ID HMGB1_MOUSE Reviewed; 215 AA. AC P63158; P07155; P27109; P27428; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 27-MAR-2024, entry version 180. DE RecName: Full=High mobility group protein B1; DE AltName: Full=High mobility group protein 1; DE Short=HMG-1; GN Name=Hmgb1; Synonyms=Hmg-1, Hmg1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=C3H/He; RX PubMed=1630928; DOI=10.1093/nar/20.13.3516; RA Yotov W.V., St Arnaud R.; RT "Nucleotide sequence of a mouse cDNA encoding the nonhistone chromosomal RT high mobility group protein-1 (HMG1)."; RL Nucleic Acids Res. 20:3516-3516(1992). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=129/Sv; TISSUE=Liver; RX PubMed=7961836; DOI=10.1016/s0021-9258(19)61977-0; RA Ferrari S., Ronfani L., Calogero S., Bianchi M.; RT "The mouse gene coding for high mobility group 1 protein (HMG1)."; RL J. Biol. Chem. 269:28803-28808(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8180479; DOI=10.1007/bf00292334; RA Pauken C.M., Nagle D.L., Bucan M., Lo C.W.; RT "Molecular cloning, expression analysis, and chromosomal localization of RT mouse Hmg1-containing sequences."; RL Mamm. Genome 5:91-99(1994). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=AKR/J; RX PubMed=9047378; DOI=10.1016/s0161-5890(96)00073-9; RA Marrugo J., Marsh D.G., Ghosh B.; RT "The conserved lymphokine element-0 in the IL5 promoter binds to a high RT mobility group-1 protein."; RL Mol. Immunol. 33:1119-1125(1996). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PROTEIN SEQUENCE OF 31-43 AND 113-127, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC STRAIN=C57BL/6J; TISSUE=Brain; RA Lubec G., Kang S.U.; RL Submitted (APR-2007) to UniProtKB. RN [7] RP SUBCELLULAR LOCATION. RX PubMed=2461949; DOI=10.1083/jcb.107.6.2293; RA Rauvala H., Merenmies J., Pihlaskari R., Korkolainen M., Huhtala M.L., RA Panula P.; RT "The adhesive and neurite-promoting molecule p30: analysis of the amino- RT terminal sequence and production of antipeptide antibodies that detect p30 RT at the surface of neuroblastoma cells and of brain neurons."; RL J. Cell Biol. 107:2293-2305(1988). RN [8] RP FUNCTION, AND IDENTIFICATION IN THE RAG COMPLEX. RX PubMed=9184213; DOI=10.1093/emboj/16.10.2665; RA van Gent D.C., Hiom K., Paull T.T., Gellert M.; RT "Stimulation of V(D)J cleavage by high mobility group proteins."; RL EMBO J. 16:2665-2670(1997). RN [9] RP DISRUPTION PHENOTYPE. RX PubMed=10391216; DOI=10.1038/10338; RA Calogero S., Grassi F., Aguzzi A., Voigtlaender T., Ferrier P., Ferrari S., RA Bianchi M.E.; RT "The lack of chromosomal protein Hmg1 does not disrupt cell growth but RT causes lethal hypoglycaemia in newborn mice."; RL Nat. Genet. 22:276-280(1999). RN [10] RP INVOLVEMENT IN SEPSIS. RX PubMed=10398600; DOI=10.1126/science.285.5425.248; RA Wang H., Bloom O., Zhang M., Vishnubhakat J.M., Ombrellino M., Che J., RA Frazier A., Yang H., Ivanova S., Borovikova L., Manogue K.R., Faist E., RA Abraham E., Andersson J., Andersson U., Molina P.E., Abumrad N.N., Sama A., RA Tracey K.J.; RT "HMG-1 as a late mediator of endotoxin lethality in mice."; RL Science 285:248-251(1999). RN [11] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=12110890; DOI=10.1038/nature00858; RA Scaffidi P., Misteli T., Bianchi M.E.; RT "Release of chromatin protein HMGB1 by necrotic cells triggers RT inflammation."; RL Nature 418:191-195(2002). RN [12] RP FUNCTION, AND INTERACTION WITH SREBF1. RX PubMed=16040616; DOI=10.1074/jbc.m414549200; RA Najima Y., Yahagi N., Takeuchi Y., Matsuzaka T., Sekiya M., Nakagawa Y., RA Amemiya-Kudo M., Okazaki H., Okazaki S., Tamura Y., Iizuka Y., Ohashi K., RA Harada K., Gotoda T., Nagai R., Kadowaki T., Ishibashi S., Yamada N., RA Osuga J., Shimano H.; RT "High mobility group protein-B1 interacts with sterol regulatory element- RT binding proteins to enhance their DNA binding."; RL J. Biol. Chem. 280:27523-27532(2005). RN [13] RP INTERACTION WITH TLR2 AND TLR4. RX PubMed=16267105; DOI=10.1152/ajpcell.00401.2005; RA Park J.S., Gamboni-Robertson F., He Q., Svetkauskaite D., Kim J.Y., RA Strassheim D., Sohn J.W., Yamada S., Maruyama I., Banerjee A., Ishizaka A., RA Abraham E.; RT "High mobility group box 1 protein interacts with multiple Toll-like RT receptors."; RL Am. J. Physiol. 290:C917-C924(2006). RN [14] RP FUNCTION. RX PubMed=16365390; DOI=10.4049/jimmunol.176.1.12; RA Mitola S., Belleri M., Urbinati C., Coltrini D., Sparatore B., Pedrazzi M., RA Melloni E., Presta M.; RT "Extracellular high mobility group box-1 protein is a proangiogenic RT cytokine."; RL J. Immunol. 176:12-15(2006). RN [15] RP PHOSPHORYLATION, SUBCELLULAR LOCATION, AND INTERACTION WITH KPNA1. RX PubMed=17114460; DOI=10.4049/jimmunol.177.11.7889; RA Youn J.H., Shin J.S.; RT "Nucleocytoplasmic shuttling of HMGB1 is regulated by phosphorylation that RT redirects it toward secretion."; RL J. Immunol. 177:7889-7897(2006). RN [16] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TLR9. RX PubMed=17548579; DOI=10.1182/blood-2006-09-044776; RA Ivanov S., Dragoi A.M., Wang X., Dallacosta C., Louten J., Musco G., RA Sitia G., Yap G.S., Wan Y., Biron C.A., Bianchi M.E., Wang H., Chu W.M.; RT "A novel role for HMGB1 in TLR9-mediated inflammatory responses to CpG- RT DNA."; RL Blood 110:1970-1981(2007). RN [17] RP FUNCTION. RX PubMed=17268551; DOI=10.1038/sj.emboj.7601552; RA Orlova V.V., Choi E.Y., Xie C., Chavakis E., Bierhaus A., Ihanus E., RA Ballantyne C.M., Gahmberg C.G., Bianchi M.E., Nawroth P.P., Chavakis T.; RT "A novel pathway of HMGB1-mediated inflammatory cell recruitment that RT requires Mac-1-integrin."; RL EMBO J. 26:1129-1139(2007). RN [18] RP FUNCTION. RX PubMed=17568691; DOI=10.1016/j.imlet.2007.04.011; RA El Mezayen R., El Gazzar M., Seeds M.C., McCall C.E., Dreskin S.C., RA Nicolls M.R.; RT "Endogenous signals released from necrotic cells augment inflammatory RT responses to bacterial endotoxin."; RL Immunol. Lett. 111:36-44(2007). RN [19] RP FUNCTION, AND INTERACTION WITH APEX1; FEN1 AND POLB. RX PubMed=17803946; DOI=10.1016/j.molcel.2007.06.029; RA Prasad R., Liu Y., Deterding L.J., Poltoratsky V.P., Kedar P.S., RA Horton J.K., Kanno S., Asagoshi K., Hou E.W., Khodyreva S.N., Lavrik O.I., RA Tomer K.B., Yasui A., Wilson S.H.; RT "HMGB1 is a cofactor in mammalian base excision repair."; RL Mol. Cell 27:829-841(2007). RN [20] RP FUNCTION, POLY-ADP-RIBOSYLATION, AND PHOSPHATIDYLSERINE-BINDING. RX PubMed=18768881; DOI=10.4049/jimmunol.181.6.4240; RA Liu G., Wang J., Park Y.J., Tsuruta Y., Lorne E.F., Zhao X., Abraham E.; RT "High mobility group protein-1 inhibits phagocytosis of apoptotic RT neutrophils through binding to phosphatidylserine."; RL J. Immunol. 