Organism-specific databases

CTDi3146.
GeneCardsiHMGB1.
H-InvDBHIX0030745.
HGNCiHGNC:4983. HMGB1.
HPAiCAB005873.
HPA003506.
MIMi163905. gene.
neXtProtiNX_P09429.
PharmGKBiPA188.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0381. Eukaryota.
COG5648. LUCA.
GeneTreeiENSGT00760000119164.
HOGENOMiHOG000197861.
HOVERGENiHBG009000.
InParanoidiP09429.
KOiK10802.
OMAiRTKGKVD.
OrthoDBiEOG7WHHBQ.
PhylomeDBiP09429.
TreeFamiTF105371.

Enzyme and pathway databases

ReactomeiR-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-211227. Activation of DNA fragmentation factor.
R-HSA-3134963. DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
R-HSA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-HSA-879415. Advanced glycosylation endproduct receptor signaling.
R-HSA-933542. TRAF6 mediated NF-kB activation.
SIGNORiP09429.

Miscellaneous databases

ChiTaRSiHMGB1. human.
EvolutionaryTraceiP09429.
GeneWikiiHMGB1.
GenomeRNAii3146.
PROiP09429.
SOURCEiSearch...

Gene expression databases

BgeeiP09429.
CleanExiHS_HMGB1.
ExpressionAtlasiP09429. baseline and differential.
GenevisibleiP09429. HS.

