HMGB1_MOUSE
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 03-AUG-2022, entry version 171.
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, Pancreas,
RC 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 CYSTEINE REDOX STATES, AND SUBCELLULAR LOCATION.
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 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 [35]
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 [36]
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 [37]
RP REVIEW ON FUNCTION RELATED TO ADAPTIVE IMUNNITY.
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 [38]
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 [39]
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 [40]
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 [41]
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 [42]
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 [43]
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 [44]
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 [45]
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 [46]
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 sensor and/or chaperone for immunogenic
CC nucleic acids implicating the activation of TLR9-mediated immune
CC responses, and mediates autophagy. Acts as danger associated molecular
CC pattern (DAMP) molecule that amplifies immune responses during tissue
CC injury. Released to the extracellular environment can bind DNA,
CC 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).
CC {ECO:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P10103,
CC ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:16040616,
CC ECO:0000269|PubMed:16267105, ECO:0000269|PubMed:17114460,
CC ECO:0000269|PubMed:17548579, ECO:0000269|PubMed:17803946,
CC ECO:0000269|PubMed:19264983, ECO:0000269|PubMed:20819940,
CC ECO:0000269|PubMed:22370717, ECO:0000269|PubMed:22544226,
CC ECO:0000269|PubMed:22842346, 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}. Secreted {ECO:0000269|PubMed:22105604}.
CC Chromosome {ECO:0000269|PubMed:12110890}. Cell membrane
CC {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}. Note=In basal state predominantly
CC nuclear. Shuttles between the cytoplasm and the nucleus
CC (PubMed:17114460). Translocates from the nucleus to the cytoplasm upon
CC autophagy stimulation (PubMed:20819940). Release from macrophages in
CC the extracellular milieu requires the activation of NLRC4 or NLRP3
CC inflammasomes (PubMed:20802146). Passively released to the
CC extracellular milieu from necrotic cells by diffusion, involving the
CC fully reduced form which subsequently gets oxidized (PubMed:12110890).
CC Also released from apoptotic cells (PubMed:25660970). Actively secreted
CC from a variety of immune and non-immune cells such as macrophages,
CC monocytes, neutrophils, dendritic cells and natural killer cells in
CC response to various stimuli, involving a nonconventional secretory
CC process via secretory lysosomes (PubMed:17548579). Secreted by plasma
CC cells in response to LPS (PubMed:21319304). Associated with the plasma
CC membrane of filipodia in process-growing cells, and also deposited into
CC the substrate-attached material (By similarity). Colocalizes with DDX58
CC on endosomal membranes (PubMed:19890330).
CC {ECO:0000250|UniProtKB:P09429, ECO:0000269|PubMed:12110890,
CC ECO:0000269|PubMed:17114460, ECO:0000269|PubMed:17548579,
CC ECO:0000269|PubMed:19890330, ECO:0000269|PubMed:20802146,
CC ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:21319304,
CC ECO:0000269|PubMed:22105604, ECO:0000269|PubMed:2461949,
CC 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:0000269|PubMed:22105604}.
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 h following birth due to
CC 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}.
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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; 12.
DR CORUM; P63158; -.
DR IntAct; P63158; 11.
DR MINT; P63158; -.
DR STRING; 10090.ENSMUSP00000082682; -.
DR ChEMBL; CHEMBL2311237; -.
DR iPTMnet; P63158; -.
DR MetOSite; P63158; -.
DR PhosphoSitePlus; P63158; -.
DR SwissPalm; P63158; -.
DR EPD; P63158; -.
DR jPOST; P63158; -.
DR PaxDb; P63158; -.
DR PeptideAtlas; P63158; -.
DR PRIDE; P63158; -.
DR ProteomicsDB; 273149; -.
DR ABCD; P63158; 1 sequenced antibody.
DR Antibodypedia; 3132; 1676 antibodies from 46 providers.
DR DNASU; 15289; -.
DR Ensembl; ENSMUST00000085546; ENSMUSP00000082682; ENSMUSG00000066551.
DR Ensembl; ENSMUST00000093196; ENSMUSP00000106131; ENSMUSG00000066551.
DR Ensembl; ENSMUST00000110505; ENSMUSP00000106132; ENSMUSG00000066551.
DR GeneID; 15289; -.
DR KEGG; mmu:15289; -.
DR UCSC; uc009apb.2; mouse.
DR CTD; 3146; -.
DR MGI; MGI:96113; Hmgb1.
DR VEuPathDB; HostDB:ENSMUSG00000066551; -.
DR eggNOG; KOG0381; Eukaryota.
DR GeneTree; ENSGT00950000183120; -.
DR InParanoid; P63158; -.
DR OMA; GEMWNSK; -.
DR OrthoDB; 1641977at2759; -.
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 73 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 112 other tissues.
DR ExpressionAtlas; P63158; baseline and differential.
DR Genevisible; P63158; MM.
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:0005769; C:early endosome; IDA:UniProtKB.
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: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: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:0008201; F:heparin binding; IEA:UniProtKB-KW.
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:0000401; F:open form four-way junction DNA 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:0061629; F:RNA polymerase II-specific DNA-binding transcription factor 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:0031497; P:chromatin assembly; 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 assembly; 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:0032689; P:negative regulation of interferon-gamma production; 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: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:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; 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:0043388; P:positive regulation of DNA binding; 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 NIK/NF-kappaB signaling; 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:0090303; P:positive regulation of wound healing; IDA:UniProtKB.
DR GO; GO:2000819; P:regulation of nucleotide-excision repair; IMP:UniProtKB.
DR GO; GO:0032072; P:regulation of restriction endodeoxyribonuclease activity; ISO:MGI.
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 DisProt; DP00384; -.
DR Gene3D; 1.10.30.10; -; 2.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR InterPro; IPR017967; HMG_boxA_CS.
DR InterPro; IPR031076; HMGB1.
DR PANTHER; PTHR48112:SF4; PTHR48112:SF4; 1.
DR Pfam; PF00505; HMG_box; 1.
DR Pfam; PF09011; HMG_box_2; 1.
DR SMART; SM00398; HMG; 2.
DR SUPFAM; SSF47095; SSF47095; 2.
DR PROSITE; PS00353; HMG_BOX_1; 1.
DR PROSITE; PS50118; HMG_BOX_2; 2.
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