181:4240-4246(2008). RN [21] RP FUNCTION. RX PubMed=18650382; DOI=10.1073/pnas.0803181105; RA Lange S.S., Mitchell D.L., Vasquez K.M.; RT "High mobility group protein B1 enhances DNA repair and chromatin RT modification after DNA damage."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10320-10325(2008). RN [22] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19890330; DOI=10.1038/nature08512; RA Yanai H., Ban T., Wang Z., Choi M.K., Kawamura T., Negishi H., Nakasato M., RA Lu Y., Hangai S., Koshiba R., Savitsky D., Ronfani L., Akira S., RA Bianchi M.E., Honda K., Tamura T., Kodama T., Taniguchi T.; RT "HMGB proteins function as universal sentinels for nucleic-acid-mediated RT innate immune responses."; RL Nature 462:99-103(2009). RN [23] RP FUNCTION, AND INTERACTION WITH CD24. RX PubMed=19264983; DOI=10.1126/science.1168988; RA Chen G.Y., Tang J., Zheng P., Liu Y.; RT "CD24 and Siglec-10 selectively repress tissue damage-induced immune RT responses."; RL Science 323:1722-1725(2009). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [25] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BECN1. RX PubMed=20819940; DOI=10.1083/jcb.200911078; RA Tang D., Kang R., Livesey K.M., Cheh C.W., Farkas A., Loughran P., RA Hoppe G., Bianchi M.E., Tracey K.J., Zeh H.J. III, Lotze M.T.; RT "Endogenous HMGB1 regulates autophagy."; RL J. Cell Biol. 190:881-892(2010). RN [26] RP ROLE OF NRLC4 AND NLRP3 INFLAMMASOMES IN HMGB1 RELEASE, AND SUBCELLULAR RP LOCATION. RX PubMed=20802146; DOI=10.4049/jimmunol.1000803; RA Lamkanfi M., Sarkar A., Vande Walle L., Vitari A.C., Amer A.O., RA Wewers M.D., Tracey K.J., Kanneganti T.D., Dixit V.M.; RT "Inflammasome-dependent release of the alarmin HMGB1 in endotoxemia."; RL J. Immunol. 185:4385-4392(2010). RN [27] RP FUNCTION. RX PubMed=21395369; DOI=10.1089/ars.2010.3666; RA Tang D., Kang R., Livesey K.M., Zeh H.J., Lotze M.T.; RT "High mobility group box 1 (HMGB1) activates an autophagic response to RT oxidative stress."; RL Antioxid. Redox Signal. 15:2185-2195(2011). RN [28] RP FUNCTION. RX PubMed=21641551; DOI=10.1016/j.cmet.2011.04.008; RA Tang D., Kang R., Livesey K.M., Kroemer G., Billiar T.R., Van Houten B., RA Zeh H.J., Lotze M.T.; RT "High-mobility group box 1 is essential for mitochondrial quality RT control."; RL Cell Metab. 13:701-711(2011). RN [29] RP FUNCTION. RX PubMed=21419643; DOI=10.1016/j.cyto.2011.02.017; RA Zhu X.M., Yao Y.M., Liang H.P., Xu C.T., Dong N., Yu Y., Sheng Z.Y.; RT "High mobility group box-1 protein regulate immunosuppression of regulatory RT T cells through toll-like receptor 4."; RL Cytokine 54:296-304(2011). RN [30] RP SUBCELLULAR LOCATION. RX PubMed=21319304; DOI=10.1002/pmic.201000491; RA Vettermann C., Castor D., Mekker A., Gerrits B., Karas M., Jack H.M.; RT "Proteome profiling suggests a pro-inflammatory role for plasma cells RT through release of high-mobility group box 1 protein."; RL Proteomics 11:1228-1237(2011). RN [31] RP FUNCTION, AND INTERACTION WITH TERT. RX PubMed=22544226; DOI=10.1007/s00412-012-0373-x; RA Polanska E., Dobsakova Z., Dvorackova M., Fajkus J., Stros M.; RT "HMGB1 gene knockout in mouse embryonic fibroblasts results in reduced RT telomerase activity and telomere dysfunction."; RL Chromosoma 121:419-431(2012). RN [32] RP FUNCTION, AND INTERACTION WITH CXCL12. RX PubMed=22370717; DOI=10.1084/jem.20111739; RA Schiraldi M., Raucci A., Munoz L.M., Livoti E., Celona B., Venereau E., RA Apuzzo T., De Marchis F., Pedotti M., Bachi A., Thelen M., Varani L., RA Mellado M., Proudfoot A., Bianchi M.E., Uguccioni M.; RT "HMGB1 promotes recruitment of inflammatory cells to damaged tissues by RT forming a complex with CXCL12 and signaling via CXCR4."; RL J. Exp. Med. 209:551-563(2012). RN [33] RP RETRACTED PAPER. RX PubMed=22105604; DOI=10.2119/molmed.2011.00389; RA Yang H., Lundback P., Ottosson L., Erlandsson-Harris H., Venereau E., RA Bianchi M.E., Al-Abed Y., Andersson U., Tracey K.J., Antoine D.J.; RT "Redox modification of cysteine residues regulates the cytokine activity of RT high mobility group box-1 (HMGB1)."; RL Mol. Med. 18:250-259(2012). RN [34] RP RETRACTION NOTICE OF PUBMED:22105604. RX PubMed=33380312; DOI=10.1186/s10020-020-00264-1; RA Yang H., Lundbaeck P., Ottosson L., Erlandsson-Harris H., Venereau E., RA Bianchi M.E., Al-Abed Y., Andersson U., Tracey K.J., Antoine D.J.; RT "Retraction Note to: Redox modification of cysteine residues regulates the RT cytokine activity of high mobility group box-1 (HMGB1)."; RL Mol. Med. 26:133-133(2020). RN [35] RP FUNCTION, AND POLY-ADP-RIBOSYLATION. RX PubMed=22204001; DOI=10.2119/molmed.2011.00203; RA Davis K., Banerjee S., Friggeri A., Bell C., Abraham E., Zerfaoui M.; RT "Poly(ADP-ribosyl)ation of high mobility group box 1 (HMGB1) protein RT enhances inhibition of efferocytosis."; RL Mol. Med. 18:359-369(2012). RN [36] RP INTERACTION WITH HAVCR2. RX PubMed=22842346; DOI=10.1038/ni.2376; RA Chiba S., Baghdadi M., Akiba H., Yoshiyama H., Kinoshita I., RA Dosaka-Akita H., Fujioka Y., Ohba Y., Gorman J.V., Colgan J.D., RA Hirashima M., Uede T., Takaoka A., Yagita H., Jinushi M.; RT "Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune RT responses through interactions between the receptor TIM-3 and the alarmin RT HMGB1."; RL Nat. Immunol. 13:832-842(2012). RN [37] RP FUNCTION. RX PubMed=23108142; DOI=10.1158/0008-5472.can-12-2704; RA He Y., Zha J., Wang Y., Liu W., Yang X., Yu P.; RT "Tissue damage-associated 'danger signals' influence T-cell responses that RT promote the progression of preneoplasia to cancer."; RL Cancer Res. 73:629-639(2013). RN [38] RP REVIEW ON FUNCTION RELATED TO ADAPTIVE IMMUNITY. RX PubMed=23519706; DOI=10.3389/fimmu.2013.00068; RA Li G., Liang X., Lotze M.T.; RT "HMGB1: The central cytokine for all lymphoid cells."; RL Front. Immunol. 