Family and domain databases

Gene3Di1.10.30.10. 2 hits.
InterProiIPR009071. HMG_box_dom.
IPR017967. HMG_boxA_CS.
[Graphical view]
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. "A human placental cDNA clone that encodes nonhistone chromosomal protein HMG-1."
    Wen L., Huang J.K., Johnson B.H., Reeck G.R.
    Nucleic Acids Res. 17:1197-1214(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "The active gene that encodes human high mobility group 1 protein (HMG1) contains introns and maps to chromosome 13."
    Ferrari S., Finelli P., Rocchi M., Bianchi M.E.
    Genomics 35:367-371(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Expression of high-mobility group-1 mRNA in human gastrointestinal adenocarcinoma and corresponding non-cancerous mucosa."
    Xiang Y.-Y., Wang D.-Y., Tanaka M., Suzuki M., Kiyokawa E., Igarashi H., Niato Y., Shen Q., Sugimura H.
    Int. J. Cancer 74:1-6(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ARG-11; GLU-149 AND GLY-190.
  4. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. He F.T., Yang Z.H., Ji Q., Li R., Peng J., Jiang Y., Zhong X.
    Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  6. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Cerebellum.
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Small intestine.
  8. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  9. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  10. SeattleSNPs variation discovery resource
    Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-156.
  11. "The DNA sequence and analysis of human chromosome 13."
    Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.
    , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.
    Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  12. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  13. "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: Brain, Cervix and Testis.
  14. "Two-dimensional electrophoretic analysis of human breast carcinoma proteins: mapping of proteins that bind to the SH3 domain of mixed lineage kinase MLK2."
    Rasmussen R.K., Ji H., Eddes J.S., Moritz R.L., Reid G.E., Simpson R.J., Dorow D.S.
    Electrophoresis 18:588-598(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 58-65 AND 113-127.
    Tissue: Mammary carcinoma.
  15. "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: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  16. "The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway."
    Gardella S., Andrei C., Ferrera D., Lotti L.V., Torrisi M.R., Bianchi M.E., Rubartelli A.
    EMBO Rep. 3:995-1001(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  17. "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.
  18. "Structural basis for the proinflammatory cytokine activity of high mobility group box 1."
    Li J., Kokkola R., Tabibzadeh S., Yang R., Ochani M., Qiang X., Harris H.E., Czura C.J., Wang H., Ulloa L., Wang H., Warren H.S., Moldawer L.L., Fink M.P., Andersson U., Tracey K.J., Yang H.
    Mol. Med. 9:37-45(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DOMAIN.
  19. "Evidence for involvement of HMGB1 protein in human DNA mismatch repair."
    Yuan F., Gu L., Guo S., Wang C., Li G.M.
    J. Biol. Chem. 279:20935-20940(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH MSH2.
  20. Cited for: INVOLVEMENT IN INFLAMMATORY DISEASES.
  21. "Reconstitution of 5'-directed human mismatch repair in a purified system."
    Zhang Y., Yuan F., Presnell S.R., Tian K., Gao Y., Tomkinson A.E., Gu L., Li G.-M.
    Cell 122:693-705(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  22. "The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism."
    Abeyama K., Stern D.M., Ito Y., Kawahara K., Yoshimoto Y., Tanaka M., Uchimura T., Ida N., Yamazaki Y., Yamada S., Yamamoto Y., Yamamoto H., Iino S., Taniguchi N., Maruyama I.
    J. Clin. Invest. 115:1267-1274(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH THBD.
  23. "Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products."
    Dumitriu I.E., Baruah P., Valentinis B., Voll R.E., Herrmann M., Nawroth P.P., Arnold B., Bianchi M.E., Manfredi A.A., Rovere-Querini P.
    J. Immunol. 174:7506-7515(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  24. "Monocytes promote natural killer cell interferon gamma production in response to the endogenous danger signal HMGB1."
    DeMarco R.A., Fink M.P., Lotze M.T.
    Mol. Immunol. 42:433-444(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  25. "The extracellular release of HMGB1 during apoptotic cell death."
    Bell C.W., Jiang W., Reich C.F., Pisetsky D.S.
    Am. J. Physiol. 291:C1318-C1325(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  26. "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.
  27. "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, MUTAGENESIS OF SER-35; SER-39; SER-42; SER-46; SER-53 AND SER-181, SUBCELLULAR LOCATION, INTERACTION WITH KPNA1.
  28. "Induction of immunological tolerance by apoptotic cells requires caspase-dependent oxidation of high-mobility group box-1 protein."
    Kazama H., Ricci J.E., Herndon J.M., Hoppe G., Green D.R., Ferguson T.A.
    Immunity 29:21-32(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-106.
  29. Cited for: FUNCTION.
  30. "Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE."
    Urbonaviciute V., Furnrohr B.G., Meister S., Munoz L., Heyder P., De Marchis F., Bianchi M.E., Kirschning C., Wagner H., Manfredi A.A., Kalden J.R., Schett G., Rovere-Querini P., Herrmann M., Voll R.E.
    J. Exp. Med. 205:3007-3018(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, INVOLVEMENT IN AUTOIMMUNE DISEASES.
  31. "HMGB1 develops enhanced proinflammatory activity by binding to cytokines."
    Sha Y., Zmijewski J., Xu Z., Abraham E.
    J. Immunol. 180:2531-2537(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH IL1B.
  32. "High mobility group box 1 protein binding to lipopolysaccharide facilitates transfer of lipopolysaccharide to CD14 and enhances lipopolysaccharide-mediated TNF-alpha production in human monocytes."
    Youn J.H., Oh Y.J., Kim E.S., Choi J.E., Shin J.S.
    J. Immunol. 180:5067-5074(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  33. "Proteomic screen defines the hepatocyte nuclear factor 1alpha-binding partners and identifies HMGB1 as a new cofactor of HNF1alpha."
    Yu M., Wang J., Li W., Yuan Y.Z., Li C.Y., Qian X.H., Xu W.X., Zhan Y.Q., Yang X.M.
    Nucleic Acids Res. 36:1209-1219(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HNF1A.
  34. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35 AND SER-100, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  35. "Proteomic analysis of ubiquitinated proteins in normal hepatocyte cell line Chang liver cells."
    Tan F., Lu L., Cai Y., Wang J., Xie Y., Wang L., Gong Y., Xu B.-E., Wu J., Luo Y., Qiang B., Yuan J., Sun X., Peng X.
    Proteomics 8:2885-2896(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-112.
    Tissue: Cervix carcinoma.
  36. "Oxidation of the alarmin high-mobility group box 1 protein (HMGB1) during apoptosis."
    Urbonaviciute V., Meister S., Furnrohr B.G., Frey B., Guckel E., Schett G., Herrmann M., Voll R.E.
    Autoimmunity 42:305-307(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: REDOX FORMS, SUBCELLULAR LOCATION.
  37. "Human HMGB1 directly facilitates interactions between nucleotide excision repair proteins on triplex-directed psoralen interstrand crosslinks."
    Lange S.S., Reddy M.C., Vasquez K.M.
    DNA Repair 8:865-872(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH XPA AND XPC.
  38. "HMGB1: the jack-of-all-trades protein is a master DNA repair mechanic."
    Lange S.S., Vasquez K.M.
    Mol. Carcinog. 48:571-580(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION RELATED TO DNA REPAIR.
  39. "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, LIGAND FOR CD24:SIGLEC10 RECEPTOR COMPLEX.
  40. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-30, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  41. "HMGB proteins: interactions with DNA and chromatin."
    Stros M.
    Biochim. Biophys. Acta 1799:101-113(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION RELATED TO DNA-BINDING.
  42. Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH BECN1.
  43. "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, DOMAIN.
  44. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  45. "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.
  46. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  47. "Identification of lipopolysaccharide-binding peptide regions within HMGB1 and their effects on subclinical endotoxemia in a mouse model."
    Youn J.H., Kwak M.S., Wu J., Kim E.S., Ji Y., Min H.J., Yoo J.H., Choi J.E., Cho H.S., Shin J.S.
    Eur. J. Immunol. 41:2753-2762(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: LPS-BINDING.
  48. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  49. "HMGB1 conveys immunosuppressive characteristics on regulatory and conventional T cells."
    Wild C.A., Bergmann C., Fritz G., Schuler P., Hoffmann T.K., Lotfi R., Westendorf A., Brandau S., Lang S.
    Int. Immunol. 24:485-494(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  50. "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.
  51. Cited for: REDOX FORMS, SUBCELLULAR LOCATION.
  52. Cited for: ACETYLATION.
  53. "High mobility group box 1 released from necrotic cells enhances regrowth and metastasis of cancer cells that have survived chemotherapy."
    Luo Y., Chihara Y., Fujimoto K., Sasahira T., Kuwada M., Fujiwara R., Fujii K., Ohmori H., Kuniyasu H.
    Eur. J. Cancer 49:741-751(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN CANCER THERAPY.
  54. "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.
  55. "Chaperone-like activity of high-mobility group box 1 protein and its role in reducing the formation of polyglutamine aggregates."
    Min H.J., Ko E.A., Wu J., Kim E.S., Kwon M.K., Kwak M.S., Choi J.E., Lee J.E., Shin J.S.
    J. Immunol. 190:1797-1806(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH HTT.
  56. "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.
  57. "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.
  58. "HMGB1-DNA complex-induced autophagy limits AIM2 inflammasome activation through RAGE."
    Liu L., Yang M., Kang R., Dai Y., Yu Y., Gao F., Wang H., Sun X., Li X., Li J., Wang H., Cao L., Tang D.
    Biochem. Biophys. Res. Commun. 450:851-856(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  59. "An immunogenic peptide in the A-box of HMGB1 protein reverses apoptosis-induced tolerance through RAGE receptor."
    LeBlanc P.M., Doggett T.A., Choi J., Hancock M.A., Durocher Y., Frank F., Nagar B., Ferguson T.A., Saleh M.
    J. Biol. Chem. 289:7777-7786(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF ASP-67, INTERACTION WITH AGER, DOMAIN, PROTEOLYTIC CLEAVAGE.
  60. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  61. "A systematic nomenclature for the redox states of high mobility group box (HMGB) proteins."
    Antoine D.J., Harris H.E., Andersson U., Tracey K.J., Bianchi M.E.
    Mol. Med. 20:135-137(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: NOMENCLATURE OF REDOX FORMS.
  62. "An overview on HMGB1 inhibitors as potential therapeutic agents in HMGB1-related pathologies."
    Musumeci D., Roviello G.N., Montesarchio D.
    Pharmacol. Ther. 141:347-357(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON INVOLVEMENT IN DISEASES AND THERAPEUTIC TARGET.
  63. "Role of high mobility group box 1 (HMGB1) in SCA17 pathogenesis."
    Lee L.C., Chen C.M., Wang P.R., Su M.T., Lee-Chen G.J., Chang C.Y.
    PLoS ONE 9:E115809-E115809(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  64. "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.
  65. "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: INVOLVEMENT AUTOIMMUNE DISEASES.
  66. "HMGB1 binds to lipoteichoic acid and enhances TNF-alpha and IL-6 production through HMGB1-mediated transfer of lipoteichoic acid to CD14 and TLR2."
    Kwak M.S., Lim M., Lee Y.J., Lee H.S., Kim Y.H., Youn J.H., Choi J.E., Shin J.S.
    J. Innate Immun. 7:405-416(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  67. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  68. "Solution structure of the tandem HMG box domain from human high mobility group protein B1."
    RIKEN structural genomics initiative (RSGI)
    Submitted (FEB-2008) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 1-166.
  69. "HMGB1-facilitated p53 DNA binding occurs via HMG-Box/p53 transactivation domain interaction, regulated by the acidic tail."
    Rowell J.P., Simpson K.L., Stott K., Watson M., Thomas J.O.
    Structure 20:2014-2024(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 2-84 IN COMPLEX WITH TP53, FUNCTION, DOMAIN.
  70. "Redox-sensitive structural change in the A-domain of HMGB1 and its implication for the binding to cisplatin modified DNA."
    Wang J., Tochio N., Takeuchi A., Uewaki J.I., Kobayashi N., Tate S.I.
    Biochem. Biophys. Res. Commun. 0:0-0(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 1-84.

