Hmdb loader
You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP13794
Secondary Accession Numbers None
Name High mobility group protein B1
Synonyms
  1. High mobility group protein 1
  2. HMG-1
Gene Name HMGB1
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone involved in replication, transcription, chromatin remodeling, V(D)J recombination, DNA repair and genome stability (Ref.71). 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 (PubMed:27362237). Released to the extracellular environment can bind DNA, nucleosomes, IL-1 beta, CXCL12, AGER isoform 2/sRAGE, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and activates cells through engagement of multiple surface receptors. 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).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).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).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).(Microbial infection) Critical for entry of human coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus NL63/HCoV-NL63. Regulates the expression of the pro-viral genes ACE2 and CTSL through chromatin modulation.
Pathways
  • Autophagy - animal
  • Base excision repair
  • Necroptosis
  • Neutrophil extracellular trap formation
Reactions Not Available
GO Classification
Biological Process
apoptotic DNA fragmentation
positive regulation of toll-like receptor 4 signaling pathway
elevation of cytosolic calcium ion concentration
positive regulation of apoptotic process
neutrophil degranulation
positive regulation of interleukin-10 production
negative regulation of interferon-gamma production
positive regulation of interleukin-8 production
positive regulation of toll-like receptor 2 signaling pathway
double-strand break repair via nonhomologous end joining
dendritic cell chemotaxis
DNA geometric change
myeloid dendritic cell activation
negative regulation of apoptotic cell clearance
negative regulation of blood vessel endothelial cell migration
negative regulation of CD4-positive, alpha-beta T cell differentiation
negative regulation of RNA polymerase II transcription preinitiation complex assembly
neutrophil clearance
plasmacytoid dendritic cell activation
positive regulation of autophagy
positive regulation of chemokine (C-X-C motif) ligand 2 production
positive regulation of dendritic cell differentiation
positive regulation of DNA ligation
positive regulation of interleukin-1 production
positive regulation of mismatch repair
positive regulation of toll-like receptor 9 signaling pathway
regulation of restriction endodeoxyribonuclease activity
regulation of T cell mediated immune response to tumor cell
inflammatory response
cellular response to interleukin-7
regulation of tolerance induction
T-helper 1 cell activation
V(D)J recombination
activation of innate immune response
positive regulation of interleukin-12 production
neuron projection development
positive regulation of DNA binding
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
positive regulation of interferon-beta production
positive regulation of vascular endothelial cell proliferation
cellular response to lipopolysaccharide
positive regulation of blood vessel endothelial cell migration
positive regulation of ERK1 and ERK2 cascade
regulation of transcription from RNA polymerase II promoter
response to glucocorticoid stimulus
positive regulation of interferon-alpha production
DNA topological change
positive regulation of monocyte chemotaxis
innate immune response
negative regulation of transcription from RNA polymerase II promoter
viral reproduction
positive regulation of transcription from RNA polymerase II promoter
base-excision repair