4:68-68(2013). RN [39] RP REVIEW ON FUNCTION RELATED TO INFLAMMATION. RX PubMed=23446148; DOI=10.1189/jlb.1212662; RA Yang H., Antoine D.J., Andersson U., Tracey K.J.; RT "The many faces of HMGB1: molecular structure-functional activity in RT inflammation, apoptosis, and chemotaxis."; RL J. Leukoc. Biol. 93:865-873(2013). RN [40] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-30; LYS-43; LYS-90 AND LYS-141, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001; RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.; RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic RT pathways."; RL Mol. Cell 50:919-930(2013). RN [41] RP FUNCTION. RX PubMed=24302768; DOI=10.1073/pnas.1320808110; RA Yanai H., Matsuda A., An J., Koshiba R., Nishio J., Negishi H., RA Ikushima H., Onoe T., Ohdan H., Yoshida N., Taniguchi T.; RT "Conditional ablation of HMGB1 in mice reveals its protective function RT against endotoxemia and bacterial infection."; RL Proc. Natl. Acad. Sci. U.S.A. 110:20699-20704(2013). RN [42] RP REVIEW. RX PubMed=23994764; DOI=10.1016/j.semcancer.2013.08.002; RA Li G., Tang D., Lotze M.T.; RT "Menage a Trois in stress: DAMPs, redox and autophagy."; RL Semin. Cancer Biol. 23:380-390(2013). RN [43] RP FUNCTION. RX PubMed=24606906; DOI=10.1016/j.cmet.2014.01.014; RA Huebener P., Gwak G.Y., Pradere J.P., Quinzii C.M., Friedman R., Lin C.S., RA Trent C.M., Mederacke I., Zhao E., Dapito D.H., Lin Y., Goldberg I.J., RA Czaja M.J., Schwabe R.F.; RT "High-mobility group box 1 is dispensable for autophagy, mitochondrial RT quality control, and organ function in vivo."; RL Cell Metab. 19:539-547(2014). RN [44] RP REVIEW ON FUNCTION RELATED TO INNATE IMMUNITY. RX PubMed=25048472; DOI=10.3349/ymj.2014.55.5.1165; RA Lee S.A., Kwak M.S., Kim S., Shin J.S.; RT "The role of high mobility group box 1 in innate immunity."; RL Yonsei Med. J. 55:1165-1176(2014). RN [45] RP FUNCTION. RX PubMed=25642769; DOI=10.1172/jci76344; RA Zhu X., Messer J.S., Wang Y., Lin F., Cham C.M., Chang J., Billiar T.R., RA Lotze M.T., Boone D.L., Chang E.B.; RT "Cytosolic HMGB1 controls the cellular autophagy/apoptosis checkpoint RT during inflammation."; RL J. Clin. Invest. 125:1098-1110(2015). RN [46] RP TISSUE SPECIFICITY, AND INVOLVEMENT IN AUTOIMMUNE DISEASE. RX PubMed=26078984; DOI=10.1155/2015/946748; RA Lu M., Yu S., Xu W., Gao B., Xiong S.; RT "HMGB1 promotes systemic lupus erythematosus by enhancing macrophage RT inflammatory response."; RL J. Immunol. Res. 2015:946748-946748(2015). RN [47] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=25660970; DOI=10.1016/j.molimm.2015.01.023; RA Li X., Yue Y., Zhu Y., Xiong S.; RT "Extracellular, but not intracellular HMGB1, facilitates self-DNA induced RT macrophage activation via promoting DNA accumulation in endosomes and RT contributes to the pathogenesis of lupus nephritis."; RL Mol. Immunol. 65:177-188(2015). CC -!- FUNCTION: Multifunctional redox sensitive protein with various roles in CC different cellular compartments. In the nucleus is one of the major CC chromatin-associated non-histone proteins and acts as a DNA chaperone CC involved in replication, transcription, chromatin remodeling, V(D)J CC recombination, DNA repair and genome stability. Proposed to be an CC universal biosensor for nucleic acids. Promotes host inflammatory CC response to sterile and infectious signals and is involved in the CC coordination and integration of innate and adaptive immune responses. CC In the cytoplasm functions as a sensor and/or chaperone for immunogenic CC nucleic acids implicating the activation of TLR9-mediated immune CC responses, and mediates autophagy. Acts as a danger associated CC molecular pattern (DAMP) molecule that amplifies immune responses CC during tissue injury. Released to the extracellular environment can CC bind DNA, nucleosomes, IL-1 beta, CXCL12, AGER isoform 2/sRAGE, CC lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and activates CC cells through engagement of multiple surface receptors. In the CC extracellular compartment fully reduced HMGB1 (released by necrosis) CC acts as a chemokine, disulfide HMGB1 (actively secreted) as a cytokine, CC and sulfonyl HMGB1 (released from apoptotic cells) promotes CC immunological tolerance (PubMed:23519706, PubMed:23446148, CC PubMed:23994764, PubMed:25048472). Has proangiogenic activity CC (PubMed:16365390). May be involved in platelet activation. Binds to CC phosphatidylserine and phosphatidylethanolamide. Bound to RAGE mediates CC signaling for neuronal outgrowth. May play a role in accumulation of CC expanded polyglutamine (polyQ) proteins (By similarity). CC {ECO:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P10103, CC ECO:0000250|UniProtKB:P12682, ECO:0000250|UniProtKB:P63159, CC ECO:0000269|PubMed:16365390, ECO:0000305|PubMed:23446148, CC ECO:0000305|PubMed:23519706, ECO:0000305|PubMed:23994764, CC ECO:0000305|PubMed:25048472}. CC -!- FUNCTION: Nuclear functions are attributed to fully reduced HGMB1. CC Associates with chromatin and binds DNA with a preference to non- CC canonical DNA structures such as single-stranded DNA, DNA-containing CC cruciforms or bent structures, supercoiled DNA and ZDNA. Can bent DNA CC and enhance DNA flexibility by looping thus providing a mechanism to CC promote activities on various gene promoters by enhancing transcription CC factor binding and/or bringing distant regulatory sequences into close CC proximity. May be involved in nucleotide excision repair (NER), CC mismatch repair (MMR) and base excision repair (BER) pathways, and CC double strand break repair such as non-homologous end joining (NHEJ) CC (PubMed:17803946, PubMed:18650382). Involved in V(D)J recombination by CC acting as a cofactor of the RAG complex: acts by stimulating cleavage CC and RAG protein binding at the 23 bp spacer of conserved recombination CC signal sequences (RSS). In vitro can displace histone H1 from highly CC bent DNA. Can restructure the canonical nucleosome leading to CC relaxation of structural constraints for transcription factor-binding CC (By similarity). Enhances binding of sterol regulatory element-binding CC proteins (SREBPs) such as SREBF1 to their cognate DNA sequences and CC increases their transcriptional activities (PubMed:16040616). CC Facilitates binding of TP53 to DNA (By similarity). Proposed to be CC involved in mitochondrial quality control and autophagy in a CC transcription-dependent fashion implicating HSPB1; however, this CC function has been questioned (PubMed:21641551, PubMed:24606906). Can CC modulate the activity of the telomerase complex and may be involved in CC telomere maintenance (PubMed:22544226). {ECO:0000250|UniProtKB:P09429, CC ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P63159, CC ECO:0000269|PubMed:16040616, ECO:0000269|PubMed:17803946, CC ECO:0000269|PubMed:18650382, ECO:0000269|PubMed:21641551, CC ECO:0000269|PubMed:22544226, ECO:0000269|PubMed:24606906}. CC -!