Entry informationi

Entry nameiHMGB1_HUMAN
AccessioniPrimary (citable) accession number: P09429
Secondary accession number(s): A5D8W9
, Q14321, Q5T7C3, Q6IBE1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: January 23, 2007
Last modified: June 8, 2016
This is version 181 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Proposed to contribute to the pathogenesis of various chronic inflammatory and autoimmune diseases, and cancer. High serum levels are found in several inflammatory events including sepsis, rheumatoid arthritis, artherosclerosis chronic kidney disease, systemic lupus erythematosus (SLE). Seems to be implicated in other diseases characterized by cell death and damage, including diabetes and Alzheimer's disease. Its nucleosome-associated release during secondory necrosis may play a role in SLE (PubMed:19064698). During chemotherapy can mediate regrowth and metastasis of remaining cells in a AGER/RAGE-depenedent manner (PubMed:23040637). Purified HMG box 1 acts as a specific antogonist to HGMB1 pro-imflammatory activities (PubMed:14695889).Curated2 Publications

Caution

Inconsistent experimental results may reflect the use of inconsistently defined redox forms. A recombinant fully reduced form has been used in a number of experiments. However, the redox states of HMGB1 administered in vivo, may interconvert among each other. Purified HMGB1 by itself has only weak pro-inflammatory activity.Curated

Keywords - Technical termi

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

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.