eye development
inflammatory response to antigenic stimulus
positive regulation of MAPK cascade
positive regulation of tumor necrosis factor production
toll-like receptor signaling pathway
positive regulation of JNK cascade
lung development
positive regulation of monocyte chemotactic protein-1 production
positive regulation of wound healing
positive regulation of interleukin-1 beta production
positive regulation of interleukin-6 production
endothelial cell proliferation
chromatin assembly
endothelial cell chemotaxis
macrophage activation involved in immune response
positive regulation of glycogen catabolic process
positive regulation of myeloid cell differentiation
regulation of nucleotide-excision repair
positive regulation of sprouting angiogenesis
DNA recombination
apoptotic cell clearance
positive regulation of activated T cell proliferation
positive regulation of NIK/NF-kappaB signaling
T-helper 1 cell differentiation
chromatin silencing
autophagy
Cellular Component
cell surface
condensed chromosome
alphav-beta3 integrin-HMGB1 complex
nucleus
early endosome
nucleoplasm
transcriptional repressor complex
endoplasmic reticulum-Golgi intermediate compartment
extracellular region
extracellular space
neuron projection
ficolin-1-rich granule lumen
secretory granule lumen
Molecular Function
lipopolysaccharide binding
C-X-C chemokine binding
DNA binding, bending
DNA polymerase binding
four-way junction DNA binding
RAGE receptor binding
repressing transcription factor binding
supercoiled DNA binding
chemoattractant activity
double-stranded RNA binding
transcription factor binding
bubble DNA binding
single-stranded DNA binding
integrin binding
phosphatidylserine binding
double-stranded DNA binding
single-stranded RNA binding
transcription coactivator activity
RNA binding
damaged DNA binding
lyase activity
protein kinase activator activity
calcium-dependent protein kinase regulator activity
cytokine activity
transcription regulatory region sequence-specific DNA binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 215
Molecular Weight 24893.58
Theoretical pI 5.739
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P09429
UniProtKB/Swiss-Prot Entry Name HMGB1_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. 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 TO, 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: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  4. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  5. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005 ]
  6. Dunham A, Matthews LH, Burton J, Ashurst JL, Howe KL, Ashcroft KJ, Beare DM, Burford DC, Hunt SE, Griffiths-Jones S, Jones MC, Keenan SJ, Oliver K, Scott CE, Ainscough R, Almeida JP, Ambrose KD, Andrews DT, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Bannerjee R, Barlow KF, Bates K, Beasley H, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burrill W, Carder C, Carter NP, Chapman JC, Clamp ME, Clark SY, Clarke G, Clee CM, Clegg SC, Cobley V, Collins JE, Corby N, Coville GJ, Deloukas P, Dhami P, Dunham I, Dunn M, Earthrowl ME, Ellington AG, Faulkner L, Frankish AG, Frankland J, French L, Garner P, Garnett J, Gilbert JG, Gilson CJ, Ghori J, Grafham DV, Gribble SM, Griffiths C, Hall RE, Hammond S, Harley JL, Hart EA, Heath PD, Howden PJ, Huckle EJ, Hunt PJ, Hunt AR, Johnson C, Johnson D, Kay M, Kimberley AM, King A, Laird GK, Langford CJ, Lawlor S, Leongamornlert DA, Lloyd DM, Lloyd C, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, McLaren SJ, McMurray A, Milne S, Moore MJ, Nickerson T, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter KM, Rice CM, Searle S, Sehra HK, Shownkeen R, Skuce CD, Smith M, Steward CA, Sycamore N, Tester J, Thomas DW, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Wilming L, Wray PW, Wright MW, Young L, Coulson A, Durbin R, Hubbard T, Sulston JE, Beck S, Bentley DR, Rogers J, Ross MT: The DNA sequence and analysis of human chromosome 13. Nature. 2004 Apr 1;428(6982):522-8. [PubMed:15057823 ]