- FUNCTION: In the cytoplasm proposed to dissociate the BECN1:BCL2 CC complex via competitive interaction with BECN1 leading to autophagy CC activation (PubMed:21395369). Can protect BECN1 and ATG5 from calpain- CC mediated cleavage and thus proposed to control their proautophagic and CC proapoptotic functions and to regulate the extent and severity of CC inflammation-associated cellular injury (PubMed:25642769). In myeloid CC cells has a protective role against endotoxemia and bacterial infection CC by promoting autophagy (PubMed:24302768). Involved in endosomal CC translocation and activation of TLR9 in response to CpG-DNA in CC macrophages (PubMed:17548579). {ECO:0000250|UniProtKB:P09429, CC ECO:0000269|PubMed:17548579, ECO:0000269|PubMed:20819940, CC ECO:0000269|PubMed:21395369, ECO:0000269|PubMed:24302768, CC ECO:0000269|PubMed:25642769}. CC -!- FUNCTION: In the extracellular compartment (following either active CC secretion or passive release) involved in regulation of the CC inflammatory response. Fully reduced HGMB1 (which subsequently gets CC oxidized after release) in association with CXCL12 mediates the CC recruitment of inflammatory cells during the initial phase of tissue CC injury; the CXCL12:HMGB1 complex triggers CXCR4 homodimerization CC (PubMed:22370717). Induces the migration of monocyte-derived immature CC dendritic cells and seems to regulate adhesive and migratory functions CC of neutrophils implicating AGER/RAGE and ITGAM (PubMed:17268551). Can CC bind to various types of DNA and RNA including microbial unmethylated CC CpG-DNA to enhance the innate immune response to nucleic acids. CC Proposed to act in promiscuous DNA/RNA sensing which cooperates with CC subsequent discriminative sensing by specific pattern recognition CC receptors (PubMed:19890330). Promotes extracellular DNA-induced AIM2 CC inflammasome activation implicating AGER/RAGE. Disulfide HMGB1 binds to CC transmembrane receptors, such as AGER/RAGE, TLR2, TLR4 and probably CC TREM1, thus activating their signal transduction pathways CC (PubMed:17568691, PubMed:19264983, PubMed:21419643). Mediates the CC release of cytokines/chemokines such as TNF, IL-1, IL-6, IL-8, CCL2, CC CCL3, CCL4 and CXCL10 (PubMed:12110890, PubMed:17548579). Promotes CC secretion of interferon-gamma by macrophage-stimulated natural killer CC (NK) cells in concert with other cytokines like IL-2 or IL-12. TLR4 is CC proposed to be the primary receptor promoting macrophage activation and CC signaling through TLR4 seems to implicate LY96/MD-2. In bacterial CC LPS- or LTA-mediated inflammatory responses binds to the endotoxins and CC transfers them to CD14 for signaling to the respective TLR4:LY96 and CC TLR2 complexes (By similarity). Contributes to tumor proliferation by CC association with ACER/RAGE (By similarity). Can bind to IL1-beta and CC signals through the IL1R1:IL1RAP receptor complex (By similarity). CC Binding to class A CpG activates cytokine production in plasmacytoid CC dendritic cells implicating TLR9, MYD88 and AGER/RAGE and can activate CC autoreactive B cells. Via HMGB1-containing chromatin immune complexes CC may also promote B cell responses to endogenous TLR9 ligands through a CC B-cell receptor (BCR)-dependent and ACER/RAGE-independent mechanism (By CC similarity). Inhibits phagocytosis of apoptotic cells by macrophages; CC the function is dependent on poly-ADP-ribosylation and involves binding CC to phosphatidylserine on the cell surface of apoptotic cells CC (PubMed:22204001, PubMed:18768881). In adaptive immunity may be CC involved in enhancing immunity through activation of effector T-cells CC and suppression of regulatory T (TReg) cells (PubMed:21419643). In CC contrast, without implicating effector or regulatory T-cells, required CC for tumor infiltration and activation of T-cells expressing the CC lymphotoxin LTA:LTB heterotrimer thus promoting tumor malignant CC progression (PubMed:23108142). Also reported to limit proliferation of CC T-cells (By similarity). Released HMGB1:nucleosome complexes formed CC during apoptosis can signal through TLR2 to induce cytokine production CC (By similarity). Involved in induction of immunological tolerance by CC apoptotic cells; its pro-inflammatory activities when released by CC apoptotic cells are neutralized by reactive oxygen species (ROS)- CC dependent oxidation specifically on Cys-106 (By similarity). During CC macrophage activation by activated lymphocyte-derived self apoptotic CC DNA (ALD-DNA) promotes recruitment of ALD-DNA to endosomes CC (PubMed:25660970). {ECO:0000250|UniProtKB:P09429, CC ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P63159, CC ECO:0000269|PubMed:12110890, ECO:0000269|PubMed:17268551, CC ECO:0000269|PubMed:17568691, ECO:0000269|PubMed:18768881, CC ECO:0000269|PubMed:19264983, ECO:0000269|PubMed:21419643, CC ECO:0000269|PubMed:22204001, ECO:0000269|PubMed:22370717, CC ECO:0000269|PubMed:23108142, ECO:0000269|PubMed:25660970, CC ECO:0000305|PubMed:19890330}. CC -!