Hmdb loader

Showing Protein High mobility group protein B1 (HMDBP13800)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP13800
Secondary Accession Numbers None
Name High mobility group protein B1
Synonyms
  1. Amphoterin
  2. Heparin-binding protein p30
  3. High mobility group protein 1
  4. 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. 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.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).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).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).
Pathways
  • Autophagy - animal
  • Base excision repair
  • Necroptosis
  • Neutrophil extracellular trap formation
Reactions Not Available
GO Classification
Biological Process
response to drug
response to glucocorticoid stimulus
regulation of inflammatory response
positive regulation of cell death
positive regulation of cell proliferation
response to glucose stimulus
circadian rhythm
positive regulation of apoptotic process
response to lipopolysaccharide
inflammatory response
cellular response to lipopolysaccharide
lung development
neuron projection development
nervous system development
negative regulation of transcription from RNA polymerase II promoter
base-excision repair
autophagy
positive regulation of mitotic cell cycle
actin cytoskeleton reorganization
response to insulin stimulus
elevation of cytosolic calcium ion concentration
cellular response to interleukin-1
positive regulation of ERK1 and ERK2 cascade
regulation of transcription from RNA polymerase II promoter
positive regulation of transcription from RNA polymerase II promoter
response to interferon-gamma
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
positive regulation of interferon-beta production
positive regulation of interferon-alpha production
positive regulation of JNK cascade
positive regulation of cell migration
chemotaxis
negative regulation of DNA replication
positive regulation of DNA binding
positive regulation of protein phosphorylation
positive regulation of activated T cell proliferation
myoblast proliferation
response to heat
positive regulation of myoblast differentiation
endothelial cell proliferation
positive regulation of interleukin-12 production
cell morphogenesis
positive regulation of neuron projection development
chromatin silencing
positive regulation of monocyte chemotaxis
negative regulation of interferon-gamma production
positive regulation of blood vessel endothelial cell migration
positive regulation of innate immune response
apoptotic cell clearance
protein-containing complex assembly
positive regulation of smooth muscle cell migration
inflammatory response to antigenic stimulus
positive regulation of tumor necrosis factor production
positive regulation of interleukin-1 beta production
positive regulation of interleukin-6 production
positive regulation of NIK/NF-kappaB signaling
T-helper 1 cell differentiation
positive regulation of interleukin-10 production
positive regulation of interleukin-8 production
positive regulation of toll-like receptor 2 signaling pathway
positive regulation of vascular endothelial cell proliferation
positive regulation of monocyte chemotactic protein-1 production
positive regulation of wound healing
activation of innate immune response
positive regulation of MAPK cascade
cellular response to interleukin-7
positive regulation of sprouting angiogenesis
eye development
positive regulation of toll-like receptor 4 signaling pathway
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
regulation of tolerance induction
T-helper 1 cell activation
V(D)J recombination
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
induction of positive chemotaxis
male-specific defense response to bacterium
positive regulation of macrophage inflammatory protein 1 alpha production
positive regulation of mesenchymal cell proliferation
positive regulation of myeloid cell apoptotic process
Cellular Component
cytosol
cytoplasm
nucleus
extracellular space
cell surface
membrane raft
endoplasmic reticulum-Golgi intermediate compartment
neuron projection
early endosome
transcriptional repressor complex
condensed chromosome
alphav-beta3 integrin-HMGB1 complex
Molecular Function
heparin binding
peptide binding
transcription coactivator activity
lyase activity
bubble DNA binding
single-stranded DNA binding
double-stranded RNA binding
transcription factor binding
double-stranded DNA binding
single-stranded RNA binding
damaged DNA binding
protein kinase activator activity
cytokine activity
5S rRNA binding
integrin binding
lipopolysaccharide binding
transcription regulatory region sequence-specific DNA binding
phosphatidylserine 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
calcium-dependent protein kinase regulator activity
bent DNA binding