  7. Rasmussen RK, Ji H, Eddes JS, Moritz RL, Reid GE, Simpson RJ, Dorow DS: Two-dimensional electrophoretic analysis of human breast carcinoma proteins: mapping of proteins that bind to the SH3 domain of mixed lineage kinase MLK2. Electrophoresis. 1997 Mar-Apr;18(3-4):588-98. [PubMed:9150946 ]
  8. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [PubMed:20068231 ]
  9. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [PubMed:23186163 ]
  10. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460 ]
  11. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569 ]
  12. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [PubMed:25944712 ]
  13. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [PubMed:21406692 ]
  14. Bonaldi T, Talamo F, Scaffidi P, Ferrera D, Porto A, Bachi A, Rubartelli A, Agresti A, Bianchi ME: Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J. 2003 Oct 15;22(20):5551-60. doi: 10.1093/emboj/cdg516. [PubMed:14532127 ]
  15. Yang H, Antoine DJ, Andersson U, Tracey KJ: The many faces of HMGB1: molecular structure-functional activity in inflammation, apoptosis, and chemotaxis. J Leukoc Biol. 2013 Jun;93(6):865-73. doi: 10.1189/jlb.1212662. Epub 2013 Feb 27. [PubMed:23446148 ]
  16. Li G, Tang D, Lotze MT: Menage a Trois in stress: DAMPs, redox and autophagy. Semin Cancer Biol. 2013 Oct;23(5):380-90. doi: 10.1016/j.semcancer.2013.08.002. Epub 2013 Aug 28. [PubMed:23994764 ]
  17. Lee SA, Kwak MS, Kim S, Shin JS: The role of high mobility group box 1 in innate immunity. Yonsei Med J. 2014 Sep;55(5):1165-76. doi: 10.3349/ymj.2014.55.5.1165. [PubMed:25048472 ]
  18. Wen L, Huang JK, Johnson BH, Reeck GR: A human placental cDNA clone that encodes nonhistone chromosomal protein HMG-1. Nucleic Acids Res. 1989 Feb 11;17(3):1197-214. doi: 10.1093/nar/17.3.1197. [PubMed:2922262 ]
  19. Ferrari S, Finelli P, Rocchi M, Bianchi ME: The active gene that encodes human high mobility group 1 protein (HMG1) contains introns and maps to chromosome 13. Genomics. 1996 Jul 15;35(2):367-71. doi: 10.1006/geno.1996.0369. [PubMed:8661151 ]
  20. Xiang YY, Wang DY, Tanaka M, Suzuki M, Kiyokawa E, Igarashi H, Naito Y, Shen Q, Sugimura H: Expression of high-mobility group-1 mRNA in human gastrointestinal adenocarcinoma and corresponding non-cancerous mucosa. Int J Cancer. 1997 Feb 20;74(1):1-6. doi: 10.1002/(sici)1097-0215(19970220)74:1<1::aid-ijc1>3.0.co;2-6. [PubMed:9036861 ]
  21. Kornblit B, Munthe-Fog L, Petersen SL, Madsen HO, Vindelov L, Garred P: The genetic variation of the human HMGB1 gene. Tissue Antigens. 2007 Aug;70(2):151-6. doi: 10.1111/j.1399-0039.2007.00854.x. [PubMed:17610420 ]
  22. Rouhiainen A, Imai S, Rauvala H, Parkkinen J: Occurrence of amphoterin (HMG1) as an endogenous protein of human platelets that is exported to the cell surface upon platelet activation. Thromb Haemost. 2000 Dec;84(6):1087-94. [PubMed:11154118 ]
  23. Gardella S, Andrei C, Ferrera D, Lotti LV, Torrisi MR, Bianchi ME, Rubartelli A: The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway. EMBO Rep. 2002 Oct;3(10):995-1001. doi: 10.1093/embo-reports/kvf198. Epub 2002 Sep 13. [PubMed:12231511 ]
  24. Li J, Kokkola R, Tabibzadeh S, Yang R, Ochani M, Qiang X, Harris HE, Czura CJ, Wang H, Ulloa L, Wang H, Warren HS, Moldawer LL, Fink MP, Andersson U, Tracey KJ, Yang H: Structural basis for the proinflammatory cytokine activity of high mobility group box 1. Mol Med. 2003 Jan-Feb;9(1-2):37-45. [PubMed:12765338 ]