- SUBUNIT: Interacts (fully reduced HMGB1) with CXCL12; probably in a 1:2 CC ratio involving two molecules of CXCL12, each interacting with one HMG CC box of HMGB1; inhibited by glycyrrhizin (PubMed:22370717). Associates CC with the TLR4:LY96 receptor complex (By similarity). Component of the CC RAG complex composed of core components RAG1 and RAG2, and associated CC component HMGB1 or HMGB2 (PubMed:9184213). Interacts (in cytoplasm upon CC starvation) with BECN1; inhibits the interaction of BECN1 and BCL2 CC leading to promotion of autophagy (PubMed:20819940). Interacts with CC KPNA1; involved in nuclear import (PubMed:17114460). Interacts with CC SREBF1, TLR2, TLR4, TLR9, APEX1, FEN1, POLB, TERT (PubMed:16040616, CC PubMed:16267105, PubMed:17548579, PubMed:17803946, PubMed:22544226). CC Interacts with AGER, PTPRZ1, IL1B, MSH2, XPA, XPC, HNF1A, TP53 (By CC similarity). Interacts with CD24; the probable CD24:SIGLEC10 complex is CC proposed to inhibit HGMB1-mediated tissue damage immune response CC (PubMed:19264983). Interacts with THBD; prevents HGMB1 interaction with CC ACER/RAGE and inhibits HGMB1 pro-inflammatory activity (By similarity). CC Interacts with HAVCR2; impairs HMGB1 binding to B-DNA and likely HMGB1- CC mediated innate immune response (PubMed:22842346). Interacts with XPO1; CC mediating nuclear export (By similarity). Interacts with receptor CC RAGE/AGER (By similarity). {ECO:0000250|UniProtKB:P09429, CC ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P63159, CC ECO:0000269|PubMed:16040616, ECO:0000269|PubMed:16267105, CC ECO:0000269|PubMed:17114460, ECO:0000269|PubMed:17548579, CC ECO:0000269|PubMed:17803946, ECO:0000269|PubMed:19264983, CC ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:22370717, CC ECO:0000269|PubMed:22544226, ECO:0000269|PubMed:22842346, CC ECO:0000269|PubMed:9184213}. CC -!- INTERACTION: CC P63158; O88597: Becn1; NbExp=3; IntAct=EBI-6665811, EBI-643716; CC P63158; Q8VIM0: Havcr2; NbExp=4; IntAct=EBI-6665811, EBI-6665112; CC P63158; Q01860: POU5F1; Xeno; NbExp=3; IntAct=EBI-6665811, EBI-475687; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17114460, CC ECO:0000269|PubMed:20819940}. Cytoplasm {ECO:0000269|PubMed:17114460, CC ECO:0000269|PubMed:20819940}. Chromosome {ECO:0000269|PubMed:12110890}. CC Cell membrane {ECO:0000269|PubMed:2461949}; Peripheral membrane protein CC {ECO:0000269|PubMed:2461949}; Extracellular side CC {ECO:0000269|PubMed:2461949}. Endosome {ECO:0000269|PubMed:19890330}. CC Endoplasmic reticulum-Golgi intermediate compartment CC {ECO:0000305|PubMed:17548579}. Secreted {ECO:0000269|PubMed:21319304}. CC Note=In basal state predominantly nuclear. Shuttles between the CC cytoplasm and the nucleus (PubMed:17114460). Translocates from the CC nucleus to the cytoplasm upon autophagy stimulation (PubMed:20819940). CC Release from macrophages in the extracellular milieu requires the CC activation of NLRC4 or NLRP3 inflammasomes (PubMed:20802146). Passively CC released to the extracellular milieu from necrotic cells by diffusion, CC involving the fully reduced form which subsequently gets oxidized CC (PubMed:12110890). Also released from apoptotic cells CC (PubMed:25660970). Actively secreted from a variety of immune and non- CC immune cells such as macrophages, monocytes, neutrophils, dendritic CC cells and natural killer cells in response to various stimuli, CC involving a nonconventional secretory process via secretory lysosomes CC (PubMed:17548579). Secreted by plasma cells in response to LPS CC (PubMed:21319304). Associated with the plasma membrane of filipodia in CC process-growing cells, and also deposited into the substrate-attached CC material (By similarity). Colocalizes with RIGI on endosomal membranes CC (PubMed:19890330). {ECO:0000250|UniProtKB:P09429, CC ECO:0000269|PubMed:12110890, ECO:0000269|PubMed:17114460, CC ECO:0000269|PubMed:17548579, ECO:0000269|PubMed:19890330, CC ECO:0000269|PubMed:20802146, ECO:0000269|PubMed:20819940, CC ECO:0000269|PubMed:21319304, ECO:0000269|PubMed:22105604, CC ECO:0000269|PubMed:2461949, ECO:0000269|PubMed:25660970}. CC -!- TISSUE SPECIFICITY: Serum levels are found elevated in mice with CC modeled systemic lupus erythematosus (SLE) and are correlated with SLE CC disease activity (PubMed:26078984). {ECO:0000269|PubMed:26078984}. CC -!- DOMAIN: HMG box 2 mediates pro-inflammatory cytokine-stimulating CC activity and binding to TLR4. However, not involved in mediating CC immunogenic activity in the context of apoptosis-induced immune CC tolerance. {ECO:0000250|UniProtKB:P09429}. CC -!- DOMAIN: The acidic C-terminal domain forms a flexible structure which CC can reversibly interact intramolecularily with the HMG boxes and CC modulate binding to DNA and other proteins. CC {ECO:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P63159}. CC -!- PTM: Acetylated on multiple sites upon stimulation with LPS (By CC similarity). Acetylation on lysine residues in the nuclear localization CC signals (NLS 1 and NLS 2) leads to cytoplasmic localization and CC subsequent secretion. Acetylation on Lys-3 results in preferential CC binding to DNA ends and impairs DNA bending activity (By similarity). CC {ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P63159}. CC -!- PTM: Phosphorylated at serine residues (PubMed:17114460). CC Phosphorylation in both NLS regions is required for cytoplasmic CC translocation followed by secretion (By similarity). CC {ECO:0000250|UniProtKB:P09429, ECO:0000269|PubMed:17114460}. CC -!- PTM: Reduction/oxidation of cysteine residues Cys-23, Cys-45 and Cys- CC 106 and a possible intramolecular disulfide bond involving Cys-23 and CC Cys-45 give rise to different redox forms with specific functional CC activities in various cellular compartments: 1- Fully reduced HGMB1 CC (HMGB1C23hC45hC106h), 2- Disulfide HMGB1 (HMGB1C23-C45C106h) and CC 3- Sulfonyl HMGB1 (HMGB1C23soC45soC106so). CC {ECO:0000250|UniProtKB:P63159}. CC -!- PTM: Poly-ADP-ribosylated by PARP1 when secreted following stimulation CC with LPS (PubMed:18768881, PubMed:22204001). CC {ECO:0000269|PubMed:18768881, ECO:0000269|PubMed:22204001}. CC -!- PTM: In vitro cleavage by CASP1 is liberating a HMG box 1-containing CC peptide which may mediate immunogenic activity; the peptide antagonizes CC apoptosis-induced immune tolerance (By similarity). Can be CC proteolytically cleaved by a thrombin:thrombomodulin complex; reduces CC binding to heparin and pro-inflammatory activities. CC {ECO:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P10103}. CC -!