crossed form four-way junction DNA binding
glycolipid binding
open form four-way junction 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 P63159
UniProtKB/Swiss-Prot Entry Name HMGB1_RAT
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. Paonessa G, Frank R, Cortese R: Nucleotide sequence of rat liver HMG1 cDNA. Nucleic Acids Res. 1987 Nov 11;15(21):9077. doi: 10.1093/nar/15.21.9077. [PubMed:3684582 ]
  12. Merenmies J, Pihlaskari R, Laitinen J, Wartiovaara J, Rauvala H: 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. J Biol Chem. 1991 Sep 5;266(25):16722-9. [PubMed:1885601 ]
  13. Rauvala H, Merenmies J, Pihlaskari R, Korkolainen M, Huhtala ML, Panula P: 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. J Cell Biol. 1988 Dec;107(6 Pt 1):2293-305. doi: 10.1083/jcb.107.6.2293. [PubMed:2461949 ]
  14. Hori O, Brett J, Slattery T, Cao R, Zhang J, Chen JX, Nagashima M, Lundh ER, Vijay S, Nitecki D, et al.: 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. J Biol Chem. 1995 Oct 27;270(43):25752-61. doi: 10.1074/jbc.270.43.25752. [PubMed:7592757 ]
  15. Milev P, Chiba A, Haring M, Rauvala H, Schachner M, Ranscht B, Margolis RK, Margolis RU: 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. J Biol Chem. 1998 Mar 20;273(12):6998-7005. doi: 10.1074/jbc.273.12.6998. [PubMed:9507007 ]
  16. Stros M, Cherny D, Jovin TM: HMG1 protein stimulates DNA end joining by promoting association of DNA molecules via their ends. Eur J Biochem. 2000 Jul;267(13):4088-97. doi: 10.1046/j.1432-1327.2000.01450.x. [PubMed:10866811 ]
  17. Taguchi A, Blood DC, del Toro G, Canet A, Lee DC, Qu W, Tanji N, Lu Y, Lalla E, Fu C, Hofmann MA, Kislinger T, Ingram M, Lu A, Tanaka H, Hori O, Ogawa S, Stern DM, Schmidt AM: Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases. Nature. 2000 May 18;405(6784):354-60. doi: 10.1038/35012626. [PubMed:10830965 ]
  18. Muller S, Bianchi ME, Knapp S: Thermodynamics of HMGB1 interaction with duplex DNA. Biochemistry. 2001 Aug 28;40(34):10254-61. doi: 10.1021/bi0100900. [PubMed:11513603 ]
  19. Huttunen HJ, Fages C, Kuja-Panula J, Ridley AJ, Rauvala H: Receptor for advanced glycation end products-binding COOH-terminal motif of amphoterin inhibits invasive migration and metastasis. Cancer Res. 2002 Aug 15;62(16):4805-11. [PubMed:12183440 ]
  20. Bonaldi T, Langst G, Strohner R, Becker PB, Bianchi ME: The DNA chaperone HMGB1 facilitates ACF/CHRAC-dependent nucleosome sliding. EMBO J. 2002 Dec 16;21(24):6865-73. doi: 10.1093/emboj/cdf692. [PubMed:12486007 ]
  21. Knapp S, Muller S, Digilio G, Bonaldi T, Bianchi ME, Musco G: 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. Biochemistry. 2004 Sep 28;43(38):11992-7. doi: 10.1021/bi049364k. [PubMed:15379539 ]
  22. Agresti A, Scaffidi P, Riva A, Caiolfa VR, Bianchi ME: GR and HMGB1 interact only within chromatin and influence each other's residence time. Mol Cell. 2005 Apr 1;18(1):109-21. doi: 10.1016/j.molcel.2005.03.005. [PubMed:15808513 ]
  23. Ugrinova I, Mitkova E, Moskalenko C, Pashev I, Pasheva E: DNA bending versus DNA end joining activity of HMGB1 protein is modulated in vitro by acetylation. Biochemistry. 2007 Feb 27;46(8):2111-7. doi: 10.1021/bi0614479. Epub 2007 Feb 1. [PubMed:17269659 ]
  24. Zhang LT, Yao YM, Dong YQ, Dong N, Yu Y, Sheng ZY: Relationship between high-mobility group box 1 protein release and T-cell suppression in rats after thermal injury. Shock. 2008 Oct;30(4):449-55. doi: 10.1097/SHK.0b013e3181672495. [PubMed:18277947 ]
  25. Yang H, Lundback P, Ottosson L, Erlandsson-Harris H, Venereau E, Bianchi ME, Al-Abed Y, Andersson U, Tracey KJ, Antoine DJ: Redox modification of cysteine residues regulates the cytokine activity of high mobility group box-1 (HMGB1). Mol Med. 2012 Mar 30;18:250-9. doi: 10.2119/molmed.2011.00389. [PubMed:22105604 ]
  26. Kim S, Kim SY, Pribis JP, Lotze M, Mollen KP, Shapiro R, Loughran P, Scott MJ, Billiar TR: Signaling of high mobility group box 1 (HMGB1) through toll-like receptor 4 in macrophages requires CD14. Mol Med. 2013 May 20;19:88-98. doi: 10.2119/molmed.2012.00306. [PubMed:23508573 ]
  27. Polanska E, Pospisilova S, Stros M: Binding of histone H1 to DNA is differentially modulated by redox state of HMGB1. PLoS One. 2014 Feb 13;9(2):e89070. doi: 10.1371/journal.pone.0089070. eCollection 2014. [PubMed:24551219 ]
  28. Weir HM, Kraulis PJ, Hill CS, Raine AR, Laue ED, Thomas JO: Structure of the HMG box motif in the B-domain of HMG1. EMBO J. 1993 Apr;12(4):1311-9. [PubMed:8467791 ]
  29. Hardman CH, Broadhurst RW, Raine AR, Grasser KD, Thomas JO, Laue ED: Structure of the A-domain of HMG1 and its interaction with DNA as studied by heteronuclear three- and four-dimensional NMR spectroscopy. Biochemistry. 1995 Dec 26;34(51):16596-607. doi: 10.1021/bi00051a007. [PubMed:8527432 ]