  25. Yuan F, Gu L, Guo S, Wang C, Li GM: Evidence for involvement of HMGB1 protein in human DNA mismatch repair. J Biol Chem. 2004 May 14;279(20):20935-40. doi: 10.1074/jbc.M401931200. Epub 2004 Mar 9. [PubMed:15014079 ]
  26. Yang H, Ochani M, Li J, Qiang X, Tanovic M, Harris HE, Susarla SM, Ulloa L, Wang H, DiRaimo R, Czura CJ, Wang H, Roth J, Warren HS, Fink MP, Fenton MJ, Andersson U, Tracey KJ: Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):296-301. doi: 10.1073/pnas.2434651100. Epub 2003 Dec 26. [PubMed:14695889 ]
  27. Zhang Y, Yuan F, Presnell SR, Tian K, Gao Y, Tomkinson AE, Gu L, Li GM: Reconstitution of 5'-directed human mismatch repair in a purified system. Cell. 2005 Sep 9;122(5):693-705. doi: 10.1016/j.cell.2005.06.027. [PubMed:16143102 ]
  28. Abeyama K, Stern DM, 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: The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism. J Clin Invest. 2005 May;115(5):1267-74. doi: 10.1172/JCI22782. Epub 2005 Apr 14. [PubMed:15841214 ]
  29. Dumitriu IE, Baruah P, Valentinis B, Voll RE, Herrmann M, Nawroth PP, Arnold B, Bianchi ME, Manfredi AA, Rovere-Querini P: Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products. J Immunol. 2005 Jun 15;174(12):7506-15. doi: 10.4049/jimmunol.174.12.7506. [PubMed:15944249 ]
  30. DeMarco RA, Fink MP, Lotze MT: Monocytes promote natural killer cell interferon gamma production in response to the endogenous danger signal HMGB1. Mol Immunol. 2005 Feb;42(4):433-44. doi: 10.1016/j.molimm.2004.07.023. [PubMed:15607795 ]
  31. Hoppe G, Talcott KE, Bhattacharya SK, Crabb JW, Sears JE: Molecular basis for the redox control of nuclear transport of the structural chromatin protein Hmgb1. Exp Cell Res. 2006 Nov 1;312(18):3526-38. doi: 10.1016/j.yexcr.2006.07.020. Epub 2006 Aug 2. [PubMed:16962095 ]
  32. Youn JH, Shin JS: Nucleocytoplasmic shuttling of HMGB1 is regulated by phosphorylation that redirects it toward secretion. J Immunol. 2006 Dec 1;177(11):7889-97. doi: 10.4049/jimmunol.177.11.7889. [PubMed:17114460 ]
  33. Kazama H, Ricci JE, Herndon JM, Hoppe G, Green DR, Ferguson TA: Induction of immunological tolerance by apoptotic cells requires caspase-dependent oxidation of high-mobility group box-1 protein. Immunity. 2008 Jul 18;29(1):21-32. doi: 10.1016/j.immuni.2008.05.013. [PubMed:18631454 ]
  34. Urbonaviciute V, Furnrohr BG, Meister S, Munoz L, Heyder P, De Marchis F, Bianchi ME, Kirschning C, Wagner H, Manfredi AA, Kalden JR, Schett G, Rovere-Querini P, Herrmann M, Voll RE: Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE. J Exp Med. 2008 Dec 22;205(13):3007-18. doi: 10.1084/jem.20081165. Epub 2008 Dec 8. [PubMed:19064698 ]
  35. Sha Y, Zmijewski J, Xu Z, Abraham E: HMGB1 develops enhanced proinflammatory activity by binding to cytokines. J Immunol. 2008 Feb 15;180(4):2531-7. doi: 10.4049/jimmunol.180.4.2531. [PubMed:18250463 ]
  36. Youn JH, Oh YJ, Kim ES, Choi JE, Shin JS: 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. J Immunol. 2008 Apr 1;180(7):5067-74. doi: 10.4049/jimmunol.180.7.5067. [PubMed:18354232 ]
  37. Yu M, Wang J, Li W, Yuan YZ, Li CY, Qian XH, Xu WX, Zhan YQ, Yang XM: Proteomic screen defines the hepatocyte nuclear factor 1alpha-binding partners and identifies HMGB1 as a new cofactor of HNF1alpha. Nucleic Acids Res. 2008 Mar;36(4):1209-19. doi: 10.1093/nar/gkm1131. Epub 2007 Dec 26. [PubMed:18160415 ]
  38. Urbonaviciute V, Meister S, Furnrohr BG, Frey B, Guckel E, Schett G, Herrmann M, Voll RE: Oxidation of the alarmin high-mobility group box 1 protein (HMGB1) during apoptosis. Autoimmunity. 2009 May;42(4):305-7. doi: 10.1080/08916930902831803. [PubMed:19811284 ]