- PTM: Forms covalent cross-links mediated by transglutaminase TGM2, CC between a glutamine and the epsilon-amino group of a lysine residue, CC forming homopolymers and heteropolymers. CC {ECO:0000250|UniProtKB:P09429}. CC -!- DISRUPTION PHENOTYPE: Rapid death within 24 hours following birth due CC to hypoglycaemia. {ECO:0000269|PubMed:10391216}. CC -!- MISCELLANEOUS: Plays a role in acute sepsis; administration of CC antibodies to HMGB1 attenuates endotoxin lethality; administration of CC HMGB1 itself is lethal (PubMed:10398600). Overexpression in ALD-DNA- CC immunized mice significantly enhances the severity of modeled SLE CC (PubMed:26078984). {ECO:0000269|PubMed:10398600, CC ECO:0000269|PubMed:26078984}. CC -!- SIMILARITY: Belongs to the HMGB family. {ECO:0000305}. CC -!- CAUTION: Was reported that reduction/oxidation of cysteine residues CC Cys-23, Cys-45 and Cys-106 and a possible intramolecular disulfide bond CC involving Cys-23 and Cys-45 give rise to different redox forms with CC specific functional activities. Was reported to be secreted. However, CC this work was later retracted, although the roles of different redox CC forms in some functional activities is supported by similarity. CC {ECO:0000305|PubMed:22105604, ECO:0000305|PubMed:33380312}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z11997; CAA78042.1; -; mRNA. DR EMBL; X80457; CAA56631.1; -; Genomic_DNA. DR EMBL; U00431; AAA20508.1; -; mRNA. DR EMBL; L38477; AAA57042.1; -; mRNA. DR EMBL; BC006586; AAH06586.1; -; mRNA. DR EMBL; BC008565; AAH08565.1; -; mRNA. DR EMBL; BC083067; AAH83067.1; -; mRNA. DR EMBL; BC085090; AAH85090.1; -; mRNA. DR CCDS; CCDS19883.1; -. DR PIR; I48688; I48688. DR RefSeq; NP_001300823.1; NM_001313894.1. DR RefSeq; NP_034569.1; NM_010439.4. DR RefSeq; XP_003945388.1; XM_003945339.3. DR PDB; 5ZDZ; X-ray; 2.80 A; N=1-163. DR PDB; 5ZE0; X-ray; 2.75 A; N=1-163. DR PDB; 5ZE1; X-ray; 3.00 A; N=1-163. DR PDB; 5ZE2; X-ray; 3.30 A; N=1-163. DR PDBsum; 5ZDZ; -. DR PDBsum; 5ZE0; -. DR PDBsum; 5ZE1; -. DR PDBsum; 5ZE2; -. DR AlphaFoldDB; P63158; -. DR SMR; P63158; -. DR BioGRID; 200322; 15. DR CORUM; P63158; -. DR IntAct; P63158; 11. DR MINT; P63158; -. DR STRING; 10090.ENSMUSP00000082682; -. DR ChEMBL; CHEMBL2311237; -. DR GlyGen; P63158; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P63158; -. DR MetOSite; P63158; -. DR PhosphoSitePlus; P63158; -. DR SwissPalm; P63158; -. DR EPD; P63158; -. DR jPOST; P63158; -. DR PaxDb; 10090-ENSMUSP00000082682; -. DR PeptideAtlas; P63158; -. DR ProteomicsDB; 273149; -. DR Pumba; P63158; -. DR ABCD; P63158; 1 sequenced antibody. DR Antibodypedia; 3132; 1862 antibodies from 46 providers. DR DNASU; 15289; -. DR Ensembl; ENSMUST00000085546.13; ENSMUSP00000082682.7; ENSMUSG00000066551.13. DR Ensembl; ENSMUST00000093196.11; ENSMUSP00000106131.2; ENSMUSG00000066551.13. DR Ensembl; ENSMUST00000110505.8; ENSMUSP00000106132.2; ENSMUSG00000066551.13. DR GeneID; 15289; -. DR KEGG; mmu:15289; -. DR UCSC; uc009apb.2; mouse. DR AGR; MGI:96113; -. DR CTD; 3146; -. DR MGI; MGI:96113; Hmgb1. DR VEuPathDB; HostDB:ENSMUSG00000066551; -. DR eggNOG; KOG0381; Eukaryota. DR GeneTree; ENSGT00950000183120; -. DR InParanoid; P63158; -. DR OMA; PHSANEV; -. DR OrthoDB; 1222485at2759; -. DR PhylomeDB; P63158; -. DR TreeFam; TF105371; -. DR Reactome; R-MMU-140342; Apoptosis induced DNA fragmentation. DR Reactome; R-MMU-445989; TAK1-dependent IKK and NF-kappa-B activation. DR Reactome; R-MMU-5620971; Pyroptosis. DR Reactome; R-MMU-5686938; Regulation of TLR by endogenous ligand. DR Reactome; R-MMU-6798695; Neutrophil degranulation. DR Reactome; R-MMU-879415; Advanced glycosylation endproduct receptor signaling. DR Reactome; R-MMU-933542; TRAF6 mediated NF-kB activation. DR BioGRID-ORCS; 15289; 26 hits in 79 CRISPR screens. DR ChiTaRS; Hmgb1; mouse. DR PRO; PR:P63158; -. DR Proteomes; UP000000589; Chromosome 5. DR RNAct; P63158; Protein. DR Bgee; ENSMUSG00000066551; Expressed in embryonic facial prominence and 114 other cell types or tissues. DR ExpressionAtlas; P63158; baseline and differential. DR GO; GO:0035868; C:alphav-beta3 integrin-HMGB1 complex; ISO:MGI. DR GO; GO:0009986; C:cell surface; ISO:MGI. DR GO; GO:0000793; C:condensed chromosome; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI. DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IEA:UniProtKB-SubCell. DR GO; GO:0005576; C:extracellular region; TAS:BHF-UCL. DR GO; GO:0005615; C:extracellular space; IDA:ARUK-UCL. DR GO; GO:0045121; C:membrane raft; ISO:MGI. DR GO; GO:0043005; C:neuron projection; IDA:MGI. DR GO; GO:0005634; C:nucleus; IDA:ARUK-UCL. DR GO; GO:0017053; C:transcription repressor complex; ISO:MGI. DR GO; GO:0008097; F:5S rRNA binding; ISO:MGI. DR GO; GO:0003681; F:bent DNA binding; ISO:MGI. DR GO; GO:0000405; F:bubble DNA binding; ISS:AgBase. DR GO; GO:0019958; F:C-X-C chemokine binding; ISO:MGI. DR GO; GO:0010858; F:calcium-dependent protein kinase regulator activity; IDA:MGI. DR GO; GO:0000402; F:crossed form four-way junction DNA binding; ISO:MGI. DR GO; GO:0005125; F:cytokine activity; IDA:MGI. DR GO; GO:0003684; F:damaged DNA binding; ISO:MGI. DR GO; GO:0008301; F:DNA binding, bending; ISS:AgBase. DR GO; GO:0070182; F:DNA polymerase binding; ISO:MGI. DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI. DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0003725; F:double-stranded RNA binding; IDA:UniProtKB. DR GO; GO:0000400; F:four-way junction DNA binding; ISS:AgBase. DR GO; GO:0051861; F:glycolipid binding; ISO:MGI. DR GO; GO:0008201; F:heparin binding; ISO:MGI. DR GO; GO:0005178; F:integrin binding; ISO:MGI. DR GO; GO:0001530; F:lipopolysaccharide binding; ISO:MGI. DR GO; GO:0016829; F:lyase activity; ISO:MGI. DR GO; GO:0003676; F:nucleic acid binding; EXP:DisProt. DR GO; GO:0000401; F:open form four-way junction DNA binding; ISO:MGI. DR GO; GO:0042277; F:peptide binding; ISO:MGI. DR GO; GO:0001786; F:phosphatidylserine binding; ISO:MGI. DR GO; GO:0030295; F:protein kinase activator activity; IDA:MGI. DR GO; GO:0050786; F:RAGE receptor binding; ISO:MGI. DR GO; GO:0048018; F:receptor ligand activity; ISO:MGI. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI. DR GO; GO:0003697; F:single-stranded DNA binding; ISO:MGI. DR GO; GO:0003727; F:single-stranded RNA binding; IDA:UniProtKB. DR GO; GO:0097100; F:supercoiled DNA binding; ISS:AgBase. DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI. DR GO; GO:0003713; F:transcription coactivator activity; ISO:MGI. DR GO; GO:0003714; F:transcription corepressor activity; ISO:MGI. DR GO; GO:0002218; P:activation of innate immune response; ISO:MGI. DR GO; GO:0043277; P:apoptotic cell clearance; ISS:UniProtKB. DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW. DR GO; GO:0006284; P:base-excision repair; IMP:UniProtKB. DR GO; GO:0098761; P:cellular response to interleukin-7; IDA:MGI. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:ARUK-UCL. DR GO; GO:0006325; P:chromatin organization; IDA:UniProtKB. DR GO; GO:0032392; P:DNA geometric change; ISS:AgBase. DR GO; GO:0035767; P:endothelial cell chemotaxis; IDA:UniProtKB. DR GO; GO:0001935; P:endothelial cell proliferation; IDA:UniProtKB. DR GO; GO:0001654; P:eye development; IMP:MGI. DR GO; GO:0005980; P:glycogen catabolic process; IMP:MGI. DR GO; GO:0031507; P:heterochromatin formation; ISO:MGI. DR GO; GO:0050930; P:induction of positive chemotaxis; ISO:MGI. DR GO; GO:0006954; P:inflammatory response; ISO:MGI. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0030324; P:lung development; IMP:MGI. DR GO; GO:0002281; P:macrophage activation involved in immune response; IMP:UniProtKB. DR GO; GO:0030099; P:myeloid cell differentiation; IDA:MGI. DR GO; GO:0001773; P:myeloid dendritic cell activation; IMP:UniProtKB. DR GO; GO:0002318; P:myeloid progenitor cell differentiation; IDA:MGI. DR GO; GO:2000426; P:negative regulation of apoptotic cell clearance; ISO:MGI. DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; ISO:MGI. DR GO; GO:0043371; P:negative regulation of CD4-positive, alpha-beta T cell differentiation; ISO:MGI. DR GO; GO:0017055; P:negative regulation of RNA polymerase II transcription preinitiation complex assembly; ISO:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0032689; P:negative regulation of type II interferon production; ISO:MGI. DR GO; GO:0097350; P:neutrophil clearance; ISS:UniProtKB. DR GO; GO:0002270; P:plasmacytoid dendritic cell activation; IMP:UniProtKB. DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISO:MGI. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI. DR GO; GO:0010508; P:positive regulation of autophagy; IMP:UniProtKB. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:MGI. DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI. DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; ISO:MGI. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:MGI. DR GO; GO:2001200; P:positive regulation of dendritic cell differentiation; ISO:MGI. DR GO; GO:0051106; P:positive regulation of DNA ligation; ISS:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB. DR GO; GO:0045819; P:positive regulation of glycogen catabolic process; IMP:MGI. DR GO; GO:0045089; P:positive regulation of innate immune response; IMP:UniProtKB. DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IMP:UniProtKB. DR GO; GO:0032728; P:positive regulation of interferon-beta production; IMP:UniProtKB. DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IMP:UniProtKB. DR GO; GO:0032732; P:positive regulation of interleukin-1 production; ISO:MGI. DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISO:MGI. DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISO:MGI. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:UniProtKB. DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:MGI. DR GO; GO:0046330; P:positive regulation of JNK cascade; ISO:MGI. DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI. DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; ISO:MGI. DR GO; GO:0032425; P:positive regulation of mismatch repair; ISO:MGI. DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISO:MGI. DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; IMP:UniProtKB. DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; ISO:MGI. DR GO; GO:0045639; P:positive regulation of myeloid cell differentiation; IDA:MGI. DR GO; GO:1905455; P:positive regulation of myeloid progenitor cell differentiation; IDA:MGI. DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; IDA:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:MGI. DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; IDA:UniProtKB. DR GO; GO:0034137; P:positive regulation of toll-like receptor 2 signaling pathway; IDA:UniProtKB. DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; IDA:UniProtKB. DR GO; GO:0034165; P:positive regulation of toll-like receptor 9 signaling pathway; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:MGI. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:UniProtKB. DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; ISO:MGI. DR GO; GO:0046598; P:positive regulation of viral entry into host cell; ISO:MGI. DR GO; GO:0090303; P:positive regulation of wound healing; IDA:UniProtKB. DR GO; GO:2000819; P:regulation of nucleotide-excision repair; IMP:UniProtKB. DR GO; GO:0002840; P:regulation of T cell mediated immune response to tumor cell; IDA:UniProtKB. DR GO; GO:0002643; P:regulation of tolerance induction; IMP:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0051384; P:response to glucocorticoid; IMP:MGI. DR GO; GO:0035711; P:T-helper 1 cell activation; ISO:MGI. DR GO; GO:0045063; P:T-helper 1 cell differentiation; ISO:MGI. DR GO; GO:0006366; P:transcription by RNA polymerase II; IMP:MGI. DR GO; GO:0033151; P:V(D)J recombination; ISO:MGI. DR CDD; cd21978; HMG-box_HMGB_rpt1; 1. DR CDD; cd21979; HMG-box_HMGB_rpt2; 1. DR DisProt; DP00384; -. DR Gene3D; 1.10.30.10; High mobility group box domain; 2. DR InterPro; IPR009071; HMG_box_dom. DR InterPro; IPR036910; HMG_box_dom_sf. DR InterPro; IPR017967; HMG_boxA_CS. DR PANTHER; PTHR48112:SF12; HIGH MOBILITY GROUP PROTEIN B1; 1. DR PANTHER; PTHR48112; HIGH MOBILITY GROUP PROTEIN DSP1; 1. DR Pfam; PF00505; HMG_box; 1. DR Pfam; PF09011; HMG_box_2; 1. DR PRINTS; PR00886; HIGHMOBLTY12. DR SMART; SM00398; HMG; 2. DR SUPFAM; SSF47095; HMG-box; 2. DR PROSITE; PS00353; HMG_BOX_1; 1. DR PROSITE; PS50118; HMG_BOX_2; 2. DR Genevisible; P63158; MM. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Adaptive immunity; ADP-ribosylation; Autophagy; KW Cell membrane; Chemotaxis; Chromosome; Cytoplasm; KW Direct protein sequencing; Disulfide bond; DNA damage; DNA recombination; KW DNA repair; DNA-binding; Endosome; Heparin-binding; Immunity; KW Inflammatory response; Innate immunity; Isopeptide bond; Membrane; Nucleus; KW Oxidation; Phosphoprotein; Reference proteome; Repeat; Secreted. FT CHAIN 1..215 FT /note="High mobility group protein B1" FT /id="PRO_0000048528" FT DNA_BIND 9..79 FT /note="HMG box 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267" FT DNA_BIND 95..163 FT /note="HMG box 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267" FT REGION 1..97 FT /note="Sufficient for interaction with HAVCR2" FT /evidence="ECO:0000269|PubMed:22842346" FT REGION 3..15 FT /note="LPS binding (delipidated)" FT /evidence="ECO:0000250|UniProtKB:P09429" FT REGION 27..43 FT /note="NLS 1" FT /evidence="ECO:0000250|UniProtKB:P63159" FT REGION 76..95 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 80..96 FT /note="LPS binding (Lipid A)" FT /evidence="ECO:0000250|UniProtKB:P09429" FT REGION 89..108 FT /note="Cytokine-stimulating activity" FT /evidence="ECO:0000250|UniProtKB:P09429" FT REGION 150..183 FT /note="Binding to AGER/RAGE" FT /evidence="ECO:0000250|UniProtKB:P63159" FT REGION 161..215 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 178..184 FT /note="NLS 2" FT /evidence="ECO:0000250|UniProtKB:P63159" FT MOTIF 27..43 FT /note="Nuclear localization signal (NLS) 1" FT /evidence="ECO:0000250|UniProtKB:P63159" FT MOTIF 178..184 FT /note="Nuclear localization signal (NLS) 2" FT /evidence="ECO:0000250|UniProtKB:P63159" FT COMPBIAS 76..94 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 161..187 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 188..215 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 1..10 FT /ligand="heparin" FT /ligand_id="ChEBI:CHEBI:28304" FT /evidence="ECO:0000250|UniProtKB:P10103" FT SITE 10..11 FT /note="Cleavage; by thrombin:thrombomodulin" FT /evidence="ECO:0000250|UniProtKB:P10103" FT SITE 67..68 FT /note="Cleavage; by CASP1" FT /evidence="ECO:0000250|UniProtKB:P09429" FT MOD_RES 3 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P10103" FT MOD_RES 7 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P10103" FT MOD_RES 8 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P10103" FT MOD_RES 12 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P10103" FT MOD_RES 23 FT /note="Cysteine sulfonic acid (-SO3H); alternate" FT /evidence="ECO:0000250|UniProtKB:P63159" FT MOD_RES 28 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P10103" FT MOD_RES 29 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P10103" FT MOD_RES 30 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 35 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09429" FT MOD_RES 43 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 45 FT /note="Cysteine sulfonic acid (-SO3H); alternate" FT /evidence="ECO:0000250|UniProtKB:P63159" FT MOD_RES 90 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 100 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09429" FT MOD_RES 106 FT /note="Cysteine sulfonic acid (-SO3H)" FT /evidence="ECO:0000250|UniProtKB:P63159" FT MOD_RES 127 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P10103" FT MOD_RES 128 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P10103" FT MOD_RES 141 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 172 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P10103" FT MOD_RES 173 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P10103" FT MOD_RES 177 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P10103" FT MOD_RES 180 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P10103" FT MOD_RES 181 FT /note="ADP-ribosylserine" FT /evidence="ECO:0000250|UniProtKB:P09429" FT MOD_RES 182 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P10103" FT MOD_RES 183 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P10103" FT MOD_RES 184 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P10103" FT MOD_RES 185 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P10103" FT DISULFID 23..45 FT /note="In disulfide HMGB1; alternate" FT /evidence="ECO:0000250|UniProtKB:P63159" FT CROSSLNK 28 FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain FT with Q-?)" FT /evidence="ECO:0000250|UniProtKB:P09429" FT CROSSLNK 43 FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain FT with Q-?)" FT /evidence="ECO:0000250|UniProtKB:P09429" FT CROSSLNK 44 FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain FT with Q-?)" FT /evidence="ECO:0000250|UniProtKB:P09429" FT CROSSLNK 68 FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain FT with Q-?)" FT /evidence="ECO:0000250|UniProtKB:P09429" FT CROSSLNK 180 FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain FT with Q-?)" FT /evidence="ECO:0000250|UniProtKB:P09429" FT CROSSLNK 182 FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain FT with Q-?)" FT /evidence="ECO:0000250|UniProtKB:P09429" FT CROSSLNK 183 FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain FT with Q-?)" FT /evidence="ECO:0000250|UniProtKB:P09429" FT CROSSLNK 184 FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain FT with Q-?)" FT /evidence="ECO:0000250|UniProtKB:P09429" FT CONFLICT 179 FT /note="E -> V (in Ref. 4; AAA57042)" FT /evidence="ECO:0000305" FT CONFLICT 190 FT /note="D -> E (in Ref. 2; CAA56631)" FT /evidence="ECO:0000305" FT HELIX 15..30 FT /evidence="ECO:0007829|PDB:5ZE0" FT HELIX 38..49 FT /evidence="ECO:0007829|PDB:5ZE0" FT HELIX 58..75 FT /evidence="ECO:0007829|PDB:5ZE0" FT HELIX 101..115 FT /evidence="ECO:0007829|PDB:5ZE0" FT HELIX 123..135 FT /evidence="ECO:0007829|PDB:5ZE0" FT HELIX 142..156 FT /evidence="ECO:0007829|PDB:5ZE0" SQ SEQUENCE 215 AA; 24894 MW; 8A868DE266D552B5 CRC64; MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKKCSERWK TMSAKEKGKF EDMAKADKAR YEREMKTYIP PKGETKKKFK DPNAPKRPPS AFFLFCSEYR PKIKGEHPGL SIGDVAKKLG EMWNNTAADD KQPYEKKAAK LKEKYEKDIA AYRAKGKPDA AKKGVVKAEK SKKKKEEEDD EEDEEDEEEE EEEEDEDEEE DDDDE //