  39. Lange SS, Reddy MC, Vasquez KM: Human HMGB1 directly facilitates interactions between nucleotide excision repair proteins on triplex-directed psoralen interstrand crosslinks. DNA Repair (Amst). 2009 Jul 4;8(7):865-72. doi: 10.1016/j.dnarep.2009.04.001. Epub 2009 May 14. [PubMed:19446504 ]
  40. Lange SS, Vasquez KM: HMGB1: the jack-of-all-trades protein is a master DNA repair mechanic. Mol Carcinog. 2009 Jul;48(7):571-80. doi: 10.1002/mc.20544. [PubMed:19360789 ]
  41. Chen GY, Tang J, Zheng P, Liu Y: CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science. 2009 Mar 27;323(5922):1722-5. doi: 10.1126/science.1168988. Epub 2009 Mar 5. [PubMed:19264983 ]
  42. Stros M: HMGB proteins: interactions with DNA and chromatin. Biochim Biophys Acta. 2010 Jan-Feb;1799(1-2):101-13. doi: 10.1016/j.bbagrm.2009.09.008. [PubMed:20123072 ]
  43. Tang D, Kang R, Livesey KM, Cheh CW, Farkas A, Loughran P, Hoppe G, Bianchi ME, Tracey KJ, Zeh HJ 3rd, Lotze MT: Endogenous HMGB1 regulates autophagy. J Cell Biol. 2010 Sep 6;190(5):881-92. doi: 10.1083/jcb.200911078. [PubMed:20819940 ]
  44. Yang H, Hreggvidsdottir HS, 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 KJ: A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release. Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11942-7. doi: 10.1073/pnas.1003893107. Epub 2010 Jun 14. [PubMed:20547845 ]
  45. Tang D, Kang R, Livesey KM, Zeh HJ 3rd, Lotze MT: High mobility group box 1 (HMGB1) activates an autophagic response to oxidative stress. Antioxid Redox Signal. 2011 Oct 15;15(8):2185-95. doi: 10.1089/ars.2010.3666. Epub 2011 Jun 6. [PubMed:21395369 ]
  46. Youn JH, Kwak MS, Wu J, Kim ES, Ji Y, Min HJ, Yoo JH, Choi JE, Cho HS, Shin JS: Identification of lipopolysaccharide-binding peptide regions within HMGB1 and their effects on subclinical endotoxemia in a mouse model. Eur J Immunol. 2011 Sep;41(9):2753-62. doi: 10.1002/eji.201141391. Epub 2011 Aug 4. [PubMed:21660935 ]
  47. Wild CA, Bergmann C, Fritz G, Schuler P, Hoffmann TK, Lotfi R, Westendorf A, Brandau S, Lang S: HMGB1 conveys immunosuppressive characteristics on regulatory and conventional T cells. Int Immunol. 2012 Aug;24(8):485-94. doi: 10.1093/intimm/dxs051. Epub 2012 Apr 3. [PubMed:22473704 ]
  48. Schiraldi M, Raucci A, Munoz LM, Livoti E, Celona B, Venereau E, Apuzzo T, De Marchis F, Pedotti M, Bachi A, Thelen M, Varani L, Mellado M, Proudfoot A, Bianchi ME, Uguccioni M: HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4. J Exp Med. 2012 Mar 12;209(3):551-63. doi: 10.1084/jem.20111739. Epub 2012 Feb 27. [PubMed:22370717 ]
  49. Lu B, Nakamura T, Inouye K, Li J, Tang Y, Lundback P, Valdes-Ferrer SI, Olofsson PS, Kalb T, Roth J, Zou Y, Erlandsson-Harris H, Yang H, Ting JP, Wang H, Andersson U, Antoine DJ, Chavan SS, Hotamisligil GS, Tracey KJ: Novel role of PKR in inflammasome activation and HMGB1 release. Nature. 2012 Aug 30;488(7413):670-4. doi: 10.1038/nature11290. [PubMed:22801494 ]
  50. Luo Y, Chihara Y, Fujimoto K, Sasahira T, Kuwada M, Fujiwara R, Fujii K, Ohmori H, Kuniyasu H: High mobility group box 1 released from necrotic cells enhances regrowth and metastasis of cancer cells that have survived chemotherapy. Eur J Cancer. 2013 Feb;49(3):741-51. doi: 10.1016/j.ejca.2012.09.016. Epub 2012 Oct 3. [PubMed:23040637 ]
  51. Li G, Liang X, Lotze MT: HMGB1: The Central Cytokine for All Lymphoid Cells. Front Immunol. 2013 Mar 20;4:68. doi: 10.3389/fimmu.2013.00068. eCollection 2013. [PubMed:23519706 ]
  52. Min HJ, Ko EA, Wu J, Kim ES, Kwon MK, Kwak MS, Choi JE, Lee JE, Shin JS: Chaperone-like activity of high-mobility group box 1 protein and its role in reducing the formation of polyglutamine aggregates. J Immunol. 2013 Feb 15;190(4):1797-806. doi: 10.4049/jimmunol.1202472. Epub 2013 Jan 9. [PubMed:23303669 ]
  53. 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: HMGB1-DNA complex-induced autophagy limits AIM2 inflammasome activation through RAGE. Biochem Biophys Res Commun. 2014 Jul 18;450(1):851-6. doi: 10.1016/j.bbrc.2014.06.074. Epub 2014 Jun 24. [PubMed:24971542 ]
  54. LeBlanc PM, Doggett TA, Choi J, Hancock MA, Durocher Y, Frank F, Nagar B, Ferguson TA, Saleh M: An immunogenic peptide in the A-box of HMGB1 protein reverses apoptosis-induced tolerance through RAGE receptor. J Biol Chem. 2014 Mar 14;289(11):7777-86. doi: 10.1074/jbc.M113.541474. Epub 2014 Jan 28. [PubMed:24474694 ]
  55. Antoine DJ, Harris HE, Andersson U, Tracey KJ, Bianchi ME: A systematic nomenclature for the redox states of high mobility group box (HMGB) proteins. Mol Med. 2014 Mar 24;20:135-7. doi: 10.2119/molmed.2014.00022. [PubMed:24531895 ]
  56. Musumeci D, Roviello GN, Montesarchio D: An overview on HMGB1 inhibitors as potential therapeutic agents in HMGB1-related pathologies. Pharmacol Ther. 2014 Mar;141(3):347-57. doi: 10.1016/j.pharmthera.2013.11.001. Epub 2013 Nov 9. [PubMed:24220159 ]
  57. Lee LC, Chen CM, Wang PR, Su MT, Lee-Chen GJ, Chang CY: Role of high mobility group box 1 (HMGB1) in SCA17 pathogenesis. PLoS One. 2014 Dec 30;9(12):e115809. doi: 10.1371/journal.pone.0115809. eCollection 2014. [PubMed:25549101 ]
  58. Lu M, Yu S, Xu W, Gao B, Xiong S: HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory Response. J Immunol Res. 2015;2015:946748. doi: 10.1155/2015/946748. Epub 2015 May 19. [PubMed:26078984 ]
  59. Kwak MS, Lim M, Lee YJ, Lee HS, Kim YH, Youn JH, Choi JE, Shin JS: HMGB1 Binds to Lipoteichoic Acid and Enhances TNF-alpha and IL-6 Production through HMGB1-Mediated Transfer of Lipoteichoic Acid to CD14 and TLR2. J Innate Immun. 2015;7(4):405-16. doi: 10.1159/000369972. Epub 2015 Feb 5. [PubMed:25660311 ]
  60. Avgousti DC, Herrmann C, Kulej K, Pancholi NJ, Sekulic N, Petrescu J, Molden RC, Blumenthal D, Paris AJ, Reyes ED, Ostapchuk P, Hearing P, Seeholzer SH, Worthen GS, Black BE, Garcia BA, Weitzman MD: A core viral protein binds host nucleosomes to sequester immune danger signals. Nature. 2016 Jul 7;535(7610):173-7. doi: 10.1038/nature18317. Epub 2016 Jun 29. [PubMed:27362237 ]
  61. Bonfiglio JJ, Fontana P, Zhang Q, Colby T, Gibbs-Seymour I, Atanassov I, Bartlett E, Zaja R, Ahel I, Matic I: Serine ADP-Ribosylation Depends on HPF1. Mol Cell. 2017 Mar 2;65(5):932-940.e6. doi: 10.1016/j.molcel.2017.01.003. Epub 2017 Feb 9. [PubMed:28190768 ]
  62. Willis WL, Wang L, Wada TT, Gardner M, Abdouni O, Hampton J, Valiente G, Young N, Ardoin S, Agarwal S, Freitas MA, Wu LC, Jarjour WN: The proinflammatory protein HMGB1 is a substrate of transglutaminase-2 and forms high-molecular weight complexes with autoantigens. J Biol Chem. 2018 Jun 1;293(22):8394-8409. doi: 10.1074/jbc.RA117.001078. Epub 2018 Apr 4. [PubMed:29618516 ]
  63. Rowell JP, Simpson KL, Stott K, Watson M, Thomas JO: HMGB1-facilitated p53 DNA binding occurs via HMG-Box/p53 transactivation domain interaction, regulated by the acidic tail. Structure. 2012 Dec 5;20(12):2014-24. doi: 10.1016/j.str.2012.09.004. Epub 2012 Oct 11. [PubMed:23063560 ]
  64. Wang J, Tochio N, Takeuchi A, Uewaki J, Kobayashi N, Tate S: Redox-sensitive structural change in the A-domain of HMGB1 and its implication for the binding to cisplatin modified DNA. Biochem Biophys Res Commun. 2013 Nov 29;441(4):701-6. [PubMed:24427810 ]